CClinicalTrials.gg
Sign In
CompletedNCT02956850Updated Feb 8, 2024Results posted

A Study in Healthy Volunteers and in Participants With Chronic Hepatitis B to Assess Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single and Multiple Doses of RO7020531

A Phase 1 interventional study of Placebo and RO7020531 in Hepatitis B, Chronic, sponsored by Hoffmann-La Roche. Completed at 18 sites in 8 countries. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-02-08.

Sponsored by Hoffmann-La Roche · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
160
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This sponsor-open, investigator- and participant-blinded, multi-center study will assess the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020531 in healthy participants and in participants with chronic hepatitis B. Part I will be conducted in two portions: Single Ascending Dose (SAD) and Multiple Ascending Dose (MAD) which will include only healthy volunteers. Part II will commence after completion of the MAD portion of Part I and will include only Chronic Hepatitis B (CHB) participants.

02

Conditions studied

  • Hepatitis B, Chronic
03

In context

Hepatitis A

2,709 studies on the registry are indexed under Hepatitis A; 142 are open to participants now.

This study's enrollment of 160 is above the median of 100 across 1,886 interventional studies indexed under Hepatitis A.

Browse Hepatitis A studies →

Lead sponsor

Hoffmann-La Roche is the lead sponsor of 2,061 studies on the registry; 85 are open to participants now.

Of its 319 completed or terminated interventional studies of FDA-regulated products, 239 (75%) have results posted.

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

04

Who can participate

Ages eligible
18 Years to 65 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Inclusion criteria

Part 1: SAD and MAD in Healthy Volunteers

  • Non-smokers, or use of less than (\<) 10 cigarettes (or equivalent nicotine-containing product) per day
  • Negative Anti-Nuclear Antibody (ANA) test; or positive with dilutions not greater than 1:40 and with no associated history or symptoms of potential connective tissue disease or other immune-mediated diseases

Part 2: CHB Participants

  • CHB infection (positive test for Hepatitis B surface antigen [HBsAg] for more than 6 months prior to randomization)
  • For Cohort 1, 2, 3 and 4: HBsAg detectable at screening
  • For Cohort 1, 2 and 3: Hepatitis B virus deoxyribose nuclic acid (HBV DNA) \< 90 international unit per milliliter (IU/mL) for at least 6 months prior to randomization; HBV DNA \< 90 IU/mL at screening by Roche Cobas assay
  • For Cohort 4: HBV DNA at screening >= 2 × 10*4 IU/mL for HBeAg positive and >= 2 x 10*3 IU/mL for hepatitis B e antigen (HBeAg) negative participants
  • For Cohort 1, 2 and 3: Alanine amino transferase (ALT) =\<1.5 × upper limit of normal (ULN) during the 6 months prior to randomization confirmed by two measurements separated by at least 14 days; ALT at screening =\< 1.5 × ULN.
  • For Cohort 4: ALT and aspartate aminotransferase (AST) at screening and Day -1 visit: =\< 5 × ULN.
  • Negative ANA test; or positive with dilutions not greater than 1:40 and with no associated history or symptoms of potential connective tissue disease or other immune-mediated diseases
  • Liver biopsy, Fibroscan® or equivalent elastography test obtained within 6 months prior to randomization demonstrating liver disease consistent with chronic HBV infection with absence of cirrhosis and absence of extensive bridging fibrosis (cirrhosis or extensive bridging fibrosis are defined as greater than or equal to (>/=) Metavir 3, recommended cut-off for Fibroscan 8.5 kilopascals [kPa])
  • For Cohort 1, 2 and 3: On treatment with tenofovir, entecavir, adefovir, or telbivudine, either as single agents or in combination, for at least 6 months
  • For Cohort 4: Hepatitis B virus (HBV) treatment naïve or not on any anti-HBV treatment for the past 6 months

Exclusion criteria

Exclusion Criteria:

Part 1: SAD and MAD in Healthy Volunteers

  • History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant psychiatric disease, acute infection (e.g., influenza), gastrointestinal (GI) disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage)
  • History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids, IFN or pegylated interferon [PEG-IFN]) within the 8 weeks prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
  • Any clinically significant concomitant disease or condition that could interfere with, or for which the treatment of might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the participant in this study
  • Positive Hepatitis A virus antibody (HAV Ab IgM), HBsAg, Hepatitis C antibody (HCV Ab), or positive for human immunodeficiency virus (HIV) at screening
  • History of clinically significant thyroid disease; also, participants with clinically significant elevated thyroid-stimulating hormone (TSH) concentrations at screening
  • Positive results for anti-mitochondrial antibody (AMA), anti-smooth muscle antibody (ASMA) or thyroid peroxidase antibody

Part 2: CHB Participants

  • History of liver cirrhosis
  • History or other evidence of bleeding from esophageal varices
  • Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or clinical evidence such as ascites or varices)
  • History or other evidence of a medical condition associated with chronic liver disease other than HBV infection (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure, thalassemia, nonalcoholic steato-hepatitis, etc.). A clinical diagnosis of fatty liver is allowed provided that non alcoholic steatohepatitis (NASH) has been excluded by liver biopsy.
  • Documented history or other evidence of metabolic liver disease within one year of randomization
  • Positive test for Hepatitis A virus (IgM anti-HAV), Hepatitis C virus (HCV), Hepatitis D virus, Hepatitis E virus (HEV), or human immunodeficiency virus (HIV).
  • History of or suspicion of hepatocellular carcinoma or alpha fetoprotein >/=13 nanograms per milliliter (ng/mL) at screening
  • History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis, multiple sclerosis, or any other autoimmune disease); clinically significant psychiatric disease; acute infection (e.g., influenza); GI disease (including inflammatory bowel disease, peptic ulcer disease, GI hemorrhage, or history of pancreatitis); clinically significant cardiovascular (including postural hypotension), endocrine, renal, ocular, pulmonary or neurological disease.
  • History of having received or currently receiving any systemic anti-neoplastic (including radiation) or immune-modulatory treatment (including systemic oral or inhaled corticosteroids,IFN or PEG-IFN) within the 8 weeks prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
  • Cohort 4: Concurrent HBV treatments
  • History of organ transplantation
  • Clinically significant thyroid disease; also, participants with clinically significant elevated TSH concentrations at screening
  • Positive results for AMA, ASMA or thyroid peroxidase antibody
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
160 participants (actual)

Study arms

  • Experimental
    Part I: SAD in Healthy Volunteers

    Healthy volunteers will receive single dose of RO7020531 or matching placebo orally on Day 1 of each cohort. A planned dose-escalation sequence for SAD is 3 milligrams (mg), 10 mg, 20 mg, 40 mg, 60 mg, 100 mg, 140 mg, and 170 mg.

    Other: Placebo · Drug: RO7020531

  • Experimental
    Part I: MAD in Healthy Volunteers

    Healthy volunteers will receive RO7020531 (100 mg, 140 mg, and 170 mg as selected based on safety, pharmacokinetic (PK) and pharmacodynamic (PD) data of SAD cohorts) or matching placebo orally every other day (QOD) from Day 1 through to Day 13.

    Other: Placebo · Drug: RO7020531

  • Experimental
    Part II: CHB Participants

    CHB participants will receive RO7020531 (150 mg and 170 mg as selected based on safety, PK and PD data of MAD cohorts) or matching placebo orally QOD from Day 1 through to Day 41, unless in Cohort 4 in case of once a week (QW) dosing as dose modification.

    Other: Placebo · Drug: RO7020531

Interventions

  • OtherPlacebo

    Placebo matching to RO7020531 will be administered as per schedule specified in the respective arm.

  • DrugRO7020531

    RO7020531 will be administered as per schedule specified in the respective arm.

