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

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).

Study Overview

• Status: Suspended
• Conditions: HIV-1
• Intervention / Treatment: Biological: CH505 TF chTrimer; Biological: 3M-052-AF; Biological: Aluminum Hydroxide Suspension; Other: Sodium Chloride for Injection

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90035
      • University of California, Los Angeles CARE Center CRS
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center CRS
    • San Francisco, California, United States, 94110
      • University of California, San Francisco HIV/AIDS CRS
    • Torrance, California, United States, 90502-2052
      • Harbor University of California Los Angeles Center CRS
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Hospital CRS
  • Georgia
    • Atlanta, Georgia, United States, 30308-2012
      • The Ponce de Leon Center CRS
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University CRS
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins University CRS
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital CRS (MGH CRS)
  • Missouri
    • St Louis, Missouri, United States, 63110-1010
      • Washington University Therapeutics (WT) CRS
  • New Jersey
    • Newark, New Jersey, United States, 07103
      • New Jersey Medical School Clinical Research Center CRS
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Uptown CRS
    • New York, New York, United States, 10010
      • Weill Cornell Chelsea CRS
    • New York, New York, United States, 10032
      • Columbia Physicians & Surgeons (P&S) CRS
    • Rochester, New York, United States, 14642
      • University of Rochester Adult HIV Therapeutic Strategies Network CRS
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7215
      • Chapel Hill CRS
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0405
      • Cincinnati CRS
    • Cleveland, Ohio, United States, 44106
      • Case CRS
    • Columbus, Ohio, United States, 43210
      • Ohio State University CRS
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Penn Therapeutics CRS
    • Pittsburgh, Pennsylvania, United States, 15213
      • University of Pittsburgh CRS
  • Tennessee
    • Nashville, Tennessee, United States, 37204
      • Vanderbilt Therapeutics (VT) CRS
  • Texas
    • Houston, Texas, United States, 77030
      • Houston Advancing Research Team CRS
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington Positive Research CRS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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
• No participation in conception process and agree to use at least one reliable form of contraception if participating in sexual activity that could lead to pregnancy during the study and for 8 weeks following the final study vaccine

Exclusion Criteria:

• 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
• Acute or serious illness requiring systemic treatment and/or hospitalization within 30 days prior to study entry
• Conditions that would preclude injection site reaction assessments (e.g., extensive tattoos, scarring, skin conditions).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)	Biological: CH505 TF chTrimer; Stabilized CH505 TF chTrimer, 300 mcg; Biological: 3M-052-AF; 3 mcg; Biological: Aluminum Hydroxide Suspension; 500 mcg
Placebo Comparator: Study Arm 2: Placebo (sodium chloride for injection, 0.9% USP)	Other: Sodium Chloride for Injection; Sodium chloride for injection, 0.9% USP volume-matched placebo injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Antibody neutralization response for vaccine-matched and related viruses	Determined using a neutralization assay and CH505 TF and related vaccine matched virus panel	Day 0 pre-vaccination to 2 weeks (14 days) after the fifth vaccination

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Duke University; Access to Advanced Health Institute (AAHI)
• Investigators: Study Chair: Madhu Choudhary, MD, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2025
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 14, 2028

Study Registration Dates

• First Submitted: November 7, 2024
• First Submitted That Met QC Criteria: November 7, 2024
• First Posted (Actual): November 8, 2024

Study Record Updates

• Last Update Posted (Actual): March 3, 2026
• Last Update Submitted That Met QC Criteria: March 2, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HIV; Therapeutic vaccine; bNab-inducing vaccine; Trimer
• Additional Relevant MeSH Terms: Therapeutics; Drug Administration Routes; Drug Therapy; Inorganic Chemicals; Chlorine Compounds; Sodium Compounds; Chlorides; Hydrochloric Acid; Injections; Sodium Chloride
• Other Study ID Numbers: A5422; 39037 (Other Identifier: DAIDS-ES ID)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie results in publication, after deidentification.
• IPD Sharing Time Frame: Beginning 3 months following publication and available throughout period of funding of the AIDS Clinical Trials Group by NIH.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No