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TerminatedNCT03762681Updated May 11, 2021Results posted

A Study of RO7239958 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers and Participants With Chronic Hepatitis B Virus Infection

A Phase 1 interventional study of RO7239958 and Placebo in Hepatitis B Virus Infection, sponsored by Hoffmann-La Roche. Terminated at 14 sites in 7 countries. Open to participants aged 18 Years to 65 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2021-05-11.

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

Why this study was terminated
The study was terminated due to program discontinuation.
Phase
Phase 1
Study type
Interventional
Enrollment
55
Allocation
Randomized
Ages
18 Years to 65 Years
Sex
All
01

Study summary

This study is designed to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of single and multiple ascending doses in healthy volunteers (HV) and participants diagnosed with chronic hepatitis B (CHB).

02

Conditions studied

  • Hepatitis B Virus Infection
03

In context

Infections

6,687 studies on the registry are indexed under Infections; 807 are open to participants now.

This study's enrollment of 55 is below the median of 120 across 4,200 interventional studies indexed under Infections.

Browse Infections 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

All Parts

-Female participants should be of non-childbearing potential and male participants who are with pregnant partners or partners of childbearing potential must agree to remain abstinent or use contraceptive measures

Part 1 (SAD HV only)

  • Healthy, as judged by the Investigator
  • Non-smoker (nor tobacco containing products) for at least 90 days prior to dosing on Day 1, and agrees to remain non-smoker during the study

Part 2 (CHB only)

  • Positive serum HBsAg status for > 6 months prior to screening
  • Serum HBsAg level ≥ 250 IU/mL at screening
  • On stable entecavir or tenofovir (alone or in combination) treatment and having received the same drug in the 3 months prior to randomisation
  • HBV DNA below the lower limit of quantification (LLQ) for ≥ 6 months prior to screening by local testing, and confirmed at screening
  • Screening laboratory values (including hematology, chemistry, urinalysis) within normal ranges
  • No past or current diagnosis of cirrhosis

Exclusion criteria

Exclusion Criteria:

All Parts

  • History or presence of significant cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrine, hematological disorders, or diagnosed central or peripheral neurological disease, capable of altering the absorption, metabolism, or elimination of drugs, or constituting a risk when taking the study treatment, or of interfering with the interpretation of the data
  • History of lymphoma, leukemia, or malignancy within the past five years
  • Positive for human immunodeficiency virus (HIV) infection
  • Participant under judicial supervision, guardianship or curatorship

Part 1 (SAD HV only)

  • Screening ECG showing clinically relevant abnormalities
  • Abnormal blood pressure
  • History or presence of liver disease, or known hepatic or biliary abnormalities
  • Alanine aminotransferase (ALT) ≥1.5 × upper limit of normal (ULN)
  • Any clinically significant out of range findings in other laboratory test results or any other clinically significant (as judged by the Investigator) abnormalities in the physical examination at screening and on Day -1
  • Positive for hepatitis B surface antigen (HBsAg), or hepatitis B core total antibody [anti-HBc]), or hepatitis C virus (HCV) antibody test result

Part 2 (CHB only)

  • History or presence of bridging fibrosis or cirrhosis or decompensated liver disease
  • History or presence of a medical condition associated with liver disease other than HBV infection. Other known hepatic or biliary abnormalities
  • History of or suspicion of hepatocellular carcinoma or alpha fetoprotein (AFP) ≥13 ng/mL
  • History of having received (in the last six months) or currently receiving any systemic antineoplastic (including radiation) or immune-modulatory treatment (including systemic corticosteroids)
  • History of organ transplantation
  • Estimated glomerular filtration rate (eGFR) \<70 mL/min/1.73m\^2
  • Confirmed QT interval corrected using Fridericia's formula (QTcF) >450 ms
  • Expected to need any other systemic antiviral therapy at any time during participation in the study
  • Positive hepatitis C antibody test
05

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Sequential assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
55 participants (actual)

Study arms

  • Experimental
    Part 1: Single Ascending Dose, HV

    Healthy volunteers will be administered a single dose of RO7239958 or placebo subcutaneously (SC).

