An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients
- Conditions
- Hepatitis C
- Interventions
- Registration Number
- NCT01467505
- Lead Sponsor
- Vertex Pharmaceuticals Incorporated
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 61
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description T/PR + Immunosuppressant Regimen (Tacrolimus) Pegylated Interferon Alfa-2a 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. T/PR + Immunosuppressant Regimen (Tacrolimus) Immunosuppressant Regimen 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. T/PR + Immunosuppressant Regimen (Tacrolimus) Ribavirin 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. T/PR + Immunosuppressant Regimen (Cyclosporine) Immunosuppressant Regimen 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. T/PR + Immunosuppressant Regimen (Tacrolimus) Telaprevir 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. T/PR + Immunosuppressant Regimen (Cyclosporine) Telaprevir 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. T/PR + Immunosuppressant Regimen (Cyclosporine) Ribavirin 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. T/PR + Immunosuppressant Regimen (Cyclosporine) Pegylated Interferon Alfa-2a 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) 12 weeks after last planned dose of study drug (up to Week 60) 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).
- Secondary Outcome Measures
Name Time Method Pharmacokinetics of Telaprevir, Peg-IFN, RBV , and Selected Immunosuppressant Medications (Tacrolimus and Cyclosporine) 48 weeks Percentage of Participants With Biopsy Confirmed and Treated Rejection 48 weeks Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24) 24 weeks after last planned dose of study drug (up to Week 72) 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.
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region 48 weeks Percentage of Participants With Rapid Viral Response (RVR) Week 4 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.
Percentage of Participants With Viral Relapse 48 weeks Percentage of Participants With Extended Rapid Viral Response (eRVR) Week 4 and 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 4 weeks and 12 weeks after the start of study treatment.
Percentage of Participants With On-Treatment Virologic Failure Baseline up to Week 48 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.
Percentage of Participants With Histological Evidence of Stabilization or Improvement in Inflammation Grade or Fibrosis Stage 48 weeks Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) Baseline up to Week 52 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.
Percentage of Participants Requiring Dose Titration of Immunosuppressant Medications 48 weeks
Trial Locations
- Locations (16)
New York
🇺🇸Rochester, New York, United States
North Carolina
🇺🇸Charlotte, North Carolina, United States
Missouri
🇺🇸St Louis, Missouri, United States
Arizona
🇺🇸Phoenix, Arizona, United States
Colorado
🇺🇸Denver, Colorado, United States
Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Texas
🇺🇸Houston, Texas, United States
Alabama
🇺🇸Birmingham, Alabama, United States
California
🇺🇸Los Angeles, California, United States
Florida
🇺🇸Miami, Florida, United States
Indiana
🇺🇸Indianapolis, Indiana, United States
Illinios
🇺🇸Evanston, Illinois, United States
Michigan
🇺🇸Detroit, Michigan, United States
Nebraska
🇺🇸Omaha, Nebraska, United States
Ohio
🇺🇸Cleveland, Ohio, United States
Massachusetts
🇺🇸Burlington, Massachusetts, United States