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

Primary Purpose

Hepatitis C

Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Telaprevir
Ribavirin
Pegylated Interferon Alfa-2a
Immunosuppressant Regimen
Sponsored by
Vertex Pharmaceuticals Incorporated
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis C

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Alabama
  • Arizona
  • California
  • Colorado
  • Florida
  • Florida
  • Illinios
  • Indiana
  • Massachusetts
  • Michigan
  • Michigan
  • Missouri
  • Nebraska
  • New York
  • New York
  • North Carolina
  • Ohio
  • Pennsylvania
  • Texas
  • Texas

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

T/PR + Immunosuppressant Regimen (Tacrolimus)

T/PR + Immunosuppressant Regimen (Cyclosporine)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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).

Secondary Outcome Measures

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.
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.
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.
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.
Percentage of Participants With Viral Relapse
Pharmacokinetics of Telaprevir, Peg-IFN, RBV , and Selected Immunosuppressant Medications (Tacrolimus and Cyclosporine)
Percentage of Participants Requiring Dose Titration of Immunosuppressant Medications
Percentage of Participants With Biopsy Confirmed and Treated Rejection
Percentage of Participants With Histological Evidence of Stabilization or Improvement in Inflammation Grade or Fibrosis Stage
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
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.

Full Information

First Posted
November 3, 2011
Last Updated
June 1, 2015
Sponsor
Vertex Pharmaceuticals Incorporated
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1. Study Identification

Unique Protocol Identification Number
NCT01467505
Brief Title
An Open Label Study of the Effect of Telaprevir in Combination With Ribavirin and Peginterferon on HCV Infection in Stable Liver Transplant Patients
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Terminated
Why Stopped
The study was terminated early by the sponsor on 13 January 2014 due to a decision to modify the drug development plan.
Study Start Date
February 2012 (undefined)
Primary Completion Date
April 2014 (Actual)
Study Completion Date
April 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Vertex Pharmaceuticals Incorporated

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis C

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
61 (Actual)

8. Arms, Groups, and Interventions

Arm Title
T/PR + Immunosuppressant Regimen (Tacrolimus)
Arm Type
Experimental
Arm Description
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.
Arm Title
T/PR + Immunosuppressant Regimen (Cyclosporine)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Telaprevir
Other Intervention Name(s)
VX-950
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
Ribavirin
Other Intervention Name(s)
Copegus®, RBV
Intervention Description
Tablet
Intervention Type
Drug
Intervention Name(s)
Pegylated Interferon Alfa-2a
Other Intervention Name(s)
Pegasys®, Peg-IFN-alfa-2a
Intervention Description
Subcutaneous Injection
Intervention Type
Drug
Intervention Name(s)
Immunosuppressant Regimen
Intervention Description
Cyclosporine (CsA) based immunosuppressant regimen or Tacrolimus (TAC) based immunosuppressant regimen, as per standard practice. Immunosuppressant regimen were not considered study drugs.
Primary Outcome Measure Information:
Title
Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12)
Description
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).
Time Frame
12 weeks after last planned dose of study drug (up to Week 60)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Sustained Viral Response 24 Weeks After Last Planned Dose of Study Drug (SVR24)
Description
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.
Time Frame
24 weeks after last planned dose of study drug (up to Week 72)
Title
Percentage of Participants With Rapid Viral Response (RVR)
Description
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.
Time Frame
Week 4
Title
Percentage of Participants With Extended Rapid Viral Response (eRVR)
Description
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.
Time Frame
Week 4 and Week 12
Title
Percentage of Participants With On-Treatment Virologic Failure
Description
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.
Time Frame
Baseline up to Week 48
Title
Percentage of Participants With Viral Relapse
Time Frame
48 weeks
Title
Pharmacokinetics of Telaprevir, Peg-IFN, RBV , and Selected Immunosuppressant Medications (Tacrolimus and Cyclosporine)
Time Frame
48 weeks
Title
Percentage of Participants Requiring Dose Titration of Immunosuppressant Medications
Time Frame
48 weeks
Title
Percentage of Participants With Biopsy Confirmed and Treated Rejection
Time Frame
48 weeks
Title
Percentage of Participants With Histological Evidence of Stabilization or Improvement in Inflammation Grade or Fibrosis Stage
Time Frame
48 weeks
Title
Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region
Time Frame
48 weeks
Title
Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to Week 52
Other Pre-specified Outcome Measures:
Title
Percentage of Participants With Sustained Viral Response 4 Weeks After Last Planned Dose of Study Drug (SVR4)
Time Frame
4 weeks after last planned dose of study drug (up to Week 52)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Monitor
Organizational Affiliation
Vertex Pharmaceuticals Incorporated
Official's Role
Study Director
Facility Information:
Facility Name
Alabama
City
Birmingham
State/Province
Alabama
Country
United States
Facility Name
Arizona
City
Phoenix
State/Province
Arizona
Country
United States
Facility Name
California
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Colorado
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Florida
City
Bradenton
State/Province
Florida
Country
United States
Facility Name
Florida
City
Miami
State/Province
Florida
Country
United States
Facility Name
Illinios
City
Evanston
State/Province
Illinois
Country
United States
Facility Name
Indiana
City
Indianapolis
State/Province
Indiana
Country
United States
Facility Name
Massachusetts
City
Burlington
State/Province
Massachusetts
Country
United States
Facility Name
Michigan
City
Ann Arbor
State/Province
Michigan
Country
United States
Facility Name
Michigan
City
Detroit
State/Province
Michigan
Country
United States
Facility Name
Missouri
City
St Louis
State/Province
Missouri
Country
United States
Facility Name
Nebraska
City
Omaha
State/Province
Nebraska
Country
United States
Facility Name
New York
City
New York
State/Province
New York
Country
United States
Facility Name
New York
City
Rochester
State/Province
New York
Country
United States
Facility Name
North Carolina
City
Charlotte
State/Province
North Carolina
Country
United States
Facility Name
Ohio
City
Cleveland
State/Province
Ohio
Country
United States
Facility Name
Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
Country
United States
Facility Name
Texas
City
Dallas
State/Province
Texas
Country
United States
Facility Name
Texas
City
Houston
State/Province
Texas
Country
United States
City
Calgary
State/Province
Alberta
Country
Canada
City
Vancouver
State/Province
British Columbia
Country
Canada

12. IPD Sharing Statement

Learn more about this trial

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

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