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).


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).