A Study of Treatment With RO6864018 in Virologically Suppressed Participants With Chronic Hepatitis B Virus (HBV) Infection

NCT02391805 | Completed Phase 2

• 1 other identifier: NP28938
• Study Type: interventional
• Target: 31
• Locations: 6 countries
• Sites: 14

Brief Summary

This randomized, multicenter, partially double-blind, placebo-controlled study is designed to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antiviral effects of treatment with RO6864018 in virologically suppressed participants with chronic HBV infection.

Conditions

Hepatitis B, Chronic

Outcome Measures

Primary Outcomes (1)

• Safety: Percentage of Participants with Adverse Events

  Baseline up to approximately 36 weeks

Secondary Outcomes (47)

• Pharmacodynamics: Peripheral Blood Levels of Interferon (IFN)-Alpha in QOD Dosing Cohorts

  Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up

• Pharmacodynamics: Peripheral Blood Levels of IFN-Alpha in QWk Dosing Cohorts

  Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up

• Pharmacodynamics: Peripheral Blood Levels of IFN-Gamma-Induced Protein (IP)-10 in QOD Dosing Cohorts

  Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Days 1, 3, 7 of Week 1; on Day 1 of Weeks 3, 5, 7; and Day 6 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up

• Pharmacodynamics: Peripheral Blood Levels of IP-10 in QWk Dosing Cohorts

  Baseline; pre-dose (0 hours) and post-dose (6, 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up

• Efficacy: Quantitative HBV Deoxyribonucleic Acid (DNA) Level in QOD Dosing Cohorts

  Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Weeks 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up; and at any point that breakthrough occurs (up to 36 weeks)

Study Arms (6)

Placebo, Every Other Day (QOD)

PLACEBO COMPARATOR

Placebo orally (PO) QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician

Drug: Entecavir; Drug: Placebo; Drug: Tenofovir

Placebo, Once a Week (QWk)

PLACEBO COMPARATOR

Placebo PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician

Drug: Entecavir; Drug: Placebo; Drug: Tenofovir

RO6864018, 1200 milligrams (mg) QOD

EXPERIMENTAL

RO6864018 1200 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician

Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir

RO6864018, 1200 mg QWk

EXPERIMENTAL

RO6864018 1200 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician

Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir

RO6864018, 800 mg QOD

EXPERIMENTAL

RO6864018 800 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician

Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir

RO6864018, 800 mg QWk

EXPERIMENTAL

RO6864018 800 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician

Drug: Entecavir; Drug: RO6864018; Drug: Tenofovir

Interventions

Entecavir DRUG

Entecavir will be administered as per local labeling.

Placebo, Every Other Day (QOD); Placebo, Once a Week (QWk); RO6864018, 1200 mg QWk; RO6864018, 1200 milligrams (mg) QOD; RO6864018, 800 mg QOD; RO6864018, 800 mg QWk

Placebo DRUG

Participants will be administered PO placebo capsules matched to RO6864018, either QOD or QWk for 12 weeks of treatment.

Placebo, Every Other Day (QOD); Placebo, Once a Week (QWk)

RO6864018 DRUG

Participants will be administered RO6864018 as 200-mg PO capsules at a dose of 800 mg or 1200 mg, either QOD or QWk for 12 weeks of treatment.

RO6864018, 1200 mg QWk; RO6864018, 1200 milligrams (mg) QOD; RO6864018, 800 mg QOD; RO6864018, 800 mg QWk

Tenofovir DRUG

Tenofovir will be administered as per local labeling.

Placebo, Every Other Day (QOD); Placebo, Once a Week (QWk); RO6864018, 1200 mg QWk; RO6864018, 1200 milligrams (mg) QOD; RO6864018, 800 mg QOD; RO6864018, 800 mg QWk

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic hepatitis B infection
• Positive test for HBsAg for more than 6 months prior to randomization
• HBsAg titer greater than or equal to (\>/=) 250 international units per milliliter (IU/mL) at Screening
• Treatment with any nucleoside/nucleotide analogue for \>/= 1 year with ongoing entecavir and/or tenofovir treatment at randomization and for at least 3 months prior to randomization
• HBV DNA less than (\<) 90 IU/mL for at least the preceding 6 months
• HBeAg positive at randomization and for at least 6 months prior to randomization

You may not qualify if:

• Pregnant or lactating women
• Documented history of HBV genotype D
• History or other evidence of bleeding from esophageal varices
• History of decompensated liver disease, chronic liver disease other than HBV infection, or any evidence of metabolic liver disease
• Positive test for hepatitis A, hepatitis C, or human immunodeficiency virus (HIV)
• Documented history of hepatitis D infection
• History of or suspicion of hepatocellular carcinoma
• History of immunologically mediated disease
• History of organ transplantation
• History of thyroid disease
• Significant acute infection

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (14)

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Prince of Wales Hospital; Special Medical Clinic

N.T., Hong Kong

Location

Hospital Ampang

Ampang, 68000, Malaysia

Location

Hospital Selayang; Medicine

Batu Caves, 68100, Malaysia

Location

University Malaya Medical Center

Kuala Lumpur, 59100, Malaysia

Location

Auckland Clinical Studies Limited

Grafton, 1010, New Zealand

Location

Waikato Hospital

Hamilton, 3248, New Zealand

Location

Changi General Hospital

Singapore, 529889, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Kaohsiung Medical Uni Chung-Ho Memorial Hospital; Dept of Internal Medicine

Kaohsiung City, 807, Taiwan

Location

National Taiwan University Hospital

Taipei, 10002, Taiwan

Location

Taipei Veterans General Hospital

Taipei, 112, Taiwan

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; Tenofovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 6, 2015
• First Posted: March 18, 2015
• Study Start: May 17, 2015
• Primary Completion: October 16, 2017
• Study Completion: October 16, 2017
• Last Updated: June 6, 2018

Record last verified: 2018-06

Locations

HK (2); MY (3); SG (1); KR (3); NZ (2); TW (3)