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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01331850
First received: March 28, 2011
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

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 t! wice a day for 24 weeks. In addition, patients in Group 6 will receive another 24 weeks of Pegasys plus Copegus treatment.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: danoprevir
Drug: ritonavir
Drug: RO5024048
Drug: Copegus
Drug: Pegasys
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Sustained virological response (SVR) of danoprevir/ritonavir with RO5024048 and Copegus in patients with previous partial or null response to peginterferon/ribavirin treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Sustained virological response (SVR) of danoprevir/ritonavir with Pegasys and Copegus in patients with previous partial response to peginterferon/ribavirin treatment [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Safety (Incidence of adverse events) of danoprevir, RO5024048 and Copegus [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Safety (Incidence of adverse events) of danoprevir, Pegasys and Copegus [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Safety (Incidence of adverse events) of danoprevir, RO5024048, Pegasys and Copegus [ Time Frame: 72 weeks ] [ Designated as safety issue: No ]
  • Virological response over time [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Change in danoprevir plasma concentration [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Change in RO5024048 plasma concentration [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • Hepatitis C virus drug resistance profile [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]

Enrollment: 381
Study Start Date: May 2011
Study Completion Date: January 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 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: RO5024048
1000 mg oral doses twice a day for 24 weeks
Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Experimental: 2 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: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly for 24 weeks
Experimental: 3 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: RO5024048
1000 mg oral doses twice a day for 24 weeks
Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly for 24 weeks
Experimental: 4 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: RO5024048
1000 mg oral doses twice a day for 24 weeks
Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Experimental: 5 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: RO5024048
1000 mg oral doses twice a day for 24 weeks
Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly for 24 weeks
Experimental: 6 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: RO5024048
1000 mg oral doses twice a day for 24 weeks
Drug: Copegus
1000 mg or 1200 mg daily oral doses for 48 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly for 48 weeks

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01331850

  Show 67 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01331850     History of Changes
Other Study ID Numbers: WV21913, 2010-019585-90
Study First Received: March 28, 2011
Last Updated: April 7, 2014
Health Authority: Italy: Comitato Etico Azienda Ospedalier Pisana-Toscana

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Ribavirin
Ritonavir
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents

ClinicalTrials.gov processed this record on April 22, 2014