A Study of Telaprevir (VX-950), Pegasys and Copegus in Hepatitis C

• Undetectable HCV RNA [ Time Frame: at the completion of treatment ] [ Designated as safety issue: No ]
  Proportion of subjects with an end of treatment response [undetectable HCV RNA at end of treatment])
• Undetectable HCV RNA [ Time Frame: 48 weeks after completion of treatment ] [ Designated as safety issue: No ]
  Proportion of Subjects with Undetectable HCV RNA at 24 Weeks AVFU for Treatment Groups Pbo/PR48,and at 48 Weeks AVFU for Treatment Groups T12/PR24, T24/PR48 and T24/P24
• Adverse Events and Clinical Laboratory Assessments, Including ALT and Other Liver Function Tests. [ Time Frame: throughout study ] [ Designated as safety issue: Yes ]
• Genotypic and Phenotypic Analyses of the NS3•4A HCV Region. [ Time Frame: throughout study ] [ Designated as safety issue: No ]
• Pharmacokinetic Assessments of Telaprevir, Peg-IFN-a-2a, and RBV. [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

• Undetectable HCV RNA at end of treatment.
• Undetectable HCV RNA 48 weeks after completion of treatment (Groups B, C, and D).
• Adverse events and clinical laboratory assessments, including ALT and other liver function tests.
• Genotypic and phenotypic analyses of the NS3•4A HCV region.
• Pharmacokinetic assessments of telaprevir, Peg-IFN-a-2a, and RBV.

The PROVE3 trial is a partially double blinded, randomized, Phase 2 research study of an investigational drug, Telaprevir (VX-950) or Placebo, with peginterferon alfa-2a (Pegasys®), and ribavirin (Copegus®) in people with genotype 1 hepatitis C who have not achieved a Sustained Viral Response (SVR) with a previous treatment of interferon therapy.

• Drug: Telaprevir
  tablet
  Other Name: VX-950
• Drug: Ribavirin
  tablet
  Other Name: RBV
• Drug: Peg-interferon Alfa-2a
  Solution for injection
  Other Name: Peg-IFN
• Drug: Matching Placebo
  Tablet

• Experimental: T12/PR24
  Telaprevir + Peg-IFN + RBV for 12 weeks followed by Placebo + Peg-IFN + RBV for 12 weeks
  Interventions:

  • Drug: Telaprevir
  • Drug: Ribavirin
  • Drug: Peg-interferon Alfa-2a
• Experimental: T24/PR48
  Telaprevir + Peg-IFN + RBV for 24 weeks followed by Peg-IFN + RBV for 24 weeks
  Interventions:

  • Drug: Telaprevir
  • Drug: Ribavirin
  • Drug: Peg-interferon Alfa-2a
• Experimental: T24/P24
  Telaprevir + Peg-IFN for 24 weeks
  Interventions:

  • Drug: Telaprevir
  • Drug: Peg-interferon Alfa-2a
• Placebo Comparator: Pbo24/PR48
  Placebo + Peg-IFN + RBV for 24 weeks followed by Peg-IFN + RBV for 24 weeks
  Interventions:

  • Drug: Ribavirin
  • Drug: Peg-interferon Alfa-2a
  • Drug: Matching Placebo

• Li S, Zhu J, Zhang W, Chen Y, Zhang K, Popescu LM, Ma X, Lau WB, Rong R, Yu X, Wang B, Li Y, Xiao C, Zhang M, Wang S, Yu L, Chen AF, Yang X, Cai J. Signature microRNA expression profile of essential hypertension and its novel link to human cytomegalovirus infection. Circulation. 2011 Jul 12;124(2):175-84. Epub 2011 Jun 20.
• McHutchison JG, Manns MP, Muir AJ, Terrault NA, Jacobson IM, Afdhal NH, Heathcote EJ, Zeuzem S, Reesink HW, Garg J, Bsharat M, George S, Kauffman RS, Adda N, Di Bisceglie AM; PROVE3 Study Team. Telaprevir for previously treated chronic HCV infection. N Engl J Med. 2010 Apr 8;362(14):1292-303.

Inclusion Criteria:

• Males and females between 18 and 70 years old
• Detectable plasma HCV RNA > or = 10,000 IU/mL
• Must have chronic hepatitis C (genotype 1) and have already received at least one prior course of peginterferon with ribavirin
• Can not also be infected with HIV (AIDS) or hepatitis B
• Must be judged to be in general good health and able to receive Pegasys® and Copegus®.
• No drug or alcohol abuse in the last year
• Must agree to use two effective methods of birth control during the study and for 6 months after you stop taking study medication. One of the methods needs to be a 'barrier' method (condom or diaphragm)
• If you are a woman, you can not be in this study if you are pregnant or nursing.

Exclusion Criteria:

• Participation in any clinical trial of a HCV protease inhibitor of any duration.
• Prior response to therapy and failure to achieve SVR which was due to treatment non-compliance
• Any other cause of significant liver disease in addition to hepatitis C; this may include but is not limited to, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis, or primary biliary cirrhosis.
• Diagnosed or suspected hepatocellular carcinoma.
• History of or current evidence of decompensated liver disease.
• Participation in any clinical trial of an investigational drug within 90 days before drug administration or participation in more than 2 drug studies in the last 12 months (exclusive of the current study).