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HCV-HIV Co-InfectionPhase 2QUADRIHNCT01725542

Pilot Study to Assess the Efficacy of and Tolerance to a QUadruple Therapy to Treat HIV-HCV Coinfected Patients Previously Null Responders

A Phase 2 study testing Asunaprevir, Daclatasvir, Ribavirin and Peginterferon alfa-2a in people with HCV-HIV Co-Infection, run by ANRS, Emerging Infectious Diseases at 1 site in France.

Completed

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

Official record
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Trial summary

Evaluation of efficacy and tolerance to a QUadruple therapy with Asunaprevir , Daclatasvir, Ribavirin and pegylated Interferon alpha-2a, in HIV-HCV genotype 1 or 4 coinfected patients previously null responders to a standard Pegylated Interferon -Ribavirin regimen. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
HCV-HIV Co-Infection
What is being tested?
Asunaprevir, Daclatasvir, Ribavirin and Peginterferon alfa-2a
Could I receive a placebo?
No, everyone receives an active treatment
How many people
75 participants
Where
1 siteFrance
Study dates
Dec 2012to Jun 2014
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 with confirmed HIV-1 or 2 infection
  • Infection with HCV genotype 1 or 4 only, confirmed and with detectable HCV-RNA ≥ 1000 IU/mL at screening.
  • Null responders to a previous treatment with Peginterferon and Ribavirin, defined by a fall of less than 2 log10 IU/ml HCV-RNA from baseline to week 12.
  • Stable antiretroviral treatment for > 1 month at screening containing any of the following drugs: Raltegravir, Enfuvirtide, Tenofovir-Emtricitabine, Abacavir-Lamivudine.
  • CD4 > 200 /mm3 and > 15% at screening
  • HIV-RNA < 400 copies/mL from ≥ 3 months at screening
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  • Any liver fibrosis stage,
  • with the assessment of the presence or not of cirrhosis at screening:
  • previous liver biopsy exhibiting cirrhosis lesions (METAVIR F4), and/or
  • significant liver biopsy (cumulative length ≥ 15 mm and ≥ 6 portal spaces), within 18 months and after the end of last HCV treatment, and/or
  • significant and reliable liver stiffness assessment (Fibroscan®) within 6 months (at least 10 measures with IQR less then 25% of the mean value and a success rate of at least 80%)
  • cirrhosis being defined as a METAVIR score F4 on liver biopsy and/or liver elastometry ≥ 15 kPa
  • the proportion of patients with cirrhosis (METAVIR F4) is limited to 50% of all patients.
  • Body weight ≥ 40 kg and ≤125 kg
  • Male patients, female patients with child-bearing potential and their heterosexual partners must use adequate contraception from 1 month before initiation of treatment to 7 months following the end of treatment for men and to 4 months following the end of treatment for women.
  • Informed and signed consent
  • For participating patients, informed and signed consent for the pharmacokinetic sub-study
  • Patients affiliated to the National Health Insurance or covered by Universal Medical Coverage
  • For the first 12 patients included (who will participate to the pharmacological substudy): stable antiretroviral treatment for > 1 month at screening, with Raltegravir+ Emtricitabine+ Tenofovir