    Drug: RO7239958 · Other: Placebo

  • Experimental
    Part 2a: Multi-dose, CHB

    Participants with chronic hepatitis B will be administered different dose levels of RO7239958 or placebo SC. Dosages will be determined from data collected from Part 1.

    Drug: RO7239958 · Other: Placebo

  • Experimental
    Part 2b: Multi-dose, CHB (Optional)

    Additional study arm to open based on data collected from Part 2a. Participants with chronic hepatitis B will be administered different doses and frequencies of RO7239958 or placebo SC.

    Drug: RO7239958 · Other: Placebo

Interventions

  • DrugRO7239958

    Solution for injection, subcutaneous use (SC).

  • OtherPlacebo

    Sodium chloride solution for injection, SC

06

What researchers measure

Primary outcomes

  1. Number of Participants With Adverse Events (AEs)

    An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product (including investigational drug) during the course of a clinical investigation. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease that was temporally associated with the use of the investigational product, regardless of whether it was considered to be related to the investigational product or not.

    Time frame: Up to approximately 16 months

  2. Number of Participants With Clinically Significant Changes in Vital Signs

    Number of participants with clinically significant abnormalities in vital signs such as systolic and diastolic blood pressure, heart rate, body temperature were evaluated.

    Time frame: Up to approximately 16 months

  3. Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings

    Time frame: Up to approximately 16 months

  4. Number of Participants With Clinically Significant Changes in Clinical Laboratory Results

    Number of participants with clinically significant abnormalities in clinical laboratory parameters such as serum chemistry, hematology, coagulation, viral serology, urinalysis were evaluated.

    Time frame: Up to approximately 16 months

  5. Number of Participants With Injection Site Reactions (ISRs)

    Injection site reactions (ISRs) referred to any localized sign or symptom, including pain, erythema, swelling and pruritus and were graded as follows: Grade 1: mild, Grade 2: moderate; Grade 3: severe. Adverse events related to ISRs were reported.

    Time frame: Up to approximately 16 months

Secondary outcomes

  1. Maximum Plasma Concentration (Cmax) of RO7239958

    Time frame: Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.

  2. Time to Cmax (Tmax) of RO7239958

    Time frame: Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.

  3. Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958

    Time frame: Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.

  4. Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958

    Time frame: Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.

  5. Half-life (t1/2) of RO7239958

    Time frame: Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.

  6. Cumulative Amount of Drug Excreted in Urine (Ae)

    The cumulative amount of drug excreted in urine (Ae) over a 24 hour period or over defined time periods linked to the pools of urine collected was analyzed.

    Time frame: Part 1: 0-4 h, 0-8 h, 0-12 h and 0-24 h on Day 1; Part 2a: 0-4 h and 0-8 h on Days 1 and 29

  7. Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels

    Time frame: Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)

  8. Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels

    Time frame: Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)

  9. Part 2a: Number of Participants With HBsAg Loss

    HBsAg loss was defined as a measurement below the lower limit of sensitivity.

    Time frame: Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)

  10. Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants

    HBeAg loss was defined as a measurement below lower limit of sensitivity. Positive HBeAg is a marker of an actively replicating HBV virus infection.

    Time frame: Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)

  11. Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants

    Anti-HbBe was defined as an antibody to HBeAg. Positive HBeAg is a marker of an actively replicating HBV virus infection.

    Time frame: Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)

  12. Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification

    Participants with HBV DNA below the assay lower limit of quantification i.e. LLOQ \<20 IU/ml at each time-point were analyzed.

    Time frame: Part 2a: Day 1 (pre-dose), 15, 29 (pre-dose); at discontinuation (DC), rebound and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)

07

Results

Posted Apr 9, 2021

Participant flow

In Part 1 all healthy volunteers were enrolled at 1 center in New Zealand. In Part 2a, participants with chronic hepatitis B (CHB) were enrolled at 7 centers across 5 countries: Bulgaria, United Kingdom, Hong Kong, Korea, and New Zealand.

