A Study of Danoprevir/Ritonavir and Copegus With RO5024048 and/or Pegasys in Patients With Chronic Hepatitis C

A Randomized Open-label Study to Evaluate the Sustained Virologic Response of Danoprevir/Ritonavir and Copegus in Combination With RO5024048 and/or Pegasys in Chronic Hepatitis C Genotype 1 Patients Who Failed Previous Standard Therapy

This randomized, open-label, multi-center study will evaluate the sustained virological response, pharmacokinetics and safety of various combinations of danoprevir/ritonavir with Copegus plus RO5024048 and/or Pegasys in patients with chronic hepatitis C infection. Patients will be divided into 2 separate cohorts. Cohort A, previous partial responders, will be randomized to Groups 1-3 and cohort B, previous null responders, will be randomized to Groups 4-6. Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Groups 1 and 4 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks; Group 2 will receive Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks; Groups 3, 5 and 6 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus treatment.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: Copegus; Drug: Copegus; Drug: RO5024048; Drug: danoprevir; Drug: ritonavir; Drug: Pegasys; Drug: Pegasys

• Study Type: Interventional
• Enrollment (Actual): 381
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
    • Kingswood, New South Wales, Australia, 2747
    • Westmead, New South Wales, Australia, 2145
  • South Australia
    • Adelaide, South Australia, Australia, 5000
  • Victoria
    • Melbourne, Victoria, Australia, 3004
    • Melbourne, Victoria, Australia, 3186
• Austria
  • Wien, Austria, 1090
• Brazil
  • RS
    • Porto Alegre, RS, Brazil, 90035-003
  • SP
    • Ribeirao Preto, SP, Brazil, 14049-900
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
    • Edmonton, Alberta, Canada, T6G 2B7
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
    • Vancouver, British Columbia, Canada, V5Z 1H2
    • Vancouver, British Columbia, Canada, V6Z 2K5
  • Ontario
    • London, Ontario, Canada, N6A 5A5
    • Ottawa, Ontario, Canada, K1H 8L6
    • Toronto, Ontario, Canada, M5G 1L7
• France
  • La Tronche, France, 38700
  • Paris, France, 75651
  • Paris, France, 75679
  • Pessac, France, 33604
  • Vandoeuvre-les-nancy, France, 54511
• Germany
  • Berlin, Germany, 13353
  • Essen, Germany, 45122
  • Kiel, Germany, 24105
  • Tübingen, Germany, 72076
• Italy
  • Campania
    • Napoli, Campania, Italy, 80135
  • Lombardia
    • Milano, Lombardia, Italy, 20162
    • Pavia, Lombardia, Italy, 27100
  • Toscana
    • Pisa, Toscana, Italy, 56124
• Mexico
  • Guadalajara, Mexico, 44650
  • Guadalajara, Mexico, 44280
• Poland
  • Bydgoszcz, Poland, 85-030
  • Czeladz, Poland, 41-250
  • Kielce, Poland, 25-317
  • Warszawa, Poland, 01-201
  • Łodz, Poland, 91-347
• Puerto Rico
  • San Juan, Puerto Rico, 00927
• Spain
  • Barcelona, Spain, 08003
  • Madrid, Spain, 28034
  • Madrid, Spain, 28222
  • Sevilla, Spain, 41014
  • Barcelona
    • Badalona, Barcelona, Spain, 08915
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
  • Dundee, United Kingdom, DD1 9SY
  • London, United Kingdom, E1 1BB
  • London, United Kingdom, W2 1PG
  • Manchester, United Kingdom, M8 5RB
• United States
  • California
    • La Jolla, California, United States, 92037-1030
    • Long Beach, California, United States, 90822
    • Sacramento, California, United States, 95817
    • San Diego, California, United States, 92103
  • Colorado
    • Aurora, Colorado, United States, 80045
  • Florida
    • Orlando, Florida, United States, 32804
  • Georgia
    • Decatur, Georgia, United States, 30033
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
  • Michigan
    • Detroit, Michigan, United States, 48202-2689
  • New York
    • Manhasset, New York, United States, 11030
    • New York, New York, United States, 10021
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7584
  • Oregon
    • Medford, Oregon, United States, 97504
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
  • Tennessee
    • Nashville, Tennessee, United States, 37211
  • Texas
    • Houston, Texas, United States, 77030
    • San Antonio, Texas, United States, 78215
    • San Antonio, Texas, United States, 78234

