Clinical trial NCT06680479: Safety and Immunogenicity of Stabilized CH505 TF chTrimer Vaccination in Adults Living With HIV-1 on Suppressive Antiretroviral Therapy
Official title: Safety and Immunogenicity of Stabilized CH505 TF chTrimer Vaccination in Adults Living With HIV-1 on Suppressive Antiretroviral Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: HIV-1
Keywords: HIV
Therapeutic vaccine
bNab-inducing vaccine
Trimer
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Duke University
name: Access to Advanced Health Institute (AAHI)
First posted: 2024-11-08
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


Eligibility criteria: 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).

Primary outcomes:
measure: 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
timeFrame: Day 0 (after initial vaccination) to 4 weeks (28 days) after the last vaccination
measure: 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
timeFrame: Day 0 pre-vaccination to 2 weeks (14 days) after the fifth vaccination
Secondary outcomes:
measure: Antibody neutralization response for vaccine-matched and related viruses
timeFrame: Day 0 pre-vaccination to 2 weeks (14 days) after the fifth vaccination
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles CARE Center CRS
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center CRS
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco HIV/AIDS CRS
state: California
city: Torrance
country: United States
facility: Harbor University of California Los Angeles Center CRS
state: California
city: Aurora
country: United States
facility: University of Colorado Hospital CRS
state: Colorado
city: Atlanta
country: United States
facility: The Ponce de Leon Center CRS
state: Georgia
city: Chicago
country: United States
facility: Northwestern University CRS
state: Illinois
city: Baltimore
country: United States
facility: Johns Hopkins University CRS
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital CRS (MGH CRS)
state: Massachusetts
city: Saint Louis
country: United States
facility: Washington University Therapeutics (WT) CRS
state: Missouri
city: Newark
country: United States
facility: New Jersey Medical School Clinical Research Center CRS
state: New Jersey
city: New York
country: United States
facility: Weill Cornell Chelsea CRS
state: New York
city: New York
country: United States
facility: Columbia Physicians & Surgeons (P&S) CRS
state: New York
city: New York
country: United States
facility: Weill Cornell Uptown CRS
state: New York
city: Rochester
country: United States
facility: University of Rochester Adult HIV Therapeutic Strategies Network CRS
state: New York
city: Chapel Hill
country: United States
facility: Chapel Hill CRS
state: North Carolina
city: Greensboro
country: United States
facility: Greensboro CRS
state: North Carolina
city: Cincinnati
country: United States
facility: Cincinnati CRS
state: Ohio
city: Cleveland
country: United States
facility: Case CRS
state: Ohio
city: Columbus
country: United States
facility: Ohio State University CRS
state: Ohio
city: Philadelphia
country: United States
facility: Penn Therapeutics CRS
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh CRS
state: Pennsylvania
city: Nashville
country: United States
facility: Vanderbilt Therapeutics (VT) CRS
state: Tennessee
city: Houston
country: United States
facility: Houston Advancing Research Team CRS
state: Texas
city: Seattle
country: United States
facility: University of Washington Positive Research CRS
state: Washington
Study officials:
affiliation: University of Pittsburgh
name: Madhu Choudhary, MD
role: STUDY_CHAIR
References: