Study Overview

This was a phase 1/2, randomized, double-masked study of VAX-24 versus PCV20 conducted in the USA. Key inclusion criteria included being a male or female aged 18 to 64 years in good health; key exclusion criteria included a previous history of pneumococcal disease, receipt of a licensed or investigational pneumococcal vaccine, or immunosuppressive therapy. Participants were randomly allocated in a 1:1:1:1 ratio by permuted block to receive one dose of VAX-24 (1·1 μg of each antigen, 2·2 μg of each antigen, or 2·2 μg of 17 antigens mixed with 4·4 μg of seven antigens), or PCV20. The safety population included all participants with safety data. The immunogenicity population was as per-treatment in phase 2. Primary outcome measures included solicited and unsolicited adverse events. Secondary outcomes included serotype-specific opsonophagocytic activity (OPA) geometric mean titres (GMT), and IgG geometric mean concentrations (GMC) were measured one month postvaccination. Traditional non-inferiority criteria included OPA geometric mean ratio (GMR), with a lower bound of the two-sided 95% CI of greater than 0·5 for shared serotypes. 

Study Results

Safety profiles were comparable among the treatment groups, with 170 of 209 participants (81%, 95% CI 75·2–86·2) to 178 of 207 participants (86%, 80·5–90·4) reporting at least one solicited adverse event among the three VAX-24 groups. 24 of 207 participants (12%, 7·6–16·8) to 32 of 209 of participants (15%, 10·7–20·9) experienced an unsolicited treatment-emergent adverse event within one month postvaccination. VAX-24 2·2 μg met traditional OPA GMR non-inferiority criteria for all 20 shared serotypes; 16 serotypes elicited GMR point estimates greater than 1·0, and four reached the lower bound of the two-sided 95% CI greater than 1·0.

Study Interpretation

VAX-24 had a safety profile similar to PCV20 at all doses, with the 2·2 μg dose showing increased serotype coverage with decreased carrier suppression.