Participation Criteria

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, age 18 years and older
• Presence of hepatitis C infection, genotype 1a or 1b
• Documentation of previous treatment failure after receiving approved doses of peginterferon plus ribavirin for at least 12 weeks
• Patients must have discontinued prior hepatitis C treatment at least 12 weeks prior to study start

Exclusion Criteria:

• Infection with any hepatitis C genotype or subtype other than genotype 1a or 1b
• Patients with cirrhosis
• Patients who were discontinued from previous peginterferon plus ribavirin therapy due to reasons other than insufficient therapeutic response
• Co-infection with hepatitis B or human immunodeficiency virus (HIV)
• History or evidence of chronic liver disease other than hepatitis C

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Previous null responders (Cohort B): Group 4; Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 4 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.	Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 24 weeks; Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 48 weeks; Drug: RO5024048; 1000 mg oral doses twice a day for 24 weeks; Drug: danoprevir; 100 mg oral doses twice a day for 24 weeks; Drug: ritonavir; 100 mg oral doses twice a day for 24 weeks
Experimental: Previous null responders (Cohort B): Group 5; Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 5 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.	Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 24 weeks; Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 48 weeks; Drug: RO5024048; 1000 mg oral doses twice a day for 24 weeks; Drug: danoprevir; 100 mg oral doses twice a day for 24 weeks; Drug: ritonavir; 100 mg oral doses twice a day for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 48 weeks
Experimental: Previous null responders (Cohort B): Group 6; Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 6 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks. In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus treatment.	Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 24 weeks; Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 48 weeks; Drug: RO5024048; 1000 mg oral doses twice a day for 24 weeks; Drug: danoprevir; 100 mg oral doses twice a day for 24 weeks; Drug: ritonavir; 100 mg oral doses twice a day for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 48 weeks
Experimental: Previous partial responders (Cohort A): Group 1; Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 1 will receive RO5024048 1000 mg twice a day and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.	Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 24 weeks; Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 48 weeks; Drug: RO5024048; 1000 mg oral doses twice a day for 24 weeks; Drug: danoprevir; 100 mg oral doses twice a day for 24 weeks; Drug: ritonavir; 100 mg oral doses twice a day for 24 weeks
Experimental: Previous partial responders (Cohort A): Group 2; Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. In addition, Group 2 will receive Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.	Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 24 weeks; Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 48 weeks; Drug: danoprevir; 100 mg oral doses twice a day for 24 weeks; Drug: ritonavir; 100 mg oral doses twice a day for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 48 weeks
Experimental: Previous partial responders (Cohort A): Group 3; Patients in all groups will receive danoprevir 100 mg twice a day and ritonavir 100 mg twice a day for 24 weeks. Group 3 will receive RO5024048 1000 mg twice a day, Pegasys 180 microgram subcutaneously once weekly and Copegus 1000 mg or 1200 mg twice a day for 24 weeks.	Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 24 weeks; Drug: Copegus; 1000 mg or 1200 mg daily oral doses for 48 weeks; Drug: RO5024048; 1000 mg oral doses twice a day for 24 weeks; Drug: danoprevir; 100 mg oral doses twice a day for 24 weeks; Drug: ritonavir; 100 mg oral doses twice a day for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 24 weeks; Drug: Pegasys; 180 microgram subcutaneously once weekly for 48 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sustained virological response (SVR) of danoprevir/ritonavir with RO5024048 and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment	24 weeks
Sustained virological response (SVR) of danoprevir/ritonavir with Pegasys and Copegus in patients with previous partial response to peginterferon/ribavirin treatment	24 weeks
Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment	24 weeks
Sustained virological response (SVR) of danoprevir/ritonavir and RO5024048 with Pegasys and Copegus followed by 24 weeks of Pegasys and Copegus treatment in patients with previous null response to peginterferon/ribavirin treatment	48 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Safety (Incidence of adverse events) of danoprevir, RO5024048 and Copegus	48 weeks
Safety (Incidence of adverse events) of danoprevir, Pegasys and Copegus	48 weeks
Safety (Incidence of adverse events) of danoprevir, RO5024048, Pegasys and Copegus	72 weeks
Virological response over time	48 weeks
Change in danoprevir plasma concentration	24 weeks
Change in RO5024048 plasma concentration	24 weeks
Hepatitis C virus drug resistance profile	24 weeks

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): January 1, 2013

Study Registration Dates

• First Submitted: March 28, 2011
• First Submitted That Met QC Criteria: April 7, 2011
• First Posted (Estimate): April 8, 2011

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: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Antimetabolites; Immunologic Factors; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Interferon-alpha; Ribavirin; Peginterferon alfa-2a; Ritonavir
• Other Study ID Numbers: WV21913; 2010-019585-90