Antiviral Effect and Safety of BI201335 +PegIFN/RBV in HCV-GT1

• Sustained Virological Response [ Time Frame: Week 48 or 72 ] [ Designated as safety issue: No ]
• End of Treatment- Response of BI 201335 NA or placebo plus 4 weeks [ Time Frame: Week 28 or 52 ] [ Designated as safety issue: No ]

• complete early virological response [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Week 4 Virological Response [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
• end of treatment response [ Time Frame: Week 24 or 48 ] [ Designated as safety issue: No ]
• sustained virological response at 12 weeks after completion of all therapy [ Time Frame: Week 36 or 60 ] [ Designated as safety issue: No ]
• time to reach a plasma HCV RNA level below the lower limit of detection [ Time Frame: n.a. ] [ Designated as safety issue: No ]
• time to loss of virological response [ Time Frame: n.a. ] [ Designated as safety issue: No ]
• Week 2 Virological Response [ Time Frame: Week 2 ] [ Designated as safety issue: No ]

The current Standard of Care (SOC) for chronic HCV infection, which is pegylated interferon-alfa as combination therapy with ribavirin for 24-48 weeks of treatment, is effective in only part of the patients and is often associated with severe adverse effects leading to discontinuation of treatment and dose modifications.

A number of compounds with direct activity are currently under clinical development, incl. BI 201335. BI 201335 works by preventing the Hepatitis C virus from replicating by binding to the HCV protease (enzyme). The main purpose of this clinical trial with BI 201335 is to see how well BI 201335 works and how safe BI 201335 is to use daily in combination with PegIFN and RBV in HCV infected patients.

• Drug: Arm 3 BI 201335 NA
  240mg BI 201335 NA once daily with a 3 days lead-in phase of PegIFN/RB, 24 weeks
• Drug: Arm 3 PegIFN/RBV
  PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks
• Drug: Arm 4 BI 201335 NA
  120mg BI 201335 NA once daily, for 24 weeks
• Drug: Arm 4 PegIFN/RBV
  PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
• Drug: Arm 5 BI 201335 NA
  240mg BI 201335 NA once daily, 24 weeks
• Drug: Arm 5 PegIFN/RBV
  PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
• Drug: Arm 6 BI 201335 NA
  240mg BI 201335 NA once daily, 24 weeks
• Drug: Arm 6 PegIFN/RBV
  PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks
• Drug: Arm 7 BI 201335 NA
  240mg BI 201335 NA twice, 24 weeks
• Drug: Arm 7 PegIFN/RBV
  PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
• Drug: Arm 1 PegIFN/RBV
  PegIFN (180 µg/wk) and RBV (1000/1200mg/d),48 weeks
• Drug: Arm 2 BI 201335 NA
  240mg BI 201335 NA once daily, 24 weeks
• Drug: Arm 2 PegIFN/RBV
  PegIFN (180 µg/wk) and RBV (1000/1200mg/d), 24 or 48 weeks

• Experimental: 2. 240 mg QD
  240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48weeks, in treatment-naive patients
  Interventions:

  • Drug: Arm 2 BI 201335 NA
  • Drug: Arm 2 PegIFN/RBV
• Experimental: 3. 240 mg QD / LI
  240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-naive patients
  Interventions:

  • Drug: Arm 3 BI 201335 NA
  • Drug: Arm 3 PegIFN/RBV
• 1. Placebo
  PegIFN/RBV for 48 weeks in treatment-naive patients
  Intervention: Drug: Arm 1 PegIFN/RBV
• Experimental: 4 .120 mg QD / LI
  120mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks in treatment-naive patients
  Interventions:

  • Drug: Arm 4 BI 201335 NA
  • Drug: Arm 4 PegIFN/RBV
• Experimental: 5. 240 mg QD
  240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks in treatment-experienced patients
  Interventions:

  • Drug: Arm 5 BI 201335 NA
  • Drug: Arm 5 PegIFN/RBV
• Experimental: 6. 240 mg QD / LI
  240mg BI 201335 NA once daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients
  Interventions:

  • Drug: Arm 6 BI 201335 NA
  • Drug: Arm 6 PegIFN/RBV
• Experimental: 7. 240 mg BID / LI
  240mg BI 201335 NA twice daily combined with PegIFN/RBV for 24 or 48 weeks, with 3-day lead-in phase of PegIFN/RBV, in treatment-experienced patients
  Interventions:

  • Drug: Arm 7 BI 201335 NA
  • Drug: Arm 7 PegIFN/RBV

Inclusion criteria:

chronic HCV GT1; therapy-naive to IFN, PegIFN, or RBV; HCV VL >=100,000 IU/mL Liver biopsy within 2 years prior to study enrolment showing necroinflammatory activity or presence of fibrosis Normal retinal finding on fundoscopy within 6 months prior to Day 1 age 18-65 years Females and males with adequate contraception

Exclusion criteria:

Mixed genotype (1/2, 1/3, or 1/4), diagnosed by genotypic testing at screening Previous treatment with protease inhibitor Evidence of liver disease due to causes other than chronic HCV infection HIV-1 or HIV-2 positive HBV positive Decompensated liver disease, or history of decompensated liver disease Active or suspected malignancy or history of malignancy within the last 5 years History of alcohol or drug abuse within the past 12 months. Usage of any investigational drug within 30 days prior to enrolment, or 5 half-lives, whichever is longer Known hypersensitivity to any ingredient of the study drugs Condition that is defined as one which in the opinion of the investigator may put the patient at risk because of participation in the study or may influence the results of the study or the patient's ability to participate in the study Alpha-fetoprotein value > 100ng/mL at screening; if >20ng/mL and <=100ng/mL, patients can be included if there is no evidence of liver cancer in two congruent imaging studies Total bilirubin > 1.5x ULN wiht ratio of direct/indirect >1. ALT or AST levels > 5x ULN INR prolonged to >1.5x ULN Exclusion criteria related to PegIFN and/or RBV restrictions.