Phase I Pediatric FMP2.1/AS02A Trial in Mali
Condition: Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 1

Summary: 
      The purpose of this study is to test the safety and dosages of a malaria vaccine in 100
      children, 1-6 years old, in Bandiagara, Mali. The study is testing the safety of the vaccine
      when it is given to people who are regularly exposed to malaria and it will provide
      information regarding optimal vaccine dosage. This study will compare 3 injections of
      different vaccine doses to a rabies vaccine that is already approved. During the study, the
      child's health will be checked in the clinic and during home visits. Children may participate
      for about 14 months, and blood will be taken from each child throughout the study. If the
      child becomes sick from malaria, he/she will be treated. Information from this study may be
      used to develop a malaria vaccine that will help control the disease.
    

Detailed description: 
      This study is a randomized, controlled, dose-escalation, phase I trial of the FMP2.1/AS02A
      malaria vaccine, using rabies vaccine as a control. This study is linked to DMID protocol
      07-0003. The primary objective of this study is to evaluate the safety and reactogenicity of
      FMP2.1/AS02A in children naturally exposed to P. falciparum malaria infection. The secondary
      objective is to measure the magnitude and duration of antibody response to FMP2.1 by
      enzyme-linked immunosorbent assay (ELISA). One hundred healthy children aged 1-6 years in
      Bandiagara, Mali, will be randomized to 1 of 3 possible groups. Twenty subjects will be
      enrolled in cohort 1 and 40 subjects each in cohorts 2 and 3. Children within each cohort
      will be randomized in a 3:1 ratio to receive 10, 25 or 50 micrograms of FMP2.1 (in cohorts 1,
      2 and 3, respectively) adjuvanted with a proportionate volume of the AS02A, or rabies
      vaccine. Thus a total of 75 children will receive the malaria vaccine and 25 the rabies
      vaccine. Immunizations will be given on days 0, 30 and 60 in a staggered fashion, with the
      first administrations of the 25 and 50 microgram dose levels of FMP2.1 following the first
      administration of the 10 and 25 microgram dose levels, respectively, by 2-3 weeks. Solicited
      adverse events will be recorded on the days of immunization and days 1, 2, 3 and 7 after each
      immunization, and unsolicited adverse events will be recorded for 30 days after each
      immunization. Children will be followed for 1 year after the last immunization. Sera will be
      collected for anti-FMP2.1 antibody titers on the days of immunization and 14 days after each
      immunization as well as 3, 6, 9 and 12 months after the first immunization. Each child will
      participate in the study for up to 414 days, which includes the screening period. The primary
      outcome measures include: occurrence of solicited symptoms after each vaccination during a
      7-day surveillance period (day of vaccination and days 1, 2, 3 and 7 after vaccination),
      occurrence of unsolicited symptoms after each vaccination during a 30-day surveillance period
      (day of vaccination and 30 subsequent days); and occurrence of serious adverse events
      throughout the study period. The secondary outcome measure is titers and activity of
      anti-FMP2.1 antibody at each time point where serology samples are analyzed, measured by
      ELISA.
    

Intervention name(s): FMP2.1/AS02A; Rabies vaccine (RabAvert)
Intervention type(s): Biological; Biological
Intervention description(s): FMP2.1 will be reconstituted in AS02A adjuvant. Dosages: 10, 25, or 50 mcg of FMP2.1 or 0.1, 0.25 or 0.5 mL of FMP2.1/AS02A administered by intramuscular injection.; RabAvert, white, freeze-dried vaccine for reconstitution with diluent. Dosage: 1.0 mL of rabies vaccine.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double
Primary purpose: Prevention
Keywords: malaria, vaccine, Mali, children