Clinical Trial to Evaluate the Safety and Immunogenicity of Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env (VRIPRO) in Adult Participants Who Previously Participated in HVTN 706

NCT06665646 | Recruiting Phase 1 FDA Drug

• 1 other identifier: HVTN 318
• Study Type: interventional
• Target: 40
• Locations: 2 countries
• Sites: 9

Brief Summary

The clinical schedule will consist of 3 injections of CD40.HIVRI.Env (VRIPRO) at weeks 0, 4, and 24.40 volunteers without HIV and in overall good health, aged 18 to 60 years, who previously participated in the HVTN 706 trial.

Conditions

HIV Infections

Outcome Measures

Primary Outcomes (10)

• Local signs and symptoms will be collected for a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO)

  Local events at the injection site include pain/tenderness, induration and erythema. These will be graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)

  For a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO)

• Systemic reactogenicity signs and symptoms will be collected

  Systemic events include increased body temperature, fatigue, generalized myalgia, generalized arthralgia, headache, chills, and nausea. These will be graded according to the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events,Corrected Version 2.1, July 2017 (exceptions apply)

  For a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO)

• Number of SAEs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product

  30 days after receipt of study vaccination up to 1 year following study product

• Number of MAAEs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product

  30 days after receipt of study vaccination up to 1 year following study product

• Number of AESIs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product

  30 days after receipt of study vaccination up to 1 year following study product

• Number of AEs leading to early participant withdrawal or permanent discontinuation will be collected throughout the study and for 1 year following study product

  30 days after receipt of study vaccination up to 1 year following study product

• Response rate of HIV-1-specific serum IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA) in HVTN 706 regimen recipients

  2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

• Magnitude of HIV-1-specific serum IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA) in HVTN 706 regimen recipients

  2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

• Response rate of HIV-1-specific serum IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA in HVTN 706 regimen recipients

  2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

• Magnitude of HIV-1-specific serum IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA in HVTN 706 regimen recipients

  2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

Secondary Outcomes (20)

• Response rate of serum HIV-1-specific IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA)

  2 weeks after the receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

• Magnitude of serum HIV-1-specific IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA)

  2 weeks after the receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

• Response rate of serum-HIV-1 specific IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA

  2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

• Magnitude of serum-HIV-1 specific IgG binding antibodies against autologous and heterologous V1V2 antigens as assessed by BAMA

  2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

• Response rate of serum HIV-1 specific IgG3 binding antibodies against autologous V1V2 antigens as assessed by BAMA

  2 weeks after receipt of the full CD40.HIVRI.Env (VRIPRO) regimen

Study Arms (2)

Group 1- Study product received in HVTN 706: Study Vaccine

EXPERIMENTAL

Participants will receive Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env(VRIPRO) as a subcutaneous injection.

Biological: CD40.HIVRI.Env (VRIPRO); Biological: Hiltonol Poly-ICLC-adjuvant

Group 2 - Study product received in HVTN 706: Placebo

EXPERIMENTAL

Participants will receive Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env(VRIPRO) as a subcutaneous injection.

Biological: CD40.HIVRI.Env (VRIPRO); Biological: Hiltonol Poly-ICLC-adjuvant

Interventions

CD40.HIVRI.Env (VRIPRO) BIOLOGICAL

To be administered subcutaneously as 1 mg admixed with Hiltonol, Poly-ICLC as a single dose.

Group 1- Study product received in HVTN 706: Study Vaccine; Group 2 - Study product received in HVTN 706: Placebo

Hiltonol Poly-ICLC-adjuvant BIOLOGICAL

Vaccine adjuvant

Group 1- Study product received in HVTN 706: Study Vaccine; Group 2 - Study product received in HVTN 706: Placebo

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Formerly participated in HVTN 706 study as active vaccine arm or placebo recipient (those enrolled in the active vaccine arm of HVTN 706 must have received all 4 vaccinations according to the HVTN 706 protocol).
• Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
• to ≤ 60 years old, on day of enrollment.
• Available for clinic follow-up through the last clinic visit, willing to undergo FNA, and willing to be contacted 12 months after the last study-product administration.
• 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.
• Agrees to discuss the potential for HIV acquisition and agrees to prevention counseling.
• Hemoglobin (Hgb):
• ≥11.0 g/dL for women
• ≥13.0 g/dL for men
• If receiving exogenous hormones for more than 6 consecutive months with dosing equivalent to parenteral testosterone ≥1000 mg every 12 weeks or estradiol valerate ≥2 mg/week, determine hemoglobin eligibility based on the exogenous hormone reported.
• Platelets = 125,000 to 550,000/mm\^3.
• Alanine aminotransferase (ALT) \< 2.5 x upper limit of institutional reference range.
• Serum creatinine ≤ 1.1 x upper limit of normal (ULN) based on the institutional normal range.
• Negative HIV test results by one of the following options:

You may not qualify if:

• 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.
• 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 vaccine within 4 weeks prior to enrollment
• 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.
• Use of injectable long-acting Cabotegravir within 18 months prior to enrollment.
• Serious adverse reactions to any vaccine, including anaphylaxis and related symptoms such as hives, respiratory difficulty, angioedema, and/or abdominal pain. (Not applicable to a participant who had a non-anaphylactic adverse reaction to pertussis vaccine as a child.)
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.
• Bleeding disorder diagnosed by a clinician that would make study procedures a contraindication.
• History of seizure(s) within the past 3 years. Also applies to volunteer using medications in order to prevent or treat seizure(s) at any time within the past 3 years.
• Asplenia or functional asplenia.
• Active duty and reserve US military personnel.
• Any other chronic or clinically significant condition that, in the clinical judgment of the investigator, would jeopardize the safety or rights of the study participant, including but not limited to: clinically significant forms of substance use or alcohol use disorder(s), serious psychiatric disorders, any suicide attempt within the past 1 year (if between 1 and 2 years, consult PSRT for approval), or cancer that, in the clinical judgement of the site investigator, has potential for recurrence (excluding basal cell carcinoma).

Sponsors & Collaborators

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

Study Sites (9)

Bridge HIV CRS

San Francisco, California, 94102, United States

RECRUITING

The Hope Clinic of the Emory Vaccine Center CRS

Decatur, Georgia, 30030, United States

WITHDRAWN

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

Boston, Massachusetts, 02115-6110, United States

RECRUITING

Columbia P&S CRS

New York, New York, 10032, United States

WITHDRAWN

Penn Prevention CRS (Site ID# 30310)

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Vanderbilt Vaccine (VV) CRS

Nashville, Tennessee, 37232, United States

RECRUITING

Seattle Vaccine and Prevention CRS

Seattle, Washington, 98104, United States

WITHDRAWN

Via Libre CRS

Lima Cercado, Lima region, 15001, Peru

NOT YET RECRUITING

Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC)

Bellavista, Provincia Constitucional del Callao, 07006, Peru

NOT YET RECRUITING

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: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 17, 2024
• First Posted: October 30, 2024
• Study Start: September 14, 2025
• Primary Completion (Estimated): July 27, 2026
• Study Completion (Estimated): May 4, 2027
• Last Updated: June 5, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7); PE (2)