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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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01483742
First received: November 30, 2011
Last updated: July 28, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
Hepatitis C, Chronic
Drug: RO5024048
Drug: danoprevir
Drug: peginterferon alfa-2a [Pegasys]
Drug: ribavirin
Drug: ritonavir
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Safety: Incidence of adverse events [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Emergence of viral resistance: HCV RNA gene sequence variations [ Time Frame: From baseline to Week 48 ] [ Designated as safety issue: No ]
  • Virologic response: HCV RNA levels [ Time Frame: approximately 1 year ] [ Designated as safety issue: No ]

Enrollment: 43
Study Start Date: April 2012
Study Completion Date: September 2013
Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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: RO5024048
1000 mg orally bid, 24 weeks
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

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01483742

  Show 27 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01483742     History of Changes
Other Study ID Numbers: NP27946  2011-004129-28 
Study First Received: November 30, 2011
Last Updated: July 28, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis C
Hepatitis, Chronic
Fibrosis
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Pathologic Processes
Ribavirin
Ritonavir
Peginterferon alfa-2a
Interferon-alpha
Lactams
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Anti-HIV Agents
Anti-Retroviral Agents
Cytochrome P-450 CYP3A Inhibitors

ClinicalTrials.gov processed this record on September 23, 2016