A Phase 3 Study of Telaprevir in Combination With Pegasys® and Copegus® in Treatment-Naive Subjects With Genotype 1 Hepatitis C Virus (HCV)

Study Overview
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Brief Summary
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A Phase 3 study to evaluate the efficacy and safety of two dosing regimens of telaprevir in combination with pegylated interferon alfa 2a (Peg-IFN-alfa-2a) and ribavirin (RBV).

Official Title
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A Phase 3 Study of 2 Dose Regimens of Telaprevir in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Treatment-Naive Subjects With Genotype 1 Chronic Hepatitis C

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Has not received any previous treatment with any approved or investigational drug or drug regimen for the treatment of hepatitis C Male and female subjects, 18 to 70 years of age, inclusive Genotype 1, chronic hepatitis C with detectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Screening laboratory values, tests, and physical exam within acceptable ranges Able and willing to follow contraception requirements Able to read and understand, and willing to sign the informed consent form and abide by the study restrictions Exclusion Criteria Subject has any contraindications to Pegasys® or Copegus® therapy Evidence of hepatic decompensation in cirrhotic subjects History of organ transplant History of, or any current medical condition which could impact the safety of the subject in participation in the 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 |
| --- | --- |
| Placebo Comparator: PBO 12 Week+Peg-IFN-alfa-2a, RBV 48 Week<br>Placebo (PBO) matched to telaprevir 750 mg 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 48 weeks. | Biological: Pegylated Interferon Alfa 2a<br>* subcutaneous injection, 180 micrograms once per week<br>* Other names: Pegasys, Peg-IFN-alfa-2a;Drug: Ribavirin<br>* 200 mg tablets administered orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing ≥75 kg<br>* Other names: Copegus, RBV;Other: Placebo<br>* Telaprevir matching placebo<br>|
| Experimental: Telaprevir 8 Week, PBO 4 Week+Peg-IFN-alfa-2a, RBV 24/48 Week<br>Telaprevir 750 mg tablet thrice daily for 8 weeks, then PBO matched to Telaprevir 750 mg tablet thrice daily for 4 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 to 48 weeks depending on individual response to telaprevir treatment. | Biological: Pegylated Interferon Alfa 2a<br>* subcutaneous injection, 180 micrograms once per week<br>* Other names: Pegasys, Peg-IFN-alfa-2a;Drug: Telaprevir<br>* 375 mg tablets administered orally every 8 hours at a dose of 750 mg<br>* Other names: VX-950;Drug: Ribavirin<br>* 200 mg tablets administered orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing ≥75 kg<br>* Other names: Copegus, RBV;Other: Placebo<br>* Telaprevir matching placebo<br>|
| Experimental: Telaprevir 12 Week+Peg-IFN-alfa-2a, RBV 24/48 Week<br>Telaprevir 750 mg tablet 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 to 48 weeks depending on individual response to telaprevir treatment. | Biological: Pegylated Interferon Alfa 2a<br>* subcutaneous injection, 180 micrograms once per week<br>* Other names: Pegasys, Peg-IFN-alfa-2a;Drug: Telaprevir<br>* 375 mg tablets administered orally every 8 hours at a dose of 750 mg<br>* Other names: VX-950;Drug: Ribavirin<br>* 200 mg tablets administered orally twice daily at a dose of 1000 mg/day for subjects weighing <75 kg and 1200 mg/day for subjects weighing ≥75 kg<br>* Other names: Copegus, RBV;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects Achieving Sustained Viral Response (SVR), Demonstrated by Achieving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels 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. Two results are reported: 1) Protocol defined SVR: undetectable HCV RNA at 24 weeks after the last planned dose of study treatment without any confirmed detectable HCV RNA between end of treatment visit (up to Week 48) and 24 weeks after last planned dose (up to Week 72); 2) SVR as per FDA guidance (snapshot analysis): undetectable HCV RNA at 24 weeks after the last planned dose of study treatment. Analysis was based only on the HCV RNA assessment in visit window (+/-2 weeks); if there were more than 1 assessment in the window, the last measurement was used. | 24 weeks after last planned dose of study treatment (up to Week 72) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Undetectable HCV RNA at Week 72 | 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. | Week 72 (24 weeks after last dose for subjects with a planned treatment duration of 48 weeks and 48 weeks after last dose for subjects with planned treatment duration of 24 weeks) | 
