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

Primary Purpose

Hepatitis B, Chronic

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Entecavir
Placebo
RO6864018
Tenofovir
Sponsored by
Hoffmann-La Roche
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Sites / Locations

  • Queen Mary Hospital
  • Prince of Wales Hospital; Special Medical Clinic
  • Seoul National University Hospital
  • Severance Hospital, Yonsei University Health System
  • Asan Medical Center
  • Hospital Ampang
  • Hospital Selayang; Medicine
  • University Malaya Medical Center
  • Auckland Clinical Studies Limited
  • Waikato Hospital
  • Changi General Hospital
  • Kaohsiung Medical Uni Chung-Ho Memorial Hospital; Dept of Internal Medicine
  • Taipei Veterans General Hospital
  • National Taiwan University Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm 5

Arm 6

Arm Type

Placebo Comparator

Placebo Comparator

Experimental

Experimental

Experimental

Experimental

Arm Label

Placebo, Every Other Day (QOD)

Placebo, Once a Week (QWk)

RO6864018, 1200 milligrams (mg) QOD

RO6864018, 1200 mg QWk

RO6864018, 800 mg QOD

RO6864018, 800 mg QWk

Arm Description

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

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

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

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

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

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

Outcomes

Primary Outcome Measures

Safety: Percentage of Participants with Adverse Events

Secondary Outcome Measures

Pharmacodynamics: Peripheral Blood Levels of Interferon (IFN)-Alpha in QOD Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IFN-Alpha in QWk Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IFN-Gamma-Induced Protein (IP)-10 in QOD Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IP-10 in QWk Dosing Cohorts
Efficacy: Quantitative HBV Deoxyribonucleic Acid (DNA) Level in QOD Dosing Cohorts
Efficacy: Quantitative HBV DNA Level in QWk Dosing Cohorts
Efficacy: Quantitative Hepatitis B Surface Antigen (HBsAg) Level in QOD Dosing Cohorts
Efficacy: Quantitative HBsAg Level in QWk Dosing Cohorts
Efficacy: Percentage of Participants with Loss of HBsAg in QOD Dosing Cohorts
Efficacy: Percentage of Participants with Loss of HBsAg in QWk Dosing Cohorts
Efficacy: Percentage of Participants with Loss of Hepatitis B Envelope Antigen (HBeAg) in QOD Dosing Cohorts
Efficacy: Percentage of Participants with Loss of HBeAg in QWk Dosing Cohorts
Efficacy: Percentage of Participants with HBsAg Seroconversion in QOD Dosing Cohorts
HBsAg Seroconversion = antibody to HBsAg (Anti-HBs) Positive Status and Loss of HBsAg
Efficacy: Percentage of Participants with HBsAg Seroconversion in QWk Dosing Cohorts
HBsAg Seroconversion = anti-HBs Positive Status and Loss of HBsAg
Efficacy: Percentage of Participants with HBeAg Seroconversion in QOD Dosing Cohorts
HBeAg Seroconversion = antibody to HBeAg (anti-HBe) Positive Status and Loss of HBeAg
Efficacy: Percentage of Participants with HBeAg Seroconversion in QWk Dosing Cohorts
HBeAg Seroconversion = anti-HBe Positive Status and Loss of HBeAg
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Pharmacokinetics: Cmax of RO6864018 Metabolite in QWk Dosing Cohorts
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Pharmacokinetics: Tmax of RO6864018 Metabolite in QWk Dosing Cohorts
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of RO6864018 Metabolite in QOD Dosing Cohorts
Pharmacokinetics: AUCinf of RO6864018 Metabolite in QWk Dosing Cohorts
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of RO6864018 Metabolite in QOD Dosing Cohorts
Pharmacokinetics: AUClast of RO6864018 Metabolite in QWk Dosing Cohorts
Pharmacokinetics: Half-life (t1/2) of RO6864018 Metabolite in QOD Dosing Cohorts
Pharmacokinetics: T1/2 of RO6864018 Metabolite in QWk Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QOD Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QWk Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of Tumor Necrosis Factor (TNF)-Alpha in QOD Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of TNF-alpha in QWk Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of Interleukin (IL)-6 in QOD Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IL-6 in QWk Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QOD Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QWk Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QOD Dosing Cohorts
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QWk Dosing Cohorts
Efficacy: Percentage of Participants with Development of Anti-HBe in QOD Dosing Cohorts
Efficacy: Percentage of Participants with Development of Anti-HBe in QWk Dosing Cohorts
Efficacy: Percentage of Participants with Development of Anti-HBs in QOD Dosing Cohorts
Efficacy: Percentage of Participants with Development of Anti-HBs in QWk Dosing Cohorts
Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QWk Cohorts
Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QOD Cohorts
Pharmacodynamics: Percentage of T Cells, B Cells, and NK Cells (TBNK)
Pharmacodynamics: Percentage of Myeloid Cells
Pharmacodynamics: Percentage of Plasmacytoid Dendritic Cells
Pharmacokinetics: Cmax of Entecavir in QWk Dosing Cohorts
Pharmacokinetics: AUCinf of Entecavir in QWk Dosing Cohorts

