Clinical Trial to Evaluate the Safety and Immunogenicity of a Priming Regimen of 426c.Mod.Core-C4b Followed by HxB2.WT.Core-C4b Boosts, Both Adjuvanted With 3M-052 AF + Alum, in Adult Participants Without HIV and in Overall Good Health

NCT06796686 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HVTN 320
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 6

Brief Summary

This is a partially randomized, open-label phase 1 study to evaluate the safety and immunogenicity of a priming regimen of 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum followed by boosts with HxB2.WT.Core-C4b adjuvanted with 3M-052 AF + Alum. The primary hypothesis is that the boosting with HxB2.WT.Core-C4b adjuvanted with 3M-052 AF + Alum will further mature broadly neutralizing antibody (bnAb)-precursor B-cell lineages elicited by 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum. 426c.Mod.Core-C4b adjuvanted with 3M-052 AF + Alum has been tested in HVTN 301 previously, whereas the HxB2.WT.Core-C4b will be first-in-human (FIH).

Conditions

HIV

Keywords

HIV Infection

Outcome Measures

Primary Outcomes (8)

• Incidence of Local Signs and Symptoms within 14 Days Post-Vaccination

  Within 14 days of receiving study vaccine

• Incidence of Systemic Reactogenicity Signs and Symptoms within 14 Days Post-Vaccination

  Within 14 days of receiving study vaccine

• Incidence of Serious Adverse Events Over 52 Weeks Post-Vaccination

  throughout the study and for 52 weeks following any receipt of the study product

• Incidence of Medically Attended Adverse Events Over 52 Weeks Post-Vaccination

  throughout the study and for 52 weeks following any receipt of the study product

• Incidence of Adverse Events of Special Interest Over 52 Weeks Post-Vaccination

  throughout the study and for 52 weeks following any receipt of the study product

• Incidence of Adverse Events Leading to Withdrawal or Discontinuation Over 52 Weeks Post-Vaccination

  throughout the study and for 52 weeks following any receipt of the study product

• Frequency of CD4-bs-specific B cells before and approximately 12 weeks after each HxB2.WT.Core-C4b boost

  assessed by flow cytometry

  12 weeks after each HxB2.WT.Core-C4b boost

• Evolution of CD4-bs-Specific BCRs Before and 12 Weeks After Each HxB2.WT.Core-C4b Boost

  Assessed by VH/VL Sequencing of Sorted B Cells

  12 Weeks After Each HxB2.WT.Core-C4b Boost

Secondary Outcomes (39)

• Response rate of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost

  2 weeks after each HxB2.WT.Core-C4b boost

• Potency of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost

  2 weeks after each HxB2.WT.Core-C4b boost

• Neutralizing breadth of serum antibodies at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost

  2 weeks after each HxB2.WT.Core-C4b boost

• Response rate of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost

  2 weeks after each HxB2.WT.Core-C4b boost

• Magnitude of Env-specific serum IgG binding antibodies will be assessed at 2 weeks after the final 426c.Mod.Core-C4b prime and 2 weeks after each HxB2.WT.Core-C4b boost

  2 weeks after each HxB2.WT.Core-C4b boost

Study Arms (3)

Group 1

ACTIVE COMPARATOR

One fractional dose of 426c.Mod.Core-C4b and two bolus doses of HxB2.WT.Core-C4b

Biological: 426c.Mod.Core-C4b; Biological: HxB2.WT.Core-C4b; Biological: 3M-052-AF adjuvant; Other: Aluminum hydroxide suspension (Alum) adjuvant; Other: Diluent

Group 2A

ACTIVE COMPARATOR

One fractional dose and one bolus dose of 426c.Mod.Core-C4b two bolus doses of HxB2.WT.Core-C4b

Biological: 426c.Mod.Core-C4b; Biological: HxB2.WT.Core-C4b; Biological: 3M-052-AF adjuvant; Other: Aluminum hydroxide suspension (Alum) adjuvant; Other: Diluent

Group 2B

ACTIVE COMPARATOR

One split dose and one bolus of 426c.Mod.Core-C4b and two bolus doses of HxB2.WT.Core-C4b

Biological: 426c.Mod.Core-C4b; Biological: HxB2.WT.Core-C4b; Biological: 3M-052-AF adjuvant; Other: Aluminum hydroxide suspension (Alum) adjuvant; Other: Diluent

Interventions

426c.Mod.Core-C4b BIOLOGICAL

426c.Mod.Core-C4b is supplied at a concentration of 2 mg/mL, 0.55 mL per vial.

Group 1; Group 2A; Group 2B

HxB2.WT.Core-C4b BIOLOGICAL

HxB2.WT.Core-C4b is supplied at a concentration of 1 mg/mL, 0.5 mL per vial

Group 1; Group 2A; Group 2B

3M-052-AF adjuvant BIOLOGICAL

immune response modifier (IRM)

Group 1; Group 2A; Group 2B

Aluminum hydroxide suspension (Alum) adjuvant OTHER

Alhydrogel.

Group 1; Group 2A; Group 2B

Diluent OTHER

Tris-NaCl buffer

Group 1; Group 2A; Group 2B

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, willing to undergo leukapheresis, and willing to be contacted after the last study-product administration, including for potential participation in additional studies.
• 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 320 PSRT are required prior to enrollment into HVTN 320.
• 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 judgment of the site investigator.
• Agrees to discuss their potential for HIV acquisition and agrees to prevention counseling.
• 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 × upper limit of institutional reference range.
• Serum creatinine ≤ 1.1 × upper limit of normal (ULN) based on the institutional normal 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 (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.
• Previous receipt of VRC01 mAb or other CD4bs mAbs.
• 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.
• 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 related vaccine or component of the study-vaccine regimen (eg, imiquimod).
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (6)

Bridge HIV, San Francisco Department of Public Health

San Francisco, California, 94102, United States

NOT YET RECRUITING

Ponce de Leon Center CRS

Atlanta, Georgia, 30308, United States

NOT YET RECRUITING

The Hope Clinic of the Emory Vaccine Research Center; Emory University

Decatur, Georgia, 30030, United States

RECRUITING

Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

Boston, Massachusetts, 02115, United States

RECRUITING

Columbia Physicians & Surgeons

New York, New York, 10032, United States

NOT YET RECRUITING

NY Blood Center CRS

New York, New York, 10065, United States

WITHDRAWN

MeSH Terms

Conditions

HIV Infections

Interventions

aluminum sulfate; Adjuvants, Pharmaceutic

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

Intervention Hierarchy (Ancestors)

Pharmaceutic Aids; Pharmaceutical Preparations; Specialty Uses of Chemicals; Chemical Actions and Uses

Study Design

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

Study Record Dates

• First Submitted: January 22, 2025
• First Posted: January 28, 2025
• Study Start: March 17, 2025
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 15, 2027
• Last Updated: September 25, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)