Trial record 13 of 21 for:    " November 09, 2011":" December 09, 2011"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]

Lipopeptide Immunisation With GTU-multiHIV Trial

This study is currently recruiting participants.
Verified July 2013 by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT01492985
First received: November 24, 2011
Last updated: January 2, 2014
Last verified: July 2013
  Purpose

The combination of GTU-MultiHIV B DNA and LIPO-5 vaccines in a prime-boost strategy is expected to induce strong and diverse HIV-specific immune responses in HIV-infected patients. The investigators will carry out the clinical therapeutic immunization "proof of concept" trial in HIV infected patients. The investigators propose a multi-center double blind randomized versus placebo phase II clinical trial in patients who are chronic asymptomatic HIV-infected patients, with undetectable viral load while treated with a potent combination of antiviral drugs. Patients will continue antiviral therapy combined with either therapeutic vaccination or placebo vaccination. Patients will undergo the procedure which includes a prime with the GTU-MultiHIV B DNA vaccine or placebo administered by IM injections via Biojector (a needle-free injection system) followed by a boost of LIPO-5 vaccine or placebo also given IM.

In total, 105 HIV-1 patients will be enrolled: 35 in the placebo arm and 70 in the vaccine arm. Patients will receive antiretroviral treatments and 3 administrations of DNA vaccine or its placebo at weeks 0, 4 and 12 (corresponding to prime vaccinations). They also receive 2 doses of LIPO-5 vaccines or its placebo at week 20 and 24 (corresponding to boost vaccinations). At week 36 antiretroviral treatments will be interrupted until week 48. Patients will be intensely monitored during the treatment interruption period. The primary efficacy endpoint is a plasma HIV-1 RNA level at week 48 (e.g. 12 weeks after stopping all antiviral treatment).

The main hypothesis for conducting a phase II randomized trial is that immune responses in vaccinated patients may be associated with a better control of viral replication following c-ART interruption as compared to placebo-vaccinated patients.


Condition Intervention Phase
HIV-1 Infection
Biological: Placebos of GTU-multiHIV B and LIPO-5 vaccines
Biological: GTU-multHIV B vaccine and LIPO-5 vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Evaluation of a Therapeutic Immunization Strategy Associating a DNA Vaccine (GTU-MultiHIV B) Followed by a Lipopeptide Vaccine (LIPO-5) in the Control of Viral Replication Following Antiretroviral Treatment Interruption in HIV-1 Infected Patients With a CD4 Cell Count ≥ 600/mm3

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Plasma HIV-1 RNA level [ Time Frame: week 48 (W48) ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Plasma HIV-RNA after stopping antiviral treatment [ Time Frame: W40, W44 and W48 ] [ Designated as safety issue: No ]
  • Percentage of patients with plasma HIV-RNA below 10 000 copies/mL [ Time Frame: W48 ] [ Designated as safety issue: No ]
  • Ultrasensitive proviral DNA [ Time Frame: W-3, W20, W32 and W44 ] [ Designated as safety issue: No ]
  • CD4 T cell counts [ Time Frame: W40, W44 and W48 or prior HAART resumption ] [ Designated as safety issue: No ]
  • Percentages of patients who resumed HAART [ Time Frame: between W36 and W48 ] [ Designated as safety issue: Yes ]
  • Percentages of patients who reached CD4 cell counts < 350/mm3 confirmed two weeks apart [ Time Frame: between W36 and W48 ] [ Designated as safety issue: Yes ]
  • Strength of HIV-specific CD4/CD8 responses [ Time Frame: W0, W16, W28 and W48 or at the time of failure ] [ Designated as safety issue: No ]
  • Proportion of responders to at least one HIV peptide pool [ Time Frame: W0, W16, W28 and W48 or at the time of failure ] [ Designated as safety issue: No ]
  • Breadth of CD4/CD8+ HIV-specific responses defined as the number of HIV pools recognized among the 18 pools [ Time Frame: W0, W16, W28 and W48 or at the time of failure ] [ Designated as safety issue: No ]
  • Polyfunctionality of HIV specific T cell responses evaluated by the mean proportion of CD4/CD8+ T cells producing IL-2 and/or IFN-g following ex-vivo stimulation with HIV-1 peptide pools [ Time Frame: W0, W16, W28 and W48 ] [ Designated as safety issue: No ]
  • Adverse Events > grade 2 [ Time Frame: W0, W4, W12, W16, W20, W24, W28, W32, W36, W38, W40, W42, W44 and W48 ] [ Designated as safety issue: Yes ]
  • AIDS-defining events and serious non-AIDS events defined as cardiovascular diseases, kidney diseases, end stage liver diseases, non-AIDS defining malignancies except basal cellular skin cancer, and bacterial infections [ Time Frame: W0, W4, W12, W16, W20, W24, W28, W32, W36, W38, W40, W42, W44 and W48 ] [ Designated as safety issue: Yes ]
  • Analysis of predictive factors for plasma HIV-RNA [ Time Frame: W48 ] [ Designated as safety issue: No ]

Estimated Enrollment: 105
Study Start Date: July 2013
Estimated Study Completion Date: January 2017
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Vaccine placebos
Vaccine placebos corresponding to the dilutant of these vaccines
Biological: Placebos of GTU-multiHIV B and LIPO-5 vaccines
Placebos corresponds respectively to 1X PBS pH = 7.2 and glucose 5%
Experimental: Vaccine arm Biological: GTU-multHIV B vaccine and LIPO-5 vaccine
Vaccines are respectively an HIV-DNA plasmid and a mixture of 5 HIV-lipopeptides.

