Phase 1 Study of the Safety, Reactogenicity, and Immunogenicity of AMA1-C1/ISA 720: Blood Stage Vaccine for Plasmodium Falciparum
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will evaluate the safety and effectiveness of a vaccine called AMA1-C1/ISA.
      Malaria is a serious infection of red blood cells caused by a parasite. There are 300 to 500
      million malaria cases worldwide each year. About 2 to 3 million deaths annually are from
      malaria alone or along with other diseases. Researchers hope to find a vaccine to fight
      malaria.

      Patients ages 18 to 45 who are in good health, are not pregnant or breast feeding, have no
      history of malaria, and have not lived for more than 1 month in an area where malaria is
      prevalent may be eligible for this study. There will be 28 participants, each assigned to one
      of three dose groups: 12 get 5 microg, 12 get 20 microg, and 4 get 80 microg of AMA 1-C1
      formulated in ISA 720. The vaccine might block the parasite from entering red blood cells and
      causing disease. This study is the first time the vaccine will be given to human beings for
      testing.

      Patients will have a medical history, physical exam, laboratory tests, and pregnancy tests.
      The study will last 48 weeks. One or two vaccinations are given by injection, at least 12
      weeks apart. After each vaccination, patients will be asked to stay in the clinic for at
      least 30 minutes for observation. They will return to the clinic on Days 1, 3, 7, 14, 28, and
      56 after each vaccination. There will be a check of vital signs, brief physical exam, history
      of symptoms and medications taken since the last visit, and blood tests to check for vaccine
      safety and effectiveness. Photographs of the injection site on the arm may be taken. Patients
      will receive a thermometer, diary card, and plastic measuring device. Each day they will
      record their temperatures and any symptoms, and measure the size of any reactions at the
      vaccination site. They will be asked to do this for 27 days after vaccinations.

      After injections, there may be pain, swelling, and redness at the vaccination site, and
      limitation of arm movement. General side effects from the vaccine may be fever, chills,
      headache, fatigue, and muscle and joint pain. Patients will be asked if they agree to have
      researchers keep any unused serum samples, for use only in research into malaria and other
      diseases. Genetic testing would not be done on those samples. Stored samples will be labeled
      with a code, and information is kept private.
    

Detailed description: 
      AMA1-C1 with Montanide ISA 720, is a blood stage malaria vaccine candidate. The objectives of
      this phase 1 trial are to study the safety, reactogenicity, and immunogenicity of this
      vaccine and to assess the level, kinetics, and the in vitro biological activity of the
      antibody response it induces. The study is an open label, dose escalation, phase 1 clinical
      trial in healthy adult volunteers. Volunteers will be screened and 28 participants will be
      enrolled into 3 dose cohorts. Cohort 1 will receive 5 micrograms of AMA1-C1/ISA 720 at each
      injection, Cohort 2 will receive 20 micrograms, and Cohort 3 will receive 80 micrograms.
      Cohorts 1 and 2 will receive 2 injections, 3 months apart. Cohort 3 will receive only 1
      vaccination. Safety outcome measures are local and systemic (including laboratory) adverse
      events. Immune responses to vaccination will be measured by enzyme-linked immunosorbent assay
      (ELISA) and parasite growth inhibition assay (GIA), and will be compared among dose groups.
    

Intervention name(s): AMA1-C1/ISA 720
Intervention type(s): Drug
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Blood Stage; Investigational; Vaccine; Malaria; Healthy Volunteer; HV