Clinical trial NCT01463956: Efficacy of PegInterferon-Ribavirin-Boceprevir Therapy in Patients Infected With G1 HCV With Cirrhosis, Awaiting Liver Transplantation
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HCV Infection
Liver Cirrhosis, Experimental
Keywords: Boceprevir
HCV infection
Antiviral therapy
Liver transplantation
Lead sponsor: ANRS, Emerging Infectious Diseases
Sponsor class: OTHER_GOV
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-11-02
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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

Detailed 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

Eligibility criteria: 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

Primary outcomes:
measure: Sustained Virologic Response (SVR) Rate
timeFrame: 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
timeFrame: From week 0 to week 144
measure: Perceived symptoms
timeFrame: at day 0, week 24, week 48 and every 24 week up liver transplant - post liver transplant: day 0, week 24 and week 48
measure: Compliance rate.
timeFrame: week 12, week 24, week 36, week 48, week 72 - after Liver transplant:Day 0
measure: SVR prognosis factors
timeFrame: Week-4 up week 144
measure: The predictive value of on-treatment HCV RNA on SVR
timeFrame: During weeks 1, 4, 5, 6, 7, 8, 12, 16, 20, and 24 (before transplantation)
measure: The percentage of virologic failure
timeFrame: week 4 and week 48
measure: The percentage of relapse after transplantation
timeFrame: Between week 16 and week 144
measure: Boceprevir resistant mutations
timeFrame: From week 5 to week 48 or after week 48
measure: Resistant mutations in plasma and liver samples (both explanted liver and graft)
timeFrame: Week 16 up to week 96
measure: Sepsis according to Systemic Inflammatory Response System (SIRS) Criteria
timeFrame: From day 0 to week 72
measure: Cirrhosis impairment
timeFrame: From day 0 to week 72
measure: Survival after transplantation
timeFrame: Week 16 up to week 96
measure: Survival rate within one year after liver transplantation
timeFrame: week 64 up to week 144
measure: The mean time elapsed between registration on the transplantation list and the date of transplantation
timeFrame: Week16 up to week 96
measure: Measurement of the residual plasma concentration (Cres) of ribavirin
timeFrame: at Week 4 and Week 8
measure: Area Under the Plasma Concentration Time Curve (AUC) From 0-8h of Boceprevir
timeFrame: At week 16 and at week 24 and if the MELD score has changed by more than three points
measure: Maximum Plasma Concentration (Cmax) of Boceprevir
timeFrame: At week 16 and at week 24 and if the MELD score has changed by more than three points
measure: Time of Maximum Plasma Concentration (Tmax) of Boceprevir
timeFrame: At week 16 and at week 24 and if the MELD score has changed by more than three points
measure: Minimum Plasma Concentration (Cmin) of Boceprevir
timeFrame: At week 16 and at week 24 and if the MELD score has changed by more than three points
measure: Correlation study between the presence of an elevated level of IP-10 during triple therapy and the absence of sustained virologic response
timeFrame: From week 4 to week 48
measure: Histological severity of HCV recurrence after liver transplantation
timeFrame: At week 20 up to week 100, at week 40 up to week 120, at week 64 up to week 144
measure: Insulin Resistance (HOMA-IR)
timeFrame: At baseline, week 48 and at the last follow-up visit
measure: Virological Response in participants with and without Insulin Resistance
timeFrame: At week 4, 8, 16, 28 and 48 during therapy
measure: Relationship between the presence of a polymorphism in the IL28B gene (donor and recipient) and SVR
timeFrame: After week 144
measure: Relationship between the presence of a polymorphism to the ITPA gene and the onset of hemolytic anemia
timeFrame: After week 144
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: Haut-Lévêque Hospital
city: Clichy
country: France
facility: Beaujon Hospital
city: Creteil
country: France
facility: Henri Mondor Hospital
city: Grenoble
country: France
facility: A Michallon Hospital
city: Lille
country: France
facility: Claude Huriez hospital
city: Lyon
country: France
facility: La Croix-Rousse
city: Marseille
country: France
facility: La Conception Hospital
city: Montpellier
country: France
facility: Saint-Eloi Hospital
city: Nice
country: France
facility: Archet Hospital
city: Paris
country: France
facility: La Pitié Salpétrière Hospital
city: Paris
country: France
facility: Cochin Hospital
city: Paris
country: France
facility: Staint Antoine Hospital
city: Rennes
country: France
facility: Pontchaillou Hospital
city: Strasbourg
country: France
facility: Civil Hospital
city: Toulouse
country: France
facility: Purpan Hospital Médecine interne
city: Toulouse
country: France
facility: Purpan Hospital
city: Tours
country: France
facility: Trousseau Hospital
city: Vandoeuvre Les Nancy
country: France
facility: Nancy Hospital
city: Villejuif
country: France
facility: Paul Brousse Hospital
Study officials:
affiliation: Hepatobiliary Center of Paul Brousse Hospital. France
name: Didier Samuel, Pr
role: PRINCIPAL_INVESTIGATOR
References: