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

NCT02309450 | Withdrawn Phase 2 DMC

• 2 other identifiers: ANRSHC33QUATTROTURBO2014-002724-27
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hepatitis C Virus Genotype 4 Infection

Outcome Measures

Primary Outcomes (1)

• HCV sustained virological response rate

  The primary endpoint is the Sustained Virological Response Rate defined by an undetectable HCV RNA at W24, that is to say 12 weeks after the end of the DCV 3DAA therapy associating Asunaprevir, Daclatasvir and BMS - 791325 (SVR12). In case of premature total or partial interruption of HCV treatment, the primary endpoint will also be assessed at week 24.

  week 24

Secondary Outcomes (13)

• Number of patients with adverse events

  up to week 36

• Treatment interruptions

  from day 0 to week12

• Causes of treatment discontinuation

  form day 0 to week 12

• Self-reported symptoms

  Day 0, week 12, week 36

• Patients adherence rate

  week 4, week 12

Study Arms (1)

Asunaprevir, Daclatasvir and BMS - 791325

EXPERIMENTAL

Drug: .Asunaprevir, Daclatasvir and BMS - 791325

Interventions

.Asunaprevir, Daclatasvir and BMS - 791325 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.

Asunaprevir, Daclatasvir and BMS - 791325

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult ≥18 years
• 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
• 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.
• Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle)

You may not qualify if:

• 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
• 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.
• 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

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead
• Bristol-Myers Squibb: collaborator

Study Sites (1)

France

All the Regions of the Country, France

Location

MeSH Terms

Interventions

asunaprevir; daclatasvir

Study Officials

• Dominique Roulot, MD

  Hopital Avicenne, APHP

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 31, 2014
• First Posted: December 5, 2014
• Study Start: December 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: August 1, 2016
• Last Updated: February 2, 2016

Record last verified: 2016-02

Locations

FR (1)