Lipopeptide Immunisation With GTU-multiHIV Trial

NCT01492985 | Completed Phase 2 DMC

• 2 other identifiers: 2009-018198-30ANRS 149 LIGHT
• Study Type: interventional
• Target: 103
• Locations: 1 country
• Sites: 1

Brief Summary

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. After start of cART treatment (at the latest in W48), a data collection from clinical car will be carried out. A blood sample with W74 will allow to study the persistence ot the immunizing responses, 1 year after the injection of the last vaccine/placebo. 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.

Conditions

HIV-1 Infection

Outcome Measures

Primary Outcomes (1)

• Plasma HIV-1 RNA level

  week 48 (W48)

Secondary Outcomes (13)

• Plasma HIV-RNA after stopping antiviral treatment

  W40, W44, W48 and W74

• Percentage of patients with plasma HIV-RNA below 10 000 copies/mL

  W48

• Ultrasensitive proviral DNA

  W-3, W20, W32 and W44

• CD4 T cell counts

  W40, W44 and W48 or prior HAART resumption and W74

• Percentages of patients who resumed HAART

  between W36 and W48

Study Arms (2)

Vaccine placebos

PLACEBO COMPARATOR

Vaccine placebos corresponding to the dilutant of these vaccines

Biological: Placebos of GTU-multiHIV B and LIPO-5 vaccines

Vaccine arm

EXPERIMENTAL

Biological: GTU-multHIV B vaccine and LIPO-5 vaccine

Interventions

Placebos of GTU-multiHIV B and LIPO-5 vaccines BIOLOGICAL

Placebos corresponds respectively to 1X PBS pH = 7.2 and glucose 5%

Vaccine placebos

GTU-multHIV B vaccine and LIPO-5 vaccine BIOLOGICAL

Vaccines are respectively an HIV-DNA plasmid and a mixture of 5 HIV-lipopeptides.

Vaccine arm

Eligibility Criteria

• Age: 18 Years - 59 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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 Under antiretroviral treatment
• 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

You may not qualify if:

• Pregnancy or lactation,
• HIV-2 infection (isolated or associated with HIV-1),
• History of (experimental) vaccinations against HIV,
• 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)

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (1)

Service d'Immunologie clinique, Centre de vaccination anti-VIH ANRS Mondor Ile-de-France, Hôpital Henri Mondor

Créteil, 94010, France

Location

Related Publications (2)

• Alexandre M, Prague M, Lhomme E, Lelievre JD, Wittkop L, Richert L, Levy Y, Thiebaut R. Definition of Virological Endpoints Improving the Design of HIV Cure Strategies Using Analytical Antiretroviral Treatment Interruption. Clin Infect Dis. 2024 Dec 17;79(6):1447-1457. doi: 10.1093/cid/ciae235.

  PMID: 38819800 DERIVED

• Levy Y, Lacabaratz C, Lhomme E, Wiedemann A, Bauduin C, Fenwick C, Foucat E, Surenaud M, Guillaumat L, Boilet V, Rieux V, Bouchaud O, Girard PM, Molina JM, Morlat P, Hocqueloux L, Richert L, Pantaleo G, Lelievre JD, Thiebaut R. A Randomized Placebo-Controlled Efficacy Study of a Prime Boost Therapeutic Vaccination Strategy in HIV-1-Infected Individuals: VRI02 ANRS 149 LIGHT Phase II Trial. J Virol. 2021 Apr 12;95(9):e02165-20. doi: 10.1128/JVI.02165-20. Print 2021 Apr 12.

  PMID: 33568510 DERIVED

Study Officials

• Yves Lévy, PU-PH

  Hôpital Henri Mondor - Créteil - France

  PRINCIPAL INVESTIGATOR

• Geneviève Chêne, PU-PH

  CMG-EC de l'INSERM U897 / ANRS

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 24, 2011
• First Posted: December 15, 2011
• Study Start: July 1, 2013
• Primary Completion: October 1, 2016
• Study Completion: April 8, 2017
• Last Updated: July 5, 2019

Record last verified: 2018-02

Locations

FR (1)