A Clinical Trial to Evaluate Safety, Tolerability, and Immunogenicity of Adjuvanted HIV-1 Fusion Peptide Conjugate Vaccine Alone or in Prime-Boost Regimens With Adjuvanted HIV-1 Envelope Trimer 4571 and HIV-1 Trimer 6931 Vaccines in Healthy Adults

NCT05470400 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: HVTN 303
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 6

Brief Summary

This is an open-label, dose-escalation study to examine the safety, tolerability, and immunogenicity of adjuvanted Fusion Peptide Vaccine alone or in prime-boost regimens with adjuvanted Trimer 4571 and Trimer 6931 vaccines in healthy adults. The hypothesis is that the vaccines will be safe, and well tolerated when administered alone, and when co-administered with HIV-1 Trimer 4571, in prime-boost regimens, and will induce detectable immune response.

Conditions

HIV

Keywords

HIV; Vaccine; FP conjugate; Trimer 4571; Trimer 6931; Adjuplex; Dose escalation

Outcome Measures

Primary Outcomes (13)

• Number of Participants Reporting Local Reactogenicity 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 after each vaccine dose (7 days after the first dose at Week 0 in all Groups, and 7 days after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants Reporting Local Reactogenicity 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 after each vaccine dose (7 days after the first dose at Week 0 in all Groups, and 7 days after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants Reporting Systemic Reactogenicity 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 following symptoms are considered as systemic reactogenicity if the onset date was within the periods of assessment specified in the protocol: malaise a

  Measured through 7 days after each vaccine dose (7 days after the first dose at Week 0 in all Groups, and 7 days after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number (Percentage) of Participants With Local Laboratory Values Recorded as Meeting Grade 1 AE Criteria or Above as Specified in the Division of AIDS Table.

  The number (percentage) of participants with local laboratory values recorded as meeting Grade 1 AE criteria or above as specified in the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events for alanine aminotransferase (ALT), creatinine, hemoglobin, lymphocyte count, neutrophil count, platelets, white blood cells (WBC) was summarized by treatment arm for each post vaccination time point.

  T1-T5: Screening, Days 0,7,14,28; T6: Screening, Days 0,7,14,84,91,98,168,175,182,252,259; T7: Screening, Days 0,7,14,28,35,42,56,63,70,84,91,98,168,175,252,259; T8: Screening, Days 0,7,14,28,35,42,56,63,70,140,147,154,231,238,252

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

  28 days after each vaccine dose (28 days after the first dose at Week 0 in all Groups, and 28 days after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants Reporting Adverse Events (AEs), by Relationship to Study Product

  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).

  28 days after each vaccine dose (28 days after the first dose at Week 0 in all Groups, and 28 days after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants Reporting Serious Adverse Events (SAEs)

  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)

  12 months after each vaccine dose (12 months after the first dose at Week 0 in all Groups, and 12 months after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants Reporting Medically Attended Adverse Events (MAAEs)

  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)

  12 months after each vaccine dose (12 months after the first dose at Week 0 in all Groups, and 12 months after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants Reporting Adverse Events of Special Interest (AESIs)

  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)

  12 months after each vaccine dose (12 months after the first dose at Week 0 in all Groups, and 12 months after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants With Study Product Discontinuation Associated With an AE or Reactogenicity

  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)

  12 months after each vaccine dose (12 months after the first dose at Week 0 in all Groups, and 12 months after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Number of Participants With Early Study Termination Associated With an AE or Reactogenicity

  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)

  12 months after each vaccine dose (12 months after the first dose at Week 0 in all Groups, and 12 months after the second dose at Week 4 in Groups 7 and 8 for participants who received the second dose).

• Response Rate of Serum Antibody Binding of FP and Envelope Trimer Antigens as Measured by the MSD Assay 2 Weeks After the Last Vaccination.

