A prospective study to evaluate the safety, effectiveness and impact of the RTS, S/AS01E vaccine in young children in sub-Saharan Africa (EPI-MALARIA-003 VS AME) (115056)

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Disease epidemiology

  Effectiveness study (incl. comparative)

  Safety study (incl. comparative)
• Data collection methods:
  Combined primary data collection and secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

  Other
• Non-interventional study design, other:
  Cluster Design

Study drug and medical condition

• Medicinal product name, other:
  Mosquirix™ (RTS,S/AS01E vaccine)
• Anatomical Therapeutic Chemical (ATC) code:
  (J07XA01) malaria vaccines

  malaria vaccines
• Medical condition to be studied:
  Meningitis

Population studied

• Short description of the study population:
  The study population is defined as study participants < 5 years of age living in a geographically limited area with a demographic surveillance system in place, and a well-developed infrastructure to monitor population health and vaccination programmes.
• Age groups:
  • Infants and toddlers (28 days – 23 months)
  • Children (2 to < 12 years)
• Estimated number of subjects:
  45000

Study design details

• Study design:
  Disease surveillance study with prospective cohort event monitoring including both temporal (before-after comparison with EPI-MAL-002; Interim Analysis only) and concurrent (cluster design comparison of exposed and ; unexposed clusters; Interim and Final Analysis) comparisons
• Main study objective:
  • To estimate the incidence of adverse events of special interest (AESI) in children vaccinated with RTS,S/AS01E. ; • To estimate the incidence of aetiology-confirmed meningitis in children vaccinated with RTS,S/AS01E.
• Setting:
  Specific locations in sub-Saharan Africa with moderate to high malaria transmission.; A geographically confined region equipped with a demographic surveillance system and robust infrastructure for tracking population health and vaccination programs.
• Outcomes:
  - Incidence rates of adverse events of special interest (AESI);; - Incidence rates of aetiology-confirmed meningitis cases;; - Incidence rates of probable meningitis (final classification);; - Incidence rates of clinically suspected meningitis (final classification);; - Number of meningitis cases identified at site level (first line laboratory);; - Incidence rates of cerebral malaria cases (diagnosed by Rapid Diagnostic Test [RDT] and/or microscopy);; - Incidence rates of malaria episodes diagnosed by RDT and/or microscopy;; - Incidence rates of anaemia cases at hospital entry among hospitalised children;; - Incidence rates of hospitalisation cases;; - Number of deaths.
• Data analysis plan:
  All data analyses will be computed in a descriptive manner. Data regarding the hospitalisation will be uniformly collected whether the child is enrolled in active surveillance or in enhanced hospitalisation surveillance.
• Summary results:
  Safety signals observed in Phase 3 were not confirmed by the EPI-MAL-003 Final Analysis, and no new signals were identified. Meningitis events were rare and evenly distributed over RTS,S/AS01E vaccinated and unvaccinated groups. Cerebral malaria events were rare and occurred both in RTS,S/AS01E vaccinated and unvaccinated groups. Deaths occurred at similar rates in males and females. There was no evidence of an ; association between vaccine exposure and any prespecified AESI. Over 1 year after the full (4-dose) vaccination schedule, a positive impact against hospitalizations due to malaria, any and severe malaria, and hospitalizations due to anemia was observed.