An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients

• The proportion of subjects who have a sustained virologic response at 12 weeks after the last planned dose of treatment (SVR12) [ Time Frame: Up to 24 weeks ] [ Designated as safety issue: No ]
• The proportion of subjects who have an SVR at 24 weeks after the last planned dose of treatment (SVR24) [ Time Frame: up to Week 24 ] [ Designated as safety issue: No ]
• The proportion of subjects who have an SVR at 4 weeks after the last planned dose of treatment (SVR4) [ Time Frame: up to Week 16 ] [ Designated as safety issue: No ]
• Proportion of subjects with viral relapse [ Time Frame: up to 96 Weeks ] [ Designated as safety issue: No ]
• PK of telaprevir, Peg-IFN, RBV, and selected immunosuppressant medications [ Time Frame: up to Week 48 ] [ Designated as safety issue: No ]
• Dose titration requirements of selected immunosuppressant medications [ Time Frame: up to week 48 ] [ Designated as safety issue: No ]
• Proportion of subjects with biopsy confirmed and treated rejection during treatment through 24 weeks after the last planned dose of study drug [ Time Frame: 24 weeks after the last planned dose of study drug ] [ Designated as safety issue: No ]
• Proportion of subjects with histological evidence of stabilization or improvement in inflammation grade or fibrosis stage, 24 weeks after the last planned dose of study drug compared to baseline [ Time Frame: 24 weeks after the last planned dose of study drug ] [ Designated as safety issue: No ]
• Changes in amino acid sequence of the HCV NS3•4A protease region [ Time Frame: up to 96 Weeks ] [ Designated as safety issue: No ]
• The proportion of subjects who have an SVR at 4 weeks after the last planned dose of treatment (SVR4) [ Time Frame: Up to 16 weeks ] [ Designated as safety issue: No ]

• Proportion of subjects who achieve undetectable HCV RNA 24 weeks after the last planned dose of study drug (SVR24) [ Time Frame: 24 weeks after the last planned dose of study drug ] [ Designated as safety issue: No ]
• Proportion of subjects who achieve undetectable HCV RNA at Week 4 (rapid viral response [RVR]), and Week 4 and Week 12 (extended RVR [eRVR]) [ Time Frame: up to Week 12 ] [ Designated as safety issue: No ]
• Proportion of subjects with on treatment virologic response defined as meeting a futility rule or having detectable HCV RNA at the end of treatment, for subjects completing assigned treatment [ Time Frame: up to Week 48 ] [ Designated as safety issue: No ]
• Proportion of subjects with viral relapse [ Time Frame: up to 96 Weeks ] [ Designated as safety issue: No ]
• Safety as assessed by adverse events (AEs), clinical laboratory results, and vital signs [ Time Frame: up to Week 52 ] [ Designated as safety issue: Yes ]
• PK of telaprevir, Peg-IFN, RBV, and selected immunosuppressant medications [ Time Frame: up to Week 48 ] [ Designated as safety issue: No ]
• Dose titration requirements of selected immunosuppressant medications [ Time Frame: up to week 48 ] [ Designated as safety issue: No ]
• Proportion of subjects with biopsy confirmed and treated rejection during treatment through 24 weeks after the last planned dose of study drug [ Time Frame: 24 weeks after the last planned dose of study drug ] [ Designated as safety issue: No ]
• Proportion of subjects with histological evidence of stabilization or improvement in inflammation grade or fibrosis stage, 24 weeks after the last planned dose of study drug compared to baseline [ Time Frame: 24 weeks after the last planned dose of study drug ] [ Designated as safety issue: No ]
• Changes in amino acid sequence of the HCV NS3•4A protease region [ Time Frame: up to 96 Weeks ] [ Designated as safety issue: No ]

To assess efficacy of telaprevir, peginterferon alfa-2a (Peg-IFN), and ribavirin (RBV) for HCV in a 48-week total treatment duration regimen following liver transplantation.

• Drug: Telaprevir
  1125 mg bid for 12 weeks
• Drug: ribavirin
  Initial dose of 600 mg total daily dose with goal of up to 1000mg-1200mg total daily dose based on body weight for 48 weeks
• Drug: peginterferon alfa-2a
  180 mcg/week for 48 weeks

Inclusion Criteria:

• Male and female subjects between the ages of 18 and 65 years
• History of orthotopic liver transplantation less than 10 years before the Screening visit but no sooner than 6 months before Day 1
• Taking a stable immunosuppressant regimen based on either tacrolimus or cyclosporine without substantial dose changes over the past 3 months
• Naive to P/R treatment or experienced with P/R prior to transplantation with relapse, partial, or null response

Exclusion Criteria:

• Documented cirrhosis after liver transplantation
• Ascites or hepatic encephalopathy within 6 months before Screening
• Retransplantation for recurrent hepatitis C
• Treatment for hepatitis C post liver transplantation
• History within the past 3 months of: rejection within 3 months or > 1 rejection within 12 months
• Current treatment with sirolimus or methylprednisolone. Low dose prednisone use (<5 mg/day) is permitted
• History within 3 months of any bacterial infection requiring > 1 week of intravenous antibiotics, cytomegalovirus viremia or cytomegalovirus infection with end-organ involvement, fungal disease (except cutaneous and mild oral thrush)
• History of post transplant lymphoproliferative disease
• Acceptable laboratory values at Screening as specified in the protocol
• Positive for HIV1/2 EIA antibody screen or Hepatitis B DNA or Hepatitis B surface antigen
• History of hepatocellular carcinoma with high risk of recurrence
• Any other cause of liver disease deemed clinically significant by the investigator in addition to hepatitis C
• Autoimmune-mediated disease
• History of acute pancreatitis within 5 years before the Screening visit
• Prior treatment with an HCV protease inhibitor