Experimental Vaccine for Malaria
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will examine the safety and immune response of healthy adult volunteers to
      AMA1-C1, an experimental malaria vaccine developed by the NIAID. Malaria affects about 300
      million to 500 million people worldwide each year, causing from 2 million to 3 million
      deaths. Increasing drug resistance to the malaria parasite, as well as widespread resistance
      of mosquitoes (the insects that transmit the parasite) to pesticides are reducing the ability
      to control malaria through these strategies. A vaccine that could reduce illness and death
      from malaria would be a valuable new resource in the fight against this disease. Early tests
      of AMA1-C1 in 66 people in the United States and in Mali, West Africa, found no serious side
      effects of the vaccine. This study will test a shorter schedule of vaccinations with AMA1-C1
      than that used in the previous studies.

      Healthy volunteers between 18 and 50 years of age who weigh at least 110 pounds and with no
      travel to malaria endemic areas in the past 12 months may be eligible for this study.
      Candidates are screened with a medical history and physical examination, blood and urine
      tests, and a urine pregnancy test for women who are able to bear children.

      Participants are randomly assigned to receive three injections of either the experimental
      malaria vaccine or a placebo (a solution that does not contain the vaccine) over a 2-month
      period. The shots are given in an upper arm muscle, each 1 month apart. On the day of each
      injection, participants give a history of symptoms since the last visit, have a brief
      physical examination and blood test and, for women, a blood or urine pregnancy test. After
      the injection, participants remain in the clinic 60 minutes for observation. In addition to
      the injections, participants undergo the following procedures:

        -  Record temperature and symptoms on a diary card daily for the first 7 days after each
           injection.

        -  Follow-up clinic visits 1, 3, 7 and 14 days after each shot to check for side effects.
           Blood samples are drawn before each injection and at each return clinic visit to check
           the safety and immune response to the vaccine.

        -  Have apheresis, a special procedure that separates certain components of the blood, 7
           days after each injection to measure the function of germ-fighting blood cells. For this
           procedure, blood is drawn through a needle in an arm vein and directed into a machine
           that separates the different types of blood cells. The white cells are collected in a
           plastic ...
    

Detailed description: 
      The study is a randomized, single-blinded (blinded to volunteers) placebo-controlled Phase 1
      clinical trial in healthy adult volunteers designed to evaluate the safety and reactogenicity
      of a new malaria blood stage vaccine candidate, and to elucidate the immunogenicity of the
      antigen, AMA1-C1, formulated on Alhydrogel [R]. The trial will last 42 weeks. Volunteers will
      be recruited and screened, and those determined to be eligible will be enrolled in the study,
      based on the inclusion and exclusion criteria described in Section 4.0 in this protocol.
      After providing written informed consent the volunteers will be enrolled and randomly
      allocated to receive 80 microgram dose of AMA1-C1 formulated on Alhydrogel [R] (12
      volunteers) or Alhydrogel [R] alone (6 volunteers) at 0, 1 and 2 months. After each
      injection, volunteers will be observed for 60 minutes for immediate reactions. Volunteers
      will return to the clinic on study days 1, 3, 7, and 14 following each injection for clinical
      assessment and collection of blood samples for evaluation of immune responses. Leukaphereses
      will be performed 7 days after the third vaccination to obtain peripheral blood mononuclear
      cells for B and T cell studies. Safety data for the cohort up to and including follow up day
      14 after the first, second and third injection will be available for review by the Medical
      Monitor.

      Immunogenicity of the vaccine will be assessed by standardized assays for antibody levels
      against AMA1-3D7 and AMA1-FVO, and an in vitro growth inhibition assay (GIA). The cellular
      basis of the immune responses will be evaluated by enumeration of relevant B and T cell
      subpopulations, including total and antigen-specific naive, memory and effector
      subpopulations specific for the antigens. The frequencies of B and T cells specific for the
      vaccine antigens in the group that received AMA1-C1/ Alhydrogel [R] will be compared to those
      in the group receiving Alhydrogel [R] alone. The total and antigen-specific cell frequencies
      in pre-immune (day 0) samples will serve as additional negative controls for the
      immunization. The goal of the study is to augment previously collected safety data for the 80
      microgram antigen dose with a larger cohort, and to study the safety and immunogenicity of an
      accelerated vaccination schedule.
    

Intervention name(s): AMA1/Alhydrogel
Intervention type(s): Drug
Intervention MeSH terms: Aluminum Hydroxide
Allocation: Randomized
Masking: Single
Primary purpose: Treatment
Keywords: B Cells; T Cells; Erythrocyte Stage; Antibody; Immunogenicity; Healthy Volunteer