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HIV InfectionsPhase 1NCT06665646

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

A Phase 1 study testing CD40.HIVRI.Env (VRIPRO) and Hiltonol Poly-ICLC-adjuvant in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
HIV Infections
What is being tested?
CD40.HIVRI.Env (VRIPRO) and Hiltonol Poly-ICLC-adjuvant
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
9 sitesin 2 countries
Study dates
14 Sep 2025to 30 Nov 2027
Phase
Phase 1
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.
  • 18 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.
  • 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 318 (Protocol Safety Review Team) PSRT are required prior to enrollment into HVTN 318. Previous enrollment in HVTN 706 study is a requirement, per inclusion criteria 1.
  • In good general health according to the clinical judgment of the site investigator.
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  • 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.
  • White blood cell (WBC) count = 2,500 to 12,000/mm^3 (WBC over 12,000/mm^3 is not exclusionary if further evaluation shows general good health and if PSRT approval is granted).
  • 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.
  • Systolic blood pressure of 90 to < 140 mmHg and diastolic blood pressure of 50 to < 90 mmHg at screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mmHg systolic and 90 mmHg diastolic. A single measurement ≥ 160 systolic mmHg or 100 mmHg diastolic during the current study evaluation is exclusionary.
  • Negative HIV test results by one of the following options:
  • For participants who received study product under HVTN 706
  • A negative result from a HVTN HIV Diagnostic Testing Laboratory within 14 days prior to enrollment (see HVTN 318 HIV testing SSP for additional details); or
  • A negative result from a non-HVTN laboratory following the external guidance for non-HVTN laboratories within 14 days prior to enrollment (external laboratory guidance for non-HVTN laboratories can be found in the guidance document, HIV Infection and VISP/R Status Diagnostic Testing at External (non-HVTN Laboratories).
  • For participants at who received placebo under HVTN 706
  • A negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA); or a chemiluminescent microparticle immunoassay (CMIA); or
  • A negative result on 2 different HIV rapid tests (one of these rapid tests must be FDA approved)
  • Negative for anti-Hepatitis C virus (HCV) Abs (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV antibodies (Abs) are detected.
  • Negative for Hepatitis B surface antigen (Ag).
  • Women with pregnancy potential:
  • Must have a negative β-HCG pregnancy test (urine or serum) on day of enrollment.
  • Must agree to use effective means of contraception from at least 21 days prior to enrollment until 8 weeks after their last scheduled vaccination. See Appendix D.
  • Women who have had a total hysterectomy, bilateral oophorectomy, or bilateral salpingectomy Consider including the cyan-highlighted parenthetical for product-specific reasons: (verified by medical records) or menopause (no menses for ≥1 year) are not required to undergo pregnancy testing.
  • Female volunteers must agree to not seek pregnancy through alternative methods, such as oocyte retrieval, artificial insemination, or in vitro fertilization from at least 21 days prior to enrollment through 8 weeks after their last scheduled vaccination timepoint.

Who cannot join

  • 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.
  • Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤ 8% within the last 6 months) or a history of isolated gestational diabetes are not exclusionary. Enrollment of individuals with Type 2 DM that is well controlled on hypoglycemic agent(s) may be considered by the PSRT on a case-by-case basis, provided that the HgbA1c is ≤ 8% within the last 6 months (sites may draw these at screening).
  • Previous or current recipient of an investigational HIV vaccine (not applicable to previous placebo/control recipients), with the exception of the HVTN 706 vaccine regimen as per Inclusion Criteria #1.
  • 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.
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  • Receipt of any vaccine within 4 weeks prior to enrollment
  • Initiation of Ag-based immunotherapy for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval.
  • 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).
  • Asthma patients will not be enrolled if the volunteer has ANY of the following:
  • Required either oral or parenteral corticosteroids for an exacerbation 2 or more times within the past year; OR
  • Needed emergency care, urgent care, hospitalization, or intubation for an acute asthma exacerbation within the past year (eg, would NOT exclude individuals with asthma who meet all other criteria but sought urgent/emergent care solely for asthma medication refills or coexisting conditions unrelated to asthma); OR
  • Uses a short-acting rescue inhaler more than 2 days per week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR
  • Uses medium- to high-dose inhaled corticosteroids (> 250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist [LABA]); OR
  • Uses more than 1 medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than 1 medication for maintenance therapy daily for greater than 2 years requires PSRT approval.
  • A participant with a history of a potential immune-mediated medical condition (PIMMC), either active or remote. Specific examples are listed in Appendix F (AESI Index). Not exclusionary: 1) Remote history of Bell's palsy (> 2 years ago) not associated with other neurologic symptoms and 2) mild psoriasis or other mild, uncomplicated, localized, or dermatologic condition that does not require ongoing systemic treatment.
  • History of allergy to local anesthetic (Novocaine, Lidocaine).
  • Volunteer who is breastfeeding or pregnant.
  • Investigator concern for difficulty with venous access based on clinical history and physical examination. For example, persons with a history of intravenous drug use or substantial difficulty with previous blood draws.

