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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT02391805
Other study ID # NP28938
Secondary ID
Status Completed
Phase Phase 2
First received
Last updated
Start date May 17, 2015
Est. completion date October 16, 2017

Study information

Verified date June 2018
Source Hoffmann-La Roche
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 31
Est. completion date October 16, 2017
Est. primary completion date October 16, 2017
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility 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

Study Design


Intervention

Drug:
Entecavir
Entecavir will be administered as per local labeling.
Placebo
Participants will be administered PO placebo capsules matched to RO6864018, either QOD or QWk for 12 weeks of treatment.
RO6864018
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.
Tenofovir
Tenofovir will be administered as per local labeling.

Locations

Country Name City State
Hong Kong Queen Mary Hospital Hong Kong
Hong Kong Prince of Wales Hospital; Special Medical Clinic N.t.
Korea, Republic of Asan Medical Center Seoul
Korea, Republic of Seoul National University Hospital Seoul
Korea, Republic of Severance Hospital, Yonsei University Health System Seoul
Malaysia Hospital Ampang Ampang
Malaysia Hospital Selayang; Medicine Batu Caves
Malaysia University Malaya Medical Center Kuala Lumpur
New Zealand Auckland Clinical Studies Limited Grafton
New Zealand Waikato Hospital Hamilton
Singapore Changi General Hospital Singapore
Taiwan Kaohsiung Medical Uni Chung-Ho Memorial Hospital; Dept of Internal Medicine Kaohsiung
Taiwan National Taiwan University Hospital Taipei
Taiwan Taipei Veterans General Hospital Taipei City

Sponsors (1)

Lead Sponsor Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Hong Kong,  Korea, Republic of,  Malaysia,  New Zealand,  Singapore,  Taiwan, 

Outcome

Type Measure Description Time frame Safety issue
Primary Safety: Percentage of Participants with Adverse Events Baseline up to approximately 36 weeks
Secondary 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
Secondary 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
Secondary 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
Secondary 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
Secondary 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)
Secondary Efficacy: Quantitative HBV DNA Level in QWk Dosing Cohorts 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)
Secondary Efficacy: Quantitative Hepatitis B Surface Antigen (HBsAg) 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
Secondary Efficacy: Quantitative HBsAg Level in QWk Dosing Cohorts 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
Secondary Efficacy: Percentage of Participants with Loss of HBsAg in QOD Dosing Cohorts Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Secondary Efficacy: Percentage of Participants with Loss of HBsAg in QWk Dosing Cohorts Baseline; on Day 7 of Week 12; then at Week 36 during follow-up
Secondary Efficacy: Percentage of Participants with Loss of Hepatitis B Envelope Antigen (HBeAg) 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
Secondary Efficacy: Percentage of Participants with Loss of HBeAg in QWk Dosing Cohorts 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
Secondary Efficacy: Percentage of Participants with HBsAg Seroconversion in QOD Dosing Cohorts HBsAg Seroconversion = antibody to HBsAg (Anti-HBs) Positive Status and Loss of HBsAg 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
Secondary Efficacy: Percentage of Participants with HBsAg Seroconversion in QWk Dosing Cohorts HBsAg Seroconversion = anti-HBs Positive Status and Loss of HBsAg 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
Secondary Efficacy: Percentage of Participants with HBeAg Seroconversion in QOD Dosing Cohorts HBeAg Seroconversion = antibody to HBeAg (anti-HBe) Positive Status and Loss of HBeAg 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
Secondary Efficacy: Percentage of Participants with HBeAg Seroconversion in QWk Dosing Cohorts HBeAg Seroconversion = anti-HBe Positive Status and Loss of HBeAg 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
Secondary Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of RO6864018 Metabolite in QOD Dosing Cohorts 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
Secondary Pharmacokinetics: Cmax of RO6864018 Metabolite in QWk Dosing Cohorts 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
Secondary Pharmacokinetics: Time to Maximum Observed Plasma Concentration (Tmax) of RO6864018 Metabolite in QOD Dosing Cohorts 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
Secondary Pharmacokinetics: Tmax of RO6864018 Metabolite in QWk Dosing Cohorts 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
Secondary Pharmacokinetics: Area Under the Plasma Concentration-Time Curve Extrapolated to Infinity (AUCinf) of RO6864018 Metabolite in QOD Dosing Cohorts 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
Secondary Pharmacokinetics: AUCinf of RO6864018 Metabolite in QWk Dosing Cohorts 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
Secondary Pharmacokinetics: Area Under the Plasma Concentration-Time Curve up to the Last Measurable Concentration (AUClast) of RO6864018 Metabolite in QOD Dosing Cohorts 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
Secondary Pharmacokinetics: AUClast of RO6864018 Metabolite in QWk Dosing Cohorts 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
Secondary Pharmacokinetics: Half-life (t1/2) of RO6864018 Metabolite in QOD Dosing Cohorts 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
Secondary Pharmacokinetics: T1/2 of RO6864018 Metabolite in QWk Dosing Cohorts 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
Secondary Pharmacodynamics: Peripheral Blood Levels of Neopterin 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
Secondary Pharmacodynamics: Peripheral Blood Levels of Neopterin 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
Secondary Pharmacodynamics: Peripheral Blood Levels of Tumor Necrosis Factor (TNF)-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
Secondary Pharmacodynamics: Peripheral Blood Levels of TNF-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
Secondary Pharmacodynamics: Peripheral Blood Levels of Interleukin (IL)-6 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
Secondary Pharmacodynamics: Peripheral Blood Levels of IL-6 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
Secondary Pharmacodynamics: Peripheral Blood Levels of IL-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
Secondary Pharmacodynamics: Peripheral Blood Levels of IL-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
Secondary Pharmacodynamics: Peripheral Blood Levels of IL-12p40 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
Secondary Pharmacodynamics: Peripheral Blood Levels of IL-12p40 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
Secondary Efficacy: Percentage of Participants with Development of Anti-HBe 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
Secondary Efficacy: Percentage of Participants with Development of Anti-HBe in QWk Dosing Cohorts 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
Secondary Efficacy: Percentage of Participants with Development of Anti-HBs 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
Secondary Efficacy: Percentage of Participants with Development of Anti-HBs in QWk Dosing Cohorts 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
Secondary Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QWk Cohorts 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
Secondary Pharmacodynamics: Transcriptional Responses as Measured by messenger ribonucleic acid (mRNA) Levels for QOD Cohorts 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
Secondary Pharmacodynamics: Percentage of T Cells, B Cells, and NK Cells (TBNK) 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
Secondary Pharmacodynamics: Percentage of Myeloid Cells 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
Secondary Pharmacodynamics: Percentage of Plasmacytoid Dendritic Cells 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
Secondary Pharmacokinetics: Cmax of Entecavir in QWk Dosing Cohorts 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
Secondary Pharmacokinetics: AUCinf of Entecavir in QWk Dosing Cohorts 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
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