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

Phase 2

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: RO5024048; Drug: peginterferon alfa-2a [Pegasys]; Drug: danoprevir; Drug: ribavirin; Drug: ritonavir

• Registration Number: NCT01483742
• Lead Sponsor: Hoffmann-La Roche

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-11-30
• Study First Submitted QC: 2011-11-30
• Study First Posted: 2011-12-01
• Study Start: 2012-04
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Status Verified: 2016-07
• Disposition First Submitted: 2016-07-20
• Disposition First Submitted QC: 2016-07-20
• Disposition First Posted: 2016-07-22
• Last Update Submitted: 2016-07-28
• Last Update Posted: 2016-08-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 43

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Combination without RO5024048	peginterferon alfa-2a [Pegasys]	Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
Combination without RO5024048	ribavirin	Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
Combination with RO5024048	danoprevir	RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys \[peginterferon alfa-2a\] and ribavirin) in prior null responder patients
Combination with RO5024048	RO5024048	RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys \[peginterferon alfa-2a\] and ribavirin) in prior null responder patients
Combination with RO5024048	peginterferon alfa-2a [Pegasys]	RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys \[peginterferon alfa-2a\] and ribavirin) in prior null responder patients
Combination without RO5024048	danoprevir	Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
Combination without RO5024048	ritonavir	Ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and ribavirin in treatment-naïve patients
Combination with RO5024048	ritonavir	RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys \[peginterferon alfa-2a\] and ribavirin) in prior null responder patients
Combination with RO5024048	ribavirin	RO5024048 added to the combination treatment (ritonavir-boosted danoprevir in combination with Pegasys \[peginterferon alfa-2a\] and ribavirin) in prior null responder patients

Primary Outcome Measures

Name	Time	Method
Pharmacokinetics (PK): Area under the concentration-time curve (AUC)	Intensive PK sample collection during initial 2 week dosing period, followed by routine sampling during treatment up to Week 24
Antiviral activity: Hepatitis C virus (HCV) RNA levels assessed by Roche COBAS Taqman HCV Test	48 weeks
Safety: Incidence of adverse events	48 weeks

Secondary Outcome Measures

Name	Time	Method
Emergence of viral resistance: HCV RNA gene sequence variations	From baseline to Week 48
Virologic response: HCV RNA levels	approximately 1 year