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

This study has been terminated.
(The study was terminated early by the sponsor on 13 January 2014 due to a decision to modify the drug development plan.)
Sponsor:
Information provided by (Responsible Party):
Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier:
NCT01467505
First received: November 3, 2011
Last updated: June 1, 2015
Last verified: June 2015
  Purpose

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.


Condition Intervention Phase
Hepatitis C
Drug: Telaprevir
Drug: Ribavirin
Drug: Pegylated Interferon Alfa-2a
Drug: Immunosuppressant Regimen
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Vertex Pharmaceuticals Incorporated:

Primary Outcome Measures:
  • Percentage of Participants With Sustained Viral Response 12 Weeks After Last Planned Dose of Study Drug (SVR12) [ Time Frame: 12 weeks after last planned dose of study drug (up to Week 60) ] [ Designated as safety issue: No ]
    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) [ Time Frame: 24 weeks after last planned dose of study drug (up to Week 72) ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
    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) [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Baseline up to Week 48 ] [ Designated as safety issue: No ]
    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 [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Pharmacokinetics of Telaprevir, Peg-IFN, RBV , and Selected Immunosuppressant Medications (Tacrolimus and Cyclosporine) [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants Requiring Dose Titration of Immunosuppressant Medications [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Biopsy Confirmed and Treated Rejection [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Percentage of Participants With Histological Evidence of Stabilization or Improvement in Inflammation Grade or Fibrosis Stage [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region [ Time Frame: 48 weeks ] [ Designated as safety issue: No ]
  • Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to Week 52 ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

Enrollment: 61
Study Start Date: February 2012
Study Completion Date: April 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T/PR + Immunosuppressant Regimen (Tacrolimus)
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
Tablet
Other Name: VX-950
Drug: Ribavirin
Tablet
Other Name: Copegus®, RBV
Drug: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Name: Pegasys®, Peg-IFN-alfa-2a
Drug: Immunosuppressant Regimen
Cyclosporine (CsA) based immunosuppressant regimen or Tacrolimus (TAC) based immunosuppressant regimen, as per standard practice. Immunosuppressant regimen were not considered study drugs.
Experimental: T/PR + Immunosuppressant Regimen (Cyclosporine)
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
Tablet
Other Name: VX-950
Drug: Ribavirin
Tablet
Other Name: Copegus®, RBV
Drug: Pegylated Interferon Alfa-2a
Subcutaneous Injection
Other Name: Pegasys®, Peg-IFN-alfa-2a
Drug: Immunosuppressant Regimen
Cyclosporine (CsA) based immunosuppressant regimen or Tacrolimus (TAC) based immunosuppressant regimen, as per standard practice. Immunosuppressant regimen were not considered study drugs.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01467505

  Show 22 Study Locations
Sponsors and Collaborators
Vertex Pharmaceuticals Incorporated
Investigators
Study Director: Medical Monitor Vertex Pharmaceuticals Incorporated
  More Information

No publications provided

Responsible Party: Vertex Pharmaceuticals Incorporated
ClinicalTrials.gov Identifier: NCT01467505     History of Changes
Other Study ID Numbers: VX11-950-117
Study First Received: November 3, 2011
Results First Received: May 2, 2015
Last Updated: June 1, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Additional relevant MeSH terms:
Hepatitis
Hepatitis C
Digestive System Diseases
Flaviviridae Infections
Hepatitis, Viral, Human
Liver Diseases
RNA Virus Infections
Virus Diseases
Immunosuppressive Agents
Interferon-alpha
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on July 26, 2015