Who cannot join

  • CHILD B and C cirrhosis, past history of decompensated cirrhosis. Patients with CHILD A cirrhosis must demonstrate the absence of significant oesophageal varices (Stages 2-3) on an upper gastrointestinal endoscopy ≤ 12 months
  • Positive HBs antigenemia with HBV DNA > 1000 IU/ml((if positive AgHBs with HBV DNA ≤ 1000 IU/mL, patient will be included provided it is treated with Ténofovir)
  • Pregnant women, breast-feeding women
  • Refusal of adequate contraception
  • Contra-indication to Ribavirin, including hypersensitivity reaction to Ribavirin
  • Contra-indication to Peginterferon, including psychiatric contra-indications. Patients with significant psychiatric past history, notably severe depression requiring hospitalization or suicide attempt, cannot be included unless they undergo a psychiatric evaluation and obtain a specific authorization for the use of interferon.
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  • Premature discontinuation (during the first six months) of a previous HCV treatment for toxicity. Patients who have stopped a previous treatment for severe anaemia or neutropenia can enter the study if erythropoietin or granulocyte growth factor had not been used during the previous treatment
  • Previous HCV therapy including HCV NS3 protease inhibitor
  • Severe pre-existing cardiac or pulmonary disease
  • History of organ transplant
  • Acute CDC stage C opportunistic infection occurring within the previouW6 months
  • Any active malignant disease including hepatocellular carcinoma for which a specific assessment is required at screening
  • Alcohol intake that may represent an obstacle for the participation of the subject in the study
  • Substance abuse that may represent an obstacle for the participation of the subject in the study. Stabilized patients included in a substitution program can participate in the study
  • Patients with previous observance problem unable to observe the study procedures
  • Participation in another clinical trial within the previous 30 days
  • Haemoglobin < 90 g/L
  • Platelets < 50 000 /mm3
  • Neutrophil count < 750 /mm3
  • Renal insufficiency defined by an estimated Glomerular Filtration Rate < 50 mL/mn (MDRD equation)
  • Absence of antiretroviral treatment or antiretroviral treatment different from the authorized combinations
  • Associated medication likely to interfere with any of the study drugs such as CPY3A4 inducers (rifampin, Millepertuis)

Trial locations and contacts

1 site in 1 country.

France1 site

  • Study site

    All the Regions of the Country (33 Centers)

Other trials in France

About this study

Official title: Pilot Study to Assess the Efficacy and Tolerance to a QUadruple Therapy With Asunaprevir , Daclatasvir, Ribavirin and Pegylated Interferon Alpha-2a, in HIV-HCV Genotype 1 or 4 Coinfected Patients Previously Null Responders to a Standard Pegylated Interferon -Ribavirin Regimen

Evaluation of efficacy and tolerance to a QUadruple therapy with Asunaprevir , Daclatasvir, Ribavirin and pegylated Interferon alpha-2a, in HIV-HCV genotype 1 or 4 coinfected patients previously null responders to a standard Pegylated Interferon -Ribavirin regimen.

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

Read the detailed description

The clinical trial is multi-center, national, Phase 2, open-label, single-arm.

Primary objective is to estimate the Sustained Virological Response rate (SVR) 12 weeks after 24 weeks of treatment with quadruple therapy combining Asunaprevir, Daclatasvir, Ribavirin and Pegylated Interferon alpha-2a in HIV-HCV genotype 1 or 4 coinfected patients previously null responders to a Pegylated Interferon -Ribavirin standard regimen.

Estimated enrolment is 65 patients during the enrolment period (9 months). The first 12 patients included will be on Raltegravir, Emtricitabine and Tenofovir and will participate to the pharmacological sub-study.

Schedule of assessments:

Evaluation of inclusion criteria: 4 to 8 weeks Anti-HCV treatment: 28 weeks (or shorter according to futility rules) Follow up: 24 weeks following the end of the treatment

Being tested
Asunaprevir, Daclatasvir, Ribavirin and Peginterferon alfa-2a
Keywords
HCV-HIV Co-Infection, Quadruple therapy, null responder to a standard Pegylated interferon/Ribavirin regimen

What participants receive

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

  • Asunaprevir, Daclatasvir, Ribavirin and Peginterferon alfa-2aDrug

Study groups in NCT01725542
Study groupRoleWhat they receive
Asunaprevir, Daclatasvir, Ribavirin and Peginterferon alfa-2aExperimental* Lead-in" Phase: day 0 to week 4 PegInterferon alpha-2a + Ribavirin * Quadruple therapy: week 4 to week 28 Asunaprevir + Daclatasvir + PegInterferon alpha-2a + Ribavirin
Receives: Drug: Asunaprevir, Daclatasvir, Ribavirin and Peginterferon alfa-2a

