CompletedNCT03020745Updated Oct 1, 2020Results posted

A Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK3389404 in Chronic Hepatitis B (CHB) Subjects

A Phase 2 interventional study of GSK3389404 and Placebo in Hepatitis B, sponsored by GlaxoSmithKline. Completed at 21 sites in 6 countries. Open to participants aged 18 Years to 70 Years. Per ClinicalTrials.gov, last updated 2020-10-01.

Sponsored by GlaxoSmithKline · Phase 2, Interventional, and Treatment

Phase: Phase 2
Study type: Interventional
Enrollment: 78
Allocation: Randomized
Ages: 18 Years to 70 Years
Sex: All

Study summary

GSK3389404 is being developed for the treatment of CHB virus infection. The development goal for GSK3389404 is the establishment of a finite duration treatment that results in sustained suppression of hepatitis B virus (HBV) replication and viral antigen production after cessation of all treatments for CHB due to the restoration of a functional immune response in the absence of high antigen levels. This study is a multicenter, randomized double-Blind (sponsor un-blinded in Part 1), Placebo-controlled Study which will evaluate the safety, tolerability, PK, and PD profile of GSK3389404 in subjects with CHB and aim to establish proof-of-mechanism. The study will be conducted in two parts. Part 1 plans to enroll subjects primarily from the Asia-pacific region, including Japan and will be conducted as a single ascending dose (SAD) study with 5 planned cohorts ranging from 30 milligram (mg) to a maximum of 240 mg GSK3389404. Within each cohort, subjects will be randomized to receive either GSK3389404 or placebo in a 3:1 ratio. Cohorts A, B, C, C1, and D will be conducted in a sequential fashion; Cohort C1 is an optional cohort and may be dosed after Cohort C or in parallel with Cohort D. Part 2 will be conducted as a multiple-dose, dose-ranging study. Subjects will be randomized to different parallel dose levels and regimens or placebo. The dose levels of Part 2 will be selected after a review of Part 1 safety, Pharmacokinetic (PK) and Pharmacodynamic (PD) data. The treatments selected are 60 mg GSK3389404 weekly, 120 mg GSK3389404 bi-weekly, 120 mg GSK3389404 weekly or placebo. An optional Japanese part-2 sub-study is planned. The total study duration for part 1 including screening, treatment, and post-treatment follow-up, will not be expected to exceed 13 weeks for each subject and for part 2, including screening, treatment and post-treatment follow-up, will not be expected to exceed 65 weeks for each subject.

Conditions studied

Hepatitis B

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Keywords

Pharmacokinetics
Safety
Pharmacodynamics
Efficacy
Chronic Hepatitis B
GSK3389404

In context

Hepatitis A

2,710 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 78 is below the median of 100 across 1,887 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

GlaxoSmithKline is the lead sponsor of 3,562 studies on the registry; 117 are open to participants now.

Of its 258 completed or terminated interventional studies of FDA-regulated products, 232 (90%) have results posted.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years to 70 Years
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Subject is able to understand and is capable of giving written informed consent, is willing to comply with protocol requirements, instructions and protocol-stated restrictions, and is likely to complete the study as planned.
Between 18 and 70 years of age, inclusive, at the time of signing the informed consent form.
A body mass index (BMI) between 18 to 30 kilogram (Kg)/meter (m\^2), inclusive.
Male or female if they satisfy the following: All females must meet the following criteria: Non-pregnant (as confirmed by a negative serum Human Chorionic Gonadotropin [hCG] test); AND Non-lactating at screening and prior to dosing; AND For Part 2, females of reproductive potential (FRP) must agree to follow (or confirm that they have and are currently following) one of the options listed in the Modified List of Highly Effective Methods for Avoiding Pregnancy in FRP from at least 28 days prior to the first dose of study treatment until Follow-up visit Day 169 in conjunction with partner's use of male condom. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. For females of non-reproductive potential at least one of the following conditions must apply: Premenopausal females without reproductive potential defined by Documented salpingectomy, Hysterectomy or Documented bilateral oophorectomy; Postmenopausal defined as 12 months of spontaneous amenorrhea; A blood sample for simultaneous Follicle-Stimulating Hormone (FSH) and estradiol levels may be collected at the discretion of the investigator or site to confirm non-reproductive potential; Male subjects with a female partner of child-bearing potential must agree to meet one of the contraception requirements from the time of first dose of study treatment until Follow-up visit Day 169; Vasectomy; Male condom plus partner's use of one of the contraceptive options below that meets the Standard Operating Procedure (SOP) effectiveness criteria including a \<1 percent rate of failure per year, as stated in the product label: Contraceptive subdermal implant, Intrauterine device or intrauterine system, Combined estrogen and progestogen oral contraceptive, Injectable progestogen, Contraceptive vaginal ring, or Percutaneous contraceptive patches. These allowed methods of contraception are only effective when used consistently, correctly and in accordance with the product label. The investigator is responsible for ensuring that subjects understand how to properly use these methods of contraception. Male subjects must refrain from donating sperm from the time of first dose of study treatment until Follow-up visit Day 169.
Documented chronic HBV infection >=6 months prior to screening.
Subjects with HBV treatment history as follows: Part 1: Treatment naive or have had prior treatment with interferon (pegylated or non pegylated) that must have ended at least 6 months prior to the Baseline visit (Day 1 pre-dose) and/or nucleos(t)ide analogue therapy that must have ended at least 6 months prior to the Baseline visit or currently receiving stable nucleos(t)ide analogue therapy, defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study. Part 2: Subjects with CHB receiving stable nucleos(t)ide analogue therapy, defined as no changes to their nucleos(t)ide regimen from at least 6 months prior to screening and with no planned changes to the stable regimen over the duration of the study. Subjects with prior treatment with interferon (pegylated or non-pegylated) must have ended treatment at least 6 months prior to the Baseline visit (Day 1 pre-dose).
Plasma or serum HBV DNA concentration: treatment naïve subjects or subjects not currently receiving treatment, there is no minimum HBV DNA requirement; Subjects who are receiving stable nucleos(t)ide analogue therapy must be adequately suppressed, defined as plasma or serum HBV DNA \<lower limit of quantification (LLOQ)
Plasma or serum HBsAg concentration >50 IU/mL.
Alanine aminotransferase (ALT) concentration: ALT \< 5 X Upper Limit of Normal (ULN) for treatment naïve subjects and for subjects who are not currently receiving treatment. ALT \<=2 times ULN for subjects who are receiving stable nucleos(t)ide analogue therapy.

Exclusion criteria

Exclusion Criteria:

Medical history: History of or active diagnosis of moderate to severe liver disease other than CHB, such as autoimmune hepatitis, non alcoholic steatohepatitis, hemochromatosis, or liver failure. History or other clinical evidence of significant or unstable cardiac disease (e.g., prolonged QT syndrome [torsade de pointes], angina, congestive heart failure, myocardial infarction, diastolic dysfunction, significant arrhythmia, coronary heart disease and/or clinically significant ECG abnormalities). Uncontrolled or history of difficult to control hypertension. History of, or active diagnosis of, primary or secondary renal disease (e.g., renal disease secondary to diabetes, hypertension, vascular disease, etc.). History of extrahepatic disorders possibly related to HBV immune complexes (e.g., glomerulonephritis and polyarteritis nodosa). History of bleeding diathesis or coagulopathy. History of or suspected presence of vasculitis. History of Gilbert's Syndrome. History of malignancy within the past 5 years with the exception of specific cancers that are cured by surgical resection (e.g., skin cancer), subjects under evaluation for possible malignancy are not eligible.
History of/sensitivity to GSK3389404 or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
Confirmed or suspected hepatocellular carcinoma (HCC) as evidenced by: Alpha-fetoprotein concentration >=200 nanogram (ng)/mL. If the screening alpha-fetoprotein concentration is >=50 ng/mL and \<200 ng/mL, the absence of liver mass must be documented by imaging within 6 months before randomization.
Liver cirrhosis or evidence of cirrhosis as determined by any of the following: Positive liver biopsy (i.e., Metavir Score F4) within 12 months of screening. Fibroscan >12 kilopascals (kPa) within 12 months of screening. AST-Platelet Index (APRI) >2 and FibroSure result >0.7 within 12 months of screening and Investigator judgment. For subjects without a test for cirrhosis in the above timeframes, APRI and FibroSure should be performed during the screening period to rule out cirrhosis.
Hepatitis C Virus (HCV) co-infection.
Human Immunodeficiency Virus (HIV) co-infection.
Hepatitis D Virus (HDV) co-infection.
Laboratory results as follows: Total bilirubin concentration >1.25 X ULN. Serum albumin concentration \<3.5 grams (g)/deciliter (dL). International normalized ratio (INR) >1.25. Platelet count \<140 X 10\^9/L. Serum creatinine concentration greater than the ULN. Glomerular Filtration Rate (GFR) \<90 mL/min as calculated by the Chronic Kidney Disease Epidemiologic Collaboration (CKD-EPI) formula. Subjects with GFR \<90 mL/min but >= 60 mL/min may be considered after consultation with the GlaxoSmithKline medical monitor. Urine Albumin to Creatinine Ratio (ACR)>=0.03 mg/mg (or >=30 mg/g). In the event of an ACR above this threshold, eligibility may be confirmed by a second measurement in cases where subjects have low urine albumin and low urine creatinine levels resulting in a urine ACR calculation >=0.03 mg/mg (or >=30 mg/g), the investigator should confirm that subject does not have a history of diabetes, hypertension or other risk factors that may affect renal function and discuss with the PPD or GSK medical monitor, or designee.
Positive test for blood in urine. In the event of a positive test, the test may be repeated once, and if repeat is negative or if urine microscopy reveals \<5 RBC per High-Power Field (HPF), the subject is considered eligible.
Fridericia's QT correction formula (QTcF) >=450 milliseconds (msec) (single ECG at screening shows QTcF >=450 msec, a mean of triplicate measurements should be used to confirm that subject meets exclusion criterion).
Currently taking, or took within 3 months of screening, any immunosuppressing drugs (e.g., prednisone), other than a short course of therapy (\<=2 weeks) or topical/inhaled steroid use.
Current alcohol use as judged by investigator to potentially interfere with participant compliance.
A positive pre-study treatment screen and an unwillingness to refrain from use of illicit drugs (or substances with abuse potential) and adhere to other protocol-stated restrictions while participating in the study [The screen refers to illicit drugs and substances with abuse potential. Medications that are used by the subject as directed, whether over-the-counter or through prescription, are acceptable and would not meet the exclusion criteria]. .
Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56 day period.
The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the first dosing day in the current study: 5 half-lives (if known) or twice the duration (if known) of the biological effect of the study treatment (whichever is longer) or 90 days (if half-life or duration is unknown).
Prior treatment with any non-GSK oligonucleotide or small interfering ribonucleic acid (RNA) (siRNA) within 12 months prior to the first dosing day or prior treatment with GSK oligonucleotide within 3 months prior to the first dosing day.
Pregnant or lactating females at screening and prior to dosing.
For Part 1, females of reproductive potential.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Single group
Masking: Double (Participant, Investigator)
Enrollment: 78 participants (actual)

Study arms

Experimental
Part 1, Cohort A : GSK3389404 30 mg SC or Placebo
Enrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 30 mg or matching placebo
Drug: GSK3389404 · Drug: Placebo
Experimental
Part 1, Cohort B: GSK3389404 60 mg SC or Placebo
Enrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 60 mg or matching placebo
Drug: GSK3389404 · Drug: Placebo
Experimental
Part 1, Cohort C: GSK3389404 120 mg SC or Placebo
Enrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 120 mg or matching placebo
Drug: GSK3389404 · Drug: Placebo
Experimental
Part 1, Cohort C1 (optional): GSK3389404 120 mg SC or Placebo
Enrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 120 mg or matching placebo
Drug: GSK3389404 · Drug: Placebo
Experimental
Part 1, Cohort D: GSK3389404 </= 240 mg SC or Placebo
Enrolled subjects (HBeAg-positive and/or HBeAg negative) will receive single SC injection of GSK3389404 \<= 240 mg or matching placebo
Drug: GSK3389404 · Drug: Placebo
Experimental
Part 2: GSK3389404 or placebo SC
Enrolled subjects will receive different parallel dose level and regimens of GSK3389404 or placebo SC at dose determined in part 1. The treatments for Part 2 are 60 mg GSK3389404 weekly, 120 mg bi-weekly GSK3389404, 120 mg GSK3389404 weekly or placebo.
Drug: GSK3389404 · Drug: Placebo

Interventions

DrugGSK3389404
GSK3389404 is available as Clear colorless to slightly yellow solution for injection.
DrugPlacebo
Placebo is available as a Clear colorless solution.

