Experimental Vaccine for Malaria in Adults in Mali
Condition: Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      This study will determine the highest dose of an experimental vaccine called AMA1-C1 that can
      safely be given to adults exposed to malaria. Malaria affects about 300 million to 500
      million people worldwide each year, causing from 2 million to 3 million deaths, mostly among
      children under 5 years of age in sub-Saharan Africa. It is the leading cause of death and
      illness among the general population of Mali in West Africa. 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. AMA1-C1 is an experimental vaccine
      developed by the NIAID. Early tests of AMA1-C1 in 30 healthy people in the United States
      found no serious harmful side effects of the vaccine. This study will look at the effect of
      AMA1-C1 in people in Mali who have been exposed to malaria.

      Residents of Don gu bougou, Mali, who are between 18 and 45 years of age and are in general
      good health may be eligible for this study. Candidates are screened with a medical history
      and physical examination, blood and urine tests, and urine pregnancy test for women.

      Participants are randomly assigned to receive three injections (shots) of either the
      experimental malaria vaccine or a hepatitis B vaccine that is approved and used in Mali. All
      shots are given in an upper arm muscle. After the first shot, the second is given 1 month
      later, and the third is given 12 months after the first. Subjects receiving AMA1-C1 will get
      one of three different doses - low, medium, or high - to find the dose that is safest and
      gives the best antibody response to the vaccine. After each shot, participants remain in the
      clinic for 30 minutes for observation. They return to the clinic 1, 2, 3, 7, and 14 days
      after each shot for a physical examination and to check for side effects. Blood samples are
      drawn before each shot and at selected return clinic visits to check for side effects and to
      measure the effect of the vaccine.

      During the rainy seasons after the second and third vaccinations, subjects come to the clinic
      once a month for an examination and a blood test. During the dry season, subjects come to the
      clinic 3 months before the last shot is given for an examination and blood test. Additional
      blood tests may be done on participants who develop malaria.

      If found to be safe in adults, further studies with this vaccine will be done in children
      exposed to malaria, as it is children who bear the brunt of this disease.
    

Detailed description: 
      The purpose of this Phase 1 clinical trial is to evaluate the safety and immunogenicity of
      the Plasmodium falciparum malaria vaccine AMA1-C1/Alhydrogel, in healthy malaria-exposed
      adult volunteers. Between 2-3 million deaths occur each year as a result of malaria. Most of
      these deaths are a result of P. falciparum malaria, in children under five years of age, in
      sub-Saharan Africa. A safe and effective vaccine that would reduce both morbidity and
      mortality secondary to P. falciparum would be a valuable resource in the fight against this
      disease. The apical membrane antigen 1 (AMA1) is a surface protein expressed during the
      asexual blood stage of P. falciparum that is thought to play a role in parasite invasion of
      erythrocytes. Clinical symptoms of malaria in humans are due to the asexual blood stage.
      Therefore, this vaccine was designed to protect an individual from illness due to the asexual
      stage of P. falciparum infection by inhibiting parasite invasion of erythrocytes. The
      AMA1-C1/Alhydrogel vaccine preparations to be studied contain an equal mixture of AMA1 from
      two different clones of Plasmodium falciparum (FVO and 3D7), both produced separately as
      recombinant proteins expressed by Pichia pastoris (AMA1 FVO and AMA1 3D7). This vaccine has
      been tested in one clinical trial of 30 malaria-unexposed human adults in the United States
      and no clinically significant risks have been identified. The study will be conducted in Don
      gu bougou, Mali, and will be a blinded, randomized and controlled trial that will evaluate
      three dose levels of AMA1-C1 (5 micro g, 20 micro g, 80 micro g). Fifty-four healthy male and
      non-pregnant female volunteers ages 18 to 45 will be enrolled. Eighteen volunteers will be
      assigned to each of the three dose groups. Within each group, twelve volunteers will be
      randomized to receive either a 5 micro g, 20 micro g, or 80 micro g dose of
      AMA1-Cl/Alhydrogel and 6 will be randomized to receive the tetanus toxoid vaccine.
      Immunizations will be administered by intramuscular injection on months 0, 1, and 12. The
      groups will be staggered such that adequate safety evaluation can be performed prior to dose
      escalation. The duration of the study is 18 months per volunteer. The primary objective of
      this trial is to determine the frequency and severity of vaccine-related adverse events for
      each dose. The secondary objective is to determine the dose that generates the highest serum
      antibody levels to AMA1 antigen at Day 42.
    

Intervention name(s): AMA1-C1; AMA1-C1/alhydrogel Malaria Vaccine
Intervention type(s): Biological; Drug
Intervention MeSH terms: Aluminum Hydroxide
Primary purpose: Treatment
Keywords: Blood-Stage; Investigational; Endemic; Malaria; Vaccine