NCT06033209

Brief Summary

HVTN 144 is a phase 1 clinical trial to being conducted to evaluate the safety and immunogenicity of an HIV envelope trimer, N332-GT5 gp140, adjuvanted with saponin/MPLA nanoparticles (SMNP) in adult participants without HIV. The study aims to evaluate the safety and tolerability of N332-GT5 gp140 adjuvanted with SMNP in adult volunteers without HIV and in overall good health, including identifying a safe and tolerable dose, route, and schedule of administration of the novel adjuvant SMNP. The study also aims to evaluate the induction of BG18-class immunoglobulin G (IgG) B-cell responses in memory B cells by the study regimens and compare the responses between the different groups. HVTN 144 will be conducted in 2 parts with 84 volunteers without HIV and in overall good health, aged 18 to 55 years. The study duration is 22 months which includes 8 months for enrollment, planned safety holds, follow-up, and Adverse Event of Special Interest (AESI) health contact 1 year after last vaccination.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
57

participants targeted

Target at P75+ for phase_1 hiv

Timeline
Completed

Started Nov 2023

Typical duration for phase_1 hiv

Geographic Reach
1 country

8 active sites

Status
completed

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

First Submitted

Initial submission to the registry

August 18, 2023

Completed
26 days until next milestone

First Posted

Study publicly available on registry

September 13, 2023

Completed
3 months until next milestone

Study Start

First participant enrolled

November 27, 2023

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 10, 2025

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 13, 2026

Completed
Last Updated

March 27, 2026

Status Verified

September 1, 2025

Enrollment Period

2 years

First QC Date

August 18, 2023

Last Update Submit

March 26, 2026

Conditions

Outcome Measures

Primary Outcomes (10)

  • Local reactogenicity signs and symptoms (solicited adverse events) will be collected

    Through study completion, an average of 1 year

  • Systemic reactogenicity signs and symptoms (solicited adverse events) will be collected

    Through study completion, an average of 1 year

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

    35 weeks and for 12 months following any receipt of study product

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

    35 weeks and for 12 months following any receipt of study product

  • Number of AESIs leading to early participant withdrawal or permanent discontinuation

    35 weeks and for 12 months following any receipt of study product

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

    35 weeks and for 12 months following any receipt of study product

  • Comparison of number of reported/assessed local and systemic reactogenicity, SAE's and AESI's and medically attended adverse events at increasing doses of adjuvant at constant dose of N332-GT5 gp140

    35 weeks

  • Frequency of BG18 epitope-specific B cells as determined by flow cytometry

    35 weeks

  • Proportion of participants with BG18-class IgG memory B cells in peripheral blood mononuclear cell (PBMCs), measured by antigen-specific B-cell sorting, B-cell receptor (BCR) sequencing, and bioinformatic analysis

    35 weeks

  • Frequency of BG18-class B cells among IgG memory B cells in PBMCs, measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis

    35 weeks

Secondary Outcomes (9)

  • Proportion of participants with BG18-class IgG B cells, measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis

    35 weeks

  • Frequency of BG18-class B cells among IgG B cells in germinal centers (GCs), measured by antigen-specific B-cell sorting, BCR sequencing, and bioinformatic analysis

    35 weeks

  • Response rate of serum binding Ab responses to N332-GT5 gp140 and BG18 epitope on the trimer measured by binding antibody multiplex assay (BAMA)

    35 weeks

  • Magnitude of serum binding Ab responses to N332-GT5 gp140 and BG18 epitope on the trimer measured by binding antibody multiplex assay (BAMA)

    35 weeks

  • Response rate of serum neutralizing antibodies (nAbs) that neutralize pseudoviruses engineered to be sensitive to BG18-precursors

    35 weeks

  • +4 more secondary outcomes

Study Arms (15)

Part A Intramuscular (IM) safety with dose finding - Group 1

EXPERIMENTAL
Biological: N332-GT5 gp140 (IM, Bolus)Biological: SMNP (IM, Bolus)

Part A IM safety with dose finding - Group 2

EXPERIMENTAL
Biological: N332-GT5 gp140 (IM, Bolus)Biological: SMNP (IM, Bolus)

Part A IM safety with dose finding - Group 3

EXPERIMENTAL
Biological: N332-GT5 gp140 (IM, Bolus)Biological: SMNP (IM, Bolus)

Part A IM safety with dose finding - Group 4

EXPERIMENTAL
Biological: N332-GT5 gp140 (IM, Bolus)Biological: SMNP (IM, Bolus)

Part A IM safety with dose finding - Group 5

EXPERIMENTAL
Biological: N332-GT5 gp140 (IM, Bolus)Biological: SMNP (IM, Bolus)

Part A IM safety with dose finding - Group 6

EXPERIMENTAL
Biological: N332-GT5 gp140 (IM, Fractioned)Biological: SMNP (IM, Fractioned)

Part A Subcutaneous (SC) safety with dose finding - Group 7

EXPERIMENTAL
Biological: N332-GT5 gp140 (SC, Bolus)Biological: SMNP (SC, Bolus)

Part A SC safety with dose finding - Group 8

EXPERIMENTAL
Biological: N332-GT5 gp140 (SC, Bolus)Biological: SMNP (SC, Bolus)

Part A SC safety with dose finding - Group 9

EXPERIMENTAL
Biological: N332-GT5 gp140 (SC, Bolus)Biological: SMNP (SC, Bolus)

Part A SC safety with dose finding - Group 10

EXPERIMENTAL
Biological: N332-GT5 gp140 (SC, Bolus)Biological: SMNP (SC, Bolus)

Part A SC safety with dose finding - Group 11

EXPERIMENTAL
Biological: N332-GT5 gp140 (SC, Bolus)Biological: SMNP (SC, Bolus)

Part A SC safety with dose finding - Group 12

EXPERIMENTAL
Biological: N332-GT5 gp140 (SC, Fractioned)Biological: SMNP (SC, Fractioned)

Part B IM Immunogenicity - Group 13

EXPERIMENTAL
Biological: N332-GT5 gp140 (IM, Bolus)Biological: SMNP (IM, Bolus)

Part B SC Immunogenicity - Group 14

EXPERIMENTAL
Biological: N332-GT5 gp140 (SC, Bolus)Biological: SMNP (SC, Bolus)

Part B Immunogenicity - Group 15

EXPERIMENTAL

Group 15 N332-GT5 gp140 with SMNP dose and route (SC or IM) is To Be Determined (TBD) based on groups 6 and 12 (Part A).

Biological: N332-GT5 gp140 (IM, Fractioned)Biological: N332-GT5 gp140 (SC, Fractioned)Biological: SMNP (IM, Fractioned)Biological: SMNP (SC, Fractioned)

Interventions

SC in the upper arm

Part A SC safety with dose finding - Group 10Part A SC safety with dose finding - Group 11Part A SC safety with dose finding - Group 8Part A SC safety with dose finding - Group 9Part A Subcutaneous (SC) safety with dose finding - Group 7Part B SC Immunogenicity - Group 14

SC in the upper arm, Fractionated escalating dose for prime

Part A SC safety with dose finding - Group 12Part B Immunogenicity - Group 15

SC in the upper arm

Part A SC safety with dose finding - Group 10Part A SC safety with dose finding - Group 11Part A SC safety with dose finding - Group 8Part A SC safety with dose finding - Group 9Part A Subcutaneous (SC) safety with dose finding - Group 7Part B SC Immunogenicity - Group 14

SC in the upper arm, Fractionated escalating dose for prime

Part A SC safety with dose finding - Group 12Part B Immunogenicity - Group 15

IM in the deltoid

Part A IM safety with dose finding - Group 2Part A IM safety with dose finding - Group 3Part A IM safety with dose finding - Group 4Part A IM safety with dose finding - Group 5Part A Intramuscular (IM) safety with dose finding - Group 1Part B IM Immunogenicity - Group 13

IM in the deltoid, Fractionated escalating dose for prime

Part A IM safety with dose finding - Group 6Part B Immunogenicity - Group 15

IM in the deltoid

Part A IM safety with dose finding - Group 2Part A IM safety with dose finding - Group 3Part A IM safety with dose finding - Group 4Part A IM safety with dose finding - Group 5Part A Intramuscular (IM) safety with dose finding - Group 1Part B IM Immunogenicity - Group 13

