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. 2025 Mar 22;13(4):341.
doi: 10.3390/vaccines13040341.

A Phase 3 Randomized Trial Investigating the Safety, Tolerability, and Immunogenicity of V116, an Adult-Specific Pneumococcal Vaccine, Compared with PPSV23, in Adults ≥50 Years of Age (STRIDE-10)

Veronika Jotterand  1 , Vinita Jagannath  2 , Andrea Accini Diaz  3 , Juan Diego Velez  4 , Arna Letica  5 , Silvia Narejos Perez  6 , Rebecca Clark  7 , Yoseph Caraco  8 , Olaf Degen  9 , Kyung-Hwa Park  10 , Serhat Ünal  11 , Frederick Wittke  12 , Kimberly Hurtado  13 , Clay Churchill  13 , Ying Zhang  13 , Doreen Fernsler  13 , Jianing Li  13 , Ulrike K Buchwald  13 , Heather Platt  13
Affiliations

A Phase 3 Randomized Trial Investigating the Safety, Tolerability, and Immunogenicity of V116, an Adult-Specific Pneumococcal Vaccine, Compared with PPSV23, in Adults ≥50 Years of Age (STRIDE-10)

Veronika Jotterand et al. Vaccines (Basel). .

Abstract

Background: V116 is a 21-valent pneumococcal conjugate vaccine (PCV) designed for adults. It contains the most prevalent serotypes associated with invasive pneumococcal disease (IPD) in adults in regions with established pediatric vaccination programs. This Phase 3 study compared the safety, tolerability, and immunogenicity of V116 with 23-valent pneumococcal polysaccharide vaccine (PPSV23) in adults ≥50 years of age. Methods: In this randomized, active comparator-controlled, parallel-group, multisite, double-blind study, participants were randomized 1:1 to receive a single dose of V116 or PPSV23 (NCT05569954). Primary immunogenicity outcomes assessed the opsonophagocytic activity (OPA) responses for (i) non-inferiority for 12 serotypes common to V116 and PPSV23 based on V116/PPSV23 geometric mean titers (GMTs) at Day 30, and (ii) superiority for nine serotypes unique to V116 using V116/PPSV23 GMTs and the proportions of participants with a ≥4-fold rise in OPA responses from baseline to 30 days post-vaccination. The primary safety outcome was evaluated as the proportion of participants with solicited injection-site and systemic adverse events through Day 5 post-vaccination, and vaccine-related serious adverse events up to 6 months post-vaccination. Findings: V116 was non-inferior to PPSV23 for all 12 common serotypes, superior to PPSV23 for all nine unique serotypes based on V116/PPSV23 GMTs, and superior to PPSV23 for eight of the nine serotypes unique to V116, based on the proportion of participants with a ≥4-fold rise in OPA responses (except for serotype 15C). The safety profile of V116 was comparable to that of PPSV23. Interpretation: In regions with established vaccination programs, V116 could broaden the serotype coverage for residual pneumococcal disease in adults.

Keywords: adult; invasive pneumococcal disease; opsonophagocytic activity; pneumococcal conjugate vaccine; serotype.

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Conflict of interest statement

V.Jag. is an employee of MSD (UK) Limited, London, UK. V. Jott. and F.W. are employees of MSD (Switzerland). K.H., C.C., Y.Z., D.F., J.L., U.K.B., and H.P. are employees of Merck Sharp & Dohme LLC (a subsidiary of Merck & Co., Inc., Rahway, NJ, USA). All may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. A.A.D., J.D.V., A.L., S.N.P., R.C., Y.C., O.D., K-H.P., and S.U. have no relevant conflicts of interest to disclose. Merck Sharp & Dohme LLC (a subsidiary of Merck & Co., Inc., Rahway, NJ, USA) funded and participated in the study design, data collection, data analysis, data interpretation, and writing of the report.

Figures

Figure 1
Figure 1
Study design. † The per-protocol population included all randomized participants without protocol deviations that could have substantially affected the results of the immunogenicity analyses. ‡ The safety population included all randomized participants who received study intervention. AE: adverse event; eVRC: electronic vaccination report card; PPSV23: 23-valent pneumococcal polysaccharide vaccine; V116: 21-valent, adult-specific pneumococcal conjugate vaccine.
Figure 2
Figure 2
CONSORT flow diagram. Each participant was counted once for trial disposition based on the latest corresponding disposition record. The reasons for screened participants not undergoing randomization were screen failures (n = 43), withdrawal by participants (n = 2), and other (n = 1). PPSV23: 23-valent pneumococcal polysaccharide vaccine; V116: 21-valent, adult-specific pneumococcal conjugate vaccine.
Figure 3
Figure 3
OPA GMTs for all 12 common serotypes at 30 days post-vaccination. Non-inferiority = lower bound of the 95% CI for the estimated GMT ratio (V116/PPSV23) > 0.5 (1-sided p-value < 0.025). CI: confidence interval; GMT: geometric mean titer; OPA: opsonophagocytic activity; PPSV23: 23-valent pneumococcal polysaccharide vaccine; V116: 21-valent, adult-specific pneumococcal conjugate vaccine.
Figure 4
Figure 4
OPA GMTs for all nine unique serotypes at 30 days post-vaccination. Superiority = lower bound of the 95% CI for estimated GMT ratio (V116/PPSV23) > 2.0 (1-sided p-value < 0.025). CI: confidence interval; GMT: geometric mean titer; OPA: opsonophagocytic activity; PPSV23: 23-valent pneumococcal polysaccharide vaccine; V116: 21-valent, adult-specific pneumococcal conjugate vaccine.
Figure 5
Figure 5
Percentage of participants with a 4-fold rise in OPA Day 1 to Day 30 for all nine unique serotypes. Superiority = lower bound of the 95% CI for the difference in response rates (V116–PPSV23) ≥ 10% (1-sided p-value < 0.025). Estimated difference, 95% CI, and p-value are based on the stratified Miettinen & Nurminen method. † Serotype 15C represents the immune response to the deOAc15B polysaccharide, as the molecular structure for deOAc15B and 15C are similar; anti-15C immune responses are assessed in this study. CI: confidence interval; OPA: opsonophagocytic activity; PPSV23: 23-valent pneumococcal polysaccharide vaccine; V116: 21-valent, adult-specific pneumococcal conjugate vaccine.
Figure 6
Figure 6
Summary of AEs by severity following vaccination. † Non-serious AEs were collected from Day 1 to Day 30 post-vaccination and SAEs were collected from Day 1 through the duration of study participation. ‡ Solicited injection-site AEs and solicited systemic AEs were collected from Day 1 to Day 5 post-vaccination. § Erythema and swelling were graded according to size and presented as intensity grade, as follows: mild (0 to ≤5.0 cm); moderate (>5.0 to ≤10.0 cm); and severe (>10.0 cm). ║ Pyrexia was defined as maximum temperature ≥100.4 °F (38.0 °C), with ≥104.0 °F (40.0 °C) defined as potentially life-threatening pyrexia. AE: adverse event; PPSV23: 23-valent pneumococcal polysaccharide vaccine; SAE: serious adverse event; V116: 21-valent, adult-specific pneumococcal conjugate vaccine.
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