NCT06694753

Safety and Immunogenicity Study of Three mRNAs Encoding HIV Immunogens in Adult Participants Without HIV and in Overall Good Health in South Africa.

A Phase 1, Placebo-controlled, Blinded, Dose-escalation Study to Evaluate the Safety and Immunogenicity of mRNAs Encoding HIV Immunogens (eOD-GT8 60mer, Core-g28v2 60mer, N332-GT5 gp151) in Adult Participants Without HIV and in Overall Good Health in South Africa.

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 96 (estimated)
• Sponsor: International AIDS Vaccine Initiative · Network
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

The purpose of this study is to evaluate the safety and immunogenicity of mRNAs encoding HIV immunogens (eOD-GT8 60mer, core-g28v2 60mer, N332-GT5 gp151) in adult participants without HIV and in overall good health in South Africa.

Detailed description

This study will evaluate the safety and immunogenicity of 3 experimental HIV vaccines in adult participants without HIV and in overall good health in South Africa. The study vaccines are called mRNA-1645-eODGT8, mRNA-1645-CoreG28v2 and mRNA-1645-N332GT5. The study will be conducted in two parts (Part A and B). Part A will include two Cohorts, each with 2 groups: Cohort 1A Group 1, Cohort 1A Group 2, Cohort 2A Group 3, and Cohort 2A Group 4. Part B will include two Cohorts, each with 2 groups: Cohort 1B Group 5, Cohort 1B Group 6, Cohort 2B Group 7, and Cohort 2B Group 8. Participants in Part A Cohort 1A will be randomly assigned to receive mRNA-1645-eODGT8 followed by mRNA-1645-CoreG28v2 or to receive placebo. Participants in Part A Cohort 2A will be randomly assigned to receive two doses of the mRNA-1645-N332GT5 vaccine or to receive placebo. Cohorts 1A and 2A in Part A will be enrolled concurrently, and randomization to study product or placebo will take place in each cohort. Depending on their group, participants will receive 10 mcg of mRNA-1645-eODGT8, mRNA-1645-N332GT5 or Placebo by injection at Week 0 and 10 mcg of mRNA-1645-CoreG28v2, mRNA-1645-N332GT5, or Placebo at Week 8. Participants in Part B Cohort 1B will be randomly assigned to receive an increased dose of the mRNA-1645-eODGT8 and mRNA-1645-CoreG28v2 vaccine or to receive placebo. Participants in Part B Cohort 2B will be randomly assigned to receive an increased dose of the mRNA-1645-N332GT5 vaccine or to receive placebo. Cohorts 1B and 2B in Part B will be enrolled concurrently, and randomization to study product or placebo will take place in each cohort. Depending on their group, participants will receive 30 mcg of mRNA-1645-eODGT8, mRNA-1645-N332GT5 or Placebo by injection at Week 0 and 30 mcg of mRNA-1645-CoreG28v2, mRNA-1645-N332GT5, or Placebo at Week 8. Additional study visits will occur at Weeks 2, 7.5, 10, 15.5, and 24. Study visits may include physical examinations, medical history, vaccine injections, blood and urine collection, electrocardiogram, leukapheresis, lymph node cell collection, pregnancy test, HIV testing, risk reduction counseling, and questionnaires.

Conditions

• HIV Infections

Interventions

Type	Name	Description
BIOLOGICAL	mRNA-1645-eODGT8	eOD-GT8 60mer is a self-assembling nanoparticle composed of 60 subunits of the engineered HIV-1 gp120 outer domain germline targeting version 8 (eOD-GT8) fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 15-amino acid Glycine-Serine linker. eOD-GT8 60mer will be delivered using an mRNA lipid nanoparticle (LNP) platform. To be administered by intramuscular (IM) injection at doses of 10 or 30 mcg.
BIOLOGICAL	mRNA-1645-CoreG28v2	core-g28v2 60mer is a nanoparticle composed of 60 protein subunits of an engineered core-gp120 fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 21-amino acid Glycine-Serine linker. Core-g28v2 60mer will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.
BIOLOGICAL	mRNA-1645-N332GT5	N332-GT5 gp151 is an HIV envelope glycoprotein gp151 trimer based on BG505 SOSIP MD39 (clade A) trimer with "germline-targeting" mutations added that confer the ability to bind germline precursors of BG18 class B cells. N332-GT5 gp151 will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.
BIOLOGICAL	Placebo	Saline

Timeline

• Start date: 2025-12-15
• Primary completion: 2026-12-08
• Completion: 2027-03-31
• First posted: 2024-11-19
• Last updated: 2026-02-20

Locations

6 sites across 1 country: South Africa

Regulatory

• FDA-regulated drug study