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

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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 BOCEPRETR

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 Summary: 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
Sponsor: French National Agency for Research on AIDS and Viral Hepatitis

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: From week 0 to week 144 ]
  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
• 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 ]
  Information on symptoms as perceived by the patients will be collected through self-administered questionnaires.
• Compliance rate. [ Time Frame: week 12, week 24, week 36, week 48, week 72 - after Liver transplant:Day 0 ]
  Treatment compliance will be assesses through a self-administered questionnaire reporting the number of medication doses prescribed and taken by the participants
• SVR prognosis factors [ Time Frame: Week-4 up week 144 ]
  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)
• 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) ]
  Quantitative assessment of HCV RNA during treatment will be performed at weeks 1, 4, 5, 6, 7, 8, 12, 16, 20, and 24 and correlated to SVR
• The percentage of virologic failure [ Time Frame: week 4 and week 48 ]
  Virological failure is defined as an increase of HCV RNA of at least 1 log IU/mL during treatment, or by the reappearance of positive viremia during treatment, after an initial negative result
• The percentage of relapse after transplantation [ Time Frame: Between week 16 and week 144 ]
  Virological relapse is characterized by an HCV RNA negative at the end of treatment but becoming detectable after cessation of therapy. The proportion of patients with virological relapse will be determined
• Boceprevir resistant mutations [ Time Frame: From week 5 to week 48 or after week 48 ]
  The proportion of patients with emergence of resistant mutations to boceprevir in case of detectable viral load during treatment (from W5) and after the discontinuation of treatment in the event of virologic failure will be assessed
• 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 ]

  Cirrhosis impairment will be assessed by studying:

  • the mean variation of MELD score between baseline and end of therapy
  • the proportion of patients with a MELD score increased by at least 3 points (in case of baseline MELD>15) or 5 points (in case of baseline MELD<15)
• 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
  
  

  Original Secondary Outcome: Same as current
  
  Information By: French National Institute for Health and Medical Research-French National Agency for Research on AID
  

  Dates:
  Date Received: October 14, 2011
  Date Started: January 6, 2012
  Date Completion:
  Last Updated: January 23, 2017
  Last Verified: January 2017