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

NCT ID: NCT02309450

Last Updated: 2016-02-02

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-12-31
• Study Completion Date: 2016-08-31

Brief 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.

Detailed Description

The clinical trial is multi-centre, national, Phase 2, open-label, single-arm. The primary objective of this study is to assess, in HCV genotype 4-infected patients in failure to prior treatment with pegylated Interferon and Ribavirin bitherapy, the rate of sustained virological response (SVR) 12 weeks after 12 weeks of treatment with an all-oral combination of 3 DAAs in a Fixed-Dose-Combination (Asunaprevir 200 mg, Daclatasvir 30 mg and BMS - 791325 75 mg) twice a day.

Estimated enrollment is 60 patients during the enrolment period (9 months).

Schedule of assessments:

w4-w8 : screening D0 : Start of anti-HCV tritherapy (Asunaprevir + Daclatasvir + BMS-791325) w12: stop tritherapy w24: Sustained virological response SVR12 assessment (12 weeks post treatment) w36 : Sustained virological response SVR24 assessment (24 weeks post treatment)

Conditions

Hepatitis C Virus Genotype 4 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Asunaprevir, Daclatasvir and BMS - 791325

Group Type: EXPERIMENTAL

.Asunaprevir, Daclatasvir and BMS - 791325

Intervention Type: DRUG

All patients will receive an all-oral HCV tritherapy with Asunaprevir (200mg), Daclatasvir (30mg) and BMS-791325 (75mg) in a fixed-dose combination (FDC) tablet, twice a day (1 tablet in the morning and 1 tablet in the evening) for 12 weeks.

Interventions

.Asunaprevir, Daclatasvir and BMS - 791325

All patients will receive an all-oral HCV tritherapy with Asunaprevir (200mg), Daclatasvir (30mg) and BMS-791325 (75mg) in a fixed-dose combination (FDC) tablet, twice a day (1 tablet in the morning and 1 tablet in the evening) for 12 weeks.

Intervention Type: DRUG

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Bristol-Myers Squibb

INDUSTRY

Sponsor Role: collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dominique Roulot, MD

Role: PRINCIPAL_INVESTIGATOR

Hopital Avicenne, APHP

Locations

France

All the Regions of the Country, , France

Countries

France

Other Identifiers

2014-002724-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

ANRSHC33QUATTROTURBO

Identifier Type: -

Identifier Source: org_study_id