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Register:	ClinicalTrials.gov
Last refreshed on:	12 December 2020
Main ID:	NCT02391805
Date of registration:	06/03/2015
Prospective Registration:	Yes
Primary sponsor:	Hoffmann-La Roche
Public title:	A Study of Treatment With RO6864018 in Virologically Suppressed Participants With Chronic Hepatitis B Virus (HBV) Infection
Scientific 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
Date of first enrolment:	May 17, 2015
Target sample size:	31
Recruitment status:	Completed
URL:	https://clinicaltrials.gov/show/NCT02391805
Study type:	Interventional
Study design:	Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Double (Participant, Investigator).
Phase:	Phase 2

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

Contacts

Name:	Clinical Trials
Address:
Telephone:
Email:
Affiliation:	Hoffmann-La Roche

Key inclusion & exclusion 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

Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Hepatitis B, Chronic

Intervention(s)

Drug: Tenofovir

Drug: Placebo

Drug: Entecavir

Drug: RO6864018

Primary Outcome(s)

Safety: Percentage of Participants with Adverse Events [Time Frame: Baseline up to approximately 36 weeks]

Secondary Outcome(s)

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]

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]

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]

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]

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]

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]

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]

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]

Efficacy: Percentage of Participants with HBeAg Seroconversion in QWk Dosing Cohorts [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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Efficacy: Percentage of Participants with HBeAg Seroconversion in QOD Dosing Cohorts [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]

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]

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]

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)]

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]

Efficacy: Percentage of Participants with HBsAg Seroconversion in QOD Dosing Cohorts [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]

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]

Efficacy: Percentage of Participants with HBsAg Seroconversion in QWk Dosing Cohorts [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]

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]

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]

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]

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)]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

Secondary ID(s)

NP28938

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Ethics review

Results

Results available:
Date Posted:
Date Completed:
URL:

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