Immunogenicity and Safety of an Inactivated Enterovirus 71 Vaccine Administered Simultaneously With Hepatitis B Vaccine and Group A Meningococcal Polysaccharide Vaccine: A Phase 4, Open-Label, Single-Center, Randomized, Noninferiority Trial.

ABSTRACT

BACKGROUND: This study tested the hypothesis that the immunogenicity and safety of the simultaneous administration of enterovirus 71 (EV71) vaccine (dose 1) with recombinant hepatitis B vaccine (HepB) on day 1 and EV71 vaccine (dose 2) with group A meningococcal polysaccharide vaccine (MenA) on day 30 is not inferior to separate administration of each vaccine. METHODS: The study was designed as a randomized, open-label, noninferiority trial. A total of 775 healthy infants aged 6 months were randomly assigned in a ratio of 111 to receive simultaneous administration of EV71 vaccine (dose 1) and HepB on day 1 and EV71 vaccine (dose 2) and MenA on day 30 (the SI group); administration of doses 1 and 2 of EV71 vaccine on days 1 and 30, respectively (the SE1 group); or administration of HepB and MenA on days 1 and 30, respectively (the SE2 group). RESULTS: According to the per protocol set, antibody responses against EV71, hepatitis B virus (HBV), and group A meningococcal polysaccharide were similar regardless of administration schedule. With the non-inferiority margin setting at 10%, the seroconversion rates of the three pathogens in the SI group (100% [98.25, 100], 44.84% [38.20, 51.63] and 27.83% [21.91, 34.38]) were not inferior to those in SE1 or SE2 group (100% [98.31, 100], 44.35% [37.82, 51.02] and 29.17% [23.20, 35.72], respectively). Frequencies of adverse reactions to each vaccination regimen were comparable (60.62% in the SI group vs 52.33% in the SE1 group and 56.98% in the SE2 group; P = .16). CONCLUSIONS: Simultaneous administration of combined EV71 vaccine with HepB and MenA has noninferior immunogenicity and safety, compared with separate administration of these vaccines. CLINICAL TRIALS REGISTRATION NCT03274102.