HIV-1
Conditions
Keywords
HIV, Therapeutic vaccine, bNab-inducing vaccine, Trimer
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).
Interventions
BIOLOGICALCH505 TF chTrimer
Stabilized CH505 TF chTrimer, 300 mcg
BIOLOGICAL3M-052-AF
3 mcg
BIOLOGICALAluminum Hydroxide Suspension
500 mcg
Sodium chloride for injection, 0.9% USP volume-matched placebo injection.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Duke University
Access to Advanced Health Institute (AAHI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Randomized (2:1), 20 participants in Arm 1 and 10 participants in Arm 2
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
United States
Contacts
STUDY_CHAIRMadhu Choudhary, MD
University of Pittsburgh
Outcome results
None listed