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Hepatitis C Virus Genotype 4 InfectionPhase 2NCT02107365

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)

A Phase 2 study testing Asunaprevir, Daclatasvir and Ribavirin in people with Hepatitis C Virus Genotype 4 Infection, run by ANRS, Emerging Infectious Diseases at 25 sites in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Hepatitis C Virus Genotype 4 Infection
What is being tested?
Asunaprevir, Daclatasvir and Ribavirin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
25 sitesFrance
Study dates
Nov 2013to Apr 2015
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult ≥18 years
  • Infection with HCV genotype 4, confirmed by detectable HCV RNA ≥ 1000 IU/ml at pre-inclusion
  • 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
Show all 14Show fewer
  • 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, 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.
  • Written informed consents (2) 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)
  • Patients with Health insurance (Sécurité Sociale or Couverture Médicale Universelle)

Who cannot join

  • 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
Show all 28Show fewer
  • Transplant recipient
  • Uncontrolled dysthyroidism
  • Uncontrolled diabetes
  • Any evolutive ongoing malignant disease, including hepatocellular carcinoma, which will be specifically screened for before inclusion
  • 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.
  • Patients taking part in another clinical trial during the 30 days preceding inclusion.
  • 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)
  • Kidney failure defined by creatinine clearance < 50mL/mn (MDRD formula)
  • Contra-indication for treatment with Ribavirin including a history of hypersensitivity to Ribavirin or to one of the excipients
  • Contra-indication for treatment with Daclatasvir or Asunaprevir including a history of hypersensitivity to one of the excipients
  • Contra-indication to treatment with Interferon including psychiatric contra-indications. A psychiatrist's opinion is compulsory in the following situations :
  • history of psychiatric disorders requiring hospitalisation of the patient or a consultation with a specialist
  • treatment with mood stabilizers or antipsychotics during the previous year
  • history of psychiatric disorders during prior treatment with Interferon alpha
  • evidence of depression episodes, a risk of suicide, bipolar disorder and/or current behavioral disorders. These patients can only be included after a psychiatric evaluation that specifically authorizes the use of Interferon.
  • History of previous HCV treatment premature cessation (in the first 6 months) for toxicity. Premature cessation for anemia or neutropenia will be authorized in the absence of the use of erythropoietin or polynuclear neutrophil growth factor, respectively.
  • Patients with a non-compliance history, who will be at risk of not complying with the study follow-up timetable
  • Associated treatment likely to interfere with the study drugs

Trial locations and contacts

25 sites in 1 country.

25 sites in 1 country

France25 sites

  • Hôpital AVICENNE

    Bobigny, 93009

  • Hôpital Jean Verdier

    Bondy, 93140

  • Hôpital de Haut Lévêque

    Bordeaux Pessac, 33601

  • Hôpital Beaujon

    Clichy, 92110

  • Centre Hospitalier Intercommunal

    Créteil, 94010

  • Hôpital Henri Mondor

    Créteil, 94010

  • Hôpital Albert Michallon

    Grenoble, 38043

  • Hôpital Claude Huriez

    Lille, 59037

  • Hôpital Dupuytren

    Limoges, 87042

  • Hôpital de la Croix Rousse

    Lyon, 69317

  • Fondation Hôpital Saint Joseph

    Marseille, 13285

  • Hôpital Saint Eloi

    Montpellier, 34295

  • Hôpital de Brabois

    Nancy, 54511

  • Hôpital de l'Hôtel Dieu

    Nantes, 44093

  • Hôpital de l'Archet

    Nice, 06202

  • Hôpital de La Source

    Orléans

  • Hôpital Saint Antoine

    Paris, 75571

  • Hôpital Pitié Salpêtrière

    Paris, 75651

  • Hôpital Cochin

    Paris, 75679

  • Hôpital Tenon

    Paris, 75970

  • Hôpital Pontchaillou

    Rennes, 35000

  • Hôpital Charles Nicolle

    Rouen, 76031

  • Institut Arnault Tzank

    Saint-Laurent-du-Var, 06721

  • Hôpital Purpan

    Toulouse, 31059

  • Hôpital Paul Brousse

    Villejuif, 94804

Other trials in France

About this study

Official title: 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

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.

Read more

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).

Read the detailed description

The population studied presents the maximum of factors of non-response to the retreatment of hepatitis C: non-response to well followed prior treatment with pegylated Interferon and Ribavirin, infection with HCV genotype 4, and the presence of cirrhosis (in less than 50% of the included patients) that could diminish the chances of SVR to a standard bitherapy.

