Overview

This trial is active, not recruiting.

Conditions hcv infection, liver cirrhosis, experimental
Treatments boceprevir, peg-interferon α-2b or peg-interferon α-2a, ribavirin
Phase phase 2
Sponsor French National Agency for Research on AIDS and Viral Hepatitis
Collaborator Merck Sharp & Dohme Corp.
Start date January 2012
End date June 2014
Trial size 58 participants
Trial identifier NCT01463956, 2011- 001089 -17

Summary

Evaluation of efficacy of triple therapy with pegylated interferon, ribavirin, and boceprevir in patients with genotype 1 chronic hepatitis C, who are treatment-naive, have relapsed, or are non-responders with cirrhosis and awaiting liver transplantation, with a MELD score less than or equal to 18

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
Lead-in phase (4 week): Pegylated interferon + Ribavirin Triple therapy regimen for 44 weeks :Boceprevir + Pegylated interferon + Ribavirin Pegylated interferon + Ribavirin therapy until transplantation (less or equal to 24 weeks)
boceprevir
Boceprevir 200 mg capsules at 2400mg/day (800mg 3 times a day) from week 4 until week 48 or until liver transplant (can be performed from week 16)
peg-interferon α-2b or peg-interferon α-2a PegIntron
Peg-Interferon α-2b by subcutaneous injection, 1.5µg/kg/week, from day 0 until week 48 or until liver transplantation, or Peg-Interferon α-2a by subcutaneous injection, 180 µg, once weekly, from day 0 until week 48 or until liver transplantation
ribavirin
Ribavirin: capsules 200 mg (weight-based daily dose: <65kg, 800 mg; 65-80kg, 1000mg; 81-105kg: 1200mg; >105kg: 1400mg), from day 0 until week 48 or until liver transplantation or, Ribavirin: Tablet Oral, weight-based dose, 1000 mg for subjects weighing below 75 kg or 1200 mg for subjects weighing equal or over75 kg, once daily, from day 0 until week 48 or until liver transplantation

Primary Outcomes

Measure
Sustained Virologic Response (SVR) Rate
time frame: Week 24 after the discontinuation of antiviral C treatment and at the time of liver transplantation or at the time of liver transplantation

Secondary Outcomes

Measure
Number of participants with adverse events as a measure of safety and tolerability
time frame: From week 0 to week 144
Perceived symptoms
time frame: at day 0, week 24, week 48 and every 24 week up liver transplant - post liver transplant: day 0, week 24 and week 48
Compliance rate.
time frame: week 12, week 24, week 36, week 48, week 72 - after Liver transplant:Day 0
SVR prognosis factors
time frame: Week-4 up week 144
The predictive value of on-treatment HCV RNA on SVR
time frame: During weeks 1, 4, 5, 6, 7, 8, 12, 16, 20, and 24 (before transplantation)
The percentage of virologic failure
time frame: week 4 and week 48
The percentage of relapse after transplantation
time frame: Between week 16 and week 144
Boceprevir resistant mutations
time frame: From week 5 to week 48 or after week 48
Resistant mutations in plasma and liver samples (both explanted liver and graft)
time frame: Week 16 up to week 96
Sepsis according to Systemic Inflammatory Response System (SIRS) Criteria
time frame: From day 0 to week 72
Cirrhosis impairment
time frame: From day 0 to week 72
Survival after transplantation
time frame: Week 16 up to week 96
Survival rate within one year after liver transplantation
time frame: week 64 up to week 144
The mean time elapsed between registration on the transplantation list and the date of transplantation
time frame: Week16 up to week 96
Measurement of the residual plasma concentration (Cres) of ribavirin
time frame: at Week 4 and Week 8
Area Under the Plasma Concentration Time Curve (AUC) From 0-8h of Boceprevir
time frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
Maximum Plasma Concentration (Cmax) of Boceprevir
time frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
Time of Maximum Plasma Concentration (Tmax) of Boceprevir
time frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
Minimum Plasma Concentration (Cmin) of Boceprevir
time frame: At week 16 and at week 24 and if the MELD score has changed by more than three points
Correlation study between the presence of an elevated level of IP-10 during triple therapy and the absence of sustained virologic response
time frame: From week 4 to week 48
Histological severity of HCV recurrence after liver transplantation
time frame: At week 20 up to week 100, at week 40 up to week 120, at week 64 up to week 144
Insulin Resistance (HOMA-IR)
time frame: At baseline, week 48 and at the last follow-up visit
Virological Response in participants with and without Insulin Resistance
time frame: At week 4, 8, 16, 28 and 48 during therapy
Relationship between the presence of a polymorphism in the IL28B gene (donor and recipient) and SVR
time frame: After week 144
Relationship between the presence of a polymorphism to the ITPA gene and the onset of hemolytic anemia
time frame: After week 144

