1184. A Phase 3, Multicenter, Randomized, Double-blind Study to Evaluate the Interchangeability of V114 and Prevnar 13™ with Respect to Safety, Tolerability, and Immunogenicity in Healthy Infants (PNEU-DIRECTION)
Authors: Bili Adroniki , Dobson Scott , Quinones Jeffrey , Phongsamart Wanatpreeya , Oberdorfer Peninnah , Kosalaraksa Pope , Dagan Ron , Wilck Marissa B , Vallejos Waldimir , Nunn Christine , McFetridge Richard , Fu Rong , Lupinacci Robert , Musey Luwy , Bickham Kara 
Published: December 2021

Abstract

Background
Pneumococcal diseases (PD) caused by Streptococcus pneumoniae are a major health concern globally. In children, currently licensed pneumococcal conjugate vaccines (PCVs) provide protection against PD from vaccine serotypes, but other non-vaccine serotypes have emerged and contribute to most residual disease. V114 is a 15-valent investigational PCV containing serotypes 22F and 33F in addition to the 13 serotypes shared by Prevnar 13TM (PCV13). This phase 3 study evaluated safety and immunogenicity of mixed PCV13/V114 regimens when changing from PCV13 to V114 at doses 2, 3, or 4.

Methods
In this double-blind trial, 900 infants were randomized in equal ratios to five treatment groups using a 3 + 1 immunization schedule (3-dose infant primary series followed by one toddler dose). Groups 2, 3, and 4 started with PCV13 and switched to V114 at doses 4, 3, and 2, respectively. Groups 1 and 5 received four doses of PCV13 and V114, respectively. Immunoglobulin G (IgG) responses to the 15 pneumococcal serotypes in V114 were measured at 30 days post-dose 3, prior to dose 4, and 30 days post-dose 4 (PD4). Primary immunogenicity analysis was based on 13 shared serotype responses at PD4. Safety was evaluated as the proportion of participants with adverse events (AEs).

Results
At 30 days PD4, IgG geometric mean concentrations (GMCs) for the 13 shared serotypes were generally comparable between V114/PCV13 mixed regimens (Groups 2-4) and participants that received the 4-dose PCV13 regimen (Group 1). Additionally, IgG GMCs for the 13 shared serotypes were generally comparable for participants that received the 4-dose V114 regimen (Group 5) and participants that received the 4-dose PCV13 regimen (Group 1). Infants given at least one dose of V114 mounted immune responses to two unique serotypes in V114 (22F and 33F). Frequency of injection-site and systemic AEs among study participants were generally comparable across all study groups.

Conclusion
V114 was well tolerated with a generally comparable safety profile to PCV13. For the 13 shared serotypes, both mixed-dose and 4-dose regimens of V114 induced generally comparable antibody responses to a PCV13 4-dose regimen. Study results support interchangeability of V114 with PCV13 in infants.

Disclosures
Adroniki Bili, MD, Merck & Co., Inc. (Employee, Shareholder) Ron Dagan, MD, Medimmune/AstraZeneca (Grant/Research Support, Scientific Research Study Investigator, Research Grant or Support)MSD (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau)Pfizer (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Research Grant or Support, Speaker’s Bureau) Marissa B. Wilck, MD, Merck & Co., Inc. (Employee, Shareholder) Waldimir Vallejos, MD, Merck & Co., Inc. (Employee, Shareholder) Christine Nunn, MS, Merck & Co., Inc. (Employee, Shareholder) Richard McFetridge, B.S., Merck & Co., Inc (Employee) Rong Fu, PhD, MSD China (Employee, Shareholder) Robert Lupinacci, M.S, Merck & Co., Inc (Employee, Shareholder) Luwy Musey, MD, Merck & Co., Inc. (Employee) Kara Bickham, MD, Merck Sharp and Dohme (Employee, Shareholder)