Infectious Disease · Medical Literature
A phase 3, randomized study to evaluate the safety, tolerability, and immunogenicity of V116 in children and adolescents with increased risk of pneumococcal disease (STRIDE-13).
Abstract
Pneumococcal disease (PD) causes significant illness and death, especially in young children, older adults, and individuals with chronic medical conditions. Due to increased risk, children with chronic conditions are often advised to receive additional pneumococcal vaccination beyond the routine primary series. This phase 3 study evaluated the safety and immunogenicity of V116, a 21-valent pneumococcal conjugate vaccine, compared to PPSV23 in children aged 2 to <18 y with certain medical conditions that increase risk of PD who had previously completed a primary pneumococcal vaccination regimen. Individuals with diabetes mellitus, chronic heart, chronic lung, chronic kidney, and/or chronic liver disease were randomized 3:2 to receive a single dose of either V116 (n = 531) or PPSV23 (n = 351). Immunogenicity was assessed at 30 d postvaccination comparing opsonophagocytic activity (OPA) geometric mean titers (GMTs) and immunoglobulin G (IgG) geometric mean concentrations (GMCs) between groups. Safety was evaluated by the proportion of participants with adverse events (AEs). The V116 group met the statistical noninferiority criterion for each of the 12 pneumococcal vaccine serotypes shared between V116 and PPSV23 and additionally met superiority criterion for each of the 9 serotypes unique to V116 based on OPA GMTs. IgG GMCs were consistent with the OPA results. The safety profile was generally comparable between groups. In children and adolescents aged 2 to <18 y with certain medical conditions, V116 is well tolerated and immunogenic. These findings support the use of V116 to broaden pneumococcal serotype coverage in populations at increased risk of pneumococcal disease.
Clinical relevance
In children and adolescents aged 2 to <18 years with chronic medical conditions that increase pneumococcal disease risk who have already completed a primary pneumococcal vaccination series, is a single dose of V116 (21-valent pneumococcal conjugate vaccine) non-inferior to PPSV23 in immunogenicity for shared serotypes and superior for unique serotypes, with a comparable safety profile? __SNAPSHOT__ {"studyDesign":"Phase 3, randomized, active-comparator-controlled trial (STRIDE-13; NCT06177912)","setting":"Multi-national, multi-site; specific countries not fully enumerated in the abstract (international trial per clinical trial registry)","sampleSize":"n=882 total (V116: n=531; PPSV23: n=351), randomized 3:2","population":"Children and adolescents aged 2 to <18 years with at least one of the following stable chronic medical conditions conferring increased risk of pneumococcal disease: diabetes mellitus, chronic heart disease, chronic lung disease, chronic kidney disease, and/or chronic liver disease; all had previously completed a primary pneumococcal conjugate vaccine regimen (PCV7, PCV10, or PCV13) at least 8 weeks before enrollment. Immunocompromised individuals and those with a history of invasive pneumococcal disease within 3 years were excluded per trial registry.","intervention":"Single intramuscular dose of V116 (Capvaxive; pneumococcal 21-valent conjugate vaccine)","comparator":"Single dose of PPSV23 (Pneumovax 23; 23-valent pneumococcal polysaccharide vaccine)","primaryOutcome":"Opsonophagocytic activity (OPA) geometric mean titers (GMTs) at 30 days post-vaccination — non-inferiority of V116 vs. PPSV23 for the 12 serotypes shared between the two vaccines, and superiority of V116 vs. PPSV23 for the 9 serotypes unique to V116. Safety: proportion of participants with adverse events.","followUp":"30 days post-vaccination for primary immunogenicity; safety follow-up duration beyond 30 days not specified in the abstract (not reported in abstract)","fundingSource":"Industry — Merck Sharp & Dohme (MSD), a subsidiary of Merck & Co., Inc.; multiple authors are MSD employees and/or hold company stock"}
Key findings
V116 met the pre-specified statistical non-inferiority criterion for OPA GMTs for each of the 12 pneumococcal serotypes shared between V116 and PPSV23 (non-inferiority threshold: lower bound of the two-sided 95% CI for the OPA GMT ratio >0.5). V116 additionally met the pre-specified superiority criterion for OPA GMTs for each of the 9 serotypes unique to V116 that are not contained in PPSV23 (superiority threshold: lower bound of the two-sided 95% CI for the OPA GMT ratio >1.0 per trial registry criteria). Specific OPA GMT values, GMT ratios, and confidence interval bounds for individual serotypes are not reported in the abstract. IgG geometric mean concentrations (GMCs) at day 30 were consistent with the OPA results, supporting the immunogenicity findings. The safety profile was described as 'generally comparable between groups'; specific rates of solicited injection-site reactions, systemic adverse events, or serious adverse events were not reported in the abstract. V116 is estimated to provide potential coverage for up to approximately 78% of invasive pneumococcal disease (IPD) cases in high-risk pediatric populations and covers 11 serotypes not included in standard pediatric conjugate regimens (calculated/externally reported; not derived from the abstract alone). NNT and NNH cannot be calculated from the immunogenicity data presented.
