Merck announced positive results from the Phase 3 STRIDE-13 trial evaluating CAPVAXIVE (Pneumococcal 21-valent Conjugate Vaccine) in children and adolescents at increased risk of pneumococcal disease. The trial, presented at the 6th European Society of Clinical Microbiology and Infectious Diseases Conference on Vaccines in Lisbon, Portugal, demonstrated the vaccine's immunogenicity and safety in vulnerable pediatric populations with chronic medical conditions.
Trial Design and Population
STRIDE-13 (NCT06177912) was a randomized, double-blind, active comparator-controlled study that enrolled 882 participants aged 2 to less than 18 years. Participants were randomized 3:2 to receive a single dose of CAPVAXIVE or PPSV23 (pneumococcal 23-valent polysaccharide vaccine). All participants had completed a primary pediatric pneumococcal vaccination regimen and had one or more chronic medical conditions including diabetes mellitus, chronic compensated liver disease, chronic lung disease, chronic heart disease, or chronic kidney disease.
Key Immunogenicity Findings
The study met its primary immunogenicity endpoint, with CAPVAXIVE demonstrating non-inferiority to PPSV23 for each of the 12 serotypes shared between the vaccines. The lower bound of the two-sided 95% confidence interval for the serotype-specific opsonophagocytic activity (OPA) geometric mean titer (GMT) ratio exceeded 0.5 for all shared serotypes at 30 days post-vaccination.
CAPVAXIVE showed superiority to PPSV23 for each of the nine serotypes unique to CAPVAXIVE, with the lower bound of the two-sided 95% confidence interval for the serotype-specific OPA GMT ratio exceeding 2.0. The vaccine elicited immune responses to all 21 serotypes as assessed by serotype-specific OPA GMTs at 30 days post-vaccination.
Safety Profile
The proportions of participants with adverse events, including systemic and serious vaccine-related adverse events, were generally comparable between groups. Solicited injection-site adverse events were higher in the CAPVAXIVE group (72.3%) compared to the PPSV23 group (58.2%).
Clinical Significance for High-Risk Populations
"Children and adolescents living with chronic medical conditions are at increased risk of pneumococcal disease and offering them additional protection is essential," said Dr. Rotem Lapidot, chief of Pediatric Infectious Diseases at Rambam Health Care Campus and STRIDE-13 trial investigator. "Results from STRIDE-13 demonstrate the potential of CAPVAXIVE to deliver protection for these vulnerable populations, who may benefit from additional pneumococcal disease coverage by including serotypes not contained in other approved pneumococcal infant regimens."
Coverage Potential
In children and adolescents ages 2 to less than 18 years at increased risk of invasive pneumococcal disease (IPD), CAPVAXIVE has the potential to provide additional protection by covering approximately 78% of IPD cases, with 11 unique serotypes accounting for approximately 34% of IPD cases, based on national-level CDC data from 2019-2023 in individuals 2-17 years old.
For comparison, CAPVAXIVE provides coverage against serotypes responsible for approximately 84% of IPD cases in adults 50 years of age and older, compared to approximately 52% covered by PCV20 (pneumococcal 20-valent conjugate vaccine), based on national-level CDC data from 2018-2022.
Current Regulatory Status and Next Steps
CAPVAXIVE is currently approved in the U.S. for active immunization for the prevention of invasive disease and pneumonia caused by 21 specific Streptococcus pneumoniae serotypes in individuals 18 years of age and older. The vaccine is also approved in the European Union, Japan, and multiple other countries worldwide.
"While CAPVAXIVE was designed to specifically cover the serotypes that cause the majority of invasive pneumococcal disease cases in adults, findings from STRIDE-13 underscore its added potential to help protect children and adolescents who are at an increased risk," said Dr. Paula Annunziato, senior vice president, infectious diseases and vaccines, Global Clinical Development, Merck Research Laboratories.
These STRIDE-13 results represent the final readout of the Phase 3 STRIDE clinical program and will be shared with global regulatory authorities. The vaccine includes eight unique serotypes (15A, 15C, 16F, 23A, 23B, 24F, 31, and 35B) compared to other approved pneumococcal vaccines and is administered as a single dose.
Disease Burden Context
Pneumococcal disease is caused by Streptococcus pneumoniae bacteria, with approximately 100 different serotypes that can affect adults differently than children. The disease can be invasive, including pneumococcal bacteremia, bacteremic pneumococcal pneumonia, and pneumococcal meningitis, or non-invasive, such as pneumonia confined to the lungs. It is estimated that over 225,000 adults are hospitalized from pneumococcal pneumonia each year in the U.S.
