Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of 16055 NFL Delta Gly4 Env Protein Trimer and Trimer 4571 Combined With 3M-052-AF + Alum Adjuvant and Ad4-Env145NFL Viral Particles as Heterologous Prime-boost Regimens in Adult Participants Without HIV.

NCT06332339 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: HVTN 313
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 6

Brief Summary

The goal of this clinical trial is to test 16055 NFL delta Gly4 Env protein trimer and Trimer 4571 combined with 3M-052-AF + Alum adjuvant and Ad4-Env145NFL viral particles as heterologous prime-boost regimens in adult participants without HIV. The main question\[s\] it aims to answer are:

• Are these vaccine regimens safe and well tolerated?
• Are the prime-boost vaccine regimens that include Ad4-Env145NFL and Trimer 4571 as heterologous boosts going contribute to the development of B-cell and antibody responses? Participants will attend scheduled study visits to receive their vaccine and will record symptoms on a daily eDiary.

Conditions

HIV

Outcome Measures

Primary Outcomes (10)

• Local reactogenicity signs and symptoms

  for a minimum of 14 days following receipt of intramuscular injections and intranasal administrations of study products.

  2 weeks following any injection

• Systemic reactogenicity signs and symptoms

  for a minimum of 14 days following receipt of intramuscular injections and intranasal administrations of study products.

  2 weeks following any injection

• Number of adverse events (AEs) reported for 30 days after receipt of any study product

  30 days following any injection

• Number of Serious Adverse Reactions (SAEs) leading to early participant withdrawal or permanent discontinuation

  12 months following receipt of any study product

• Number of Medically Attended Adverse Event (MAAEs) leading to early participant withdrawal or permanent discontinuation

  12 months following receipt of any study product

• Number of Adverse Events of Special Interest (AESIs) that are Potential Immune Mediated Medical Conditions (PIMMCs) leading to early participant withdrawal or permanent discontinuation

  12 months following receipt of any study product

• Number of Adverse Events (AEs) leading to early participant withdrawal or permanent discontinuation

  12 months following receipt of any study product

• Occurrence of serum IgG binding antibodies to vaccine-matched HIV-1 Env trimers and specific epitopes (e.g., CD4 binding site, V2, base of trimer, etc)

  Measured by binding antibody multiplex assay (BAMA) after the fourth and fifth vaccinations.

  Week 34 (following the 4th vaccine), Week 54 for Group 1, 2, and Week for Group 3 (following the 5th vaccine)

• Magnitude of serum IgG binding antibodies to vaccine-matched HIV-1 Env trimers and specific epitopes (e.g., CD4 binding site, V2, base of trimer, etc.)

  measured by binding antibody multiplex assay (BAMA) after the fourth and fifth vaccinations

  Week 34 (following the 4th vaccine), Week 54 for Group 1, 2, and Week for Group 3 (following the 5th vaccine)

• Response Rate of serum IgG binding antibodies to vaccine-matched HIV-1 Env trimers and specific epitopes (e.g., CD4 binding site, V2, base of trimer, etc.)

  measured by binding antibody multiplex assay (BAMA) after the fourth and fifth vaccinations

  Week 34 (following the 4th vaccine), Week 54 for Group 1, 2, and Week for Group 3 (following the 5th vaccine)

Secondary Outcomes (19)

• Occurrence of serum antibody neutralization of the autologous pseudovirus HIV-1 strains (including vaccine-matched deglycosylated 16055, WT 16055, BG505, 1086)

  2 weeks after the second vaccination and following subsequent vaccinations

• Magnitude of serum antibody neutralization of the autologous pseudovirus HIV-1 strains (including vaccine-matched deglycosylated 16055, WT 16055, BG505, 1086)

  2 weeks after the second vaccination and following subsequent vaccinations

• Response Rate of serum antibody neutralization of the autologous pseudovirus HIV-1 strains (including vaccine-matched deglycosylated 16055, WT 16055, BG505, 1086)

  2 weeks after the second vaccination and following subsequent vaccinations

• Occurrence of serum antibody neutralization of HIV-1 strains

  Through study completion, an average of 1 year

• Magnitude of serum antibody neutralization of HIV-1 strains

  Week 34 (following the 4th vaccine), Week 54 for Group 1, 2, and Week for Group 3 (following the 5th vaccine)

Study Arms (3)

Treatment 1

EXPERIMENTAL

16055 NFL delta Gly4 trimer, 200 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate intramuscular (IM) injections (0.27 mL each) at months 0, 2, 4, 8, and 12.

