Hepatitis B Virus Infection
Conditions
Brief 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).
Interventions
OTHERPlacebo
Sodium chloride solution for injection, SC
DRUGRO7239958
Solution for injection, subcutaneous use (SC).
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | Up to approximately 16 months | 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. |
| Number of Participants With Clinically Significant Changes in Vital Signs | Up to approximately 16 months | Number of participants with clinically significant abnormalities in vital signs such as systolic and diastolic blood pressure, heart rate, body temperature were evaluated. |
| Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | Up to approximately 16 months | — |
| Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Up to approximately 16 months | Number of participants with clinically significant abnormalities in clinical laboratory parameters such as serum chemistry, hematology, coagulation, viral serology, urinalysis were evaluated. |
| Number of Participants With Injection Site Reactions (ISRs) | Up to approximately 16 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Amount of Drug Excreted in Urine (Ae) | 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 | 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. |
| Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | 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) | — |
| Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | 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) | — |
| Maximum Plasma Concentration (Cmax) of RO7239958 | 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. | — |
| Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | 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) | HBeAg loss was defined as a measurement below lower limit of sensitivity. Positive HBeAg is a marker of an actively replicating HBV virus infection. |
| Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | 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) | Anti-HbBe was defined as an antibody to HBeAg. Positive HBeAg is a marker of an actively replicating HBV virus infection. |
| Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | 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) | Participants with HBV DNA below the assay lower limit of quantification i.e. LLOQ \<20 IU/ml at each time-point were analyzed. |
| Part 2a: Number of Participants With HBsAg Loss | 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) | HBsAg loss was defined as a measurement below the lower limit of sensitivity. |
| Time to Cmax (Tmax) of RO7239958 | 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. | — |
| Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | 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. | — |
| Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | 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. | — |
| Half-life (t1/2) of RO7239958 | 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. | — |
Countries
Bulgaria, Hong Kong, New Zealand, Poland, South Korea, Taiwan, United Kingdom
Participant flow
Recruitment details
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.
Pre-assignment details
Part 1, single ascending dose (SAD), enrolled healthy volunteers. In Part 2a, two doses of RO7239958 at two dose levels were administered in participants with CHB. No additional arms were opened in Part 2a. Part 2B of the study was not conducted due to early termination of the study.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Cohorts 1-4: Placebo Healthy volunteers were administered a single dose of placebo subcutaneously (SC). | 8 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC. | 8 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC. | 8 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC. | 8 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC. | 8 |
| Part 2a: Placebo Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W). | 2 |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 Participants with CHB were administered two doses of 0.2 mg/kg RO7239958 SC at a dosing frequency of Q4W. | 8 |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 Participants with CHB were administered two doses of 0.4 mg/kg RO7239958 SC at a dosing frequency of Q4W. | 5 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Part 1 | Withdrawal by Subject | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Part 2a | Pandemic Travel Restrictions | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1, Cohorts 1-4: Placebo | Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Part 2a: Placebo | Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 37.0 years STANDARD_DEVIATION 12.7 | 36.5 years STANDARD_DEVIATION 15.1 | 28.9 years STANDARD_DEVIATION 9.1 | 31.8 years STANDARD_DEVIATION 14.1 | 28.8 years STANDARD_DEVIATION 7.2 | 46.0 years STANDARD_DEVIATION 18.4 | 47.5 years STANDARD_DEVIATION 7.4 | 45.6 years STANDARD_DEVIATION 7.3 | 36.4 years STANDARD_DEVIATION 12.7 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 8 Participants | 7 Participants | 7 Participants | 6 Participants | 8 Participants | 2 Participants | 7 Participants | 5 Participants | 50 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 4 Participants | 1 Participants | 11 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 5 Participants | 7 Participants | 3 Participants | 5 Participants | 6 Participants | 0 Participants | 3 Participants | 4 Participants | 33 Participants |
| Sex: Female, Male Female | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Sex: Female, Male Male | 7 Participants | 8 Participants | 7 Participants | 8 Participants | 8 Participants | 2 Participants | 8 Participants | 5 Participants | 53 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 2 | 0 / 8 | 0 / 5 |
