Trial Outcomes & Findings for A Study of RO7239958 to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics in Healthy Volunteers and Participants With Chronic Hepatitis B Virus Infection (NCT NCT03762681)

Last Updated: 2021-05-11

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE1

Target enrollment

55 participants

Primary outcome timeframe

Up to approximately 16 months

Results posted on

2021-05-11

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, 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.

Participant milestones

Participant milestones
Measure	Part 1, Cohorts 1-4: Placebo Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	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).	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.	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.
Part 1 STARTED	8	8	8	8	8	0	0	0
Part 1 COMPLETED	8	8	8	7	8	0	0	0
Part 1 NOT COMPLETED	0	0	0	1	0	0	0	0
Part 2a STARTED	0	0	0	0	0	2	8	5
Part 2a COMPLETED	0	0	0	0	0	2	8	4
Part 2a NOT COMPLETED	0	0	0	0	0	0	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1, Cohorts 1-4: Placebo Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	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).	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.	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.
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

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=2 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	Part 2a, Arm 1: 0.2 mg/kg RO7239958 n=8 Participants Participants with CHB were administered two doses of 0.2 mg/kg RO7239958 SC at a dosing frequency of Q4W.	Part 2a, Arm 2: 0.4 mg/kg RO7239958 n=5 Participants Participants with CHB were administered two doses of 0.4 mg/kg RO7239958 SC at a dosing frequency of Q4W.	Total n=55 Participants Total of all reporting groups
Age, Continuous	37.0 years STANDARD_DEVIATION 12.7 • n=99 Participants	36.5 years STANDARD_DEVIATION 15.1 • n=107 Participants	28.9 years STANDARD_DEVIATION 9.1 • n=206 Participants	31.8 years STANDARD_DEVIATION 14.1 • n=7 Participants	28.8 years STANDARD_DEVIATION 7.2 • n=31 Participants	46.0 years STANDARD_DEVIATION 18.4 • n=30 Participants	47.5 years STANDARD_DEVIATION 7.4 • n=3 Participants	45.6 years STANDARD_DEVIATION 7.3 • n=6 Participants	36.4 years STANDARD_DEVIATION 12.7 • n=114 Participants
Sex: Female, Male Female	1 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	2 Participants n=114 Participants
Sex: Female, Male Male	7 Participants n=99 Participants	8 Participants n=107 Participants	7 Participants n=206 Participants	8 Participants n=7 Participants	8 Participants n=31 Participants	2 Participants n=30 Participants	8 Participants n=3 Participants	5 Participants n=6 Participants	53 Participants n=114 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=99 Participants	1 Participants n=107 Participants	1 Participants n=206 Participants	2 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants	0 Participants n=6 Participants	5 Participants n=114 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	8 Participants n=99 Participants	7 Participants n=107 Participants	7 Participants n=206 Participants	6 Participants n=7 Participants	8 Participants n=31 Participants	2 Participants n=30 Participants	7 Participants n=3 Participants	5 Participants n=6 Participants	50 Participants n=114 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	0 Participants n=114 Participants
Race (NIH/OMB) Asian	2 Participants n=99 Participants	1 Participants n=107 Participants	2 Participants n=206 Participants	1 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	4 Participants n=3 Participants	1 Participants n=6 Participants	11 Participants n=114 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	1 Participants n=7 Participants	1 Participants n=31 Participants	0 Participants n=30 Participants	1 Participants n=3 Participants	0 Participants n=6 Participants	4 Participants n=114 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants	0 Participants n=107 Participants	0 Participants n=206 Participants	0 Participants n=7 Participants	0 Participants n=31 Participants	1 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	1 Participants n=114 Participants
Race (NIH/OMB) White	5 Participants n=99 Participants	7 Participants n=107 Participants	3 Participants n=206 Participants	5 Participants n=7 Participants	6 Participants n=31 Participants	0 Participants n=30 Participants	3 Participants n=3 Participants	4 Participants n=6 Participants	33 Participants n=114 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants	0 Participants n=107 Participants	1 Participants n=206 Participants	0 Participants n=7 Participants	1 Participants n=31 Participants	1 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	3 Participants n=114 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants	0 Participants n=107 Participants	2 Participants n=206 Participants	1 Participants n=7 Participants	0 Participants n=31 Participants	0 Participants n=30 Participants	0 Participants n=3 Participants	0 Participants n=6 Participants	3 Participants n=114 Participants