Biological: 16055 NFL delta Gly4 trimer

Treatment 2

EXPERIMENTAL

16055 NFL delta Gly4 trimer, 200 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.27 mL each) at months 0 and 2. Ad4-Env145NFL, 5 x 108 viral particles (vp) to be administered intranasally (IN) (0.07 mL into 1 nostril) at month 4. Trimer 4571, 100 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.2 mL each) at months 8 and 12.

Biological: 16055 NFL delta Gly4 trimer; Biological: Trimer 4571; Biological: Ad4-Env145NFL, 5 x 108 viral particles (vp)

Treatment 3

EXPERIMENTAL

16055 NFL delta Gly4 trimer, 200 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.27 mL each) at months 0 and 2. Trimer 4571, 100 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.2 mL each) at month 4. Ad4-Env145NFL, 5 x 108 vp to be administered IN (0.07 mL into 1 nostril) at months 8 and 12.

Biological: 16055 NFL delta Gly4 trimer; Biological: Trimer 4571; Biological: Ad4-Env145NFL, 5 x 108 viral particles (vp)

Interventions

16055 NFL delta Gly4 trimer BIOLOGICAL

200 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.27 mL each)

Treatment 1; Treatment 2; Treatment 3

Trimer 4571 BIOLOGICAL

100 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.2 mL each)

Treatment 2; Treatment 3

Ad4-Env145NFL, 5 x 108 viral particles (vp) BIOLOGICAL

to be administered intranasally (IN) (0.07 mL into 1 nostril)

Treatment 2; Treatment 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 an understanding of this study and completes a questionnaire prior to signing the informed consent form with verbal demonstration of understanding of questionnaire items that were answered incorrectly.
• to 55 years old, inclusive, on day of enrollment.
• Available for clinic follow-up and willing to undergo study procedures through the last clinic visit.
• 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 313 PSRT are required prior to enrollment into HVTN 313
• 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 by clinical staff as having a low likelihood of acquiring HIV per guidelines, agrees to discuss their potential for HIV acquisition, agrees to risk-reduction counseling, and agrees to avoid behaviors associated with a higher likelihood of acquiring HIV through the final study visit. Low likelihood may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed.
• Hemoglobin (Hgb):
• ≥ 11.0 g/dL for volunteers who were assigned female sex at birth (AFAB)
• ≥ 13.0 g/dL for volunteers who were assigned male sex at birth (AMAB) and for 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 volunteers 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 to 550,000/mm³.
• Alanine aminotransferase (ALT) within the institutional normal range.
• Serum creatinine ≤ 1.1 x upper limit of normal (ULN) based on the institutional normal range.

You may not qualify if:

• Volunteer who is breastfeeding or pregnant.
• 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 on a case-by-case basis.
• Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
• Receipt of non-HIV experimental 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).
• Congenital or acquired immunodeficiency, including systemic medication (includes oral, intramuscular, or intravenously administrated medications) use likely to impair immune response to vaccine in the opinion of the site investigator, such as systemic 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, replicating vaccine within 4 weeks prior to enrollment or planned administration within 4 weeks after enrollment. Note for ACAM2000 vaccine for mpox (formerly known as Monkeypox): the vaccination scab must no longer be present and at least 4 weeks is required prior to enrollment.
• Receipt or planned receipt of any killed/subunit/inactivated/non-replicating vaccine within 2 weeks prior to enrollment or planned administration within 2 weeks after enrollment. This applies to Jynneos vaccine for mpox which is non- replicating.
• 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 (e.g., 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 clinician which would make study procedures a contraindication.
• Asplenia or functional asplenia.
• Active duty and reserve US military personnel.

Sponsors & Collaborators

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

Study Sites (6)

Alabama CRS

Birmingham, Alabama, 35222, United States

Location

The Hope Clinic of the Emory Vaccine Center CRS Site# 31440

Decatur, Georgia, 30030, United States

Location

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

Boston, Massachusetts, 02115, United States

Location

Columbia P&S CRS

New York, New York, 10032, United States

Location

University of Rochester HIV/AIDS CTU

Rochester, New York, 14642, United States

Location

University of Pennsylvania HIV Therapeutics and Prevention Clinical Trials Unit

Philadelphia, Pennsylvania, 19104, United States

Location

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: February 21, 2024
• First Posted: March 27, 2024
• Study Start: March 15, 2024
• Primary Completion (Estimated): November 11, 2026
• Study Completion (Estimated): November 11, 2026
• Last Updated: November 5, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)