| other Total, other adverse events | 7 / 8 | 3 / 8 | 4 / 8 | 7 / 8 | 5 / 8 | 1 / 2 | 4 / 8 | 1 / 5 |
| serious Total, serious adverse events | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 2 | 0 / 8 | 0 / 5 |
Outcome results
Primary
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
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Number of Participants With Adverse Events (AEs) | 7 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Number of Participants With Adverse Events (AEs) | 3 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Number of Participants With Adverse Events (AEs) | 4 Participants |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Number of Participants With Adverse Events (AEs) | 7 Participants |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Number of Participants With Adverse Events (AEs) | 5 Participants |
| Part 2a: Placebo | Number of Participants With Adverse Events (AEs) | 1 Participants |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Number of Participants With Adverse Events (AEs) | 4 Participants |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Number of Participants With Adverse Events (AEs) | 1 Participants |
Primary
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
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 1 Participants |
| Part 1, Cohorts 1-4: Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 1 Participants |
| Part 1, Cohorts 1-4: Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 1 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 1 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 1 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 0 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 0 Participants |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 0 Participants |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 0 Participants |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 1 Participants |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 2 Participants |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 0 Participants |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 1 Participants |
| Part 2a: Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 0 Participants |
| Part 2a: Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 1 Participants |
| Part 2a: Placebo | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 0 Participants |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 0 Participants |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 0 Participants |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 0 Participants |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Absolute Neutrophil Count, Low (<10^9/L) | 0 Participants |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High | 0 Participants |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Clinical Laboratory Results | Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings
Time frame: Up to approximately 16 months
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part 2a: Placebo | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings | 0 Participants |
Primary
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
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 2a: Placebo | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Number of Participants With Clinically Significant Changes in Vital Signs | 0 Participants |
Primary
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
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Number of Participants With Injection Site Reactions (ISRs) | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Number of Participants With Injection Site Reactions (ISRs) | 1 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Number of Participants With Injection Site Reactions (ISRs) | 0 Participants |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Number of Participants With Injection Site Reactions (ISRs) | 0 Participants |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Number of Participants With Injection Site Reactions (ISRs) | 0 Participants |
| Part 2a: Placebo | Number of Participants With Injection Site Reactions (ISRs) | 0 Participants |
| Part 2a, Arm 1: 0.2 mg/kg RO7239958 | Number of Participants With Injection Site Reactions (ISRs) | 1 Participants |
| Part 2a, Arm 2: 0.4 mg/kg RO7239958 | Number of Participants With Injection Site Reactions (ISRs) | 0 Participants |
Secondary
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.
Population: PK population included all study participants who received active treatment unless there were significant violations of inclusion or exclusion criteria, or if data were unavailable or insufficient to allow for full analysis. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 1 | 33.9 h*nmol/L | Standard Deviation 3.07 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 1 | 98.4 h*nmol/L | Standard Deviation 22.6 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 1 | 481 h*nmol/L | Standard Deviation 150 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 1 | 819 h*nmol/L | Standard Deviation 227 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 1 | 54.9 h*nmol/L | Standard Deviation 11.5 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 29 | 58.0 h*nmol/L | Standard Deviation 19.9 |
| Part 2a: Placebo | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 29 | 119 h*nmol/L | Standard Deviation 5.36 |
| Part 2a: Placebo | Area Under the Curve From Time 0 to 24 Hours (AUC0-24) of RO7239958 | Day 1 | 125 h*nmol/L | Standard Deviation 15.9 |
Secondary
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.