| Number of Subjects Achieving Rapid Viral Response (RVR), Demonstrated by Achieving Undetectable HCV RNA 4 Weeks After Starting Study Treatment | 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. | Week 4 | 
| Number of Subjects Achieving Extended Rapid Viral Response (eRVR), Demonstrated by Achieving Undetectable HCV RNA at Week 4 and at Week 12 | 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 Week 4 and Week 12. | Week 4 and Week 12 | 
| Number of Subjects With Undetectable HCV RNA at Week 12 | 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. | Week 12 | 
| Number of Subjects With Undetectable HCV RNA at End of Treatment (EOT) | 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. | End of treatment (up to Week 48) | 
| Number of Subjects With Undetectable HCV RNA 12 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 IU/mL and the lower limit of detection was 10 IU/mL. | 12 weeks after last planned dose of study treatment (up to Week 60) | 
| Number of Subjects With Undetectable HCV RNA 24 Weeks After Last Actual Dose of Study Treatment | 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. | 24 weeks after last actual dose of study treatment (up to Week 72) | 
| Number of Subjects With Viral Relapse Planned and Viral Relapse Actual | 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 quantification was 25 IU/mL and the lower limit of detection was 10 IU/mL. For viral relapse, 2 analyses were performed: planned and actual. The planned analyses was measured from the end of treatment (EOT) visit to 24 weeks after the last planned dose of study treatment. The actual analyses was measured from the EOT visit to 24 weeks after the last actual dose of study treatment. | After last dose of study drug up to 24 week antiviral follow-up (up to Week 72) | 
| Biochemical Response: Number of Subjects With Grade 3 and 4 Shifts From Baseline in Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) Levels | Criteria for grading severity (toxicity) of ALT and AST: Grade 0 (<1.25*upper limit of normal [ULN]); Grade 1 (mild=1.25 to 2.5*ULN); Grade 2 (moderate=2.6 to 5.0*ULN); Grade 3 (severe= greater than 5.0 to 20.0*ULN); Grade 4 (life-threatening= greater than 20.0*ULN). Number of subjects with Grade 3 shift (from Grade 0, Grade 1 or Grade 2 baseline) and Grade 4 shift (from Grade 0, Grade 1, Grade 2 or Grade 3 baseline) are reported. If a subject experienced more than 1 severity grade shifts during post baseline assessments, the maximum severity grade shift was considered. | Baseline up to Week 48 | 
| Noninvasive Markers of Fibrosis: Number of Subjects With Improvement in FibroTest Analysis | FibroTest analysis was a biomarker analysis test used to generate a score that was correlated with the degree of liver damage. The FibroTest score was calculated from the results of a six-parameter blood test, combining six serum markers (alpha-2-macroglobulin, haptoglobin, apolipoprotein A1, gamma-glutamyl transpeptidase, total bilirubin, and alanine transaminase). The FibroTest score (F score) may range from 0.00 (Grade F0) to 1.00 (Grade F4), where F0= no fibrosis and F4=cirrhosis. Results were presented separately for subjects who achieved SVR at 24 weeks after the last planned dose of study treatment and those who did not achieve SVR at 24 weeks after the last planned dose of study treatment. Improvement was defined as decrease of at least 1 grade relative to baseline. | Baseline through 24 weeks after last planned dose of study treatment (up to Week 72) | 
| Fatigue Severity Scale (FSS) Total Score | FSS was a 9-item questionnaire where each item was scored on a scale of 1 to 7 (higher scores indicated higher influence of fatigue). FSS total score was calculated as the average of individual items on the questionnaire and FSS total score ranged from 1 to 7, where higher score indicated higher influence of fatigue. | Baseline, Week 4, 12, 24, 36, 48, 72 | 
| 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 | 

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