A Study of Ritonavir-Boosted Danoprevir and RO5024048 in Different Combinations in Null Responder or Treatment-Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis

July 28, 2016 updated by: Hoffmann-La Roche

A Study to Evaluate Safety, Tolerability, Pharmacokinetics and Antiviral Activity of Ritonavir-Boosted DANOPREVIR and RO5024048 in Different Combinations in Null Responder or Treatment Naïve Patients With Chronic Hepatitis C and Compensated Cirrhosis

This open-label, parallel cohort study will evaluate the safety, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients, and with RO5024048 added to the combination treatment in prior null responder patients with chronic hepatitis C genotype 1 or 4 and compensated cirrhosis. All patients will receive danoprevir 100 mg orally twice daily (bid) , ritonavir 100 mg orally bid, Pegasys 180 mcg subcutaneously weekly and ribavirin 1000-1200 mg/kg/day orally. Prior non-responders will receive RO5024048 1000 mg orally bid additionally. Anticipated time on study treatment is 24 weeks.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

43

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • South Australia
      • Fitzroy, South Australia, Australia, 3065
    • Victoria
      • Melbourne, Victoria, Australia, 3124
  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 2C7
    • Ontario
      • Toronto, Ontario, Canada, M5G 2C4
  • France
      • Montpellier, France, 34094
  • New Zealand
      • Auckland, New Zealand, 1142
      • Christchurch, New Zealand, 8140
  • Poland
      • Chorzów, Poland, 41-500
      • Myslowice, Poland, 41-400
      • Warszawa, Poland, 02-507
      • Wrocław, Poland, 51-149
  • Slovakia
      • Bratislava, Slovakia, 833 05
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
    • California
      • Anaheim, California, United States, 92801
      • Coronado, California, United States, 92118
      • La Jolla, California, United States, 92037
      • Long Beach, California, United States, 90807
    • Florida
      • DeLand, Florida, United States, 32720
      • Miami, Florida, United States, 33136
      • Orlando, Florida, United States, 32803
    • Georgia
      • Atlanta, Georgia, United States, 30308
      • Atlanta, Georgia, United States, 30309
    • Louisiana
      • New Orleans, Louisiana, United States, 70112
    • Michigan
      • Detroit, Michigan, United States, 48202-2689
    • New Jersey
      • Hillsborough, New Jersey, United States, 08844
    • New York
      • New York, New York, United States, 10021
    • Texas
      • San Antonio, Texas, United States, 78215

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients, 18 to 65 years of age inclusive
  • Chronic hepatitis C, genotype 1 or 4
  • Cohort 1: Treatment-naïve for hepatitis C
  • Cohort 2: Prior null responder to treatment with approved doses of pegylated interferon plus ribavirin
  • Liver biopsy confirming cirrhosis
  • Compensated cirrhosis (Child-Pugh A)

Exclusion Criteria:

  • Pregnant or lactating women or male partners of women who are pregnant
  • History or presence of decompensated liver disease (ascites, hepatic encephalopathy, hepatocellular carcinoma, or bleeding esophageal varices)
  • Cohort 2: Patients who discontinued previous pegylated interferon plus ribavirin treatment due to reasons other than null response
  • History of clinically significant cardiovascular or cerebrovascular disease

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Combination without RO5024048
Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
Drug: danoprevir
100 mg orally bid, 24 weeks
Drug: peginterferon alfa-2a [Pegasys]
180 mcg weekly, 24 weeks
Drug: ribavirin
1000-1200 mg/kg/day orally in two divided doses, 24 weeks
Drug: ritonavir
100 mg orally bid, 24 weeks
Experimental: Combination with RO5024048
RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys [peginterferon alfa-2a] and ribavirin) in prior null responder patients
Drug: danoprevir
100 mg orally bid, 24 weeks
Drug: peginterferon alfa-2a [Pegasys]
180 mcg weekly, 24 weeks
Drug: ribavirin
1000-1200 mg/kg/day orally in two divided doses, 24 weeks
Drug: ritonavir
100 mg orally bid, 24 weeks
Drug: RO5024048
1000 mg orally bid, 24 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Safety: Incidence of adverse events
Time Frame: 48 weeks
48 weeks
Pharmacokinetics (PK): Area under the concentration-time curve (AUC)
Time Frame: Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24
Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24
Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test
Time Frame: 48 weeks
48 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Emergence of viral resistance: HCV RNA gene sequence variations
Time Frame: From baseline to Week 48
From baseline to Week 48
Virologic response: HCV RNA levels
Time Frame: approximately 1 year
approximately 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Hoffmann-La Roche

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2012

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

November 30, 2011

First Submitted That Met QC Criteria

November 30, 2011

First Posted (Estimate)

December 1, 2011

Study Record Updates

Last Update Posted (Estimate)

August 1, 2016

Last Update Submitted That Met QC Criteria

July 28, 2016

Last Verified

July 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NP27946
  • 2011-004129-28 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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