Phase II AMA-1 Malaria Vaccine FMP2.1/AS02A Trial in Mali
Condition: Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 2

Summary: 
      Malaria is a disease that affects many people in Africa. Malaria is caused by germs spread by
      mosquito bites. The purpose of this study is to compare the number of children who get
      malaria after receiving an experimental malaria vaccine (FMP2.1/AS02A) to the number of
      children who get malaria after receiving a vaccine for rabies (an approved vaccine that does
      not prevent malaria). The children will be assigned to one of the vaccine groups by chance.
      Participants and doctors will not know which vaccine was given. Study participants will
      include 400 children, ages 1-6 years, living in Bandiagara, Mali. Children will receive 3
      vaccine doses, by injection, to their upper arm. Study procedures will include physical exams
      and several blood samples. Participants will be involved in the study for 26 months.
    

Detailed description: 
      This is a randomized, controlled, phase II clinical trial to evaluate the efficacy, safety
      and immunogenicity of the apical membrane antigen-1 of Plasmodium (P.) falciparum (AMA-1)
      malaria vaccine FMP2.1/AS02A using rabies vaccine as a control in healthy children 1-6 years
      old in Bandiagara, Mali. This study is linked to DMID protocol 05-0146, which is a phase I
      dose escalation trial at the same site in the same population. In this study, 400 subjects
      will be randomized in a 1:1 ratio to receive either 50 micrograms of FMP2.1 in 0.5 mL AS02A
      or rabies vaccine. Immunizations will be given on days 0, 30 and 60. Solicited adverse events
      will be recorded on the days of immunization and at 1, 2, 3 and 7 days after each
      immunization. Unsolicited adverse events will be recorded for 30 days after each
      immunization. Passive case detection will be used to capture clinical malaria episodes and
      adverse events including serious adverse events, and will occur by continuous availability of
      clinical care in a population with high utilization of this care. Active surveillance will be
      used to capture malaria infections and adverse events including serious adverse events. For
      active case detection, following the third dose, participants will be followed monthly for 6
      months and then at 12, 18 and 24 months after randomization, for clinical assessment, malaria
      smear and hemoglobin. Routine monthly malaria smears will not be read immediately unless
      symptoms are present. Children will be followed for 2 years after the first immunization.
      Sera will be collected for anti-FMP2.1 antibody titers on the days of immunization and 1, 3,
      6, 8, 12, 18 and 24 months after the first immunization. Peripheral blood mononuclear cells
      (PBMCs) will be collected on the days of immunization, 30 days after the third immunization
      and 8, 12, 18 and 24 months after the first immunization. The study Final Report will be
      based on data collected up to 6 months after the assigned date of the third immunization. A
      supplemental report will include data from the entire 24-month observation period. Primary
      study objectives are to: determine the efficacy of FMP2.1/AS02A in children aged 1-6 years
      against first clinical malaria episodes (axillary temperature of greater than or equal to
      37.5 degrees Celsius and parasitemia of greater than or equal to 2500/mm^3) occurring between
      randomization and 6 months after the assigned date of the third immunization; and assess the
      safety of the vaccine in children aged 1-6 years. Secondary study objectives are to: describe
      the dynamics of anti-AMA-1 antibody responses in recipients of the malaria vaccine compared
      to natural responses in the control group; determine whether serum anti-AMA-1 IgG titer by
      enzyme linked immunosorbent assay (ELISA) 1 month after the third immunization correlates
      with protection against clinical malaria episode; measure allele-specific efficacy against
      parasites with AMA-1 genotypes homologous to and heterologous to the 3D7 clone of P.
      falciparum; determine vaccine efficacy against clinical malaria episodes occurring between
      randomization and 6 months after the assigned date of the third immunization; and if efficacy
      is observed based on the primary endpoint, to determine vaccine efficacy against first
      clinical malaria episode and all clinical episodes (using increasing parasitemia thresholds)
      occurring during 2 years after randomization.
    

Intervention name(s): FMP2.1/AS02A; Rabies Vaccine
Intervention type(s): Biological; Biological
Intervention description(s): 3 doses administered a month apart: 50 µg recombinant subunit protein FMP2.1 (Plasmodium falciparum Apical Membrane Antigen-1 from strain 3D7 expressed in and purified from Escherichia coli), adjuvanted with 0.5 mL of AS02A (proprietary oil-in-water emulsion and phosphate buffered saline with the immunostimulants monophosphoral lipid A and QS21).; White, freeze-dried vaccine for reconstitution with the diluent prior to use; dosage 1.0 mL of rabies vaccine.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: malaria, Mali, children, Plasmodium falciparum, vaccine