NCT05903339

Brief Summary

This first-in-human (FIH) phase 1 clinical trial will evaluate a prime-boost regimen of immunogens designed to induce HIV-1 Env V3-glycan-specific broadly neutralizing antibodies (V3G bNAbs). The priming immunogen (V3G CH848 Pr-NP1) consists of ferritin NPs expressing 8 copies of an Env trimer. This immunogen will be boosted with an mRNA LNP (V3G CH848 mRNA-Tr2), encoding a soluble Env trimer which does not utilize the ferritin NP design.

Trial Health

75
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
36

participants targeted

Target at P50-P75 for phase_1 hiv

Timeline
7mo left

Started Aug 2023

Longer than P75 for phase_1 hiv

Geographic Reach
1 country

6 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress83%
Aug 2023Dec 2026

First Submitted

Initial submission to the registry

June 5, 2023

Completed
10 days until next milestone

First Posted

Study publicly available on registry

June 15, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

August 29, 2023

Completed
3.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 18, 2026

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 18, 2026

Last Updated

April 20, 2026

Status Verified

April 1, 2026

Enrollment Period

3.3 years

First QC Date

June 5, 2023

Last Update Submit

April 16, 2026

Conditions

Outcome Measures

Primary Outcomes (7)

  • Local reactogenicity signs and symptoms for a minimum of 14 days following receipt of any study vaccine

    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)

    2 weeks following any injection

  • Systemic reactogenicity signs and symptoms for a minimum of 14 days following receipt of any study vaccine.

    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)

    2 weeks following any injection

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

    12 months following receipt of any study product

  • Number of MAAEs (medically attended adverse event) leading to early participant withdrawal or permanent discontinuation

    12 months following receipt of any study product

  • Number of AESIs (Adverse events of special interest) leading to early participant withdrawal or permanent discontinuation

    12 months following receipt of any study product

  • Number of AEs (adverse events) leading to early participant withdrawal or permanent discontinuation

    12 months following receipt of any study product

  • Frequency of the V3G-specific precursor IgM+ and IgG+ B cells.

    Measured by flow cytometry analysis

    2 weeks following injection

Secondary Outcomes (9)

  • Response rate of serum IgG binding Abs

    2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2

  • Magnitude of serum IgG binding Abs

    2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2

  • Response rate of serum IgG binding Abs

    2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2

  • Magnitude of serum IgG binding Abs

    2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2

  • Response rate of serum Ab autologous neutralization of vaccine-matched tier 2 HIV-1 strains

    2 weeks after the priming regimen and 2 weeks after the boost with V3G CH848 mRNA-Tr2

  • +4 more secondary outcomes

Study Arms (4)

Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + Alum

EXPERIMENTAL

3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Drug: V3G CH848 Pr-NP1 60mcgDrug: 3M-052-AF 5mcgDrug: Alum 500 mcgDrug: V3G CH848 mRNA-Tr2 50mcg

Group 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1

EXPERIMENTAL

3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Drug: V3G CH848 Pr-NP1 60mcgDrug: V3G CH848 mRNA-Tr2 50mcgDrug: ACU-026-001-1 2.0mg

Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum

EXPERIMENTAL

3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Drug: 3M-052-AF 5mcgDrug: Alum 500 mcgDrug: V3G CH848 mRNA-Tr2 50mcgDrug: V3G CH848 Pr-NP1 100mcg

Group 4: V3G CH848 Pr-NP1 with ACU-026-001-1

EXPERIMENTAL

3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Drug: V3G CH848 mRNA-Tr2 50mcgDrug: ACU-026-001-1 2.0mgDrug: V3G CH848 Pr-NP1 100mcg

Interventions

(50 mcg)

Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + AlumGroup 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + AlumGroup 4: V3G CH848 Pr-NP1 with ACU-026-001-1

(2.0 mg)

Group 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1Group 4: V3G CH848 Pr-NP1 with ACU-026-001-1

(100 mcg)

Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + AlumGroup 4: V3G CH848 Pr-NP1 with ACU-026-001-1

(60 mcg)

Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + AlumGroup 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1

(5 mcg)

Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + AlumGroup 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum

(500 mcg)

Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + AlumGroup 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (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 first vaccination 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 through the last clinic visit, willing to undergo lymph node fine needle aspiration and leukapheresis, 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 307 PSRT are required prior to enrollment into HVTN 307.
  • 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 AFAB
  • ≥ 13.0 g/dL for volunteers AMAB and for volunteers AFAB or intersex at birth who have been on masculinizing hormone therapy for more than 6 consecutive months
  • ≥ 12.0 g/dL for volunteers AMAB or intersex at birth who have been on feminizing hormone therapy for more than 6 consecutive months
  • For transgender or intersex volunteers who have been on hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth
  • Platelets = 125,000 to 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.
  • +12 more criteria

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 approval.
  • Previous or current recipient of an investigational HIV vaccine (previous placebo/ control 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), 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, 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 of the following within 4 weeks prior to enrollment;
  • Live replicating vaccines
  • Any mRNA-based vaccine with FDA licensure, FDA emergency use authorization (EUA), or World Health Organization (WHO) emergency use listing
  • ACAM2000 vaccine \> 28 days prior with a vaccination scab still present.
  • Receipt of any vaccines that are not covered in #8 within 14 days prior to enrollment. Please note this includes replication incompetent vaccines such as the Jynneos vaccine for the prevention of mpox (formerly known as monkeypox) disease.
  • 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 greater than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.
  • 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.
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

Alabama CRS [Site ID: 31788]

Birmingham, Alabama, 35294-2170, United States

Location

Emory University School of Medicine, The Ponce de Leon Center CRS [Site ID: 5802]

Atlanta, Georgia, 30303, United States

Location

Brigham & Women's Hospital [Site ID: 30007]

Boston, Massachusetts, 02115, United States

Location

BIDMC VCRS [Site ID: 32077]

Boston, Massachusetts, 02215, United States

Location

Vanderbilt Vaccine (VV) CRS [Site ID: 30352]

Nashville, Tennessee, 37232-2582, United States

Location

Seattle Vaccine and Prevention CRS [Site ID: 30331]

Seattle, Washington, 98104, United States

Location

MeSH Terms

Conditions

Acquired Immunodeficiency Syndrome

Interventions

aluminum sulfate

Condition Hierarchy (Ancestors)

HIV InfectionsBlood-Borne InfectionsCommunicable DiseasesInfectionsSexually Transmitted Diseases, ViralSexually Transmitted DiseasesLentivirus InfectionsRetroviridae InfectionsRNA Virus InfectionsVirus DiseasesSlow Virus DiseasesGenital DiseasesUrogenital DiseasesImmunologic Deficiency SyndromesImmune 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

June 5, 2023

First Posted

June 15, 2023

Study Start

August 29, 2023

Primary Completion (Estimated)

December 18, 2026

Study Completion (Estimated)

December 18, 2026

Last Updated

April 20, 2026

Record last verified: 2026-04

Data Sharing

IPD Sharing
Will not share

Locations