What researchers measure

Primary outcomes

Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points
SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Day 1: 1 hour, Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30
Part 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 169-Interim Analysis)
SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 450-Optional Follow-up)
SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Day 270 and Day 450
Part 1: Change From Baseline in Heart Rate at Indicated Time Points
Heart rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Day 1: 1 hour, Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30
Part 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 169-Interim Analysis)
Heart rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)
Heart rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Day 270 and Day 450
Part 1: Change From Baseline in Respiratory Rate at Indicated Time Points
Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 3, 8 and 30
Part 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 169-Interim Analysis)
Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)
Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Day 270 and Day 450
Part 1: Change From Baseline in Body Temperature at Indicated Time Points
Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 3, 8 and 30
Part 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 169-Interim Analysis)
Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 450-Optional Follow-up)
Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Day 270 and Day 450
Part 1: Number of Participants With Abnormal Findings in Physical Examination
Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.
Time frame: Up to Day 60
Part 2: Number of Participants With Abnormal Findings in Physical Examination (Up to Day 169-Interim Analysis)
Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.
Time frame: Up to Day 169
Part 2: Number of Participants With Abnormal Findings in Physical Examination (Up to Day 450-Optional Follow-up)
Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.
Time frame: Up to Day 450
Part 1: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters
Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, Activated partial thromboplastin time (aPTT), Prothrombin international normalized ratio (INR) and Prothrombin time (PT). Laboratory parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.
Time frame: Up to Day 60
Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 169-Interim Analysis)
Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, aPTT, Prothrombin INR and PT. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.
Time frame: Up to Day 169
Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 450-Optional Follow-up)
Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, aPTT, Prothrombin INR and PT. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.
Time frame: Up to Day 450
Part 1: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points
Blood samples were collected from participants to assess complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 60
Part 2: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points (Up to Day 169-Interim Analysis)
Blood samples were collected from participants to assess complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 169
Part 2: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points (Up to Day 450-Optional Follow-up)
Blood samples were planned to be collected from participants to evaluate change from Baseline in complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Change From Baseline in Complement Bb Level at Indicated Time Points
Blood samples were collected from participants to assess complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 60
Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 169-Interim Analysis)
Blood samples were collected from participants to assess complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 169
Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 450-Optional Follow-up)
Blood samples were collected from participants to evaluate change from Baseline in complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Change From Baseline in Complement C5a Level at Indicated Time Points
Blood samples were collected from participants to assess complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 60
Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 169-Interim Analysis)
Blood samples were collected from participants to assess complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 169
Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 450-Optional Follow-up)
Blood samples were collected from participants to evaluate change from Baseline in complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters
Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low) and Urate. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.
Time frame: Up to Day 60
Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 169-Interim Analysis)
Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low), Urate and glomerular filtration rate (GFR). Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.
Time frame: Up to Day 169
Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 450-Optional Follow-up)
Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low), Urate and glomerular filtration rate (GFR). Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.
Time frame: Up to Day 450
Part 1: Change From Baseline in Urine Albumin at Indicated Time Points
Urine samples were collected from participants to assess urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 30 and Follow-up (Day 60)
Part 2: Change From Baseline in Urine Albumin at Indicated Time Points (Up to Day 169-Interim Analysis)
Urine samples were collected from participants to assess urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 15, 29, 43, 57, 71, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Urine Albumin at Indicated Time Points (Up to Day 450-Optional Follow-up)
Urine samples were planned to be collected from participants to evaluate change from Baseline in urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Change From Baseline in Urine Creatinine at Indicated Time Points
Urine samples were collected from participants to assess urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 30 and Follow-up (Day 60)
Part 2: Change From Baseline in Urine Creatinine at Indicated Time Points (Up to Day 169-Interim Analysis)
Urine samples were collected from participants to assess urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 15, 29, 43, 57, 71, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Urine Creatinine at Indicated Time Points (Up to Day 450-Optional Follow-up)
Urine samples were planned to be collected from participants to evaluate change from Baseline in urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) at Indicated Time Points
Urine samples were collected from participants to assess urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)
Part 2: Change From Baseline in Urine pH at Indicated Time Points (Up to Day 169-Interim Analysis)
Urine samples were collected from participants to assess urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Urine pH at Indicated Time Points (Up to Day 450-Optional Follow-up)
Urine samples were planned to be collected from participants to evaluate change from Baseline in urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Change From Baseline in Urine Specific Gravity at Indicated Time Points
Urine samples were collected from participants to assess urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)
Part 2: Change From Baseline in Urine Specific Gravity at Indicated Time Points (Up to Day 169-Interim Analysis)
Urine samples were collected from participants to assess urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Urine Specific Gravity at Indicated Time Points (Up to Day 450-Optional Follow-up)
Urine samples were planned to be collected from participants to evaluate change from Baseline in urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Change From Baseline in Urobilinogen at Indicated Time Points
Urine samples were collected from participants to assess urobilinogen levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)
Part 2: Change From Baseline in Urobilinogen at Indicated Time Points (Up to Day 169-Interim Analysis)
Urine samples were collected from participants to assess urobilinogen levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in Urobilinogen at Indicated Time Points (Up to Day 450-Optional Follow-up)
Urine samples were planned to be collected from participants to evaluate change from Baseline in urobilinogen. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Electrocardiograms were obtained after 5 minutes of rest in the semi-supine or supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.
Time frame: Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30
Part 2: Number of Participants With Abnormal ECG Findings (Up to Day 169-Interim Analysis)
Electrocardiogram were obtained after 5 minutes of rest in the semi-supine or supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals. CS and NCS abnormal ECG findings have been presented. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.
Time frame: Days 29, 57, 85 and 169
Part 2: Number of Participants With Abnormal ECG Findings (Up to Day 450-Optional Follow-up)
ECGs were planned to be obtained after 5 minutes of rest in the semi-supine or supine position using ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals.
Time frame: Days 270, 360 and 450
Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Time frame: Up to Day 60
Part 2: Number of Participants With AEs and SAEs (Up to Day 169-Interim Analysis)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Time frame: Up to Day 169
Part 2: Number of Participants With AEs and SAEs (Up to Day 450-Optional Follow-up)
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.
Time frame: Up to Day 450
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for GSK3389404
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: AUC (0-t) for GSK3389404
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) for GSK3389404
Blood samples were collected to measure AUC (0-infinity) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: AUC (0-infinity) for GSK3389404
Blood samples were collected to measure AUC (0-infinity) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3389404
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: Cmax of GSK3389404
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Time to Achieve Cmax (Tmax) of GSK3389404
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: Tmax of GSK3389404
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Apparent Terminal Phase Half-life(t1/2) of GSK3389404
Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: t1/2 of GSK3389404
Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Apparent Subcutaneous Plasma Clearance (CL/F) of GSK3389404
Blood samples were collected to measure CL/F at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: CL/F of GSK3389404
Blood samples were collected to measure CL/F at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Number of Participants Achieving Response Rate (RR) Based on Reduction of Hepatitis B Surface Antigen (HBsAg) Level From Baseline
The RR was based on the proportion of participants with at least a 1.5 logarithm to the base 10 (log10) international units per milliliter (IU/mL) reduction of HBsAg levels from Baseline at any time up to Day 60. Number of participants who achieved \>1.5 log10 IU/mL decrease in HBsAg levels at any time up to Day 60 are presented.
Time frame: Up to Day 60
Part 2: Number of Participants Achieving RR Based on Reduction of HBsAg Level From Baseline
The RR was based on the proportion of participants with at least a 1.5 log10 IU/mL reduction of HBsAg levels from Baseline at any time up to Day 85. Number of participants who achieved \>1.5 log10 IU/mL decrease in HBsAg levels at any time up to Day 85 are presented.
Time frame: Up to Day 85

Secondary outcomes

Part 1: Change From Baseline in log10 Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Indicated Time Points
Blood samples were collected from participants to assess HBV DNA viral load. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose), Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60
Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)
Blood samples were collected from participants to assess HBV DNA viral load. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose) and Up to Day 169
Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)
Blood samples were collected from participants to assess HBV DNA viral load. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose) and Up to Day 450
Part 1: Change From Baseline in log10 Hepatitis B Virus Surface Antigen (HBsAg) Levels in Plasma at Indicated Time Points
Blood samples were collected from participants to assess HBsAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose) and Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60
Part 2: Change From Baseline in log10 HBsAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)
Blood samples were collected from participants to assess HBsAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in log10 HBsAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)
Blood samples were collected from participants to assess HBsAg level. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose), Day 270, Day 360 and Day 450
Part 1: Change From Baseline in log10 Hepatitis B Virus E-antigen (HBeAg) Levels in Plasma at Indicated Time Points
Blood samples were collected from participants to assess HBeAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose) and Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60
Part 2: Change From Baseline in log10 HBeAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)
Blood samples were collected from participants to assess HBeAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Part 2: Change From Baseline in log10 HBeAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)
Blood samples were collected from participants to assess HBeAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).
Time frame: Baseline (Day 1 pre-dose), Day 270, Day 360 and Day 450
Part 1: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)
Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Cmax of GSK3389404 Metabolite (ISIS 505358)
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: Cmax of GSK3389404 Metabolite (ISIS 505358)
Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: Tmax of GSK3389404 Metabolite (ISIS 505358)
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: Tmax of GSK3389404 Metabolite (ISIS 505358)
Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Part 1: t1/2 of GSK3389404 Metabolite (ISIS 505358)
Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Part 2: t1/2 of GSK3389404 Metabolite (ISIS 505358)
Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.
Time frame: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169

Results

Posted Jan 22, 2020

Participant flow

This was a Phase 2a study examining the first administration of GSK3389404 in participants with chronic hepatitis B (CHB). The study was conducted in 2 parts- Part 1 (dose escalation) and Part 2 (dose expansion and optional follow-up period).

Part 1 (Up to 60 Days)

Participant flow — Part 1 (Up to 60 Days)
Milestone	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Started	3	3	6
Completed	3	3	6
Not completed	0	0	0

Part 2 (Up to 169 Days)

Participant flow — Part 2 (Up to 169 Days)
Milestone	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Started	10	6	20	15	15
Completed	10	6	19	14	15
Not completed	0	0	1	1	0
Withdrew: Adverse event	0	0	0	1	0
Withdrew: Withdrawal by subject	0	0	1	0	0

Part 2:Optional FU (Up to 450 Days)

Participant flow — Part 2:Optional FU (Up to 450 Days)
Milestone	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Started	10	5	17	13	15
Completed	9	5	17	10	15
Not completed	1	0	0	3	0
Withdrew: Lost to follow-up	1	0	0	1	0
Withdrew: Withdrawal by subject	0	0	0	2	0

Outcome measures

PrimaryPart 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points

SBP and DBP were measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Day 1: 1 hour, Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30
Reported as:: Mean · Millimeters of mercury (mmHg)

Part 1: Change From Baseline in Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) at Indicated Time Points
Millimeters of mercury (mmHg)	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
DBP, Day 1: 1 hour, n=3,3,6	-3.67 ± 16.073	3.00 ± 7.550	0.50 ± 11.554
DBP, Day 1: 2 hour, n=3,3,6	-5.33 ± 9.018	-3.33 ± 3.055	-4.33 ± 8.847
DBP, Day 1: 4 hour, n=3,3,6	-8.50 ± 7.365	-7.67 ± 1.528	-10.50 ± 6.626
DBP, Day 1: 8 hour, n=3,3,6	-7.17 ± 16.510	-0.50 ± 2.784	-3.17 ± 7.414
DBP, Day 3, n=3,3,6	-7.00 ± 20.075	-5.83 ± 5.107	-2.33 ± 5.538
DBP, Day 8, n=2,3,6	-7.50 ± 20.506	-1.00 ± 7.000	-1.50 ± 9.731
DBP, Day 30, n=3,3,6	-6.33 ± 19.604	-6.00 ± 1.000	-3.00 ± 10.431
SBP, Day 1: 1 hour, n=3,3,6	-0.17 ± 4.072	5.72 ± 9.595	-2.33 ± 16.367
SBP, Day 1: 2 hour, n=3,3,6	-3.83 ± 17.061	6.89 ± 13.040	-6.00 ± 12.083
SBP, Day 1: 4 hour, n=3,3,6	-13.33 ± 14.012	0.06 ± 6.646	-8.00 ± 14.269
SBP, Day 1: 8 hour, n=3,3,6	-5.50 ± 13.611	0.89 ± 4.550	-5.67 ± 12.644
SBP, Day 3, n=3,3,6	-3.00 ± 21.633	-7.94 ± 3.084	-0.83 ± 9.261
SBP, Day 8, n=2,3,6	6.00 ± 32.527	4.06 ± 5.149	0.17 ± 4.070
SBP, Day 30, n=3,3,6	-2.00 ± 26.514	4.89 ± 12.303	3.67 ± 13.736

PrimaryPart 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · mmHg

Part 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 169-Interim Analysis)
mmHg	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
DBP, Day 8, n=10,6,20,15,15	5.8 ± 8.90	2.3 ± 8.71	-1.9 ± 7.13	1.0 ± 8.86	-0.7 ± 8.61
DBP, Day 15, n=10,6,20,14,15	2.1 ± 8.46	-4.0 ± 13.02	-0.3 ± 9.09	-0.3 ± 7.09	-2.7 ± 7.32
DBP, Day 22, n=10,6,20,14,15	3.4 ± 9.49	-2.0 ± 6.20	0.3 ± 8.77	1.6 ± 9.80	-3.0 ± 9.13
DBP, Day 29, n=10,6,20,13,15	3.9 ± 8.77	3.3 ± 2.25	-1.7 ± 8.55	2.1 ± 9.71	-0.7 ± 7.35
DBP, Day 36, n=10,6,20,14,15	1.8 ± 8.90	-1.7 ± 9.35	-0.8 ± 8.84	1.9 ± 8.46	-0.1 ± 6.38
DBP, Day 43, n=10,6,20,14,15	4.2 ± 12.33	0.0 ± 6.45	-0.3 ± 12.38	0.9 ± 10.99	-0.8 ± 6.12
DBP, Day 50, n=10,6,19,14,15	11.0 ± 17.26	2.8 ± 8.93	0.1 ± 9.95	1.3 ± 10.25	-3.2 ± 7.74
DBP, Day 57, n=10,6,20,14,15	4.0 ± 9.88	-0.2 ± 8.73	-0.5 ± 9.10	1.6 ± 8.34	-0.8 ± 8.16
DBP, Day 64, n=10,6,20,14,15	3.2 ± 9.67	0.3 ± 9.31	-1.9 ± 10.27	2.1 ± 9.71	-1.8 ± 9.93
DBP, Day 71, n=10,6,20,14,15	2.9 ± 9.56	3.8 ± 7.11	-0.6 ± 9.83	3.1 ± 9.92	1.4 ± 9.74
DBP, Day 78, n=10,6,20,14,15	4.6 ± 5.50	1.2 ± 6.59	-0.8 ± 8.80	5.0 ± 8.71	-4.2 ± 9.85
DBP, Day 85, n=10,6,20,14,15	4.9 ± 7.20	1.0 ± 9.47	-1.2 ± 12.35	6.4 ± 11.21	-2.3 ± 10.69
DBP, Day 92, n=10,6,19,14,15	2.9 ± 7.39	3.8 ± 7.63	-2.2 ± 9.52	3.9 ± 9.08	-1.1 ± 10.00
DBP, Day 99, n=10,6,20,14,15	4.3 ± 10.27	3.0 ± 9.86	0.3 ± 10.80	1.3 ± 10.38	0.1 ± 10.80
DBP, Day 113, n=10,6,20,14,15	5.9 ± 9.71	2.7 ± 8.80	-1.2 ± 10.96	4.9 ± 8.28	2.9 ± 8.17
DBP, Day 141, n=10,6,20,14,15	7.5 ± 10.20	1.2 ± 8.33	0.7 ± 12.37	0.8 ± 8.51	1.1 ± 11.28
DBP, Day 169, n=10,6,19,14,15	5.8 ± 10.13	6.3 ± 11.71	0.5 ± 11.14	3.4 ± 12.07	-0.3 ± 8.83
SBP, Day 8, n=10,6,20,15,15	7.7 ± 11.17	5.0 ± 7.40	-2.6 ± 10.45	0.8 ± 14.35	2.1 ± 9.59
SBP, Day 15, n=10,6,20,14,15	8.0 ± 11.60	1.7 ± 14.42	-0.4 ± 10.02	2.1 ± 12.77	0.1 ± 11.03
SBP, Day 22, n=10,6,20,14,15	5.7 ± 13.72	1.5 ± 6.57	-2.2 ± 8.66	2.4 ± 11.54	-2.1 ± 14.36
SBP, Day 29, n=10,6,20,13,15	6.1 ± 13.20	1.7 ± 4.27	-3.1 ± 11.83	2.9 ± 16.89	1.5 ± 10.29
SBP, Day 36, n=10,6,20,14,15	0.2 ± 11.43	-0.5 ± 12.05	-5.6 ± 10.54	0.4 ± 16.21	2.1 ± 12.90
SBP, Day 43, n=10,6,20,14,15	5.6 ± 9.91	4.7 ± 13.22	-0.6 ± 11.89	1.7 ± 16.11	0.0 ± 12.53
SBP, Day 50, n=10,6,19,14,15	5.2 ± 14.88	4.7 ± 9.65	-3.4 ± 11.93	1.6 ± 12.74	-2.2 ± 11.36
SBP, Day 57, n=10,6,20,14,15	1.7 ± 13.86	2.5 ± 13.40	-4.2 ± 10.21	0.1 ± 14.91	0.9 ± 17.26
SBP, Day 64, n=10,6,20,14,15	5.1 ± 11.98	0.2 ± 9.11	-4.1 ± 9.17	1.4 ± 16.29	0.5 ± 15.50
SBP, Day 71, n=10,6,20,14,15	4.6 ± 11.98	5.0 ± 10.22	-2.2 ± 11.97	4.8 ± 17.68	4.2 ± 12.46
SBP, Day 78, n=10,6,20,14,15	5.2 ± 12.28	5.0 ± 6.16	-4.4 ± 10.09	4.1 ± 13.95	-0.1 ± 12.99
SBP, Day 85, n=10,6,20,14,15	7.2 ± 15.22	5.2 ± 9.06	-5.0 ± 12.73	6.2 ± 15.62	-3.5 ± 14.30
SBP, Day 92, n=10,6,19,14,15	5.0 ± 12.57	4.3 ± 8.50	-4.1 ± 12.60	4.6 ± 13.87	-0.1 ± 12.14
SBP, Day 99, n=10,6,20,14,15	7.1 ± 16.84	3.3 ± 15.45	-0.5 ± 14.05	1.6 ± 16.46	2.2 ± 16.34
SBP, Day 113, n=10,6,20,14,15	7.3 ± 13.30	5.7 ± 9.35	-3.2 ± 11.64	4.9 ± 12.07	6.6 ± 10.72
SBP, Day 141, n=10,6,20,14,15	10.9 ± 11.51	3.5 ± 9.81	-0.9 ± 12.77	2.9 ± 15.93	4.6 ± 16.85
SBP, Day 169, n=10,6,19,14,15	11.8 ± 12.41	9.7 ± 12.45	0.8 ± 11.61	5.1 ± 17.41	4.9 ± 12.85

PrimaryPart 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 450-Optional Follow-up)

Time frame:: Baseline (Day 1 pre-dose), Day 270 and Day 450
Reported as:: Mean · mmHg

Part 2: Change From Baseline in SBP and DBP at Indicated Time Points (Up to Day 450-Optional Follow-up)
mmHg	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
DBP, Day 270, n=1,0,0,0,0	-9.0 ± NA	—	—	—	—
DBP, Day 450, n=0,0,1,0,0	—	—	7.0 ± NA	—	—
SBP, Day 270, n=1,0,0,0,0	-18.0 ± NA	—	—	—	—
SBP, Day 450, n=0,0,1,0,0	—	—	3.0 ± NA	—	—

PrimaryPart 1: Change From Baseline in Heart Rate at Indicated Time Points

Heart rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Day 1: 1 hour, Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30
Reported as:: Mean · Beats per minute

Part 1: Change From Baseline in Heart Rate at Indicated Time Points
Beats per minute	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 1: 1 hour, n=3,3,6	4.78 ± 3.977	1.44 ± 8.694	-5.00 ± 2.530
Day 1: 2 hour, n=3,3,6	13.94 ± 12.537	4.61 ± 17.472	-2.17 ± 6.338
Day 1: 4 hour, n=3,3,6	8.11 ± 3.564	-0.22 ± 16.201	-0.17 ± 7.055
Day 1: 8 hour, n=3,3,6	5.61 ± 5.029	-5.22 ± 15.827	-0.17 ± 3.430
Day 3, n=3,3,6	12.11 ± 4.439	2.11 ± 3.657	2.50 ± 9.503
Day 8, n=2,3,6	8.00 ± 4.243	-2.89 ± 13.104	2.00 ± 10.863
Day 30, n=3,3,6	6.44 ± 16.194	3.28 ± 14.958	1.50 ± 10.134

PrimaryPart 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Beats per minute

Part 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 169-Interim Analysis)
Beats per minute	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=10,6,20,15,15	9.9 ± 9.22	6.2 ± 9.15	2.8 ± 9.92	5.7 ± 8.96	5.2 ± 8.97
Day 15, n=10,6,20,14,15	9.2 ± 13.89	-3.0 ± 6.90	3.6 ± 10.64	2.1 ± 6.92	2.3 ± 9.54
Day 22, n=10,6,20,14,15	6.3 ± 13.53	4.7 ± 7.89	3.8 ± 11.57	2.6 ± 7.78	1.6 ± 9.52
Day 29, n=10,6,20,13,15	5.5 ± 11.32	3.5 ± 7.92	1.2 ± 10.25	1.8 ± 8.99	1.3 ± 6.84
Day 36, n=10,6,20,14,15	7.8 ± 10.99	5.7 ± 11.69	2.1 ± 7.32	4.0 ± 9.97	1.5 ± 8.70
Day 43, n=10,6,20,14,15	5.1 ± 13.76	5.0 ± 11.03	2.8 ± 12.53	3.0 ± 11.57	4.8 ± 9.92
Day 50, n=10,6,19,14,15	7.9 ± 12.52	5.3 ± 11.38	2.6 ± 10.89	4.6 ± 11.47	1.5 ± 9.85
Day 57, n=10,6,20,14,15	2.9 ± 12.78	-4.0 ± 11.01	1.1 ± 10.19	2.1 ± 8.39	1.1 ± 8.33
Day 64, n=10,6,20,14,15	5.1 ± 13.24	-1.2 ± 9.43	3.0 ± 10.50	4.5 ± 11.35	1.9 ± 7.90
Day 71, n=10,6,20,14,15	4.8 ± 14.30	-2.2 ± 9.58	4.7 ± 12.01	0.6 ± 9.70	2.5 ± 9.13
Day 78, n=10,6,20,14,15	3.9 ± 13.70	0.2 ± 10.80	5.5 ± 10.31	2.4 ± 6.59	3.0 ± 7.63
Day 85, n=10,6,20,14,15	7.2 ± 15.30	-0.2 ± 10.38	3.6 ± 10.63	1.4 ± 8.04	0.5 ± 9.56
Day 92, n=10,6,19,14,15	6.4 ± 14.01	1.2 ± 8.95	4.6 ± 10.23	4.3 ± 10.29	0.5 ± 9.23
Day 99, n=10,6,20,14,15	3.9 ± 11.93	6.7 ± 11.27	4.0 ± 12.09	2.5 ± 8.23	4.5 ± 10.59
Day 113, n=10,6,20,14,15	7.5 ± 15.92	3.8 ± 9.33	1.5 ± 9.14	3.6 ± 6.50	4.8 ± 8.54
Day 141, n=10,6,20,14,15	5.7 ± 16.89	0.8 ± 14.74	3.4 ± 8.32	5.1 ± 8.77	4.3 ± 10.22
Day 169, n=10,6,19,14,15	7.9 ± 16.31	2.8 ± 13.04	4.3 ± 9.59	4.7 ± 8.72	3.1 ± 6.75

PrimaryPart 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)

Time frame:: Baseline (Day 1 pre-dose), Day 270 and Day 450
Reported as:: Mean · Beats per minute

Part 2: Change From Baseline in Heart Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)
Beats per minute	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 270, n=1,0,0,0,0	-26.0 ± NA	—	—	—	—
Day 450, n=0,0,1,0,0	—	—	-11.0 ± NA	—	—

PrimaryPart 1: Change From Baseline in Respiratory Rate at Indicated Time Points

Respiratory rate was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Days 3, 8 and 30
Reported as:: Mean · Breaths per minute

Part 1: Change From Baseline in Respiratory Rate at Indicated Time Points
Breaths per minute	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 3, n=3,3,6	-0.67 ± 0.577	-1.00 ± 1.732	-0.33 ± 1.862
Day 8, n=2,3,6	-0.50 ± 0.707	-1.00 ± 1.000	0.00 ± 2.280
Day 30, n=3,3,6	-1.33 ± 1.155	-0.67 ± 1.528	0.50 ± 2.258

PrimaryPart 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Breaths per minute

Part 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 169-Interim Analysis)
Breaths per minute	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=10,6,20,15,15	0.00 ± 1.94	-0.8 ± 4.49	0.5 ± 1.82	-0.3 ± 1.35	-0.3 ± 1.94
Day 15, n=10,6,20,14,15	-0.2 ± 2.25	-1.3 ± 5.28	-0.1 ± 0.91	-0.3 ± 1.64	-0.6 ± 2.53
Day 22, n=10,6,20,14,15	0.1 ± 2.77	-1.3 ± 5.28	0.6 ± 1.36	-0.4 ± 1.28	-0.2 ± 1.74
Day 29, n=10,6,20,13,15	-0.6 ± 2.37	0.2 ± 3.71	-0.7 ± 2.49	-0.9 ± 1.61	-0.7 ± 2.23
Day 36, n=10,6,20,14,15	-0.3 ± 3.27	-0.8 ± 5.00	0.6 ± 1.23	-0.7 ± 1.49	0.2 ± 1.90
Day 43, n=10,6,20,14,15	0.0 ± 2.36	-0.8 ± 5.00	0.2 ± 1.46	-0.3 ± 1.27	-0.1 ± 1.41
Day 50, n=10,6,19,14,15	-0.2 ± 2.44	-1.0 ± 5.51	0.4 ± 1.07	-0.5 ± 1.34	0.1 ± 1.39
Day 57, n=10,6,20,14,15	-0.3 ± 3.09	0.0 ± 3.85	0.5 ± 1.64	0.0 ± 1.04	0.2 ± 2.54
Day 64, n=10,6,20,14,15	0.0 ± 2.45	-0.7 ± 4.89	0.4 ± 1.10	-0.3 ± 1.27	0.2 ± 1.74
Day 71, n=10,6,20,14,15	-0.1 ± 2.38	-0.7 ± 4.89	0.2 ± 1.24	-0.2 ± 1.31	0.4 ± 1.50
Day 78, n=10,6,20,14,15	0.2 ± 2.78	-1.0 ± 5.51	0.5 ± 1.50	0.3 ± 1.64	-0.7 ± 2.06
Day 85, n=10,6,20,14,15	0.4 ± 2.63	-0.8 ± 5.19	0.3 ± 1.63	0.1 ± 1.49	0.0 ± 1.31
Day 92, n=10,6,19,14,15	0.4 ± 2.01	-1.3 ± 5.50	0.1 ± 1.37	-0.4 ± 1.79	0.3 ± 1.29
Day 99, n=10,6,20,14,15	0.2 ± 2.15	-1.0 ± 4.29	-0.1 ± 1.85	0.1 ± 1.54	0.5 ± 1.46
Day 113, n=10,6,20,14,15	0.7 ± 3.09	-1.0 ± 4.90	0.3 ± 1.38	-0.1 ± 1.44	0.0 ± 1.93
Day 141, n=10,6,20,14,15	0.5 ± 3.27	-1.0 ± 4.90	0.4 ± 1.19	-0.2 ± 1.42	-0.1 ± 2.03
Day 169, n=10,6,19,14,15	0.1 ± 2.69	-1.0 ± 4.90	0.6 ± 1.30	0.0 ± 1.36	0.1 ± 2.15

PrimaryPart 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)

Time frame:: Baseline (Day 1 pre-dose), Day 270 and Day 450
Reported as:: Mean · Breaths per minute

Part 2: Change From Baseline in Respiratory Rate at Indicated Time Points (Up to Day 450-Optional Follow-up)
Breaths per minute	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 270, n=1,0,0,0,0	0.0 ± NA	—	—	—	—
Day 450, n=0,0,1,0,0	—	—	2.0 ± NA	—	—

PrimaryPart 1: Change From Baseline in Body Temperature at Indicated Time Points

Body temperature was measured in a supine or semi-supine position after approximately 5 minutes rest. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Days 3, 8 and 30
Reported as:: Mean · Degrees Celsius

Part 1: Change From Baseline in Body Temperature at Indicated Time Points
Degrees Celsius	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 3, n=3,3,6	0.10 ± 0.100	0.37 ± 0.306	0.25 ± 0.345
Day 8, n=2,3,6	0.20 ± 0.283	-0.03 ± 0.351	0.08 ± 0.343
Day 30, n=3,3,6	0.10 ± 0.173	0.20 ± 0.361	0.10 ± 0.358

PrimaryPart 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Degrees Celsius

Part 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 169-Interim Analysis)
Degrees Celsius	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=10,6,20,15,15	0.24 ± 0.366	-0.02 ± 0.366	0.18 ± 0.466	-0.15 ± 0.385	-0.11 ± 0.337
Day 15, n=10,6,20,14,15	0.18 ± 0.447	-0.12 ± 0.397	0.07 ± 0.443	-0.07 ± 0.350	0.08 ± 0.428
Day 22, n=10,6,20,14,15	0.01 ± 0.692	0.07 ± 0.344	0.06 ± 0.491	0.05 ± 0.277	-0.09 ± 0.350
Day 29, n=10,6,20,13,15	0.21 ± 0.370	-0.13 ± 0.423	0.19 ± 0.433	0.00 ± 0.430	0.05 ± 0.505
Day 36, n=10,6,20,14,15	0.25 ± 0.354	0.15 ± 0.266	0.15 ± 0.501	-0.09 ± 0.421	-0.10 ± 0.606
Day 43, n=10,6,20,14,15	0.10 ± 0.365	0.05 ± 0.243	0.25 ± 0.399	-0.15 ± 0.313	-0.04 ± 0.557
Day 50, n=10,6,19,14,15	0.12 ± 0.609	0.07 ± 0.258	0.26 ± 0.352	-0.12 ± 0.428	-0.07 ± 0.746
Day 57, n=10,6,20,14,15	0.06 ± 0.395	0.02 ± 0.366	0.15 ± 0.380	-0.06 ± 0.332	0.07 ± 0.575
Day 64, n=10,6,20,14,15	0.07 ± 0.581	-0.03 ± 0.301	0.17 ± 0.386	-0.04 ± 0.393	-0.01 ± 0.536
Day 71, n=10,6,20,14,15	0.26 ± 0.599	-0.25 ± 0.207	0.26 ± 0.425	-0.14 ± 0.413	0.08 ± 0.684
Day 78, n=10,6,20,14,15	0.14 ± 0.450	-0.13 ± 0.216	0.20 ± 0.349	-0.08 ± 0.283	0.00 ± 0.679
Day 85, n=10,6,20,14,15	0.19 ± 0.716	0.08 ± 0.240	0.25 ± 0.412	-0.09 ± 0.398	0.04 ± 0.622
Day 92, n=10,6,19,14,15	-0.11 ± 0.729	-0.07 ± 0.280	0.24 ± 0.356	-0.14 ± 0.337	0.01 ± 0.645
Day 99, n=10,6,20,14,15	0.16 ± 0.443	0.15 ± 0.259	0.26 ± 0.378	-0.13 ± 0.305	-0.04 ± 0.505
Day 113, n=10,6,20,14,15	0.03 ± 0.397	0.05 ± 0.281	0.20 ± 0.419	-0.03 ± 0.327	-0.10 ± 0.535
Day 141, n=10,6,20,14,15	0.14 ± 0.556	-0.13 ± 0.320	0.14 ± 0.547	-0.19 ± 0.366	-0.03 ± 0.635
Day 169, n=10,6,19,14,15	0.12 ± 0.592	-0.08 ± 0.240	0.21 ± 0.494	-0.02 ± 0.412	0.04 ± 0.612

PrimaryPart 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 450-Optional Follow-up)

Time frame:: Baseline (Day 1 pre-dose), Day 270 and Day 450
Reported as:: Mean · Degrees Celsius

Part 2: Change From Baseline in Body Temperature at Indicated Time Points (Up to Day 450-Optional Follow-up)
Degrees Celsius	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 270, n=1,0,0,0,0	-0.40 ± NA	—	—	—	—
Day 450, n=0,0,1,0,0	—	—	0.40 ± NA	—	—

PrimaryPart 1: Number of Participants With Abnormal Findings in Physical Examination

Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.

Time frame:: Up to Day 60

No measurements were reported for this outcome.

PrimaryPart 2: Number of Participants With Abnormal Findings in Physical Examination (Up to Day 169-Interim Analysis)

Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.

Time frame:: Up to Day 169

No measurements were reported for this outcome.

PrimaryPart 2: Number of Participants With Abnormal Findings in Physical Examination (Up to Day 450-Optional Follow-up)

Physical examinations included assessment of the dermatologic, cardiovascular, respiratory, gastrointestinal, and neurological systems. Data was not collected and not captured in the database.

Time frame:: Up to Day 450

No measurements were reported for this outcome.

PrimaryPart 1: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters

Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, Activated partial thromboplastin time (aPTT), Prothrombin international normalized ratio (INR) and Prothrombin time (PT). Laboratory parameters were graded according to Division of Acquired Immune Deficiency Syndrome (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

Time frame:: Up to Day 60
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters
Participants	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Hemoglobin, Grade 1	0	0	0
Hemoglobin, Grade 2	0	0	0
Hemoglobin, Grade 3	0	0	0
Hemoglobin, Grade 4	0	0	0
Leukocyte, Grade 1	0	0	0
Leukocyte, Grade 2	0	0	0
Leukocyte, Grade 3	0	0	0
Leukocyte, Grade 4	0	0	0
Lymphocyte, Grade 1	0	0	0
Lymphocyte, Grade 2	0	0	1
Lymphocyte, Grade 3	0	0	0
Lymphocyte, Grade 4	0	0	0
Neutrophil, Grade 1	0	0	0
Neutrophil, Grade 2	0	0	0
Neutrophil, Grade 3	0	0	0
Neutrophil, Grade 4	0	0	0
Platelet, Grade 1	0	0	0
Platelet, Grade 2	0	0	0
Platelet, Grade 3	0	0	0
Platelet, Grade 4	0	0	0
aPTT, Grade 1	1	1	1
aPTT, Grade 2	0	0	0
aPTT, Grade 3	0	0	0
aPTT, Grade 4	0	0	0
Prothrombin INR, Grade 1	0	0	0
Prothrombin INR, Grade 2	0	0	0
Prothrombin INR, Grade 3	0	0	0
Prothrombin INR, Grade 4	0	0	0
PT, Grade 1	0	0	1
PT, Grade 2	0	0	0
PT, Grade 3	0	0	0
PT, Grade 4	0	0	0

PrimaryPart 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 169-Interim Analysis)

Blood samples were collected for the analysis of following hematology and coagulation parameters: Hemoglobin, Leukocytes, Lymphocytes, Neutrophils, Platelets, aPTT, Prothrombin INR and PT. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those hematology and coagulation parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

Time frame:: Up to Day 169
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 169-Interim Analysis)
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Hemoglobin, Grade 1	0	1	0	0	0
Hemoglobin, Grade 2	0	0	0	0	0
Hemoglobin, Grade 3	0	0	0	0	0
Hemoglobin, Grade 4	0	0	0	0	0
Leukocyte, Grade 1	0	0	0	1	1
Leukocyte, Grade 2	0	0	0	0	0
Leukocyte, Grade 3	0	0	0	0	0
Leukocyte, Grade 4	0	0	0	0	0
Lymphocyte, Grade 1	0	0	0	0	0
Lymphocyte, Grade 2	0	0	0	0	0
Lymphocyte, Grade 3	0	0	0	0	0
Lymphocyte, Grade 4	0	0	0	0	0
Neutrophil, Grade 1	0	0	0	1	3
Neutrophil, Grade 2	0	0	0	0	0
Neutrophil, Grade 3	0	0	0	0	0
Neutrophil, Grade 4	0	0	0	0	0
Platelet, Grade 1	0	0	1	0	2
Platelet, Grade 2	0	0	0	0	1
Platelet, Grade 3	0	0	0	0	0
Platelet, Grade 4	0	0	0	0	0
aPTT, Grade 1	1	2	5	4	5
aPTT, Grade 2	0	0	0	0	1
aPTT, Grade 3	0	0	0	0	0
aPTT, Grade 4	0	0	0	0	0
Prothrombin INR, Grade 1	0	0	3	0	1
Prothrombin INR, Grade 2	0	0	0	0	1
Prothrombin INR, Grade 3	0	0	0	0	0
Prothrombin INR, Grade 4	0	0	0	0	0
PT, Grade 1	0	0	6	0	5
PT, Grade 2	0	0	0	0	0
PT, Grade 3	0	0	0	0	1
PT, Grade 4	0	0	0	0	0

PrimaryPart 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 450-Optional Follow-up)

Time frame:: Up to Day 450
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Hematology and Coagulation Parameters (Up to Day 450-Optional Follow-up)
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Hemoglobin, Grade 1	0	1	0	0	0
Hemoglobin, Grade 2	0	0	0	0	0
Hemoglobin, Grade 3	0	0	0	0	0
Hemoglobin, Grade 4	0	0	0	0	0
Leukocyte, Grade 1	0	0	0	1	1
Leukocyte, Grade 2	0	0	0	0	0
Leukocyte, Grade 3	0	0	0	0	0
Leukocyte, Grade 4	0	0	0	0	0
Lymphocyte, Grade 1	0	0	0	0	0
Lymphocyte, Grade 2	0	0	0	0	0
Lymphocyte, Grade 3	0	0	0	0	0
Lymphocyte, Grade 4	0	0	0	0	0
Neutrophil, Grade 1	0	0	0	1	3
Neutrophil, Grade 2	0	0	0	0	0
Neutrophil, Grade 3	0	0	0	0	0
Neutrophil, Grade 4	0	0	0	0	0
Platelet, Grade 1	0	0	1	0	2
Platelet, Grade 2	0	0	0	0	1
Platelet, Grade 3	0	0	0	0	0
Platelet, Grade 4	0	0	0	0	0
aPTT, Grade 1	1	2	5	4	5
aPTT, Grade 2	0	0	0	0	1
aPTT, Grade 3	0	0	0	0	0
aPTT, Grade 4	0	0	0	0	0
Prothrombin INR, Grade 1	0	0	3	0	1
Prothrombin INR, Grade 2	0	0	0	0	1
Prothrombin INR, Grade 3	0	0	0	0	0
Prothrombin INR, Grade 4	0	0	0	0	0
PT, Grade 1	0	1	6	0	5
PT, Grade 2	0	0	0	0	0
PT, Grade 3	0	0	0	0	1
PT, Grade 4	0	0	0	0	0

PrimaryPart 1: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points

Blood samples were collected from participants to assess complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 60
Reported as:: Mean · Milligram per deciliter

Part 1: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points
Milligram per deciliter	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Complement C3	-8.7 ± 11.24	-13.0 ± 3.00	-16.3 ± 7.74
Complement C4	-2.0 ± 2.00	-2.3 ± 0.58	-4.2 ± 3.76

PrimaryPart 2: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 169
Reported as:: Mean · Milligram per deciliter

Part 2: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points (Up to Day 169-Interim Analysis)
Milligram per deciliter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Complement C3	-11.0 ± 16.10	-13.5 ± 9.14	-11.3 ± 10.38	-10.9 ± 15.19	-17.7 ± 13.98
Complement C4	-3.5 ± 2.12	-4.7 ± 4.41	-3.8 ± 2.57	-3.4 ± 2.13	-5.6 ± 3.07

PrimaryPart 2: Change From Baseline in Complement C3 and Complement C4 Level at Indicated Time Points (Up to Day 450-Optional Follow-up)

Blood samples were planned to be collected from participants to evaluate change from Baseline in complement C3 and complement C4 levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450

No measurements were reported for this outcome.

PrimaryPart 1: Change From Baseline in Complement Bb Level at Indicated Time Points

Blood samples were collected from participants to assess complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 60
Reported as:: Mean · Milligram per liter

Part 1: Change From Baseline in Complement Bb Level at Indicated Time Points
Milligram per liter	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Change From Baseline in Complement Bb Level at Indicated Time Points	0.193 ± 0.2409	0.023 ± 0.0950	0.150 ± 0.2119

PrimaryPart 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 169
Reported as:: Mean · Milligram per liter

Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 169-Interim Analysis)
Milligram per liter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 169-Interim Analysis)	0.245 ± 0.319	0.198 ± 0.143	0.315 ± 0.740	0.115 ± 0.222	-0.007 ± 0.30

PrimaryPart 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 450-Optional Follow-up)

Blood samples were collected from participants to evaluate change from Baseline in complement Bb levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450
Reported as:: Mean · Milligram per liter

Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 450-Optional Follow-up)
Milligram per liter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Change From Baseline in Complement Bb Level at Indicated Time Points (Up to Day 450-Optional Follow-up)	0.304 ± 0.295	0.365 ± 0.269	0.436 ± 0.679	0.173 ± 0.213	0.107 ± 0.367

PrimaryPart 1: Change From Baseline in Complement C5a Level at Indicated Time Points

Blood samples were collected from participants to assess complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 60
Reported as:: Mean · Microgram per liter

Part 1: Change From Baseline in Complement C5a Level at Indicated Time Points
Microgram per liter	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Change From Baseline in Complement C5a Level at Indicated Time Points	1.497 ± 0.6306	0.373 ± 0.9952	-1.267 ± 5.7581

PrimaryPart 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 169
Reported as:: Mean · Microgram per liter

Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 169-Interim Analysis)
Microgram per liter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 169-Interim Analysis)	1.112 ± 1.481	0.860 ± 1.625	1.781 ± 2.524	0.353 ± 1.323	-0.093 ± 1.54

PrimaryPart 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 450-Optional Follow-up)

Blood samples were collected from participants to evaluate change from Baseline in complement C5a levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450
Reported as:: Mean · Milligrams per liter

Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 450-Optional Follow-up)
Milligrams per liter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Change From Baseline in Complement C5a Level at Indicated Time Points (Up to Day 450-Optional Follow-up)	1.324 ± 1.415	2.053 ± 3.456	2.040 ± 2.481	0.470 ± 1.205	0.567 ± 1.354

PrimaryPart 1: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters

Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low) and Urate. Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

Time frame:: Up to Day 60
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters
Participants	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Alanine aminotransferase, Grade 1	0	0
Alanine aminotransferase, Grade 2	0	1
Alanine aminotransferase, Grade 3	0	0
Alanine aminotransferase, Grade 4	0	0
Albumin, Grade 1	0	0
Albumin, Grade 2	0	0
Albumin, Grade 3	0	0
Albumin, Grade 4	0	0
Alkaline phosphatase, Grade 1	0	0
Alkaline phosphatase, Grade 2	0	0
Alkaline phosphatase, Grade 3	0	0
Alkaline phosphatase, Grade 4	0	0
Aspartate aminotransferase, Grade 1	0	1
Aspartate aminotransferase, Grade 2	0	0
Aspartate aminotransferase, Grade 3	0	0
Aspartate aminotransferase, Grade 4	0	0
Bilirubin, Grade 1	1	1
Bilirubin, Grade 2	0	0
Bilirubin, Grade 3	0	0
Bilirubin, Grade 4	0	0
Calcium (high), Grade 1	0	1
Calcium (high), Grade 2	0	0
Calcium (high), Grade 3	0	0
Calcium (high), Grade 4	0	0
Calcium (low), Grade 1	0	0
Calcium (low), Grade 2	0	0
Calcium (low), Grade 3	0	0
Calcium (low), Grade 4	0	0
Creatine kinase, Grade 1	1	0
Creatine kinase, Grade 2	0	0
Creatine kinase, Grade 3	0	0
Creatine kinase, Grade 4	0	0
Creatinine, Grade 1	0	0
Creatinine, Grade 2	0	0
Creatinine, Grade 3	0	0
Creatinine, Grade 4	0	0
Glucose (high), Grade 1	0	1
Glucose (high), Grade 2	0	0
Glucose (high), Grade 3	0	0
Glucose (high), Grade 4	0	0
Glucose (low), Grade 1	0	0
Glucose (low), Grade 2	0	0
Glucose (low), Grade 3	0	0
Glucose (low), Grade 4	0	0
Magnesium, Grade 1	0	0
Magnesium, Grade 2	0	0
Magnesium, Grade 3	0	0
Magnesium, Grade 4	0	0
Phosphate, Grade 1	0	0
Phosphate, Grade 2	0	0
Phosphate, Grade 3	0	0
Phosphate, Grade 4	0	0
Potassium (high), Grade 1	0	0
Potassium (high), Grade 2	0	0
Potassium (high), Grade 3	0	0
Potassium (high), Grade 4	0	0
Potassium (low), Grade 1	0	0
Potassium (low), Grade 2	0	0
Potassium (low), Grade 3	0	0
Potassium (low), Grade 4	0	0
Sodium (high), Grade 1	0	0
Sodium (high), Grade 2	0	0
Sodium (high), Grade 3	0	0
Sodium (high), Grade 4	0	0
Sodium (low), Grade 1	0	0
Sodium (low), Grade 2	0	0
Sodium (low), Grade 3	0	0
Sodium (low), Grade 4	0	0
Urate, Grade 1	1	0
Urate, Grade 2	0	0
Urate, Grade 3	0	0
Urate, Grade 4	0	0

PrimaryPart 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 169-Interim Analysis)

Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low), Urate and glomerular filtration rate (GFR). Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

