Clinical trial NCT03855995: A Study Assessing the Safety, Efficacy, and Impact of GlaxoSmithKline Biologicals' RTS, S/AS01E Malaria Vaccine in Young Children Across Sub-Saharan Africa
Official title: A Prospective Study to Evaluate the Safety, Effectiveness and Impact of the RTS, S/AS01E Vaccine in Young Children in Sub-Saharan Africa
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Malaria
Malaria Vaccines
Keywords: Malaria
Plasmodium falciparum
Vaccine effectiveness
Sub-Saharan Africa
Active surveillance
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2019-02-27
Enrollment: 78000
Sex: ALL
Maximum age (years): 5
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The target population for the introduction of the RTS,S/AS01E vaccine are children living in the SSA.

Brief summary: The RTS, S/AS01E vaccine was developed to protect children in sub-Saharan Africa from malaria as part of routine immunization programs. This study aims to check the vaccine's safety after it has been introduced. Along with safety, researchers will also assess how well the vaccine works and its overall impact on children's health.

Detailed description: This is a disease surveillance study with prospective cohort event monitoring including both temporal and concurrent comparisons of the occurrence of adverse and malaria events between vaccinated and unvaccinated subjects living in exposed or unexposed clusters located in sub-Saharan Africa (SSA) countries, and eligible for RTS,S/AS01E vaccination for those living in the exposed clusters. The design includes active surveillance and enhanced hospitalization surveillance in both exposed and unexposed clusters.

The study targeted enrolling at least 45,000 children in active surveillance, including 22,500 in the exposed clusters and 22,500 in the unexposed clusters for evaluation of the vaccine safety, effectiveness, and impact.

All data analyses will be computed in a descriptive manner. Data regarding the hospitalization will be uniformly collected whether the child is enrolled in active surveillance or in enhanced hospitalization surveillance.

Eligibility criteria: Inclusion Criteria

All study participants must satisfy ALL the following criteria at study entry:

* Study participants' parent(s)/ LAR(s) who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
* Written informed consent provided from either the parent(s) or LAR of the study participant.
* Study participant living in the HDSS or equivalent surveillance system area.
* For enrolment in the active surveillance - DTP group: children must be aged less than (\<) 18 months, identified at any administration of DTP/HepB/Hib (or at hospitalisation before 3rd dose of DTP/HepB/Hib in case of hospitalisation and vaccinated with at least one dose of DTP/HepB/Hib). (This group will include children from exposed and unexposed clusters.) OR For enrolment in the active surveillance - Catch-up group: children must be aged \<18 months, received at least one dose of DTP/HepB/Hib vaccine, whose age corresponds to the age after the 3rd dose of DTP/HepB/Hib vaccine, (=who either received all DTP/HepB/Hib doses before study start or received at least one dose of DTP/HepB/Hib and are older than the age corresponding to the 3rd DTP/HepB/Hib dose at study start) and identified at 1st RTS,S/AS01E dose administration (This group will include children from exposed clusters only).

OR For enrolment in the enhanced hospitalisation surveillance: children must be aged at least 6 weeks and \<5 years at the time of hospitalisation at any time during the study. (This group will include children from exposed and unexposed clusters.) Parents/LARs of children meeting all eligibility criteria for active surveillance, not having completed the visits for DTP/HepB/Hib, and first identified during hospitalisation, must first be proposed enrolment in active surveillance (if recruitment is not completed).

Children already enrolled in active surveillance will have hospitalization monitored as part of the procedures related to the active surveillance and can therefore not be enrolled in enhanced hospitalization surveillance.

Exclusion Criteria:

• Child in care = A child who has been placed under the control or protection of an agency, organization, institution or entity by the courts, the government, or a government body, acting in accordance with powers conferred on them by law or regulation. The definition of a child in care can include a child cared for by foster parents or living in a care home or institution, provided that the arrangement falls within the definition above. The definition of a child in care does not include a child who is adopted or has an appointed legal guardian.

Primary outcomes:
measure: Incidence rates of adverse events of special interest (AESI)
timeFrame: During the entire study period (From Day 0 up to Month 62)
measure: Incidence rates of aetiology-confirmed meningitis
timeFrame: During the entire study period (From Day 0 up to Month 62)
Secondary outcomes:
measure: Incidence rate of probable meningitis (final classification)
timeFrame: During the entire study period (From Day 0 up to Month 62)
measure: Incidence rates of clinically suspected meningitis (final classification)
timeFrame: During the entire study period (From Day 0 up to Month 62)
measure: Number of meningitis cases identified at site level (first line laboratory)
timeFrame: During the entire study period (From Day 0 up to Month 62)
measure: Incidence rates of cerebral malaria (diagnosed by Rapid Diagnostic Test [RDT] and/or microscopy)
timeFrame: During the entire study period (From Day 0 up to Month 62)
measure: Incidence rates of malaria episodes diagnosed by RDT and/or microscopy
timeFrame: During the entire study period (From Day 0 up to Month 62)
measure: Incidence rates of anaemia cases at hospital entry among hospitalised children
timeFrame: During the entire study period (From Day 0 up to Month 62)
measure: Incidence rates of hospitalisation cases
timeFrame: During the entire study period (From Day 0 up to month 62)
measure: Number of deaths
timeFrame: During the entire study period (From Day 0 up to month 62)
Other outcomes:
Locations:
city: Kintampo
country: Ghana
facility: GSK Investigational Site
city: Navrongo
country: Ghana
facility: GSK Investigational Site
city: Kisumu
country: Kenya
facility: GSK Investigational Site
city: Kisumu
country: Kenya
facility: GSK Investigational Site
city: Kisumu
country: Kenya
facility: GSK Investigational Site
city: Chikwawa
country: Malawi
facility: GSK Investigational Site
city: Mangochi
country: Malawi
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: