Hepatitis B, Chronic Clinical Trial
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
Verified date | June 2018 |
Source | Hoffmann-La Roche |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
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 |
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 |
Lead Sponsor | Collaborator |
---|---|
Hoffmann-La Roche |
Hong Kong, Korea, Republic of, Malaysia, New Zealand, Singapore, Taiwan,
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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