Population: PK population included all study participants who received active treatment unless there were significant violations of inclusion or exclusion criteria, or if data were unavailable or insufficient to allow for full analysis. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 1 | 34.5 h*nmol/L | Standard Deviation 3.07 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 1 | 106 h*nmol/L | Standard Deviation 26.4 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 1 | 508 h*nmol/L | Standard Deviation 152 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 1 | 868 h*nmol/L | Standard Deviation 230 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 1 | 59.4 h*nmol/L | Standard Deviation 17.7 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 29 | 63.9 h*nmol/L | Standard Deviation 24.6 |
| Part 2a: Placebo | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 29 | 161 h*nmol/L | Standard Deviation 10.1 |
| Part 2a: Placebo | Area Under the Curve From Time 0 to the Last Measurable Concentration (AUClast) of RO7239958 | Day 1 | 153 h*nmol/L | Standard Deviation 22.1 |
Secondary
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
Population: Pharmacokinetic (PK) population included all study participants who received active treatment unless there were significant violations of inclusion or exclusion criteria, or if data were unavailable or insufficient to allow for full analysis. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0- 4 h | 16.4 micrograms (µg) | Standard Deviation 8.87 |
| Part 1, Cohorts 1-4: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-8 h | 23.1 micrograms (µg) | Standard Deviation 12.3 |
| Part 1, Cohorts 1-4: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-12 h | 23.5 micrograms (µg) | Standard Deviation 16.5 |
| Part 1, Cohorts 1-4: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-24 h | 23.8 micrograms (µg) | Standard Deviation 20 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-12 h | 51.2 micrograms (µg) | Standard Deviation 51 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0- 4 h | 35.4 micrograms (µg) | Standard Deviation 33.7 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-8 h | 50.1 micrograms (µg) | Standard Deviation 48.2 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-24 h | 51.7 micrograms (µg) | Standard Deviation 55.9 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-8 h | 153 micrograms (µg) | Standard Deviation 76 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-12 h | 172 micrograms (µg) | Standard Deviation 81.3 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0- 4 h | 104 micrograms (µg) | Standard Deviation 72.6 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-24 h | 189 micrograms (µg) | Standard Deviation 92.1 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0- 4 h | 290 micrograms (µg) | Standard Deviation 272 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-8 h | 446 micrograms (µg) | Standard Deviation 359 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-12 h | 474 micrograms (µg) | Standard Deviation 379 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-24 h | 497 micrograms (µg) | Standard Deviation 383 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 29, accumulation interval 0-4 h | 23.4 micrograms (µg) | Standard Deviation 14.5 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-8 h | 35.2 micrograms (µg) | Standard Deviation 22.3 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 29, accumulation interval 0-8 h | 38.1 micrograms (µg) | Standard Deviation 23.3 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0- 4 h | 25.0 micrograms (µg) | Standard Deviation 14.1 |
| Part 2a: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0- 4 h | 81.9 micrograms (µg) | Standard Deviation 125 |
| Part 2a: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 1, accumulation interval 0-8 h | 127 micrograms (µg) | Standard Deviation 170 |
| Part 2a: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 29, accumulation interval 0-4 h | 46.4 micrograms (µg) | Standard Deviation 44.4 |
| Part 2a: Placebo | Cumulative Amount of Drug Excreted in Urine (Ae) | Day 29, accumulation interval 0-8 h | 85.1 micrograms (µg) | Standard Deviation 56.9 |
Secondary
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.
Population: PK population included all study participants who received active treatment unless there were significant violations of inclusion or exclusion criteria, or if data were unavailable or insufficient to allow for full analysis. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Half-life (t1/2) of RO7239958 | Day 1 | 5.36 h |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Half-life (t1/2) of RO7239958 | Day 1 | 151 h |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Half-life (t1/2) of RO7239958 | Day 1 | 411 h |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Half-life (t1/2) of RO7239958 | Day 1 | 515 h |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Half-life (t1/2) of RO7239958 | Day 1 | 3.13 h |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Half-life (t1/2) of RO7239958 | Day 29 | 3.04 h |
| Part 2a: Placebo | Half-life (t1/2) of RO7239958 | Day 29 | 231 h |
| Part 2a: Placebo | Half-life (t1/2) of RO7239958 | Day 1 | 499 h |
Secondary
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.
