Trial of a Falciparum Malaria Protein (FMP012), E. Coli-expressed PfCelTOS, in Healthy Malaria-Naive Adults
Condition: Malaria
MeSH terms: Malaria; Malaria, Falciparum
Intervention: 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 description: 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
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 36.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Interference of malaria infection

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.
    

Eligibility criteria:

        -  Healthy adults (male or non-pregnant, non-lactating female) 18 to 50 years of age at
             the time of screening

          -  If the subject is female,

          -  Non-childbearing potential , abstinent or using adequate contraceptive precautions
             during this study and must agree to continue such precautions until three months after
             challenge

          -  A negative pregnancy test at the time of enrollment

          -  Free of significant health problems as established by medical history, laboratory, and
             clinical examination before entering the study

          -  Low cardiac risk factors

          -  Available to participate and reachable by phone for duration of study (approximately 8
             months)

          -  No plans to travel to outside the Washington DC area between the day of challenge and
             either completion of treatment course (post-challenge) or, if subject remains
             uninfected, 28 days post-challenge

          -  No plans to travel to a malaria endemic area during the course of the study

          -  Written informed consent must be obtained from the subject before screening procedures

          -  Subjects must score at least 80% correct on a multiple-choice quiz that assesses their
             understanding of this study

          -  Active duty military must obtain approval from his or her supervisor

        Exclusion Criteria:

          -  History of malaria infection

          -  History of travel to P. falciparum endemic areas in the 3 months prior to day of first
             vaccination or day of challenge

          -  History of receiving a malaria vaccine

          -  Receipt of any licensed vaccine within 7 days prior to first vaccination

          -  History of receipt of malaria prophylaxis during the 2 months prior to day of first
             vaccination or day of challenge

          -  History of use of any drugs with significant antimalarial activity during the course
             of the study period

          -  Prior receipt of any vaccine containing either QS-21, MPL or GLA-SE in the previous 5
             years (including Cervarix®, GSK)

          -  Use of any investigational or non-registered drug or vaccine within 30 days preceding
             the first dose of study vaccine or planned use during the study period.

          -  Any history of allergic reaction or anaphylaxis to previous vaccination

          -  Allergy to kanamycin, nickel, or imidazole Pregnant or lactating female at screening
             or plans to become pregnant or breastfeed from the time of enrollment until three
             months after challenge

          -  Allergy to antimalarial drugs or use of medications known to interact with both CQ and
             artemether/lumefantrine

          -  Significant (eg, systemic) hypersensitivity reactions to mosquito bites

          -  History of sickle cell disease

          -  History of psoriasis or porphyria

          -  History of splenectomy

          -  Any confirmed or suspected immunodeficiency, including HIV infection

          -  Administration of chronic (defined as more than 14 days) immunosuppressive drugs or
             other immune-modifying drugs within six months of vaccination

          -  Inhaled and topical steroids are allowed

          -  A family history of congenital or hereditary immunodeficiency

          -  Acute or chronic, clinically significant, pulmonary, cardiovascular, hepatic, or renal
             functional abnormality, as determined by history, physical examination, or laboratory
             evaluation

          -  Chronic or active neurologic disease including seizure disorder and chronic migraine
             headaches

          -  Administration of immunoglobulins and/or any blood products within the three months
             preceding the first dose of study vaccine or any planned administration during the
             study period

          -  Any abnormal baseline laboratory screening tests listed below (normal values are
             defined in the adverse event section of this protocol):

          -  Seropositive for HIV or Hepatitis C virus or HBsAg positive

          -  Hepatomegaly, right upper quadrant abdominal pain or tenderness

          -  An abnormal baseline screening EKG.

          -  Suspected or known current alcohol or drug abuse as determined from the medical
             history or by physical examination

          -  Any other significant finding that in the opinion of the PI would increase the risk of
             having an adverse outcome from participating in this study