  Meso Scale Discovery Immunogenicity Assay (MSD) was used to measure the IgG binding antibody responses to fusion protein (FP), Trimer 4571, and Trimer 6931 based on two distinct positivity call methods: Method 1, known for its liberal approach, and Method 2, acknowledged for its conservative nature. Method 1 is using the cutoffs from the lab based on the 80 naïve samples (the 95th percentile). Method 2 is using the cutoffs (mean + 3\*SD of AUC to each analyte) based on the 80 naïve samples after filtering out %CV\>= 30% plus the baseline values from this study. The readout was the area under the curve (AUC) that were calculated from 8 serial dilutions (8-fold) for each sample. Group 5 and Group 6 were combined in the summary of IgG response rate.

  Measured at week 2, 2 weeks after the 1st vaccination, for Groups T5+T6, T7, and T8 and week 6, 2 weeks after the 2nd vaccination for Groups T7 and T8.

• Magnitude of Serum Antibody Binding of FP and Envelope Trimer Antigens as Measured by the MSD Assay 2 Weeks After the Last Vaccination.

  Meso Scale Discovery Immunogenicity Assay (MSD) was used to measure the IgG binding antibody responses to fusion protein (FP), Trimer 4571, and Trimer 6931 based on two distinct positivity call methods: Method 1, known for its liberal approach, and Method 2, acknowledged for its conservative nature. Method 1 is using the cutoffs from the lab based on the 80 naïve samples (the 95th percentile). Method 2 is using the cutoffs (mean + 3\*SD of AUC to each analyte) based on the 80 naïve samples after filtering out %CV\>= 30% plus the baseline values from this study. The readout was the area under the curve (AUC) that were calculated from 8 serial dilutions (8-fold) for each sample. The Unit of Measure is expressed as Mean Electrochemiluminescence Signal\*1/dilution to reflect the AUC of responses across serial dilutions. Group 5 and Group 6 were combined in the summary of IgG magnitudes.

  Measured at week 2, 2 weeks after the 1st vaccination, for Groups T5+T6, T7, and T8 and week 6, 2 weeks after the 2nd vaccination for Groups T7 and T8.

Study Arms (8)

Dose Escalation - Group 1

EXPERIMENTAL

Dose Escalation will evaluate the safety, tolerability, and immunogenicity of single adjuvanted doses of the FP conjugate, Trimer 4571 or Trimer 6931 vaccines, in a dose-escalation design. Each product must be assessed as safe prior to use in Prime Boost Regimen.

Biological: FP conjugate vaccine (25 mcg)

Dose Escalation - Group 2

EXPERIMENTAL

Dose Escalation will evaluate the safety, tolerability, and immunogenicity of single adjuvanted doses of the FP conjugate, Trimer 4571 or Trimer 6931 vaccines, in a dose-escalation design. Each product must be assessed as safe prior to use in Prime Boost Regimen.

Biological: FP conjugate vaccine (200 mcg)

Dose Escalation - Group 3

EXPERIMENTAL

Dose Escalation will evaluate the safety, tolerability, and immunogenicity of single adjuvanted doses of the FP conjugate, Trimer 4571 or Trimer 6931 vaccines, in a dose-escalation design. Each product must be assessed as safe prior to use in Prime Boost Regimen.

Biological: Trimer 6931 (100 mcg)

Dose Escalation - Group 4

EXPERIMENTAL

Dose Escalation will evaluate the safety, tolerability, and immunogenicity of single adjuvanted doses of the FP conjugate, Trimer 4571 or Trimer 6931 vaccines, in a dose-escalation design. Each product must be assessed as safe prior to use in Prime Boost Regimen.

Biological: Trimer 6931 (200 mcg)

Dose Escalation - Group 5

EXPERIMENTAL

Dose Escalation will evaluate the safety, tolerability, and immunogenicity of single adjuvanted doses of the FP conjugate, Trimer 4571 or Trimer 6931 vaccines, in a dose-escalation design. Each product must be assessed as safe prior to use in Prime Boost Regimen.

Biological: Trimer 4571 (200 mcg)

Prime Boost Regimen - Group 6

EXPERIMENTAL

Prime Boost Regimen will evaluate the safety, tolerability, and immunogenicity of adjuvanted vaccines: FP conjugate prime, Trimer 4571 prime, or an FP plus Trimer 4571 prime, all followed by subsequent doses of Trimer 4571, Trimer 6931 and both Trimers combined.

