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 Hepatitis

Status and phase: Completed; Phase 2

Conditions: Liver Cirrhosis, Experimental; HCV Infection

Treatments: Drug: Ribavirin; Biological: Peg-Interferon α-2b or Peg-Interferon α-2a; Drug: Boceprevir

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01463956

2011- 001089 -17

Details and patient eligibility

About

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

Full 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

Enrollment: 58 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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58 participants in 1 patient group

Boceprevir, Pegylated interferon and Ribavirin

Experimental group

Description:

* 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)

Treatment:

Drug: Ribavirin

Biological: Peg-Interferon α-2b or Peg-Interferon α-2a

Drug: Boceprevir