Time frame:: Up to Day 169
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 169-Interim Analysis)
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Alanine aminotransferase, Grade 1	1	0	2	0	4
Alanine aminotransferase, Grade 2	0	0	0	1	1
Alanine aminotransferase, Grade 3	0	0	0	0	0
Alanine aminotransferase, Grade 4	0	0	0	0	0
Albumin, Grade 1	0	0	0	0	0
Albumin, Grade 2	0	0	0	0	0
Albumin, Grade 3	0	0	0	0	0
Albumin, Grade 4	0	0	0	0	0
Alkaline phosphatase, Grade 1	0	0	1	0	0
Alkaline phosphatase, Grade 2	0	0	0	0	0
Alkaline phosphatase, Grade 3	0	0	0	0	0
Alkaline phosphatase, Grade 4	0	0	0	0	0
Aspartate aminotransferase, Grade 1	1	0	2	1	1
Aspartate aminotransferase, Grade 2	1	0	0	0	0
Aspartate aminotransferase, Grade 3	0	0	0	0	0
Aspartate aminotransferase, Grade 4	0	0	0	0	0
Bilirubin, Grade 1	1	1	1	0	0
Bilirubin, Grade 2	0	0	0	0	1
Bilirubin, Grade 3	0	0	0	0	0
Bilirubin, Grade 4	0	0	0	0	0
Calcium (high), Grade 1	0	0	1	1	1
Calcium (high), Grade 2	0	0	0	0	0
Calcium (high), Grade 3	0	0	0	0	0
Calcium (high), Grade 4	0	0	0	0	0
Calcium (low), Grade 1	0	0	0	0	0
Calcium (low), Grade 2	0	0	0	0	0
Calcium (low), Grade 3	0	0	2	0	0
Calcium (low), Grade 4	0	0	0	0	0
Creatine kinase, Grade 1	0	0	0	1	2
Creatine kinase, Grade 2	0	0	0	0	0
Creatine kinase, Grade 3	0	0	0	1	0
Creatine kinase, Grade 4	2	0	0	0	0
Creatinine, Grade 1	0	0	0	0	0
Creatinine, Grade 2	0	0	0	0	0
Creatinine, Grade 3	1	1	1	0	1
Creatinine, Grade 4	0	0	0	0	0
Glucose (high), Grade 1	6	5	10	6	7
Glucose (high), Grade 2	2	0	0	3	3
Glucose (high), Grade 3	0	0	0	1	1
Glucose (high), Grade 4	0	0	0	0	0
Glucose (low), Grade 1	0	0	0	0	1
Glucose (low), Grade 2	1	0	0	0	0
Glucose (low), Grade 3	0	0	0	0	0
Glucose (low), Grade 4	0	0	0	0	0
Magnesium, Grade 1	0	0	2	0	0
Magnesium, Grade 2	0	0	0	0	0
Magnesium, Grade 3	0	0	0	0	0
Magnesium, Grade 4	0	0	0	0	0
Phosphate, Grade 1	1	1	0	1	4
Phosphate, Grade 2	1	1	1	1	0
Phosphate, Grade 3	0	0	0	0	0
Phosphate, Grade 4	0	0	0	0	0
Potassium (high), Grade 1	0	0	0	0	1
Potassium (high), Grade 2	0	0	0	0	0
Potassium (high), Grade 3	0	0	0	0	0
Potassium (high), Grade 4	0	0	0	0	0
Potassium (low), Grade 1	0	0	2	0	0
Potassium (low), Grade 2	0	0	1	0	0
Potassium (low), Grade 3	0	0	0	0	0
Potassium (low), Grade 4	0	0	0	0	0
Sodium (high), Grade 1	3	0	2	1	5
Sodium (high), Grade 2	0	0	0	0	0
Sodium (high), Grade 3	0	0	0	0	0
Sodium (high), Grade 4	0	0	0	0	0
Sodium (low), Grade 1	0	0	1	0	0
Sodium (low), Grade 2	0	0	0	0	0
Sodium (low), Grade 3	0	0	0	0	0
Sodium (low), Grade 4	0	0	0	0	0
Urate, Grade 1	2	1	1	8	3
Urate, Grade 2	0	0	0	0	0
Urate, Grade 3	0	0	0	0	0
Urate, Grade 4	0	0	0	0	0
GFR, Grade 1	0	0	0	0	0
GFR, Grade 2	0	0	0	0	0
GFR, Grade 3	0	0	0	0	0
GFR, Grade 4	0	0	0	0	0

PrimaryPart 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 450-Optional Follow-up)

Blood samples were collected for the analysis of following clinical chemistry parameters: Alanine aminotransferase, Albumin, Alkaline phosphatase, Aspartate aminotransferase, Bilirubin, Calcium (high), Calcium (low), Creatine kinase, Creatinine, Glucose (high), Glucose (low), Magnesium, Phosphate, Potassium (high), Potassium (low), Sodium (high), Sodium (low), Urate and glomerular filtration rate (GFR). Laboratory parameters were graded according to DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Grade 1: mild; Grade 2: moderate; Grade 3: severe; and Grade 4: potentially life-threatening consequences. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Only those clinical chemistry parameters with maximum post-Baseline grade (Grade 1 to Grade 4) have been presented.

Time frame:: Up to Day 450
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Maximum Post-Baseline Grade by Category in Clinical Chemistry Parameters (Up to Day 450-Optional Follow-up)
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Alanine aminotransferase, Grade 1	2	0	3	0	4
Alanine aminotransferase, Grade 2	0	0	0	1	1
Alanine aminotransferase, Grade 3	0	0	0	0	0
Alanine aminotransferase, Grade 4	0	0	0	0	0
Albumin, Grade 1	0	0	0	0	0
Albumin, Grade 2	0	0	0	0	0
Albumin, Grade 3	0	0	0	0	0
Albumin, Grade 4	0	0	0	0	0
Alkaline phosphatase, Grade 1	0	0	2	0	0
Alkaline phosphatase, Grade 2	0	0	0	0	0
Alkaline phosphatase, Grade 3	0	0	0	0	0
Alkaline phosphatase, Grade 4	0	0	0	0	0
Aspartate aminotransferase, Grade 1	1	0	2	1	1
Aspartate aminotransferase, Grade 2	1	0	0	0	0
Aspartate aminotransferase, Grade 3	0	0	0	0	0
Aspartate aminotransferase, Grade 4	0	0	0	0	0
Bilirubin, Grade 1	1	1	1	0	0
Bilirubin, Grade 2	0	0	0	0	1
Bilirubin, Grade 3	0	0	0	0	0
Bilirubin, Grade 4	0	0	0	0	0
Calcium (high), Grade 1	0	0	1	1	2
Calcium (high), Grade 2	0	0	0	0	0
Calcium (high), Grade 3	0	0	0	0	0
Calcium (high), Grade 4	0	0	0	0	0
Calcium (low), Grade 1	0	0	0	0	0
Calcium (low), Grade 2	0	0	0	0	0
Calcium (low), Grade 3	0	0	2	0	0
Calcium (low), Grade 4	0	0	0	0	0
Creatine kinase, Grade 1	0	1	0	2	2
Creatine kinase, Grade 2	0	0	0	0	0
Creatine kinase, Grade 3	0	0	0	1	0
Creatine kinase, Grade 4	2	0	0	0	0
Creatinine, Grade 1	0	0	0	0	0
Creatinine, Grade 2	0	0	0	0	0
Creatinine, Grade 3	1	1	1	0	1
Creatinine, Grade 4	0	0	0	0	0
Glucose (high), Grade 1	6	5	11	6	7
Glucose (high), Grade 2	2	0	0	3	3
Glucose (high), Grade 3	0	0	0	1	1
Glucose (high), Grade 4	0	0	0	0	0
Glucose (low), Grade 1	0	0	1	0	1
Glucose (low), Grade 2	1	0	0	0	0
Glucose (low), Grade 3	0	0	0	0	0
Glucose (low), Grade 4	0	0	0	0	0
Magnesium, Grade 1	0	0	2	0	0
Magnesium, Grade 2	0	0	0	0	0
Magnesium, Grade 3	0	0	0	0	0
Magnesium, Grade 4	0	0	0	0	0
Phosphate, Grade 1	2	1	0	1	4
Phosphate, Grade 2	1	1	1	1	0
Phosphate, Grade 3	0	0	0	0	0
Phosphate, Grade 4	0	0	0	0	0
Potassium (high), Grade 1	0	0	0	0	1
Potassium (high), Grade 2	0	0	0	0	0
Potassium (high), Grade 3	0	0	0	0	0
Potassium (high), Grade 4	0	0	0	0	0
Potassium (low), Grade 1	0	0	2	0	0
Potassium (low), Grade 2	0	0	1	0	0
Potassium (low), Grade 3	0	0	0	0	0
Potassium (low), Grade 4	0	0	0	0	0
Sodium (high), Grade 1	3	0	2	1	6
Sodium (high), Grade 2	0	0	0	0	0
Sodium (high), Grade 3	0	0	0	0	0
Sodium (high), Grade 4	0	0	0	0	0
Sodium (low), Grade 1	0	0	1	0	0
Sodium (low), Grade 2	0	0	0	0	0
Sodium (low), Grade 3	0	0	0	0	0
Sodium (low), Grade 4	0	0	0	0	0
Urate, Grade 1	2	1	2	8	3
Urate, Grade 2	0	0	0	0	0
Urate, Grade 3	0	0	0	0	0
Urate, Grade 4	0	0	0	0	0
GFR, Grade 1	0	0	0	0	0
GFR, Grade 2	0	0	0	0	0
GFR, Grade 3	0	0	0	0	0
GFR, Grade 4	0	0	0	0	0

PrimaryPart 1: Change From Baseline in Urine Albumin at Indicated Time Points

Urine samples were collected from participants to assess urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Days 8, 30 and Follow-up (Day 60)
Reported as:: Mean · Milligram per deciliter

Part 1: Change From Baseline in Urine Albumin at Indicated Time Points
Milligram per deciliter	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 8	-0.090 ± 0.1559	0.000 ± 0.0000	-0.003 ± 0.0082
Day 30	-0.090 ± 0.1559	0.000 ± 0.0000	-0.003 ± 0.0082
Follow-up (Day 60)	-0.083 ± 0.1620	0.000 ± 0.0000	-0.003 ± 0.0082

PrimaryPart 2: Change From Baseline in Urine Albumin at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 15, 29, 43, 57, 71, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Milligram per deciliter

Part 2: Change From Baseline in Urine Albumin at Indicated Time Points (Up to Day 169-Interim Analysis)
Milligram per deciliter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 15, n=10,6,20,14,14	0.484 ± 1.5305	0.000 ± 0.0000	0.004 ± 0.0157	-0.044 ± 0.3593	0.054 ± 2.1129
Day 29, n=10,6,20,13,15	-0.038 ± 0.1202	0.000 ± 0.0000	0.102 ± 0.4265	-0.100 ± 0.4276	-0.293 ± 1.2710
Day 43, n=9,6,20,14,15	-0.076 ± 0.2267	0.027 ± 0.0653	0.047 ± 0.2247	1.356 ± 5.1498	-0.263 ± 1.2876
Day 57, n=10,6,20,14,15	-0.068 ± 0.2150	0.252 ± 0.6165	0.157 ± 0.6699	7.142 ± 27.1610	-0.345 ± 1.2457
Day 71, n=10,6,20,14,15	-0.068 ± 0.2150	0.147 ± 0.3593	0.067 ± 0.2858	-0.108 ± 0.4036	-0.276 ± 1.2739
Day 85, n=10,6,20,14,15	-0.068 ± 0.2150	0.260 ± 0.6369	0.105 ± 0.3408	-0.028 ± 0.5206	-0.249 ± 1.2805
Day 92, n=10,6,19,14,15	0.386 ± 1.4751	0.088 ± 0.1613	0.031 ± 0.1811	-0.034 ± 0.1256	-0.113 ± 1.6274
Day 99, n=10,6,20,14,15	-0.068 ± 0.2150	0.000 ± 0.0000	0.287 ± 1.1198	-0.028 ± 0.4733	-0.307 ± 1.2558
Day 113, n=10,6,19,13,15	-0.020 ± 0.2766	0.057 ± 0.1388	0.376 ± 1.1353	-0.060 ± 0.4801	-0.342 ± 1.2507
Day 141, n=10,6,20,14,15	-0.068 ± 0.2150	0.000 ± 0.0000	0.061 ± 0.2350	0.014 ± 0.3879	-0.317 ± 1.2571
Day 169, n=10,6,19,14,15	-0.068 ± 0.2150	0.223 ± 0.5471	0.436 ± 1.3939	-0.095 ± 0.3555	-0.317 ± 1.2678

PrimaryPart 2: Change From Baseline in Urine Albumin at Indicated Time Points (Up to Day 450-Optional Follow-up)

Urine samples were planned to be collected from participants to evaluate change from Baseline in urine albumin levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450

No measurements were reported for this outcome.

PrimaryPart 1: Change From Baseline in Urine Creatinine at Indicated Time Points

Urine samples were collected from participants to assess urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Days 8, 30 and Follow-up (Day 60)
Reported as:: Mean · Millimoles per liter

Part 1: Change From Baseline in Urine Creatinine at Indicated Time Points
Millimoles per liter	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 8	-6.333 ± 4.8003	-7.500 ± 10.8586	-0.500 ± 5.4468
Day 30	-4.133 ± 7.2947	-7.467 ± 12.1763	-0.533 ± 5.5824
Follow-up (Day 60)	1.800 ± 14.5000	-12.500 ± 12.4386	-1.917 ± 6.3031

PrimaryPart 2: Change From Baseline in Urine Creatinine at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 15, 29, 43, 57, 71, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Millimoles per liter

Part 2: Change From Baseline in Urine Creatinine at Indicated Time Points (Up to Day 169-Interim Analysis)
Millimoles per liter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 15, n=10,6,20,14,14	1.250 ± 3.9769	3.100 ± 7.2812	1.620 ± 5.9265	0.621 ± 6.6401	1.129 ± 7.8266
Day 29, n=10,6,20,13,15	-0.250 ± 8.1437	-1.183 ± 2.2516	1.645 ± 4.2540	0.185 ± 6.7815	0.307 ± 6.2369
Day 43, n=9,6,20,14,15	-1.989 ± 7.6522	1.933 ± 3.4518	-0.615 ± 3.4238	-1.614 ± 8.1636	-0.160 ± 5.5418
Day 57, n=10,6,20,14,15	0.730 ± 6.3381	4.283 ± 6.9975	-0.005 ± 4.1111	-2.336 ± 7.3438	-0.707 ± 5.1370
Day 71, n=10,6,20,14,15	-0.420 ± 8.0098	3.383 ± 4.1427	1.625 ± 7.4370	-2.571 ± 5.5116	-0.560 ± 4.8550
Day 85, n=10,6,20,14,15	-0.380 ± 5.2742	-0.350 ± 3.1507	1.335 ± 6.3596	-1.500 ± 7.3661	0.127 ± 5.1497
Day 92, n=10,6,19,14,15	1.900 ± 6.0566	3.367 ± 4.6224	1.353 ± 5.6700	-0.679 ± 8.1936	-1.013 ± 5.4487
Day 99, n=10,6,20,14,15	1.180 ± 6.5445	-0.833 ± 2.7500	1.775 ± 4.6852	-1.593 ± 7.3409	0.020 ± 5.1870
Day 113, n=10,6,19,13,15	1.640 ± 12.4484	-0.200 ± 1.9819	0.395 ± 4.2339	-0.515 ± 8.9447	-1.273 ± 4.9312
Day 141, n=10,6,20,14,15	-3.440 ± 8.1759	-0.150 ± 4.7218	1.090 ± 4.9374	0.464 ± 7.7548	-0.713 ± 5.9545
Day 169, n=10,6,19,14,15	-1.520 ± 6.5367	2.150 ± 2.6251	2.484 ± 5.4097	0.386 ± 7.7418	-2.980 ± 5.0428

PrimaryPart 2: Change From Baseline in Urine Creatinine at Indicated Time Points (Up to Day 450-Optional Follow-up)

Urine samples were planned to be collected from participants to evaluate change from Baseline in urine creatinine levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450

No measurements were reported for this outcome.