Population: PK population included all study participants who received active treatment unless there were significant violations of inclusion or exclusion criteria, or if data were unavailable or insufficient to allow for full analysis. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 1 | 5.93 nanomoles/liter (nmol/L) | Standard Deviation 1.37 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 1 | 19.9 nanomoles/liter (nmol/L) | Standard Deviation 5.65 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 1 | 102 nanomoles/liter (nmol/L) | Standard Deviation 43.7 |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 1 | 166 nanomoles/liter (nmol/L) | Standard Deviation 64.8 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 29 | 8.81 nanomoles/liter (nmol/L) | Standard Deviation 3.51 |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 1 | 9.21 nanomoles/liter (nmol/L) | Standard Deviation 1.69 |
| Part 2a: Placebo | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 29 | 19.3 nanomoles/liter (nmol/L) | Standard Deviation 2.77 |
| Part 2a: Placebo | Maximum Plasma Concentration (Cmax) of RO7239958 | Day 1 | 21.2 nanomoles/liter (nmol/L) | Standard Deviation 2.96 |
Secondary
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)
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 43 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Baseline | 0.48 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 8 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 15 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 22 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 29 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 57 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 85 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 113 | 0.00 log10[IU/mL] | — |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 29 | 0.01 log10[IU/mL] | Standard Deviation 0.04 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 57 | 0.02 log10[IU/mL] | Standard Deviation 0.06 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Baseline | 0.50 log10[IU/mL] | Standard Deviation 0.08 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 85 | 0.02 log10[IU/mL] | Standard Deviation 0.07 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 43 | 0.02 log10[IU/mL] | Standard Deviation 0.05 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 8 | 0.02 log10[IU/mL] | Standard Deviation 0.05 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 22 | 0.02 log10[IU/mL] | Standard Deviation 0.06 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 113 | 0.02 log10[IU/mL] | Standard Deviation 0.06 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 15 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 113 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 22 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 85 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 29 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 43 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 15 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Baseline | 0.48 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 57 | 0.00 log10[IU/mL] | Standard Deviation 0 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels | Change at Day 8 | 0.00 log10[IU/mL] | Standard Deviation 0 |
Secondary
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)
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 22 | -0.40 log10[international units (IU)/mL] | Standard Deviation 0.4 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 113 | 0.23 log10[international units (IU)/mL] | — |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 43 | 0.04 log10[international units (IU)/mL] | Standard Deviation 0.02 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 29 | -0.06 log10[international units (IU)/mL] | Standard Deviation 0.19 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Baseline | 3.66 log10[international units (IU)/mL] | Standard Deviation 0.5 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 85 | -0.01 log10[international units (IU)/mL] | Standard Deviation 0.09 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 15 | -0.20 log10[international units (IU)/mL] | Standard Deviation 0.27 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 8 | -0.20 log10[international units (IU)/mL] | Standard Deviation 0.44 |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 57 | 0.05 log10[international units (IU)/mL] | Standard Deviation 0.01 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 29 | -0.09 log10[international units (IU)/mL] | Standard Deviation 0.11 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Baseline | 3.52 log10[international units (IU)/mL] | Standard Deviation 0.61 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 8 | -0.05 log10[international units (IU)/mL] | Standard Deviation 0.18 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 15 | -0.05 log10[international units (IU)/mL] | Standard Deviation 0.31 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 22 | -0.05 log10[international units (IU)/mL] | Standard Deviation 0.12 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 43 | -0.11 log10[international units (IU)/mL] | Standard Deviation 0.35 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 57 | -0.12 log10[international units (IU)/mL] | Standard Deviation 0.3 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 85 | -0.14 log10[international units (IU)/mL] | Standard Deviation 0.24 |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 113 | -0.03 log10[international units (IU)/mL] | Standard Deviation 0.09 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 15 | -0.13 log10[international units (IU)/mL] | Standard Deviation 0.17 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Baseline | 3.22 log10[international units (IU)/mL] | Standard Deviation 0.38 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 57 | -0.19 log10[international units (IU)/mL] | Standard Deviation 0.26 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 8 | -0.13 log10[international units (IU)/mL] | Standard Deviation 0.16 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 113 | -0.05 log10[international units (IU)/mL] | Standard Deviation 0.09 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 29 | -0.08 log10[international units (IU)/mL] | Standard Deviation 0.23 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 22 | -0.17 log10[international units (IU)/mL] | Standard Deviation 0.23 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 85 | -0.06 log10[international units (IU)/mL] | Standard Deviation 0.08 |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels | Change at Day 43 | -0.26 log10[international units (IU)/mL] | Standard Deviation 0.33 |
