A Study to Evaluate the Safety and Immunogenicity of the V3-region Directed Immunogens DV700P-RNA Followed by DV701B1.1-RNA in Adults Without HIV

NCT06919016 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: HVTN 321
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 8

Brief Summary

This is a phase 1, first-in-human (FIH) trial for two vaccines, DV700P-RNA and DV701B1.1-RNA. This means it is the first time these study products are being tested in people. The purpose of this study is to see if the study products are safe, if people are able to take them without becoming too uncomfortable, and how a person's immune system responds to them (a person's immune system protects them from infections and disease). Forty-five volunteers without HIV and in overall good health, aged 18 to 55 years, will be enrolled and be in this study for about 16 months (about 12 visits), Study procedures will include blood draws, injections, and the collection of white blood cells and cells from their lymph nodes.

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (9)

• Incidence of local reactogenicity signs and symptoms

  At days 15, 71, 183 and 295 (14 days following receipt of any study vaccine)

• Incidence of systemic reactogenicity signs and symptoms

  At days 15, 71, 183 and 295 (14 days following receipt of any study vaccine)

• Number of participants experiencing Serious adverse events (SAEs)

  Baseline through Month 22

• Number of participants experiencing medically attended adverse events (MAAEs)

  Baseline through Month 22

• Number of participants experiencing adverse events of special interest (AESIs)

  Baseline through Month 22

• Number of participants experiencing adverse events (AEs) leading to early participant withdrawal or permanent discontinuation will be collected throughout the study

  Baseline through Month 22

• Response rate of V3G-specific IgG+ B cells, as assessed by flow cytometry

  At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)

• Response rate of differential serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by the TZM-bl assay

  At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)

• Magnitude of differential serum antibody neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by the TZM-bl assay

  At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)

Secondary Outcomes (6)

• Response rate of serum IgG binding antibodies to autologous and heterologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA)

  At weeks 26 and 42 (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

  At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)

• Response rate of serum antibody (Ab) neutralization of heterologous tier 2 HIV-1 strains, as measured by TZM-bl assay

  At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)

• Magnitude of serum Ab neutralization of heterologous tier 2 HIV-1 strains, as measured by TZM-bl assay

  At weeks 26 and 42 (2 weeks after the third and fourth vaccinations)

• Frequency of V3G bnAb lineage sequences, as measured by B-cell receptor (BCR) single-cell sequencing of V3G-specific IgG+ B cells

  Baseline though Month 22

Study Arms (3)

Group 1

EXPERIMENTAL

DV700P-RNA: 50 mcg at weeks 0, 8, and 24 DV701B1.1-RNA: 50 mcg at week 40

Biological: DV700P-RNA; Biological: DV701B1.1-RNA

Group 2

EXPERIMENTAL

DV700P-RNA: 100 mcg at weeks 0, 8, and 24 DV701B1.1-RNA: 100 mcg at week 40

Biological: DV700P-RNA; Biological: DV701B1.1-RNA

Group 3

EXPERIMENTAL

DV700P-RNA: 150 mcg at weeks 0, 8, and 24 DV701B1.1-RNA: 150 mcg at week 40

Biological: DV700P-RNA; Biological: DV701B1.1-RNA

Interventions

DV700P-RNA BIOLOGICAL

Intramuscular (IM) injection

Group 1; Group 2; Group 3

DV701B1.1-RNA BIOLOGICAL

IM injection

Group 1; Group 2; Group 3

Eligibility Criteria

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

You may qualify if:

• Understands the study and agrees to complete the consent process.
• Can attend all clinic visits until the end of the study.
• Agrees to follow all study procedures.
• Will not join another study with experimental treatments during this trial, unless approved by both study sponsors.
• Generally healthy according to the study doctor.
• Physical exam and lab results show no major issues that could affect safety or study results.
• Agrees to discuss HIV risk and prevention.
• Hemoglobin levels: at least 11.0 g/dL for women and 13.0 g/dL for men.
• White blood cell count between 2,500 to 12,000/mm³ (higher levels okay if health is otherwise good and approved).
• Platelet count between 125,000 to 550,000/mm³.
• ALT enzyme level less than 2.5 times the upper limit of normal.
• Serum creatinine level within 1.1 times the upper limit of normal.
• Serum calcium level at least 8.5 mg/dL.
• Blood pressure within acceptable range (systolic 90-140 mmHg, diastolic 50-90 mmHg), with average below 140/90 mmHg and no single reading over 160/100 mmHg.
• Negative HIV test.

You may not qualify if:

• Breastfeeding or pregnant.
• Body mass index (BMI) of 40 or higher, unless in good health and approved.
• Diabetes, unless it is well-controlled Type 2 diabetes or gestational diabetes.
• Previous or current investigational HIV vaccine recipients (placebo recipients are allowed).
• Received non-HIV investigational vaccines within the last year, unless they are now licensed or authorized.
• Immunodeficiency or medications that impair immune response, such as high-dose steroids.
• Received blood products or immunoglobulin within 16 weeks before enrollment.
• Received certain vaccines within the last 4 weeks before enrollment.
• Received other vaccines within 14 days before enrollment.
• History of myocarditis or pericarditis.
• Started allergy immunotherapy in the past year (unless stable and approved).
• Taken investigational research agents recently.
• Serious allergic reactions to any mRNA vaccine or drugs containing polyethylene glycol.
• History of hereditary or acquired angioedema.
• Any episode of hives (urticaria) within the past year.

Sponsors & Collaborators

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

Study Sites (8)

University of Alabama Medical Center (Site ID: 31788)

Birmingham, Alabama, 35222, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS (Site ID: 31440)

Decatur, Georgia, 30030, United States

Location

Brigham and Women's Hospital (Site ID: 30007)

Boston, Massachusetts, 02215, United States

Location

Columbia P&S CRS (Site ID: 30329)

New York, New York, 10032, United States

Location

University of Rochester Medical Center (Site ID: 31467)

Rochester, New York, 14642, United States

Location

University of Pittsburgh (Site ID: 1001)

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt University Medical Center (Site ID: 30352)

Nashville, Tennessee, 37232, United States

Location

Seattle Vaccine and Prevention CRS (Site ID: 30331)

Seattle, Washington, 98104, United States

Location

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: April 2, 2025
• First Posted: April 9, 2025
• Study Start: August 6, 2025
• Primary Completion (Estimated): March 25, 2027
• Study Completion (Estimated): March 25, 2027
• Last Updated: December 16, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)