The efficacy and safety of a quadrivalent live attenuated influenza nasal vaccine in Japanese children: A phase 3, randomized, placebo-controlled study.

BACKGROUND: Vaccination is the primary method of preventing influenza infection and complications in young children. We evaluated the efficacy and safety of a single dose of MEDI3250 (intranasal, quadrivalent, live attenuated influenza vaccine) in healthy Japanese children during the 2016/17 influenza season. METHODS: In this multicenter, randomized, double-blind, phase 3 study (jRCT2080223345), participants aged 2-18 years received MEDI3250 or placebo (2:1), stratified by age (2-6 years, 7-18 years). The primary and secondary endpoints were the incidence of confirmed symptomatic onset of influenza caused by a circulating wild-type strain or by a vaccine-matched strain, respectively. Safety outcomes included the incidence of adverse events (AEs) and vaccine-related AEs. RESULTS: Overall, 910 participants received MEDI3250 (n = 608) or placebo (n = 302). For the primary endpoint (regardless of the influenza subtype), the incidence of influenza onset was 25.5 % (MEDI3250) and 35.9 % (placebo); relative risk reduction, 28.8 % (95 % confidence interval, 12.5 %-42.0 %). For the secondary endpoint (vaccine-matched strain), the incidence was 10.9 % (MEDI3250) and 17.2 % (placebo); relative risk reduction, 36.6 % (95 % confidence interval, 6.5 %-56.8 %). Solicited AEs occurred in 67.6 % (MEDI3250) and 63.6 % (placebo). Most events were mild; nasal discharge was most common (59.2 % [MEDI3250] and 52.6 % [placebo]). Unsolicited AEs occurred in 36.0 % (MEDI3250) and 33.1 % (placebo). The most common unsolicited vaccine-related AE was diarrhea (2.3 %, both groups). CONCLUSIONS: MEDI3250 had a greater preventive effect against influenza onset in Japanese children than placebo; no new safety signals were observed relative to previous clinical and post-marketing studies of MEDI3250.

Phase III, open-label, single-arm study of a new MMR vaccine (JVC-001); measles AIK-C, mumps RIT 4385, rubella Takahashi, as a second vaccine dose in healthy Japanese children aged 5-6 years.

PURPOSE: This Phase III, multicenter, open-label, single-arm study evaluated the safety and immunogenicity of the measles-mumps-rubella (MMR) combined vaccine, JVC-001, as a second MMR vaccination. METHODS: Healthy Japanese children aged 5-6 years received a single dose of JVC-001 following a first measles, mumps, and rubella vaccination (measles-rubella bivalent and mumps monovalent vaccine [Hoshino or Torii strain] or JVC-001) or the MMR vaccine received between ages 1 to <4 years. Immunogenicity was evaluated using antibody titers before and after vaccination (Day 1/Day 43). The primary endpoint was the seroprotection rate of antibody titers against each virus; geometric mean titer (GMT) was also evaluated. Adverse events (AEs) and adverse drug reactions (ADRs) were monitored. RESULTS: One-hundred participants completed the study. The seroprotection rate of antibody titers against measles, rubella, and mumps virus (genotype D) were 100.0 % (95 % confidence interval [CI] 96.4 %, 100.0 %), 100.0 % (95 % CI 96.4 %, 100.0 %), and 100.0 % (95 % CI 96.3 %, 100.0 %), respectively. GMT (fold) increases (Day 1 to Day 43) were 16.0 to 55.7 for measles virus, 35.5 to 99.0 for rubella virus, and 25.7 to 89.5 for mumps virus (genotype D). Solicited ADRs occurred in 40.0 % of participants (injection site, 34.0 %; systemic, 13.0 %). CONCLUSIONS: The second MMR vaccination with JVC-001 demonstrated sufficient antibody coverage against all three viruses; the safety profile was tolerable. CLINICAL TRIAL REGISTRATION: jRCT2080225022.