Safety of the Inactivated Japanese Encephalitis Virus Vaccine IXIARO in Children An Open-label, Randomized, Active-controlled, Phase 3 Study

Background: Japanese encephalitis remains a serious health concern in Asian countries and has sporadically affected pediatric travelers. In the present study, we monitored the safety profile of the Japanese encephalitis virus vaccine IXIARO (Valneva Austria GmbH, Vienna, Austria) in a pediatric population. Methods: We randomized 1869 children between 2 months and 17 years of age in an age-stratified manner to vaccination with IXIARO or one of the control vaccines, Prevnar (formerly Wyeth Pharmaceuticals Inc., now Pfizer Inc., Kent, United Kingdom) and HAVRIX 720 (GlaxoSmithKline Biologicals, Rixensart, Belgium). Adverse events (AEs) (unsolicited and solicited local and systemic AEs), serious AEs and medically attended AEs were assessed up to day 56 and month 7 after the first dose. Results: Incidences of AEs, serious AEs or medically attended AEs did not differ significantly between the groups in any age stratum. AEs were most frequent in children < 1 year of age and decreased with age. AEs of special interest, predefined as AEs associated with potential hypersensitivity/allergy or neurologic disorders up to day 56, were reported in 4.6% (IXIARO) versus 6.3% (Prevnar) in the >= 2 months to < 1 year age group and 3.4% (IXIARO) versus 3.3% (HAVRIX) in the >= 1 to < 18 years age group. Fever, the most frequent systemic reaction in 23.7% of infants to 3.8% of adolescents, decreased with age and did not differ between groups. Conclusions: The safety profile of IXIARO was comparable to the control vaccines in terms of overall AE rates, serious AEs and medically attended AEs.