Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy

NCT04985760 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: DAIDS-ES 38763U01AI152969
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 2

Brief Summary

Trimer 4571 is a vaccine designed to stimulate the development of broadly neutralizing antibodies (bnAbs) against HIV. Trimer 4571 is investigational, meaning it is not approved by the US Food and Drug Administration (FDA). There is limited human experience with the Trimer 4571 vaccine administered with aluminum hydroxide (alum) and the vaccine has not been tested in people with HIV prior to this study although it has been tested in healthy volunteers. The goal of this study is to see if Trimer 4571 is safe and well tolerated and to see if it will help the immune system produce bnAbs against HIV.

Conditions

HIV Infections

Keywords

HIV; Vaccine; Vaccination; Immune system; Antibody; Antibodies; broadly neutralizing; bnabs

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of three vaccinations of Trimer 4571 vaccine in adults with HIV on suppressive ART

  The proportion of participants experiencing at least one Grade 3 or higher adverse event will be summarized within and across the Trimer 4571 vaccine 100mcg, Trimer 4571 vaccine 500mcg and placebo control vaccine groups. The number of adverse events in each group will also be summarized by severity, body system, and relationship to study vaccine using frequencies, percent, and 95% confidence intervals.

  Day 0 through Week 44

Secondary Outcomes (1)

• Immunogenicity of three vaccinations of Trimer 4571 vaccine in adults with HIV on suppressive ART

  Baseline and Week 22

Study Arms (4)

Randomized Blinded Trimer 4571 Vaccine 100mcg

EXPERIMENTAL

Six (6) participants will receive Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant as a 1ml intramuscular injection at Day 0, Week 8 and Week 20.

Biological: Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant

Randomized Blinded Placebo for Trimer 4571 Vaccine 100mcg

PLACEBO COMPARATOR

Two (2) participants will receive the placebo control for Trimer 4571 vaccine 100mcg as a 1ml intramuscular injection at Day 0, Week 8 and Week 20.

Biological: Placebo control for Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant

Randomized Blinded Trimer 4571 Vaccine 500mcg

EXPERIMENTAL

Eighteen (18) participants will receive Trimer 4571 vaccine 500mcg with 500mcg alum adjuvant as a 1.1ml intramuscular injection at Day 0, Week 8 and Week 20.

Biological: Trimer 4571 vaccine 500mcg with 500mcg alum adjuvant

Randomized Blinded Placebo for Trimer 4571 Vaccine 500mcg

PLACEBO COMPARATOR

Six (6) participants will receive the placebo control for Trimer 4571 vaccine 500mcg as a 1.1ml intramuscular injection at Day 0, Week 8 and Week 20.

Biological: Placebo control for Trimer 4571 vaccine 500mcg with 500mcg alum adjuvant

Interventions

Placebo control for Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant BIOLOGICAL

Volume matched control for Trimer 4571 vaccine 100mcg

Also known as: Phosphate buffered saline

Randomized Blinded Placebo for Trimer 4571 Vaccine 100mcg

Trimer 4571 vaccine 500mcg with 500mcg alum adjuvant BIOLOGICAL

Investigational vaccine composed of Trimer 4571 500mcg, alum (aluminum hydroxide suspension) adjuvant 500mcg, and phosphate buffered saline diluent

Also known as: HIV-1 Trimer 4571 Vaccine, VRC-HIVRGP096-00-VP

Randomized Blinded Trimer 4571 Vaccine 500mcg

Placebo control for Trimer 4571 vaccine 500mcg with 500mcg alum adjuvant BIOLOGICAL

Volume matched control for Trimer 4571 vaccine 500mcg

Also known as: Phosphate buffered saline

Randomized Blinded Placebo for Trimer 4571 Vaccine 500mcg

Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant BIOLOGICAL

Investigational vaccine composed of Trimer 4571 100mcg, alum (aluminum hydroxide suspension) adjuvant 500mcg, and phosphate buffered saline diluent

