ANNAPURNA: A Study of The Combination of RO5466731, RO5190591, Ritonavir and Copegus (Ribavirin) With or Without RO5024048 in Patients With Chronic Hepatitis C Who Are Either Treatment-Naïve or Have Previously Experienced a Null Response to Interferon-Based Treatment

November 1, 2016 updated by: Hoffmann-La Roche

Randomized, Open-Label, Multicenter Study of Safety, Efficacy, and Tolerability of the Combination of RO5466731, RO5190591, Ritonavir, and Copegus With or Without RO5024048 in HCV Genotype 1 Infected Patients Who Are Either Treatment Naïve or Null Responders to Previous Interferon-Based Treatment

This randomized, open-label, multicenter study will evaluate the safety , efficacy and tolerability of the combination treatment RO5466731, RO5190591, ritonavir and Copegus (ribavirin) with or without RO5024048 in patients with chronic hepatitis C genotype 1. In Part 1, treatment-naïve patients will be randomized to receive treatment with RO5466731, RO5190591 plus ritonavir, and Copegus, with or without RO5024048. In Part 2, further treatment-naïve patients will receive a successful regimen from Part 1, or a reduced intensity regimen, and patients who have previously experienced null response to interferon-based treatment will be added to the study.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

110

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
    • New South Wales
      • Kingswood, New South Wales, Australia
      • Sydney, New South Wales, Australia, 2050
      • Westmead, New South Wales, Australia, 2145
    • Queensland
      • Herston, Queensland, Australia, 4029
    • Victoria
      • Parkville, Victoria, Australia, 3052
  • Germany
      • Berlin, Germany, 13353
      • Frankfurt Am Main, Germany, 60590
      • Hamburg, Germany, 20099
      • Hannover, Germany, 30625
  • New Zealand
      • Dunedin, New Zealand, 9016
      • Grafton, New Zealand, 1010
      • Hamilton, New Zealand
  • Poland
      • Bialystok, Poland, 15-540
      • Chorzow, Poland, 41-500
      • Lodz, Poland, 91-357
      • Myslowice, Poland, 41-400
  • United States
    • California
      • LaJolla, California, United States, 92037
    • Colorado
      • Englewood, Colorado, United States, 80113
    • Florida
      • South Miami, Florida, United States, 33143
    • Georgia
      • Marietta, Georgia, United States, 30060
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
    • Illinois
      • Chicago, Illinois, United States, 60637
    • Kansas
      • Kansas City, Kansas, United States, 66160
    • Michigan
      • Detroit, Michigan, United States, 48202
    • Missouri
      • Saint Louise, Missouri, United States, 63104
    • North Carolina
      • Asheville, North Carolina, United States, 28801
    • Texas
      • Dallas, Texas, United States, 75246
      • Houston, Texas, United States, 77030
      • San Antonio, Texas, United States, 78215
      • San Antonio, Texas, United States, 78234
    • Washington
      • Vancouver, Washington, United States, 98664

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Chronic hepatitis C genotype 1 of >/= 6 months duration at screening
  • Part 1 and Part 2: Naïve to treatment with interferon (pegylated or non-pegylated). Patients who have participated in studies investigating a direct-acting antiviral agent with or without interferon are excluded
  • Part 2: Treatment experienced patients having a previous null response to treatment with interferon containing regimen
  • Liver biopsy or non-invasive (e.g. Fibroscan) evaluation in the past 24 calendar months showing absence of cirrhosis or incomplete/transition to cirrhosis
  • Body mass index (BMI) 18 to 35 kg/m2 inclusive and body weight >/= 45 kg

Exclusion Criteria:

  • Pregnant or lactating women or males with female partners who are pregnant or lactating
  • Decompensated liver disease or impaired liver function (as defined by protocol)
  • Cirrhosis or incomplete/transition to cirrhosis
  • Non- hepatitis C chronic liver disease
  • Positive for hepatitis B or HIV infection
  • History of pre-existing renal disease
  • History of severe cardiac disease
  • History of neoplastic disease within the last 5 years, except for localized or in situ carcinoma of the skin
  • History of drug abuse within the last year; history of cannabinoid use is not excluded
  • Evidence of alcohol abuse within 1 year of screening and consumption of more than 2 units of alcohol per day
  • Medical condition that requires use of systemic corticosteroids
  • Received warfarin or other anticoagulants during the 21 days immediately prior to screening or is expected to require warfarin or other anticoagulants during the study
  • Anticipated use or need for significant medical treatment during the study or use of concomitant medications or nutrients that are excluded by protocol (e.g. drugs that are contraindicated with ritonavir, hormonal methods of contraception)

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
Drug: ritonavir
Drug: RO5024048
Drug: RO5190591
Drug: RO5466731
Drug: ribavirin [Copegus]
Experimental: B: GT1a 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
Drug: ritonavir
Drug: RO5024048
Drug: RO5190591
Drug: RO5466731
Drug: ribavirin [Copegus]
Experimental: C: GT1a 2DAA
including RO5466731, RO5190591, ritonavir and ribavirin [Copegus]
Drug: ritonavir
Drug: RO5190591
Drug: RO5466731
Drug: ribavirin [Copegus]
Experimental: D: GT1b 3DAA
including RO5466731, RO5190591, ritonavir, ribavirin [Copegus] and RO5024048
Drug: ritonavir
Drug: RO5024048
Drug: RO5190591
Drug: RO5466731
Drug: ribavirin [Copegus]
Experimental: E: GT1b 2DAA
including RO54664731, RO5190591, ritonavir and ribavirin [Copegus]
Drug: ritonavir
Drug: RO5190591
Drug: RO5466731
Drug: ribavirin [Copegus]
Experimental: Part II
Drug: ritonavir
Drug: RO5024048
Drug: RO5190591
Drug: RO5466731
Drug: ribavirin [Copegus]

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Sustained virological response (defined as undetectable serum HCV RNA) 12 weeks after end of treatment
Time Frame: approximately 20 months
approximately 20 months
Safety: Incidence of adverse events
Time Frame: approximately 20 months
approximately 20 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Antiviral activity: Change in serum HCV RNA levels
Time Frame: from baseline to 24 weeks after end of treatment
from baseline to 24 weeks after end of treatment
Pharmacokinetics in coadministration: Area under the concentration-time curve (AUC)
Time Frame: Pre-dose Weeks 1, 2, 3, 4, 6, 10, and 12 and up to 12 hours post-dose Weeks 1, and 4 or 3 and 6
Pre-dose Weeks 1, 2, 3, 4, 6, 10, and 12 and up to 12 hours post-dose Weeks 1, and 4 or 3 and 6
HCV drug resistance
Time Frame: approximately 20 months
approximately 20 months
Quality of life: Short-Form 36v2/Brief Fatigue Inventory questionnaires
Time Frame: approximately 20 months
approximately 20 months

Collaborators and Investigators

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

Sponsor

Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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

June 1, 2012

Primary Completion (Actual)

November 1, 2013

Study Completion (Actual)

November 1, 2013

Study Registration Dates

First Submitted

June 22, 2012

First Submitted That Met QC Criteria

June 22, 2012

First Posted (Estimate)

June 26, 2012

Study Record Updates

Last Update Posted (Estimate)

November 2, 2016

Last Update Submitted That Met QC Criteria

November 1, 2016

Last Verified

November 1, 2016

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NP28266
  • 2012-000638-21 (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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