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

NCT04842682 | Completed Phase 1 DMC

• 2 other identifiers: 2020-001814-40ANRS VRI06
• Study Type: interventional
• Target: 72
• Locations: 2 countries
• Sites: 3

Brief 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.

Conditions

Healthy Adults

Outcome Measures

Primary Outcomes (1)

• Safety Part 1 - Proportion of participants without any grade 3 or 4 adverse event

  Proportion of participants without any grade 3 or 4 biological or clinical solicited local/systemic or unsolicited adverse evens, considered to be related or possibly related to IMP administration.

  Between weeks 0 and 48

Secondary Outcomes (2)

• Safety - Number of unsolicited adverse events

  Between weeks 0 and 48 ; Between weeks LB and LB+24

• Safety - Number of solicited local and systemic adverse events

  Between weeks 0 and 48 ; Between weeks LB and LB+24

Other Outcomes (17)

• Safety - Number of serious adverse events

  Between weeks 0 and 48 ; Between weeks LB and LB+24

• Safety Part 1 - Number of Events leading to discontinuation of the vaccine regime

  Between weeks 0 and 48

• Immunological analyses : % of participants with Env-specific antibodies (Ab)

  Weeks 2, 6, 26, 48 and 76; Weeks LB+2 and LB+24

Study Arms (3)

Part 1: Active intervention

EXPERIMENTAL

Solo groups : CD40.HIVRI.Env vaccine (solution at 5.0 mg/ml) adjuvanted with Poly-ICLC (Hiltonol, solution at 1.8 mg/ml) Combi groups : CD40.HIVRI.Env vaccine (solution at 5.0 mg/ml) adjuvanted with Poly-ICLC (Hiltonol, solution at 1.8 mg/ml) and combined with DNA-HIV-PT123 HIV-1 vaccine (solution at 4.0 mg/ml)

Biological: Solo 0.3 group; Biological: Solo 1 group; Biological: Solo 3 group; Biological: Combi 0.3 group; Biological: Combi 1 group; Biological: Combi 3 group

Part 1: Placebo

PLACEBO COMPARATOR

Commercial Sodium Chloride at 0.9% (NaCl 0.9%)

Biological: Solo 0.3 group; Biological: Solo 1 group; Biological: Solo 3 group; Biological: Combi 0.3 group; Biological: Combi 1 group; Biological: Combi 3 group

Part 2: Active intervention

EXPERIMENTAL

CD40.HIVRI.Env vaccine (solution at 5.0 mg/ml) adjuvanted or not with Poly-ICLC (Hiltonol, solution at 1.8 mg/ml)

Biological: Late boost CD40 alone; Biological: Late boost CD40 adjuvanted

Interventions

Solo 0.3 group BIOLOGICAL

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 0.3 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24.

Part 1: Active intervention; Part 1: Placebo

Solo 1 group BIOLOGICAL

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 1.0 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid at weeks 0, 4 and 24.

Part 1: Active intervention; Part 1: Placebo

Solo 3 group BIOLOGICAL

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 3.0 and 1.0 mg/injection, i.e. 1.2 ml subcutaneous route in right deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1.2 ml subcutaneous route in right deltoid at weeks 0, 4 and 24.

Part 1: Active intervention; Part 1: Placebo

Combi 0.3 group BIOLOGICAL

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 0.3 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid; and combined with DNA-HIV-PT123 HIV-1 at 4.0 mg/injection, i.e. 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid and 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24.

Part 1: Active intervention; Part 1: Placebo

Combi 1 group BIOLOGICAL

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 1.0 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid; and combined with DNA at 4.0 mg/injection, i.e. 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1 ml subcutaneous route in right deltoid and 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24.

Part 1: Active intervention; Part 1: Placebo

Combi 3 group BIOLOGICAL

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 3.0 and 1.0 mg/injection, i.e. 1.2 ml subcutaneous route in right deltoid; and combined with DNA at 4.0 mg/injection, i.e. 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24 Or, NaCl at 0.9%, i.e 1.2 ml subcutaneous route in right deltoid and 1 ml intramuscular route in left deltoid at weeks 0, 4 and 24.