Also known as: HIV-1 Trimer 4571 Vaccine, VRC-HIVRGP096-00-VP

Randomized Blinded Trimer 4571 Vaccine 100mcg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infection, documented by any FDA-approved assay. NOTE: The term 'licensed' refers to a US FDA approved kit, which is required for all investigational new drug (IND) studies.
• Receiving continuous antiretroviral therapy (ART) for at least 24 months (defined as no interruptions longer than 30 consecutive days) and with no changes in the components of the ART for at least 8 weeks prior to study entry. A change in formulation (for example tenofovir disaproxil fumarate to tenofovir alafenamide) will not be considered a change in ART.
• Screening CD4+ cell count ≥200cells/mm3 obtained within 60 days prior to study entry by any US laboratory that has a CLIA certification or its equivalent.
• Plasma HIV-1 RNA levels \< 50 copies/ml for at least 24 months on ART prior to study entry using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent. Participants must have at least one documented HIV-1 RNA \< 50 copies/ml within 12 months prior to study entry. All available HIV-1 RNA measurements must be \< 50 copies/ml during the 24 months prior to study entry except as allowed by the following note.
• NOTE: Unconfirmed plasma HIV-1 RNA \> 50 copies/ml but \<200 copies/mL is allowed if followed by a subsequent value \< 50 copies/ml.
• Screening HIV-1 RNA levels \<50 copies/mL using a FDA-approved assay performed by any laboratory that has a CLIA certification or its equivalent within 60 days prior to entry.
• Men and women ages \> 18 years.
• The following laboratory values obtained within 60 days prior to entry:
• Hemoglobin ≥10 g/dL
• Absolute neutrophil count (ANC) ≥1000/mm3
• Platelet count ≥100,000/mm3
• Creatinine ≤ 1.5x upper limit of normal (ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) (SGPT) ≤2.5x ULN
• Ability and willingness of participant to provide informed consent.
• In the opinion of the investigator, no medical, mental health or other condition that precludes participation.

You may not qualify if:

• Known to have been started on antiretroviral therapy within 3 months of the presumed or known date of first acquiring HIV-1 infection; i.e., treated during acute HIV-1 infection
• Currently breastfeeding or pregnant
• Known allergy/sensitivity or any hypersensitivity to components of study vaccine or their formulation.
• Known chronic inflammatory conditions such as, but not limited to, rheumatoid arthritis, systemic lupus erythematosus, sarcoidosis, inflammatory bowel disease (i.e., Crohn's disease or ulcerative colitis), chronic pancreatitis, or autoimmune hepatitis, myositis, or myopathy.
• Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
• Serious medical illness that requires systemic treatment and/or hospitalization within 30 days prior to entry.
• Use of systemic immunomodulators (e.g., interleukins, interferons, Cyclosporine), systemic cytotoxic chemotherapy, or investigational therapy within 60 days prior to study entry.
• NOTE: Participants receiving stable physiologic doses of glucocorticoids, defined as the equivalent of prednisone ≤10 mg/day, will not be excluded. Stable physiologic glucocorticoid doses should not be discontinued for the duration of the study. In addition, participants receiving inhaled or topical corticosteroids, or topical imiquimod will not be excluded.
• Receipt of any investigational HIV immunotherapy or HIV therapeutic vaccination within 12 months prior to study entry.
• History of positive HCV antibody with detectable HCV RNA in plasma within 48 Weeks prior to study entry. NOTE: Persons with positive HCV Ab but negative plasma HCV RNA are allowed to participate. Sites must document negative HCV RNA within 24 weeks of study entry.
• Treatment for hepatitis C within 6 months prior to study entry.
• History of positive HBsAg within 48 weeks prior to study entry.
• History of severe reaction or anaphylaxis to prior vaccinations.
• Body Mass Index \>40kg/m2.
• Receipt of Blood products or immune globulins within 16 weeks prior to Enrollment as per protocol section 5.3.2.

Sponsors & Collaborators

• Madhu Chhanda Choudhary: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (2)

AIDS Clinical Trials Unit/The Ohio State University

Columbus, Ohio, 43210, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

Location

MeSH Terms

Conditions

HIV Infections

Interventions

Aluminum Hydroxide

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Hydroxides; Alkalies; Inorganic Chemicals; Aluminum Compounds; Anions; Ions; Electrolytes

Study Officials

• Madhu Choudhary, MD

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: Randomized, double-blind, dose escalation

Study Record Dates

• First Submitted: July 21, 2021
• First Posted: August 2, 2021
• Study Start: September 30, 2021
• Primary Completion: January 16, 2026
• Study Completion: January 16, 2026
• Last Updated: January 22, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)