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

Phase 1

Completed

• Conditions: Malaria,Falciparum
• Interventions: Biological: Pfs230D1-EPA/Matrix-M Vaccine; Biological: Verorab Rabies Vaccine

• Registration Number: NCT05135273
• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Brief 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.

Study Timeline

• Study Start: 2021-10-22
• Study First Submitted: 2021-11-17
• Study First Submitted QC: 2021-11-17
• Study First Posted: 2021-11-26
• Primary Completion: 2023-02-17
• Study Completion: 2023-06-21
• Results First Submitted: 2024-02-21
• Status Verified: 2024-05
• Results First Submitted QC: 2024-05-03
• Last Update Submitted: 2024-05-03
• Results First Posted: 2024-05-06
• Last Update Posted: 2024-05-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2a (Main Group)	Pfs230D1-EPA/Matrix-M Vaccine	(n=15) to receive 12.5 µg Pfs230D1-EPA/25 µg Matrix-M on D1, D29, D57
1a (Pilot Group)	Pfs230D1-EPA/Matrix-M Vaccine	(n=5) to receive 12.5 µg Pfs230D1-EPA/25 µg Matrix-M on D1, D29, D57
2b (Main Group)	Pfs230D1-EPA/Matrix-M Vaccine	(n=15) to receive 20 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57
2c (Main Group)	Pfs230D1-EPA/Matrix-M Vaccine	(n=15) to receive 40 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57
1d (Pilot Group)	Verorab Rabies Vaccine	(n=4) to receive rabies vaccine (standard dose) on D1, D29, D57
2d (Main Group)	Verorab Rabies Vaccine	(n=16) to receive rabies vaccine (standard dose) on D1, D29, D57
1b (Pilot Group)	Pfs230D1-EPA/Matrix-M Vaccine	(n=5) to receive 20 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57
1c (Pilot Group)	Pfs230D1-EPA/Matrix-M Vaccine	(n=5) to receive 40 µg Pfs230D1-EPA/50 µg Matrix-M on D1, D29, D57

Primary Outcome Measures

Name	Time	Method
Number of Local and Systemic Adverse Events (AEs) to Assess the Safety of the Study Drug	Adverse Events monitored/assessed for 7 days after each vaccination at days 1, 29, and 57; All-Cause Mortality monitored/assessed through 14 months	The analyses included only subjects who received at least one vaccination
Number of Local and Systemic Serious Adverse Events (SAEs) to Assess the Safety of the Study Drug	Serious Adverse Events monitored/assessed for 7 days after each vaccination at days 1, 29, and 57; All-Cause Mortality monitored/assessed through 14 months

Trial Locations

Locations (1)

Malaria Research Training Center; 🇲🇱 Bamako, Mali