Secondary
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)
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With HBsAg Loss | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With HBsAg Loss | 0 Participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With HBsAg Loss | 0 Participants |
Secondary
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)
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Baseline | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 8 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 15 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 22 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 29 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 43 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 57 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 85 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B e Antibody (Anti-HBe) Seroconversion in HBeAg-positive Participants | Anti-HBe Seroconversion at Day 113 | 0 Participants |
Secondary
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)
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Baseline | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 8 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 15 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 22 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 29 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 43 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 57 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 85 | 0 Participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants | HBeAg Loss at Day 113 | 0 Participants |
Secondary
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)
Population: Safety population included all study participants who received at least one dose of RO7239958 or placebo. Data are reported for participants HBeAg positive or negative at baseline. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Baseline | 2 participants |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 29 | 2 participants |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 15 | 2 participants |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 57 | 2 participants |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 113 | 1 participants |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 43 | 2 participants |
| Part 1, Cohorts 1-4: Placebo | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 85 | 2 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 43 | 5 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg+: Baseline | 3 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Baseline | 5 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg+: Day 15 | 3 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 15 | 4 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg+: Day 29 | 3 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 29 | 5 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg+: Day 43 | 2 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg+: Day 57 | 3 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 57 | 5 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg+: Day 85 | 3 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 85 | 5 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg+: Day 113 | 3 participants |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 113 | 4 participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 15 | 5 participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 43 | 5 participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Baseline | 5 participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 29 | 5 participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 85 | 4 participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 57 | 4 participants |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Part 2a: Number of Participants With Hepatitis B Virus Deoxyribonucleic Acid (HBV DNA) Below the Assay Lower Limit of Quantification | HBeAg-: Day 113 | 4 participants |
Secondary
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.
Population: PK population included all study participants who received active treatment unless there were significant violations of inclusion or exclusion criteria, or if data were unavailable or insufficient to allow for full analysis. Number analyzed is the number of participants with data available for analyses.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Part 1, Cohorts 1-4: Placebo | Time to Cmax (Tmax) of RO7239958 | Day 1 | 1.75 hours (h) |
| Part 1, Cohort 1: 0.1 mg/kg RO7239958 | Time to Cmax (Tmax) of RO7239958 | Day 1 | 2.00 hours (h) |
| Part 1, Cohort 2: 0.3 mg/kg RO7239958 | Time to Cmax (Tmax) of RO7239958 | Day 1 | 2.00 hours (h) |
| Part 1, Cohort 3: 1.0 mg/kg RO7239958 | Time to Cmax (Tmax) of RO7239958 | Day 1 | 2.00 hours (h) |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Time to Cmax (Tmax) of RO7239958 | Day 1 | 1.00 hours (h) |
| Part 1, Cohort 4: 1.5 mg/kg RO7239958 | Time to Cmax (Tmax) of RO7239958 | Day 29 | 2.00 hours (h) |
| Part 2a: Placebo | Time to Cmax (Tmax) of RO7239958 | Day 29 | 2.00 hours (h) |
| Part 2a: Placebo | Time to Cmax (Tmax) of RO7239958 | Day 1 | 1.00 hours (h) |