STRIDE-3 Trial Design and Key Findings
STRIDE-3 was a randomized, double-blind, active comparator-controlled, international phase 3 trial that evaluated V116 (a 21-valent pneumococcal conjugate vaccine) against PCV20 in adults, demonstrating non-inferiority for shared serotypes and superiority for most unique serotypes. 1
Study Design
The trial enrolled adults with or without stable chronic medical conditions at 112 clinical sites across 11 countries or territories 1. The study utilized:
- Randomization method: Central electronic interactive response technology system
- Blinding: Double-blind design with investigators, participants, and trial personnel masked to treatment assignment
- Study period: July 13 to November 22,2022 for enrollment 1
Population Characteristics
Cohort Structure
Cohort 1 (≥50 years):
- Stratified by age groups: 50-64,65-74,75-84, and ≥85 years
- Randomized 1:1 to V116 (n=1,179) or PCV20 (n=1,177)
- Total vaccinated: 2,356 participants 1
Cohort 2 (18-49 years):
- Randomized 2:1 to V116 (n=200) or PCV20 (n=100)
- Total vaccinated: 300 participants 1
Overall enrollment: 2,754 screened, 2,663 randomly assigned, 2,656 vaccinated 1
Interventions
Participants received a single intramuscular dose of either:
- V116: 21-valent pneumococcal conjugate vaccine (investigational)
- PCV20: 20-valent pneumococcal conjugate vaccine (active comparator)
Blood samples were collected at baseline (day 1) and post-vaccination (day 30) to measure serotype-specific responses 1.
Primary Outcomes and Results
Four Primary Immunogenicity Endpoints
1. Non-inferiority for shared serotypes (Cohort 1):
- V116 met non-inferiority criteria compared to PCV20 for all 10 common serotypes
- Criterion: Lower bound of 95% CI for OPA GMT ratio >0.5
- Result: p<0.0001 for each common serotype 1
2. Superiority for unique serotypes - OPA GMT ratios (Cohort 1):
- V116 met superiority criteria for 10 of 11 unique serotypes
- Criterion: Lower bound of 95% CI for OPA GMT ratio >2.0
- Exception: Serotype 15C (p=0.41) did not meet superiority
- All other unique serotypes: p<0.0001 1
3. Superiority for unique serotypes - Four-fold rise (Cohort 1):
- V116 demonstrated superiority for 10 of 11 unique serotypes based on proportion with ≥4-fold OPA rise
- Criterion: Lower bound of 95% CI for difference in proportions >10%
- Exception: Serotype 15C (p=0.67)
- All other unique serotypes: p<0.0001 1
4. Immunobridging between age groups (Cohort 2):
- Immune responses in 18-49 year-olds were non-inferior to 50-64 year-olds for all 21 V116 serotypes
- Criterion: Lower bound of 95% CI for OPA GMT ratio >0.5
- Result: p<0.0001 for all V116 serotypes 1
Safety Outcomes
Adverse Event Rates
Cohort 1 (≥50 years):
- V116: 685 participants (58.2%) reported ≥1 adverse event
- PCV20: 778 participants (66.2%) reported ≥1 adverse event 1
Cohort 2 (18-49 years):
- V116: 164 participants (82.0%) reported ≥1 adverse event
- PCV20: 79 participants (79.0%) reported ≥1 adverse event 1
Serious Adverse Events
- Six deaths occurred, all in Cohort 1, none vaccine-related:
- V116 group: 4 deaths (sepsis, cerebrovascular accident, myocardial infarction, hepatic cirrhosis/encephalopathy)
- PCV20 group: 2 deaths (cardiac arrest, abdominal abscess)
- Zero vaccine-related serious adverse events 1
Clinical Significance
The FDA approval of V116 (marketed as CAPVAXIVE) was based on STRIDE-3 along with STRIDE-5 and STRIDE-6 trials 2, 3. The study demonstrated that V116 elicited comparable immune responses to PCV20 for shared serotypes while providing additional coverage for serotypes not included in other pneumococcal vaccines 4.
Key Limitation
The notable exception of serotype 15C failing to meet superiority criteria represents an important consideration, though the immune response was numerically higher compared to PCV20 1. This finding was consistent across both OPA GMT ratios and four-fold rise analyses.