Clinical Trial: Pilot Study to Assess the Efficacy of and Tolerance to a QUadruple Therapy to Treat HIV-HCV Coinfected Patients Previously Null Responders

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

Official Title: Pilot Study to Assess the Efficacy and Tolerance to a QUadruple Therapy With Asunaprevir , Daclatasvir, Ribavirin and Pegylated Interferon Alpha-2a, in HIV-HCV Genotype 1 or 4 Coinfected Patients Prev

Brief Summary:

Evaluation of efficacy and tolerance to a QUadruple therapy with Asunaprevir , Daclatasvir, Ribavirin and pegylated Interferon alpha-2a, in HIV-HCV genotype 1 or 4 coinfected patients previously null responders to a standard Pegylated Interferon -Ribavirin regimen.

The proportion of patients presenting cirrhosis (defined by a METAVIR F4 score on liver biopsy and/or with hepatic impulse elastometry ≥ 15 kPa) will be limited to 50% of all of the patients included


Detailed Summary:

The clinical trial is multi-center, national, Phase 2, open-label, single-arm.

Primary objective is to estimate the Sustained Virological Response rate (SVR) 12 weeks after 24 weeks of treatment with quadruple therapy combining Asunaprevir, Daclatasvir, Ribavirin and Pegylated Interferon alpha-2a in HIV-HCV genotype 1 or 4 coinfected patients previously null responders to a Pegylated Interferon -Ribavirin standard regimen.

Estimated enrolment is 65 patients during the enrolment period (9 months). The first 12 patients included will be on Raltegravir, Emtricitabine and Tenofovir and will participate to the pharmacological sub-study.

Schedule of assessments:

Evaluation of inclusion criteria: 4 to 8 weeks Anti-HCV treatment: 28 weeks (or shorter according to futility rules) Follow up: 24 weeks following the end of the treatment


Sponsor: French National Institute for Health and Medical Research-French National Agency for Research on AID

Current Primary Outcome: HCV Sustained virological response rate [ Time Frame: wk40 ]

the undetectable HCV RNA at wk40 (ie 12 weeks after the end of the quadritherapy associating Asunaprevir, Daclatasvir, Pegylated interferon alpha-2a and Ribavirin in case of premature total or partial discontinuation of HCV treatment, the principal endpoint will also be assessed at wk40)


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: during throughout all the study ]
    • Clinical and biological Adverse Events
    • Treatment premature discontinuations
    • Perceived symptoms (ANRS AC24 Symptom Perception Scale)
    • Adherence (ANRS observance scale and effective dispensation by the pharmacy)
  • Kinetics of HCV Virological response [ Time Frame: wk4, wk5, wk6, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk40 and wk52 ]
    Measurements of HCV RNA at wk4, wk5, wk6, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk40 and wk52 (ie 24 weeks after the end of the treatment), globally or according to the HCV genotype (1 or 4) and sub-type (1a or 1b, 4a or 4c/d)
  • Immunological and virological evolution of HIV infection [ Time Frame: wk0, wk4, wk8, wk12,wk16, wk24, wk28, wk40 et wk52 ]
    • HIV RNA levels
    • CD4 and CD8
  • Evolution of cirrhosis (for cirrhotic patients) [ Time Frame: wk12, wk28, wk40 and wk52 ]
    • Child-Pugh and MELD scores
    • end stage liver disease onset
    • hepatocarcinoma onset
  • Number of Participants with HIV and non HIV related clinical events [ Time Frame: through the study ]
    • AIDS classifying clinical events
    • Severe non-AIDS clinical events.
  • Minimum Plasma Concentration (Cmin) of ribavirin [ Time Frame: wk4 and wk8 ]
  • Pharmacokinetics of Antiretroviral drugs [ Time Frame: wk0 and wk8 ]
    • sub-group study ((focusing on patients on Raltegravir, Emtricitabine and Tenofovir)
    • plasma drugs concentrations from H0 to H10
    • Cmin (Minimum Plasma Concentration), Cmax (Maximum Plasma Concentration) and AUC (Area Under the Plasma Concentration)
  • Pharmacokinetics of Asunaprevir and Daclatasvir [ Time Frame: wk8 ]
    • sub-group study (focusing on patients on Raltegravir, Emtricitabine, Tenofovir)
    • plasma Asunaprevir and Daclatasvir concentrations from H0 to H10
    • Cmin, Cmax and AUC


Original Secondary Outcome:

  • Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: during throughout all the study ]
    • Clinical and biological Adverse Events
    • Treatment premature discontinuations
    • Perceived symptoms (ANRS AC24 Symptom Perception Scale)
    • Adherence (ANRS observance scale and effective dispensation by the pharmacy)
  • Kinetics of HCV Virological response [ Time Frame: wk4, wk5, wk6, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk40 and wk52 ]
    Measurements of HCV RNA at wk4, wk5, wk6, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk40 and wk52 (ie 24 weeks after the end of the treatment), globally or according to the HCV genotype (1 or 4) and sub-type (1a or 1b, 4a or 4c/d)
  • Immunological and virological evolution of HIV infection [ Time Frame: wk0, wk4, wk8, wk12,wk16, wk24, wk28, wk40 et wk52 ]
    • HIV RNA levels
    • CD4 and CD8
  • Evolution of cirrhosis (for cirrhotic patients) [ Time Frame: wk12, wk28, wk40 and wk52 ]
    • Child-Pugh and MELD scores
    • end stage liver disease onset
    • hepatocarcinoma onset
  • Number of Participants with HIV and non HIV related clinical events [ Time Frame: wk0, wk4, wk8, wk12,wk16, wk24, wk28, wk40 and wk52 ]
    • AIDS classifying clinical events
    • Severe non-AIDS clinical events.
  • Minimum Plasma Concentration (Cmin) of ribavirin [ Time Frame: wk4 and wk8 ]
  • Pharmacokinetics of Antiretroviral drugs [ Time Frame: wk0 and wk8 ]
    • sub-group study ((focusing on patients on Raltegravir, Emtricitabine and Tenofovir)
    • plasma drugs concentrations from H0 to H10
    • Cmin (Minimum Plasma Concentration), Cmax (Maximum Plasma Concentration) and AUC (Area Under the Plasma Concentration)
  • Pharmacokinetics of Asunaprevir and Daclatasvir [ Time Frame: wk8 ]
    • sub-group study (focusing on patients on Raltegravir, Emtricitabine, Tenofovir)
    • plasma Asunaprevir and Daclatasvir concentrations from H0 to H10
    • Cmin, Cmax and AUC


Information By: French National Institute for Health and Medical Research-French National Agency for Research on AID

Dates:
Date Received: October 22, 2012
Date Started: December 2012
Date Completion:
Last Updated: September 5, 2014
Last Verified: March 2014