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

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

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.

Study Overview

• Status: Terminated
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Other: Matching Placebo; Drug: RO7020322

• Study Type: Interventional
• Enrollment (Actual): 49
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• New Zealand
  • Grafton, New Zealand, 1010
    • Auckland Clinical Studies Limited
  • Tauranga, New Zealand, 3143
    • Tauranga Hospital
• Taiwan
  • Kaohsiung, Taiwan, 807
    • Kaohsiung Medical University Chung-Ho Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2015
• Primary Completion (Actual): May 9, 2016
• Study Completion (Actual): May 9, 2016

Study Registration Dates

• First Submitted: November 10, 2015
• First Submitted That Met QC Criteria: November 10, 2015
• First Posted (Estimate): November 13, 2015

Study Record Updates

• Last Update Posted (Actual): May 25, 2017
• Last Update Submitted That Met QC Criteria: May 23, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic
• Other Study ID Numbers: BP29948

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No