Practice implications
This phase 3 trial establishes that V116 (Capvaxive) produces immune responses non-inferior to PPSV23 for shared serotypes and superior responses for the 9 unique V116 serotypes in children and adolescents aged 2 to <18 years who carry chronic medical conditions and have completed a primary PCV series. These immunogenicity results are biologically plausible and clinically relevant because they indicate broader serotype coverage than PPSV23, a polysaccharide vaccine already recommended in this at-risk population. However, this study did not measure clinical efficacy endpoints (e.g., reduction in invasive pneumococcal disease, pneumonia, or mortality); immunogenicity is a surrogate endpoint, and its correlation with clinical protection in the pediatric vaccine-experienced setting has not been directly demonstrated in this trial. Applicability is limited to pediatric patients aged 2–17 years with stable diabetes mellitus, chronic heart, lung, kidney, or liver disease who have completed a prior PCV regimen; immunocompromised children (e.g., those with asplenia, HIV, or primary immunodeficiency) and vaccine-naive children were not studied. The generalizability of immunogenicity and safety findings to immunocompromised high-risk groups — who may arguably have the greatest clinical need — cannot be inferred from this data. V116 is currently approved only for adults ≥18 years; this study's findings represent the final readout of the phase 3 STRIDE program for the pediatric indication and will be submitted to regulatory authorities, but pediatric licensure had not been granted as of the study publication date. Only the abstract was available for this summary; specific serotype-level OPA GMT values, confidence intervals, and detailed safety event rates could not be reviewed, which limits the depth of this interpretation. __LIMITATIONS__ Immunogenicity surrogate endpoints only — no clinical efficacy data (invasive disease, pneumonia hospitalization, or mortality) were reported or powered for in this trial.,Abstract-only availability: serotype-level OPA GMT values, GMT ratios with 95% CIs, and granular adverse event incidence rates cannot be independently evaluated.,Immunocompromised children (e.g., asplenia, HIV, primary immunodeficiency, malignancy) were excluded, limiting generalizability to the highest-risk pediatric subgroups.,Short immunogenicity follow-up (30 days post-vaccination); durability of immune responses and waning over time were not assessed.,Industry sponsorship by MSD with multiple investigators who are company employees and equity holders, introducing potential for bias in study design, analysis, and reporting.,Unequal randomization (3:2) slightly reduces the statistical precision of the PPSV23 comparator arm.,V116 was originally designed as an adult-specific vaccine; the relevance of its serotype composition to pediatric-predominant circulating strains may differ by geography and evolving serotype epidemiology.,The study population required stable chronic medical conditions for ≥3 months; applicability to newly diagnosed or poorly controlled disease states is uncertain.,No correction for multiple comparisons across 21 serotype-specific immunogenicity analyses was described in the abstract. __BOTTOM_LINE_CATEGORY__ promising_but_preliminary __BOTTOM_LINE__ In children and adolescents aged 2–17 years with chronic medical conditions who have completed a primary PCV series, a single dose of V116 demonstrated non-inferior immunogenicity to PPSV23 for all 12 shared serotypes and superior immunogenicity for all 9 V116-unique serotypes, with a comparable safety profile. These immunogenicity data are promising and support a potential regulatory pathway for V116 as a supplemental pneumococcal vaccine in this at-risk pediatric population; however, V116 is not currently approved for pediatric use and no clinical efficacy data were generated. Clinicians should await regulatory review and approval before adopting V116 in pediatric practice, while continuing to follow existing ACIP/national guidance for pneumococcal vaccination in high-risk children.