What is being measured

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

  1. HCV Sustained virological response rate

    the undetectable HCV RNA at wk40 (ie 12 weeks after the end of the quadritherapy associating Asunaprevir, Daclatasvir, Pegylated interferon alpha-2a and Ribavirin in case of premature total or partial discontinuation of HCV treatment, the principal endpoint will also be assessed at wk40)

    Measured: wk40

Secondary outcomes (8)

  1. Number of participants with adverse events as a measure of safety and tolerability

    • Clinical and biological Adverse Events
    • Treatment premature discontinuations
    • Perceived symptoms (ANRS AC24 Symptom Perception Scale)
    • Adherence (ANRS observance scale and effective dispensation by the pharmacy)

    Measured: during throughout all the study

  2. Kinetics of HCV Virological response

    Measurements of HCV RNA at wk4, wk5, wk6, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk40 and wk52 (ie 24 weeks after the end of the treatment), globally or according to the HCV genotype (1 or 4) and sub-type (1a or 1b, 4a or 4c/d)

    Measured: wk4, wk5, wk6, wk8, wk12, wk16, wk20, wk24, wk28, wk32, wk40 and wk52

  3. Immunological and virological evolution of HIV infection

    • HIV RNA levels
    • CD4 and CD8

    Measured: wk0, wk4, wk8, wk12,wk16, wk24, wk28, wk40 et wk52

  4. Evolution of cirrhosis (for cirrhotic patients)

    • Child-Pugh and MELD scores
    • end stage liver disease onset
    • hepatocarcinoma onset

    Measured: wk12, wk28, wk40 and wk52

  5. Number of Participants with HIV and non HIV related clinical events

    • AIDS classifying clinical events
    • Severe non-AIDS clinical events.

    Measured: through the study

  6. Minimum Plasma Concentration (Cmin) of ribavirin

    Measured: wk4 and wk8

  7. Pharmacokinetics of Antiretroviral drugs

    • sub-group study ((focusing on patients on Raltegravir, Emtricitabine and Tenofovir)
    • plasma drugs concentrations from H0 to H10
    • Cmin (Minimum Plasma Concentration), Cmax (Maximum Plasma Concentration) and AUC (Area Under the Plasma Concentration)

    Measured: wk0 and wk8

  8. Pharmacokinetics of Asunaprevir and Daclatasvir

    • sub-group study (focusing on patients on Raltegravir, Emtricitabine, Tenofovir)
    • plasma Asunaprevir and Daclatasvir concentrations from H0 to H10
    • Cmin, Cmax and AUC

    Measured: wk8

Timeline

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

  1. First posted14 Nov 2012 (estimated)
  2. Study startDec 2012
  3. Primary completionApr 2014
  4. Study completionJun 2014

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
Diagnosis
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
75 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01725542
Sponsor's protocol ID
ANRS HC30 QUADRIH
Other IDs
2012-002589-11
Acronym
QUADRIH
Status last verified
Mar 2014
First submitted
22 Oct 2012
Last updated
8 Sep 2014
Results posted
No
Data monitoring committee
Yes

Publications

  • Piroth L, Paniez H, Taburet AM, Vincent C, Rosenthal E, Lacombe K, Billaud E, Rey D, Zucman D, Bailly F, Bronowicki JP, Simony M, Diallo A, Izopet J, Aboulker JP, Meyer L, Molina JM; ANRS HC30 QUADRIH Study Group. High Cure Rate With 24 Weeks of Daclatasvir-Based Quadruple Therapy in Treatment-Experienced, Null-Responder Patients With HIV/Hepatitis C Virus Genotype 1/4 Coinfection: The ANRS HC30 QUADRIH Study. Clin Infect Dis. 2015 Sep 1;61(5):817-25. doi: 10.1093/cid/civ381. Epub 2015 May 14.

    PubMed 25977266

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Asunaprevir, Daclatasvir, Ribavirin and Peginterferon alfa-2a in people with HCV-HIV Co-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 19 inclusion and 22 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 8 Sep 2014. 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 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?

HCV Sustained virological response rate (time frame: wk40). 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 NCT01725542, 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 8 Sep 2014.

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