Full Information

First Posted
March 6, 2015
Last Updated
June 5, 2018
Sponsor
Hoffmann-La Roche
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1. Study Identification

Unique Protocol Identification Number
NCT02391805
Brief Title
A Study of Treatment With RO6864018 in Virologically Suppressed Participants With Chronic Hepatitis B Virus (HBV) Infection
Official Title
A Multiple-Center, Randomized, Partially Double-Blind, Placebo-Controlled Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antiviral Effects of 12-Week Treatment With RO6864018 in Virologically Suppressed Patients With Chronic Hepatitis B Virus Infection
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
May 17, 2015 (Actual)
Primary Completion Date
October 16, 2017 (Actual)
Study Completion Date
October 16, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hoffmann-La Roche

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
31 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo, Every Other Day (QOD)
Arm Type
Placebo Comparator
Arm Description
Placebo orally (PO) QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Arm Title
Placebo, Once a Week (QWk)
Arm Type
Placebo Comparator
Arm Description
Placebo PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Arm Title
RO6864018, 1200 milligrams (mg) QOD
Arm Type
Experimental
Arm Description
RO6864018 1200 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Arm Title
RO6864018, 1200 mg QWk
Arm Type
Experimental
Arm Description
RO6864018 1200 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Arm Title
RO6864018, 800 mg QOD
Arm Type
Experimental
Arm Description
RO6864018 800 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Arm Title
RO6864018, 800 mg QWk
Arm Type
Experimental
Arm Description
RO6864018 800 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Intervention Type
Drug
Intervention Name(s)
Entecavir
Intervention Description
Entecavir will be administered as per local labeling.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Participants will be administered PO placebo capsules matched to RO6864018, either QOD or QWk for 12 weeks of treatment.
Intervention Type
Drug
Intervention Name(s)
RO6864018
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tenofovir
Intervention Description
Tenofovir will be administered as per local labeling.
Primary Outcome Measure Information:
Title
Safety: Percentage of Participants with Adverse Events
Time Frame
Baseline up to approximately 36 weeks
Secondary Outcome Measure Information:
Title
Pharmacodynamics: Peripheral Blood Levels of Interferon (IFN)-Alpha in QOD Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IFN-Alpha in QWk Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IFN-Gamma-Induced Protein (IP)-10 in QOD Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IP-10 in QWk Dosing Cohorts
Time Frame
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
Title
Efficacy: Quantitative HBV Deoxyribonucleic Acid (DNA) Level in QOD Dosing Cohorts
Time Frame
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)
Title
Efficacy: Quantitative HBV DNA Level in QWk Dosing Cohorts
Time Frame
Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 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)
Title
Efficacy: Quantitative Hepatitis B Surface Antigen (HBsAg) Level in QOD Dosing Cohorts
Time Frame
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
Title
Efficacy: Quantitative HBsAg Level in QWk Dosing Cohorts
Time Frame
Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Efficacy: Percentage of Participants with Loss of HBsAg in QOD Dosing Cohorts
Time Frame
Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Title
Efficacy: Percentage of Participants with Loss of HBsAg in QWk Dosing Cohorts
Time Frame
Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Title
Efficacy: Percentage of Participants with Loss of Hepatitis B Envelope Antigen (HBeAg) in QOD Dosing Cohorts
Time Frame
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
Title
Efficacy: Percentage of Participants with Loss of HBeAg in QWk Dosing Cohorts
Time Frame
Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Efficacy: Percentage of Participants with HBsAg Seroconversion in QOD Dosing Cohorts
Description
HBsAg Seroconversion = antibody to HBsAg (Anti-HBs) Positive Status and Loss of HBsAg
Time Frame
Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Week 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Efficacy: Percentage of Participants with HBsAg Seroconversion in QWk Dosing Cohorts
Description
HBsAg Seroconversion = anti-HBs Positive Status and Loss of HBsAg
Time Frame
Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Efficacy: Percentage of Participants with HBeAg Seroconversion in QOD Dosing Cohorts
Description
HBeAg Seroconversion = antibody to HBeAg (anti-HBe) Positive Status and Loss of HBeAg
Time Frame
Baseline; pre-dose (0 hours) on Day 7 of Week 1 and Day 1 of Week 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Efficacy: Percentage of Participants with HBeAg Seroconversion in QWk Dosing Cohorts
Description
HBeAg Seroconversion = anti-HBe Positive Status and Loss of HBeAg
Time Frame
Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 5; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Title
Pharmacokinetics: Cmax of RO6864018 Metabolite in QWk Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Title
Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of RO6864018 Metabolite in QOD Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Title
Pharmacokinetics: Tmax of RO6864018 Metabolite in QWk Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Title
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of RO6864018 Metabolite in QOD Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Title
Pharmacokinetics: AUCinf of RO6864018 Metabolite in QWk Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Title
Pharmacokinetics: Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of RO6864018 Metabolite in QOD Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Title
Pharmacokinetics: AUClast of RO6864018 Metabolite in QWk Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Title
Pharmacokinetics: Half-life (t1/2) of RO6864018 Metabolite in QOD Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Days 1, 7 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 3, 5, 7, 12 and Day 6 of Week 12
Title
Pharmacokinetics: T1/2 of RO6864018 Metabolite in QWk Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Title
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QOD Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of Neopterin in QWk Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of Tumor Necrosis Factor (TNF)-Alpha in QOD Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of TNF-alpha in QWk Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of Interleukin (IL)-6 in QOD Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IL-6 in QWk Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QOD Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IL-10 in QWk Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QOD Dosing Cohorts
Time Frame
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
Title
Pharmacodynamics: Peripheral Blood Levels of IL-12p40 in QWk Dosing Cohorts
Time Frame
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
Title
Efficacy: Percentage of Participants with Development of Anti-HBe in QOD Dosing Cohorts
Time Frame
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
Title
Efficacy: Percentage of Participants with Development of Anti-HBe in QWk Dosing Cohorts
Time Frame
Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Efficacy: Percentage of Participants with Development of Anti-HBs in QOD Dosing Cohorts
Time Frame
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
Title
Efficacy: Percentage of Participants with Development of Anti-HBs in QWk Dosing Cohorts
Time Frame
Baseline; pre-dose (0 hours) on Day 1 of Weeks 2, 3, 5, 7; on Day 7 of Week 12; then at Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QWk Cohorts
Time Frame
QWk: Baseline; pre-dose (0 hours) and post-dose (6 and 24 hours) on Day 1 of Weeks 1, 2, 3, 5, 7, 12, and Day 7 of Week 12; then Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QOD Cohorts
Time Frame
Baseline; pre-dose; post-dose (6 and 24 hours) on Days 1, 3, and 7 for Week 1, Day 1 of Weeks 3, 5, 7, Day 6 of Week 12; then Weeks 16, 20, 24, 28, 32, 36 during follow-up
Title
Pharmacodynamics: Percentage of T Cells, B Cells, and NK Cells (TBNK)
Time Frame
For QOD and QWk Cohorts: Baseline; pre-dose (0 hours) on Day 1 of Weeks 1, 2, 5; then Weeks 20, 28, 36 during follow-up
Title
Pharmacodynamics: Percentage of Myeloid Cells
Time Frame
For QOD and QWk Cohorts: Baseline; pre-dose (0 hours) on Day 1 of Weeks 1, 2, 5; then Weeks 20, 28, 36 during follow-up
Title
Pharmacodynamics: Percentage of Plasmacytoid Dendritic Cells
Time Frame
For QOD and QWk Cohorts: Baseline; pre-dose (0 hours) on Day 1 of Weeks 1, 2, 5; then Weeks 20, 28, 36 during follow-up
Title
Pharmacokinetics: Cmax of Entecavir in QWk Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12
Title
Pharmacokinetics: AUCinf of Entecavir in QWk Dosing Cohorts
Time Frame
Pre-dose (0 hours) and post-dose (0.25, 1, 2, 4, 6, 8, 12, 24 hours) on Day 1 of Week 1; pre-dose (0 hours) and post-dose (1, 2-4 hours) on Day 1 of Weeks 2, 3, 5, 7, 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Trials
Organizational Affiliation
Hoffmann-La Roche
Official's Role
Study Director
Facility Information:
Facility Name
Queen Mary Hospital
City
Hong Kong
Country
Hong Kong
Facility Name
Prince of Wales Hospital; Special Medical Clinic
City
N.t.
Country
Hong Kong
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Severance Hospital, Yonsei University Health System
City
Seoul
ZIP/Postal Code
03722
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Hospital Ampang
City
Ampang
ZIP/Postal Code
68000
Country
Malaysia
Facility Name
Hospital Selayang; Medicine
City
Batu Caves
ZIP/Postal Code
68100
Country
Malaysia
Facility Name
University Malaya Medical Center
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
Auckland Clinical Studies Limited
City
Grafton
ZIP/Postal Code
1010
Country
New Zealand
Facility Name
Waikato Hospital
City
Hamilton
ZIP/Postal Code
3248
Country
New Zealand
Facility Name
Changi General Hospital
City
Singapore
ZIP/Postal Code
529889
Country
Singapore
Facility Name
Kaohsiung Medical Uni Chung-Ho Memorial Hospital; Dept of Internal Medicine
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
Taipei Veterans General Hospital
City
Taipei City
ZIP/Postal Code
112
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan

12. IPD Sharing Statement

Learn more about this trial

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

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