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

NCT06557785 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: HVTN 31239019
• Study Type: interventional
• Target: 53
• Locations: 2 countries
• Sites: 7

Brief 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. 1.the CH505M5 N197D mRNA-gp160 will expand CH235-like B cell precursors,
2. 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. 3.these mRNA-LNPs will be safe and well tolerated among individuals living without HIV.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (11)

• 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 Outcomes (11)

• 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

Study Arms (4)

Group 1 (25 mcg)

EXPERIMENTAL

25 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 25 mcg of CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

Biological: CH505M5 N197D mRNA-gp160; Biological: CH505 TF mRNA-gp160

Group 2 (50 mcg)

EXPERIMENTAL

50 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 50 mcg of CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

Biological: CH505M5 N197D mRNA-gp160; Biological: CH505 TF mRNA-gp160

Group 3 (100 mcg)

EXPERIMENTAL

100 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 100 mcg of CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

Biological: CH505M5 N197D mRNA-gp160; Biological: CH505 TF mRNA-gp160

Group 4 (150 mcg)

EXPERIMENTAL

150 mcg of CH505M5 N197D mRNA-gp160, to be administered as a split dose intramuscularly at weeks 0, 8, and 16. Followed by: 150 mcg CH505 TF mRNA-gp160, to be administered as a split dose intramuscularly at week 24.

Biological: CH505M5 N197D mRNA-gp160; Biological: CH505 TF mRNA-gp160

Interventions

CH505M5 N197D mRNA-gp160 BIOLOGICAL

To be administered intramuscularly as a split dose

Group 1 (25 mcg); Group 2 (50 mcg); Group 3 (100 mcg); Group 4 (150 mcg)

CH505 TF mRNA-gp160 BIOLOGICAL

To be administered intramuscularly as a split dose

Group 1 (25 mcg); Group 2 (50 mcg); Group 3 (100 mcg); Group 4 (150 mcg)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
• to 55 years old, inclusive, on day of enrollment.
• Available for clinic follow-up through the last clinic visit and willing to undergo FNA of an axillary lymph node and undergo leukapheresis.
• Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 312 Protocol Safety Review Team (PSRT) are required prior to enrollment into HVTN 312.
• In good general health according to the clinical judgment of the site investigator.
• Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgement of the site investigator.
• For US sites: Agrees to discuss their potential for HIV acquisition and agrees to prevention counseling.
• For non-US sites: Assessed by clinical staff as having a low likelihood of acquiring HIV per guidelines, agrees to discuss their potential for HIV acquisition, agrees to prevention counseling, and agrees to avoid behaviors associated with a higher likelihood of acquiring HIV through the final study visit. "Low likelihood" may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed.
• Hemoglobin (Hgb):
• ≥ 11.0 g/dL for AFAB volunteers
• ≥ 13.0 g/dL for cisgender AMAB volunteers or for volunteers who have been on masculinizing hormone therapy for more than 6 consecutive months
• ≥ 12.0 g/dL for AMAB volunteers who have been on feminizing hormone therapy for more than 6 consecutive months
• For volunteers who have been on gender-affirming hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth.
• Platelets = 125,000 to 550,000/mm3.
• Alanine aminotransferase (ALT) \< 2.5 x upper limit of institutional reference range.

You may not qualify if:

• Volunteer who is breastfeeding/chestfeeding or pregnant.
• Body mass index (BMI) ≥ 40. Enrollment of individuals with BMI ≥ 40, whom the site investigator assesses are in good health, may be considered by PSRT approval.
• Previous or current recipient of an investigational HIV vaccine or HIV mAb (previous placebo/control recipients are not excluded).
• Receipt of non-HIV investigational vaccine(s) received within the last 1 year. Exceptions include vaccines that have subsequently undergone licensure or Emergency Use Authorization (EUA) by the FDA or World Health Organization (WHO) Emergency Use Listing (EUL), or if outside the US, by the national Regulatory Authority (RA) authorizing this clinical trial.
• Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, such as glucocorticoid use, ≥ prednisone 10 mg/day within 3 months prior to enrollment.
• Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
• Receipt of any of the following within 4 weeks prior to enrollment:
• Live replicating vaccine
• Any mRNA-based vaccine with FDA licensure, FDA EUA, or WHO EUL
• ACAM2000 vaccine \> 28 days prior with a vaccination scab still present.
• History of myocarditis and/or pericarditis.
• Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life of more than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.
• History of serious reaction (eg, hypersensitivity, anaphylaxis) to any mRNA vaccine, including Comirnaty® (Pfizer) and Spikevax® (Moderna), or to any drug administered systemically as a polyethylene glycol containing LNP, including doxorubicin (Doxil, Caelyx, ThermoDox), cisplatin (Lipoplatin) and irinotecan (Onivyde).
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• History of chronic urticaria or urticaria previously associated with immunization.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator
• Department of Health and Human Services: collaborator

Study Sites (7)

Beth Israel Deaconess Medical Center (Site ID: 32077)

Boston, Massachusetts, 02215, United States

Location

Columbia P&S (Site ID: 30329)

New York, New York, 10032, United States

Location

New York Blood Center (Site ID: 31801)

New York, New York, 10065, United States

Location

Penn Prevention (Site ID: 30310)

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh (Site ID: 1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

Seattle Vaccine and Prevention (Site ID: 30331)

Seattle, Washington, 98104, United States

Location

Vaccine Trial Centre, Mahidol University CRS (Site ID: 32021)

Bangkok, Ratchathewi, 10400, Thailand

Location

MeSH Terms

Conditions

HIV Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2024
• First Posted: August 16, 2024
• Study Start: November 25, 2024
• Primary Completion (Estimated): March 9, 2027
• Study Completion (Estimated): March 9, 2027
• Last Updated: January 14, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (6); TH (1)