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria: - Adult 18 years and older - Chronic infection with hepatitis C virus proven with positive PCR for more than 6 months - Viral genotype 1 - Cirrhosis while awaiting liver transplantation - MELD score < or equal to 18 - With or without hepatocellular carcinoma - Naive to antiviral C treatment - Failure on a previous treatment. Failure is defined as the persistence of detectable HCV RNA. The previous HCV failure treatment profile must be able to be documented according to the following terminology:- Relapsing patient: HCV RNA undetectable at the end of treatment, becoming detectable again after the discontinuation of treatment- Breakthrough: increase of viremia of 1 log or more during the treatment - Non-responding patient with partial response: HCV RNA detectable at W24 without ever having been undetectable and with a decrease in HCV RNA ≥ 2 log at W12 - Non-responding patient with nul response: decrease in HCV RNA < 2 log at W12 - No need for prior treatment wash-out - Negative pregnancy test in women of child-bearing age - Double method of contraception in men and women of child-bearing age during the entire duration of treatment and the 6 months following its discontinuation - Free, informed, and written consent (signed on the day of pre-enrollment at the latest and before all exams required by the study) - Person enrolled in or a beneficiary of a social security/Universal Health Insurance Coverage - Inclusion approved by the Decision Support Committee Exclusion Criteria: - Previous HCV treatment with boceprevir or telaprevir - Alcohol consumption > 40 g/day - Toxicomania constituting a barrier for starting therapy according to the opinion of the investigator. Patients included in a methadone or buprenorphine replacement program may be enrolled - MELD > 18 - Non controlled sepsis - Platelets < 50,000/mm3 - Neutrophil granulocyte levels < 1000/mm3 - Creatinine clearance < 50 mL/min (MDRD) - Hb < 10 g/dL - Uncontrolled psychiatric problems - Contraindications to boceprevir - Contraindication to interferon or ribavirin - Subject with major complications of cirrhosis - HIV coinfection - HBV coinfection (unless this is treated effectively with analogues, as proven by undetectable viremia for at least 12 months) - Other infectious disease underway - Neoplastic disease other than hepatocellular carcinoma during the previous year, or neoplastic disease for which the prognosis is less than 3 years - Treatment with immunosuppressors (including corticosteroids), antivirals other than those for the study, except aciclovir - Consumption of St. John's wort - Associated treatments including a molecule or substance that could interfere with the pharmacokinetic characteristics of boceprevir - History of a lactose allergy - Person participating in another study including an exclusion period that is still underway during pre-enrollment - So-called vulnerable populations (minors, people under guardianship or protection, or a private individual under protection from making legal or administrative decisions) - Pregnancy, breast-feeding

Additional Information

Official title Pilot Study on the Efficacy of Pegylated Interferon-Ribavirin-Boceprevir Triple Therapy in Patients Infected With Genotype 1 HCV With Cirrhosis and Awaiting Liver Transplantation (ANRS HC 29 BOCEPRETRANSPLANT)
Principal investigator Didier Samuel, Pr
Description Evaluation of sustained virological response defined as the proportion of patients with undetectable hepatitis C virus RNA 24 weeks after discontinuation of therapy and/or after liver transplantation in patients with genotype 1, who are treatment-naive, have relapsed, or are non-responders with cirrhosis and awaiting liver transplantation, with a MELD score less than or equal to 18
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS).