An Efficacy and Safety Study of Telaprevir in Patients With Genotype 1 Hepatitis C Infection After Liver Transplantation (REPLACE)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Janssen-Cilag International NV
ClinicalTrials.gov Identifier:
NCT01571583
First received: December 16, 2011
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

The purpose of this study is to evaluate the effectiveness of telaprevir in combination with Peg-IFN-alfa-2a and ribavirin in stable liver transplant patients with chronic hepatitis C virus (HCV) genotype 1.


Condition Intervention Phase
Chronic Hepatitis C Virus (HCV) Infection
Drug: Telaprevir
Drug: Pegylated interferon alfa-2a
Drug: Ribavirin
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open-Label, Phase 3b Study To Determine Efficacy and Safety of Telaprevir, Pegylated-Interferon-alfa-2a and Ribavirin in Hepatitis C Genotype 1 Infected, Stable Liver Transplant Subjects

Resource links provided by NLM:


Further study details as provided by Janssen-Cilag International NV:

Primary Outcome Measures:
  • Number of patients achieving sustained virologic response (SVR) 12 planned [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
    SVR12 planned is defined as having plasma hepatitis C virus (HCV ) ribonucleic acid (RNA) level less than 25 IU/mL 12 weeks after the last planned dose of study medication.


Secondary Outcome Measures:
  • Number of patients achieving SVR12 planned(c) [ Time Frame: Week 60 ] [ Designated as safety issue: No ]
    SVR12 planned(c) is defined as having undetectable plasma HCV RNA levels 12 weeks after the last planned dose of study drugs.

  • Number of patients achieving SVR24 planned [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    SVR24 planned is defined as having plasma HCV RNA levels less than 25 IU/mL 24 weeks after the last planned dose of study medication.

  • Number of patients achieving SVR24 planned(c) [ Time Frame: Week 72 ] [ Designated as safety issue: No ]
    SVR24 planned(c) is defined as having an undetectable plasma HCV RNA level 24 weeks after the last planned dose of study medication.

  • Number of patients having an undetectable HCV RNA level at Week 4 of treatment [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
  • Number of patients having an undetectable HCV RNA level at Week 12 of treatment [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
  • Number of patients having undetectable HCV RNA levels at Week 4 and Week 12 of treatment [ Time Frame: Week 4 and Week 12 ] [ Designated as safety issue: No ]
  • Number of patients having an undetectable HCV RNA level at the actual end of treatment [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of patients having an undetectable HCV RNA level at the planned end of treatment [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of patients having less than 25 IU/mL at the planned end of treatment [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
  • Number of patients with on-treatment virologic failure [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Virologic failure is defined as patients who meet a virologic stopping rule and/or meet the definition of viral breakthrough.

  • Number of patients with relapse after undetectable HCV RNA at actual end of treatment [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (less than 25 IU/mL, target not detected) at actual end of treatment.

  • Number of patients with relapse after undetectable HCV RNA at planned end of treatment [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (less than 25 IU/mL, target not detected) at planned end of treatment.

  • Number of patients with relapse after previous HCV RNA less than 25 IU/mL at planned end of treatment [ Time Frame: Week 48 ] [ Designated as safety issue: No ]
    Number of patients who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous HCV RNA less than 25 IU/mL at planned end of treatment.

  • Number of patients with viral breakthrough [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    Number of patients with viral breakthrough (defined as an increase more than 1 log in HCV RNA level from the lowest level reached, or a value of HCV RNA more than 100 IU/mL in patients whose HCV RNA has previously become less than 25 IU/mL during treatment).

  • Change from baseline in log HCV RNA values [ Time Frame: Up to Week 52 ] [ Designated as safety issue: No ]
    Change from baseline in log HCV RNA values at each time point during treatment.

