A Study of Ritonavir-Boosted Danoprevir in Combination With Pegasys (Peginterferon Alfa-2a) and Copegus (Ribavirin) in Patients of Asian Origin With Chronic Hepatitis C Genotype 1 With or Without Cirrhosis

• Safety: Incidence of adverse events [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
• Pharmacokinetics: Area under the concentration-time curve (AUC) for danoprevir/ritonavir [ Time Frame: up to 14 days ] [ Designated as safety issue: No ]
• Antiviral activity: Change in HCV RNA levels, measured using Roche COBAS TaqMan HCV Test v2.0 for High Pure System [ Time Frame: from baseline to Week 36/48 ] [ Designated as safety issue: No ]
• Antiviral activity: Proportion of patients with unquantifiable/undetectable HCV RNA during the study [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]

• Incidence of viral resistance to danoprevir [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
• Rapid virological response (RVR): Proportion of patients with undetectable HCV RNA at Week 4 [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
• Complete early virological response (cEVR): Proportion of patients with undetectable HCV RNA at Week 12 [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
• Sustained virological response 12 weeks after end of treatment (SVR-12), defined as unquantifiable HCV RNA 8-20 weeks after the last day of study drug administration [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
• Sustained virological response 24 weeks after end of treatment (SVR-24), defined as unquantifiable HCV RNA > 20 weeks after the last day of study drug administration [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]
• SVR measured as HCV RNA log10 IU/mL change from baseline to Week 12 [ Time Frame: approximately 1.5 years ] [ Designated as safety issue: No ]

This Phase II, open-label, parallel-arm study will evaluate the safety, tolerability, pharmacokinetics and antiviral activity of ritonavir-boosted danoprevir in combination with Pegasys (peginterferon alfa-2a) and Copegus (ribavirin) in treatment-naïve patients of Asian origin with chronic hepatitis C genotype 1. Patients will receive danoprevir 125 mg plus ritonavir 100 mg as fixed dose tablet orally twice daily in combination with weekly Pegasys 180 mcg subcutaneously and Copegus 1000-1200 mg orally daily in divided doses. Treatment duration is 12 weeks in patients without cirrhosis and 24 weeks in patients with compensated cirrhosis.

• Drug: danoprevir + ritonavir
  125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 12 weeks
• Drug: danoprevir + ritonavir
  125 mg danoprevir + 100 mg ritonvir fixed-dose combination tablet, orally b.i.d., 24 weeks
• Drug: peginterferon alfa-2a [Pegasys]
  180 mcg sc weekly, 12 weeks
• Drug: peginterferon alfa-2a [Pegasys]
  180 mcg sc weekly, 24 weeks
• Drug: ribavirin [Copegus]
  1000-1200 mg orally daily in divided doses, 12 weeks
• Drug: ribavirin [Copegus]
  1000-1200 mg orally daily in divided doses, 24 weeks

• Experimental: with cirrhosis
  Interventions:

  • Drug: danoprevir + ritonavir
  • Drug: peginterferon alfa-2a [Pegasys]
  • Drug: ribavirin [Copegus]
• Experimental: without cirrhosis
  Interventions:

  • Drug: danoprevir + ritonavir
  • Drug: peginterferon alfa-2a [Pegasys]
  • Drug: ribavirin [Copegus]

Inclusion Criteria:

• Adult patients of East Asian or Southeast Asian origin, >/= 18 years of age
• Presence of chronic genotype 1 hepatitis C infection
• Treatment-naïve

Exclusion Criteria:

• History or presence of decompensated liver disease
• Presence or history of non-hepatitis C chronic liver disease
• Positive for hepatitis B or HIV infection