Safety and Immunogenicity of Stabilized CH505 TF chTrimer Vaccination in Adults Living With HIV-1 on Suppressive Antiretroviral Therapy

NCT06680479 | Suspended Phase 1 FDA Drug

• 2 other identifiers: A542239037
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 24

Brief Summary

A5422 is a phase 1, randomized, double-blind, placebo-controlled clinical trial to assess the safety, tolerability, and immunogenicity of a vaccination with stabilized CH505 TF chTrimer admixed with 3M-052-AF + Aluminum hydroxide (Alum), to assess the effect of CH505 TF chTrimer vaccine as a therapeutic vaccine in adults living with HIV-1 on suppressive antiretroviral therapy (ART) with the aim of inducing new HIV-1 Envelope (Env) B-cell neutralizing immune responses. Participants will be on study for up to 100 weeks (52 weeks on study treatment plus 48 weeks follow-up).

Conditions

HIV-1

Keywords

HIV; Therapeutic vaccine; bNab-inducing vaccine; Trimer

Outcome Measures

Primary Outcomes (2)

• Proportion of participants who initiated active study treatment (CH505 TF chTrimer, 3M-052-AF and Alum) who met the study-defined primary safety composite endpoint

  The study-defined primary safety endpoint is a composite endpoint. A participant who has initiated active study treatment is considered to have met the endpoint if the participant has experienced any treatment-related (i.e., related to CH505 TF chTrimer, 3M-052-AF or Alum as judged by the core team, blinded to study treatment) 1) serious adverse event (SAE), or 2) Grade 3+ adverse event (AE), or 3) AE that led to permanent discontinuation of study treatment regardless of grade

  Day 0 (after initial vaccination) to 4 weeks (28 days) after the last vaccination

• Number of the viruses with antibody neutralization response for a cross-clade global panel of 9 viruses expressing heterologous envelopes determined using a neutralization assay

  Day 0 pre-vaccination to 2 weeks (14 days) after the fifth vaccination

Secondary Outcomes (1)

• Antibody neutralization response for vaccine-matched and related viruses

  Day 0 pre-vaccination to 2 weeks (14 days) after the fifth vaccination

Study Arms (2)

Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)

EXPERIMENTAL

Biological: CH505 TF chTrimer; Biological: 3M-052-AF; Biological: Aluminum Hydroxide Suspension

Study Arm 2: Placebo (sodium chloride for injection, 0.9% USP)

PLACEBO COMPARATOR

Other: Sodium Chloride for Injection

Interventions

CH505 TF chTrimer BIOLOGICAL

Stabilized CH505 TF chTrimer, 300 mcg

Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)

3M-052-AF BIOLOGICAL

3 mcg

Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)

Sodium Chloride for Injection OTHER

Sodium chloride for injection, 0.9% USP volume-matched placebo injection.

Study Arm 2: Placebo (sodium chloride for injection, 0.9% USP)

Aluminum Hydroxide Suspension BIOLOGICAL

500 mcg

Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)

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
• On a suppressive ART regimen for at least 24 months with no changes in the 90 days prior to study entry
• CD4+ cell count greater than 200 cells/mm3 obtained within 56 days prior to study entry
• HIV-1 RNA \<200 copies/mL obtained within 56 days prior to study entry
• Plasma HIV-1 RNA levels \<200 copies/mL for at least 12 months on ART prior to study entry
• The following laboratory values obtained within 56 days prior to study entry
• White blood cell count ≥2,500 cells/mm3
• Absolute neutrophil count (ANC) \>750/mm3
• Hemoglobin ≥11 g/dL for cisgender men/transgender women and ≥10 g/dL for cisgender women/transgender men
• Platelet count ≥100,000/mm3
• Creatinine \<1.5x upper limit of normal (ULN)
• Alanine aminotransferase (ALT) (SGPT) ≤1.5 ULN
• Hepatitis C Virus (HCV) antibody-negative or HCV RNA negative result if indicated, within 56 days prior to study entry
• Negative hepatitis B surface antigen (HBsAg) result obtained within 56 days prior to study entry
• For study candidates of child-bearing potential, negative serum or urine pregnancy test at screening and within 48 hours prior to study entry

