Therapy With Asunaprevir, Daclatasvir, Ribavirin and Pegylated Interferon Alpha-2a in HCV Genotype 4-infected Patients Who Have Failed to a Previous Therapy With Peg-Interferon/Ribavirin (ANRS HC32 QUATTRO)
Pilot Study to Assess Efficacy and Safety of a Quadruple Therapy With Asunaprevir, Daclatasvir, Ribavirin and Pegylated Interferon Alpha-2a in HCV Genotype 4-infected Patients Non-responders to Pegylated Interferon-Ribavirin Regimen
2 other identifiers
interventional
60
1 country
25
Brief Summary
Success rates, after retreatment with Peg-Interferon/Ribavirin bitherapy, in patients infected with HCV (hepatitis C virus) genotype 4 and non-responders to a first standard treatment, are disappointing. The association of Asunaprevir and Daclatasvir in combination with the standard-of-care bitherapy has been shown to increase the efficacy of the treatment in non-responders genotype 1-infected patients. Given the absence of current solutions and urgent therapeutic needs for HCV genotype 4-infected patients previously treated with pegylated Interferon/Ribavirin, this pilot study aims to evaluate the efficacy and safety of a quadritherapy associating Asunaprevir, Daclatasvir, pegylated Interferon alpha-2a and Ribavirin, in this very difficult to treat population. 60 subjects will be enrolled. The primary endpoint will be the rate of sustained virological response (SVR), defined by an undetectable HCV RNA, at Week 36 (12 weeks after the end of a 24 weeks quadritherapy).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Nov 2013
Shorter than P25 for phase_2
25 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
November 1, 2013
CompletedFirst Submitted
Initial submission to the registry
March 31, 2014
CompletedFirst Posted
Study publicly available on registry
April 8, 2014
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2015
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2015
CompletedApril 13, 2026
January 1, 2017
1.3 years
March 31, 2014
April 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
SVR12 Rate
HCV RNA measured 12 weeks after the end of the HCV treatment (Week 36)
Week 36
Secondary Outcomes (14)
Number of patients with adverse events
Up to Week 48
Treatment discontinuations
Up to Week 24
Self-reported symptoms
Day 0, Week 12, Week 36
Patients' adherence
Week 4, Week 12, Week 24
SVR 24 rate
Week 48
- +9 more secondary outcomes
Study Arms (1)
Asunaprevir, Daclatasvir, Ribavirin, Peg-Interferon alpha-2a
EXPERIMENTALQuadritherapy from Day 0 to Week 24
Interventions
Asunaprevir 100 mg, 1 capsule twice a day from Day 0 to Week 24
Daclatasvir 60 mg, 1 tablet once a day from Day 0 to Week 24
Ribavirin tablets or capsules 200 mg, weight-based daily dose ( \<75 kg : 1000 mg ; ≥ 75 kg : 1200 mg), from Day 0 to Week 24
Pegylated Interferon alpha-2a, by subcutaneous injection 180µg / week, from Day 0 to Week 24
Eligibility Criteria
You may qualify if:
- Adult ≥18 years
- Non-responders to a prior treatment with pegylated Interferon and Ribavirin, with non-response being defined as follows:
- Null-response: reduction of less than 2 log10 IU/ml of HCV viral load between D0 of the treatment and week 12
- Partial response: reduction of at least 2 log10 IU/ml of HCV viral load between D0 of the treatment and week 12 but detectable HCV RNA at week 12 and week 24 and without an undetectable viral load by 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, and/or
- good quality (length ≥ 15 mm and ≥ 6 portal spaces) liver puncture biopsy from less than 18 months to establish the METAVIR, and/or
- hepatic impulse elastometry (Fibroscan®) from less than 6 months and of good quality (at least 10 measurements on an incidence with an IQR of less than 30% of the mean elastometry measured and a success rate of 60%)
- Body weight ≥ 40 kg and ≤125 kg
- Men and women of child-bearing age and their heterosexual partners must use two adequate contraceptions from 1 month before initiation of treatment up to 7 months after the end of treatment for men and up to 4 months after treatment for women.
- Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle)
You may not qualify if:
- CHILD B or C cirrhosis or a history of decompensated cirrhosis. If Child A cirrhosis, presence of varices presenting an hemorrhagic risk (grade II with red spots or grade III) on a fibroscopy dating from less than 3 years
- Previous HCV therapy including HCV NS3 protease inhibitor, and/or HCV NS5A replication complex inhibitor and/or HCV NS5B polymerase inhibitor
- Positive HBs Antigen
- Confirmed HIV-1 or HIV-2 infection
- Pregnant or breast-feeding women
- Severe heart or lung disease
- Transplant recipient
- Uncontrolled dysthyroidism
- Uncontrolled diabetes
- Consumption of alcohol which, in the opinion of the investigator, will be an obstacle to participation of the patient and to his remaining in the study
- Drug addiction which, in the the investigator's opinion, will be an obstacle to the patient's participation and to his or her remaining in the study. Patients included in a programme of substitution with methadone or buprenorphine could be included. The opinion of a consultant in addictology is recommended for patients presenting with current drug use or drug use in the past year.
- Patient under guardianship, trusteeship or judicial protection
- Hb \< 110 g/L
- Platelets \< 80 000/mm3
- Polynuclear neutrophils \< 1000 /mm3 (for European patients) and \< 750 /mm3 (for African patients)
- +11 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- ANRS, Emerging Infectious Diseaseslead
- Bristol-Myers Squibbcollaborator
Study Sites (25)
Hôpital AVICENNE
Bobigny, 93009, France
Hôpital Jean Verdier
Bondy, 93140, France
Hôpital de Haut Lévêque
Bordeaux Pessac, 33601, France
Hôpital Beaujon
Clichy, 92110, France
Centre Hospitalier Intercommunal
Créteil, 94010, France
Hôpital Henri Mondor
Créteil, 94010, France
Hôpital Albert Michallon
Grenoble, 38043, France
Hôpital Claude Huriez
Lille, 59037, France
Hôpital Dupuytren
Limoges, 87042, France
Hôpital de la Croix Rousse
Lyon, 69317, France
Fondation Hôpital Saint Joseph
Marseille, 13285, France
Hôpital Saint Eloi
Montpellier, 34295, France
Hôpital de Brabois
Nancy, 54511, France
Hôpital de l'Hôtel Dieu
Nantes, 44093, France
Hôpital de l'Archet
Nice, 06202, France
Hôpital de La Source
Orléans, France
Hôpital Saint Antoine
Paris, 75571, France
Hôpital Pitié Salpêtrière
Paris, 75651, France
Hôpital Cochin
Paris, 75679, France
Hôpital Tenon
Paris, 75970, France
Hôpital Pontchaillou
Rennes, 35000, France
Hôpital Charles Nicolle
Rouen, 76031, France
Institut Arnault Tzank
Saint-Laurent-du-Var, 06721, France
Hôpital Purpan
Toulouse, 31059, France
Hôpital Paul Brousse
Villejuif, 94804, France
Related Publications (1)
Roulot D, Thibault V, Laforest C, Fontaine H, Bronowicki JP, Asselah T, Bourliere M, Canva V, Leroy V, Loustaud-Ratti V, Ouzan D, Zoulim F, Schischmanoff O, Rousseau C, Renault A, Petrov-Sanchez V, Diallo A, Bellissant E, Serfaty L; ANRS HC32 QUATTRO study group. Efficacy of daclatasvir-based quadruple therapy in nonresponder patients infected by hepatitis C virus genotype 4: the ANRS HC32 QUATTRO study. Eur J Gastroenterol Hepatol. 2018 Mar;30(3):302-309. doi: 10.1097/MEG.0000000000001035.
PMID: 29271782RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Dominique ROULOT, MD, PhD
Bobigny University Hospital
- STUDY CHAIR
Eric BELLISSANT, MD, PhD
Rennes University Hospital
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
March 31, 2014
First Posted
April 8, 2014
Study Start
November 1, 2013
Primary Completion
February 1, 2015
Study Completion
April 1, 2015
Last Updated
April 13, 2026
Record last verified: 2017-01