A Clinical Trial to Evaluate the Safety, Efficacy and Immune Responses After Vaccination With an Investigational RNA-based Vaccine Against Malaria

Part A of this trial will be observer‐blind and assess the reactogenicity, safety, andimmunogenicity of up to 9 dose combinations in a 3‐dose regimen of the 3 components ofBNT165e. One dose combination will also be tested in a Day 1, Day 29, and Day 57 dosingschedule in Cohort 10. Participants will be randomized 5:1 active:placebo.In Cohorts 1 to 9, the initial two doses will be administered 8 weeks apart and thethird dose will be administered 18 weeks after the second dose. In Cohort 10, theinvestigational medicinal product (IMP) will be administered 28 days apart on Day 1, Day29, and Day 57.Participants who are out of window for dosing in the event of a trial pause can bediscontinued from further vaccination. If a participant is discontinued either fromfurther vaccination or discontinued from the trial, the sponsor can decide to replacethis participant with a new participant. Participants will be randomized to the vacancyin the open cohort until that cohort has filled. The number of participants may beincreased up to 177 in the event of participant replacement or re‐enrollment.The planned trial duration is up to a maximum of 84 weeks for each participant in Cohorts1 to 9, and 66 weeks for each participant in Cohort 10. Trial duration may exceed thelisted maximum time in the event of a trial pause.An amendment will be submitted to the Health Authorities detailing Part B, which willexplore the efficacy of BNT165e in a controlled human malaria infection model.