Reactogenicity and safety of AS03_B-adjuvanted H5N1 influenza vaccine in children: an open-label, one-way, crossover trial

Abstract

Background Human cases of highly pathogenic avian-origin influenza A/H5N1 infection continue to be reported to the World Health Organization, and recent outbreaks of human cases of other zoonotic influenza strains highlight the continued need for strategies to mitigate influenza pandemic potential. Methods A Phase II–III randomized, placebo-controlled, observer-blind trial was conducted to assess the immunogenicity, reactogenicity, and safety of two 1.9 μg hemagglutinin doses of AS03B-adjuvanted H5N1 (AS03B-H5N1; A/Indonesia) vaccine in children (6 months to <18 years old) of Thailand, the United States, and Canada (Year 1, published elsewhere). After database lock in Year 1, the trial was unblinded, and children who had been randomized to receive placebo and continued to fulfill the eligibility criteria were invited to participate in an open-label, one-way, crossover safety extension phase, in which they received AS03B-H5N1 vaccine. Here we report the safety analysis in Year 2. Results A total of 155 children were vaccinated in Year 2. The most frequent solicited adverse event (AE) during 7 days post vaccination was injection site pain. Irritability or fussiness was reported in about one-third of younger children (aged <6 years) during 7 days post vaccination and was the most common solicited general AE in this age group. Postvaccination temperature (≥38°C) was reported in 4 (5.1%) children. The most common solicited general AEs in older children (aged ≥6 years) were muscle aches, headache, and fatigue. The AS03B-H5N1 vaccine had a clinically acceptable safety profile up to 385 days post vaccination. Conclusions Safety in the crossover phase was acceptable and consistent with that observed in vaccine recipients in the randomized, blinded phase of the study. Clinical trial registration ClinicalTrials.gov: NCT01310413.