Efficacy of a 12-Week Regimen of Telaprevir, Pegylated Interferon, and Ribavirin in Treatment-Naive and Prior Relapser Subjects With Interleukin28B (IL28B) CC Genotype

Study Overview
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Brief Summary
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The purpose of this study is to evaluate if a 12-week total regimen of telaprevir in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV) (T12/PR12) is safe and effective in subjects who have the interleukin-28B (IL28B) CC genotype. The subjects enrolled in this study will have chronic hepatitis C virus (HCV) infection and will not have cirrhosis of the liver.

Official Title
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A Phase 3b Study of 2 Treatment Durations of Telaprevir, Peg-IFN (Pegasys®), and Ribavirin (Copegus®) in Treatment-Naive and Prior Relapser Subjects With Genotype 1 Chronic Hepatitis C and IL28B CC Genotype

Conditions
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Hepatitis C, Chronic

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, 18 to 70 years of age, inclusive Treatment-naive OR subjects (prior relapsers) may be included who did not achieve sustained viral response 24 weeks after last planned dose of study drug (SVR24) after at least 1 prior course of Peg-IFN/RBV therapy of standard duration and had a documented undetectable HCV RNA level at the planned end of treatment of at least 42-week duration Subjects have IL28B CC genotype determined during screening Subjects have genotype 1 chronic hepatitis C and laboratory evidence of HCV infection for at least 6 months, defined by (1) documented HCV serology test at least 6 months before the first screening visit demonstrating the presence of anti-HCV antibody, or (2) documented presence of HCV RNA by a sensitive and specific assay at least 6 months before the first screening visit, or (3) documented histologic evidence of chronic hepatitis C demonstrated by fibrosis on a standardized histologic grading system at least 6 months before the first screening visit. If only inflammation is present in the liver histologic report, then 6 months of laboratory evidence is required Exclusion Criteria: Subjects have received previous treatment with telaprevir or any other protease inhibitor(s) for chronic hepatitis C Subjects who did not achieve SVR24 after at least 1 prior course of Peg-IFN/RBV therapy of standard duration and never achieved undetectable HCV RNA while on treatment Subjects have evidence of hepatic decompensation Subjects have evidence of cirrhosis Subjects have diagnosed or suspected hepatocellular carcinoma Subjects have 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, or primary biliary cirrhosis. Steatosis is allowed if clinically asymptomatic

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized)<br>Telaprevir 1125 milligram (mg) tablet twice 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 12 weeks. Only subjects who completed initial 12 week of telaprevir and Peg-IFN/RBV and met rapid viral response (RVR, undetectable Hepatitis C Virus [HCV] Ribonucleic Acid [RNA] at Week 4) criteria, were randomized in this group, as planned, and did not receive any further treatment. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Peg-IFN-Alfa-2a;Drug: Ribavirin<br>* Tablet<br>* Other names: RBV;|
| Experimental: Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized)<br>Telaprevir 1125 mg tablet twice 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. Only subjects who completed initial 12 week of telaprevir and Peg-IFN/RBV and met RVR criteria, were randomized in this group, as planned. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Peg-IFN-Alfa-2a;Drug: Ribavirin<br>* Tablet<br>* Other names: RBV;|
| Experimental: Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Non Randomized)<br>Telaprevir 1125 mg tablet twice 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. Only subjects with RVR who permanently discontinued telaprevir, Peg-IFN-alfa-2a, or RBV treatment before Week 12, and had extended rapid viral response (eRVR, undetectable HCV RNA at Weeks 4 and 12), were included in this group, as planned. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Peg-IFN-Alfa-2a;Drug: Ribavirin<br>* Tablet<br>* Other names: RBV;|
| Experimental: Telaprevir 12 Wk +Peg-IFN-alfa-2a,RBV 48 Wk (Non Randomized)<br>Telaprevir 1125 mg tablet twice 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 48 weeks. Only subjects with no RVR or no RVR assessment, and subjects with RVR who permanently discontinued telaprevir, Peg-IFN-alfa-2a, or RBV treatment before Week 12, who did not have eRVR or eRVR assessment, were included in this group, as planned. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Peg-IFN-Alfa-2a;Drug: Ribavirin<br>* Tablet<br>* Other names: RBV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) | SVR12 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 12 weeks after last planned dose of study drug. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups. | 12 weeks after last planned dose of study drug (up to Week 36) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Sustained Viral Response 4 Weeks After Last Planned Dose of Study Drug (SVR4) | SVR4 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 4 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups. | 4 weeks after last planned dose of study drug (up to Week 28) | 
| Percentage of Subjects With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) | SVR24 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at 24 weeks after last planned dose of study treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups. | 24 weeks after last planned dose of study drug (up to Week 48) | 
| Percentage of Subjects With Sustained Viral Response at Week 72 (SVR72) | SVR72 was defined as an undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 72. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 international units per milliliter (IU/mL) and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups. | Week 72 | 
| Percentage of Subjects With Viral Relapse | Viral relapse was defined as having detectable HCV RNA during antiviral follow-up in subjects who had HCV RNA less than (<) lower limit of quantification (LLOQ) at end of treatment. The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The LLOQ was 25 IU/mL and the lower limit of detection was 10 IU/mL. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups. | After last dose of study drug up to 4 weeks (up to Week 28), 12 weeks (up to Week 36), 24 weeks (up to Week 48) antiviral follow-up | 
| Percentage of Subjects With On-Treatment Virologic Failure | On-treatment virologic failure was defined as subjects who met futility (as per investigator discretion) or who completed the assigned treatment duration and had detectable HCV RNA at planned end of treatment (up to 48 weeks). This outcome was planned to be assessed in all reporting groups and results were to be reported for total arm as well. | Baseline up to Week 48 | 
| Number of Subjects With Rapid Viral Response (RVR) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. RVR was defined as undetectable HCV RNA 4 weeks after the start of study treatment. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups. | Week 4 | 
| Number of Subjects With Extended Rapid Viral Response (eRVR) | The plasma HCV RNA level was measured using Roche TaqMan HCV RNA assay. The lower limit of quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. eRVR was defined as undetectable HCV RNA at both 4 weeks and 12 weeks after the start of study treatment. This outcome was planned to be assessed only in Telaprevir 12 Week (Wk)+Peg-IFN-alfa-2a,RBV 12 Wk (Randomized) and Telaprevir 12 Wk+Peg-IFN-alfa-2a,RBV 24 Wk (Randomized) reporting groups. | Week 4 and Week 12 | 
| 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 administered during the course of the study. | Baseline up to Week 48 | 

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