  • Number of patients who have changes in liver graft biopsy histology [ Time Frame: Up to Week 72 ] [ Designated as safety issue: No ]
  • Number of patients with adverse events [ Time Frame: Up to Week 72 ] [ Designated as safety issue: Yes ]

Enrollment: 74
Study Start Date: February 2012
Study Completion Date: July 2014
Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Telaprevir+Peg-IFN-alfa-2a+Ribavirin
Patients will be treated for 12 weeks with telaprevir in combination with Pegylated interferon alfa-2a (Peg-IFN-alfa-2a) and ribavirin followed by 36 weeks of treatment with Peg-IFN-alfa-2a and ribavirin alone.
Drug: Telaprevir
Type=exact number, unit=mg, number=375, form=tablet, route=oral. Patients will receive 2 oral tablets (750 mg) every 8 hours for 12 weeks.
Drug: Pegylated interferon alfa-2a
Type=exact number, unit=µg, number=180, form=injection, route=subcutaneous. 180 microgram (µg) per week, subcutaneous injection, for 48 weeks.
Drug: Ribavirin
Type=exact number, unit=mg, number=200, form=tablet, route=oral. Starting from 600 mg (3 tablets) per day on Day 1. This dose will become higher or lower based on blood results and the investigators opinion (to a goal of 1000 to 1200 mg/day [5 to 6 tablets] based on subject weight), twice daily regimen, for 48 weeks.

Detailed Description:

This is an open-label (all people know the identity of the intervention), multicenter study in genotype 1 chronic HCV infected liver transplant patients who will be treated for 12 weeks with telaprevir 750 mg every 8 hours given in combination with Peg-IFN-alfa-2a and ribavirin followed by 36 weeks of treatment with Peg-IFN-alfa-2a and ribavirin alone. The total treatment duration will be 48 weeks. Safety will be evaluated throughout the study and will include evaluations of adverse events, clinical laboratory tests, electrocardiogram, vital signs, and physical examination.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • First time liver transplant recipient whose primary pre-transplant diagnosis was chronic hepatitis C genotype 1
  • More than 6 months to 10 years post-liver transplant
  • Patient did or did not receive treatment for HCV prior to liver transplantation
  • Patient must agree to have a liver graft biopsy during the screening period unless they had a biopsy within three months of the screening period (for patients between 6 months and one year post transplant) or within six months of the screening period (for patients who are more than one year post transplant)
  • A female patient of childbearing potential and a nonvasectomized male patient who has a female partner of childbearing potential must agree to the use of 2 effective methods of birth control from screening until 6 months (female patient) or 7 months (male patient) after the last dose of ribavirin

Exclusion Criteria:

  • Patient is currently infected or co-infected with HCV of another genotype than genotype 1
  • Patient received treatment for hepatitis C following liver transplantation
  • Patient has history of decompensated liver disease or shows evidence of significant liver disease in addition to hepatitis C
  • Patient with human immunodeficiency virus or hepatitis B virus co-infection
  • Patient with active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma or hepatocellular carcinoma)
  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: NCT01571583

Locations
Austria
Linz, Austria
Wien, Austria
Belgium
Brussels, Belgium
Leuven, Belgium
Liege, Belgium
France
Clichy, France
Marseille, France
Montpellier, France
Rennes Cedex N/A, France
Villejuif Cedex, France
Germany
Essen, Germany
Frankfurt A. M., Germany
Hannover, Germany
Leipzig, Germany
Münster, Germany
Spain
Barcelona, Spain
Madrid, Spain
Valencia, Spain
United Kingdom
Birmingham, United Kingdom
London, United Kingdom
Sponsors and Collaborators
Janssen-Cilag International NV
Investigators
Study Director: Janssen-Cilag International NV, Belgium Clinical Trial Janssen-Cilag International NV
  More Information

No publications provided

Responsible Party: Janssen-Cilag International NV
ClinicalTrials.gov Identifier: NCT01571583     History of Changes
Other Study ID Numbers: CR018721, VX-950HPC3006, 2011-004724-35
Study First Received: December 16, 2011
Last Updated: September 8, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios
Germany: Ethics Commission
Great Britain: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Janssen-Cilag International NV:
Chronic HCV infection
Genotype 1 chronic HCV
Liver transplantation
Hepatitis C
Hep C
HCV
Telaprevir
Pegylated-Interferon-alfa-2a
Ribavirin

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

ClinicalTrials.gov processed this record on October 21, 2014