IM in the deltoid, Fractionated escalating dose for prime

Part A IM safety with dose finding - Group 6Part B Immunogenicity - Group 15

Eligibility Criteria

Age18 Years - 55 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • General and demographic criteria:
  • Age of 18 through 55 years
  • Access to a participating HVTN Clinical Research Site (CRS) and willingness to be followed for the planned duration of the study
  • Ability and willingness to provide informed consent
  • Assessment of Understanding (AoU): Volunteer demonstrates understanding of this study by completing a questionnaire prior to the first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly
  • Agrees not to enroll in another study of an investigational research agent until completion of the study
  • Good general health as shown by medical history, physical exam, and screening laboratory tests
  • HIV-related criteria:
  • Willingness to receive HIV test results
  • Willingness to discuss HIV risks and amenable to HIV risk-reduction counseling
  • Assessed by the clinic staff as having a low likelihood of acquiring HIV and is committed to avoiding behaviors associated with a higher likelihood of acquiring HIV through the last required protocol clinic visit
  • 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 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
  • +16 more criteria

You may not qualify if:

  • General criteria:
  • Blood products received within 120 days before first vaccination
  • Investigational research agents received within 30 days before first vaccination
  • Body mass index (BMI) ≥ 40, or BMI ≥ 35 with 2 or more of the following: Age \> 45, systolic blood pressure \> 140 mm Hg, diastolic blood pressure \> 90 mm Hg, current smoker, known hyperlipidemia
  • Intent to participate in any other study that requires non-HVTN HIV Ab testing during the planned duration of the HVTN 144 study
  • Pregnant or breastfeeding
  • Active duty and reserve US military personnel
  • Vaccines and other injections criteria:
  • HIV vaccine(s) received in a prior HIV vaccine trial. For volunteers who have received control/placebo in an HIV vaccine trial, the HVTN 144 Protocol Safety Review Team (PSRT) will determine eligibility on a case-by-case basis.
  • Previous receipt of monoclonal antibodies (mAbs), whether licensed or investigational. Exceptions may be made by the HVTN 144 PSRT on a case-by-case basis.
  • Non-HIV experimental vaccine(s) received within the last 1 year in a prior vaccine trial. Exceptions may be made by the HVTN 144 PSRT for vaccines that have subsequently undergone licensure by the FDA. For volunteers who have received control/placebo in an experimental vaccine trial, the HVTN 144 PSRT will determine eligibility on a case-by-case basis. For volunteers who have received an experimental vaccine(s) more than 1 year ago, eligibility for enrollment will be determined by the HVTN 144 PSRT on a case-by-case basis.
  • Live attenuated vaccines received within 30 days before the first vaccination or scheduled within 28 days after injection (eg, measles, mumps, and rubella (MMR); oral polio vaccine (OPV); varicella; yellow fever; live attenuated influenza vaccine). ACAM2000 vaccine \>28 days prior with a vaccination scab still present.
  • Any vaccines that are not live attenuated vaccines and were received within 14 days prior to the first vaccination (eg, tetanus, pneumococcal, Hepatitis A or B). Please note this includes incompetent vaccine such as the Jynneos vaccine for the prevention of mpox disease.
  • Allergy treatment with antigen injections within 30 days before the first vaccination or that are scheduled within 14 days after the first vaccination
  • Immune system criteria:
  • +21 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Bridge HIV CRS

San Francisco, California, 94102, United States

Location

Atlanta - Hope Clinic

Decatur, Georgia, 30030, United States

Location

Brigham & Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 100032, United States

Location

New York Blood Center

New York, New York, 10065, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Penn Prevention CRS [Site ID: 30310]

Philadelphia, Pennsylvania, 19104, United States

Location

Vanderbilt Institute for Infection, Immunology and Inflammation

Nashville, Tennessee, 37232-2582, United States

Location

Study Officials

  • Lindsey Baden

    Brigham and Women's Hospital

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
SEQUENTIAL
Model Details: The overall design of this trial involves 2 parts. In Part A, the goal is to establish the tolerability of both N332-GT5 and the SMNP adjuvant. This is a partially randomized design - Part A is nonrandomized, and Part B is randomized.
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 18, 2023

First Posted

September 13, 2023

Study Start

November 27, 2023

Primary Completion

December 10, 2025

Study Completion

March 13, 2026

Last Updated

March 27, 2026

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

Locations