PRIMARY outcome

Timeframe: Up to approximately 16 months

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

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=2 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	Part 2a, Arm 1: 0.2 mg/kg RO7239958 n=8 Participants Participants with CHB were administered two doses of 0.2 mg/kg RO7239958 SC at a dosing frequency of Q4W.	Part 2a, Arm 2: 0.4 mg/kg RO7239958 n=5 Participants Participants with CHB were administered two doses of 0.4 mg/kg RO7239958 SC at a dosing frequency of Q4W.
Number of Participants With Adverse Events (AEs)	7 Participants	3 Participants	4 Participants	7 Participants	5 Participants	1 Participants	4 Participants	1 Participants

PRIMARY outcome

Timeframe: Up to approximately 16 months

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

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

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=2 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	Part 2a, Arm 1: 0.2 mg/kg RO7239958 n=8 Participants Participants with CHB were administered two doses of 0.2 mg/kg RO7239958 SC at a dosing frequency of Q4W.	Part 2a, Arm 2: 0.4 mg/kg RO7239958 n=5 Participants Participants with CHB were administered two doses of 0.4 mg/kg RO7239958 SC at a dosing frequency of Q4W.
Number of Participants With Clinically Significant Changes in Vital Signs	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to approximately 16 months

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

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=2 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	Part 2a, Arm 1: 0.2 mg/kg RO7239958 n=8 Participants Participants with CHB were administered two doses of 0.2 mg/kg RO7239958 SC at a dosing frequency of Q4W.	Part 2a, Arm 2: 0.4 mg/kg RO7239958 n=5 Participants Participants with CHB were administered two doses of 0.4 mg/kg RO7239958 SC at a dosing frequency of Q4W.
Number of Participants With Clinically Significant Changes in Electrocardiogram (ECG) Findings	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to approximately 16 months

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

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

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=2 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	Part 2a, Arm 1: 0.2 mg/kg RO7239958 n=8 Participants Participants with CHB were administered two doses of 0.2 mg/kg RO7239958 SC at a dosing frequency of Q4W.	Part 2a, Arm 2: 0.4 mg/kg RO7239958 n=5 Participants Participants with CHB were administered two doses of 0.4 mg/kg RO7239958 SC at a dosing frequency of Q4W.
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Alanine Transaminase (ALT) or Serum Glutamic Pyruvic Transaminase (SGPT), High	0 Participants	0 Participants	0 Participants	0 Participants	2 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Aspartate Aminotransferase (AST) or Serum Glutamic-Oxaloacetic Transaminase (SGOT), High	1 Participants	1 Participants	1 Participants	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Clinically Significant Changes in Clinical Laboratory Results Absolute Neutrophil Count, Low (<10^9/L)	1 Participants	1 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants	0 Participants

PRIMARY outcome

Timeframe: Up to approximately 16 months

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

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.

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=2 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	Part 2a, Arm 1: 0.2 mg/kg RO7239958 n=8 Participants Participants with CHB were administered two doses of 0.2 mg/kg RO7239958 SC at a dosing frequency of Q4W.	Part 2a, Arm 2: 0.4 mg/kg RO7239958 n=5 Participants Participants with CHB were administered two doses of 0.4 mg/kg RO7239958 SC at a dosing frequency of Q4W.
Number of Participants With Injection Site Reactions (ISRs)	0 Participants	1 Participants	0 Participants	0 Participants	0 Participants	0 Participants	1 Participants	0 Participants

