Assessment of the therapeutic properties of the VAC-3S immunoprotective vaccine when combined with standard antiretroviral therapy (ART) in the course of HIV-1 infection. A European multicenter, randomized, double-blind, placebo-controlled, phase II study

INTERVENTION: Product Code: VAC‐3S Pharmaceutical Form: Suspension for injection Current Sponsor code: IVV‐3S Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 0,032 and 0,064‐ Pharmaceutical form of the placebo: Suspension for injection Route of administration of the placebo: Intramuscular use CONDITION: Chronically infected HIV‐1 patients under viral control on Anti‐Retroviral therapy ; MedDRA version: 18.0 Level: LLT Classification code 10068341 Term: HIV‐1 infection System Organ Class: 100000004862 Therapeutic area: Diseases [C] ‐ Immune System Diseases [C20] PRIMARY OUTCOME: Main Objective: The primary objective of the current Phase 2 study is to evaluate the immunogenicity of VAC‐3S at doses of 16 µg, 32 µg and 64 µg at 4 weeks after 3 vaccinations q4weeks in virologically controlled HIV‐1 infected patients with CD4+ T cell counts between 200 and 500 cells/mm3 who are receiving standard‐of‐care antiretroviral treatment. Primary end point(s): The primary efficacy endpoint is the change in anti‐3S antibody titers after 3 vaccinations q4weeks measured 4 weeks after the third vaccination. Secondary Objective: The secondary objectives of the study are:; • to evaluate the safety, tolerability and virological impact of anti‐3S antibody titers following vaccination with VAC‐3S 3 times every 4 weeks, and maintenance vaccinations 3 times every 12 weeks after the initial vaccination schedule;; • to evaluate the overall immunogenicity of VAC‐3S at doses of 16 µg and 32 µg after 3 maintenance vaccinations at the end of the full immunization scheme;; • to evaluate anti‐3S antibody decay rates over time;; • to assess the impact of VAC‐3S immunotherapy on CD4 cell counts and percentages in a cohort of virologically controlled HIV‐1 infected patients with stable CD4 cell counts;; • to assess the impact of VAC‐3S on immunologic markers panels including NKp44L expression on the surface of CD4 T lymphocytes and phenotypic markers of lymphocyte activation and differentiation. ; • to evaluate the impact of VAC‐3S on inflammatory biomarkers.; Timepoint(s) of evaluation of this end point: Between week 0 and week 12 SECONDARY OUTCOME: Secondary end point(s): 1. Assessment of safety & tolerability ; • Overall general clinical tolerance, ; • Local tolerance, ; • Laboratory monitoring of clinical safety, ; • HIV RNA monitoring of viral blips. ; 2. Evaluation of the inflammatory/immunological interface ; • Impact on chronic inflammatory biomarkers. ; 3. Assessment of immunogenic characteristics of VAC‐3S ; • Evaluation of the effect of the base immunization schedule of 3 vaccinations at 4‐week intervals (total of 3 vaccinations), ; • Evaluation of the effect of 1, 2 and 3 maintenance vaccinations (a total of 6 vaccinations). ; 4. Assessment of immunological effects ; • NKP44L expression, ; • Immune activation, ; • Immune differentiation. ; 5. Evaluation of secondary virological effects ; • Impact on markers of HIV reservoir. ; 6. Specific secondary assessments not covered under secondary objectives number 1 to 5: ; • Characterization of anti‐3S antibodies, ; • Identification of composite endpoints, ; • Identification of factors predictive of response, ; • Specific statistical analysis to identify patient subgroups, ; • Response in subgroups of patients as a function of ongoing treatments [type of ART, statins], ; • Estimation of the optimal time to re‐vaccinate subjects after the last dose of VAC‐3S (defined as the median/mean time to an anti‐3S antibody titer <50 AU), ; • Evaluation of increasing doses of VAC‐3S on: ; ‐ Safety/Tolerability of VAC‐3S, ; ‐ Maximum anti‐3S antibody titers, ; ‐ Time to reach the maximum anti‐3S antibody titer, ; ‐ Decay of anti‐3S antibody titers over time after the last vaccination with VAC‐3S, ; • Evaluation of the impact of different levels of CD4+ T cell count on the: ; ‐ Safety/Tolerability of VAC‐3S, ; ‐ Maximum anti‐3S antibody titer, ; ‐ Time to reach the maximum anti‐3S antibody titer, ; ‐ Decay of anti‐3S antibody titers over time after the last dose of VAC‐3S. ; • Evaluation of the effect of the maximum anti‐3S antibody titer on: ; ‐ Safety/tolerability, ; ‐ Time to decay based upon an initially maximum anti‐3S antibody titer, including subgroup evaluation by CD4 strata. ; • Evaluation of anti‐carrier antibody titers or surrogate markers thereof. ; • Impact on metabolic endpoints. Timepoint(s) of evaluation of this end point: Between week 0 and week 72 INCLUSION CRITERIA: 1. Documented HIV‐1 infection, 2. Adults > 18 and < 60 years of age, 3. Able and willing to comply with the protocol, including availability for all scheduled study visits, 4. Provided a signed written informed consent, 5. Meets study screening physical, medical history and laboratory assessments (defined below), 6. On stable antiretroviral therapy that is consistent with the current standard of care for at least 12 months prior to study screening, 7. Plasma HIV RNA < 50 cps/mL during the previous 12 months, 8. CD4+ T cell count at screening > 200 and < 500 cells/mm3, 9. Adequate hematology, biochemistry, and metabolic blood tests defined as being less than grade 2 according to the Division of AIDS Adverse Events (See Appendix 23.1), except for the numeration of CD4 and for the numeration of lymphocytes, 10. Adequate hepatic and renal function defined as being less than Grade 2 according to t