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

Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01467505
• Other study ID #: VX11-950-117
• Status: Terminated
• Phase: Phase 2
• First received: November 3, 2011
• Last updated: June 1, 2015
• Start date: February 2012
• Est. completion date: April 2014

Study information

• Verified date: June 2015
• Source: Vertex Pharmaceuticals Incorporated
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationCanada: Health Canada
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 61
• Est. completion date: April 2014
• Est. primary completion date: April 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

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

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C

Intervention

Drug:
• Telaprevir
Tablet
• Ribavirin
Tablet
• Pegylated Interferon Alfa-2a
Subcutaneous Injection
• Immunosuppressant Regimen
Cyclosporine (CsA) based immunosuppressant regimen or Tacrolimus (TAC) based immunosuppressant regimen, as per standard practice. Immunosuppressant regimen were not considered study drugs.

Locations

Country	Name	City	State
United States	Michigan	Ann Arbor	Michigan
United States	Alabama	Birmingham	Alabama
United States	Florida	Bradenton	Florida
United States	Massachusetts	Burlington	Massachusetts
United States	North Carolina	Charlotte	North Carolina
United States	Ohio	Cleveland	Ohio
United States	Texas	Dallas	Texas
United States	Colorado	Denver	Colorado
United States	Michigan	Detroit	Michigan
United States	Illinios	Evanston	Illinois
United States	Texas	Houston	Texas
United States	Indiana	Indianapolis	Indiana
United States	California	Los Angeles	California
United States	Florida	Miami	Florida
United States	New York	New York	New York
United States	Nebraska	Omaha	Nebraska
United States	Pennsylvania	Philadelphia	Pennsylvania
United States	Arizona	Phoenix	Arizona
United States	New York	Rochester	New York
United States	Missouri	St Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Vertex Pharmaceuticals Incorporated

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percentage of Participants With Sustained Viral Response 4 Weeks After Last Planned Dose of Study Drug (SVR4)		4 weeks after last planned dose of study drug (up to Week 52)	No
Primary	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 (	12 weeks after last planned dose of study drug (up to Week 60)	No
Secondary	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)	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Percentage of Participants With Viral Relapse		48 weeks	No
Secondary	Pharmacokinetics of Telaprevir, Peg-IFN, RBV , and Selected Immunosuppressant Medications (Tacrolimus and Cyclosporine)		48 weeks	No
Secondary	Percentage of Participants Requiring Dose Titration of Immunosuppressant Medications		48 weeks	No
Secondary	Percentage of Participants With Biopsy Confirmed and Treated Rejection		48 weeks	No
Secondary	Percentage of Participants With Histological Evidence of Stabilization or Improvement in Inflammation Grade or Fibrosis Stage		48 weeks	No
Secondary	Number of Participants With Telaprevir Resistant HCV Variant at Non-Structural Viral Protein 3-4A (NS3-4A) Region		48 weeks	No
Secondary	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	Yes