A Study of RO7239958 to Evaluate Safety, Tolerability, Ph... | NCT03762681

NCT03762681

ID	Type	Description	Link
2018-003530-32	EudraCT Number

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part 1: Single Ascending Dose, HV	Experimental	Healthy volunteers will be administered a single dose of RO7239958 or placebo subcutaneously (SC).	Drug: RO7239958 Other: Placebo
Part 2a: Multi-dose, CHB	Experimental	Participants with chronic hepatitis B will be administered different dose levels of RO7239958 or placebo SC. Dosages will be determined from data collected from Part 1.	Drug: RO7239958 Other: Placebo
Part 2b: Multi-dose, CHB (Optional)	Experimental	Additional study arm to open based on data collected from Part 2a. Participants with chronic hepatitis B will be administered different doses and frequencies of RO7239958 or placebo SC.	Drug: RO7239958 Other: Placebo

Interventions

Name	Type	Description	Arm Group Labels	Other Names
RO7239958	Drug	Solution for injection, subcutaneous use (SC).	Part 1: Single Ascending Dose, HV Part 2a: Multi-dose, CHB Part 2b: Multi-dose, CHB (Optional)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Up to approximately 16 months
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.	Up to approximately 16 months
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	Number of participants with clinically significant abnormalities in clinical laboratory parameters such as serum chemistry, hematology, coagulation, viral serology, urinalysis were evaluated.	Up to approximately 16 months
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.	Up to approximately 16 months

Secondary Outcomes

Measure	Description	Time Frame
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.
Time to Cmax (Tmax) of RO7239958

Eligibility Module

Eligibility Criteria

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

Contacts/Locations Module

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Director

Facility	Status	City	State	ZIP	Country	Contacts
Acibadem City Clinic Tokuda Hospital Ead		Sofia		1407	Bulgaria
COMAC Medical; Clinical Research Unit for Phase I

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
41186228	Derived	Geretti AM, Sostelly A, Buatois S, Lu S, Lemenuel A, Attley G, Bopst M, Alvarez-Sanchez R, Mueller H, Gane E. Safety, pharmacokinetics, and pharmacodynamics of the antisense oligonucleotide RO7239958 in healthy volunteers and adults with chronic hepatitis B infection. Antimicrob Agents Chemother. 2025 Dec 10;69(12):e0067925. doi: 10.1128/aac.00679-25. Epub 2025 Nov 4.

IPD Sharing Statement Module

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).
FG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Uploaded Document Information

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Feb 18, 2020

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

No data available

No data is available for this block.

Masking Info

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

Arm/Group Information

ID	Title	Description
BG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).
BG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
BG002	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
BG003	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
BG004	Part 1, Cohort 4: 1.5 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.
BG005	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).
BG006	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.
BG007	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.
BG008	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00037.0± 12.7 BG00136.5± 15.1 BG00228.9± 9.1 BG003

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0001 BG0010 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0000 BG0011 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0010 BG002

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

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.

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

Posted

Count of Participants

Participants

Up to approximately 16 months

ID	Title	Description
OG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).
OG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG004	Part 1, Cohort 4: 1.5 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.
OG005	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).
OG006	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.
OG007	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.

Units	Counts
Participants	OG0008 OG0018 OG0028 OG003

Title

Denominators

Categories

Title	Measurements
	OG0007 OG0013 OG0024 OG003

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.

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

Posted

Count of Participants

Participants

Up to approximately 16 months

ID	Title	Description
OG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).
OG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.

Primary

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

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

Posted

Count of Participants

Participants

Up to approximately 16 months

ID	Title	Description
OG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).
OG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG004	Part 1, Cohort 4: 1.5 mg/kg RO7239958

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.

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

Posted

Count of Participants

Participants

Up to approximately 16 months

ID	Title	Description
OG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).
OG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.

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.

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

Posted

Count of Participants

Participants

Up to approximately 16 months

ID	Title	Description
OG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).
OG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.

Secondary

Maximum Plasma Concentration (Cmax) of RO7239958

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.

Posted

Mean

Standard Deviation

nanomoles/liter (nmol/L)

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.

ID	Title	Description
OG000	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG001	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 4: 1.5 mg/kg RO7239958

Secondary

Time to Cmax (Tmax) of RO7239958

Posted

Median

Full Range

hours (h)

ID	Title	Description
OG000	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG001	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 4: 1.5 mg/kg RO7239958

Secondary

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

Posted

Mean

Standard Deviation

h*nmol/L

ID	Title	Description
OG000	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG001	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 4: 1.5 mg/kg RO7239958

Secondary

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

Posted

Mean

Standard Deviation

h*nmol/L

ID	Title	Description
OG000	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG001	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 4: 1.5 mg/kg RO7239958

Secondary

Half-life (t1/2) of RO7239958

Posted

Median

Full Range

ID	Title	Description
OG000	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG001	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG003	Part 1, Cohort 4: 1.5 mg/kg RO7239958

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.

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.

Posted

Mean

Standard Deviation

micrograms (µg)

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

ID	Title	Description
OG000	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.
OG001	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.
OG002	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.
OG003

Secondary

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

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.

Posted

Mean

Standard Deviation

log10[international units (IU)/mL]

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)

ID	Title	Description
OG000	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).
OG001	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.
OG002	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.

Units

Secondary

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

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.

Posted

Mean

Standard Deviation

log10[IU/mL]

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)

ID	Title	Description
OG000	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).
OG001	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.
OG002	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.

Units	Counts

Secondary

Part 2a: Number of Participants With HBsAg Loss

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

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

Posted

Count of Participants

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)

ID	Title	Description
OG000	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).
OG001	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.
OG002	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.

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.

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.

Posted

Count of Participants

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)

ID	Title	Description
OG000	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).
OG001	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.
OG002	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.

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.

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.

Posted

Count of Participants

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)

ID	Title	Description
OG000	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).
OG001	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.
OG002	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.

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.

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.

Posted

Number

participants

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)

ID	Title	Description
OG000	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).
OG001	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.
OG002	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.

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Part 1, Cohorts 1-4: Placebo	Healthy volunteers were administered a single dose of placebo subcutaneously (SC).	8	8	7	8
EG001	Part 1, Cohort 1: 0.1 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.1 mg/kg RO7239958 SC.	8	8	3	8
EG002	Part 1, Cohort 2: 0.3 mg/kg RO7239958	Healthy volunteers were administered a single dose of 0.3 mg/kg RO7239958 SC.	8	8	4	8
EG003	Part 1, Cohort 3: 1.0 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.0 mg/kg RO7239958 SC.	8	8	7	8
EG004	Part 1, Cohort 4: 1.5 mg/kg RO7239958	Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.	8	8	5	8
EG005	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	2	1	2
EG006	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	8	4	8
EG007	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	5	1	5

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Abdominal discomfort	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG0030 events0 affected8 at risk EG0040 events0 affected8 at risk EG0050 events0 affected2 at risk EG0060 events0 affected8 at risk EG0070 events0 affected5 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Gingival bleeding	Gastrointestinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Catheter site bruise	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Catheter site inflammation	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected8 at risk EG0020 events0 affected8 at risk EG003
Catheter site paraesthesia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Fatigue	General disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Influenza like illness	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Injection site reaction	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0011 events1 affected8 at risk EG0020 events0 affected8 at risk EG003
Medical device site dermatitis	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Pyrexia	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Vessel puncture site bruise	General disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0012 events2 affected8 at risk EG0020 events0 affected8 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0002 events2 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Viral infection	Infections and infestations	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Arthropod bite	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Contusion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Ligament sprain	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Medication error	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Nail avulsion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Scratch	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Skin abrasion	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Sunburn	Injury, poisoning and procedural complications	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Transaminases increased	Investigations	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Musculoskeletal stiffness	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Plantar fasciitis	Musculoskeletal and connective tissue disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Dizziness	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Headache	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Presyncope	Nervous system disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Epistaxis	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Oropharyngeal pain	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Rhinorrhoea	Respiratory, thoracic and mediastinal disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003
Dermatitis contact	Skin and subcutaneous tissue disorders	MedDRA 23.0	Systematic Assessment	EG0000 events0 affected8 at risk EG0010 events0 affected8 at risk EG0021 events1 affected8 at risk EG003
Flushing	Vascular disorders	MedDRA 23.0	Systematic Assessment	EG0001 events1 affected8 at risk EG0010 events0 affected8 at risk EG0020 events0 affected8 at risk EG003

ID	Term
D006509	Hepatitis B

Ancestor Terms

ID	Term
D000086982	Blood-Borne Infections
D003141	Communicable Diseases
D007239	Infections
D018347	Hepadnaviridae Infections
D004266	DNA Virus Infections
D014777	Virus Diseases
D006525	Hepatitis, Viral, Human
D006505	Hepatitis
D008107	Liver Diseases
D004066	Digestive System Diseases

Healthy volunteers were administered a single dose of 1.5 mg/kg RO7239958 SC.

EG0041 events1 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0061 events1 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0041 events1 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0041 events1 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0071 events1 affected5 at risk

EG0042 events2 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0071 events1 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0061 events1 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0062 events1 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0051 events1 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0044 events3 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0041 events1 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0042 events2 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0071 events1 affected5 at risk

EG0042 events2 affected8 at risk

EG0050 events0 affected2 at risk

EG0062 events2 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0041 events1 affected8 at risk

EG0050 events0 affected2 at risk

EG0062 events2 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

EG0041 events1 affected8 at risk

EG0050 events0 affected2 at risk

EG0061 events1 affected8 at risk

EG0070 events0 affected5 at risk

EG0041 events1 affected8 at risk

EG0050 events0 affected2 at risk

EG0062 events2 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0061 events1 affected8 at risk

EG0070 events0 affected5 at risk

EG0040 events0 affected8 at risk

EG0050 events0 affected2 at risk

EG0060 events0 affected8 at risk

EG0070 events0 affected5 at risk

OG0041.00(0.50 to 2.00)

OG0051.00(1.00 to 2.00)

OG0043.13(2.87 to 512)

OG005499(395 to 743)

SD was not estimable for 1 participant.