Efficacy of PegInterferon-Ribavirin-Boceprevir Therapy in Patients Infected With G1 HCV With Cirrhosis, Awaiting Liver Transplantation

French National Agency for Research on AIDS and Viral Hepatitis58 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

HCV Infection Liver Cirrhosis, Experimental

Interventions

BoceprevirDRUG

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-2aBIOLOGICAL

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

RibavirinDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (19)

Haut-Lévêque Hospital

Bordeaux, France

Beaujon Hospital

Clichy, France

Outcomes

Primary Outcomes

Sustained Virologic Response (SVR) Rate

Evaluation of sustained virologic response to antiviral C treatment depends of time of liver transplantation that can be performed between week 16 and week 96 of the trial: * If the liver transplant is realized after the discontinuation of antiviral C treatment,sustained virologic response should be evaluated 6 months after the discontinuation of antiviral C treatment and at the time of liver transplantation. * If the liver transplant is realized before the discontinuation of antiviral C treatment,sustained virologic response should be evaluated at the time of liver transplantation.

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

Number of participants with adverse events as a measure of safety and tolerability

Information on adverse events will be collected by the investigator during medical visits and reported in the CRF. Adverse events will be classified as: a) Flu-like symptoms b) Musculoskeletal symptoms c) Neurologic symptoms d) Psychiatric symptoms e) Constitutional symptoms

Time frame: From week 0 to week 144

Perceived symptoms

Information on symptoms as perceived by the patients will be collected through self-administered questionnaires.

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.

Treatment compliance will be assesses through a self-administered questionnaire reporting the number of medication doses prescribed and taken by the participants

Time frame: week 12, week 24, week 36, week 48, week 72 - after Liver transplant:Day 0

SVR prognosis factors

Participants with undetectable plasma HCV-RNA 24 weeks after treatment cessation and/or liver transplantation will be considered as SVR. Factors potentially associated with SVR will be studied through a logistic regression analysis. These factors include demographical (age, gender), virological (baseline viral load), clinical (disease severity measured by MELD score) and genetic factors (IL28B polymorphism: TT, CT, or CC)

Data from ClinicalTrials.gov

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