Trial record 113 of 506 for:    hepatitis b | Open Studies

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT02391805
First received: March 6, 2015
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Hepatitis B, Chronic
Drug: Entecavir
Drug: Placebo
Drug: RO6864018
Drug: Tenofovir
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Safety: Percentage of participants with adverse events [ Time Frame: Up to 36 weeks (scheduled visits at Baseline; at Weeks 1, 2, 3, 5, 7, 9 and 12 during treatment; then at Weeks 16, 20, 24, 28, 32, and 36 during follow-up) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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) ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Efficacy: Percentage of participants with HBsAg seroconversion (antibody to HBsAg [anti-HBs] positive status and loss of HBsAg) 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 ] [ Designated as safety issue: No ]
  • Efficacy: Percentage of participants with HBsAg seroconversion (anti-HBs positive status and loss of HBsAg) 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 ] [ Designated as safety issue: No ]
  • Efficacy: Percentage of participants with HBeAg seroconversion (antibody to HBeAg [anti-HBe] positive status and loss of HBeAg) 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 ] [ Designated as safety issue: No ]
  • Efficacy: Percentage of participants with HBeAg seroconversion (anti-HBe positive status and loss of HBeAg) 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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Maximum observed plasma concentration (Cmax) of RO6864018 metabolite in every other day (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 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Cmax of RO6864018 metabolite in every week (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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: May 2015
Estimated Study Completion Date: September 2017
Estimated Primary Completion Date: September 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo, QOD
Placebo orally (PO) QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Drug: Entecavir
Entecavir will be administered as per local labeling.
Drug: Placebo
Participants will be administered PO placebo capsules matched to RO6864018, either QOD or QWk for 12 weeks of treatment.
Drug: Tenofovir
Tenofovir will be administered as per local labeling.
Placebo Comparator: Placebo, QWk
Placebo PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Drug: Entecavir
Entecavir will be administered as per local labeling.
Drug: Placebo
Participants will be administered PO placebo capsules matched to RO6864018, either QOD or QWk for 12 weeks of treatment.
Drug: Tenofovir
Tenofovir will be administered as per local labeling.
Experimental: RO6864018, 1200 mg QOD
RO6864018 1200 milligrams (mg) PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Drug: Entecavir
Entecavir will be administered as per local labeling.
Drug: RO6864018
Participants will be administered RO6864018 as 200-mg PO capsules at a daily dosage of 800 or 1200 mg, either QOD or QWk for 12 weeks of treatment.
Drug: Tenofovir
Tenofovir will be administered as per local labeling.
Experimental: RO6864018, 1200 mg QWk
RO6864018 1200 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Drug: Entecavir
Entecavir will be administered as per local labeling.
Drug: RO6864018
Participants will be administered RO6864018 as 200-mg PO capsules at a daily dosage of 800 or 1200 mg, either QOD or QWk for 12 weeks of treatment.
Drug: Tenofovir
Tenofovir will be administered as per local labeling.
Experimental: RO6864018, 800 mg QOD
RO6864018 800 mg PO QOD for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Drug: Entecavir
Entecavir will be administered as per local labeling.
Drug: RO6864018
Participants will be administered RO6864018 as 200-mg PO capsules at a daily dosage of 800 or 1200 mg, either QOD or QWk for 12 weeks of treatment.
Drug: Tenofovir
Tenofovir will be administered as per local labeling.
Experimental: RO6864018, 800 mg QWk
RO6864018 800 mg PO QWk for 12 weeks + noninvestigational entecavir or tenofovir as prescribed by participant's physician
Drug: Entecavir
Entecavir will be administered as per local labeling.
Drug: RO6864018
Participants will be administered RO6864018 as 200-mg PO capsules at a daily dosage of 800 or 1200 mg, either QOD or QWk for 12 weeks of treatment.
Drug: Tenofovir
Tenofovir will be administered as per local labeling.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults 18 to 65 years of age
  • 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 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02391805

Contacts
Contact: Reference Study ID Number: NP28938 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

Locations
Hong Kong
Recruiting
Hong Kong, Hong Kong
Recruiting
Shatin, New Territories, Hong Kong
Korea, Republic of
Not yet recruiting
Gyeongsangnam-do, Korea, Republic of, 50612
Not yet recruiting
Seoul, Korea, Republic of, 03080
Recruiting
Seoul, Korea, Republic of, 03722
Recruiting
Seoul, Korea, Republic of, 05505
Malaysia
Recruiting
Ampang, Malaysia, 68000
Recruiting
Batu Caves, Malaysia, 68100
Recruiting
Kuala Lumpur, Malaysia, 59100
New Zealand
Recruiting
Grafton, New Zealand, 1010
Recruiting
Hamilton, New Zealand, 3248
Singapore
Not yet recruiting
Singapore, Singapore, 529889
Taiwan
Not yet recruiting
Kaohsiung, Taiwan, 807
Recruiting
Taipei, Taiwan, 00112
Not yet recruiting
Taipei, Taiwan, 10002
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02391805     History of Changes
Other Study ID Numbers: NP28938 
Study First Received: March 6, 2015
Last Updated: July 1, 2016
Health Authority: New Zealand: MEDSAFE, Ministry of Health

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis B
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Tenofovir
Entecavir
Antiviral Agents
Anti-Infective Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 28, 2016