06

What researchers measure

Primary outcomes

  1. Part 1: Percentage of SAD Participants With Adverse Events (AEs)

    An AE is any untoward medical occurrence in a clinical investigation healthy volunteer (HV)/participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition and recurrence of an intermittent medical condition (e.g., headache) not present at baseline.

    Time frame: From randomization up to Day 29

  2. Part 1: Percentage of MAD Participants With AEs

    An AE is any untoward medical occurrence in a clinical investigation healthy volunteer (HV)/participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition and recurrence of an intermittent medical condition (e.g., headache) not present at baseline.

    Time frame: From randomization up to Day 41

  3. Part 2: Percentage of Chronic Hepatitis B Participants With AEs

    An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition and recurrence of an intermittent medical condition (e.g., headache) not present at baseline.

    Time frame: From randomization up to Week 12

  4. Part 1: Percentage of SAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

    For all laboratory parameters included, there exists a Roche predefined standard reference range. Laboratory values falling outside this standard reference range were labeled "H" for high or "L" for low in HV/participant listings of laboratory data.

    Time frame: From randomization up to Day 8

  5. Part 1: Percentage of MAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

    For all laboratory parameters included, there exists a Roche predefined standard reference range. Laboratory values falling outside this standard reference range were labeled "H" for high or "L" for low in HV/participant listings of laboratory data.

    Time frame: From randomization up to Day 20

  6. Part 2: Percentage of Chronic Hepatitis B Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

    For all laboratory parameters included, there exists a Roche predefined standard reference range. Laboratory values falling outside this standard reference range were labeled "H" for high or "L" for low in HV/participant listings of laboratory data.

    Time frame: From randomization up to Week 12

  7. Part 1: Percentage of SAD Participants With Abnormalities in Electrocardiograph (ECG) Parameters

    Triplicate 12-lead ECGs were obtained after the participant has been in a supine position for at least 10 minutes. Clinically significant RO7020531-related changes included confirmation of mean QTc 500 milliseconds (msec) or 60 msec longer than the pre-dose baseline.

    Time frame: From randomization up to Day 8

  8. Part 1: Percentage of MAD Participants With Abnormalities in ECG Parameters

    Triplicate 12-lead ECGs were obtained after the participants has been in a supine position for at least 10 minutes. Clinically significant RO7020531-related changes included confirmation of mean QTc 500 msec or 60 msec longer than the pre-dose baseline.

    Time frame: From randomization up to Day 20

  9. Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in ECG Parameters

    Triplicate 12-lead ECGs were obtained after the participant has been in a supine position for at least 10 minutes. Clinically significant RO7020531-related changes included confirmation of mean QTc 500 msec or 60 msec longer than the pre-dose baseline.

    Time frame: From randomization up to Week 12

  10. Part 1: Percentage of SAD Participants With Abnormalities in Vital Signs

    Vital signs include blood pressure, pulse rate, respiratory rate and body temperature. Blood pressure, respiratory rate and pulse rate were obtained after the participant had been in a supine or sitting position for at least 5 minutes. Blood pressure measurement were performed in triplicate (can be as short as 20 second to 1 minute interval between measurements).

    Time frame: From randomization up to Day 8

  11. Part 1: Percentage of MAD Participants With Abnormalities in Vital Signs

    Vital signs include blood pressure, pulse rate, respiratory rate and body temperature. Blood pressure, respiratory rate and pulse rate were obtained after the participant had been in a supine or sitting position for at least 5 minutes. Blood pressure measurement were performed in triplicate (can be as short as 20 second to 1 minute interval between measurements).

    Time frame: From randomization up to Day 20

  12. Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in Vital Signs

    Vital signs include blood pressure, pulse rate, respiratory rate and body temperature. Blood pressure, respiratory rate and pulse rate were obtained after the participant had been in a supine or sitting position for at least 5 minutes. Blood pressure measurement were performed in triplicate (can be as short as 20 second to 1 minute interval between measurements).

    Time frame: From randomization up to Week 12

Secondary outcomes

  1. Part 1: Maximum Observed Plasma Concentration (Cmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

    Time frame: SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13

  2. Part 2: Cmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

    Time frame: Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

  3. Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

    Time frame: SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13

  4. Part 2: Tmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

    Time frame: Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

  5. Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

    Time frame: SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13

  6. Part 2: AUCinf of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

    Time frame: Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

  7. Part 1: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

    Time frame: SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13

  8. Part 2: AUClast of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

    Time frame: Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

  9. Part 1: Half Life (t1/2) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD

    Time frame: SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13

  10. Part 2: t1/2 of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805

    Time frame: Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41

  11. Part 1: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine: SAD

    Total amount of the study drug and metabolites recovered in urine was reported.

    Time frame: 0 to 24 hrs Postdose on Day 1

  12. Part 1:Mean Concentration of Interferon Alpha (IFN-alpha): SAD and MAD

    Mean concentrations of IFN-alpha for SAD were calculated following single-dose and for MAD it was calculated following multiple doses. The standard deviation (SD) presented is actually the log transformed geometric standard deviation.

    Time frame: SAD: Predose, 2, 6, 12 and 24 hrs Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20

  13. Part 2: Mean Concentration of IFN-alpha

    Mean concentrations of IFN-alpha for Part 2 were calculated following multiple doses. The SD presented is actually the log transformed geometric standard deviation.

    Time frame: Predose, 6, 8 and 24 hrs Postdose on Day 1; Predose, 4-6, 24 hrs Postdose on Days 3, 7 and 21; Predose, 6, 24 hrs Postdose on Day 41

  14. Part 1: Mean Fold Change From Baseline in Cytokine Markers: SAD and MAD

    Cytokines markers include Chemokine (C-X-C Motif) Ligand 10 (IP-10), Interleukin 6 (IL-6), Interleukin 10 (IL-10), Interleukin 12 p40 (IL-12 p40), Neopterin, Tumor Necrosis Factor-Alpha (TNF-alpha). The SD presented is actually the log transformed geometric standard deviation.

    Time frame: SAD: Predose, 2, 6, 12, 24, 48 (only Neopterin) and 96 hrs (only Neopterin) Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20

  15. Part 2: Mean Fold Change From Baseline in Cytokine Markers

    Cytokines markers included IP- 10, IL- 6, IL-1 10, IL-12 p40, Neopterin and TNF -alpha. The SD presented is actually the log transformed geometric standard deviation.

    Time frame: Predose, 6, 8 and 24 hrs Postdose on Day 1; Predose, 4-6, 24 hrs Postdose on Days 3, 7 and 21; Predose, 6, 24 hrs Postdose on Day 41

  16. Part 1:Mean Fold Change From Baseline in Markers of Transcriptional Responses: SAD and MAD

    Markers of transcriptional responses includes messenger ribonucleic acid interferon-stimulated gene 15(mRNA ISG15), messenger RNA oligoadenylate synthetase 1 (mRNA OAS1), messenger RNA myxovirus resistance 1 gene (mRNA MX-1), messenger RNA Toll-like receptor (mRNA TLR7). The SD presented is actually the log transformed geometric standard deviation.

    Time frame: SAD: Predose, 2, 6, 12 and 24 Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20

  17. Part 2: Mean Fold Change From Baseline in Markers of Transcriptional Responses

    Transcriptional markers include mRNA ISG15, mRNA OAS1, mRNA MX-1, mRNA TLR7. The SD presented is actually the log transformed geometric standard deviation.