Part 1
Participant flow — Part 1
MilestonePart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Started88888000
Completed88878000
Not completed00010000
Withdrew: Withdrawal by subject00010000
Part 2a
Participant flow — Part 2a
MilestonePart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Started00000285
Completed00000284
Not completed00000001
Withdrew: Pandemic travel restrictions00000001

Outcome measures

PrimaryNumber of Participants With Adverse Events (AEs)

An adverse event (AE) was defined as any untoward medical occurrence in a participant who was administered a pharmaceutical product (including investigational drug) during the course of a clinical investigation. An AE could therefore be any unfavorable and unintended sign (including abnormal laboratory findings), symptom, or disease that was temporally associated with the use of the investigational product, regardless of whether it was considered to be related to the investigational product or not.

Time frame:
Up to approximately 16 months
Reported as:
Count of participants · Participants
Number of Participants With Adverse Events (AEs)
ParticipantsPart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Number of Participants With Adverse Events (AEs)73475141
PrimaryNumber of Participants With Clinically Significant Changes in Vital Signs

Number of participants with clinically significant abnormalities in vital signs such as systolic and diastolic blood pressure, heart rate, body temperature were evaluated.

Time frame:
Up to approximately 16 months
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes in Vital Signs
ParticipantsPart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Number of Participants With Clinically Significant Changes in Vital Signs00000000
PrimaryNumber of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings
Time frame:
Up to approximately 16 months
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings
ParticipantsPart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings00000000
PrimaryNumber of Participants With Clinically Significant Changes in Clinical Laboratory Results

Number of participants with clinically significant abnormalities in clinical laboratory parameters such as serum chemistry, hematology, coagulation, viral serology, urinalysis were evaluated.

Time frame:
Up to approximately 16 months
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results
ParticipantsPart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Absolute Neutrophil Count, Low (<10^9/L)11000100
Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High00002000
Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High11111000
PrimaryNumber of Participants With Injection Site Reactions (ISRs)

Injection site reactions (ISRs) referred to any localized sign or symptom, including pain, erythema, swelling and pruritus and were graded as follows: Grade 1: mild, Grade 2: moderate; Grade 3: severe. Adverse events related to ISRs were reported.

Time frame:
Up to approximately 16 months
Reported as:
Count of participants · Participants
Number of Participants With Injection Site Reactions (ISRs)
ParticipantsPart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Number of Participants With Injection Site Reactions (ISRs)01000010
SecondaryMaximum Plasma Concentration (Cmax) of RO7239958
Time frame:
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Reported as:
Mean · nanomoles/liter (nmol/L)
Maximum Plasma Concentration (Cmax) of RO7239958
nanomoles/liter (nmol/L)Part 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Day 15.93 ± 1.3719.9 ± 5.65102 ± 43.7166 ± 64.89.21 ± 1.6921.2 ± 2.96
Day 29————8.81 ± 3.5119.3 ± 2.77
SecondaryTime to Cmax (Tmax) of RO7239958
Time frame:
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Reported as:
Median · hours (h)
Time to Cmax (Tmax) of RO7239958
hours (h)Part 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Day 11.75 (1.50 to 4.00)2.00 (1.53 to 4.00)2.00 (1.00 to 4.00)2.00 (1.50 to 3.00)1.00 (0.50 to 2.00)1.00 (1.00 to 2.00)
Day 29————2.00 (1.92 to 4.00)2.00 (1.00 to 2.00)
SecondaryArea Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958
Time frame:
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Reported as:
Mean · h*nmol/L
Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958
h*nmol/LPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Day 134.5 ± 3.07106 ± 26.4508 ± 152868 ± 23059.4 ± 17.7153 ± 22.1
Day 29————63.9 ± 24.6161 ± 10.1
SecondaryArea Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958
Time frame:
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Reported as:
Mean · h*nmol/L
Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958
h*nmol/LPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Day 133.9 ± 3.0798.4 ± 22.6481 ± 150819 ± 22754.9 ± 11.5125 ± 15.9
Day 29————58.0 ± 19.9119 ± 5.36
SecondaryHalf-life (t1/2) of RO7239958
Time frame:
Part 1: pre-dose on Day 1 and post-dose at 15 minutes (min), 30 min, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, 24, 30, 36, 48, 72, 96, 120, 168 hours. Part 2a: pre-dose on Days 1 and 29 and post-dose at 30 min, 1, 2, 4, 6, 8, 24 hours.
Reported as:
Median · h
Half-life (t1/2) of RO7239958
hPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Day 15.36 (1.83 to 58.7)151 (126 to 293)411 (333 to 836)515 (305 to 1000)3.13 (2.87 to 512)499 (395 to 743)
Day 29————3.04 (2.67 to 3.87)231 (181 to 284)
SecondaryCumulative Amount of Drug Excreted in Urine (Ae)