You may not qualify if:

• Known to have started ART during acute HIV infection
• Known to have HIV-related opportunistic infections within the last 2 years prior to study entry.
• History of malignancy within the last 5 years prior to study entry.
• Currently breastfeeding
• History of or active autoimmune disorders
• HIV vaccination (prophylactic and/or therapeutic) within 1 year prior to study entry
• Receipt of any anti-HIV-1 bNAbs within 2 years prior to study entry
• Vaccination within 4 weeks prior to study entry
• Use of any infusion blood product or immune globulin within 16 weeks prior to study entry (Exception: COVID-19-specific monoclonal antibodies are allowed)
• Use of systemic immunomodulators, systemic cytotoxic chemotherapy, or non-FDA approved investigational therapy within 60 days prior to study entry
• Intent to use immunomodulators during the course of the study
• Immune deficiency other than HIV
• HCV antiviral therapy within 90 days prior to screening
• Known allergy/sensitivity or any hypersensitivity to components of study drug(s) or their formulation
• Active drug or alcohol use or dependence that would interfere with adherence to study requirements

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Duke University: collaborator
• Access to Advanced Health Institute (AAHI): collaborator

Study Sites (24)

University of California, Los Angeles CARE Center CRS

Los Angeles, California, 90035, United States

Location

UCSD Antiviral Research Center CRS

San Diego, California, 92103, United States

Location

University of California, San Francisco HIV/AIDS CRS

San Francisco, California, 94110, United States

Location

Harbor University of California Los Angeles Center CRS

Torrance, California, 90502-2052, United States

Location

University of Colorado Hospital CRS

Aurora, Colorado, 80045, United States

Location

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308-2012, United States

Location

Northwestern University CRS

Chicago, Illinois, 60611, United States

Location

Johns Hopkins University CRS

Baltimore, Maryland, 21287, United States

Location

Massachusetts General Hospital CRS (MGH CRS)

Boston, Massachusetts, 02114, United States

Location

Washington University Therapeutics (WT) CRS

St Louis, Missouri, 63110-1010, United States

Location

New Jersey Medical School Clinical Research Center CRS

Newark, New Jersey, 07103, United States

Location

Weill Cornell Chelsea CRS

New York, New York, 10010, United States

Location

Columbia Physicians & Surgeons (P&S) CRS

New York, New York, 10032, United States

Location

Weill Cornell Uptown CRS

New York, New York, 10065, United States

Location

University of Rochester Adult HIV Therapeutic Strategies Network CRS

Rochester, New York, 14642, United States

Location

Chapel Hill CRS

Chapel Hill, North Carolina, 27599-7215, United States

Location

Cincinnati CRS

Cincinnati, Ohio, 45267-0405, United States

Location

Case CRS

Cleveland, Ohio, 44106, United States

Location

Ohio State University CRS

Columbus, Ohio, 43210, United States

Location

Penn Therapeutics CRS

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Therapeutics (VT) CRS

Nashville, Tennessee, 37204, United States

Location

Houston Advancing Research Team CRS

Houston, Texas, 77030, United States

Location

University of Washington Positive Research CRS

Seattle, Washington, 98104, United States

Location

MeSH Terms

Interventions

Sodium Chloride; Injections

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds; Drug Administration Routes; Drug Therapy; Therapeutics

Study Officials

• Madhu Choudhary, MD

  University of Pittsburgh

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Randomized (2:1), 20 participants in Arm 1 and 10 participants in Arm 2
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 7, 2024
• First Posted: November 8, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 14, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• Access Criteria: * With whom? Researchers who provide a methodologically sound proposal for use of the data that is approved by the AIDS Clinical Trials Group. * For what types of analyses? To achieve aims in the proposal approved by the AIDS Clinical Trials Group. * By what mechanism will data be made available? Researchers may submit a request for access to data using the AIDS Clinical Trials Group "Data Request" form at: https://actgnetwork.org/submit-a-proposal/. Researchers of approved proposals will need to sign an AIDS Clinical Trials Group Data Use Agreement before receiving the data.

Locations

US (24)