A Clinical Trial to Evaluate the Safety and Immunogenicity of CH505M5 N197D mRNA-gp160 Followed by CH505 TF mRNA-gp160 in Adults in Overall Good Health Without HIV
NCT Number: NCT06557785
Status: NOT_YET_RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1
Conditions: HIV Infections
Interventions: BIOLOGICAL: CH505M5 N197D mRNA-gp160|BIOLOGICAL: CH505 TF mRNA-gp160
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators: National Institutes of Health (NIH)|Department of Health and Human Services
Sex: ALL
Age: ADULT
Enrollment: 48
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: PREVENTION
Start Date: 2024-08-21
Completion Date: 2026-06-21
Locations: Beth Israel Deaconess Medical Center (Site ID: 32077), Boston, Massachusetts, 02215, United States|Columbia P&S (Site ID: 30329), New York, New York, 10032, United States|New York Blood Center (Site ID: 31801), New York, New York, 10065, United States|Penn Prevention (Site ID: 30310), Philadelphia, Pennsylvania, 19104, United States|University of Pittsburgh (Site ID: 1001), Pittsburgh, Pennsylvania, 15213, United States|Seattle Vaccine and Prevention (Site ID: 30331), Seattle, Washington, 98104, United States|Vaccine Trial Centre, Mahidol University CRS (Site ID: 32021), Bangkok, Ratchathewi, 10400, Thailand

Summary:
This is a multicenter, open-label, non-randomized, dose escalation, first-in-human (FIH) trial to evaluate the safety and immunogenicity of CH505M5 N197D mRNA-gp160 and CH505 TF mRNA-gp160. Both products are mRNA encapsulated in lipid nanoparticles (LNPs) (subsequently referred to as mRNA-LNPs). The primary hypotheses are:

1. the CH505M5 N197D mRNA-gp160 will expand CH235-like B cell precursors,
2. the CH505 TF mRNA-gp160 will boost CH235-like bnAb B cell precursors to acquire more functional mutations needed for broadly neutralizing antibody (bnAb) development, and
3. these mRNA-LNPs will be safe and well tolerated among individuals living without HIV.

Primary Outcome Measures: Frequency of local reactogenicity signs and symptoms after receipt of any study vaccine, Day 15, 71, 127 and 183 (14 days following receipt of any study vaccine)|Frequency of systemic reactogenicity signs and symptoms after receipt of any study vaccine, Day 15, 71, 127 and 183 (14 days following receipt of any study vaccine)|Number of serious adverse events (SAEs) leading to early participant withdrawal or permanent discontinuation, 20 months|Number of medically attended adverse events (MAAEs) leading to early participant withdrawal or permanent discontinuation, 20 months|Number of adverse events of special interest (AESIs) leading to early participant withdrawal or permanent discontinuation, 20 months|Number of adverse events (AEs) leading to early participant withdrawal or permanent discontinuation, 20 months|Response rate of CD4-bs and CH505M5-specific IgG+ B cells as assessed by flow cytometry, Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Response rate of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains, as measured by TZM-bl assay, Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Magnitude of serum Ab neutralization of vaccine-matched tier 2 HIV-1 strains, as measured by TZM-bl assay, Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Response rate of differential serum antibody neutralization of precursor detection virus and corresponding epitope KO virus, as measured by the TZM-bl assay, Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Magnitude of differential serum antibody neutralization of precursor detection virus and corresponding epitope KO virus, as measured by the TZM-bl assay, Day 127 and 183 (2 weeks after the third and fourth vaccinations)
Secondary Outcome Measures: Response rate of serum IgG binding antibodies to autologous and heterologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA), Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Magnitude of serum IgG binding antibodies to autologous and heterologous HIV Env stabilized trimers, as assessed by BAMA, Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Response rate of serum Ab neutralization of heterologous HIV-1 strains as measured by TZM-bl assay, Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Magnitude of serum Ab neutralization of heterologous HIV-1 strains as measured by TZM-bl assay, Day 127 and 183 (2 weeks after the third and fourth vaccinations)|Frequency of CD4-bs specific sequences, as measured by BCR single cell sequencing of CD4-bs and CH505M5-specific IgG+ B cells, 20 months|Epitope specific response rates as measured by electron microscopy-based polyclonal epitope mapping (EMPEM), Day 183 (2 weeks after the fourth vaccination)|Response rate of serum IgG binding Abs to Env Trimers and neutralizing epitopes as assessed by BAMA, Day 337 (24 weeks after the fourth vaccination)|Magnitude of serum IgG binding Abs to Env Trimers and neutralizing epitopes as assessed by BAMA, Day 337 (24 weeks after the fourth vaccination)|Response rate of serum Ab neutralization of autologous, heterologous and precursor HIV-1 strains as measured by TZM-bl assay, Day 337 (24 weeks after the fourth vaccination)|Magnitude of serum Ab neutralization of autologous, heterologous and precursor HIV-1 strains as measured by TZM-bl assay, Day 337 (24 weeks after the fourth vaccination)|Response rate of CD4-bs and CH505M5-specific IgG+ B cells as measured by flow cytometry, Day 337 (24 weeks after the fourth vaccination)