The cumulative amount of drug excreted in urine (Ae) over a 24 hour period or over defined time periods linked to the pools of urine collected was analyzed.

Time frame:
Part 1: 0-4 h, 0-8 h, 0-12 h and 0-24 h on Day 1; Part 2a: 0-4 h and 0-8 h on Days 1 and 29
Reported as:
Mean · micrograms (µg)
Cumulative Amount of Drug Excreted in Urine (Ae)
micrograms (µg)Part 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Day 1, accumulation interval 0- 4 h16.4 ± 8.8735.4 ± 33.7104 ± 72.6290 ± 27225.0 ± 14.181.9 ± 125
Day 1, accumulation interval 0-8 h23.1 ± 12.350.1 ± 48.2153 ± 76.0446 ± 35935.2 ± 22.3127 ± 170
Day 1, accumulation interval 0-12 h23.5 ± 16.551.2 ± 51.0172 ± 81.3474 ± 379——
Day 1, accumulation interval 0-24 h23.8 ± 20.051.7 ± 55.9189 ± 92.1497 ± 383——
Day 29, accumulation interval 0-4 h————23.4 ± 14.546.4 ± 44.4
Day 29, accumulation interval 0-8 h————38.1 ± 23.385.1 ± 56.9
SecondaryPart 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels
Time frame:
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Reported as:
Mean · log10[international units (IU)/mL]
Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels
log10[international units (IU)/mL]Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Baseline3.66 ± 0.503.52 ± 0.613.22 ± 0.38
Change at Day 8-0.20 ± 0.44-0.05 ± 0.18-0.13 ± 0.16
Change at Day 15-0.20 ± 0.27-0.05 ± 0.31-0.13 ± 0.17
Change at Day 22-0.40 ± 0.40-0.05 ± 0.12-0.17 ± 0.23
Change at Day 29-0.06 ± 0.19-0.09 ± 0.11-0.08 ± 0.23
Change at Day 430.04 ± 0.02-0.11 ± 0.35-0.26 ± 0.33
Change at Day 570.05 ± 0.01-0.12 ± 0.30-0.19 ± 0.26
Change at Day 85-0.01 ± 0.09-0.14 ± 0.24-0.06 ± 0.08
Change at Day 1130.23 ± NA-0.03 ± 0.09-0.05 ± 0.09
SecondaryPart 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels
Time frame:
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Reported as:
Mean · log10[IU/mL]
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels
log10[IU/mL]Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Baseline0.48 ± 0.000.50 ± 0.080.48 ± 0.00
Change at Day 80.00 ± 0.000.02 ± 0.050.00 ± 0.00
Change at Day 150.00 ± 0.000.00 ± 0.000.00 ± 0.00
Change at Day 220.00 ± 0.000.02 ± 0.060.00 ± 0.00
Change at Day 290.00 ± 0.000.01 ± 0.040.00 ± 0.00
Change at Day 430.00 ± 0.000.02 ± 0.050.00 ± 0.00
Change at Day 570.00 ± 0.000.02 ± 0.060.00 ± 0.00
Change at Day 850.00 ± 0.000.02 ± 0.070.00 ± 0.00
Change at Day 1130.00 ± NA0.02 ± 0.060.00 ± 0.00
SecondaryPart 2a: Number of Participants With HBsAg Loss

HBsAg loss was defined as a measurement below the lower limit of sensitivity.