    Time frame: Predose, 6, 8, 24 hrs postdose on Day 1; Predose, 4-6, 24 hrs postdose on Days 3, 7, 21; Predose, 6, 24 hrs postdose on Day 41

  18. Effect of RO7020531 Dosing on ECG Parameters (PR [PQ], QRS, QT, QTcF in Miliseconds [ms]) Using Exposure-response Analysis: SAD and MAD

    Time frame: SAD: Predose, 0.5, 1, 2, 4, 6, 12, 24 and 48 hrs Post dose on Day 1; MAD: Predose, 0.5, 1,2,4 and 12 hrs Postdose on Day 1 and 13; Predose, 2 and 6 hrs Postdose on Day 3, Predose, 6 and 24 hrs Postdose on Day , 7, 9, and 11

  19. Part 2: Plasma Concentrations of Tenofovir, Tenofovir Alafenamide, Entecavir, Adefovir and Telbivudine

    Adefovir was not administered to any participants in the study. Hence, no data could be collected for plasma concentration of adefovir. As participants in each cohort received different NUCs the data for Cohorts 1, 2 and 3 have been reported separately.

    Time frame: Pre-dose and 2-4 hours post-dose on Day 1, Day 21 and Day 41

07

Results

Posted Feb 8, 2024

Participant flow

Participants were enrolled at 16 investigative sites in New Zealand, Hong Kong, Thailand, Taiwan, New Zealand, Bulgaria, United Kingdom, Italy and Netherlands from 12 December 2016 to 15 June 2021.

Participant flow — Overall Study
MilestonePart 1 Cohorts 1-8, Single Ascending Dose (SAD): PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, Multiple Ascending Dose (MAD): PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3Part 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Started168888888868886168515
Completed168888888868886168514
Not completed000000000000000001
Withdrew: Withdrawal by subject000000000000000001

Outcome measures

PrimaryPart 1: Percentage of SAD Participants With Adverse Events (AEs)

An AE is any untoward medical occurrence in a clinical investigation healthy volunteer (HV)/participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition and recurrence of an intermittent medical condition (e.g., headache) not present at baseline.

Time frame:
From randomization up to Day 29
Reported as:
Number · percentage of participants
Part 1: Percentage of SAD Participants With Adverse Events (AEs)
percentage of participantsPart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8
Part 1: Percentage of SAD Participants With Adverse Events (AEs)31.325.050.025.025.025.025.025.037.5
PrimaryPart 1: Percentage of MAD Participants With AEs

An AE is any untoward medical occurrence in a clinical investigation healthy volunteer (HV)/participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition and recurrence of an intermittent medical condition (e.g., headache) not present at baseline.

Time frame:
From randomization up to Day 41
Reported as:
Number · percentage of participants
Part 1: Percentage of MAD Participants With AEs
percentage of participantsPart 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
Part 1: Percentage of MAD Participants With AEs83.375.087.587.5
PrimaryPart 2: Percentage of Chronic Hepatitis B Participants With AEs

An AE is any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, regardless of causal attribution. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product, any new disease or exacerbation of an existing disease (a worsening in the character, frequency, or severity of a known condition and recurrence of an intermittent medical condition (e.g., headache) not present at baseline.

Time frame:
From randomization up to Week 12
Reported as:
Number · percentage of participants
Part 2: Percentage of Chronic Hepatitis B Participants With AEs
percentage of participantsPart 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Part 2: Percentage of Chronic Hepatitis B Participants With AEs50.068.875.060.080.0
SecondaryPart 1: Maximum Observed Plasma Concentration (Cmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Time frame:
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Reported as:
Mean · nanograms per milliliter (ng/mL)
Part 1: Maximum Observed Plasma Concentration (Cmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
nanograms per milliliter (ng/mL)Part 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
RO7020531: Day 10.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00——1.87 ± NA
RO7011785: Day 130.2 ± 10.4115 ± 69.0182 ± 71.4508 ± 203598 ± 2181270 ± 5051830 ± 2381670 ± 6541060 ± 4281680 ± 7352150 ± 746
RO7011785: Day 13————————1100 ± 4481470 ± 5572100 ± 838
RO7018822: Day 12.01 ± 1.128.96 ± 5.1520.0 ± 16.052.3 ± 24.954.4 ± 32.1101 ± 37.7166 ± 79.3189 ± 52.598.3 ± 42.3144 ± 52.1234 ± 163
RO7018822: Day 13————————77.7 ± 42.2125 ± 47.6220 ± 143
RO7033805: Day 10.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.285 ± 0.8061.24 ± NA—2.30 ± 0.339
RO7033805: Day 13——————————1.90 ± 0.600
SecondaryPart 2: Cmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Time frame:
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Reported as:
Mean · ng/mL
Part 2: Cmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
ng/mLPart 2: Cohort 1 and 2Part 2: Cohort 4Part 2: Cohort 3
RO7020531: Day 11.70 ± NA——
RO7011785: Day 11690 ± 6391500 ± 6681980 ± 891
RO7011785: Day 411580 ± 5911430 ± 4571990 ± 999
RO7018822: Day 1167 ± 93.2203 ± 110218 ± 113
RO7018822: Day 41193 ± 114194 ± 134184 ± 90.9
RO7033805: Day 1—1.43 ± NA—
RO7033805: Day 411.51 ± NA——
SecondaryPart 1: Time to Maximum Observed Plasma Concentration (Tmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Time frame:
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Reported as:
Median · hours (hr)
Part 1: Time to Maximum Observed Plasma Concentration (Tmax) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
hours (hr)Part 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
RO7020531: Day 10.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)——0.25 (0.25 to 0.25)
RO7011785: Day 10.75 (0.50 to 3.00)0.51 (0.50 to 1.50)1.00 (0.50 to 1.00)0.78 (0.50 to 1.08)0.75 (0.50 to 1.00)1.00 (0.50 to 2.00)1.00 (0.50 to 1.50)0.52 (0.50 to 1.50)1.00 (0.50 to 2.00)1.00 (0.50 to 1.52)0.76 (0.50 to 1.00)
RO7011785: Day 13————————1.00 (0.50 to 1.00)1.00 (0.50 to 1.50)0.50 (0.50 to 1.50)
RO7018822: Day 10.50 (0.00 to 1.50)0.50 (0.50 to 1.50)0.50 (0.25 to 1.00)0.50 (0.50 to 1.50)0.50 (0.50 to 2.00)1.00 (0.50 to 2.00)0.75 (0.25 to 1.50)0.77 (0.50 to 2.00)0.75 (0.50 to 2.00)1.00 (0.50 to 1.52)0.52 (0.50 to 1.00)
RO7018822: Day 13————————1.00 (0.25 to 2.00)0.73 (0.50 to 1.00)0.50 (0.50 to 1.00)
RO7033805: Day 10.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.00 (0.00 to 0.00)0.50 (0.50 to 0.50)—0.51 (0.50 to 0.52)
RO7033805: Day 13——————————0.50 (0.50 to 0.50)
SecondaryPart 2: Tmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Time frame:
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Reported as:
Median · hr
Part 2: Tmax of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
hrPart 2: Cohort 1 and 2Part 2: Cohort 4Part 2: Cohort 3
RO7020531: Day 10.25 (0.25 to 0.25)——
RO7011785: Day 11.00 (0.25 to 2.00)1.00 (0.25 to 2.00)1.00 (0.92 to 2.00)
RO7011785: Day 411.040 (0.92 to 2.00)1.00 (0.92 to 2.00)1.00 (0.92 to 4.00)
RO7018822: Day 11.00 (0.25 to 2.00)1.00 (0.25 to 2.00)1.00 (0.25 to 2.00)
RO7018822: Day 411.00 (0.92 to 2.00)1.00 (0.25 to 2.00)1.00 (0.28 to 4.00)
RO7033805: Day 1—0.25 (0.25 to 0.25)—
RO7033805: Day 411.00 (1.00 to 1.00)——
SecondaryPart 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Time frame:
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Reported as:
Mean · hours*nanogram per milliliter (h*ng/mL)
Part 1: Area Under the Plasma Concentration Versus Time Curve Extrapolated to Infinity (AUCinf) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
hours*nanogram per milliliter (h*ng/mL)Part 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
RO7011785: Day 150.9 ± 28.9138 ± 40.8253 ± 58.3596 ± 103770 ± 1131600 ± 2282190 ± 5322690 ± 8571450 ± 2782250 ± 8382700 ± 572
RO7011785: Day 13————————1420 ± 2882150 ± 7342730 ± 472
RO7018822: Day 1—8.59 ± 2.6119.0 ± 5.6643.3 ± 15.549.1 ± 19.995.4 ± 21.3139 ± 40.2224 ± 81.697.4 ± 32.2164 ± 53.6231 ± 110
RO7018822: Day 13————————84.5 ± 24.0158 ± 42.1216 ± 71.4
SecondaryPart 2: AUCinf of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Time frame:
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Reported as:
Mean · h*ng/mL
Part 2: AUCinf of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
h*ng/mLPart 2: Cohort 1 and 2Part 2: Cohort 4Part 2: Cohort 3
RO7011785: Day 12770 ± 9682430 ± 7653060 ± 1030
RO7011785: Day 412740 ± 7622500 ± 6552960 ± 909
RO7018822: Day 1338 ± 147326 ± 139374 ± 261
RO7018822: Day 41498 ± 176482 ± 249327 ± 105
SecondaryPart 1: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Time frame:
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Reported as:
Mean · h*ng/mL
Part 1: Area Under the Plasma Concentration Versus Time Curve up to the Last Measurable Concentration (AUClast) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
h*ng/mLPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
RO7020531: Day 1——————————0.234 ± NA
RO7011785: Day 148.2 ± 27.3135 ± 40.1249 ± 58.8587 ± 104763 ± 1141590 ± 2272180 ± 5332680 ± 8571440 ± 2762240 ± 8372690 ± 573
RO7011785: Day 13————————1410 ± 2882150 ± 7332720 ± 472
RO7018822: Day 11.43 ± 1.476.73 ± 2.8116.4 ± 5.9641.6 ± 15.548.5 ± 19.193.8 ± 21.7143 ± 41.2222 ± 81.695.9 ± 32.3161 ± 52.9228 ± 109
RO7018822: Day 13————————80.6 ± 23.5154 ± 39.7210 ± 64.9
RO7033805: Day 1———————0.285 ± NA0.155 ± NA—0.434 ± 0.224
RO7033805: Day 13——————————0.316 ± 0.155
SecondaryPart 2: AUClast of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Time frame:
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Reported as:
Mean · h*ng/mL
Part 2: AUClast of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
h*ng/mLPart 2: Cohort 1 and 2Part 2: Cohort 4Part 2: Cohort 3
RO7020531: Day 10.213 ± NA——
RO7011785: Day 12820 ± 9792400 ± 7623030 ± 1040
RO7011785: Day 412730 ± 7712470 ± 6532930 ± 915
RO7018822: Day 1220 ± 124253 ± 127255 ± 134
RO7018822: Day 41297 ± 214301 ± 228243 ± 87.8
RO7033805: Day 1—0.179 ± NA—
RO7033805: Day 410.566 ± NA——
SecondaryPart 1: Half Life (t1/2) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
Time frame:
SAD: Predose and 0.5, 1, 1.5 , 2, 3, 4, 6,8, 12,18, and 24hours post dose on Day 1; MAD: Predose and 0.25, 0.5, 1, 1.5, 2 , 3, 4, 6, 8, 12,18, and 24 hours post dose on Days 1 and 13
Reported as:
Mean · hr
Part 1: Half Life (t1/2) of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805: SAD and MAD
hrPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
RO7011785: Day 11.11 ± 0.3701.56 ± 0.3191.81 ± 0.5062.78 ± 0.4792.82 ± 0.5993.35 ± 0.5733.26 ± 0.2543.39 ± 0.6163.23 ± 0.6352.80 ± 0.5383.00 ± 0.692
RO7011785: Day 13————————3.63 ± 0.7403.23 ± 0.5283.45 ± 1.12
RO7018822: Day 1—0.610 ± 0.09860.655 ± 0.2760.579 ± 0.1440.567 ± 0.1900.585 ± 0.07800.564 ± 0.08270.645 ± 0.1370.548 ± 0.1110.586 ± 0.05070.601 ± 0.113
RO7018822: Day 13————————0.578 ± 0.05280.620 ± 0.08120.744 ± 0.204
SecondaryPart 2: t1/2 of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
Time frame:
Predose and 0.25, 1, 2, 4, 6, 8, and 24 hours post dose on Days 1 and 41
Reported as:
Mean · hr
Part 2: t1/2 of RO7020531 and Its Metabolites Including RO7011785, RO7018822 and RO7033805
hrPart 2: Cohort 1 and 2Part 2: Cohort 4Part 2: Cohort 3
RO7011785: Day 13.09 ± 0.9822.63 ± 1.193.06 ± 0.934
RO7011785: Day 413.09 ± 0.6972.77 ± 1.192.90 ± 0.980
RO7018822: Day 11.19 ± 0.8860.665 ± 0.04310.648 ± 0.0317
RO7018822: Day 410.776 ± 0.1460.714 ± 0.1120.720 ± 0.774
SecondaryPart 1: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine: SAD