Trial locations and contacts

9 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

9 sites in 2 countries

United States7 sites, 4 recruiting
  • Brigham and Women's Hospital Vaccine CRS (BWH VCRS)

    Boston, Massachusetts, 02115-6110

    Jose Licona, MD, 1-617-5259433, jlicona@partners.org

    Recruiting
  • The Hope Clinic of the Emory Vaccine Center CRS

    Decatur, Georgia, 30030

    Withdrawn
  • Vanderbilt Vaccine (VV) CRS

    Nashville, Tennessee, 37232

    Shonda Sumner, BSN, 1-615-3436906, Shonda.sumner@vumc.org

    Recruiting
  • Columbia P&S CRS

    New York, New York, 10032

    Withdrawn
  • Penn Prevention CRS (Site ID# 30310)

    Philadelphia, Pennsylvania, 19104

    Debora Dunbar, MSN, CRNP, 1-215-7463713, ddunbar@pennmedicine.upenn.edu

    Recruiting
  • Bridge HIV CRS

    San Francisco, California, 94102

    Emily Schaeffer, BA, 1-415-2141085, emily.schaeffer@sfdph.org

    Recruiting
  • Seattle Vaccine and Prevention CRS

    Seattle, Washington, 98104

    Withdrawn

Other trials in United States

Peru2 sites, 2 recruiting
  • Centro de Investigaciones Tecnológicas, Biomédicas y Medioambientales CRS (CITBM) - Unidad de Ensayos Clínicos (UNIDEC)

    Bellavista, Provincia Constitucional del Callao, 07006

    Fanny G. Rosas Benancio, 51-1-4800401 ext. 1007, frosas@citbm.pe

    Not yet recruiting
  • Via Libre CRS

    Lima Cercado, Lima region, 15001

    Carlos Anton Talledo, 51-12-039900 ext. 156, canton@vialibre.org.pe

    Not yet recruiting

Other trials in Peru

About this study

Official title: A Phase 1 Open-label, Non-randomized, 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

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
Being tested
CD40.HIVRI.Env (VRIPRO), Hiltonol Poly-ICLC-adjuvant
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • CD40.HIVRI.Env (VRIPRO)Biological

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

  • Hiltonol Poly-ICLC-adjuvantBiological

    Vaccine adjuvant

Study groups in NCT06665646
Study groupRoleWhat they receive
Group 1- Study product received in HVTN 706: Study VaccineExperimentalParticipants will receive Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env(VRIPRO) as a subcutaneous injection.
Receives: Biological: CD40.HIVRI.Env (VRIPRO); Biological: Hiltonol Poly-ICLC-adjuvant
Group 2 - Study product received in HVTN 706: PlaceboExperimentalParticipants will receive Hiltonol, Poly-ICLC-adjuvanted CD40.HIVRI.Env(VRIPRO) as a subcutaneous injection.
Receives: Biological: CD40.HIVRI.Env (VRIPRO); Biological: Hiltonol Poly-ICLC-adjuvant

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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)

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

  2. 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)

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

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

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

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

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

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

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

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

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

  7. 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

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

  8. 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

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

  9. 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

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

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

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

Secondary outcomes (20)
  1. Response rate of serum HIV-1-specific IgG binding antibodies against autologous and heterologous Env antigens as assessed by binding Ab multiplex assay (BAMA)

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

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

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

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

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

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

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

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

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

  6. Magnitude of serum HIV-1 specific IgG3 binding antibodies against autologous V1V2 antigens as assessed by BAMA

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

  7. Response rate of serum HIV-1 specific IgG3 binding antibodies against heterologous V1V2 antigens as assessed by BAMA

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

  8. Magnitude of serum HIV-1 specific IgG3 binding antibodies against heterologous V1V2 antigens as assessed by BAMA

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

  9. Response rate of serum Ab neutralization of autologous HIV-1 strains as measured by the TZM-bl assay

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

  10. Magnitude of serum Ab neutralization of autologous HIV-1 strains as measured by the TZM-bl assay

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

  11. Response rate of serum Ab neutralization of heterologous HIV-1 strains as measured by TZM-bl assay

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

  12. Magnitude of serum Ab neutralization of heterologous HIV-1 strains as measured by TZM-bl assay

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

  13. Response rate of CD4+ and CD8+ T-cell responses as assessed by intracellular cytokine staining, Epimax, or other assays, as needed

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

  14. Magnitude of CD4+ and CD8+ T-cell responses as assessed by intracellular cytokine staining, Epimax, or other assays, as needed

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

  15. Response rate of antibody-dependent cellular cytotoxicity (ADCC)

    Measured: at baseline and 2 weeks after the last vaccination

  16. Magnitude of antibody-dependent cellular cytotoxicity (ADCC)

    Measured: at baseline and 2 weeks after the last vaccination

  17. Response rate of antibody-dependent cellular phagocytosis (ADCP)

    Measured: at baseline and 2 weeks after the last vaccination

  18. Magnitude of antibody-dependent cellular phagocytosis (ADCP)

    Measured: at baseline and 2 weeks after the last vaccination

  19. Magnitude of Env-specific binding Abs assessed by the slope of BAMA titers

    Measured: weeks 26 and 48

  20. Frequency of total memory B cells and vaccine-specific B cell receptors

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Oct 2024
  2. Study start14 Sep 2025
  3. Primary completion30 Nov 2027 (estimated)
  4. Study completion30 Nov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Prevention
Allocation
Non-randomised
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06665646
Sponsor's protocol ID
HVTN 318
Status last verified
Sep 2026
First submitted
17 Sep 2024
Last updated
18 Sep 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing CD40.HIVRI.Env (VRIPRO) and Hiltonol Poly-ICLC-adjuvant in people with HIV Infections, run by National Institute of Allergy and Infectious Diseases (NIAID) at 9 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 31 inclusion and 28 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites in United States, Peru. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Each site lists its own contact: choose the nearest one under Trial locations. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Local signs and symptoms will be collected for a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO) (time frame: For a minimum of 14 days following receipt of adjuvanted CD40.HIVRI.Env (VRIPRO)). The study lists 10 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2026.

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