Efficacy, Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Evaluating Different Dose Schedules in a Sporozoite Challenge Model in Healthy Malaria-naïve Adults
Condition: Malaria
MeSH terms: Malaria
Study type: Interventional
Phase: Phase 2

Summary: 
      This study is designed to evaluate efficacy, immunogenicity and safety of various dose
      schedules of GSK Biologicals' candidate malaria vaccines RTS,S/AS01B (adult formulation) and
      RTS,S/AS01E (pediatric formulation) in healthy malaria-naïve subjects aged 18-55 years. The
      purpose of this study is to investigate whether changes in dosing schedule are associated
      with increased or equivalent protection, and to evaluate the immune mechanisms associated
      with vaccine efficacy under varying dosing schedules.
    

Detailed description: 
      Protocol Amendment 1 incorporated: additional blood sampling for assessment of parasitemia
      (polymerase chain reaction [PCR] testing); clarification that blood samples for both
      peripheral blood mononuclear cells (PBMC) and plasma will be collected for repository
      storage; revision of volume of whole blood samples to be taken for parasitemia assessment;
      clarification that urine pregnancy tests will be conducted for all females and not just those
      of childbearing potential; deletion of visit at Day 1 post day of challenge; clarification
      that RNA sequencing and not deep sequencing will be performed in this study.

      Note that as a result of internal change in data standards terminology, the study data
      collected was converted to cDISC and the statistical analysis plan was amended accordingly.
      "Day 0" in the study design was replaced by "Day 1"; consequently, "Day n" was replaced by
      "Day n+1". Thus, the timeframes (Day 0, Day n) of Outcome Measures described in this study
      record are different to that denoted in the full protocol document posted.
    

Intervention name(s): RTS,S/AS01E; RTS,S/AS01B; Sporozoite-infected mosquitoes challenge.
Intervention type(s): Biological; Biological; Procedure
Intervention description(s): Subjects will receive intramuscular injection of RTS,S/AS01E.; Subjects will receive intramuscular injection of RTS,S/AS01B.; Mosquitoes infected approximately 2-3 weeks earlier that are likely to contain sporozoites in their salivary glands will be allowed to feed on the subjects. For each subject, five mosquitoes will be allowed to feed over five minutes, after which they will be dissected to confirm how many were infected, and the salivary glands scored. If required additional mosquitoes will be allowed to feed until a total of five infected mosquitoes with a minimum of 2+ salivary gland scores have fed.
The challenge occurs approximately 90 days (three months) after the last vaccination.
Subjects will be monitored during 28 days after having bitten by mosquitoes and when parasites are found in their blood, they will be treated with appropriate anti-malarial drugs.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: healthy volunteers; Malaria; malaria vaccine; controlled human challenge; RTS,S/AS01