Study of the Transmission-Blocking Vaccine Pfs230D1-EPA/Matrix-M Against Malaria in Adults in Mali
Condition: Malaria,Falciparum
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

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.
    

Intervention name(s): Pfs230D1-EPA/Matrix-M Vaccine; Verorab Rabies Vaccine
Intervention type(s): Biological; Biological
Intervention description(s): 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.; 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.
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Prevention
Keywords: Malaria; Reactogenicity; Antibody; Mosquito; Vaccine