Elsevier

Vaccine

Volume 39, Issue 38, 7 September 2021, Pages 5428-5435
Vaccine

A phase 3, randomized, double-blind study to evaluate the immunogenicity and safety of 3 lots of 20-valent pneumococcal conjugate vaccine in pneumococcal vaccine-naive adults 18 through 49 years of age

https://doi.org/10.1016/j.vaccine.2021.07.004Get rights and content
open access

Highlights

  • This was a phase 3 randomized, double-blind PCV20 study in adults 18–49 years old.

  • The immunogenicity of 3 PCV20 lots was evaluated and safety of PCV20 was described.

  • Equivalence of vaccine responses was observed for 20 serotypes across 3 PCV20 lots.

  • All of the PCV20 lots elicited robust immune responses to the vaccine serotypes.

  • Safety and tolerability of PCV20 was acceptable and similar to PCV13.

Abstract

Introduction

Introduction of pneumococcal conjugate vaccines (PCVs), including the 13-valent PCV (PCV13), has considerably reduced pneumococcal disease burden. However, additional serotypes not in PCV13 continue to present a substantial disease burden. The 20-valent PCV (PCV20) was developed to expand protection against pneumococcal disease beyond PCV13. As part of the phase 3 clinical development program, the current study assessed consistency of immune responses across 3 lots of PCV20 and described the safety profile of PCV20.

Methods

This phase 3, randomized, multicenter, double-blind study of pneumococcal vaccine-naive adults 18–49 years of age randomized 1710 participants in a 2:2:2:1 ratio to receive 1 of 3 lots of PCV20 or PCV13. Immunogenicity was assessed through serotype-specific opsonophagocytic activity (OPA) titers before and approximately 1 month (28–42 days) after vaccination. Reported local reactions within 10 days, systemic events within 7 days, adverse events (AEs) within 30 days, and serious AEs (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) within 6 months after vaccination were evaluated.

Results

Equivalence in immune responses (OPA geometric mean titers) for all 20 vaccine serotypes was demonstrated across the 3 PCV20 lots. Robust responses, assessed by OPA geometric mean fold rises, percentage of participants achieving ≥4-fold rises, and percentage of participants with OPA titers ≥lower limit of quantitation, were observed after PCV20. Reported rates of local reactions, systemic events, and AEs were similar between the pooled PCV20 lots and PCV13; most events were mild or moderate. Reported rates of SAEs and NDCMCs were low and similar between the PCV20 and PCV13 groups.

Conclusions

Three different lots of PCV20 demonstrated robust and consistent immunogenicity. The safety and tolerability of PCV20 was acceptable and similar to that of PCV13. (Clinicaltrials.gov: NCT03828617).

Keywords

Clinical trial
Lot consistency
Immunogenicity and safety
Streptococcus pneumoniae
20-valent pneumococcal conjugate vaccine

Abbreviations

AE
adverse event
CRM197
cross-reactive material 197
GMFR
geometric mean fold rise
GMR
geometric mean ratio
GMT
geometric mean titer
IPD
invasive pneumococcal disease
LLOQ
lower limit of quantitation
NDCMC
newly diagnosed chronic medical condition
OPA
opsonophagocytic activity
PCV
pneumococcal conjugate vaccine
PCV7
7-valent pneumococcal conjugate vaccine
PCV13
13-valent pneumococcal conjugate vaccine
PCV20
20-valent pneumococcal conjugate vaccine
PPSV23
23-valent pneumococcal polysaccharide vaccine
SAE
serious adverse event

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