A Clinical Trial to Evaluate the Safety and Immunogenicity of Synthetic DNAs Encoding a Native-like HIV Env Trimer and Interleukin-12 (INO-6160), Alone or in a Prime-boost Regimen With 3M-052-AF + Alum Adjuvanted VRC HIV Env Trimer 4571 in Adult Participants Without HIV

NCT05828095 | Completed Phase 1 Results FDA Drug

• 1 other identifier: HVTN 304
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This is a randomized open-label trial to examine the safety and immunogenicity of INO-6160 (synthetic DNAs encoding a native-like HIV Env Trimer and Interleukin-12), alone or in a prime-boost regimen with VRC HIV Env Trimer 4571 adjuvanted with 3M-052-AF + Alum. The primary hypothesis is that the vaccine regimen will elicit HIV-1 envelope protein-specific binding antibody (Ab) and T-cell responses

Conditions

HIV-1-infection

Outcome Measures

Primary Outcomes (12)

• 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 for 14 days after each injection

• 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 for 14 days after each injection

• Number of Participants Reporting Systemic Solicited Adverse Events Signs and Symptoms

  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 for 14 days after each injection

• Number of Participants Reporting Unsolicited Adverse Events (AEs)

  The number (percentage) of Participants Reporting Unsolicited Adverse Events (AEs) was summarized by arm

  Measured for 30 days after any receipt of study vaccination.

• 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 6

• 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 10

• Response Rate of Vaccine-matched IgG Binding Antibody (Ab) Responses as Assessed by Multiplex Assay 2 Weeks Following the Fourth Vaccination

  The Binding Antibody Multiplex Assay (BAMA) assay was used to evaluate binding antibody responses of each serum specimen against BG505 SOSIP (vaccine trimer immunogen) and Trimer 4571 (vaccine matched immunogen). Positivity criteria include (1) the net Mean Fluorescence Intensity (MFI), or MFI - Blank, values are ≥ antigen-specific cutoff at the 1:50 dilution level for IgG (based on the 95th percentile of the baseline visit serum samples and at least 100 MFI minus Blank), (2) the net MFI values are greater than 3 times the baseline (day 0) net MFI, and (3) the MFI values are greater than 3 times the baseline MFI values. The AB05 antigen was used to assess binding antibody responses to the vaccine-matched trimer INO-6160. The wildtype antigen (BG505 MD39.3) captured both base and non-base specific antibodies, whereas the mutant antigen (BG505 MD39.3-BaseKO), captured only non-base specific antibodies.

  Measured at Months 1.5, 3.5, and 6.5

• Magnitude of Vaccine-matched IgG Binding Antibody (Ab) Responses as Assessed by Multiplex Assay 2 Weeks Following the Third and Fourth Vaccination

  The Binding Antibody Multiplex Assay (BAMA) assay was used to evaluate binding antibody responses of each serum specimen against BG505 SOSIP (vaccine trimer immunogen) and Trimer 4571 (vaccine matched immunogen). Epitope specificities are assessed via wildtype-mutant pairs. The AB05 antigen was used to assess binding antibody responses to the vaccine-matched trimer INO-6160. The wildtype antigen (BG505 MD39.3) captured both base and non-base specific antibodies, whereas the mutant antigen (BG505 MD39.3-BaseKO), captured only non-base specific antibodies.

  Measured at Months 1.5, 3.5, and 6.5

• Response Rate of CD4 + T-cell Responses Measured by Flow Cytometry, to HIV-1-specific Env Peptide Pools, 2 Weeks Following the Third and Fourth Vaccination

  Flow cytometry is employed to examine HIV-1-specific CD4+ and CD8+ T-cell responses using a validated Intracellular Cytokine Staining (ICS) assay. To determine positivity, a one-sided Fisher's exact test is applied to a two-by-two contingency table, testing whether the number of cytokine-producing cells for the stimulated data is equal to that for the negative control data.

  Measured at Months 3.5 and 6.5

• Magnitude of CD4 + T-cell Responses Measured by Flow Cytometry, to HIV-1-specific Env Peptide Pools, 2 Weeks Following the Third and Fourth Vaccination

  Flow cytometry is employed to examine HIV-1-specific CD4+ and CD8+ T-cell responses using a validated ICS assay

  Measured at Months 3.5 and 6.5

• Response Rate of CD8+ T-cell Responses Measured by Flow Cytometry, to HIV-1-specific Env Peptide Pools, 2 Weeks Following the Third and Fourth Vaccination

  Flow cytometry is employed to examine HIV-1-specific CD4+ and CD8+ T-cell responses using a validated Intracellular Cytokine Staining (ICS) assay. To determine positivity, a one-sided Fisher's exact test is applied to a two-by-two contingency table, testing whether the number of cytokine-producing cells for the stimulated data is equal to that for the negative control data.

