NCT05135273

Study of the Transmission-Blocking Vaccine Pfs230D1-EPA/Matrix-M Against Malaria in Adults in Mali

Phase 1, Dose-Escalating, Double-Blind, Randomized, Comparator-Controlled Trial of the Safety, Tolerability, and Immunogenicity of the Transmission-Blocking Vaccine Pfs230D1-EPA/Matrix-M™ Against Plasmodium Falciparum in Adults in Mali

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 80 (actual)
• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) · NIH
• Sex: All
• Age: 18 Years – 50 Years
• Healthy volunteers: Accepted

Summary

Background: Researchers are trying to develop a vaccine that will safely reduce the spread of malaria in the community by preventing mosquitos from carrying malaria from person to person. Objective: To assess in African adults the safety of and immune response to the administration of Pfs230D1-EPA/Matrix-M vaccine as compared to the rabies vaccine control. Eligibility: Healthy adults (18 to 50 years of age) who reside in Sotuba and surrounding villages in Mali Design: Participants will be screened with: * Medical history * Physical exam * Blood, urine, and heart tests * Malaria comprehension exam Participants will be randomly assigned to get either the experimental vaccine or the approved rabies vaccine. They will not know which they are getting. Participants will get 3 doses of the study or comparator vaccine via injection in the upper arm. This occurs at the first visit, 1 month, and 2 months later. Participants will have up to 23 scheduled visits over 14 to 16 months. Each visit includes a physical exam, and blood will be collected at most visits. Participants will be followed up to 1 year after the final vaccination. If participants develop an injection site rash or reaction, photographs may be taken of the site.

Detailed description

A vaccine to interrupt malaria transmission (VIMT), targeting disruption of parasite transmission through both human and mosquito, would be a valuable additional resource in the fight to eliminate this disease. Transmission-blocking vaccines (TBVs) induce anti-sporogonic antibodies that disrupt parasite transmission to the mosquito, thereby halting transmission to another human host. Malaria-exposed populations acquire antibody against Pfs230, a parasite protein expressed by gametocytes in the human stage of P. falciparum and a surface antigen of gametes and zygotes in the mosquito stage, which suggests that a Pfs230-based vaccine may be boosted by natural malaria infection. Pfs230D1 has become one of the leading transmission-blocking antigens for consideration as a licensed TBV to be used either alone or in combination with other transmission-blocking antigens. Clinical trials with this antigen adjuvanted with either Alhydrogel or AS01 have provided very encouraging results. This is a Phase 1, dose-escalating, randomized, double-blind, comparator-controlled study to assess the safety, tolerability, immunogenicity and transmission-blocking activity (TBA) of a 3 dose regimen of Pfs230D1-EPA/Matrix-M versus rabies vaccine in healthy adults. This will be a first-in-human assessment of Pfs230D1-EPA/Matrix-M and will be conducted as a dose-escalation trial. Participants will be randomized to 1 of the study arms to receive 1 of 3 dose levels of Pfs230D1-EPA/Matrix-M or a standard dose of comparator rabies vaccine administered as an intramuscular injection at 3 timepoints. For the 3 Pfs230D1-EPA/Matrix-M antigen dosages, we will start with a Pilot Group of 5 subjects in each Pfs230D1-EPA/Matrix-M arm and the rabies vaccine control arm. For the Pilot Group, the different dosage administrations are separated by approximately 2 weeks. Safety outcomes will include the frequency of systemic and local adverse events and serious adverse events. Immunogenicity outcomes will be antibody responses measured by ELISA against Pfs230D1. Functional activity will be assessed by standard membrane feeding assays.

Conditions

• Malaria,Falciparum

Interventions

Type	Name	Description
BIOLOGICAL	Pfs230D1-EPA/Matrix-M Vaccine	Each single-use vial of Pfs230D1M-EPA contains 160 µg/mL of conjugated Pfs230D1M and 124 µg/mL or 143 µg/mL of conjugated EPA in 4 mM phosphate-buffered saline (PBS), in a volume of 0.5 mL. Each vial of Matrix-M1 contains saponin content of 0.375 mg/mL in PBS, at a pH of 7.2, in a final volume of 0.75 mL. Components will be combined in volumes defined in the protocol at point of use.
BIOLOGICAL	Verorab Rabies Vaccine	Verorab Rabies Vaccine is a purified inactivated rabies vaccine (Wistar rabies PM/WI 38 1503-3M strain) prepared on Vero cells. It is supplied as a powder and solvent for suspension for injection in a prefilled syringe. Before reconstitution, the powder is a white and homogeneous pellet. The solvent is a limpid solution.

Timeline

• Start date: 2021-10-22
• Primary completion: 2023-02-17
• Completion: 2023-06-21
• First posted: 2021-11-26
• Last updated: 2024-05-06
• Results posted: 2024-05-06

Locations

1 site across 1 country: Mali

Regulatory

• FDA-regulated drug study