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Hepatitis C Virus Genotype 4 InfectionPhase 2QUATTROTURBONCT02309450

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

A Phase 2 study testing .Asunaprevir, Daclatasvir and BMS - 791325 in people with Hepatitis C Virus Genotype 4 Infection, run by ANRS, Emerging Infectious Diseases at 1 site in France.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. 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 BMS - 791325
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteFrance
Study dates
Dec 2014to Aug 2016
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
  • 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.
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  • 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)

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • France

    All the Regions of the Country

Other trials in France

About this study

Official title: 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

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.

Read the 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)

Being tested
.Asunaprevir, Daclatasvir and BMS - 791325

What participants receive

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

  • .Asunaprevir, Daclatasvir and BMS - 791325Drug

    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.

Study groups in NCT02309450
Study groupRoleWhat they receive
Asunaprevir, Daclatasvir and BMS - 791325ExperimentalNot described
Receives: Drug: .Asunaprevir, Daclatasvir and BMS - 791325

What is being measured

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

  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.

    Measured: week 24

Secondary outcomes (13)

  1. Number of patients with adverse events

    Measured: up to week 36

  2. Treatment interruptions

    Number of patients who totally or partially interrupt,treatment

    Measured: from day 0 to week12

  3. Causes of treatment discontinuation

    toxicity or side effects

    Measured: form day 0 to week 12

  4. Self-reported symptoms

    self-questionnaire (ANRS AC24 perceived symptoms scale)

    Measured: Day 0, week 12, week 36

  5. Patients adherence rate

    measured using the (ANRS) self -questionnaire

    Measured: week 4, week 12

  6. HCV viral load

    Measured: day 0, week 1, week 2, week 4, week 8, week 12, week 16, week 20, week 24, week 36.

  7. Evaluation of the relationship between HCV subtypic distribution at baseline (by sequencing of the HCV NS5B domain) and the virological kinetics and response

    Measured: at screening

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

    Measured: up to week 12

  9. Child-Pugh score (composite measure)

    For cirrhotic patients

    Encephalopathy None+1 Mild to moderate (grade 1 or 2)+2 Severe (grade 3 or 4)+3

    Ascites None+1 Mild to moderate (diuretic responsive)+2 Severe (diuretic refractory)+3

    Bilirubin (mg/dL) < 2+1 2-3+2 > 3+3

    Albumin (g/dL) > 3.5+1 2.8-3.5+2 < 2.8+3

    International normalized ratio < 1.7+1 1.7-2.3+2 > 2.3+3 Total score of 5-6 = Grade A (well compensated disease) Total score of 7-9 = Grade B (disease with significant functional compromise) Total score of 10-15 = Grade C (decompensated liver disease)

    Measured: at screening

  10. Insulin resistance measured using the HOMA-IR score

    Measured: Day 0, week 36

  11. Parameters that define metabolic syndrome

    Measured: Day 0, week 36

  12. Evolution of liver fibrosis

    Fibrotest® or imaging Fibroscan®. Fibrosis will be evaluated with the same method (Fibroscan® or Fibrotest®) at baseline and week 36.

    Measured: Day 0, week 36

  13. MELD score (composite measure)

    For cirrhotic patients

    MELDScore = 10 * ((0.957 * ln(Creatinine)) + (0.378 * ln(Bilirubin)) + (1.12 * ln(INR))) + 6.43

    Measured: at screening

Timeline

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

  1. First posted5 Dec 2014 (estimated)
  2. Study startDec 2014
  3. Primary completionNov 2015 (estimated)
  4. Study completionAug 2016 (estimated)

Why it stopped: BMS decision

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
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02309450
Sponsor's protocol ID
ANRSHC33QUATTROTURBO
Other IDs
2014-002724-27, 2014
Acronym
QUATTROTURBO
Status last verified
Feb 2016
First submitted
31 Oct 2014
Last updated
2 Feb 2016
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing .Asunaprevir, Daclatasvir and BMS - 791325 in people with Hepatitis C Virus Genotype 4 Infection, run by ANRS, Emerging Infectious Diseases at 1 site 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 15 inclusion and 20 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: withdrawn, as of the sponsor's last update on 2 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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 was withdrawn before enrolling participants, so there are no results.

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?

HCV sustained virological response rate (time frame: week 24). 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 NCT02309450.

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 2 Feb 2016.

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