Time frame:
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Reported as:
Count of participants · Participants
Part 2a: Number of Participants With HBsAg Loss
ParticipantsPart 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Part 2a: Number of Participants With HBsAg Loss000
SecondaryPart 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants

HBeAg loss was defined as a measurement below lower limit of sensitivity. Positive HBeAg is a marker of an actively replicating HBV virus infection.

Time frame:
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Reported as:
Count of participants · Participants
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants
ParticipantsPart 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
HBeAg Loss at Baseline—0—
HBeAg Loss at Day 8—0—
HBeAg Loss at Day 15—0—
HBeAg Loss at Day 22—0—
HBeAg Loss at Day 29—0—
HBeAg Loss at Day 43—0—
HBeAg Loss at Day 57—0—
HBeAg Loss at Day 85—0—
HBeAg Loss at Day 113—0—
SecondaryPart 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants

Anti-HbBe was defined as an antibody to HBeAg. Positive HBeAg is a marker of an actively replicating HBV virus infection.

Time frame:
Part 2a: Days 1 (pre-dose), 8, 15, 22, 29 (pre-dose); at discontinuation (DC) and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Reported as:
Count of participants · Participants
Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants
ParticipantsPart 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Anti-HBe Seroconversion at Baseline—0—
Anti-HBe Seroconversion at Day 8—0—
Anti-HBe Seroconversion at Day 15—0—
Anti-HBe Seroconversion at Day 22—0—
Anti-HBe Seroconversion at Day 29—0—
Anti-HBe Seroconversion at Day 43—0—
Anti-HBe Seroconversion at Day 57—0—
Anti-HBe Seroconversion at Day 85—0—
Anti-HBe Seroconversion at Day 113—0—
SecondaryPart 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification

Participants with HBV DNA below the assay lower limit of quantification i.e. LLOQ \<20 IU/ml at each time-point were analyzed.

Time frame:
Part 2a: Day 1 (pre-dose), 15, 29 (pre-dose); at discontinuation (DC), rebound and at follow-up visits 14, 28, 56, and 84 days after the last dose of study drug (up to 16 weeks)
Reported as:
Number · participants
Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification
participantsPart 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
HBeAg+: Baseline—3—
HBeAg-: Baseline255
HBeAg+: Day 15—3—
HBeAg-: Day 15245
HBeAg+: Day 29—3—
HBeAg-: Day 29255
HBeAg+: Day 43—2—
HBeAg-: Day 43255
HBeAg+: Day 57—3—
HBeAg-: Day 57254
HBeAg+: Day 85—3—
HBeAg-: Day 85254
HBeAg+: Day 113—3—
HBeAg-: Day 113144

Adverse events

Collected over Up to approximately 16 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Part 1, Cohorts 1-4: Placebo0/8 (0%)0/8 (0%)7/8 (87.5%)
Part 1, Cohort 1: 0.1 mg/kg RO72399580/8 (0%)0/8 (0%)3/8 (37.5%)
Part 1, Cohort 2: 0.3 mg/kg RO72399580/8 (0%)0/8 (0%)4/8 (50%)
Part 1, Cohort 3: 1.0 mg/kg RO72399580/8 (0%)0/8 (0%)7/8 (87.5%)
Part 1, Cohort 4: 1.5 mg/kg RO72399580/8 (0%)0/8 (0%)5/8 (62.5%)
Part 2a: Placebo0/2 (0%)0/2 (0%)1/2 (50%)
Part 2a, Arm 1: 0.2 mg/kg RO72399580/8 (0%)0/8 (0%)4/8 (50%)
Part 2a, Arm 2: 0.4 mg/kg RO72399580/5 (0%)0/5 (0%)1/5 (20%)
Most frequent other events
Showing 10 of 37
Most frequent other events
EventPart 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958
Upper respiratory tract infectionInfections and infestations2/80/80/80/80/81/20/80/5
ContusionInjury, poisoning and procedural complications0/80/80/80/83/80/20/80/5
Catheter site inflammationGeneral disorders0/82/80/80/80/80/20/80/5
Influenza like illnessGeneral disorders0/80/80/80/82/80/20/81/5
Vessel puncture site bruiseGeneral disorders0/82/80/81/80/80/20/80/5
Transaminases increasedInvestigations1/80/80/80/82/80/20/80/5
HeadacheNervous system disorders1/80/80/81/82/80/22/80/5
CoughRespiratory, thoracic and mediastinal disorders0/80/80/80/81/80/22/80/5
RhinorrhoeaRespiratory, thoracic and mediastinal disorders0/80/80/80/81/80/22/80/5
FatigueGeneral disorders1/80/80/80/81/80/20/81/5

