Randomized, double-blind, placebo-controlled phase 3 trial of the safety and tolerability of IC51, an inactivated Japanese encephalitis vaccine

Background. Japanese encephalitis (JE) is the most important mosquito-borne viral encephalitis and has a high case fatality rate. It is caused by Japanese encephalitis virus. Improved vaccines are urgently needed for residents in countries of endemicity, travelers, and the military. The aim of the present trial was to evaluate the safety and tolerability of IC51, Intercell's Vero cell-derived, purified, inactivated JE vaccine. Methods. This was a randomized (3:1), double-blind, placebo-controlled, multicenter phase 3 trial. Healthy subjects were randomized to receive 2 doses of IC51 (n = 2012) or placebo (n = 663) at a 4-week interval. Adverse events following immunization (AEFI) were documented over a period of 2 months. Results. The rate of severe AEFI was similar in the IC51 group (0.5%) and the placebo group (0.9%). The rate of medically attended AEFI and all AEFI was also similar in the IC51 group and the placebo group. The same applied for all adverse events, including local and systemic tolerability. Importantly, there were no signs of acute allergic reactions. Conclusion. The Intercell JE vaccine IC51 had a safety profile similar to that of placebo. These data, together with the immunogenicity data from a recent phase 3 trial, form the basis of application for licensure of this vaccine. Trial registration. ClinicalTrials.gov identifier: NCT00605058.