A Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7565020 in Healthy Participants and in Participants With Chronic Hepatitis B Virus Infection

Study Overview
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Brief Summary
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This is a first in human (FIH), multi-center, dose-finding, and dose-escalation Phase I clinical study of RO7565020 to investigate the safety and tolerability and to characterize the pharmacokinetics and pharmacodynamics following single and/or multiple doses of RO7565020 in healthy participants and/or virologically suppressed participants with chronic hepatitis B (CHB).

Official Title
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A Phase I Study to Investigate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of RO7565020 in Healthy Participants and in Participants With Chronic Hepatitis B Virus Infection

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: RO7565020
* Other: Placebo
* Drug: Nucleos(t)ide analogue (NUC) treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy volunteers: Healthy participants Body mass index (BMI) between 18 and 32 kg/m^2 CHB participants: CHB infection (HBsAg-positive for >/= 6 months) On NUC (ETV, TAF, or TDF) monotherapy for >/= 12 months Liver biopsy, FibroScan, or equivalent test within the past 6 months demonstrating liver disease consistent with chronic HBV infection without evidence of bridging fibrosis or cirrhosis BMI between 18 and 32 kg/m^2 Exclusion Criteria: Healthy volunteers: History of any clinically significant disease Concomitant disease that could interfere with treatment or conduct of study Use of any treatment within the 2 weeks or within 5 half-lives prior to first dosing (whichever is longer) CHB participants: Evidence of liver cirrhosis or decompensated liver disease History or suspicion of hepatocellular carcinoma (HCC) History or evidence of a medical condition associated with chronic liver disease other than HBV infection, or clinically significant and not adequately controlled non-hepatic disease History of or currently receiving any systemic anti-neoplastic or immune-modulatory treatment within the 8 weeks prior to the first dosing or the expectation that such treatment will be needed at any time during the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RO7565020<br> | Drug: RO7565020<br>* RO7565020 will be administered by subcutaneous injection or intravenous infusion.<br>Drug: Nucleos(t)ide analogue (NUC) treatment<br>* NUC treatment, including tenofovir disoproxil fumarate (TDF), tenofovir alafenamide (TAF), or entecavir (ETV), will be administered orally per local prescribing information.<br>|
| Placebo Comparator: Placebo<br> | Other: Placebo<br>* Matching placebo will be administered by subcutaneous injection or intravenous infusion.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Healthy Volunteers With Adverse Events |  | Up to 104 weeks | 
| Percentage of Participants With Chronic Hepatitis B With Adverse Events |  | Up to 104 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Concentrations of RO7565020 |  | Up to 104 weeks | 
| Change from Baseline in Serum Quantitative Hepatitis B Surface Antigen (HBsAg) |  | Up to 104 weeks | 
| Maximum Reduction from Baseline of Serum HBsAg Across All Timepoints |  | Up to 104 weeks | 
| Percentage of Participants With HBsAg Loss |  | Up to 104 weeks | 
| Percentage of Participants With HBsAg Seroconversion |  | Up to 104 weeks | 
| Percentage of Participants With Hepatitis B e Antigen (HBeAg) Loss Among HBeAg-positive Participants at Baseline |  | Up to 104 weeks | 
| Percentage of Participants With HBeAg Seroconversion Among HBeAg-positive Participants at Baseline |  | Up to 104 weeks |