PrimaryPart 1: Change From Baseline in Urine Potential of Hydrogen (pH) at Indicated Time Points

Urine samples were collected from participants to assess urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)
Reported as:: Mean · pH

Part 1: Change From Baseline in Urine Potential of Hydrogen (pH) at Indicated Time Points
pH	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 3	0.333 ± 0.2887	0.167 ± 0.2887	0.083 ± 0.4916
Day 8	0.000 ± 0.0000	1.000 ± 0.5000	0.333 ± 0.6831
Day 30	0.167 ± 0.2887	0.333 ± 1.0408	0.167 ± 0.5164
Follow-up (Day 60)	0.167 ± 0.2887	0.500 ± 1.0000	0.250 ± 0.5244

PrimaryPart 2: Change From Baseline in Urine pH at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · pH

Part 2: Change From Baseline in Urine pH at Indicated Time Points (Up to Day 169-Interim Analysis)
pH	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=10,6,19,14,13	0.300 ± 0.9487	-0.333 ± 0.8165	-0.132 ± 0.7040	-0.071 ± 0.4746	-0.077 ± 0.6405
Day 15, n=10,6,19,13,14	0.200 ± 0.6325	-0.500 ± 1.0488	-0.026 ± 0.6341	-0.154 ± 0.6887	0.000 ± 0.5547
Day 22, n=9,6,19,13,14	0.333 ± 0.7071	-0.667 ± 0.5164	-0.211 ± 0.7133	-0.308 ± 0.6304	-0.143 ± 1.0271
Day 29, n=10,6,19,12,14	0.200 ± 0.6325	-0.167 ± 0.7528	0.000 ± 0.4714	0.000 ± 0.7385	-0.286 ± 0.6112
Day 36, n=10,6,19,13,14	0.050 ± 0.8960	-0.333 ± 1.0328	-0.105 ± 0.4588	-0.077 ± 0.6405	-0.107 ± 0.7888
Day 43, n=9,6,19,13,14	0.111 ± 0.7817	-0.167 ± 0.7528	0.000 ± 0.5774	0.077 ± 0.8623	-0.214 ± 0.6993
Day 50, n=9,6,18,13,14	0.000 ± 0.7071	-0.167 ± 1.1690	0.000 ± 0.5941	-0.231 ± 0.7250	0.036 ± 0.8872
Day 57, n=10,6,19,13,14	0.100 ± 0.9944	-0.167 ± 0.7528	0.000 ± 0.4714	0.077 ± 0.7596	-0.071 ± 0.4746
Day 64, n=10,6,19,13,14	0.200 ± 0.6325	-0.167 ± 0.7528	-0.105 ± 0.6578	0.000 ± 0.5774	-0.214 ± 0.5789
Day 71, n=10,6,19,13,14	0.200 ± 0.7888	-0.167 ± 0.7528	0.000 ± 0.4714	0.077 ± 0.6405	-0.071 ± 0.7300
Day 78, n=10,6,19,13,14	0.100 ± 0.5676	0.000 ± 0.6325	-0.053 ± 0.5243	0.000 ± 0.7071	0.143 ± 0.7703
Day 85, n=10,6,19,13,14	0.000 ± 1.0541	0.000 ± 0.8944	-0.105 ± 0.6578	0.000 ± 0.5774	-0.214 ± 0.5789
Day 92, n=10,6,18,13,14	0.000 ± 0.8165	0.167 ± 0.4082	0.056 ± 0.5393	0.000 ± 0.7071	-0.214 ± 0.6993
Day 99, n=10,6,19,13,14	0.100 ± 0.5676	0.167 ± 0.9832	-0.158 ± 0.5015	-0.154 ± 0.9871	-0.214 ± 0.5789
Day 113, n=10,6,17,12,14	0.000 ± 0.8165	0.000 ± 0.6325	-0.176 ± 0.5286	0.000 ± 0.9535	-0.143 ± 0.9493
Day 141, n=10,6,19,13,14	0.300 ± 0.6749	0.167 ± 0.7528	0.053 ± 0.6213	-0.077 ± 0.6405	-0.143 ± 0.7703
Day 169, n=10,6,18,13,14	-0.200 ± 0.7888	0.000 ± 0.6325	-0.278 ± 0.4609	0.077 ± 0.6405	-0.071 ± 0.4746

PrimaryPart 2: Change From Baseline in Urine pH at Indicated Time Points (Up to Day 450-Optional Follow-up)

Urine samples were planned to be collected from participants to evaluate change from Baseline in urine pH levels. Urine pH is an acid-base measurement. pH is measured on a numeric scale ranging from 0 to 14; values on the scale refer to the degree of alkalinity or acidity. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450

No measurements were reported for this outcome.

PrimaryPart 1: Change From Baseline in Urine Specific Gravity at Indicated Time Points

Urine samples were collected from participants to assess urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)
Reported as:: Mean · Ratio

Part 1: Change From Baseline in Urine Specific Gravity at Indicated Time Points
Ratio	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 3	0.005 ± 0.0091	-0.011 ± 0.0061	-0.001 ± 0.0029
Day 8	0.003 ± 0.0081	-0.014 ± 0.0151	0.000 ± 0.0087
Day 30	-0.001 ± 0.0112	-0.013 ± 0.0175	0.000 ± 0.0066
Follow-up (Day 60)	0.006 ± 0.0125	-0.014 ± 0.0123	-0.001 ± 0.0079

PrimaryPart 2: Change From Baseline in Urine Specific Gravity at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Ratio

Part 2: Change From Baseline in Urine Specific Gravity at Indicated Time Points (Up to Day 169-Interim Analysis)
Ratio	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=10,6,19,15,14	-0.001 ± 0.0080	0.004 ± 0.0049	-0.001 ± 0.0060	0.000 ± 0.0055	0.000 ± 0.0063
Day 15, n=10,6,20,14,15	0.002 ± 0.0054	0.004 ± 0.0085	0.001 ± 0.0058	0.000 ± 0.0083	0.000 ± 0.0088
Day 22, n=10,6,20,14,15	-0.001 ± 0.0082	0.003 ± 0.0045	-0.001 ± 0.0073	0.001 ± 0.0063	0.000 ± 0.0070
Day 29, n=10,6,20,13,15	0.001 ± 0.0098	-0.001 ± 0.0060	0.001 ± 0.0052	0.000 ± 0.0051	0.001 ± 0.0064
Day 36, n=10,6,20,14,15	0.004 ± 0.0100	0.002 ± 0.0067	-0.002 ± 0.0065	-0.001 ± 0.0067	-0.003 ± 0.0082
Day 43, n=9,6,20,14,15	-0.003 ± 0.0098	0.002 ± 0.0060	0.000 ± 0.0050	-0.001 ± 0.0070	0.000 ± 0.0064
Day 50, n=9,6,19,14,15	-0.003 ± 0.0081	0.002 ± 0.0079	-0.002 ± 0.0065	-0.001 ± 0.0095	0.000 ± 0.0076
Day 57, n=10,6,20,14,15	0.000 ± 0.0082	0.005 ± 0.0078	-0.001 ± 0.0044	-0.003 ± 0.0073	0.000 ± 0.0069
Day 64, n=10,6,20,14,15	-0.002 ± 0.0103	0.003 ± 0.0093	0.000 ± 0.0055	-0.001 ± 0.0059	0.001 ± 0.0052
Day 71, n=10,6,20,14,15	-0.001 ± 0.0100	0.003 ± 0.0052	0.001 ± 0.0072	-0.003 ± 0.0059	0.001 ± 0.0053
Day 78, n=10,6,20,14,15	-0.002 ± 0.0069	0.002 ± 0.0022	0.000 ± 0.0078	-0.004 ± 0.0085	-0.001 ± 0.0081
Day 85, n=10,6,20,14,15	0.001 ± 0.0074	-0.002 ± 0.0023	0.000 ± 0.0057	-0.003 ± 0.0074	0.000 ± 0.0058
Day 92, n=10,6,19,14,15	0.001 ± 0.0070	0.002 ± 0.0051	0.001 ± 0.0063	-0.002 ± 0.0079	0.000 ± 0.0058
Day 99, n=10,6,20,14,15	0.002 ± 0.0081	-0.001 ± 0.0039	0.001 ± 0.0050	-0.002 ± 0.0061	0.000 ± 0.0048
Day 113, n=10,6,18,13,15	0.000 ± 0.0101	0.000 ± 0.0043	0.000 ± 0.0054	-0.001 ± 0.0090	-0.001 ± 0.0047
Day 141, n=10,6,20,14,15	-0.003 ± 0.0107	-0.001 ± 0.0068	0.001 ± 0.0056	0.000 ± 0.0086	0.000 ± 0.0066
Day 169, n=10,6,19,14,15	-0.001 ± 0.0072	0.002 ± 0.0053	0.001 ± 0.0047	0.000 ± 0.0077	-0.003 ± 0.0052

PrimaryPart 2: Change From Baseline in Urine Specific Gravity at Indicated Time Points (Up to Day 450-Optional Follow-up)

Urine samples were planned to be collected from participants to evaluate change from Baseline in urine specific gravity. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450

No measurements were reported for this outcome.

PrimaryPart 1: Change From Baseline in Urobilinogen at Indicated Time Points

Urine samples were collected from participants to assess urobilinogen levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose), Days 3, 8, 30 and Follow-up (Day 60)
Reported as:: Mean · Milligram per deciliter

Part 1: Change From Baseline in Urobilinogen at Indicated Time Points
Milligram per deciliter	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 3	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000
Day 8	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000
Day 30	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000
Follow-up (Day 60)	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000

PrimaryPart 2: Change From Baseline in Urobilinogen at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Milligram per deciliter

Part 2: Change From Baseline in Urobilinogen at Indicated Time Points (Up to Day 169-Interim Analysis)
Milligram per deciliter	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=10,6,19,15,14	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000
Day 15, n=10,6,20,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.090 ± 0.4025	0.000 ± 0.0000	0.000 ± 0.0000
Day 22, n=10,6,20,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000
Day 29, n=10,6,20,13,15	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.120 ± 0.4648
Day 36, n=10,6,20,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.120 ± 0.4648
Day 43, n=9,6,20,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.180 ± 0.5540	0.000 ± 0.0000	0.000 ± 0.0000
Day 50, n=9,6,19,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000
Day 57, n=10,6,20,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.090 ± 0.4025	0.000 ± 0.0000	0.000 ± 0.0000
Day 64, n=10,6,20,14,15	0.180 ± 0.5692	0.000 ± 0.0000	0.180 ± 0.5540	0.000 ± 0.0000	0.240 ± 0.6334
Day 71, n=10,6,19,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.240 ± 0.6334
Day 78, n=10,6,20,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.180 ± 0.5540	0.000 ± 0.0000	0.000 ± 0.0000
Day 85, n=10,6,20,14,14	0.000 ± 0.0000	0.000 ± 0.0000	0.090 ± 0.4025	0.000 ± 0.0000	0.000 ± 0.0000
Day 92, n=10,6,19,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.189 ± 0.5675	0.000 ± 0.0000	0.000 ± 0.0000
Day 99, n=10,6,19,14,15	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.000 ± 0.0000	0.120 ± 0.4648
Day 113, n=10,6,17,13,15	0.000 ± 0.0000	0.000 ± 0.0000	0.106 ± 0.4366	0.000 ± 0.0000	0.000 ± 0.0000
Day 141, n=10,6,19,14,15	0.180 ± 0.5692	0.000 ± 0.0000	0.095 ± 0.4129	0.000 ± 0.0000	0.000 ± 0.0000
Day 169, n=10,6,19,14,14	0.000 ± 0.0000	0.000 ± 0.0000	0.095 ± 0.4129	0.000 ± 0.0000	0.129 ± 0.4811

PrimaryPart 2: Change From Baseline in Urobilinogen at Indicated Time Points (Up to Day 450-Optional Follow-up)

Urine samples were planned to be collected from participants to evaluate change from Baseline in urobilinogen. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Change from Baseline was to be calculated by subtracting Baseline value from the post-dose visit value.

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450

No measurements were reported for this outcome.

PrimaryPart 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings

Electrocardiograms were obtained after 5 minutes of rest in the semi-supine or supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QT duration corrected for heart rate by Fridericia's formula (QTcF) intervals. Clinically significant (CS) and not clinically significant (NCS) abnormal ECG findings have been presented. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.

Time frame:: Day 1: 2 hours, Day 1: 4 hours, Day 1: 8 hours, Day 3, Day 8 and Day 30
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Abnormal Electrocardiogram (ECG) Findings
Participants	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Abnormal NCS, Day 1: 2 hour, n=3,3,6	2	1	5
Abnormal CS, Day 1: 2 hour, n=3,3,6	0	0	0
Abnormal NCS, Day 1: 4 hour, n=3,3,6	2	2	3
Abnormal CS, Day 1: 4 hour, n=3,3,6	0	0	0
Abnormal NCS, Day 1: 8 hour, n=3,3,6	2	2	5
Abnormal CS, Day 1: 8 hour, n=3,3,6	0	0	0
Abnormal NCS, Day 3, n=3,3,6	2	1	3
Abnormal CS, Day 3, n=3,3,6	0	0	0
Abnormal NCS, Day 8, n=2,3,6	1	1	2
Abnormal CS, Day 8, n=2,3,6	0	0	0
Abnormal NCS, Day 30, n=3,3,6	2	1	2
Abnormal CS, Day 30, n=3,3,6	0	0	0

PrimaryPart 2: Number of Participants With Abnormal ECG Findings (Up to Day 169-Interim Analysis)

Electrocardiogram were obtained after 5 minutes of rest in the semi-supine or supine position using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and QTcF intervals. CS and NCS abnormal ECG findings have been presented. Clinical significance was based on the medical and scientific judgement of the investigator or qualified designee.

Time frame:: Days 29, 57, 85 and 169
Reported as:: Count of participants · Participants

Part 2: Number of Participants With Abnormal ECG Findings (Up to Day 169-Interim Analysis)
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 29, NCS, n=10,6,20,13,15	2	2	6	6	5
Day 29, CS, n=10,6,20,13,15	0	0	0	0	0
Day 57, NCS, n=10,6,20,14,15	5	3	6	3	6
Day 57, CS, n=10,6,20,14,15	0	0	0	0	0
Day 85, NCS, n=10,6,20,14,15	3	3	4	4	4
Day 85, CS, n=10,6,20,14,15	0	0	0	0	0
Day 169, NCS, n=10,6,19,14,15	2	2	4	5	5
Day 169, CS, n=10,6,19,14,15	0	0	0	0	0

PrimaryPart 2: Number of Participants With Abnormal ECG Findings (Up to Day 450-Optional Follow-up)

ECGs were planned to be obtained after 5 minutes of rest in the semi-supine or supine position using ECG machine that automatically calculates the heart rate and measures PR, QRS, QT and QTcF intervals.

Time frame:: Days 270, 360 and 450

No measurements were reported for this outcome.

PrimaryPart 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect or any other situation according to medical or scientific judgment were categorized as SAE.