The likelihood of SVR with standard bitherapy in this study population is thus considered low, around 15%.

The principal objective of this multicentric, national, single-arm, open-labeled, non-randomized phase II pilot study in 60 patients, is to assess the rate of SVR 12 weeks after 24 weeks of quadritherapy and to determine whether this rate is significantly greater than 20%.

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

Being tested
Asunaprevir, Daclatasvir, Ribavirin, Pegylated Interferon alpha-2a
Keywords
Hepatitis C, HCV infection, HCV genotype 4, Non-responders HCV infected patients, Asunaprevir, Daclatasvir, Pegylated Interferon, Ribavirin
Medical subject headings
Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AsunaprevirDrug

    Asunaprevir 100 mg, 1 capsule twice a day from Day 0 to Week 24

  • DaclatasvirDrug

    Daclatasvir 60 mg, 1 tablet once a day from Day 0 to Week 24

  • RibavirinDrug

    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-2aDrug

    Pegylated Interferon alpha-2a, by subcutaneous injection 180µg / week, from Day 0 to Week 24

Study groups in NCT02107365
Study groupRoleWhat they receive
Asunaprevir, Daclatasvir, Ribavirin, Peg-Interferon alpha-2aExperimentalQuadritherapy from Day 0 to Week 24
Receives: Drug: Asunaprevir; Drug: Daclatasvir; Drug: Ribavirin; Drug: Pegylated Interferon alpha-2a

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. SVR12 Rate

    HCV RNA measured 12 weeks after the end of the HCV treatment (Week 36)

    Measured: Week 36

Secondary outcomes (14)

  1. Number of patients with adverse events

    Measured: Up to Week 48

  2. Treatment discontinuations

    Number and causes of treatment discontinuations

    Measured: Up to Week 24

  3. Self-reported symptoms

    ANRS AC24 perceived symptoms scale

    Measured: Day 0, Week 12, Week 36

  4. Patients' adherence

    ANRS questionnaire

    Measured: Week 4, Week 12, Week 24

  5. SVR 24 rate

    Undetectable HCV RNA 24 weeks after the end of the HCV treatment

    Measured: Week 48

  6. HCV viral load

    Measured: Day 0, Weeks 1, 2, 4, 8, 12, 16, 20, 24, 28, 36, 48

  7. Number of patients with virological failure under treatment

    Patients with detectable HCV viral load at Week 8, or Patients with HCV breakthrough : a) undetectable HCV viral load at Week 8 and detectable at any visit after Week 8 or b) undetectable HCV viral load at any time point before Week 8 and who presents a new confirmed detectable viral load before Week 8

    Measured: Up to Week 24

  8. HCV subtypic distribution

    Measured: Baseline

  9. Proportion of patients with resistance mutations to Asunaprevir and/or Daclatasvir in case of virological failure

    Measured: Up to Week 48

  10. Cirrhosis evaluation

    For cirrhotic patients : Child-Pugh and MELD scores ; cirrhosis decompensation evaluation on clinical examination

    Measured: Baseline, Week 12, Week 24, Week 36, Week 48

  11. Insulin resistance : HOMA-IR score

    Measured: Day 0, Week 36

  12. Metabolic syndrome parameters

    Waist circumference, blood pressure, fasting glucose, triglycerides, HDL cholesterol (composite measure)

    Measured: Day 0, Week 36

  13. Liver fibrosis

    Evolution of liver fibrosis on biological parameters (Fibrotest®) and imaging (Fibroscan®)

    Measured: Between baseline and Week 48

  14. Polymorphism of the gene of IL28B

    Measured: Day 0

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Apr 2014 (estimated)
  2. Study startNov 2013
  3. Primary completionFeb 2015
  4. Study completionApr 2015

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02107365
Sponsor's protocol ID
ANRS HC32 QUATTRO
Other IDs
2013-002367-25
Status last verified
Jan 2017
First submitted
31 Mar 2014
Last updated
13 Apr 2026
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 29271782

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Asunaprevir, Daclatasvir and Ribavirin in people with Hepatitis C Virus Genotype 4 Infection, run by ANRS, Emerging Infectious Diseases at 25 sites in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 25 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

SVR12 Rate (time frame: Week 36). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02107365, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Apr 2026.

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