Part 1: Active intervention; Part 1: Placebo

Late boost CD40 alone BIOLOGICAL

CD40.HIVRI.Env at 0.3 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at week LB (late boost)

Part 2: Active intervention

Late boost CD40 adjuvanted BIOLOGICAL

CD40.HIVRI.Env and Poly-ICLC (Hiltonol), respectively at 0.3 and 1.0 mg/injection, i.e. 1 ml subcutaneous route in right deltoid at week LB (late boost)

Part 2: Active intervention

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age of 18 to 65 years at the time of the screening visit (week -4)
• Willingness and availability to be followed for the planned duration of the study in one of the dedicated investigative centers
• Informed and signed consent
• Agree to be registered in the French Health Ministry computerised file (for France only)
• Being covered by the Health Insurance
• Willingness to understake HIV testing and receive HIV test results
• Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
• Assessed by the clinic staff as being at "low risk" for HIV infection:
• no history of injecting drug use in the previous ten years;
• no STI in the last six months, untreated or incompletely treated syphilis infection in the past;
• no high risk partner (e.g., injecting drug user, HIV positive partner) either currently or within the past six months;
• no unprotected anal intercourse in the last six months, outside a relationship with a regular partner known/presumed to be HIV negative;
• no unprotected vaginal intercourse in the last six months outside a relationship with a regular known/presumed HIV negative partner.
• Participants who were born female: negative serum or urine beta human chorionic gonadotropin (β-HCG) pregnancy test performed on the day of initial IMP administration (week 0) and before randomisation
• Reproductive status: if heterosexually active female, consistently using an effective method of contraception with partner for sexual activity that could lead to pregnancy from at least 21 days prior to enrolment through 4 months after the last administration. Effective contraception is defined as using any of the following methods:

You may not qualify if:

• Intent to participate in another study of an investigational research agent during the planned duration of the study
• Participants who are not able to understand and to follow all required study procedures for the whole period of the study in the judgment of the investigator
• Under tutorship (only for France), guardianship, or deprived of liberty by a juridical or administrative decision
• Planned absence that could affect participation in the study (travel abroad, relocation, impending professional mutation...)
• Pregnant or breastfeeding
• Clinically significant medical condition, physical examination findings, clinically significant abnormal laboratory results, or past medical history with clinically significant implications for current health. A clinically significant condition or process includes but is not limited to:
• A process that would affect the immune response;
• A process that would require medication that affects the immune response;
• Any contraindication to repeated injections or blood draws;
• A condition that requires active medical intervention or monitoring to avert grave danger to the participant's health or well-being during the study period;
• A condition or process for which signs or symptoms could be confused with reactions to vaccine;
• Immunodeficiency
• Asthma other than mild, well-controlled asthma. (Symptoms of asthma severity as defined in the most recent National Asthma Education and Prevention Program (NAEPP) Expert Panel report).
• Exclude a participant who:
• Uses a short-acting rescue inhaler (typically a beta 2 agonist) daily, or

Sponsors & Collaborators

• ANRS, Emerging Infectious Diseases: lead

Study Sites (3)

Hôpital Henri Mondor

Créteil, France

Location

CIC 1417 - Hôpital Cochin

Paris, France

Location

Centre Hospitalier Universitaire Vaudois (CHUV)

Lausanne, Switzerland

Location

Study Officials

• Yves LEVY, Pr

  Hopital Henri Mondor

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Within each group, participants will be randomized in a double blind manner to active intervention or placebo in a 5:1 ratio. Randomization will be stratified by group. All groups will be double-blind until W6. Formal individual unblinding (with communication of individual volunteer allocation to active vs. placebo) will only performed at the end of the W48 visits of all participants in a given group. Long term follow-up to study the persistence of immune responses at W76 will be unblinded. The second part of the trial will be single blind. Allocation of the use of the unadjuvanted vs. adjuvanted CD40. HIVRI.Env boost will be randomized. Randomisation will be stratified by the initial group (Solo or Combi with its dose level).
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: Multicenter double-blind placebo controlled phase I dose-escalation trial to evaluate different dose levels of CD40.HIVRI.Env (adjuvanted with Hiltonol®) alone and in co-administration with DNA-HIV-PT123

Study Record Dates

• First Submitted: March 24, 2021
• First Posted: April 13, 2021
• Study Start: March 29, 2021
• Primary Completion: November 29, 2024
• Study Completion: November 29, 2024
• Last Updated: December 17, 2024

Record last verified: 2024-12

Locations

FR (2); CH (1)