Total amount of the study drug and metabolites recovered in urine was reported.

Time frame:
0 to 24 hrs Postdose on Day 1
Reported as:
Mean · mg
Part 1: Total Amount of RO7020531, RO7011785, RO7018822 and RO7033805 in Urine: SAD
mgPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8
RO70205310.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00—
RO70117851.70 ± 0.2745.04 ± 1.2311.0 ± 1.9218.2 ± 8.9625.5 ± 7.8148.1 ± 17.768.6 ± 16.783.5 ± 17.4
RO70188220.0137 ± 0.01670.0754 ± 0.02740.188 ± 0.03990.271 ± 0.1710.372 ± 0.1450.728 ± 0.3371.10 ± 0.4171.87 ± 1.00
RO70338050.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.000.00 ± 0.00—
SecondaryPart 1:Mean Concentration of Interferon Alpha (IFN-alpha): SAD and MAD

Mean concentrations of IFN-alpha for SAD were calculated following single-dose and for MAD it was calculated following multiple doses. The standard deviation (SD) presented is actually the log transformed geometric standard deviation.

Time frame:
SAD: Predose, 2, 6, 12 and 24 hrs Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20
Reported as:
Geometric mean · picogram per milliliter (pg/mL)
Part 1:Mean Concentration of Interferon Alpha (IFN-alpha): SAD and MAD
picogram per milliliter (pg/mL)Part 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
Part 1:Mean Concentration of Interferon Alpha (IFN-alpha): SAD and MAD0.0484 ± 1.31660.0475 ± 1.42880.0438 ± 1.13160.0447 ± 1.11660.0436 ± 1.06000.0494 ± 1.57180.0533 ± 1.52050.1385 ± 3.84170.1358 ± 3.81260.0530 ± 1.01350.0761 ± 1.97690.1148 ± 3.10800.3349 ± 5.5985
SecondaryPart 2: Mean Concentration of IFN-alpha

Mean concentrations of IFN-alpha for Part 2 were calculated following multiple doses. The SD presented is actually the log transformed geometric standard deviation.

Time frame:
Predose, 6, 8 and 24 hrs Postdose on Day 1; Predose, 4-6, 24 hrs Postdose on Days 3, 7 and 21; Predose, 6, 24 hrs Postdose on Day 41
Reported as:
Geometric mean · pg/mL
Part 2: Mean Concentration of IFN-alpha
pg/mLPart 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2 Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Part 2: Mean Concentration of IFN-alpha0.0533 ± 1.06680.3801 ± 9.14420.2831 ± 9.05210.0574 ± 1.27370.3161 ± 8.0853
SecondaryPart 1: Mean Fold Change From Baseline in Cytokine Markers: SAD and MAD

Cytokines markers include Chemokine (C-X-C Motif) Ligand 10 (IP-10), Interleukin 6 (IL-6), Interleukin 10 (IL-10), Interleukin 12 p40 (IL-12 p40), Neopterin, Tumor Necrosis Factor-Alpha (TNF-alpha). The SD presented is actually the log transformed geometric standard deviation.

