A phase 2, randomized, blinded, dose-finding, controlled clinical trial to evaluate the safety, tolerability, and immunogenicity of a 24-valent pneumococcal conjugate vaccine (VAX-24) in healthy adults 65 years and older

Abstract

Despite current polysaccharide and conjugate vaccine use, pneumococcal diseases remain prevalent in older adults. VAX-24 is a 24-valent pneumococcal conjugate vaccine (PCV) containing eCRM, a proprietary carrier protein with non-native amino acids (para-azidomethyl-L-phenylalanine) that undergo site-specific conjugation to pneumococcal polysaccharides that have been activated with a small-molecule linker (dibenzocyclooctyne). Site-specific conjugation utilizing click chemistry enables consistent exposure of T-cell epitopes, reduction in carrier protein to pneumococcal polysaccharide ratio, and enhances manufacturing process consistency to improve PCVs by increasing serotype coverage while minimizing carrier suppression. Healthy adults aged 65 or older were randomized in a 1:1:1:1 ratio to receive a single injection of VAX-24 at 1 of 3 dose levels (1.1, 2.2, or a mixed dose of 2.2 or 4.4 mcg) or Prevnar 20® (PCV20) in a phase 2, blinded study. Primary outcome measures were solicited local and systemic events within 7 days post-vaccination, unsolicited adverse events (AEs) within 1 month, and serious AEs, medically attended AEs, or new onset of chronic disease within 6 months of vaccination. Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) were measured pre-vaccination and at 1 month post-vaccination. Of 207 participants enrolled, 200 completed the trial. Safety profiles were comparable across the three VAX-24 doses and PCV20. Robust OPA and IgG immune responses were seen for all 24 serotypes. On average, immune responses to VAX-24 2.2 mcg dose were similar or higher compared to PCV20. In adults ≥ 65 years, VAX-24 had a safety profile similar to PCV20 through six months post-vaccination and induced robust OPA and IgG responses to all 24 serotypes, supporting prior data showing that site-specific conjugation allows for increased serotype coverage with similar or higher immune response vs other PCVs. The outcome of this phase 2 study further supports use of VAX-24 2.2 mcg dose in phase 3 trials. Clinicaltrials.gov: NCT05297578.

Keywords: Clinical study; Dose-ranging; Immunogenicity; Pneumococcal conjugate vaccine; Safety; ≥65 years.