Clinical Trial to Evaluate the Safety and Immunogenicity of Synthetic DNAs Encoding NP-GT8 and IL-12, With or Without a TLR-agonist-Adjuvanted HIV Env Trimer 4571 Boost, in Adults Without HIV

NCT05781542 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HVTN 305
• Study Type: interventional
• Target: 46
• Locations: 2 countries
• Sites: 8

Brief Summary

This is an open-label study to examine the safety and immunogenicity of synthetic DNAs encoding NP-GT8 and IL-12 with or without a TLR-agonist-adjuvanted Env Trimer 4571 boost in adults without HIV. The primary hypothesis is that vaccination with this recombinant DNA vaccine encoding a germline-targeting epitope followed by a trimeric protein boost will elicit VRC01-class B-cell responses as well as antigen-specific T-cell responses.

Conditions

HIV Infections

Keywords

HIV

Outcome Measures

Primary Outcomes (7)

• Number of Participants Reporting Local Solicited Adverse Events Signs and Symptoms: Pain and/or Tenderness

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

  Measured through 7 days following vaccine administration for INO-6172 alone and 14 days following vaccine administration for Trimer 4571 + 3M-052-AF/Alum

• Number of Participants Reporting Local Solicited Adverse Events Signs and Symptoms: Erythema and/or Induration

  Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.1 \[July 2017\]. The maximum grade observed for each symptom over the time frame is presented

  Measured through 7 days following vaccine administration for INO-6172 alone and 14 days following vaccine administration for Trimer 4571 + 3M-052-AF/Alum

• Number of Participants Reporting Unsolicited Adverse Events (AEs), by Severity Grade

  The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm and severity grade. The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm and severity grade. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)

  Measured through 7 days following vaccine administration for INO-6172 alone and 14 days following vaccine administration for Trimer 4571 + 3M-052-AF/Alum

• Number of Participants Reporting Unsolicited Adverse Events (AEs), by Severity Grade

  The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm and severity grade. Graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1, July 2017 (exceptions apply)

  Measured for 30 days after any receipt of study vaccination

• Number of Participants Reporting Medically Attended Adverse Events (MAAEs), by Severity Grade

  The number (percentage) of Participants Reporting Medically Attended Adverse Events (MAAEs) was summarized by arm and severity grade

  Measured through Month 12 following any receipt of study products

• Number of Participants With Early Discontinuation of Vaccinations and Reason for Discontinuation

  The number (percentage) of participants with early discontinuation of vaccinations and reason for discontinuation was summarized by arm

  Measured through Month 12 following any receipt of study products

• Number of Participants With Early Study Termination and Reason for Early Study Termination

  The number (percentage) of participants with early study termination and reason for early study termination was summarized by arm

  Measured through Month 12 following any receipt of study products

Study Arms (3)

Group 1

EXPERIMENTAL

a total of approximately 9 participants will receive 3 administrations of sD-NP-GT8 DNA at a dose of 0.4 mg, coformulated with IL-12 DNA at a dose of 0.1 mg at days 1, 29, and 85. Study products will be administered intradermally via EP of the skin on each upper arm

Biological: sD-NP-GT8 DNA; Biological: IL-12 DNA

Group 2

EXPERIMENTAL

a total of approximately 18 participants will receive 3 administrations of sD-NP-GT8 DNA at a dose of 1.6 mg, coformulated with IL-12 DNA at a dose of 0.4 mg at days 1, 29, and 85. Study products will be administered intradermally via EP of the skin on each upper arm

Biological: sD-NP-GT8 DNA; Biological: IL-12 DNA

Group 3

EXPERIMENTAL

a total of approximately 18 participants will receive 3 administrations of sD-NP-GT8 DNA at a dose of 1.6 mg, coformulated with IL-12 DNA at a dose of 0.4 mg at days 1, 29, and 85. These doses will be administered intradermally via EP of the skin on each upper arm. All participants in Group 3 will also receive 2 administrations of Trimer 4571 at a dose of 100 mcg adjuvanted with 5 mcg of 3M-052-AF + 500 mcg Alum via IM injections into the deltoid muscle at days 85 and 169

Biological: sD-NP-GT8 DNA; Biological: IL-12 DNA; Biological: Trimer 4571; Biological: 3M-052-AF; Drug: Alum

Interventions

sD-NP-GT8 DNA BIOLOGICAL

0.4 mg

Group 1

IL-12 DNA BIOLOGICAL

0.1 mg

Group 1

Trimer 4571 BIOLOGICAL

100 mcg

Group 3

3M-052-AF BIOLOGICAL

5 mcg

Group 3

Alum DRUG

500 mcg

Group 3

Eligibility Criteria

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

You may qualify if:

• Able and willing to complete the informed consent process, including an Assessment of Understanding (AoU): volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly.
• to 55 years old, inclusive, on day of enrollment.
• Available for clinic follow-up through the last clinic visit and willing to be contacted at least 12 months after the last vaccine administration.
• Willing to undergo leukapheresis.
• Agrees not to enroll in another study of an investigational agent during participation in the trial.
• In good general health according to the clinical judgement 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.
• Assessed as low risk for HIV acquisition per low-risk guidelines, agrees to discuss HIV-infection risks, agrees to risk-reduction counseling, and agrees to avoid behaviors associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking HIV pre-exposure prophylaxis (PrEP) as prescribed for 6 months or longer.
• Hemoglobin:
• ≥ 11.0 g/dL for volunteers who were assigned female sex at birth.
• ≥ 13.0 g/dL for volunteers who were assigned male sex at birth and transgender males who have been on hormone therapy for more than 6 consecutive months.
• ≥ 12.0 g/dL for transgender females who have been on hormone therapy for more than 6 consecutive months.
• For transgender participants who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth.
• Platelets = 125,000-550,000/mm3
• Alanine aminotransferase (ALT) \< 2.5 x upper limit of normal (ULN) based on the institutional normal range.

You may not qualify if:

• Volunteer who is breast-feeding or pregnant.
• Morbid obesity. Enrollment of individuals with body mass index (BMI) that is
• ≥ 40, whom the site investigator assesses are in good health, may be considered by PSRT on a case-by-case basis.
• Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
• Systemic glucocorticoid use equal to or greater than prednisone 10 mg/day within 3 months prior to enrollment, congenital or acquired immunodeficiency, or other systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator.
• 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 live attenuated vaccine within 4 weeks prior to enrollment. (Note: ACAM2000 vaccine for Monkeypox received within 30 days prior to enrollment or receipt of study vaccine, or if ACAM2000 received greater than 30 days prior to enrollment, or prior to receipt of study vaccine and vaccination scab still present; or planned administration within 30 days after enrollment or receipt of study vaccine).
• Receipt of any vaccines that are not live attenuated within 14 days prior to enrollment; replication incompetent vaccines such as the Jynneos vaccine for the prevention of monkeypox disease are not considered to be live vaccines.
• Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be made by the HVTN 305 PSRT for vaccines that have subsequently undergone licensure or Emergency Use Authorization by the FDA or, if outside the United States, equivalent authorization by the national regulatory authority.
• 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 greater than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.
• Serious reactions to vaccines that preclude receipt of study injections as determined by the principal investigator (PI) or designee, including history of serious reaction (eg, hypersensitivity, anaphylaxis) to any or any component of the study vaccine.
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• Idiopathic urticaria within the past year.
• Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
• Asplenia or functional asplenia.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• HIV Vaccine Trials Network: collaborator
• The Wistar Institute: collaborator
• The Betty and Dale Bumpers Vaccine Research Center (VRC): collaborator
• Inovio Pharmaceuticals: collaborator
• Access to Advanced Health Institute (AAHI): collaborator
• Department of Health and Human Services: collaborator

Study Sites (8)

Alabama CRS (Site ID: 31788)

Birmingham, Alabama, 35294, United States

Location

Bridge HIV CRS

San Francisco, California, 94102, United States

Location

San Francisco Vaccine and Prevention CRS

San Francisco, California, 94102, United States

Location

Brigham and Women's Hospital Vaccine CRS [30007]

Boston, Massachusetts, 02115, United States

Location

Soweto HVTN CRS

Johannesburg, Gauteng, South Africa

Location

CAPRISA eThekwini CRS

Durban, KwaZulu-Natal, 4013, South Africa

Location

Durban Adult HIV CRS

Durban, KwaZulu-Natal, South Africa

Location

Groote Schuur HIV CRS (Site ID: 31708)

Cape Town, Western Cape, 7925, South Africa

Location

MeSH Terms

Conditions

HIV Infections

Interventions

aluminum sulfate

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

Results Point of Contact

• Title: Jessica Andriesen, PhD, Associate Director of HVTN SDMC Operations
• Organization: Fred Hutchinson Cancer Center

hvtn.covpn.sdmc@hvtn.org

206-667-5812

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: March 23, 2023
• Study Start: April 10, 2023
• Primary Completion: October 2, 2024
• Study Completion: April 14, 2025
• Last Updated: November 14, 2025
• Results First Posted: November 14, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

ZA (4); US (4)