Time frame:
SAD: Predose, 2, 6, 12, 24, 48 (only Neopterin) and 96 hrs (only Neopterin) Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20
Reported as:
Geometric mean · Fold change
Part 1: Mean Fold Change From Baseline in Cytokine Markers: SAD and MAD
Fold changePart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
Neopterin0.9861 ± 1.18331.0561 ± 1.36781.0175 ± 1.26650.9878 ± 1.23000.9975 ± 1.15030.9896 ± 1.24750.9738 ± 1.17911.0688 ± 1.39261.1257 ± 1.42980.9331 ± 1.14461.5842 ± 1.36371.1228 ± 1.52601.5453 ± 1.5431
IP-100.9067 ± 1.31010.8751 ± 1.47130.9112 ± 1.36240.9250 ± 1.29660.9754 ± 1.23280.9267 ± 1.27541.0390 ± 1.21981.6532 ± 2.02661.2909 ± 1.80031.0256 ± 1.48531.2010 ± 1.41861.2076 ± 1.75431.7327 ± 2.3938
IL-12 p401.0276 ± 1.22320.9414 ± 1.34311.0419 ± 1.21980.9706 ± 1.09571.0000 ± 1.00001.0012 ± 1.01561.0000 ± 1.00001.0025 ± 1.18171.0009 ± 1.00490.6782 ± 1.70250.8672 ± 1.34740.9588 ± 1.34700.9002 ± 1.3373
IL-100.9692 ± 1.50130.7042 ± 2.09701.0568 ± 1.51390.9622 ± 1.34610.9483 ± 1.48710.7451 ± 2.30951.0047 ± 1.33221.1900 ± 1.63281.1926 ± 1.42080.6841 ± 3.42861.0961 ± 1.45600.8834 ± 1.56621.1232 ± 1.5901
IL-61.4493 ± 2.42251.9626 ± 2.98401.2293 ± 1.92091.2464 ± 2.56941.2857 ± 1.84370.9486 ± 1.99421.3207 ± 2.09601.4167 ± 2.31111.6928 ± 2.19811.8290 ± 2.83231.3521 ± 2.24731.9065 ± 2.23251.1306 ± 2.3792
TNF-alpha1.0875 ± 1.87011.0374 ± 1.75610.9435 ± 1.43600.8698 ± 2.17211.0781 ± 1.43580.8825 ± 1.79910.9249 ± 1.65300.9663 ± 1.78461.1756 ± 1.55051.0830 ± 1.61541.2136 ± 1.58280.9887 ± 1.51060.8985 ± 1.6625
SecondaryPart 2: Mean Fold Change From Baseline in Cytokine Markers

Cytokines markers included IP- 10, IL- 6, IL-1 10, IL-12 p40, Neopterin and TNF -alpha. The SD presented is actually the log transformed geometric standard deviation.

Time frame:
Predose, 6, 8 and 24 hrs Postdose on Day 1; Predose, 4-6, 24 hrs Postdose on Days 3, 7 and 21; Predose, 6, 24 hrs Postdose on Day 41
Reported as:
Geometric mean · Fold change
Part 2: Mean Fold Change From Baseline in Cytokine Markers
Fold changePart 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2 Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Neopterin1.0473 ± 1.24261.5596 ± 1.78241.7935 ± 1.92671.0591 ± 1.51541.4676 ± 1.7203
IP-100.9007 ± 1.33682.2323 ± 2.68102.1018 ± 2.95600.8939 ± 1.35571.8598 ± 2.6359
IL-12 p401.0000 ± 1.00001.0109 ± 1.17630.9624 ± 1.12611.0000 ± 1.00000.9740 ± 1.1886
IL-101.0428 ± 1.37671.2587 ± 1.54151.3441 ± 1.97260.8232 ± 1.60601.2540 ± 1.8818
IL-61.0172 ± 1.12511.0909 ± 1.49621.4235 ± 2.19690.8127 ± 1.44781.1596 ± 1.6084
TNF-alpha0.9848 ± 1.41861.2674 ± 1.61691.0527 ± 1.66051.0415 ± 1.30141.0418 ± 1.5470
SecondaryPart 1:Mean Fold Change From Baseline in Markers of Transcriptional Responses: SAD and MAD

Markers of transcriptional responses includes messenger ribonucleic acid interferon-stimulated gene 15(mRNA ISG15), messenger RNA oligoadenylate synthetase 1 (mRNA OAS1), messenger RNA myxovirus resistance 1 gene (mRNA MX-1), messenger RNA Toll-like receptor (mRNA TLR7). The SD presented is actually the log transformed geometric standard deviation.

Time frame:
SAD: Predose, 2, 6, 12 and 24 Postdose; MAD: Predose, 2, 6, 12, and 24 hrs Postdose on Day 1; Predose, 2, 6 and 24 hrs Postdose on Days 3, 5, 7, 13 and 20
Reported as:
Geometric mean · Fold change
Part 1:Mean Fold Change From Baseline in Markers of Transcriptional Responses: SAD and MAD
Fold changePart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
mRNA ISG150.9709 ± 1.27521.1708 ± 1.93261.0525 ± 1.39850.9386 ± 1.59241.0799 ± 1.39801.0190 ± 1.62951.6951 ± 2.57353.0359 ± 4.04563.1083 ± 3.90141.1703 ± 1.68411.9408 ± 2.63722.3632 ± 2.84534.8748 ± 4.1091
mRNA OAS11.0251 ± 1.22951.0414 ± 1.45711.0338 ± 1.28760.9666 ± 1.40600.8584 ± 1.74991.0680 ± 1.48511.4093 ± 1.78082.3437 ± 2.52542.2308 ± 2.49931.0651 ± 1.52531.8186 ± 2.38712.1467 ± 2.26103.2312 ± 3.0239
mRNA Mx-11.0179 ± 1.30780.9750 ± 1.52091.0166 ± 1.41430.9045 ± 1.48440.8811 ± 1.58841.0837 ± 1.63141.5271 ± 2.30702.8672 ± 3.51702.6646 ± 3.09440.9813 ± 1.56612.3613 ± 2.83392.0847 ± 2.81183.2388 ± 3.9277
mRNA TLR71.0698 ± 1.31241.1518 ± 1.36971.0401 ± 1.26671.0658 ± 1.22371.0965 ± 1.36981.1289 ± 1.27101.2120 ± 1.33281.5925 ± 1.64731.5596 ± 2.14031.2315 ± 1.64281.2089 ± 1.67161.2626 ± 1.56961.6081 ± 1.8082
SecondaryPart 2: Mean Fold Change From Baseline in Markers of Transcriptional Responses

Transcriptional markers include mRNA ISG15, mRNA OAS1, mRNA MX-1, mRNA TLR7. The SD presented is actually the log transformed geometric standard deviation.

