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

• Register: EUCTR
• Last refreshed on: 23 March 2015
• Main ID: EUCTR2011-004724-35-IT
• Date of registration: 22/12/2011
• Prospective Registration: Yes
• Primary sponsor: JANSSEN-CILAG INTERNATIONAL N.V.
• 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: 22/02/2012
• 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: Open: Single blind: Double blind: Parallel group: Cross over: Other: If controlled, specify comparator, Other Medicinial Product: Placebo: Other: Number of treatment arms in the trial: 1

Countries of recruitment

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

Contacts

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

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

Key inclusion & exclusion criteria

Inclusion criteria:
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.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
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:
Subject is infected or co-infected with non-genotype 1 HCV. 2. Subject received treatment with a direct acting antiviral for hepatitis C. 3. Subject received HCV treatment (approved or investigational medication) following liver transplantation. 4. Subject has histological evidence of rejection on the most recent liver graft biopsy obtained at screening or within 3 months (no serial liver graft biopsies taken) to 6 months (if serial liver graft biopsies have been taken) prior to the screening visit. 5. Subject has a contraindication to the administration of Peg-IFN-alfa or RBV, including but not limited to any of the following: - hypersensitivity to Peg-IFN-alfa, RBV, or any of their components; - hemoglobinopathies (including thalassemia major, sickle-cell disease);history or clinical evidence of significant or unstable cardiac disease (e.g., angina, congestive heart failure, recent (within 1 year) myocardial infarction, significant arrhythmia), and/or clinically significant ECG abnormalities; - abnormal thyroid function that is not adequately controlled; - poorly controlled diabetes mellitus as evidenced by hemoglobin A1c (HbA1c) = 8.5% at screening; - antinuclear antibody (ANA) titer = 1:640 at screening, evidence of autoimmune-mediated disease (e.g., Crohn’s disease, ulcerative colitis, idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis), and/or evidence of autoimmune hepatitis.


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

Health Condition(s) or Problem(s) studied

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

Chronic hepatitis C infection
MedDRA version: 14.1 Level: LLT Classification code 10008912 Term: Chronic hepatitis C System Organ Class: 10021881 - Infections and infestations

Intervention(s)

Trade Name: INCIVO
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: TELAPREVIR
CAS Number: 402957-28-2
Current Sponsor code: VX-950
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 375-

Trade Name: PEGASYS*SC 1FL 180MCG/1ML
Pharmaceutical Form: Solution for injection
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*28CPR RIV 200MG
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)

Secondary Objective: . confrontare la percentuale di SVR ricavata in questo studio con una percentuale di SVR storica di controllo ricavata dalla letteratura su soggetti trattati con Peg-IFN ed RBV; • valutare le concentrazioni di HCV RNA e le risposte nel tempo, durante il trattamento e durante il follow-up; • valutare le variazioni istologiche della biopsia del fegato trapiantato confrontando l'ultima biopsia pre-trattamento con la biopsia eseguita 24 settimane dopo il trattamento; • valutare la sicurezza e la tollerabilità di telaprevir in associazione a Peg-IFN-alfa-2a, RBV e tacrolimus (TAC) o ciclosporina A (CsA); • valutare la farmacocinetica (PK) di telaprevir e le concentrazioni di TAC o CsA; • valutare i requisiti di titolazione della dose per TAC e CsA; • valutare l'incidenza del rigetto del fegato trapiantato;

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

Primary end point(s): Proportion of patients achieving undetectable plasma HCV ribonucleic acid (RNA) levels.

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 Outcome(s)

Timepoint(s) of evaluation of this end point: - 24 weeks after last planned dose of study drugs - actual end 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 end point(s): Proportion of subjects achieving SVR24planned, defined as having an undetectable plasma HCV RNA level 24 weeks after the last planned dose of study medication. o Proportion of subjects having an undetectable HCV RNA level at Week 4 of treatment (RVR). o Proportion of subjects having an undetectable HCV RNA level at Week 12 of treatment. o Proportion of subjects having undetectable HCV RNA levels at Week 4 and Week 12 of treatment (eRVR). o Proportion of subjects having an undetectable HCV RNA level at the actual end of treatment (i.e., Week 48 or early discontinuation). o Proportion of subjects having an undetectable HCV RNA level at the planned end of treatment (i.e., Week 48). o Proportion of subjects having < 25 IU/mL at the planned end of treatment (i.e., Week 48). o Proportion of subjects with on-treatment virologic failure (subjects who meet a virologic stopping rule and/or meet the definition of viral breakthrough). o Proportion of subjects who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (< 25 IU/mL, undetectable) at actual end of treatment (i.e., Week 48 or early discontinuation). o Proportion of subjects who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous undetectable HCV RNA (< 25 IU/mL, undetectable) at planned end of treatment (i.e., Week 48). o Proportion of subjects who relapse, defined as having confirmed detectable HCV RNA during the follow-up period after previous HCV RNA < 25 IU/mL at planned end of treatment (i.e., Week 48). o Proportion of subjects with viral breakthrough (defined as 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). o Change from baseline in log HCV RNA values at each time point during treatment. o Proportion of subjects who have changes in liver graft biopsy histology.

Secondary ID(s)

2011-004724-35-DE

VX-950HPC3006

Source(s) of Monetary Support

JANSSEN CILAG SPA