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

• Register: EUCTR
• Last refreshed on: 2 August 2021
• Main ID: EUCTR2011-004724-35-ES
• Date of registration: 27/10/2011
• 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
• Date of first enrolment: 13/12/2011
• 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:
1. Male or female liver transplant recipient, 18 to 65 years old.
2. First time liver transplant recipient whose primary pre-transplant diagnosis was chronic
hepatitis C and who is genotype 1 HCV RNA infected following transplantation. Genotype 1
must be confirmed during screening.
3. One of the following based on clinical history or by documented HCV RNA and treatment history:
a) Treatment-naïve subject who did not receive any treatment with any approved or
investigational medication or drug regimen for the treatment of HCV prior to liver
transplantation;
OR
b) Treatment-experienced subject who received treatment for HCV prior to liver
transplantation. Where documentation is available, treatment-experienced subjects who were treated with Peg-IFN/RBV and received 80% or more of the intended dose of Peg-IFN/RBV should be categorized based on their response as either:
- Relapser: Subject had an undetectable HCV RNA level at the end of treatment (6 weeks or less after the last dose of medication) but did not achieve SVR;
- Partial responder: Subject had a ? 2 log10 decrease in HCV RNA at approximately Week 12 of previous therapy, but never achieved
undetectable HCV RNA while on treatment;
- Null responder: Subject failed to decrease HCV RNA by ? 2 log10 after approximately 12 weeks of therapy.
4. > 12 months to 10 years post-liver transplant.
5. Subject must be on a stable TAC or CsA containing immunosuppressive regimen defined as no change in immunosuppressive agents and dose for 3 months prior to the screening visit. Low-dose prednisone (average daily dose ? 5 mg) being used as an immunosuppressant is allowed. Subject should not be on dual therapy with TAC and CsA, and combination treatment with mycophenolate mofetil (Cellcept) is not allowed. Subjects may not use any other immunosuppressive agents.
6. Subject must agree to have a liver graft biopsy within the screening period, except:
- A liver graft biopsy does not need to be repeated within the screening period if a liver
graft biopsy was performed within 3 months prior to the screening visit, the biopsy report
is available, and slides can be sent to the study appointed hepatopathologist for
centralized reading.
- A liver graft biopsy does not need to be repeated within the screening period if the subject has had serial (approximately yearly) liver graft biopsies which show a stable stage of hepatic fibrosis over the past 3 years, the last biopsy was performed within 6 months prior to the screening visit, the biopsy report is available, and the slides from this biopsy can be sent to the study appointed hepatopathologist for centralized reading.
7. The last pre-treatment liver graft biopsy report must reveal fibrosis stage (Metavir) F0-F3. Subjects with F0 are only allowed if they also have:
- Necro-inflammation Grade > 2; or
- Alanine aminotransferase (ALT) > 2 times the upper limit of normal (ULN).
8. Subject is judged to be in moderately good health (other than HCV infection following liver transplantation) in the opinion of the investigator, on the basis of medical history and physical examination (including vital signs and screening electrocardiogram [ECG]), with any chronic medical conditions being stable.
9. If heterosexually active, a female subject of childbearing potential and a non- vasectomized male subject who has a female partner of childbearing potential must agree to the use of 2 effective methods of contraception from screening onwards until 6 months (female subject)
Exclusion criteria:
Reference is made to section 4.2 Exclusion criteria, pages 43-46 of the Clinical Trial Protocol


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

Health Condition(s) or Problem(s) studied

Chronic hepatitis C infection
MedDRA version: 14.0 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
Product Code: L03AB11
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)

Timepoint(s) of evaluation of this end point: 12 weeks after last planned dose of study drugs

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 an undetectable HCV ribonucleic 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): Proportion of patients achieving undetectable plasma HCV ribonucleic acid (RNA) levels.

Secondary Outcome(s)

Secondary end point(s): - Proportion of patients having undetectable plasma HCV ribonucleic acid (RNA levels)
- Proportion of patients having undetectable plasma HCV ribonucleic acid (RNA levels)
- Proportion of patients having undetectable plasma HCV ribonucleic acid (RNA levels)
- Proportion of patients having detectable plasma HCV ribonucleic acid (RNA levels) of <25IU/mL
- Proportion of patients having confirmed detectable HCV ribonucleic acid (RNA levels)
- Proportion of patients having confirmed detectable HCV ribonucleic acid (RNA levels)
- Proportion of patients having confirmed detectable HCV RNA during the follow-up period after previous HCV RNA < 25 IU/mL at
planned end of treatment
- Proportion of patients having an increase > 1 log in HCV RNA level from the lowest level reached, or a value of HCV RNA > 100 IU/mL in subjects whose HCV RNA has previously become < 25 IU/mL during treatment

Timepoint(s) of evaluation of this end point: - 24 weeks after last planned dose
- actual end of study drugs
- week 48 of study drugs
- week 48 of study drugs
- follow-up period after previous undetectable HCV RNA levels at actual end of study drugs
- follow-up period after previous undetectable HCV RNA levels at week 48
-follow-up period after previous undetectable HCV RNA levels at week 48
-From day 1 till week 48

Secondary ID(s)

2011-004724-35-DE

VX-950HPC3006

Source(s) of Monetary Support

Janssen-Cilag International NV

Ethics review

Status: Approved
Approval date: 25/11/2011
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