Time frame:
Predose, 6, 8, 24 hrs postdose on Day 1; Predose, 4-6, 24 hrs postdose on Days 3, 7, 21; Predose, 6, 24 hrs postdose on Day 41
Reported as:
Geometric mean · Fold change
Part 2: Mean Fold Change From Baseline in Markers of Transcriptional Responses
Fold changePart 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2 Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
mRNA ISG151.0745 ± 1.61354.2007 ± 3.90596.8997 ± 4.13130.8661 ± 1.59143.9424 ± 3.3660
mRNA OAS10.9617 ± 1.29263.1021 ± 2.67664.0466 ± 2.73180.7973 ± 1.44253.0355 ± 2.4692
mRNA Mx-10.9140 ± 1.48473.1760 ± 3.26065.0962 ± 3.37440.8296 ± 1.33093.4811 ± 2.9921
mRNA TLR71.0848 ± 1.43061.5280 ± 1.75271.5745 ± 1.74111.0240 ± 1.36201.3211 ± 1.9422
SecondaryEffect of RO7020531 Dosing on ECG Parameters (PR [PQ], QRS, QT, QTcF in Miliseconds [ms]) Using Exposure-response Analysis: SAD and MAD
Time frame:
SAD: Predose, 0.5, 1, 2, 4, 6, 12, 24 and 48 hrs Post dose on Day 1; MAD: Predose, 0.5, 1,2,4 and 12 hrs Postdose on Day 1 and 13; Predose, 2 and 6 hrs Postdose on Day 3, Predose, 6 and 24 hrs Postdose on Day , 7, 9, and 11

No measurements were reported for this outcome.

SecondaryPart 2: Plasma Concentrations of Tenofovir, Tenofovir Alafenamide, Entecavir, Adefovir and Telbivudine

Adefovir was not administered to any participants in the study. Hence, no data could be collected for plasma concentration of adefovir. As participants in each cohort received different NUCs the data for Cohorts 1, 2 and 3 have been reported separately.

Time frame:
Pre-dose and 2-4 hours post-dose on Day 1, Day 21 and Day 41
Reported as:
Mean · ng/mL
Part 2: Plasma Concentrations of Tenofovir, Tenofovir Alafenamide, Entecavir, Adefovir and Telbivudine
ng/mLPart 2 Cohorts 1Part 2 Cohort 2Part 2 Cohort 3
Entecavir - Day 1: Predose0.467 ± 0.130.420 ± 0.100.590 ± 0.62
Entecavir - Day 1: 2-4 hours Post Dose1.974 ± 1.081.455 ± 0.531.019 ± 0.60
Entecavir - Day 21: Predose0.494 ± 0.070.365 ± 0.090.810 ± 0.92
Entecavir - Day 21: 2-4 hours Post Dose1.543 ± 0.761.568 ± 0.800.935 ± 0.20
Entecavir - Day 41: Predose0.406 ± 0.100.308 ± 0.080.887 ± 0.89
Entecavir - Day 41: 2-4 hours Post Dose1.373 ± 0.661.267 ± 0.501.427 ± 0.69
Tenofovir - Day 1: Predose54.93 ± 32.760.00 ± 26.571.12 ± 35.7
Tenofovir - Day 1: 2-4 hours Post Dose155.1 ± 106214.2 ± 64.0245.0 ± 49.8
Tenofovir - Day 21: Predose63.90 ± 29.558.40 ± 21.457.02 ± 28.0
Tenofovir - Day 21: 2-4 hours Post Dose206.6 ± 81.4273.0 ± 177222.2 ± 70.8
Tenofovir - Day 41: Predose66.82 ± 34.064.06 ± 32.756.56 ± 26.3
Tenofovir - Day 41: 2-4 hours Post Dose250.9 ± 108250.4 ± 112188.4 ± 58.7
Tenofovir Alafenamide - Day 1: 2-4 hours Post Dose—0.058 ± 0.058—
Telbivudine - Day 1: Predose—602.0 ± 602.0330.0 ± 330.0
Telbivudine - Day 1: 2-4 hours Post Dose—4760 ± 47602820 ± 2820
Telbivudine - Day 21: Predose—1030 ± 1030314.0 ± 314.0
Telbivudine - Day 21: 2-4 hours Post Dose—2030 ± 20301790 ± 1790
Telbivudine - Day 41: Predose—935.0 ± 935.0260.0 ± 260.0
Telbivudine - Day 41: 2-4 hours Post Dose—2850 ± 28502450 ± 2450
PrimaryPart 1: Percentage of SAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

For all laboratory parameters included, there exists a Roche predefined standard reference range. Laboratory values falling outside this standard reference range were labeled "H" for high or "L" for low in HV/participant listings of laboratory data.

Time frame:
From randomization up to Day 8
Reported as:
Number · percentage of participants
Part 1: Percentage of SAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results
percentage of participantsPart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8
Eosinophils Absolute - High00000016.700
Erythrocyte Mean Corpuscular HGB Concentration - Low0012.512.50012.5012.5
Erythrocyte Mean Corpuscular Hemoglobin - Low6.700000000
Erythrocyte Mean Corpuscular Volume - High0012.5000000
Hematocrit - Low6.725.012.500025.012.512.5
Hemoglobin - Low6.325.012.512.5025.0025.00
Hemoglobin - High0000000012.5
Lymphocytes Absolute - Low012.500000012.5
Monocytes Absolute - High012.512.5000000
Neutrophils, Total, Absolute - Low7.114.312.50016.7012.50
Neutrophils, Total, Absolute - High000000012.50
Platelet - Low000012.5012.500
Platelet - High000000012.50
Red Blood Cell Count - Low6.3012.50012.512.500
Red Blood Cell Count - High6.700000000
Reticulocytes, Pct - High0012.5012.50000
White Blood Cell Count - Low13.30012.500000
White Blood Cell Count - High000000012.50
Albumin - Low00000014.312.512.5
Alkaline Phosphatase - Low00000012.500
Alkaline Phosphatase - High00012.500000
Bicarbonate CO2 - Low6.3012.5012.500012.5
Blood Glucose, Fasting - High7.112.550.000042.912.514.3
Blood Urea Nitrogen - Low7.112.5014.314.30040.040.0
Blood Urea Nitrogen - High6.3012.500012.500
Calcium - High6.3000012.5000
Chloride - Low6.3000000012.5
Cholesterol - High8.320.00025.0016.714.30
Creatinine - Low012.50000000
Creatinine - High0012.500012.500
Cystatin C - Low0000000012.5
Cystatin C - High13.312.50012.50012.525.0
Direct Bilirubin - High14.300000000
Phosphorus - High6.300012.50012.50
Potassium - Low000012.50000
Protein, Total - Low20.014.325.025.012.525.016.728.612.5
Protein, Total - High0000000012.5
SGOT/AST - High0012.50012.5012.50
SGPT/ALT - High0012.5014.312.50012.5
Sodium - High6.300000000
Triglycerides, Fasting - High0014.3028.60000
Uric Acid - High7.10014.325.0016.712.50
Creatinine Clearance - Low00000035.700
Creatinine Clearance - High23.1016.720.020.025.0000
PrimaryPart 1: Percentage of MAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

For all laboratory parameters included, there exists a Roche predefined standard reference range. Laboratory values falling outside this standard reference range were labeled "H" for high or "L" for low in HV/participant listings of laboratory data.

Time frame:
From randomization up to Day 20
Reported as:
Number · percentage of participants
Part 1: Percentage of MAD Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results
percentage of participantsPart 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
Eosinophils Absolute - High012.500
Erythrocyte Mean Corpuscular HGB Concentration - Low0028.642.9
Erythrocyte Mean Corpuscular HGB Concentration - High014.300
Erythrocyte Mean Corpuscular Hemoglobin - Low00012.5
Hematocrit - Low16.762.562.537.5
Hemoglobin - Low16.750.062.537.5
Neutrophils, Total, Absolute16.725.016.737.5
Red blood cell count - Low0025.025.0
Reticulocytes, Pct - High0025.012.5
White Blood Cell Count - Low0020.025.0
Albumin - Low40.037.537.525.0
Alkaline Phosphatase - Low0012.50
Bicarbonate CO2 - Low16.712.500
Blood Glucose, Fasting - High20.012.516.714.3
Blood Urea Nitrogen - Low33.333.380.0100.0
Cholesterol - High16.712.520.014.3
Creatinine - Low025.0042.9
Cystatin C - High033.300
Direct Bilirubin - High20.014.3014.3
Phosphorus - High012.512.525.0
Protein, Total - Low25.075.050.062.5
SGOT/AST - High012.500
SGPT/ALT - High012.5014.3
Uric Acid - Low012.500
Uric Acid - High16.712.500
Creatinine Clearance - Low16.7000
Creatinine Clearance - High66.733.320.033.3
PrimaryPart 2: Percentage of Chronic Hepatitis B Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results

For all laboratory parameters included, there exists a Roche predefined standard reference range. Laboratory values falling outside this standard reference range were labeled "H" for high or "L" for low in HV/participant listings of laboratory data.

