A Safety and Effectiveness Study of Telaprevir in Chronic, Genotype 1, Hepatitis C Patients That Failed Previous Standard Treatment

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, efficacy and tolerability of using two regimens of telaprevir (with and without delayed start) with standard treatment compared to standard treatment alone in participants with chronic, genotype 1, hepatitis C.

Detailed Description
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This is a randomized, double-blind, placebo-controlled Phase III trial with telaprevir in patients with chronic Hepatitis C Virus (HCV), genotype 1, infection who failed prior treatment with standard treatment. Standard treatment is defined as treatment with Peg-INF and RBV. The trial is designed to compare the efficacy, safety, and tolerability of 2 regimens of telaprevir (with and without delayed start) combined with standard treatment versus standard treatment alone. The trial will consist of a screening period of approximately 4 weeks, a 48-week treatment period, and a 24-week follow-up period. Patients will be eligible to enroll in the trial if they (1) had an undetectable HCV Ribonucleic Acid (RNA) level at the end of a prior course of standard treatment but did not achieve a response (viral relapsers), or (2) never had an undetectable HCV RNA level during or at the end of a prior course of standard treatment (non-responders). Approximately 650 patients (350 prior relapsers and 300 prior non-responders) will be randomized in a 2:2:1 ratio to one of 3 treatment groups: Treatment group A will receive telaprevir with standard treatment for 12 weeks; followed by placebo with standard treatment for 4 weeks; followed by standard treatment for 32 weeks. Treatment group B will receive placebo with standard treatment for 4 weeks; followed by telaprevir with standard treatment for 12 weeks; followed by standard treatment for 32 weeks. Treatment group C will receive placebo with standard treatment for 16 weeks; followed by standard treatment for 32 weeks. In both telaprevir regimens (A and B), patients will receive 12 weeks of 750 mg of telaprevir every 8 hours along with 48 weeks of standard treatment. Telaprevir or placebo will be given by mouth at a dose of 750 mg every 8 hours for 16 weeks. Peg-INF will be given as an injection under the skin at a dose of 180 mcg once every week for 48 weeks. RBV will be given by mouth at a dose of either 1000 or 1200 mg (depending on your body weight) two times per day for 48 weeks.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Phase III Trial of 2 Regimens of Telaprevir (With and Without Delayed Start) Combined With Pegylated Interferon Alfa-2a (Pegasys) and Ribavirin (Copegus) in Subjects With Chronic, Genotype 1, Hepatitis C Infection Who Failed Prior Standard Treatment

Conditions
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Hepatitis C, Chronic

Intervention / Treatment
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* Drug: Telaprevir
* Drug: Peg-IFN-alfa-2a
* Drug: Ribavirin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient must have chronic hepatitis C infection (genotype 1) with HCV RNA level >= 1000 IU/mL Patient must have failed at least 1 prior course of Peg-IFN/RBV therapy (standard treatment) Patient must be willing to use 2 effective methods of birth control for up to 7 months after last dose of study medication Exclusion Criteria: Patient is a previous non-responder that is classified as a viral breakthrough case Patient is infected with Hepatitis C virus, genotype 1, exhibiting more than one subtype Patient has Hepatitis C virus, genotype 1, and exhibits co-infection with any other genotype Evidence of decompensated liver disease Patient has condition that requires use of systemic corticosteroids