Baseline characteristics

Safety population included all study participants who received at least one dose of RO7239958 or placebo.

Age, Continuous
Age, Continuous(years)Part 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958Total
Mean37.0 ± 12.736.5 ± 15.128.9 ± 9.131.8 ± 14.128.8 ± 7.246.0 ± 18.447.5 ± 7.445.6 ± 7.336.4 ± 12.7
Sex: Female, Male
Sex: Female, Male(Participants)Part 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958Total
Female101000002
Male7878828553
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Part 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958Total
Hispanic or Latino011200105
Not Hispanic or Latino8776827550
Unknown or Not Reported000000000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Part 1, Cohorts 1-4: PlaceboPart 1, Cohort 1: 0.1 mg/kg RO7239958Part 1, Cohort 2: 0.3 mg/kg RO7239958Part 1, Cohort 3: 1.0 mg/kg RO7239958Part 1, Cohort 4: 1.5 mg/kg RO7239958Part 2a: PlaceboPart 2a, Arm 1: 0.2 mg/kg RO7239958Part 2a, Arm 2: 0.4 mg/kg RO7239958Total
American Indian or Alaska Native000000000
Asian2121004111
Native Hawaiian or Other Pacific Islander100110104
Black or African American000001001
White5735603433
More than one race001011003
Unknown or Not Reported002100003
08

Study locations

14 sites
  • Acibadem City Clinic Tokuda Hospital Ead
    Sofia, 1407, Bulgaria
  • COMAC Medical; Clinical Research Unit for Phase I
    Sofia, 1612, Bulgaria
  • Queen Mary Hospital
    Hong Kong, Hong Kong
  • Pusan National University Hospital
    Busan, 49241, Korea, Republic of
  • Asan Medical Center.
    Seoul, 138-736, Korea, Republic of
  • Auckland Clinical Studies Limited
    Auckland, 1010, New Zealand
  • ID Clinic
    Myslowice, 41-400, Poland
  • Kaohsiung Medical University
    Kaohsiung, 807, Taiwan
  • National Cheng Kung University Hospital
    Tainan, 70457, Taiwan
  • Western General Hospital
    Edinburgh, EH4 2XU, United Kingdom
  • Royal Liverpool University Hospital
    Liverpool, L7 8XP, United Kingdom
  • King College Hospital NHS Foundation Trust
    London, SE5 9RS, United Kingdom
  • Chelsea & Westminster Hospital
    London, SW10 9NH, United Kingdom
  • St George's Hospital
    London, SW17 0QT, United Kingdom
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Feb 18, 2020

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

Individual participant data

Plan to share: Yes — Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on May 11, 2021, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03762681
Lead sponsor
Hoffmann-La Roche
Responsible party
Sponsor
First posted
Dec 4, 2018
Start date
Dec 14, 2018
Primary completion
Apr 6, 2020
Completion
Apr 6, 2020
Results posted
Apr 9, 2021
Last update
May 11, 2021

Study contacts

Clinical Trials
study director · Hoffmann-La Roche

Oversight

FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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