An efficacy and safety study of Telaprevir in patients with genotype 1 Hepatitis C infection after liver transplantation

• Register: EUCTR
• Last refreshed on: 30 June 2019
• Main ID: EUCTR2011-004724-35-GB
• Date of registration: 01/11/2011
• Prospective Registration: Yes
• Primary sponsor: Janssen-Cilag International NV
• Public title: An efficacy and safety study of Telaprevir in patients with genotype 1 Hepatitis C infection after liver transplantation
• Scientific 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 - REPLACE
• Date of first enrolment: 15/12/2011
• Target sample size: 72
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-004724-35
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Austria, Belgium, Germany, Italy, Spain, United Kingdom

Contacts

• Name: Janssen Biologics BV
• Affiliation: Janssen-Cilag International NV - Clinical Registry Group

• Name: Janssen Biologics BV
• Affiliation: Janssen-Cilag International NV - Clinical Registry Group

Key inclusion & exclusion 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 within the screening period with exception made if recent serial biopsy with stable stage of hepatic fibrosis
- 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

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 has human immunodeficiency virus or hepatitis B virus coinfection
- Patient has active malignant disease or history of malignant disease within the past 5 years (with the exception of treated basal cell carcinoma or hepatocellular carcinoma)


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Chronic hepatitis C infection
MedDRA version: 14.1 Level: LLT Classification code 10019752 Term: Hepatitis C virus (HCV) System Organ Class: 10022891 - Investigations

Therapeutic area: Diseases [C] - Virus Diseases [C02]

Intervention(s)

Trade Name: INCIVO
Product Name: INCIVO
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Telaprevir
CAS Number: 402957-28-2
Other descriptive name: TELAPREVIR
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 375-

Trade Name: Pegasys
Product Name: Pegasys
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: PEGINTERFERON ALFA-2A
CAS Number: 198153-51-4
Concentration unit: µg/ml microgram(s)/millilitre
Concentration type: equal
Concentration number: 360-

Trade Name: Copegus
Product Name: Copegus
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RIBAVIRIN
CAS Number: 36791-04-5
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 200-

Primary Outcome(s)

Main Objective: to determine the efficacy of telaprevir administered as 750 mg every 8 hours (q8h) in combination with pegylated interferon (Peg-IFN)-alfa-2a and ribavirin (RBV) in genotype 1 chronic HCV infected liver transplant patients as measured by sustained virologic response (SVR12planned). SVR12planned is defined as having HCV ribonucleic <25 IU/mL acid (RNA) level 12 weeks after the last planned dose of study medication.

Secondary Objective: - to compare the SVR rate from this study to a historical control SVR rate derived from the literature in subjects treated with Peg-IFN and RBV;
- to evaluate HCV RNA levels and responses over time, on treatment and during follow-up;
- to evaluate changes in liver graft biopsy histology comparing the last pre-treatment biopsy to the 24-week post-treatment biopsy;
- to evaluate safety and tolerability of telaprevir in combination with Peg-IFN-alfa-2a, RBV, and tacrolimus (TAC) or cyclosporin A (CsA);
- to evaluate the pharmacokinetics (PK) of telaprevir and concentrations of TAC or CsA;
- to evaluate dose titration requirements for TAC and CsA;
- to evaluate the incidence of liver graft rejection;
- to evaluate relapse rates and virologic failure rates;
- to evaluate changes from baseline in the amino acid sequence of HCV NS3-4A protease.

Primary end point(s): Number of patients achieving sustained virologic response (SVR) 12planned (SVR12planned is defined as having plasma HCV (hepatitis C virus) RNA (ribonucleic acid) level <25 IU/mL 12 weeks after the last planned dose of study medication.)

Timepoint(s) of evaluation of this end point: week 60

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: - Week 60
- Week 72
- Week 72
- Week 4
- Week 12
- Week 4 and Week 12
- Up to week 48
- Week 48
- Week 48
- Up to week 48
- Up to week 48
- Up to week 48
- Up to week 48
- Up to week 48
- Up to week 72
- Up to week 72

Secondary end point(s): - Number of patients achieving SVR12planned(c) (SVR12planned(c) is defined as having undetectable plasma HCV RNA levels 12 weeks after the last planned dose of study drugs.)
- Number of patients achieving SVR24planned (SVR24planned is defined as having plasma HCV RNA levels <25 IU/mL 24 weeks after the last planned dose of study medication.)
- Number of patients achieving SVR24planned(c) (SVR24planned(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
- Number of patients having an undetectable HCV RNA level at Week 12 of treatment
- Number of patients having undetectable HCV RNA levels at Week 4 and Week 12 of treatment
- Number of patients having an undetectable HCV RNA level at the actual end of treatment
- Number of patients having an undetectable HCV RNA level at the planned end of treatment
- Number of patients having < 25 IU/mL at the planned end of treatment
- Number of patients with ontreatment virologic failure
- Number of patients with relapse at actual end of treatment
- Number of patients with relapse at planned end of treatment
- Number of patients with viral breakthrough
- Change from baseline in log HCV RNA values
- Number of patients who have changes in liver graft biopsy histology
- Number of patients with adverse events

Secondary ID(s)

VX-950HPC3006

2011-004724-35-DE

Source(s) of Monetary Support

Janssen-Cilag International NV

Ethics review

Status: Approved
Approval date:
Contact:

Results

• Results available: Yes
• Date Posted: 31/07/2015
• Date Completed: 15/07/2014
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-004724-35/results