A Study of Induction Dosing With PEGASYS (Peginterferon Alfa-2a [40KD]) Plus Copegus in Treatment-Naive Patients With Chronic Hepatitis C

• SVR-24 (Actual Treatment Period) [ Time Frame: 24 weeks after end of treatment ] [ Designated as safety issue: No ]
  SVR-24 according to the actual treatment period was defined as the percentage of patients with undetectable HCV RNA at least 20 weeks after the last dose of study drug.
• SVR-12 (Scheduled Treatment Period) [ Time Frame: 12 weeks after end of treatment ] [ Designated as safety issue: No ]
  SVR-12 according to the scheduled treatment period was defined as the percentage of patients with undetectable HCV RNA at 12 weeks after the scheduled treatment period (a single last HCV RNA PCR <15 IU/mL measured at or after week 60).
• SVR-12 (Actual Treatment Period) [ Time Frame: 12 weeks after end of treatment ] [ Designated as safety issue: No ]
  SVR-12 according to the actual treatment period was defined as the percentage of patients with undetectable HCV RNA at least 12 weeks after the last dose of study drug.

This 4-arm study will compare the efficacy and safety of PEGASYS induction and maintenance dosing, versus standard fixed dosing in combination with Copegus, and the efficacy and safety of higher dose versus standard dose Copegus in combination with PEGASYS. Patients with chronic hepatitis C (CHC) genotype 1 infection of high viral titer, and baseline body weight ≥85 kg, will be randomized to one of 4 groups, to receive one of the following: a) PEGASYS 180 µg subcutaneously (sc) weekly plus Copegus 1200 mg orally (po) daily; b) PEGASYS 180 µg sc weekly plus Copegus 1400-1600 mg po daily; c)PEGASYS 360 µg sc weekly (induction) followed by 180 µg sc weekly (maintenance) plus Copegus 1200 mg po daily; or d) PEGASYS 360 µg sc weekly (induction) followed by 180 µg sc weekly (maintenance) plus Copegus 1400-1600 mg po daily. Following 48 weeks treatment, there will be a 24-week period of treatment-free follow-up. The anticipated time on study treatment is 3-12 months, and the target sample size is 500+ individuals.

• Drug: peginterferon alfa-2a
  180 µg sc weekly for 48 weeks
  Other Name: Pegasys
• Drug: Ribavirin
  1200 mg po daily for 48 weeks
  Other Name: Copegus
• Drug: peginterferon alfa-2a
  360 µg sc weekly decreasing to 180 µg sc weekly for 48 weeks
  Other Name: Pegasys
• Drug: Ribavirin
  1400-1600 mg po daily for 48 weeks
  Other Name: Copegus

• Experimental: PEG-IFN 180 µg + Ribavirin 1200 mg
  Interventions:

  • Drug: peginterferon alfa-2a
  • Drug: Ribavirin
• Experimental: PEG-IFN 180 µg + Ribavirin 1400/1600 mg
  Interventions:

  • Drug: peginterferon alfa-2a
  • Drug: Ribavirin
• Experimental: PEG-IFN 360/180 µg + Ribavirin 1200 mg
  Interventions:

  • Drug: Ribavirin
  • Drug: peginterferon alfa-2a
• Experimental: PEG-IFN 360/180 µg + Ribavirin 1400/1600 mg
  Interventions:

  • Drug: peginterferon alfa-2a
  • Drug: Ribavirin

Inclusion Criteria:

• Adult patients, ≥18 years of age
• CHC infection, genotype 1
• Hepatitis C virus (HCV) RNA ≥400,000 IU/mL
• Baseline body weight ≥85 kg
• Liver biopsy (within 24 months of first dose) with results consistent with CHC

Exclusion Criteria:

• Previous treatment with interferon, ribavirin, viramidine, levovirin, HCV polymerase or protease inhibitors
• Other forms of liver disease, including liver cancer
• Human immunodeficiency virus infection