Time frame:: Up to Day 60
Reported as:: Count of participants · Participants

Part 1: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Participants	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
AEs	1	0	1
SAEs	0	0	0

PrimaryPart 2: Number of Participants With AEs and SAEs (Up to Day 169-Interim Analysis)

Time frame:: Up to Day 169
Reported as:: Count of participants · Participants

Part 2: Number of Participants With AEs and SAEs (Up to Day 169-Interim Analysis)
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
AEs	9	4	16	11	12
SAEs	1	0	0	2	0

PrimaryPart 2: Number of Participants With AEs and SAEs (Up to Day 450-Optional Follow-up)

Time frame:: Up to Day 450
Reported as:: Count of participants · Participants

Part 2: Number of Participants With AEs and SAEs (Up to Day 450-Optional Follow-up)
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
AEs	9	4	18	11	12
SAEs	1	0	0	2	1

PrimaryPart 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for GSK3389404

Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for GSK3389404
Hours*nanogram per milliliter	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Area Under the Concentration-time Curve From Time Zero (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC[0-t]) for GSK3389404	1230 ± 14.3	17000 ± 39.5

PrimaryPart 2: AUC (0-t) for GSK3389404

Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 2: AUC (0-t) for GSK3389404
Hours*nanogram per milliliter	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: AUC (0-t) for GSK3389404	1930 ± 21.4	5920 ± 36.2	12000 ± 38.5	14400 ± 49.1

PrimaryPart 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) for GSK3389404

Blood samples were collected to measure AUC (0-infinity) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) for GSK3389404
Hours*nanogram per milliliter	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Area Under the Plasma Concentration-time Curve From Time Zero (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) for GSK3389404	1460 ± 15.5	17100 ± 23.2

PrimaryPart 2: AUC (0-infinity) for GSK3389404

Blood samples were collected to measure AUC (0-infinity) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 2: AUC (0-infinity) for GSK3389404
Hours*nanogram per milliliter	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: AUC (0-infinity) for GSK3389404	2030 ± 17.7	5990 ± 35.3	12300 ± 37.5	14600 ± 47.3

PrimaryPart 1: Maximum Observed Plasma Concentration (Cmax) of GSK3389404

Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Nanogram per milliliter

Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3389404
Nanogram per milliliter	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Maximum Observed Plasma Concentration (Cmax) of GSK3389404	227 ± 11.0	1880 ± 72.4

PrimaryPart 2: Cmax of GSK3389404

Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Nanogram per milliliter

Part 2: Cmax of GSK3389404
Nanogram per milliliter	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Cmax of GSK3389404	214 ± 54.3	865 ± 41.3	1660 ± 34.4	1940 ± 78.2

PrimaryPart 1: Time to Achieve Cmax (Tmax) of GSK3389404

Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Median · Hours

Part 1: Time to Achieve Cmax (Tmax) of GSK3389404
Hours	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Time to Achieve Cmax (Tmax) of GSK3389404	1.40 (1.33 to 2.00)	3.50 (1.93 to 6.00)

PrimaryPart 2: Tmax of GSK3389404

Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Median · Hours

Part 2: Tmax of GSK3389404
Hours	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Tmax of GSK3389404	2.04 (0.90 to 3.98)	3.46 (1.98 to 5.98)	4.05 (2.02 to 6.03)	4.02 (2.98 to 4.07)

PrimaryPart 1: Apparent Terminal Phase Half-life(t1/2) of GSK3389404

Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Hours

Part 1: Apparent Terminal Phase Half-life(t1/2) of GSK3389404
Hours	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Apparent Terminal Phase Half-life(t1/2) of GSK3389404	3.12 ± 54.7	4.31 ± 3.7

PrimaryPart 2: t1/2 of GSK3389404

Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Hours

Part 2: t1/2 of GSK3389404
Hours	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: t1/2 of GSK3389404	3.90 ± 55.0	3.24 ± 26.0	4.24 ± 29.5	2.89 ± 48.4

PrimaryPart 1: Apparent Subcutaneous Plasma Clearance (CL/F) of GSK3389404

Blood samples were collected to measure CL/F at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Liters per hour

Part 1: Apparent Subcutaneous Plasma Clearance (CL/F) of GSK3389404
Liters per hour	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Apparent Subcutaneous Plasma Clearance (CL/F) of GSK3389404	20.6 (-7.914 to 49.34)	7.03 (3.090 to 11.22)

PrimaryPart 2: CL/F of GSK3389404

Blood samples were collected to measure CL/F at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Liters per hour

Part 2: CL/F of GSK3389404
Liters per hour	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: CL/F of GSK3389404	14.8 (12.37 to 17.57)	10.0 (6.960 to 14.03)	9.75 (1.914 to 18.41)	8.23 (0.02305 to 17.51)

PrimaryPart 1: Number of Participants Achieving Response Rate (RR) Based on Reduction of Hepatitis B Surface Antigen (HBsAg) Level From Baseline

The RR was based on the proportion of participants with at least a 1.5 logarithm to the base 10 (log10) international units per milliliter (IU/mL) reduction of HBsAg levels from Baseline at any time up to Day 60. Number of participants who achieved \>1.5 log10 IU/mL decrease in HBsAg levels at any time up to Day 60 are presented.

Time frame:: Up to Day 60
Reported as:: Count of participants · Participants

Part 1: Number of Participants Achieving Response Rate (RR) Based on Reduction of Hepatitis B Surface Antigen (HBsAg) Level From Baseline
Participants	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Number of Participants Achieving Response Rate (RR) Based on Reduction of Hepatitis B Surface Antigen (HBsAg) Level From Baseline	0	0	0

PrimaryPart 2: Number of Participants Achieving RR Based on Reduction of HBsAg Level From Baseline

The RR was based on the proportion of participants with at least a 1.5 log10 IU/mL reduction of HBsAg levels from Baseline at any time up to Day 85. Number of participants who achieved \>1.5 log10 IU/mL decrease in HBsAg levels at any time up to Day 85 are presented.

Time frame:: Up to Day 85
Reported as:: Count of participants · Participants

Part 2: Number of Participants Achieving RR Based on Reduction of HBsAg Level From Baseline
Participants	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Number of Participants Achieving RR Based on Reduction of HBsAg Level From Baseline	0	0	1	1	1

SecondaryPart 1: Change From Baseline in log10 Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Indicated Time Points

Blood samples were collected from participants to assess HBV DNA viral load. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

Time frame:: Baseline (Day 1 pre-dose), Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60
Reported as:: Mean · Log10 (IU/mL)

Part 1: Change From Baseline in log10 Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) Viral Load in Plasma at Indicated Time Points
Log10 (IU/mL)	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 1: 8 hour, n=2,3,5	-0.19 ± 0.202	-0.03 ± 0.055	0.50 ± 0.716
Day 3, n=2,3,6	-0.06 ± 0.065	0.41 ± 0.754	0.20 ± 0.539
Day 8, n=2,3,6	0.06 ± 0.265	0.37 ± 0.788	-0.02 ± 0.075
Day 15, n=2,3,6	0.17 ± 0.173	-0.05 ± 0.086	-0.17 ± 0.317
Day 22, n=2,3,6	0.16 ± 0.224	-0.07 ± 0.114	-0.09 ± 0.165
Day 30, n=2,3,6	-0.12 ± 0.077	0.34 ± 0.821	0.13 ± 0.573
Day 60, n=2,3,6	-0.30 ± 0.292	-0.04 ± 0.075	0.12 ± 0.199

SecondaryPart 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 169
Reported as:: Mean · Log10 (IU/mL)

Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)
Log10 (IU/mL)	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)	-0.128 ± 0.4044	-0.426 ± 0.6603	-0.643 ± 0.6594	-0.341 ± 0.7591	-0.256 ± 0.5295

SecondaryPart 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)

Time frame:: Baseline (Day 1 pre-dose) and Up to Day 450
Reported as:: Mean · Log10 (IU/mL)

Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)
Log10 (IU/mL)	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Change From Baseline in log10 HBV DNA Viral Load in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)	-0.128 ± 0.4044	-0.426 ± 0.6603	-0.643 ± 0.6594	-0.426 ± 0.7893	-0.256 ± 0.5295

SecondaryPart 1: Change From Baseline in log10 Hepatitis B Virus Surface Antigen (HBsAg) Levels in Plasma at Indicated Time Points

Blood samples were collected from participants to assess HBsAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

Time frame:: Baseline (Day 1 pre-dose) and Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60
Reported as:: Mean · Log10 (IU/mL)

Part 1: Change From Baseline in log10 Hepatitis B Virus Surface Antigen (HBsAg) Levels in Plasma at Indicated Time Points
Log10 (IU/mL)	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 1: 8 hour	-0.03 ± 0.027	0.02 ± 0.023	-0.02 ± 0.032
Day 3	0.01 ± 0.016	0.00 ± 0.014	-0.05 ± 0.038
Day 8	-0.01 ± 0.078	0.01 ± 0.051	-0.09 ± 0.079
Day 15	0.00 ± 0.066	-0.02 ± 0.043	-0.10 ± 0.075
Day 22	0.03 ± 0.052	-0.04 ± 0.066	-0.14 ± 0.114
Day 30	-0.01 ± 0.038	-0.02 ± 0.021	-0.12 ± 0.139
Day 60	-0.00 ± 0.064	0.01 ± 0.057	-0.05 ± 0.038

SecondaryPart 2: Change From Baseline in log10 HBsAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Log10 (IU/mL)

Part 2: Change From Baseline in log10 HBsAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)
Log10 (IU/mL)	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=10,6,20,15,15	-0.0149 ± 0.07545	-0.0057 ± 0.05207	-0.0376 ± 0.08685	-0.0573 ± 0.03889	-0.0944 ± 0.08417
Day 15, n=10,6,20,14,15	-0.0175 ± 0.07296	-0.0296 ± 0.03871	-0.0872 ± 0.12991	-0.0690 ± 0.06427	-0.2103 ± 0.13356
Day 22, n=10,6,20,15,15	-0.0248 ± 0.06304	-0.0302 ± 0.03943	-0.1543 ± 0.16457	-0.1200 ± 0.09169	-0.3345 ± 0.17978
Day 29, n=10,6,20,13,15	-0.0252 ± 0.06330	-0.0416 ± 0.07503	-0.2197 ± 0.25896	-0.1793 ± 0.08003	-0.4512 ± 0.22095
Day 36, n=10,6,20,14,15	-0.0280 ± 0.06764	-0.0895 ± 0.06557	-0.2650 ± 0.28541	-0.2105 ± 0.08617	-0.4798 ± 0.21487
Day 43, n=10,6,20,14,15	-0.0334 ± 0.08425	-0.1010 ± 0.06003	-0.2671 ± 0.31301	-0.2370 ± 0.12134	-0.4923 ± 0.23961
Day 50, n=10,6,19,14,15	-0.0118 ± 0.06170	-0.0959 ± 0.06731	-0.3131 ± 0.28058	-0.2603 ± 0.10027	-0.5600 ± 0.31750
Day 57, n=10,6,20,14,15	-0.0307 ± 0.05677	-0.1250 ± 0.08371	-0.3171 ± 0.27547	-0.2925 ± 0.09666	-0.5962 ± 0.34848
Day 64, n=10,6,20,14,15	-0.0178 ± 0.07303	-0.1388 ± 0.08620	-0.3307 ± 0.25414	-0.3628 ± 0.20369	-0.6261 ± 0.40132
Day 71, n=10,6,20,14,15	-0.0124 ± 0.06586	-0.1689 ± 0.13050	-0.3249 ± 0.24978	-0.3722 ± 0.28298	-0.6357 ± 0.42715
Day 78, n=10,6,19,14,15	-0.0130 ± 0.08312	-0.1065 ± 0.09399	-0.3438 ± 0.29089	-0.4532 ± 0.46786	-0.7088 ± 0.57034
Day 85, n=9,6,20,14,14	-0.0212 ± 0.08048	-0.1312 ± 0.06855	-0.3374 ± 0.31804	-0.4429 ± 0.50368	-0.7531 ± 0.64776
Day 92, n=10,6,19,14,13	-0.0462 ± 0.12954	-0.1431 ± 0.08963	-0.3411 ± 0.22578	-0.4291 ± 0.56931	-0.6794 ± 0.62942
Day 99, n=10,6,20,14,15	-0.0502 ± 0.10885	-0.1084 ± 0.06213	-0.3018 ± 0.20862	-0.4327 ± 0.55294	-0.5981 ± 0.48977
Day 113, n=10,6,20,14,15	-0.0395 ± 0.08067	-0.0874 ± 0.05607	-0.2389 ± 0.12015	-0.3612 ± 0.55395	-0.4228 ± 0.36072
Day 141, n=10,6,20,14,15	-0.0132 ± 0.09127	-0.0417 ± 0.04609	-0.1420 ± 0.10442	-0.2246 ± 0.38875	-0.2729 ± 0.23994
Day 169, n=10,6,19,14,15	-0.0046 ± 0.09142	-0.0295 ± 0.03644	-0.0975 ± 0.08478	-0.1038 ± 0.22824	-0.1822 ± 0.21674

SecondaryPart 2: Change From Baseline in log10 HBsAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)

Blood samples were collected from participants to assess HBsAg level. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

Time frame:: Baseline (Day 1 pre-dose), Day 270, Day 360 and Day 450
Reported as:: Mean · Log10 (IU/mL)

Part 2: Change From Baseline in log10 HBsAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)
Log10 (IU/mL)	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 270, n=10,5,17,13,15	-0.0177 ± 0.08736	0.0308 ± 0.07338	0.0627 ± 0.21462	0.0400 ± 0.05783	-0.0047 ± 0.35902
Day 360, n=10,5,17,12,14	-0.0723 ± 0.11352	-0.0397 ± 0.06918	-0.0265 ± 0.08988	-0.0239 ± 0.07252	-0.1175 ± 0.21454
Day 450, n=9,5,17,11,15	-0.1282 ± 0.09933	-0.0551 ± 0.11173	-0.0615 ± 0.08487	-0.0350 ± 0.08041	-0.1557 ± 0.18720

SecondaryPart 1: Change From Baseline in log10 Hepatitis B Virus E-antigen (HBeAg) Levels in Plasma at Indicated Time Points

Blood samples were collected from participants to assess HBeAg levels. Baseline was defined as the last assessment before the first dose of the study treatment (Day 1 pre-dose). Log10 change from Baseline was calculated as log10(Post-Dose Visit Value/Baseline).