Time frame:
From randomization up to Week 12
Reported as:
Number · percentage of participants
Part 2: Percentage of Chronic Hepatitis B Participants With Laboratory Abnormalities Based on Hematology, Clinical Chemistry, Coagulation and Urinalysis Test Results
percentage of participantsPart 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Eosinophil Absolute - High06.30——
Erythrocyte Mean Corpuscular HGB Concentration - Low———06.7
Erythrocyte Mean Corpuscular Volume - High06.70——
Hemoglobin - Low———06.7
Lymphocytes Absolute - Low16.725.025.020.013.3
Lymphocytes Absolute - High00020.00
Monocytes Absolute - Low16.78.314.3026.7
Monocytes Absolute - High16.76.3000
Neutrophils, Total, Absolute - Low20.035.762.5046.2
Neutrophils, Total, Absolute - High06.3000
Platelet - Low018.812.506.7
Red Blood Cell Count - Low0012.506.7
Reticulocytes, Pct - High06.312.5——
White Blood Cell Count - Low20.046.242.920.050.0
White Blood Cell Count - High06.3000
Bicarbonate CO2 - Low06.312.520.07.1
Bicarbonate CO2 - High06.3006.7
Bilirubin - High06.3007.1
Blood Glucose, Fasting - Low16.712.5020.00
Blood Glucose, Fasting - High16.735.70014.3
Blood Urea Nitrogen - High33.326.712.506.7
Calcium - Low06.3006.7
Chloride - Low013.3000
Chloride - High16.70020.00
Cholesterol - High014.325.080.012.5
Creatinine - High07.1020.00
Cystatin C - High20.026.7006.7
Indirect Bilirubin - Low16.718.8050.053.3
Indirect Bilirubin - High06.3007.1
Phosphorus - Low043.8006.7
Phosphorus - High06.3020.07.1
Potassium - High33.36.312.540.013.3
Protein, Total - Low00006.7
Protein, Total - High06.712.520.00
SGOT/AST - High06.70042.9
SGPT/ALT - High16.76.3025.036.4
Sodium - High0012.520.00
Triglycerides, Fasting - High16.750.012.550.014.3
Uric Acid - High06.712.5014.3
Activated Partial Thromboplastin Time - High06.70013.3
International Normalized Ratio - High16.700014.3
Prothrombin Time - High20.030.814.366.741.7
PrimaryPart 1: Percentage of SAD Participants With Abnormalities in Electrocardiograph (ECG) Parameters

Triplicate 12-lead ECGs were obtained after the participant has been in a supine position for at least 10 minutes. Clinically significant RO7020531-related changes included confirmation of mean QTc 500 milliseconds (msec) or 60 msec longer than the pre-dose baseline.

Time frame:
From randomization up to Day 8
Reported as:
Number · percentage of participants
Part 1: Percentage of SAD Participants With Abnormalities in Electrocardiograph (ECG) Parameters
percentage of participantsPart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8
Average Heart Rate (12-Lead Trip.) - Low6.300000000
Average Heart Rate (12-Lead Trip.) - High0012.5000000
Average PR (12-Lead Trip.) - Low00012.514.30000
Average PR (12-Lead Trip.) - High00012.500012.50
Average QRS (12-Lead Trip.) - High0000012.5012.50
Average QTcF (12-Lead Trip.) - High012.50000000
PrimaryPart 1: Percentage of MAD Participants With Abnormalities in ECG Parameters

Triplicate 12-lead ECGs were obtained after the participants has been in a supine position for at least 10 minutes. Clinically significant RO7020531-related changes included confirmation of mean QTc 500 msec or 60 msec longer than the pre-dose baseline.

Time frame:
From randomization up to Day 20
Reported as:
Number · percentage of participants
Part 1: Percentage of MAD Participants With Abnormalities in ECG Parameters
percentage of participantsPart 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
Average PR (12-Lead Trip.) - Low00012.5
Average PR (12-Lead Trip.) - High014.314.30
PrimaryPart 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in ECG Parameters

Triplicate 12-lead ECGs were obtained after the participant has been in a supine position for at least 10 minutes. Clinically significant RO7020531-related changes included confirmation of mean QTc 500 msec or 60 msec longer than the pre-dose baseline.

Time frame:
From randomization up to Week 12
Reported as:
Number · percentage of participants
Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in ECG Parameters
percentage of participantsPart 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Average Heart Rate (12-Lead Trip.) - High00006.7
Average PR (12-Lead Trip.) - Low00006.7
Average PR (12-Lead Trip.) - High00020.00
Average QTcF (12-Lead Trip.) - Low06.3000
Average QTcF (12-Lead Trip.) - High16.70007.1
PrimaryPart 1: Percentage of SAD Participants With Abnormalities in Vital Signs

Vital signs include blood pressure, pulse rate, respiratory rate and body temperature. Blood pressure, respiratory rate and pulse rate were obtained after the participant had been in a supine or sitting position for at least 5 minutes. Blood pressure measurement were performed in triplicate (can be as short as 20 second to 1 minute interval between measurements).

Time frame:
From randomization up to Day 8
Reported as:
Number · percentage of participants
Part 1: Percentage of SAD Participants With Abnormalities in Vital Signs
percentage of participantsPart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8
Average Diastolic BP - High012.525.0000000
Average Systolic BP - High6.30012.512.512.5000
Pulse Rate - Low6.300000000
Pulse Rate - High0012.5000000
Respiratory Rate - High26.7028.600012.525.00
Temperature - Low71.4100.0100.0—100.0100.0100.080.040.0
Temperature - High12.5012.5000025.00
PrimaryPart 1: Percentage of MAD Participants With Abnormalities in Vital Signs

Vital signs include blood pressure, pulse rate, respiratory rate and body temperature. Blood pressure, respiratory rate and pulse rate were obtained after the participant had been in a supine or sitting position for at least 5 minutes. Blood pressure measurement were performed in triplicate (can be as short as 20 second to 1 minute interval between measurements).

Time frame:
From randomization up to Day 20
Reported as:
Number · percentage of participants
Part 1: Percentage of MAD Participants With Abnormalities in Vital Signs
percentage of participantsPart 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3
Average Diastolic BP - High00012.5
Average Systolic BP - High025.012.512.5
Pulse Rate - High00012.5
Respiratory Rate - High33.325.037.550.0
Temperature - Low100.0100.075.050.0
Temperature - High0025.037.5
PrimaryPart 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in Vital Signs

Vital signs include blood pressure, pulse rate, respiratory rate and body temperature. Blood pressure, respiratory rate and pulse rate were obtained after the participant had been in a supine or sitting position for at least 5 minutes. Blood pressure measurement were performed in triplicate (can be as short as 20 second to 1 minute interval between measurements).