Biological: Trimer 6931 (100 mcg); Biological: Trimer 6931 (200 mcg); Biological: Trimer 4571 (200 mcg); Biological: Trimer 4571 (100 mcg)

Prime Boost Regimen - Group 7

EXPERIMENTAL

Prime Boost Regimen will evaluate the safety, tolerability, and immunogenicity of adjuvanted vaccines: FP conjugate prime, Trimer 4571 prime, or an FP plus Trimer 4571 prime, all followed by subsequent doses of Trimer 4571, Trimer 6931 and both Trimers combined.

Biological: FP conjugate vaccine (200 mcg); Biological: Trimer 6931 (100 mcg); Biological: Trimer 6931 (200 mcg); Biological: Trimer 4571 (200 mcg); Biological: Trimer 4571 (100 mcg)

Prime Boost Regimen - Group 8

EXPERIMENTAL

Prime Boost Regimen will evaluate the safety, tolerability, and immunogenicity of adjuvanted vaccines: FP conjugate prime, Trimer 4571 prime, or an FP plus Trimer 4571 prime, all followed by subsequent doses of Trimer 4571, Trimer 6931 and both Trimers combined.

Biological: FP conjugate vaccine (200 mcg); Biological: Trimer 6931 (100 mcg); Biological: Trimer 6931 (200 mcg); Biological: Trimer 4571 (200 mcg); Biological: Trimer 4571 (100 mcg)

Interventions

FP conjugate vaccine (25 mcg) BIOLOGICAL

FP8v1-rTTHC (FP conjugate vaccine) is an HIV-1 fusion peptide conjugated to recombinant tetanus toxoid heavy chain fragment C (rTTHC) via sulfo-SIAB chemical linker. Study vaccines will be admixed with Adjuplex adjuvant and administered intramuscularly (IM) via needle and syringe in two injection sites.

Also known as: FP8v1-rTTHC

Dose Escalation - Group 1

Trimer 6931 (100 mcg) BIOLOGICAL

HIV-1 Trimer 6931 (Trimer 6931) is a synthetic soluble HIV-1 envelope product that consists of an HIV-1 envelope (Env) trimer variant, derived from consensus clade C sequence (ConC). Study vaccines will be admixed with Adjuplex adjuvant and administered intramuscularly (IM) via needle and syringe in two injection sites.

Also known as: HIV-1 Trimer 6931

Dose Escalation - Group 3; Prime Boost Regimen - Group 6; Prime Boost Regimen - Group 7; Prime Boost Regimen - Group 8

FP conjugate vaccine (200 mcg) BIOLOGICAL

FP8v1-rTTHC (FP conjugate vaccine) is an HIV-1 fusion peptide conjugated to recombinant tetanus toxoid heavy chain fragment C (rTTHC) via sulfo-SIAB chemical linker. Study vaccines will be admixed with Adjuplex adjuvant and administered intramuscularly (IM) via needle and syringe in two injection sites.

Also known as: FP8v1-rTTHC

Dose Escalation - Group 2; Prime Boost Regimen - Group 7; Prime Boost Regimen - Group 8

Trimer 6931 (200 mcg) BIOLOGICAL

HIV-1 Trimer 6931 (Trimer 6931) is a synthetic soluble HIV-1 envelope product that consists of an HIV-1 envelope (Env) trimer variant, derived from consensus clade C sequence (ConC). Study vaccines will be admixed with Adjuplex adjuvant and administered intramuscularly (IM) via needle and syringe in two injection sites.

Also known as: HIV-1 Trimer 6931

Dose Escalation - Group 4; Prime Boost Regimen - Group 6; Prime Boost Regimen - Group 7; Prime Boost Regimen - Group 8

Trimer 4571 (200 mcg) BIOLOGICAL

HIV-1 Trimer 4571 (Trimer 4571) is a synthetic soluble HIV-1 envelope product that consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505. Study vaccines will be admixed with Adjuplex adjuvant and administered intramuscularly (IM) via needle and syringe in two injection sites.

