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

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).

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).