A Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7020322 Following Oral Administration in Healthy Participants and Chronic Hepatitis B Patients

Study Overview
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Brief Summary
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This is a multiple-center, randomized, double-blind, placebo-controlled, single-ascending dose and multiple-ascending dose, adaptive parallel study to investigate the safety, tolerability, pharmacokinetics and pharmacodynamics of RO7020322 following oral administration in healthy participants and chronic hepatitis B patients.

Official Title
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A Multiple-Center, Randomized, Double-Blind, Placebo-Controlled, Single-Ascending Dose and Multiple-Ascending Dose, Adaptive Parallel Study to Investigate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of RO7020322 Following Oral Administration in Healthy Subjects and Chronic Hepatitis B Patients

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Other: Matching Placebo
* Drug: RO7020322


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Participants' Inclusion Criteria: A Body Mass Index (BMI) between 18 to 30 kg/m^2, inclusive, and a body weight of at least 50 kg Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm during the study Women should be of non-childbearing potential Able to comply with study restrictions Non-smoker (nor tobacco-containing products) for at least 90 days prior to dosing on Day 1 and agreeing not to smoke during the study Chronic Hepatitis B-Infected Participants' Inclusion Criteria: Chronic hepatitis B infection A BMI between 18 to 32 kg/m^2, inclusive Positive test for HBsAg for more than 6 months prior to randomization On entecavir or tenofovir treatment for at least 6 months prior to randomization and remaining on stable treatment during the study Liver biopsy, fibroscan® or equivalent test obtained within the past 6 months demonstrating liver disease consistent with chronic hepatitis B (HBV) infection without evidence of bridging fibrosis or cirrhosis Males must agree to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agree to refrain from donating sperm during the study Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least until the end of the follow-up period Exclusion Criteria: Healthy Participants' Exclusion Criteria: Women who are lactating Any suspicion or history of alcohol and/or other substance abuse or dependence in the past 6 months Positive urine drug and alcohol screen (barbiturates, benzodiazepines, methadone, amphetamines, methamphetamines, opiates, cocaine, cannabinoids, and alcohol), or positive cotinine test at Day -1 Positive result on HBV, hepatitis C (HCV), or human immunodeficiency virus (HIV) 1 and 2 A personal history of unexplained blackouts or faints, or known risk factors for Torsade de Pointes Clinically significant abnormalities (as judged by the Investigator) in the physical examination and in the laboratory test results (including hepatic and renal panels, complete blood count, chemistry panel and urinalysis) at screening and on Day -1 Participation in an investigational drug or device study within 90 days prior to screening or 5 times the half-life of the investigational drug (whichever is longer) Donation of blood over 500 mL within three months prior to screening Concomitant disease or condition (including allergic reactions against any drug, or multiple allergies) that could interfere with, or treatment of which might interfere with, the conduct of the study, or that would, in the opinion of the Investigator, pose an unacceptable risk to the healthy participant in this study Chronic Hepatitis B-Infected Participants' Exclusion Criteria: Women who are pregnant (positive pregnancy test) or lactating History or other evidence of bleeding from esophageal varices Decompensated liver disease History or other evidence of a medical condition associated with chronic liver disease other than HBV infection Documented history or other evidence of metabolic liver disease within one year of randomization Positive test for hepatitis A (IgM anti-HAV), hepatitis C, or HIV Documented history of infection with hepatitis D virus Expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study, with the exception of oral therapy for herpes simplex virus (HSV) I or HSV II History of immunologically-mediated disease

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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy Participants (Multiple-Ascending Dosing)<br> | Other: Matching Placebo<br>* Oral dosing with placebo capsules to match RO7020322.<br>Drug: RO7020322<br>* Adaptive oral dosing with RO7020322 capsules, starting at 1 mg daily, with ascending or adjusted dosing based on the results of previous dosing.<br>|
| Experimental: Healthy Participants (Single-Ascending Dosing)<br> | Other: Matching Placebo<br>* Oral dosing with placebo capsules to match RO7020322.<br>Drug: RO7020322<br>* Adaptive oral dosing with RO7020322 capsules, starting at 1 mg daily, with ascending or adjusted dosing based on the results of previous dosing.<br>|
| Experimental: Healthy Participants (Study of Food Effect)<br> | Other: Matching Placebo<br>* Oral dosing with placebo capsules to match RO7020322.<br>Drug: RO7020322<br>* Adaptive oral dosing with RO7020322 capsules, starting at 1 mg daily, with ascending or adjusted dosing based on the results of previous dosing.<br>|
| Experimental: Participants with Chronic Hepatitis B (Proof of mechanism)<br> | Other: Matching Placebo<br>* Oral dosing with placebo capsules to match RO7020322.<br>Drug: RO7020322<br>* Adaptive oral dosing with RO7020322 capsules, starting at 1 mg daily, with ascending or adjusted dosing based on the results of previous dosing.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse events |  | Up to 8 weeks | 
| Intensity of adverse events |  | Up to 8 weeks | 
| Number of participants with clinically significant laboratory abnormalities |  | Up to 8 weeks | 
| Number of participants with clinically significant electrocardiogram (ECG) abnormalities |  | Up to 8 weeks | 
| Number of participants with clinically significant vital signs abnormalities |  | Up to 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum observed plasma concentration (Cmax) of RO7020322 |  | Up to 18 days | 
| Time from dosing to Cmax (Tmax) of RO7020322 |  | Up to 18 days | 
| Trough plasma concentrations (Ctrough) of RO7020322 |  | Up to 18 days | 
| Area under the plasma concentration-time curve between time zero (pre-dose) and the time of the last quantifiable concentration (AUClast) of RO7020322 |  | Up to 18 days | 
| Area under the plasma concentration-time curve between time zero (pre-dose) extrapolated to infinity (AUC0-Inf) of RO7020322 |  | Up to 18 days | 
| Apparent clearance (CL/F) of RO7020322 |  | Up to 18 days | 
| Apparent volume (V/F) of RO7020322 |  | Up to 18 days | 
| Apparent terminal phase half-life (t1/2) of RO7020322 |  | Up to 18 days | 
| Area under the plasma concentration-time curve (AUC0-t,ss) of RO7020322 at steady state |  | Up to 18 days | 
| Area under the plasma concentration-time curve (AUC0-t) of RO7020322 on Day 1 |  | Up to 18 days | 
| Plasma concentration of hepatitis B surface antigen (HBsAg) |  | Up to 8 weeks |