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=5 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	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.	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.
Maximum Plasma Concentration (Cmax) of RO7239958 Day 1	5.93 nanomoles/liter (nmol/L) Standard Deviation 1.37	19.9 nanomoles/liter (nmol/L) Standard Deviation 5.65	102 nanomoles/liter (nmol/L) Standard Deviation 43.7	166 nanomoles/liter (nmol/L) Standard Deviation 64.8	9.21 nanomoles/liter (nmol/L) Standard Deviation 1.69	21.2 nanomoles/liter (nmol/L) Standard Deviation 2.96	—	—
Maximum Plasma Concentration (Cmax) of RO7239958 Day 29	—	—	—	—	8.81 nanomoles/liter (nmol/L) Standard Deviation 3.51	19.3 nanomoles/liter (nmol/L) Standard Deviation 2.77	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=5 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	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.	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.
Time to Cmax (Tmax) of RO7239958 Day 1	1.75 hours (h) Interval 1.5 to 4.0	2.00 hours (h) Interval 1.53 to 4.0	2.00 hours (h) Interval 1.0 to 4.0	2.00 hours (h) Interval 1.5 to 3.0	1.00 hours (h) Interval 0.5 to 2.0	1.00 hours (h) Interval 1.0 to 2.0	—	—
Time to Cmax (Tmax) of RO7239958 Day 29	—	—	—	—	2.00 hours (h) Interval 1.92 to 4.0	2.00 hours (h) Interval 1.0 to 2.0	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=5 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	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.	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.
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	106 h*nmol/L Standard Deviation 26.4	508 h*nmol/L Standard Deviation 152	868 h*nmol/L Standard Deviation 230	59.4 h*nmol/L Standard Deviation 17.7	153 h*nmol/L Standard Deviation 22.1	—	—
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	161 h*nmol/L Standard Deviation 10.1	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=5 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	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.	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.
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	98.4 h*nmol/L Standard Deviation 22.6	481 h*nmol/L Standard Deviation 150	819 h*nmol/L Standard Deviation 227	54.9 h*nmol/L Standard Deviation 11.5	125 h*nmol/L Standard Deviation 15.9	—	—
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	119 h*nmol/L Standard Deviation 5.36	—	—

SECONDARY outcome

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=5 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	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.	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.
Half-life (t1/2) of RO7239958 Day 1	5.36 h Interval 1.83 to 58.7	151 h Interval 126.0 to 293.0	411 h Interval 333.0 to 836.0	515 h Interval 305.0 to 1000.0	3.13 h Interval 2.87 to 512.0	499 h Interval 395.0 to 743.0	—	—
Half-life (t1/2) of RO7239958 Day 29	—	—	—	—	3.04 h Interval 2.67 to 3.87	231 h Interval 181.0 to 284.0	—	—

SECONDARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=8 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	Part 2a: Placebo n=5 Participants Participants with chronic hepatitis B (CHB) were administered two doses of placebo SC at a dosing frequency of once every four weeks (Q4W).	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.	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.
Cumulative Amount of Drug Excreted in Urine (Ae) Day 1, accumulation interval 0-8 h	23.1 micrograms (µg) Standard Deviation 12.3	50.1 micrograms (µg) Standard Deviation 48.2	153 micrograms (µg) Standard Deviation 76.0	446 micrograms (µg) Standard Deviation 359	35.2 micrograms (µg) Standard Deviation 22.3	127 micrograms (µg) Standard Deviation 170	—	—
Cumulative Amount of Drug Excreted in Urine (Ae) Day 1, accumulation interval 0-12 h	23.5 micrograms (µg) Standard Deviation 16.5	51.2 micrograms (µg) Standard Deviation 51.0	172 micrograms (µg) Standard Deviation 81.3	474 micrograms (µg) Standard Deviation 379	—	—	—	—
Cumulative Amount of Drug Excreted in Urine (Ae) Day 1, accumulation interval 0- 4 h	16.4 micrograms (µg) Standard Deviation 8.87	35.4 micrograms (µg) Standard Deviation 33.7	104 micrograms (µg) Standard Deviation 72.6	290 micrograms (µg) Standard Deviation 272	25.0 micrograms (µg) Standard Deviation 14.1	81.9 micrograms (µg) Standard Deviation 125	—	—
Cumulative Amount of Drug Excreted in Urine (Ae) Day 1, accumulation interval 0-24 h	23.8 micrograms (µg) Standard Deviation 20.0	51.7 micrograms (µg) Standard Deviation 55.9	189 micrograms (µg) Standard Deviation 92.1	497 micrograms (µg) Standard Deviation 383	—	—	—	—
Cumulative Amount of Drug Excreted in Urine (Ae) Day 29, accumulation interval 0-4 h	—	—	—	—	23.4 micrograms (µg) Standard Deviation 14.5	46.4 micrograms (µg) Standard Deviation 44.4	—	—
Cumulative Amount of Drug Excreted in Urine (Ae) Day 29, accumulation interval 0-8 h	—	—	—	—	38.1 micrograms (µg) Standard Deviation 23.3	85.1 micrograms (µg) Standard Deviation 56.9	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=2 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=5 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	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).	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.	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.
Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels Baseline	3.66 log10[international units (IU)/mL] Standard Deviation 0.50	3.52 log10[international units (IU)/mL] Standard Deviation 0.61	3.22 log10[international units (IU)/mL] Standard Deviation 0.38	—	—	—	—	—
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	-0.05 log10[international units (IU)/mL] Standard Deviation 0.18	-0.13 log10[international units (IU)/mL] Standard Deviation 0.16	—	—	—	—	—
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	-0.05 log10[international units (IU)/mL] Standard Deviation 0.31	-0.13 log10[international units (IU)/mL] Standard Deviation 0.17	—	—	—	—	—
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 0.40	-0.05 log10[international units (IU)/mL] Standard Deviation 0.12	-0.17 log10[international units (IU)/mL] Standard Deviation 0.23	—	—	—	—	—
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	-0.09 log10[international units (IU)/mL] Standard Deviation 0.11	-0.08 log10[international units (IU)/mL] Standard Deviation 0.23	—	—	—	—	—
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	-0.11 log10[international units (IU)/mL] Standard Deviation 0.35	-0.26 log10[international units (IU)/mL] Standard Deviation 0.33	—	—	—	—	—
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	-0.12 log10[international units (IU)/mL] Standard Deviation 0.30	-0.19 log10[international units (IU)/mL] Standard Deviation 0.26	—	—	—	—	—
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	-0.14 log10[international units (IU)/mL] Standard Deviation 0.24	-0.06 log10[international units (IU)/mL] Standard Deviation 0.08	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antigen (HBsAg) Levels Change at Day 113	0.23 log10[international units (IU)/mL] Standard Deviation NA SD was not estimable for 1 participant.	-0.03 log10[international units (IU)/mL] Standard Deviation 0.09	-0.05 log10[international units (IU)/mL] Standard Deviation 0.09	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=2 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=5 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	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).	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.	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.
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 113	0.00 log10[IU/mL] Standard Deviation NA SD was not estimable for 1 participant.	0.02 log10[IU/mL] Standard Deviation 0.06	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Baseline	0.48 log10[IU/mL] Standard Deviation 0.00	0.50 log10[IU/mL] Standard Deviation 0.08	0.48 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 8	0.00 log10[IU/mL] Standard Deviation 0.00	0.02 log10[IU/mL] Standard Deviation 0.05	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 15	0.00 log10[IU/mL] Standard Deviation 0.00	0.00 log10[IU/mL] Standard Deviation 0.00	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 22	0.00 log10[IU/mL] Standard Deviation 0.00	0.02 log10[IU/mL] Standard Deviation 0.06	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 29	0.00 log10[IU/mL] Standard Deviation 0.00	0.01 log10[IU/mL] Standard Deviation 0.04	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 43	0.00 log10[IU/mL] Standard Deviation 0.00	0.02 log10[IU/mL] Standard Deviation 0.05	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 57	0.00 log10[IU/mL] Standard Deviation 0.00	0.02 log10[IU/mL] Standard Deviation 0.06	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—
Part 2a: Change From Baseline in Hepatitis B Surface Antibody (Anti-HBs) Levels Change at Day 85	0.00 log10[IU/mL] Standard Deviation 0.00	0.02 log10[IU/mL] Standard Deviation 0.07	0.00 log10[IU/mL] Standard Deviation 0.00	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo n=2 Participants Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=8 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 n=5 Participants Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	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).	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.	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.
Part 2a: Number of Participants With HBsAg Loss	0 Participants	0 Participants	0 Participants	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=3 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	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).	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.	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.
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 29	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 43	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 57	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Baseline	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 8	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 15	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 22	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 85	—	0 Participants	—	—	—	—	—	—
Part 2a: Number of Participants With Hepatitis B Envelope Antigen (HBeAg) Loss in HBeAg-positive Participants HBeAg Loss at Day 113	—	0 Participants	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 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.

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

Outcome measures

Outcome measures
Measure	Part 1, Cohorts 1-4: Placebo Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	Part 1, Cohort 1: 0.1 mg/kg RO7239958 n=3 Participants Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	Part 1, Cohort 2: 0.3 mg/kg RO7239958 Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	Part 1, Cohort 3: 1.0 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	Part 1, Cohort 4: 1.5 mg/kg RO7239958 Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	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).	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.	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.
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 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 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 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 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 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 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 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 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 outcome

Timeframe: 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.

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