A Safety and Efficacy Study of the Combination of VX-222 and Telaprevir in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C Virus Infection

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and efficacy of combination treatment with VX-222 and telaprevir administered for 12 weeks with and without peginterferon-alfa-2a and/or ribavirin. The subjects enrolled in this study are chronically infected with hepatitis C virus (HCV) genotype 1 and will not have previously received treatment for their HCV infection. This study will include an Investigational Phase and Extension Phase. These phases will contain a Treatment Period and a Follow-up Period. All subjects will be enrolled in the Investigational Phase of this study. Subjects who fail treatment during the Investigational Phase will have the option to enter the Extension Phase at which point they will be eligible to receive peginterferon alfa-2a and ribavirin for a total of 48 weeks. Based on an evaluation of on-treatment safety, pharmacokinetic and antiviral data from patients in each arm of the trial, Vertex may elect to enroll up to two additional treatment arms (Treatment Arm E and Treatment Arm F) that will evaluate telaprevir/VX-222-based combination therapy. The components of the treatment regimens of these arms will be selected based on clinical data that emerges from the four initially-studied regimens. If enacted, up to 25 patients are expected to enroll in each additional treatment arm. If Treatment Arm E or Treatment Arm F is discontinued subjects meeting certain criteria will have the option to enter a telaprevir-containing Rollover Phase. Subjects who do not meet the eligibility criteria to enter the Rollover Phase may elect to enter the Extension Phase.

Official Title
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A Randomized, Parallel-Group, Dose-Ranging Study to Evaluate Efficacy, Safety, Pharmacokinetics, and Antiviral Activity of VX-222 and Telaprevir in Combination With and Without Peginterferon-Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment-Naïve Subjects With Genotype 1 Chronic Hepatitis C

Conditions
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Chronic Hepatitis C Virus Infection

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females of non-childbearing potential Genotype 1 chronic hepatitis C Laboratory evidence of HCV infection for 6 months Histologic evidence of chronic hepatitis C Subjects who have a body mass index (BMI) of ≤35 kg/m² (BMI = weight in kg / height² in meters) Treatment Arm E: This arm will enroll only subjects infected with HCV genotype 1b virus Treatment Arm F: This arm will enroll only subjects infected with HCV genotype 1a virus Exclusion Criteria: Subjects who have received any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C Subjects with any contraindications to peginterferon alfa-2a and/or ribavirin Subjects with any other cause of significant liver disease in addition to hepatitis C, which may include, but is not limited to malignancy with hepatic involvement, hepatitis B, drug or alcohol-related cirrhosis, autoimmune hepatitis, hemochromatosis, Wilson's disease, nonalcoholic steatohepatitis (NASH), or primary biliary cirrhosis Histologic evidence of hepatic cirrhosis

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Arm A<br>Treatment Arm A was discontinued as a result of patients meeting a pre-defined stopping rule related to viral breakthrough during the first four weeks of dosing. | Drug: telaprevir<br>* tablet, 1125-mg, twice daily<br>Drug: VX-222<br>* capsule, 100-mg, twice daily<br>|
| Experimental: Treatment Arm B<br>Treatment Arm B was discontinued as a result of patients meeting a pre-defined stopping rule relating to viral breakthrough. | Drug: telaprevir<br>* tablet, 1125-mg, twice daily<br>Drug: VX-222<br>* capsule, 400-mg, twice daily<br>|
| Experimental: Treatment Arm C<br>Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 12 weeks for a total treatment duration of 24 weeks. Enrollment for this arm is complete. No additional subjects will be recruited. | Drug: telaprevir<br>* tablet, 1125-mg, twice daily<br>Drug: VX-222<br>* capsule, 100-mg, twice daily<br>Drug: ribavirin<br>* tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily<br>Biological: peginterferon-alfa-2a<br>* subcutaneous injection, 180-mcg, once weekly<br>|
| Experimental: Treatment Arm D<br>Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 12 weeks for a total treatment duration of 24 weeks. Enrollment for this arm is complete. No additional subjects will be recruited. | Drug: telaprevir<br>* tablet, 1125-mg, twice daily<br>Drug: ribavirin<br>* tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily<br>Biological: peginterferon-alfa-2a<br>* subcutaneous injection, 180-mcg, once weekly<br>Drug: VX-222<br>* capsule, 400-mg, twice daily<br>|
| Experimental: Treatment Arm E<br>Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 24 weeks for a total treatment duration of 36 weeks. | Drug: telaprevir<br>* tablet, 1125-mg, twice daily<br>Drug: ribavirin<br>* tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily<br>Drug: VX-222<br>* capsule, 400-mg, twice daily<br>|
| Experimental: Treatment Arm F<br>Subjects who meet pre-specified viral response criteria will stop their assigned treatment at 12 weeks. Subjects who do not meet the pre-specified viral response criteria will receive peginterferon alfa-2a and ribavirin for an additional 24 weeks for a total treatment duration of 36 weeks. | Drug: telaprevir<br>* tablet, 1125-mg, twice daily<br>Drug: ribavirin<br>* tablet, 1000-mg for subjects weighing <75-kg or 1200-mg for subjects weighing ≥75-kg, twice daily<br>Drug: VX-222<br>* capsule, 400-mg, twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability | Assessed by adverse events, physical examinations, vital signs, 12 lead electrocardiograms (ECGs), and laboratory assessments (serum chemistry, hematology, and urinalysis) vital signs, 12-lead electrocardiograms (ECGs), and laboratory assessments (clinical chemistry, hematology, and urinalysis) | 40 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects Who Achieve a Sustained Viral Response |  | 24 weeks after the completion of the last dose of the assigned study drug treatment regimen | 
| Undetectable HCV RNA Measurements | Time to undetectability Proportion of subjects who achieve undetectable HCV RNA levels at Week 2, Week 4, Week 8, and Week 12 Proportion of subjects who achieve undetectable HCV RNA levels at Week 2 and Week 8 Proportion of subjects who have undetectable HCV RNA levels at the end of treatment | 36 weeks | 
| Proportion of Subjects Who Have a Viral Breakthrough or Relapse |  | 60 weeks | 
| Plasma Exposures of VX-222 and Telaprevir |  | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VX-950