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: October 20, 2014
Last verified: October 2014
  Purpose

This randomized, open-label, multi-center study will evaluate the sustained viro logical response, pharmacokinetics and safety of various combinations of danopre vir/ritonavir with Copegus plus RO5024048 and/or Pegasys in patients with chroni c hepatitis C infection. Patients will be divided into 2 separate cohorts. Cohor t 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 gro ups 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 recei ve 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 tw ice 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 recei ve another 24 weeks of Pegasys plus Copegus treatment.


Condition Intervention Phase
Hepatitis C, Chronic
Drug: Copegus
Drug: Pegasys
Drug: RO5024048
Drug: danoprevir
Drug: ritonavir
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: Copegus
1000 mg or 1200 mg daily oral doses for 24 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: 2 Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly 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: 3 Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly for 24 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: 4 Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 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: 5 Drug: Copegus
1000 mg or 1200 mg daily oral doses for 24 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly for 24 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: 6 Drug: Copegus
1000 mg or 1200 mg daily oral doses for 48 weeks
Drug: Pegasys
180 microgram subcutaneously once weekly 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

  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
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: 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: October 20, 2014
Health Authority: Italy: Comitato Etico Azienda Ospedalier Pisana-Toscana

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

ClinicalTrials.gov processed this record on October 23, 2014