Overview
Pilot Study to Assess Efficacy and Safety of a Triple Therapy With Asunaprevir, Daclatasvir, and BMS-791325 in HCV Genotype 4-infected Patients After Failure of Pegylated Interferon-Ribavirin Regimen
Status:
Withdrawn
Withdrawn
Trial end date:
2016-08-01
2016-08-01
Target enrollment:
0
0
Participant gender:
All
All
Summary
ANRS HC 33 is a pilot study to assess efficacy and safety of a DCV 3DAA therapy with Asunaprevir, Daclatasvir and BMS-791325 in HCV genotype 4-infected patients after failure of pegylated Interferon-Ribavirin regimen. Proportion of patients with cirrhosis will be limited to 50% of all patients included, cirrhosis being defined as a METAVIR score of F4 on the liver biopsy or an hepatic impulse elastometry ≥ 14 kPa or a Fibrotest® result > 0,75.Phase:
Phase 2Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
ANRS, Emerging Infectious DiseasesFrench National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Collaborator:
Bristol-Myers SquibbTreatments:
AsunaprevirInterferons
Ribavirin
Criteria
Inclusion Criteria:- Adult ≥18 years
- Infection with HCV genotype 4, confirmed by detectable HCV RNA ≥ 1000 IU/ml at
pre-inclusion
- Failure to a prior treatment with pegylated Interferon and Ribavirin, with failure
being defined as follows:
- Non-response: HCV viral load remaining detectable during and at the end of P/R
treatment.
- Relapse: undetectable HCV viral load during P/R treatment and detectable after
the end of the treatment.
- HCV breakthrough: undetectable HCV viral load during P/R treatment becoming
detectable before the end of treatment.
- Anti-HCV treatment discontinued for at least the last 3 months
- Fibrosis at any stage, with documentation of the presence or absence of cirrhosis at
the pre-inclusion visit:
- history of liver biopsy showing cirrhosis lesions (METAVIR F4), at any time in
the patient's history, or
- good quality (length ≥ 1 cm and ≥ 5 portal spaces) liver biopsy dating from less
than 18 months to establish the METAVIR, or
- hepatic impulse elastometry (Fibroscan®) dating from less than 6 months and of
good quality (at least 10 measurements on an incidence with IQR of less than 30%
of the median elastometry measured and a success rate of 60%) or
- interpretable Fibrotest® dating from less than 6 months The proportion of
patients with cirrhosis will be limited to 50% of all patients included,
cirrhosis being defined as a METAVIR score of F4 on the liver biopsy or an
hepatic impulse elastometry ≥ 14 kPa or a Fibrotest® result > 0,75.
- Men and women of a child-bearing age and their heterosexual partners must use adequate
contraception during treatment and up to 8 weeks after the end of treatment for women,
12 weeks after the end of treatment for men.
- Written informed consent signed by the patient and the investigator (on the day of the
pre-inclusion at the latest and before any examination required by the study) (article
L1122-1-1 Public Health Code)
- Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle)
Exclusion Criteria:
Medical history
- CHILD B or C cirrhosis
- Previous HCV therapy including HCV NS3 protease inhibitor, and/or HCV NS5A replication
complex inhibitor and/or HCV NS5B polymerase inhibitor
Current condition
- Positive HBs Antigen
- Confirmed HIV-1 or HIV-2 infection
- Pregnant or breast-feeding women
- Transplant recipients
- Any evolutive ongoing malignant disease, including hepatocellular carcinoma, which
will be specifically screened for before inclusion
- Consumption of alcohol which, in the investigator's opinion, will be an obstacle to
the patient's participation and to his/her remaining in the study
- Drug addiction which, in the investigator's opinion, will be an obstacle to the
patient's participation and to his/her remaining in the study. Patients included in a
programme of substitution with methadone or buprenorphine could be included. The
opinion of an addictology consultant is recommended for patients presenting with
current drug use or drug use in the past year.
- Patients taking part in another clinical trial during the 30 days prior to inclusion
- Patient under guardianship, trusteeship or judicial protection
Biological criteria
- ALT ≥ 5xULN
- Total bilirubin ≥ 34 µmol/L, unless a documented history of Gilbert's disease
- Hb < 85 g/L
- Platelets < 50 000/mm3
- Kidney failure defined by creatinine clearance < 50mL/mn (MDRD formula)
- QTc > 440 msec for males or 460 msec for females