A Study to Evaluate the Efficacy and Safety of Quadruple Therapy (VX-222, Telaprevir,Peginterferon-Alfa-2a, Ribavirin) in Subjects With Chronic Hepatitis C With Compensated Cirrhosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and efficacy of a quadruple regimen (VX-222, telaprevir, pegylated interferon, and ribavirin)in subjects with hepatitis C with cirrhosis.

Official Title
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A Multicenter, Open-Label Phase 2b Pilot Study to Evaluate the Efficacy and Safety of Quadruple Therapy (VX-222, Telaprevir, Peginterferon-Alfa-2, and Ribavirin) in Subjects With Genotype 1 Chronic Hepatitis C With Compensated Cirrhosis

Conditions
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Chronic Hepatitis C Virus

Intervention / Treatment
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* Drug: VX-222
* Drug: telaprevir
* Drug: ribavirin
* Biological: peginterferon-alfa-2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects must have genotype 1 Chronic Hepatitis C Subjects must have compensated cirrhosis Subjects may either be treatment naïve, or may have received a course of Peg IFN/RBV without evidence of response. Subjects who are considered to be relapsers to Peg IFN/RBV, or who are partial or null responders will be considered Subjects with hemophilia may be permitted to enroll with permission of the medical monitor Exclusion Criteria: Any previous treatment with an investigational drug or drug regimen for the treatment of hepatitis C, or previous treatment with an approved protease inhibitor Any contraindication to Peg-IFN or RBV therapy Evidence of hepatic decompensation: history of ascites, hepatic encephalopathy, or bleeding esophageal varices A history of acquired immunodeficiency infection, organ transplantation or have an ongoing requirement for immunosuppressive medicines

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Quadruple Regimen<br>All subjects will receive active study drugs (quadruple regimen: VX-222, telaprevir,Peg-IFN, and RBV) for a fixed treatment duration of 24 weeks. | Drug: VX-222<br>* tablet, 400-mg twice daily<br>Drug: telaprevir<br>* tablet, 1125-mg twice daily<br>* Other names: Incivek, VX-950, Incivo;Drug: ribavirin<br>* tablet, 1000-mg per day for subjects weighing <75 kg and 1200 mg per day for subjects weighing ≥75 kg, twice daily<br>* Other names: Copegus;Biological: peginterferon-alfa-2a<br>* subcutaneous injection, 180-mcg, once weekly<br>* Other names: Pegasys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects who have a sustained virologic response at 12 weeks after the last planned dose of treatment (SVR12) |  | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The safety and tolerability as assessed by adverse events, vital signs, 12-lead electrocardiograms and laboratory assessments. |  | up to 48 weeks | 
| The proportion of subjects who have an SVR 24 weeks after the last planned dose of the study drug (SVR24) |  | 24 weeks | 
| The proportion of subjects who achieve undetectable HCV RNA at Weeks 2, 4, 8, and 12 after the first dose of study drug, and at the end of planned study drug treatment |  | up to week 12 | 
| The proportion of subjects who have on-treatment virologic failure defined as subjects who either meet a futility rule or who complete the assigned treatment duration and have HCV RNA at the end of study drug treatment |  | up to 48 weeks | 
| The association of the IL-28B genotype with SVR12 | Proportion of subjects who have SVR12 by IL-28B genotype | 12 weeks | 
| The amino acid sequence of the nonstructural (NS)3 and NS5B proteins in subjects who have treatment failure | The identity and observed frequency of viral variants as compared to wild-type virus will be measured. | After the last planned dose of study drug or after time of failure | 
| VX-222, telaprevir, and RBV plasma concentrations and Peg-IFN serum concentrations |  | 12 weeks |