A Study of Telaprevir (VX-950), Pegasys and Copegus in Hepatitis C (PROVE3)

Study Overview
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Brief Summary
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The PROVE3 trial is a partially double blinded, randomized, Phase 2 research study of an investigational drug, Telaprevir (VX-950) or Placebo, with Pegylated Interferon Alfa 2a (Peg-IFN-alfa-2a, Pegasys®), and Ribavirin (RBV, Copegus®) in people with genotype 1 hepatitis C who have not achieved a Sustained Viral Response (SVR) with a previous treatment of interferon therapy.

Official Title
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A Phase 2 Study of Telaprevir (VX-950) in Combination With Peginterferon Alfa-2a (Pegasys®), and Ribavirin (Copegus®) in Subjects With Genotype 1 Hepatitis C Who Have Not Achieved Sustained Viral Response With a Prior Course of Interferon Based Therapy

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females between 18 and 70 years old Detectable plasma hepatitis C virus (HCV) ribonucleic acid (RNA) greater than or equal to (>=) 10,000 international units per milliliter (IU/mL) Must have chronic hepatitis C (genotype 1) and have already received at least one prior course of pegylated interferon alfa 2a with ribavirin Cannot also be infected with Human Immunodeficiency Virus 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 cannot 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)

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week<br>Single loading dose of telaprevir 1125 milligram (mg) tablet orally on Day 1 followed by 750 mg telaprevir tablet 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) tablet 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 24 weeks. | Drug: Telaprevir<br>* tablet<br>* Other names: VX-950;Drug: Ribavirin<br>* tablet<br>* Other names: RBV;Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>* Other names: Peg-IFN-alfa-2a;|
| Experimental: Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week<br>Single loading dose of telaprevir 1125 mg tablet orally on Day 1 followed by 750 mg telaprevir tablet thrice daily for 24 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 48 weeks. | Drug: Telaprevir<br>* tablet<br>* Other names: VX-950;Drug: Ribavirin<br>* tablet<br>* Other names: RBV;Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>* Other names: Peg-IFN-alfa-2a;|
| Experimental: Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week<br>Single loading dose of telaprevir 1125 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 24 weeks. | Drug: Telaprevir<br>* tablet<br>* Other names: VX-950;Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>* Other names: Peg-IFN-alfa-2a;|
| Placebo Comparator: PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week<br>Placebo (PBO) matched to telaprevir tablet orally thrice daily for 24 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 48 weeks. | Drug: Ribavirin<br>* tablet<br>* Other names: RBV;Drug: Pegylated Interferon Alfa 2a<br>* Solution for injection<br>* Other names: Peg-IFN-alfa-2a;Drug: Matching Placebo<br>* Tablet<br>|

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 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) | 
| Percentage of Subjects With Undetectable Plasma HCV RNA | Percentage of subjects with undetectable HCV RNA at 24 weeks after last dose of study drug for treatment group PBO 24 Week+Peg-IFN-alfa-2a, RBV 48 Week and at 48 weeks after last dose of study drug for treatment groups Telaprevir 12 Week+Peg-IFN-alfa-2a,RBV 24 Week, Telaprevir 24 Week+Peg-IFN-alfa-2a,RBV 48 Week and Telaprevir 24 Week+Peg-IFN-alfa-2a 24 Week were presented. 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). | Up to Week 96 (24 weeks after last dose of study drug for PBO group; 48 weeks after last dose of study drug for telaprevir groups) | 
| 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 2 weeks after last dose of study drug (up to Week 50) | 
| 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 24 week 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. | Week 2, 4, 8, 12, 16, 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genotype 1