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: Group A: T12/PR48<br>Participants will receive 12 weeks of 750 mg telaprevir eight hourly followed by 4 weeks of Placebo in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses. | Drug: Telaprevir<br>* Participants will receive telaprevir tablets of 750 mg orally eight hourly for 12 weeks in group A and B.<br>Drug: Peg-IFN-alfa-2a<br>* Participants will receive 180 µg subcutaneous (under the skin) injection of Peg-IFN-alfa-2a once weekly for 48 weeks in Group A, B and C.<br>Drug: Ribavirin<br>* Participants will receive ribavirin tablets of 1000-1200 mg orally twice daily for 48 weeks in Group A, B, and C.<br>Drug: Placebo<br>* Participants will receive telaprevir matching placebo tablets orally for 4 weeks in Group A and B. Participants will receive telaprevir matching placebo tablets orally for 16 weeks in Group C.<br>|
| Experimental: Group B: T12(DS)/PR48<br>Participants will receive 4 weeks of Placebo followed by 12 weeks of 750 mg telaprevir eight hourly in combination with 48 weeks of Peg-IFN-alfa-2a and ribavirin at standard doses. | Drug: Telaprevir<br>* Participants will receive telaprevir tablets of 750 mg orally eight hourly for 12 weeks in group A and B.<br>Drug: Peg-IFN-alfa-2a<br>* Participants will receive 180 µg subcutaneous (under the skin) injection of Peg-IFN-alfa-2a once weekly for 48 weeks in Group A, B and C.<br>Drug: Ribavirin<br>* Participants will receive ribavirin tablets of 1000-1200 mg orally twice daily for 48 weeks in Group A, B, and C.<br>Drug: Placebo<br>* Participants will receive telaprevir matching placebo tablets orally for 4 weeks in Group A and B. Participants will receive telaprevir matching placebo tablets orally for 16 weeks in Group C.<br>|
| Experimental: Group C: Pbo/PR48<br>Participants will receive placebo in combination with Peg- IFN-alfa-2a and ribavirin for 16 weeks. Participants will receive Peg- IFN-alfa-2a and ribavirin for next 32 weeks. | Drug: Peg-IFN-alfa-2a<br>* Participants will receive 180 µg subcutaneous (under the skin) injection of Peg-IFN-alfa-2a once weekly for 48 weeks in Group A, B and C.<br>Drug: Ribavirin<br>* Participants will receive ribavirin tablets of 1000-1200 mg orally twice daily for 48 weeks in Group A, B, and C.<br>Drug: Placebo<br>* Participants will receive telaprevir matching placebo tablets orally for 4 weeks in Group A and B. Participants will receive telaprevir matching placebo tablets orally for 16 weeks in Group C.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Sustained Virologic Response (SVR) 24 Weeks After the Last Planned Dose of Study Medication - SVR24 Planned | SVR24 planned is defined as having undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) levels 24 weeks after the last planned dose of study medication. | Week 72 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Acheiving Rapid Virologic Response (RVR) at Week 4 | RVR was defined as having undetectable Hepatitis C virus (HCV) ribonucleic acid (RNA) at Week 4. | Week 4 | 
| Number of Participants Acheiving Undetectable Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) Levels at Week 48 (End of Treatment) |  | Week 48 | 
| Number of Participants With Sustained Virologic Response (SVR) 12 Weeks After the Last Planned Dose of Study Medication - SVR12 Planned | SVR12 planned was defined as having undetectable plasma Hepatitis C virus (HCV) ribonucleic acid (RNA) levels 12 weeks after the last planned dose of study medication (SVR12 planned). | Week 60 | 
| Number of Participants Who Meet the Telaprevir Stopping Rule at Week 4, Week 6, or Week 8 | Telaprevir stopping rule is defined as having Hepatitis C virus (HCV) ribonucleic acid (RNA) levels >100 IU/mL at Week 4, Week 6, or Week 8 after start of telaprevir. | Week 4, Week 6, or Week 8 | 
| Number of Participants Who Have Viral Relapse During Entire Follow-up Period (up to Week 72) | Viral relapse was defined as having confirmed detectable Hepatitis C virus (HCV) ribonucleic acid (RNA) levels during entire follow-up period (up to Week 72). | Up to Week 72 | 
| Change From Baseline in log10 Hepatitis C Virus (HCV) Ribonucleic Acid (RNA) at Week 4 |  | Baseline (Day 1) to Week 4 | 
| Number of Participants Acheiving Extended Rapid Virologic Response at Week 4 and Week 12 | Extended rapid virologic response was defined as undetectable Hepatitis C virus (HCV) ribonucleic acid (RNA) levels. | Week 4 and Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis C, Chronic, Telaprevir, Peg-IFN-alfa-2a, Ribavirin