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

Phase 1

Not yet recruiting

• Conditions: HIV-1
• Interventions: Biological: CH505 TF chTrimer; Other: Sodium Chloride for Injection; Biological: 3M-052-AF; Biological: Aluminum Hydroxide Suspension

• Registration Number: NCT06680479
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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).

Detailed Description

Not available

Basic Information
|
Recruitment & Eligibility
|
Study & Design
|
Trial Locations

Study Timeline

• Status Verified: 2024-11
• Study First Submitted: 2024-11-07
• Study First Submitted QC: 2024-11-07
• Study First Posted: 2024-11-08
• Last Update Submitted: 2024-11-27
• Last Update Posted: 2024-12-02
• Study Start: 2025-02-15
• Primary Completion: 2026-10-13
• Study Completion: 2027-08-13

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

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

Read More

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).

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)	CH505 TF chTrimer	-
Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)	3M-052-AF	-
Study Arm 1: CH505 TF chTrimer (300 mcg) admixed with 3M-052-AF (3 mcg) and Alum (500 mcg)	Aluminum Hydroxide Suspension	-
Study Arm 2: Placebo (sodium chloride for injection, 0.9% USP)	Sodium Chloride for Injection	-

Primary Outcome Measures

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

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

Trial Locations

Locations (25)

University of California, Los Angeles CARE Center CRS; 🇺🇸 Los Angeles, California, United States

UCSD Antiviral Research Center CRS; 🇺🇸 San Diego, California, United States

University of California, San Francisco HIV/AIDS CRS; 🇺🇸 San Francisco, California, United States

Harbor University of California Los Angeles Center CRS; 🇺🇸 Torrance, California, United States

University of Colorado Hospital CRS; 🇺🇸 Aurora, Colorado, United States

The Ponce de Leon Center CRS; 🇺🇸 Atlanta, Georgia, United States

Northwestern University CRS; 🇺🇸 Chicago, Illinois, United States

Johns Hopkins University CRS; 🇺🇸 Baltimore, Maryland, United States

Massachusetts General Hospital CRS (MGH CRS); 🇺🇸 Boston, Massachusetts, United States

Washington University Therapeutics (WT) CRS; 🇺🇸 Saint Louis, Missouri, United States

New Jersey Medical School Clinical Research Center CRS; 🇺🇸 Newark, New Jersey, United States

Weill Cornell Chelsea CRS; 🇺🇸 New York, New York, United States

Columbia Physicians & Surgeons (P&S) CRS; 🇺🇸 New York, New York, United States

Weill Cornell Uptown CRS; 🇺🇸 New York, New York, United States

University of Rochester Adult HIV Therapeutic Strategies Network CRS; 🇺🇸 Rochester, New York, United States

Chapel Hill CRS; 🇺🇸 Chapel Hill, North Carolina, United States

Greensboro CRS; 🇺🇸 Greensboro, North Carolina, United States

Cincinnati CRS; 🇺🇸 Cincinnati, Ohio, United States

Case CRS; 🇺🇸 Cleveland, Ohio, United States

Ohio State University CRS; 🇺🇸 Columbus, Ohio, United States

Penn Therapeutics CRS; 🇺🇸 Philadelphia, Pennsylvania, United States

University of Pittsburgh CRS; 🇺🇸 Pittsburgh, Pennsylvania, United States

Vanderbilt Therapeutics (VT) CRS; 🇺🇸 Nashville, Tennessee, United States

Houston Advancing Research Team CRS; 🇺🇸 Houston, Texas, United States

University of Washington Positive Research CRS; 🇺🇸 Seattle, Washington, United States