Time frame:: Baseline (Day 1 pre-dose) and Day 1: 8 hours, Days 3, 8, 15, 22, 30 and 60
Reported as:: Mean · Log10 (IU/mL)

Part 1: Change From Baseline in log10 Hepatitis B Virus E-antigen (HBeAg) Levels in Plasma at Indicated Time Points
Log10 (IU/mL)	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Day 1: 8 hour, n=3,3,5	0.15 ± 0.237	-0.03 ± 0.053	0.00 ± 0.000
Day 3, n=3,3,4	-0.01 ± 0.020	-0.02 ± 0.039	0.00 ± 0.000
Day 8, n=3,3,4	0.02 ± 0.036	0.03 ± 0.044	0.94 ± 1.885
Day 15, n=3,3,4	0.02 ± 0.036	-0.01 ± 0.025	0.00 ± 0.000
Day 22, n=3,3,4	0.03 ± 0.052	0.01 ± 0.012	0.08 ± 0.151
Day 30, n=3,3,4	0.22 ± 0.331	-0.02 ± 0.039	0.17 ± 0.342
Day 60, n=3,3,4	0.00 ± 0.000	0.00 ± 0.000	0.00 ± 0.000

SecondaryPart 2: Change From Baseline in log10 HBeAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)

Time frame:: Baseline (Day 1 pre-dose), Days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, 113, 141 and 169
Reported as:: Mean · Log10 (IU/mL)

Part 2: Change From Baseline in log10 HBeAg Levels in Plasma at Indicated Time Points (Up to Day 169-Interim Analysis)
Log10 (IU/mL)	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 8, n=7,6,15,11,10	0.039 ± 0.0750	0.023 ± 0.0565	0.010 ± 0.0555	-0.051 ± 0.0802	0.012 ± 0.0586
Day 15, n=7,6,13,10,9	0.101 ± 0.2223	-0.030 ± 0.0516	-0.020 ± 0.0519	-0.044 ± 0.0728	-0.009 ± 0.0976
Day 22, n=7,6,13,11,9	0.008 ± 0.0215	-0.008 ± 0.0203	-0.054 ± 0.0732	-0.068 ± 0.1008	-0.081 ± 0.1414
Day 29, n=7,6,13,10,9	0.050 ± 0.0937	0.003 ± 0.0552	-0.049 ± 0.1086	-0.059 ± 0.0959	-0.039 ± 0.2732
Day 36, n=7,6,12,10,9	0.120 ± 0.2791	-0.028 ± 0.0695	-0.129 ± 0.2040	-0.062 ± 0.1232	-0.057 ± 0.1380
Day 43, n=7,6,13,10,9	0.008 ± 0.0397	-0.006 ± 0.0603	-0.113 ± 0.1285	-0.067 ± 0.1146	0.013 ± 0.5325
Day 50, n=7,6,12,10,9	0.007 ± 0.0186	-0.012 ± 0.0574	-0.091 ± 0.1283	0.017 ± 0.3365	-0.122 ± 0.1563
Day 57, n=7,6,13,10,9	0.002 ± 0.0111	-0.024 ± 0.0592	-0.110 ± 0.1288	-0.040 ± 0.1506	-0.068 ± 0.2413
Day 64, n=7,6,13,10,9	0.008 ± 0.0139	0.018 ± 0.1297	-0.120 ± 0.1296	-0.073 ± 0.1216	-0.109 ± 0.1562
Day 71, n=7,6,13,10,9	0.061 ± 0.1113	0.001 ± 0.0457	-0.111 ± 0.1141	-0.060 ± 0.1002	-0.101 ± 0.1618
Day 78, n=7,6,12,10,9	-0.027 ± 0.1334	0.086 ± 0.2363	-0.100 ± 0.1224	-0.071 ± 0.1232	-0.118 ± 0.1636
Day 85, n=6,6,13,10,8	0.018 ± 0.0438	0.059 ± 0.1518	-0.101 ± 0.1161	-0.017 ± 0.1918	-0.117 ± 0.1544
Day 92, n=7,6,12,10,9	-0.019 ± 0.1253	-0.004 ± 0.0551	-0.089 ± 0.0944	-0.042 ± 0.0926	-0.085 ± 0.1200
Day 99, n=7,6,13,10,9	-0.025 ± 0.1243	0.010 ± 0.0624	-0.080 ± 0.0946	-0.002 ± 0.1413	-0.085 ± 0.1189
Day 113, n=7,6,13,10,9	0.015 ± 0.0628	-0.003 ± 0.0666	-0.040 ± 0.0773	-0.022 ± 0.0543	-0.011 ± 0.1237
Day 141, n=7,6,13,10,9	0.209 ± 0.4253	0.017 ± 0.1427	-0.040 ± 0.1006	-0.020 ± 0.0405	0.015 ± 0.0858
Day 169, n=7,6,12,9,9	0.093 ± 0.1966	0.004 ± 0.0398	-0.099 ± 0.2382	-0.028 ± 0.0556	0.022 ± 0.0883

SecondaryPart 2: Change From Baseline in log10 HBeAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)

Time frame:: Baseline (Day 1 pre-dose), Day 270, Day 360 and Day 450
Reported as:: Mean · Log10 (IU/mL)

Part 2: Change From Baseline in log10 HBeAg Level in Plasma at Indicated Time Points (Up to Day 450-Optional Follow-up)
Log10 (IU/mL)	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Day 270, n=7,5,11,10,9	0.050 ± 0.1771	-0.028 ± 0.3263	-0.120 ± 0.3325	-0.041 ± 0.0670	0.014 ± 0.0877
Day 360, n=7,5,11,9,9	-0.153 ± 0.3744	-0.122 ± 0.2189	-0.084 ± 0.2531	-0.035 ± 0.0689	-0.003 ± 0.1408
Day 450, n=6,5,12,8,9	0.000 ± 0.0000	-0.119 ± 0.1866	-0.088 ± 0.2225	-0.155 ± 0.2663	-0.035 ± 0.0627

SecondaryPart 1: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)

Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 1: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)
Hours*nanogram per milliliter	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)	NA ± NA	44.2 ± 419.1

SecondaryPart 2: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)

Blood samples were collected to measure AUC(0-t) at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Hours*nanogram per milliliter

Part 2: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)
Hours*nanogram per milliliter	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: AUC(0-t) for Metabolite of GSK3389404 (ISIS 505358)	—	NA ± NA	NA ± NA	17.1 ± 169.7

SecondaryPart 1: Cmax of GSK3389404 Metabolite (ISIS 505358)

Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Nanogram per milliliter

Part 1: Cmax of GSK3389404 Metabolite (ISIS 505358)
Nanogram per milliliter	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Cmax of GSK3389404 Metabolite (ISIS 505358)	—	2.93 ± 60.1

SecondaryPart 2: Cmax of GSK3389404 Metabolite (ISIS 505358)

Blood samples were collected to measure Cmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Nanogram per milliliter

Part 2: Cmax of GSK3389404 Metabolite (ISIS 505358)
Nanogram per milliliter	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Cmax of GSK3389404 Metabolite (ISIS 505358)	—	NA ± NA	NA ± NA	2.91 ± 77.5

SecondaryPart 1: Tmax of GSK3389404 Metabolite (ISIS 505358)

Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Median · Hours

Part 1: Tmax of GSK3389404 Metabolite (ISIS 505358)
Hours	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: Tmax of GSK3389404 Metabolite (ISIS 505358)	—	7.88 (4.00 to 48.08)

SecondaryPart 2: Tmax of GSK3389404 Metabolite (ISIS 505358)

Blood samples were collected to measure Tmax at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Median · Hours

Part 2: Tmax of GSK3389404 Metabolite (ISIS 505358)
Hours	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: Tmax of GSK3389404 Metabolite (ISIS 505358)	—	7.93 (7.93 to 7.93)	7.93 (7.93 to 7.93)	8.00 (4.05 to 8.02)

SecondaryPart 1: t1/2 of GSK3389404 Metabolite (ISIS 505358)

Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 0.5, 1, 1.5, 2, 3, 4, 6, 8 hours post-dose), Days 3, 8 and 30
Reported as:: Geometric mean · Hours

Part 1: t1/2 of GSK3389404 Metabolite (ISIS 505358)
Hours	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg
Part 1: t1/2 of GSK3389404 Metabolite (ISIS 505358)	—	18.75 ± NA

SecondaryPart 2: t1/2 of GSK3389404 Metabolite (ISIS 505358)

Blood samples were collected to measure t1/2 at indicated time-points. Pharmacokinetic parameters were determined using standard non-compartmental methods.

Time frame:: Day 1 (Pre-dose and at 1, 2, 3, 4, 6, 8, 12, 24 hours post-dose), Days 29 and 57 (Pre-dose and at 1, 2, 3 hours post-dose), Day 169
Reported as:: Geometric mean · Hours

Part 2: t1/2 of GSK3389404 Metabolite (ISIS 505358)
Hours	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Part 2: t1/2 of GSK3389404 Metabolite (ISIS 505358)	—	—	—	10.66 ± NA

Adverse events

Collected over SAEs and non-SAEs were collected from the start of study treatment up to Day 60 for Part 1 and up to Day 450 (inclusion of optional follow-up duration) for Part 2. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Part 1: Placebo	0/3 (0%)	0/3 (0%)	1/3 (33.3%)
Part 1: GSK3389404 30 mg	0/3 (0%)	0/3 (0%)	0/3 (0%)
Part 1: GSK3389404 120 mg	0/6 (0%)	0/6 (0%)	1/6 (16.7%)
Part 2: Placebo	0/10 (0%)	1/10 (10%)	9/10 (90%)
Part 2: GSK3389404 30 mg Weekly	0/6 (0%)	0/6 (0%)	4/6 (66.7%)
Part 2: GSK3389404 60 mg Weekly	0/20 (0%)	0/20 (0%)	18/20 (90%)
Part 2: GSK3389404 120 mg Bi-weekly	0/15 (0%)	2/15 (13.3%)	11/15 (73.3%)
Part 2: GSK3389404 120 mg Weekly	0/15 (0%)	1/15 (6.7%)	12/15 (80%)

Most frequent serious events

Most frequent serious events
Event	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Hepatic lesionHepatobiliary disorders	0/3	0/3	0/6	1/10	0/6	0/20	0/15	0/15
Renal colicRenal and urinary disorders	0/3	0/3	0/6	0/10	0/6	0/20	1/15	0/15
Prinzmetal anginaCardiac disorders	0/3	0/3	0/6	0/10	0/6	0/20	1/15	0/15
Putamen haemorrhageNervous system disorders	0/3	0/3	0/6	0/10	0/6	0/20	0/15	1/15

Most frequent other events

Showing 10 of 133

Most frequent other events
Event	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly
Injection site erythemaGeneral disorders	0/3	0/3	0/6	0/10	0/6	7/20	2/15	1/15
NasopharyngitisInfections and infestations	1/3	0/3	0/6	2/10	1/6	6/20	2/15	2/15
Injection site pruritusGeneral disorders	0/3	0/3	0/6	0/10	0/6	5/20	1/15	1/15
MalaiseGeneral disorders	0/3	0/3	0/6	1/10	1/6	1/20	1/15	3/15
GingivitisInfections and infestations	0/3	0/3	0/6	2/10	0/6	1/20	0/15	1/15
Upper respiratory tract infectionInfections and infestations	0/3	0/3	0/6	1/10	0/6	2/20	2/15	3/15
Blood creatine phosphokinase increasedInvestigations	0/3	0/3	0/6	2/10	0/6	0/20	1/15	2/15
CoughRespiratory, thoracic and mediastinal disorders	0/3	0/3	0/6	2/10	1/6	1/20	0/15	1/15
Injection site reactionGeneral disorders	0/3	0/3	0/6	0/10	1/6	1/20	1/15	2/15
GastroenteritisInfections and infestations	0/3	0/3	0/6	0/10	1/6	0/20	0/15	0/15

Baseline characteristics

No participants were enrolled in two cohorts of Part 1 (GSK3389404 60 mg and GSK3389404 240 mg) as per decision made by the dose escalation committee.

Age, Categorical
Age, Categorical(Participants)	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly	Total
<=18 years	0	0	0	0	0	0	0	0	0
Between 18 and 65 years	3	3	6	8	5	20	15	15	75
>=65 years	0	0	0	2	1	0	0	0	3

Sex: Female, Male
Sex: Female, Male(Participants)	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly	Total
Female	1	0	3	4	1	10	2	2	23
Male	2	3	3	6	5	10	13	13	55

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Part 1: Placebo	Part 1: GSK3389404 30 mg	Part 1: GSK3389404 120 mg	Part 2: Placebo	Part 2: GSK3389404 30 mg Weekly	Part 2: GSK3389404 60 mg Weekly	Part 2: GSK3389404 120 mg Bi-weekly	Part 2: GSK3389404 120 mg Weekly	Total
Asian-East Asian Heritage	1	0	3	4	0	9	11	9	37
Asian-Japanese Heritage	0	0	0	4	6	7	3	5	25
Asian-South East Asian Heritage	2	3	3	2	0	4	1	0	15
Mixed Asian Race	0	0	0	0	0	0	0	1	1

Study locations

21 sites

GSK Investigational Site
Guangzhou, Guangdong 510150, China
GSK Investigational Site
Beijing, 100015, China
GSK Investigational Site
Beijing, 100050, China
GSK Investigational Site
Beijing, 100069, China
GSK Investigational Site
Shanghai, 200025, China
GSK Investigational Site
Pokfulam, Hong Kong
GSK Investigational Site
Aichi, 467-8602, Japan
GSK Investigational Site
Hiroshima, 734-8551, Japan
GSK Investigational Site
Hokkaidou, 060-0033, Japan
GSK Investigational Site
Kanagawa, 213-8587, Japan
GSK Investigational Site
Tokyo, 105-8470, Japan
GSK Investigational Site
Tokyo, 180-8610, Japan
GSK Investigational Site
Busan, 49241, Korea, Republic of
GSK Investigational Site
Busan, 614-735, Korea, Republic of
GSK Investigational Site
Daegu, 41944, Korea, Republic of
GSK Investigational Site
Gyeonggi-do, 15355, Korea, Republic of
GSK Investigational Site
Seoul, 3080, Korea, Republic of
GSK Investigational Site
Cebu, 6000, Philippines
GSK Investigational Site
Makati City, 1229, Philippines
GSK Investigational Site
Singapore, 119074, Singapore
GSK Investigational Site
Singapore, 169608, Singapore

References and documents

Publications

Yuen MF, Heo J, Kumada H, Suzuki F, Suzuki Y, Xie Q, Jia J, Karino Y, Hou J, Chayama K, Imamura M, Lao-Tan JY, Lim SG, Tanaka Y, Xie W, Yoon JH, Duan Z, Kurosaki M, Park SJ, Labio ME, Kumar R, Kweon YO, Yim HJ, Tao Y, Cremer J, Elston R, Davies M, Baptiste-Brown S, Han K, Campbell FM, Paff M, Theodore D. Phase IIa, randomised, double-blind study of GSK3389404 in patients with chronic hepatitis B on stable nucleos(t)ide therapy. J Hepatol. 2022 Oct;77(4):967-977. doi: 10.1016/j.jhep.2022.05.031. Epub 2022 Jun 15. PubMed 35714812 ↗

Study documents

Study protocol · Jun 13, 2018
Statistical analysis plan · Nov 19, 2018

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — IPD for this study will be made available via the Clinical Study Data Request Site

Supporting information: Study protocol, Sap, Icf, Csr

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Oct 1, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT03020745
Lead sponsor: GlaxoSmithKline
Responsible party: Sponsor
First posted: Jan 13, 2017
Start date: Feb 14, 2017
Primary completion: Jan 28, 2019
Completion: Nov 6, 2019
Results posted: Jan 22, 2020
Last update: Oct 1, 2020

Study contacts

GSK Clinical Trials

study director · GlaxoSmithKline

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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A Study to Assess the Safety, Tolerability, Pharmacokinetics (PK) and Pharmacodynamics (PD) of GSK3389404 in Chronic Hepatitis B (CHB) Subjects

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