Time frame:
From randomization up to Week 12
Reported as:
Number · percentage of participants
Part 2: Percentage of Chronic Hepatitis B Participants With Abnormalities in Vital Signs
percentage of participantsPart 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Average Diastolic BP - High33.335.712.560.06.7
Average Systolic BP - High50.031.312.520.06.7
Pulse Rate - Low00006.7
Pulse Rate - High00040.040.0
Respiratory Rate - High16.76.312.506.7
Temperature - Low—100.0100.0100.0100.0
Temperature - High012.50020.0

Adverse events

Collected over From Randomization to End of Study (up to 4.5 years). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part 1 Cohorts 1-8 SAD: Placebo0/16 (0%)0/16 (0%)5/16 (31.3%)
Part 1 SAD: Cohort 10/8 (0%)0/8 (0%)2/8 (25%)
Part 1 SAD: Cohort 20/8 (0%)0/8 (0%)4/8 (50%)
Part 1 SAD: Cohort 30/8 (0%)0/8 (0%)2/8 (25%)
Part 1 SAD: Cohort 40/8 (0%)0/8 (0%)2/8 (25%)
Part 1 SAD: Cohort 50/8 (0%)0/8 (0%)2/8 (25%)
Part 1 SAD: Cohort 60/8 (0%)0/8 (0%)2/8 (25%)
Part 1 SAD: Cohort 70/8 (0%)0/8 (0%)2/8 (25%)
Part 1 SAD: Cohort 80/8 (0%)0/8 (0%)3/8 (37.5%)
Part 1 Cohorts 1-3, MAD: Placebo0/6 (0%)0/6 (0%)5/6 (83.3%)
Part 1 MAD: Cohort 10/8 (0%)0/8 (0%)6/8 (75%)
Part 1 MAD: Cohort 20/8 (0%)0/8 (0%)7/8 (87.5%)
Part 1 MAD: Cohort 30/8 (0%)0/8 (0%)7/8 (87.5%)
Part 2 Cohorts 1-3: Placebo0/6 (0%)0/6 (0%)3/6 (50%)
Part 2: Cohort 1 and 20/16 (0%)0/16 (0%)11/16 (68.8%)
Part 2: Cohort 30/8 (0%)0/8 (0%)6/8 (75%)
Part 2 Cohort 4: Placebo0/5 (0%)0/5 (0%)3/5 (60%)
Part 2: Cohort 40/15 (0%)1/15 (6.7%)12/15 (80%)
Most frequent serious events
Most frequent serious events
EventPart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3Part 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
Influenza like illnessGeneral disorders0/160/80/80/80/80/80/80/80/80/60/80/80/80/60/160/80/51/15
Most frequent other events
Showing 10 of 92
Most frequent other events
EventPart 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3Part 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4
HeadacheNervous system disorders0/160/82/81/80/80/80/81/81/81/63/83/83/81/63/164/80/54/15
Dermatitis contactSkin and subcutaneous tissue disorders0/160/80/80/80/80/80/81/80/83/60/80/80/80/60/160/81/51/15
NauseaGastrointestinal disorders0/160/81/80/81/80/80/80/80/81/63/81/83/80/61/160/80/51/15
Catheter site bruiseGeneral disorders0/160/80/80/80/80/80/81/81/82/61/83/80/80/60/161/80/51/15
Catheter site painGeneral disorders0/160/80/80/80/80/80/80/80/80/60/80/83/80/60/160/80/50/15
Decreased appetiteMetabolism and nutrition disorders0/160/80/80/80/80/80/80/80/80/60/80/83/80/61/160/80/52/15
DiarrhoeaGastrointestinal disorders0/161/80/80/80/80/80/80/80/82/60/80/80/80/61/160/80/50/15
Catheter site phlebitisGeneral disorders0/160/80/80/80/80/80/80/80/82/60/80/80/80/60/160/80/50/15
Influenza like illnessGeneral disorders0/160/80/80/80/80/80/80/80/80/60/80/80/80/62/161/80/54/15
Abdominal pain upperGastrointestinal disorders0/160/80/80/80/80/80/80/80/80/60/80/82/80/60/160/80/50/15

Baseline characteristics

Safety population included all participants who had received at least 1 dose of the study drug.

Age, Continuous
Age, Continuous(years)Part 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3Part 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4Total
Mean28.7 ± 10.131.5 ± 15.837.6 ± 16.222.6 ± 2.723.8 ± 4.529.3 ± 7.033.4 ± 12.525.8 ± 3.529.5 ± 10.927.2 ± 4.026.8 ± 3.926.5 ± 2.925.0 ± 7.549.3 ± 13.347.6 ± 8.942.4 ± 10.542.6 ± 11.540.1 ± 9.333.3 ± 12.2
Sex: Female, Male
Sex: Female, Male(Participants)Part 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3Part 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4Total
Female52222213222421421948
Male11666667564646512646112
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Part 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3Part 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4Total
Hispanic or Latino2010011100000000006
Not Hispanic or Latino148788777868886158514152
Not Stated0000000000000000011
Unknown0000000000000010001
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Part 1 Cohorts 1-8 SAD: PlaceboPart 1 SAD: Cohort 1Part 1 SAD: Cohort 2Part 1 SAD: Cohort 3Part 1 SAD: Cohort 4Part 1 SAD: Cohort 5Part 1 SAD: Cohort 6Part 1 SAD: Cohort 7Part 1 SAD: Cohort 8Part 1 Cohorts 1-3, MAD: PlaceboPart 1 MAD: Cohort 1Part 1 MAD: Cohort 2Part 1 MAD: Cohort 3Part 2 Cohorts 1-3: PlaceboPart 2: Cohort 1 and 2Part 2: Cohort 3Part 2 Cohort 4: PlaceboPart 2: Cohort 4Total
Asian22102131400321952644
Black or African American0100000000001010003
Native Hawaiian or other Pacific Islander1110000000010110017
White1346867573674445338103
Multiple0000000010101000003
08

Study locations

18 sites
  • Gastroenterology department, Second clinic of internal diseases
    Sofia, 1407, Bulgaria
  • COMAC Medical; Clinical Research Unit for Phase I
    Sofia, 1612, Bulgaria
  • Queen Mary Hospital
    Hong Kong, 999077, Hong Kong
  • The Chinese University of Hong Kong
    Shatin, 123456, Hong Kong
  • Azienda Ospedaliero Universitaria Di Modena Policlinico; U.O. Farmacia
    Modena, Emilia-Romagna 41124, Italy
  • ASST PAPA GIOVANNI XXIII; Epatologia e gastroenterologia pediatrica e dei trapianti
    Bergamo, Lombardia 24127, Italy
  • Medicina Generale ed Epatologia (Humanitas-Rozzano)
    Rozzano, Lombardia 20089, Italy
  • Academisch Medisch Centrum Universiteit Amsterdam; Dermatology and VU University Medical Center
    Amsterdam, 1100 DD, Netherlands
  • Auckland Clinical Studies
    Auckland, 1142, New Zealand
  • National Cheng Kung University Hospital
    Tainan, 70457, Taiwan
  • Taipei Veterans General Hospital
    Taipei City, 112, Taiwan
  • Chang Gung Memorial Hospital
    Taoyuan, 333, Taiwan
  • Taichung Veterans General Hospital
    Xitun Dist., 40705, Taiwan
  • King Chulalongkorn Memorial Hospital
    Bangkok, 10330, Thailand
  • Siriraj Hospital
    Bangkok, 10700, Thailand
  • Maharaj Nakorn Chiang Mai Hospital
    Chiang Mai, 50200, Thailand
  • Royal Liverpool University Hospital
    Liverpool, L7 8XP, United Kingdom
  • King College Hospital NHS Foundation Trust
    London, SE5 9RS, United Kingdom
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jun 24, 2020

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

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Feb 8, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT02956850
Lead sponsor
Hoffmann-La Roche
Responsible party
Sponsor
First posted
Nov 6, 2016
Start date
Dec 12, 2016
Primary completion
Jun 15, 2021
Completion
Jun 15, 2021
Results posted
Feb 8, 2024
Last update
Feb 8, 2024

Study contacts

Clinical Trials
study director · Hoffmann-La Roche
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Feb 2024. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Hepatitis A→

Other studies from this sponsor

Hoffmann-La Roche

Start the discussion