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

• Register: EUCTR
• Last refreshed on: 6 January 2015
• Main ID: EUCTR2011-004724-35-DE
• Date of registration: 24/10/2011
• 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
• 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

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. 18 to 70 years old.
2. First time liver transplant recipient
3. One of the following based on clinical history or by documented HCV RNA and treatment history:
a) Treatment-naïve subject
OR
- Relapser:
- Partial responder: ;
- Null responder:.
4. > 6 months to 10 years post-liver transplant.
5. Subject must be on a stable TAC or CsA containing immunosuppressive regimen, combination with MMF is allowed
6. Subject must agree to have a liver graft biopsy: >1 year of liver transplantation within 6 months prior to screening, 6-12 months of transplantation within 3 months,
7. The last pre-treatment liver graft biopsy report must reveal fibrosis stage (Metavir) F0-F3.
8. Subject is judged to be in moderately good health
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) or 7 months (male subject) after the last dose of RBV. Male subjects must also agree not to donate sperm during the study and for 7 months after the last intake of RBV.
10. Subject or female partner is not pregnant, planning to become pregnant, or breastfeeding.
11. Subject is willing and able to refrain from the concomitant use of medications as described in the section “Disallowed Medication”
12. Subject is able to read and understand, and is willing to sign the Informed Consent Form (ICF) voluntarily.
13. Subject should agree not to participate in other clinical studies for the duration of his/her participation in this study, except for non-interventional or observational studies.

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 13
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1

Exclusion criteria:
1. 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 following liver transplantation.
4. Subject has histological evidence of rejection on the most recent liver graft biopsy
5. Subject has a contraindication to the administration of Peg-IFN-alfa or RBV,
6. Subject has a pre-existing psychiatric condition that could interfere with the subject’s participation in and completion of the study,:
7. Following transplantation, subject has history of decompensated liver disease:
8. Subject’s liver graft biopsy used to meet study eligibility criteria and/or clinical condition shows evidence of liver disease in addition to hepatitis C,
9. Subject 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 (HCC) cured by liver transplant).
10. Family history of congenital QT prolongation or sudden death. History of congenital QT prolongation, drug-induced QT prolongation or Torsade de Pointes, nonsustained or sustained ventricular tachycardia, or baseline QTcF >450 msec.
11. Subject has history of seizure disorders unrelated to calcineurin toxicity.
12. Uncontrolled diabetes or hypertension post transplantwithin 3 months prior to the screening visit.
13. Subject has history or other evidence of clinically significant retinopathy or ophthalmological disorder,
14. Subject has history or other clinical evidence of chronic pulmonary disease
15. Subject has active hemophilia or other bleeding disorder.
16. Subject has evidence of serious or severe bacterial or fungal infection(s), including active tuberculosis.
17. Subject has HIV or HBV co-infection.
18. Subject has a history of acute or chronic pancreatitis post transplant with exception of gallstone or post ERCP pancreatitis.
19. Knowledge of alcohol, barbiturate, amphetamine, recreational or narcotic drug use, current or within 2 years prior to the screening visit that in the investigator’s opinion would compromise the subject’s safety and/or compliance with study procedures.
20. Subject has a confirmed Grade 4 laboratory abnormality as defined by the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events (“DAIDS AE grading table”) or any other clinically relevant abnormalities in the opinion of the investigator. Subjects with Grade 4 elevations of gamma- glutamyltransferase (GGT) will be allowed to enter the study if there are no other clinically relevant laboratory abnormalities as judged by the investigator.
The screening laboratory values of the following variables should meet the acceptable values defined below:
- absolute neutrophil count (ANC) = 1,000/mm3;
- platelet count = 75,000/mm3;
- hemoglobin = 11g/dL;
- estimated creatinine clearance (Cockroft-Gault) > 60 mL/min at screening;
- potassium and magnesium within normal range;
- Grade = 1 uric acid;
- Thyroxin stimulating hormone (TSH) and free thyroxine (T4) within normal range, or hyperthyroid and adequately controlled with thyroid treatment, or TSH or free T4 abnormal but considered to be clinically insignificant as judged by the investigator.



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

Health Condition(s) or Problem(s) studied

Chronic hepatitis C infection
MedDRA version: 16.0 Level: LLT Classification code 10019752 Term: Hepatitis C virus (HCV) System Organ Class: 100000004848

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 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.

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.

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 of study drugs
- 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)

VX-950HPC3006

Source(s) of Monetary Support

Janssen-Cilag International NV