An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients

Study Overview
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Brief Summary
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To assess efficacy of telaprevir, pegylated interferon alfa-2a (Peg-IFN-alfa-2a), and ribavirin (RBV) for hepatitis C virus (HCV) in a 48-week total treatment duration regimen following liver transplantation.

Official Title
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A 2-Part, Open Label Study of Telaprevir in Combination With Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) in Subjects Chronically Infected With Genotype 1 Hepatitis C Virus Following Liver Transplantation

Conditions
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Hepatitis C

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female participants between the ages of 18 and 65 years History of orthotopic liver transplantation less than 10 years before the Screening visit but no sooner than 6 months before Day 1 Taking a stable immunosuppressant regimen based on either tacrolimus or cyclosporine without substantial dose changes over the past 3 months Naive to pegylated interferon/ribavirin treatment or experienced with pegylated interferon/ribavirin prior to transplantation with relapse, partial, or null response Exclusion Criteria: Documented cirrhosis after liver transplantation Ascites or hepatic encephalopathy within 6 months before Screening Retransplantation for recurrent hepatitis C Treatment for hepatitis C post liver transplantation History within the past 3 months of: rejection within 3 months or greater than (>) 1 rejection within 12 months Current treatment with sirolimus or methylprednisolone. Low dose prednisone use (<5 milligram per day) is permitted History within 3 months of any bacterial infection requiring >1 week of intravenous antibiotics, cytomegalovirus viremia or cytomegalovirus infection with end-organ involvement, fungal disease (except cutaneous and mild oral thrush) History of post transplant lymphoproliferative disease Acceptable laboratory values at Screening as specified in the protocol Positive for human immunodeficiency virus 1/2 (HIV1/2) enzyme immunoassay (EIA) antibody screen or Hepatitis B deoxyribonucleic acid (DNA) or Hepatitis B surface antigen History of hepatocellular carcinoma with high risk of recurrence Any other cause of liver disease deemed clinically significant by the investigator in addition to hepatitis C Autoimmune-mediated disease History of acute pancreatitis within 5 years before the Screening visit Prior treatment with an hepatitis C virus (HCV) protease inhibitor

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: T/PR + Immunosuppressant Regimen (Tacrolimus)<br>Participants who were receiving tacrolimus (TAC) based immunosuppressant regimen at baseline, received telaprevir (T) 1125 milligram (mg) tablet twice daily for 12 weeks in combination with pegylated interferon alfa 2a (P) (Peg-IFN-alfa-2a) 180 microgram per week (mcg/week) subcutaneous injection and ribavirin (R) (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. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Ribavirin<br>* Tablet<br>* Other names: Copegus®, RBV;Drug: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Pegasys®, Peg-IFN-alfa-2a;Drug: Immunosuppressant Regimen<br>* Cyclosporine (CsA) based immunosuppressant regimen or Tacrolimus (TAC) based immunosuppressant regimen, as per standard practice. Immunosuppressant regimen were not considered study drugs.<br>|
| Experimental: T/PR + Immunosuppressant Regimen (Cyclosporine)<br>Participants who were receiving cyclosporine (CsA) based immunosuppressant regimen at baseline, received 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. Participants continued their immunosuppressant regimen, as per standard practice and investigator discretion. | Drug: Telaprevir<br>* Tablet<br>* Other names: VX-950;Drug: Ribavirin<br>* Tablet<br>* Other names: Copegus®, RBV;Drug: Pegylated Interferon Alfa-2a<br>* Subcutaneous Injection<br>* Other names: Pegasys®, Peg-IFN-alfa-2a;Drug: Immunosuppressant Regimen<br>* Cyclosporine (CsA) based immunosuppressant regimen or Tacrolimus (TAC) based immunosuppressant regimen, as per standard practice. Immunosuppressant regimen were not considered study drugs.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants 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 (<lower limit of quantification) at 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 international units per milliliter (IU/mL). | 12 weeks after last planned dose of study drug (up to Week 60) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) | SVR24 was defined as an undetectable HCV 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 IU/mL. | 24 weeks after last planned dose of study drug (up to Week 72) | 
| Percentage of Participants 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. | Week 4 | 
| Percentage of Participants 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. | Week 4 and Week 12 | 
| Percentage of Participants With On-Treatment Virologic Failure | On-treatment virologic failure was defined as subjects who met futility or who completed the assigned treatment duration and had detectable HCV RNA at planned end of treatment (up to 48 weeks). Data for this outcome was not planned to be reported by prior response. | Baseline up to Week 48 | 
| Percentage of Participants With Viral Relapse |  | 48 weeks | 
| Pharmacokinetics of Telaprevir, Peg-IFN, RBV , and Selected Immunosuppressant Medications (Tacrolimus and Cyclosporine) |  | 48 weeks | 
| Percentage of Participants Requiring Dose Titration of Immunosuppressant Medications |  | 48 weeks | 
| Percentage of Participants With Biopsy Confirmed and Treated Rejection |  | 48 weeks | 
| Percentage of Participants With Histological Evidence of Stabilization or Improvement in Inflammation Grade or Fibrosis Stage |  | 48 weeks | 
| Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region |  | 48 weeks | 
| Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) | Any adverse change from the participant'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 52 |