A Phase 2 Study of the Immunogenicity, Safety, and Tolerability of MenB-FHbp, a Bivalent Meningococcal B Vaccine, in Healthy Toddlers

Abstract

Background: MenB-FHbp (bivalent rLP2086) is licenced at a 120- µg dose given on a two- or three-dose schedule to prevent meningococcal serogroup B (MenB) disease in adolescents and adults. This phase 2, observer-blinded, active-controlled, dose-escalation, sentinel-design study evaluated MenB-FHbp safety and immunogenicity in toddlers 12 to <24 months of age. Methods: Participants (N=396) were randomised (2:1 ratio) to receive MenB-FHbp (60 or 120 μg at months 0,2,6) or hepatitis A virus vaccine (HAV) (months 0,6) and saline (month 2). Primary endpoints were immune responses measured by serum bactericidal assays using human complement (hSBAs) against four representative MenB test strains. Safety was assessed by electronic diary collection of reactogenicity events occurring during the 7 days postvaccination and standard safety data collection endpoints. Findings: Percentages of participants achieving hSBA titres ≥LLOQ at either dose level after MenB-FHbp vaccination 3 ranged from 71·6% to 100·0% depending on test strain. Geometric mean titres rose from 4·0−8·5 (baseline) to 15·1−171·4 after vaccination 3. Reactogenicity events were more common among MenB-FHbp recipients and were mostly transient (median, 1−3 days) and mild or moderate in severity. Fever (axillary temperature ≥38°C) occurred in 37·3% and 15·2% of 120-µg MenB-FHbp and HAV/saline recipients. Percentages of participants experiencing any adverse events (AEs) were similar across groups. Two MenB-FHbp recipients at the 120-µg dose level withdrew for safety-related reasons. Interpretation: MenB-FHbp given on a 0,2,6-month schedule at either dose level induced robust immune responses in a majority of toddlers with an acceptable tolerability profile. Clinical Trial Number: ClinicalTrials.gov identifier: NCT02534935 Funding Statement: The funding sponsor (Pfizer Inc.) of the study was involved in study design, data collection, data analysis, data interpretation, and writing of the study report. All authors had full access to the data in the study and had final responsibility for the decision to submit the manuscript for publication. Declaration of Interests: HSM, TV, PCR, and LS are investigators for vaccine trials sponsored by Pfizer. HSM’s institution has received funding for investigator-led research from Pfizer. S-SL has no interests to declare. JB, JDM, JE, KUJ, JA, GC, RM, TRJ, SLH, LJY, and JLP are current or former employees of Pfizer and may hold stock or stock options. Helen Marshall receives funding from NHMRC CDF2 APP1084951. Ethics Approval Statement: The protocol and informed consent form were reviewed and approved by institutional independent ethics committees of participating investigative sites. Written informed consent was obtained from parents or legal guardians prior to any study activities being performed.