An Efficacy and Safety Study of Telaprevir in Patients With Genotype 1 Hepatitis C Infection After Liver Transplantation

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness of telaprevir in combination with Peg-IFN-alfa-2a and ribavirin in stable liver transplant patients with chronic hepatitis C virus (HCV) genotype 1.

Detailed Description
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This is an open-label (all people know the identity of the intervention), multicenter study in genotype 1 chronic HCV infected liver transplant patients who will be treated for 12 weeks with telaprevir 750 mg every 8 hours given in combination with Peg-IFN-alfa-2a and ribavirin followed by 36 weeks of treatment with Peg-IFN-alfa-2a and ribavirin alone. The total treatment duration will be 48 weeks. Safety will be evaluated throughout the study and will include evaluations of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination.

Official Title
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Open-Label, Phase 3b Study To Determine Efficacy and Safety of Telaprevir, Pegylated-Interferon-alfa-2a and Ribavirin in Hepatitis C Genotype 1 Infected, Stable Liver Transplant Subjects

Conditions
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Chronic Hepatitis C Virus (HCV) Infection

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: First time liver transplant recipient whose primary pre-transplant diagnosis was chronic hepatitis C genotype 1 More than 6 months to 10 years post-liver transplant Patient did or did not receive treatment for HCV prior to liver transplantation Patient must agree to have a liver graft biopsy during the screening period unless they had a biopsy within three months of the screening period (for patients between 6 months and one year post transplant) or within six months of the screening period (for patients who are more than one year post transplant) A female patient of childbearing potential and a nonvasectomized male patient who has a female partner of childbearing potential must agree to the use of 2 effective methods of birth control from screening until 6 months (female patient) or 7 months (male patient) after the last dose of ribavirin Exclusion Criteria: Patient is currently infected or co-infected with HCV of another genotype than genotype 1 Patient received treatment for hepatitis C following liver transplantation Patient has history of decompensated liver disease or shows evidence of significant liver disease in addition to hepatitis C Patient with human immunodeficiency virus or hepatitis B virus co-infection Patient with active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma or hepatocellular carcinoma)

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Telaprevir+Peg-IFN-alfa-2a+Ribavirin<br>Patients will be treated for 12 weeks with telaprevir in combination with Pegylated interferon alfa-2a (Peg-IFN-alfa-2a) and ribavirin followed by 36 weeks of treatment with Peg-IFN-alfa-2a and ribavirin alone. | Drug: Telaprevir<br>* Type=exact number, unit=mg, number=375, form=tablet, route=oral. Patients will receive 2 oral tablets (750 mg) every 8 hours for 12 weeks.<br>Drug: Pegylated interferon alfa-2a<br>* Type=exact number, unit=µg, number=180, form=injection, route=subcutaneous. 180 microgram (µg) per week, subcutaneous injection, for 48 weeks.<br>Drug: Ribavirin<br>* Type=exact number, unit=mg, number=200, form=tablet, route=oral. Starting from 600 mg (3 tablets) per day on Day 1. This dose will become higher or lower based on blood results and the investigators opinion (to a goal of 1000 to 1200 mg/day [5 to 6 tablets] based on subject weight), twice daily regimen, for 48 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients achieving sustained virologic response (SVR) 12 planned | SVR12 planned is defined as having plasma hepatitis C virus (HCV ) ribonucleic acid (RNA) level less than 25 IU/mL 12 weeks after the last planned dose of study medication. | Week 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients achieving SVR12 planned(c) | SVR12 planned(c) is defined as having undetectable plasma HCV RNA levels 12 weeks after the last planned dose of study drugs. | Week 60 | 
| Number of patients achieving SVR24 planned | SVR24 planned is defined as having plasma HCV RNA levels less than 25 IU/mL 24 weeks after the last planned dose of study medication. | Week 72 | 
| Number of patients achieving SVR24 planned(c) | SVR24 planned(c) is defined as having an undetectable plasma HCV RNA level 24 weeks after the last planned dose of study medication. | Week 72 | 
| Number of patients having an undetectable HCV RNA level at Week 4 of treatment |  | Week 4 | 
| Number of patients having an undetectable HCV RNA level at Week 12 of treatment |  | Week 12 | 
| Number of patients having undetectable HCV RNA levels at Week 4 and Week 12 of treatment |  | Week 4 and Week 12 | 
| Number of patients having an undetectable HCV RNA level at the actual end of treatment |  | Week 48 | 
| Number of patients having an undetectable HCV RNA level at the planned end of treatment |  | Week 48 | 
| Number of patients having less than 25 IU/mL at the planned end of treatment |  | Week 48 | 
| Number of patients with on-treatment virologic failure | Virologic failure is defined as patients who meet a virologic stopping rule and/or meet the definition of viral breakthrough. | Week 48 | 
| Number of patients with relapse after undetectable HCV RNA at actual end of treatment | Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (less than 25 IU/mL, target not detected) at actual end of treatment. | Week 48 | 
| Number of patients with relapse after undetectable HCV RNA at planned end of treatment | Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (less than 25 IU/mL, target not detected) at planned end of treatment. | Week 48 | 
| Number of patients with relapse after previous HCV RNA less than 25 IU/mL at planned end of treatment | Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous HCV RNA less than 25 IU/mL at planned end of treatment. | Week 48 | 
| Number of patients with viral breakthrough | Number of patients with viral breakthrough (defined as an increase more than 1 log in HCV RNA level from the lowest level reached, or a value of HCV RNA more than 100 IU/mL in patients whose HCV RNA has previously become less than 25 IU/mL during treatment). | Week 48 | 
| Change from baseline in log HCV RNA values | Change from baseline in log HCV RNA values at each time point during treatment. | Up to Week 52 | 
| Number of patients who have changes in liver graft biopsy histology |  | Up to Week 72 | 
| Number of patients with adverse events |  | Up to Week 72 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic HCV infection, Genotype 1 chronic HCV, Liver transplantation, Hepatitis C, Hep C, HCV, Telaprevir, Pegylated-Interferon-alfa-2a, Ribavirin