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

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

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.

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