  Eligibility

Ages Eligible for Study:   18 Years to 59 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria:

  • Documented HIV-1 infection (ELISA and Western blot)
  • Age ≥ 18 years and < 60 years
  • No history of CDC category C clinical events (1993), including cutaneous Kaposi's sarcoma
  • CD4 Nadir ≥ 300/mm3
  • CD4 ≥ 600/mm3 on all measurements within the previous 6 months* prior to W-3 screening visit (one single CD4 value between 550-600 cells/ mm3 is permitted)
  • CD4 value ≥ 600/ mm3 at W-3 screening visit
  • Plasma HIV1-RNA < 50 copies/mL on all measurements within the previous 6 months* (An occasional measurement of HIV-1 RNA (so-called " blip " between 50 and 200 copies/mL is permitted)
  • HIV1-RNA < 50 copies/mL at W-3 screening visit

    * In the absence of measurement in the last 6 months, a measurement performed in the last 12 months is accepted

  • Treatment with a combination of antiviral drugs (cART) for at least 18 months regardless of the combination, under condition that :

    • in the W24 visit the non-nucleoside inhibitors are replaced by a protease inhibitor potentiated by ritonavir
    • no failure or resistance to the protease inhibitor was previously reported
  • With adequate method of contraception and negative pregnancy test (βHCG plasma) for women of childbearing potential
  • Laboratory parameters at W-3:

    • polynuclear neutrophils ≥ 1,000/mm3
    • haemoglobin ≥ 10 g/dl
    • platelets ≥ 100,000/mm3
    • creatinine ≤ 1.5 x N
    • AST, ALT, bilirubin ≤ 2.5 x N
    • proteinuria ≤ 1 g/L (++)
    • anti-nuclear antibodies ≤ 1/320
    • anticardiolipin antibodies ≤ 30 U
    • no lupus anticoagulant
  • Participant agreeing to be treated and followed for at least 48 weeks according to the protocol
  • Participant agreeing to interrupt his/her cART treatment and, if applicable, to replace the non-nucleoside inhibitors by a protease inhibitor potentiated by ritonavir at W24
  • Participant covered by HealthInsurance (article L1121-11 of Code de la Santé Publique)
  • Written informed consent (at the latest the day of pre-inclusion and before all exams to be done in the context of the trial) (article L1122-1-1 of Code de la Santé Publique).

Exclusion criteria

  • Pregnancy or lactation,
  • HIV-2 infection (isolated or associated with HIV-1),
  • History of (experimental) vaccinations against HIV,
  • Treatment with chemotherapy or interferon alpha (IFN-α-2b), sargramostim (GM-CSF), IL-2 or IL-7 ongoing or in the previous12 weeks before inclusion (W0),
  • Treatment with corticoids or immunosuppressive agents ongoing or in the previous12 weeks before inclusion in the trial (W0),
  • Administration of a live vaccine within 60 days prior to inclusion in the trial (W0) or any other inactivated vaccine within 14 days before W0 visit
  • Planned administration, during the follow-up of participants, of a vaccine other than those recommended in France as part of the usual care of patients
  • History of cancer (except basal cellular skin carcinoma),
  • History of cardiovascular disease (angina, myocardial infarction, transient ischemic attack, stroke),
  • History of renal failure related to HIV,
  • History of thrombocytopenia related to HIV (<50,000/mm3),
  • Ongoing cardiac, pulmonary, thyroid, renal or neurological (peripheral or central) diseases,
  • Progressive infection,
  • Co-infection with hepatitis B (HBsAg + or isolated anti-HBc antibodies +) or hepatitis C (anti-HCV antibody and PCR +),
  • Known allergy to aminoglycosides,
  • Person placed under juridical protection (article L1122-2 of Code de la Santé Publique)
  • Person participating in another biomedical research with an exclusion period always ongoing at screening.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01492985

Locations
France
Service d'Immunologie clinique, Centre de vaccination anti-VIH ANRS Mondor Ile-de-France, Hôpital Henri Mondor Recruiting
Créteil, France, 94010
Contact: Yves Lévy, PU-PH    33 (0) 1 49 81 44 42    yves.levy@hmn.aphp.fr   
Contact: Jean-Daniel Lelièvre    33 (0) 1 49 81 44 42    jean-daniel.lelievre@hmn.aphp.fr   
Principal Investigator: Jean-Daniel Lelièvre, PU-PH         
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Yves Lévy, PU-PH Hôpital Henri Mondor - Créteil - France
Study Director: Geneviève Chêne, PU-PH CMG-EC de l'INSERM U897 / ANRS
  More Information

No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier: NCT01492985     History of Changes
Other Study ID Numbers: 2009-018198-30, ANRS 149 LIGHT
Study First Received: November 24, 2011
Last Updated: January 2, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Additional relevant MeSH terms:
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases

ClinicalTrials.gov processed this record on April 17, 2014