Trial of a Falciparum Malaria Protein (FMP012), E. Coli-expressed PfCelTOS, in Healthy Malaria-Naive Adults
Condition: Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      Malaria has remained a major concern for the US military. During World War II, malaria was
      the leading cause of disease and non-battle injury with 500-700 men infected per day,
      resulting in 24,000 malaria-related casualties.(10) Currently, the methods used for
      protecting troops against malaria are insecticidal nets, clothing, and antimalarial
      treatment. To be effective, these methods must be self-administered and be used consistently,
      often unattainable in field or combat situations. The United States Army Medical Research and
      Development Command (USAMRMC), through the United States Army Medical Materiel Development
      Activity (USAMMDA) and the Walter Reed Army Institute of Research (WRAIR) are actively
      pursuing the development of an effective vaccine against P. falciparum malaria; development
      of such a vaccine is a high priority for the US military and other individuals who travel to
      endemic regions, and is equally important to populations residing in those areas.

      A Phase 1 study using FMP012, a recombinant E.coli expressed malaria protein (CelTOS) vaccine
      will

        1. assess the safety and reactogenicity of candidate P. falciparum malaria vaccine
           FMP012/GLA-SE

           Secondary:

        2. measure the humoral immune response to FMP012/GLA-SE using enzyme-linked immunosorbent
           assay (ELISA)

        3. assess the protective efficacy of FMP012/GLA-SE against a P. falciparum sporozoite
           challenge.
    

Detailed description: 
      Single center, non-randomized, open label, dose escalation Phase 1study with sporozoite
      challenge. The antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion
      (GLA-SE), a proprietary adjuvant produced by the Infectious Disease Research Institute
      (IDRI). This is a first-in-human study of FMP012. Thirty subjects, divided into 3 groups (10
      subjects per group), will receive 3 doses of the FMP012/GLA-SE vaccine. Group 1 will receive
      10 µg of FMP012 formulated with 2 µg GLA-SE adjuvant and Group 2 will receive 10 µg of FMP012
      formulated with 5 µg GLA-SE adjuvant. Group 3 will receive 50 µg of FMP012 formulated with
      either 5 µg GLA-SE adjuvant (Group 3a) or 2 µg GLA-SE adjuvant (Group 3b). Determination of
      whether to proceed with Group 3a or Group 3b will be made by the principal investigator (PI)
      and the independent medical monitor after the second vaccination dose in Group 2 has been
      completed, based on predefined safety and group hold criteria in this protocol. There will be
      a staggered start for Group 1 and Group 2 separated by a minimum of 14 days. Group 3a or
      Group 3b will start vaccinations 2 weeks after the second vaccination for Group 2. The first
      and second vaccination doses in each group will be separated by 28 days and all groups will
      receive the third vaccination dose on the same day. The second and third vaccination doses in
      Group 1 will be separated by 84 days, Group 2 by 70 days, and Group 3 by 28 days. Six
      non-immunized infectivity control subjects will be enrolled prior to the challenge phase. All
      subjects from the Vaccination Group and Infectivity Control Group will participate in the
      primary malaria sporozoite challenge and will be required to stay at a hotel for evaluation
      for a maximum of 10 nights starting 9 days after the challenge. A directly monitored,
      sequentially allocated, open-label oral regimen of chloroquine or artemether/lumefantrine
      will be administered to all parasitemic subjects.
    

Intervention name(s): Group 1: 10 ug FMP012 with 2 ug GLA-SE; Group 2: 10 ug FMP012 with 5 ug GLA-SE; 50 ug FMP012 with 5 ug GLA-SE or 2 ug GLA-SE; Controlled group-Challenged Only: no vaccination
Intervention type(s): Biological; Biological; Biological; Other
Intervention description(s): Biological/vaccine; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipid A Stable emulsion (GLA-SE), a proprietary adjuvant; E-coli expressed antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant; E-coli expressed malaria antigen FMP012 adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant; The control group participated in the primary malaria sporozoite challenge.E-coli expressed antigen FMP012 will be adjuvanted with Glucopyranosyl lipd A stable emulsion (GLA-SE), a proprietary adjuvant
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Interference of malaria infection