Dose Escalation Trial of CD40.HIVRI.Env Vaccine Combined or Not With a DNA-HIV-PT123 HIV-1 Vaccine in Healthy Volunteers

Summary

FIRST PART: DOSE ESCALATION Multicenter double-blind placebo controlled phase I dose-escalation trial that will be conducted in France and Switzerland to evaluate different dose levels of CD40.HIVRI.Env (adjuvanted with Hiltonol) alone and in co-administration with DNA-HIV-PT123. A total of 72 eligible healthy participants will be recruited into 6 groups. Within each group, participants will be randomized in a double blind manner to active intervention or placebo in a 5:1 ratio. Enrolment into a given group (other than group "Solo 0.3") will open sequentially depending on the " go-criterion " based on the safety data of the preceding group(s). The primary objective is to assess the safety of three dose levels of CD40.HIVRI.Env (0.3; 1; 3 mg) adjuvanted with Poly-ICLC (Hiltonol®), alone and in combination with DNA-HIV-PT123, administered at weeks 0, 4 and 24 in healthy participants. Secondary objectives are to assess the capacity of poly-ICLC-adjuvanted CD40.HIVRI.Env alone and in combination with DNA-HIV-PT123 to elicit immune responses against HIV (immunogenicity): * Humoral (antibody) responses ; * B-cell responses ; * T-cell responses. SECOND PART: BOOST VACCINATION AND FOLLOW-UP Preliminary safety results allow consideration of long-term follow-up and evaluation of an additional CD40.HIVRI.Env booster injection in volunteers. An admendment was approved to complete the follow-up with two visits: 2 weeks (WLB+02) and 24 weeks (WLB+24) after the boost (WLB). Volunteers who received the active strategy in the first part of the trial (n=60) will be randomized in a single blind design and will receive an additional 0.3 mg dose of CD40HIVRI.Env vaccine either combined with Hiltonol adjuvant, as in the first part of the trial, or unadjuvanted. Part 2 will take place after the W48 visit and the participant's unblinding of Part 1. It will address the following secondary objectives: * To evaluate tolerance * To evaluate the evolution of long-term vaccine responses (immunogenicity) and the effect of a booster injection of CD40.HIVRI.Env alone or adjuvanted with Poly ICLC- Hiltonol®. The tests that will be performed will be identical to those performed during the first phase of the trial allowing the monitoring of the evolution of responses.

Timeline

Start

2021-03-29

Primary completion

2024-11-29

Completion

2024-11-29

Publications

• Levy Y, Moog C, Wiedemann A, Launay O, Candotti F, Hardel L, Durand M, Hejblum BP, Rieux V, Diallo A, Lacabaratz C, Cardinaud S, Zurawski S, Zurawski G, Tomaras GD, Ding S, Centlivre M, Thiebaut R, Pantaleo G, Lelievre JD, Richert L; ANRS VRI06 Study Group. CD40.HIVEnv, an antibody mediated vaccine, induces long-term and recall immunogenicity in non-HIV-1 infected volunteers. Sci Rep. 2026 May 29. doi: 10.1038/s41598-026-52363-4. Online ahead of print.

Drugs

Indications

No indication recorded.