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. Issue 38 (7th September 2021)

• Record Type: Journal Article
• Authors: Klein, Nicola P.; Peyrani, Paula; Yacisin, Kari; Caldwell, Nicole; Xu, Xia; Scully, Ingrid L.; Scott, Daniel A.; Jansen, Kathrin U.; Gruber, William C.; Watson, Wendy
• Is Part Of: Vaccine. Volume 39:Issue 38(2021)
• Page Start: 5428
• Page End: 5435
• Publication Date: 2021-09-07
• Subjects: Clinical trial -- Lot consistency -- Immunogenicity and safety -- Streptococcus pneumoniae -- 20-valent pneumococcal conjugate vaccine; 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; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2021.07.004
• Languages: English
• ISSNs: 0264-410X

Abstract

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).