  Measured at Months 3.5 and 6.5

• Magnitude of CD8+ T-cell Responses Measured by Flow Cytometry, to HIV-1-specific Env Peptide Pools, 2 Weeks Following the Third and Fourth Vaccination

  Flow cytometry is employed to examine HIV-1-specific CD4+ and CD8+ T-cell responses using a validated ICS assay

  Measured at Months 3.5 and 6.5

Secondary Outcomes (15)

• Neutralizing Ab Magnitude Against Autologous and Tier 1a HIV-1 Isolates as Assessed by TZM-bl Neutralization Assay Following the Third and Fourth Vaccinations

  Measured at baseline (screening), Month 3.5, and Month 6.5

• Neutralizing Ab Response Rate Against Autologous and Tier 1a HIV-1 Isolates as Assessed by TZM-bl Neutralization Assay Following the Third and Fourth Vaccinations

  Measured at baseline (screening), Month 3.5, and Month 6.5

• Differential Binding Response Rates of HIV-1 Specific IgG Binding Ab Responses as Assessed by Multiplex Assay

  Measured at Months 1.5, 3.5, and 6.5

• Epitope Specificity of HIV-1 Specific IgG Binding Ab Responses

  2 weeks following third vaccination

• Response Rate of CD4 +T-cell Responses

  2 weeks following third vaccination

Study Arms (2)

Group #1: INO-6160/ 2.0 mg

EXPERIMENTAL

The dose of INO-6160, 2 mg, will be administered as 2 separate intradermal (ID) injections, one in each arm

Biological: INO-6160, 2 mg

Group #2: INO-6160/ 2.0 mg with Trimer-4571 / 100 mcg 3M-052-AF (5 mcg) + Alum (500 mcg)

EXPERIMENTAL

The dose of INO-6160, 2 mg, will be administered as 2 separate intradermal (ID) injections, one in each arm. The dose of Trimer 4571, 100 mcg, will be administered as 2 injections delivered intramuscularly (IM), one in each arm.

Biological: INO-6160, 2 mg; Biological: Trimer-4571 / 100 mcg 3M-052-AF (5 mcg) + Alum (500 mcg)

Interventions

INO-6160, 2 mg BIOLOGICAL

ID EP at month 0,1,3 and 6

Group #1: INO-6160/ 2.0 mg; Group #2: INO-6160/ 2.0 mg with Trimer-4571 / 100 mcg 3M-052-AF (5 mcg) + Alum (500 mcg)

Trimer-4571 / 100 mcg 3M-052-AF (5 mcg) + Alum (500 mcg) BIOLOGICAL

IM at month 3 and 6

Group #2: INO-6160/ 2.0 mg with Trimer-4571 / 100 mcg 3M-052-AF (5 mcg) + Alum (500 mcg)

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: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of questionnaire items that were answered incorrectly
• years old, inclusive, on day of enrollment
• Available for clinic follow-up through the last clinic visit and willing to be contacted 12 months after the last vaccine administration
• Agrees not to enroll in another study of an investigational agent during participation in the trial
• 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
• 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 behavior associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking 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 men who have been on hormone therapy for more than 6 consecutive months
• ≥ 12.0 g/dL for transgender women 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 their 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
• Serum creatinine ≤ 1.1 x ULN based on the institutional normal range

You may not qualify if:

• Volunteer who is breast-feeding or pregnant
• Body mass index (BMI). Enrollment of individuals with BMI ≥ 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)
• 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 equal to or greater than 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 live attenuated vaccine within 4 weeks prior to enrollment
• ACAM2000 vaccine for Monkeypox received within 30 days prior to enrollment or receipt of study product, or if ACAM2000 received greater than 30 days prior to enrollment, or prior to receipt of study product, vaccination scab still present; or planned administration within 30 days after enrollment or receipt of study product
• 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
• Receipt of non-HIV experimental vaccine(s) received within the last 1 year. Exceptions may be made by the PSRT for vaccines that have subsequently undergone licensure or Emergency Use Authorization by the FDA or, if outside the United States, by the national regulatory authority or World Health Organization. For volunteers who have received control/placebo in an experimental vaccine trial, the PSRT will determine eligibility on a case-by-case basis
• 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
• History of serious reaction (eg, hypersensitivity, anaphylaxis) to any related vaccine or component of the study vaccine regimen
• 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

Study Sites (3)

New York Blood Center CRS

New York, New York, 10065, United States

Location

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbuilt Vaccine (VV) CRS

Nashville, Tennessee, 37232, United States

Location

MeSH Terms

Interventions

aluminum sulfate

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: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 13, 2023
• First Posted: April 25, 2023
• Study Start: April 5, 2023
• Primary Completion: January 23, 2025
• Study Completion: January 23, 2025
• Last Updated: September 2, 2025
• Results First Posted: July 4, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)