NCT06069544

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

A Randomized, Dose-escalation Phase I/IIa Trial With Controlled Human Malaria Infection to Evaluate Safety, Tolerability, Immunogenicity and Efficacy of an Investigational RNA-based Vaccine for Prevention of P. Falciparum Malaria in Healthy Malaria naïve Adults

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 163 (actual)
• Sponsor: BioNTech SE · Industry
• Sex: All
• Age: 18 Years – 55 Years
• Healthy volunteers: Accepted

Summary

This is a randomized, dose-escalation Phase I/IIa trial to evaluate safety, tolerability, immunogenicity and efficacy of an investigational RNA-based vaccine (BNT165e) for prevention of P. falciparum malaria in healthy malaria-naive adults. The multi-antigen malaria vaccine (designated BNT165e) is a combination of three distinct RNAs, BNT165c and BNT165d (composed of BNT165d1 and BNT165d2), encoding P. falciparum antigens encapsulated in lipid nanoparticles. The BNT165c RNA encodes the full Plasmodium falciparum circumsporozoite protein. The BNT165d1 and BNT165d2 RNAs both encode conserved, immunogenic segments of liver stage-expressed proteins.

Detailed description

Part A of this trial will be observer-blind and assess the reactogenicity, safety, and immunogenicity of up to 9 dose combinations in a 3-dose regimen of the 3 components of BNT165e. One dose combination will also be tested in a Day 1, Day 29, and Day 57 dosing schedule 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 the third dose will be administered \~18 weeks after the second dose. In Cohort 10, the investigational medicinal product (IMP) will be administered 28 days apart on Day 1, Day 29, and Day 57. Participants who are out of window for dosing in the event of a trial pause can be discontinued from further vaccination. If a participant is discontinued either from further vaccination or discontinued from the trial, the sponsor can decide to replace this participant with a new participant. Participants will be randomized to the vacancy in the open cohort until that cohort has filled. The number of participants may be increased 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 Cohorts 1 to 9, and 66 weeks for each participant in Cohort 10. Trial duration may exceed the listed maximum time in the event of a trial pause. An amendment will be submitted to the Health Authorities detailing Part B, which will explore the efficacy of BNT165e in a controlled human malaria infection model.

Conditions

• Malaria

Interventions

Type	Name	Description
BIOLOGICAL	BNT165e	Multi-antigen RNA-based vaccine for active immunization against malaria administered as intramuscular injection
OTHER	Placebo	Isotonic NaCl solution (0.9%)

Timeline

• Start date: 2023-11-13
• Primary completion: 2025-05-28
• Completion: 2026-03-20
• First posted: 2023-10-06
• Last updated: 2026-04-15

Locations

5 sites across 1 country: United States

Regulatory

• FDA-regulated drug study