Phase 2 Study of VX-950, Pegasys® With and Without Copegus® in Hepatitis C

Study Overview
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Brief Summary
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Compare the effectiveness of telaprevir (VX-950) in combination with Pegylated Interferon Alfa 2a (Peg-IFN-alfa-2a) with and without Ribavirin (RBV) in reducing plasma hepatitis C virus (HCV) ribonucleic acid (RNA) levels

Official Title
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A Phase 2 Study of VX-950 in Combination With Peginterferon Alfa-2a (Pegasys®), With and Without Ribavirin (Copegus®) in Subjects With Hepatitis C

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: Ribavirin
* Drug: Pegylated Interferon Alfa 2a
* Drug: Placebo
* Drug: Telaprevir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Hepatitis C virus Genotype 1 with detectable plasma hepatitis C virus RNA Have been infected with Hepatitis C virus for greater than (>) 6 months Seronegative for hepatitis B surface antigen and human immunodeficiency virus 1 and 2 Must agree to use 2 methods of contraception, including 1 barrier method, during and for 24 weeks after the completion of the study (unless the subject is a female of documented non-child-bearing potential) Female subjects must have a negative pregnancy test at all visits before the first dose. Exclusion Criteria: Received any approved or investigational drug or drug regimen for the treatment of hepatitis C. Any medical contraindications to Peg-IFN-alfa-2a or Ribavirin therapy 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. Histologic evidence of hepatic cirrhosis (including compensated cirrhosis) based on a liver biopsy taken within 2 years before Study start. Alcohol/drug abuse or excessive use in the last 12 months. Participation in any investigational drug study within 90 days before drug administration or participation in more than 2 drug studies in the last 12 months (exclusive of the current study).

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week<br>Placebo (PBO) matched to telaprevir tablet orally thrice daily for 12 weeks in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (RBV) orally twice daily at a dose of 1000 milligram per day (mg/day) for subjects weighing less than (<) 75 kilogram (kg) and 1200 mg/day for subjects weighing greater than or equal to (>=) 75 kg, for 48 weeks. | Drug: Ribavirin<br>* tablet<br>Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>Drug: Placebo<br>* tablet<br>|
| Experimental: Telaprevir 12 Week +Peg-IFN-alfa-2a,RBV 24 Week<br>Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet orally thrice daily for 12 weeks in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 24 weeks. | Drug: Ribavirin<br>* tablet<br>Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>Drug: Telaprevir<br>* tablet<br>* Other names: VX-950;|
| Experimental: Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 12 Week<br>Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection and RBV tablet orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing >=75 kg, for 12 weeks. | Drug: Ribavirin<br>* tablet<br>Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>Drug: Telaprevir<br>* tablet<br>* Other names: VX-950;|
| Experimental: Telaprevir 12 Week+Peg-IFN-alfa-2a 12 Week<br>Single loading dose of telaprevir 1250 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily in combination with Peg-IFN-alfa-2a 180 mcg/week subcutaneous injection, for 12 weeks. | Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>Drug: Telaprevir<br>* tablet<br>* Other names: VX-950;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Undetectable Plasma Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 24 After the Completion of Study Drug Dosing | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). | 24 weeks after the completion of study drug dosing (up to Week 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Undetectable Plasma HCV RNA at Week 12 After the Completion of Study Drug Dosing | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). | 12 weeks after the completion of study drug dosing (up to Week 60) | 
| Percentage of Subjects With Undetectable Plasma HCV RNA at Completion of Study Drug Dosing | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). | Completion of study drug dosing (up to Week 48) | 
| Number of Subjects With Adverse Events (AEs) and Serious Adverse Events (SAEs) | AE: any adverse change from the subject's baseline (pre-treatment) condition, including any adverse experience, abnormal recording or clinical laboratory assessment value which occurs during the course of the study, whether it is considered related to the study drug or not. An adverse event includes any newly occurring event or previous condition that has increased in severity or frequency since the administration of study drug. SAE: medical event or condition, which falls into any of the following categories, regardless of its relationship to the study drug: death, life threatening adverse experience, in-patient hospitalization/prolongation of hospitalization, persistent/significant disability or incapacity, congenital anomaly/birth defect, important medical event. Study drug includes all investigational agents (including placebo, if applicable) administered during the course of the study. | Baseline up to Week 48 | 
| Number of Subjects With Viral Relapse | Viral relapse was defined as having detectable HCV RNA during antiviral follow-up. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of detection was 10 international units per milliliter (IU/mL). | After last dose of study drug up to antiviral follow-up (up to Week 72) | 
| Maximum (Cmax), Minimum (Cmin) and Average (Cavg) Plasma Concentration of Telaprevir | Only subjects who received telaprevir were to be analyzed for this outcome. Maximum, minimum and average plasma concentrations observed during assessment period were reported. | Day 1, 4, 8, 15, 22, 29, 43, 57, 71, 85 |