Also known as: HIV-1 Trimer 4571

Dose Escalation - Group 5; Prime Boost Regimen - Group 6; Prime Boost Regimen - Group 7; Prime Boost Regimen - Group 8

Trimer 4571 (100 mcg) BIOLOGICAL

HIV-1 Trimer 4571 (Trimer 4571) is a synthetic soluble HIV-1 envelope product that consists of an HIV-1 envelope (Env) trimer variant, derived from clade A, strain BG505. Study vaccines will be admixed with Adjuplex adjuvant and administered intramuscularly (IM) via needle and syringe in two injection sites.

Also known as: HIV-1 Trimer 4571

Prime Boost Regimen - Group 6; Prime Boost Regimen - Group 7; Prime Boost Regimen - Group 8

Eligibility Criteria

• Age: 18 Years - 50 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.
• years old, inclusive, on day of enrollment.
• Agrees to comply with planned study procedures and be available for clinic follow-up through the last clinic visit.
• Agrees not to enroll in another study of an investigational agent during participation in the trial, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) investigational agents that may subsequently obtain emergency use authorization (EUA) or undergo licensure by the FDA. If a potential participant is already enrolled in a SARS-CoV-2 clinical trial, prior approvals from the SARS-COV-2 study sponsor and HVTN 303 PSRT are required prior to enrollment in HVTN 303.
• In good general health without clinically significant medical history.
• Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity.
• Body Mass Index (BMI) ≤ 40.
• Assessed as low risk for HIV acquisition.
• Suitable injection sites in the deltoid muscle of each arm, as assessed by a clinician.
• White blood cells (WBCs) 2,500-12,000/mm3
• WBC differential either within institutional normal range or approved by the Investigator of Record (IoR) as "not clinically significant."
• Platelets = 125,000 - 500,000/mm3
• 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

You may not qualify if:

• Active duty and reserve US military personnel.
• Breast-feeding or planning to become pregnant from at least 21 days prior to enrollment through 12 weeks after the last product administration.
• An investigational HIV vaccine (previous placebo recipients are not excluded).
• Blood products within 60 days prior to enrollment
• Monoclonal antibodies (mAbs), whether licensed or investigational. Exceptions may be made by the HVTN 303 PSRT on a case-by-case basis
• Receipt of any of the following:
• Within 4 weeks prior to enrollment:
• Any licensed live, attenuated vaccine
• Any adenoviral-vectored SARS-CoV-2 vaccine with FDA Emergency Use Authorization (EUA), FDA licensure or World Health Organization (WHO) Emergency Use Listing (EUL)
• Within 2 weeks prior to enrollment:
• Any licensed killed/subunit/inactivated vaccine
• Any mRNA based or protein SARS-CoV-2 vaccines with FDA EUA, FDA licensure, or WHO EUL
• 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.
• Current allergen immunotherapy with antigen injections, unless on maintenance schedule.
• Current anti-TB prophylaxis or therapy.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• National Institutes of Health (NIH): collaborator
• Department of Health and Human Services: collaborator

Study Sites (6)

Atlanta - Hope Clinic

Atlanta, Georgia, 30308, United States

Location

BIDMC Vcrs [32077]

Boston, Massachusetts, 02115, United States

Location

New York Blood Center CRS [31801]

New York, New York, 10065, United States

Location

Columbia P&S CRS [30329]

New York, New York, 30329, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS [31467]

Rochester, New York, 14642, United States

Location

University of Pittsburgh CRS [1001]

Pittsburgh, Pennsylvania, 15213, United States

Location

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

Study Officials

• Troy Martin

  HVTN LOC, Fred Hutch

  STUDY CHAIR

• Michael Keefer, M.D.

  Univ. of Rochester Med. Ctr., HVTU

  STUDY CHAIR

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

Study Record Dates

• First Submitted: June 29, 2022
• First Posted: July 22, 2022
• Study Start: August 15, 2022
• Primary Completion: January 24, 2024
• Study Completion: January 24, 2024
• Last Updated: April 23, 2026
• Results First Posted: March 21, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)