Lot-to-lot consistency, safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in healthy adults aged >50 years: A randomized phase 3 trial (PNEU-TRUE)

Background: Older adults are at risk of pneumococcal disease and associated morbidity and mortality. This phase 3 study (V114-020) assessed lot-to-lot consistency across safety and immunogenicity outcomes for V114, a 15-valent pneumococcal conjugate vaccine (PCV), in healthy adults aged > 50 years. Methods: Adults were randomized in a 3:3:3:1 ratio to receive a single dose of one of three lots of V114 or 13-valent PCV (PCV13), stratified by age (50-64 years, 65-74 years, and > 75 years). Serotype-specific opsonophagocytic activity (OPA) and immunoglobulin G (IgG) antibodies were evaluated at baseline (Day 1) and 30 days post-vaccination. Non-serious and serious adverse events (AEs) were evaluated post-vaccination through 14 days and Month 6, respectively. Results: Of 2340 participants enrolled, 2282 (97.5%) completed the study. Proportions of participants experiencing > 1 AE were 81.0%, 77.4%, and 78.0% for V114 lots 1, 2, and 3, respectively. Comparison of V114 combined lots with PCV13 showed that proportions of participants experiencing AEs, solicited AEs, and serious AEs were comparable for both vaccines, with the exception of injection-site pain (more frequently reported with V114). OPA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) at 30 days post-vaccination were comparable across V114 lots, and all lots met predefined equivalence criteria for all 15 vaccine serotypes (lower and upper limits of the 95% confidence intervals of serotype-specific OPA GMT ratios for all possible pairwise comparisons across the three lots were within the equivalence margin of 0.5-2.0). Serotype-specific OPA GMTs and IgG GMCs were comparable in the V114 combined lots and PCV13 groups for the 13 shared serotypes and higher in the V114 group for serotypes unique to V114 (22F and 33F). Conclusions: V114 is well tolerated with a consistent safety profile and immune response across manufacturing lots. Clinical trials registration: NCT03950856 (www.clinicaltrials.gov); 2018-004266-33 (EudraCT). (c) 2022 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA and The Author (s). Published by Elsevier Ltd. All rights reserved. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).