A Study Assessing the Safety, Efficacy, and Impact of GlaxoSmithKline Biologicals' RTS, S/AS01E Malaria Vaccine in Young Children Across Sub-Saharan Africa

NCT03855995 | Completed

• 1 other identifier: 115056
• Study Type: observational
• Target: 77,953
• Locations: 3 countries
• Sites: 6

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.

Conditions

Malaria Vaccines; Malaria

Keywords

Malaria; Plasmodium falciparum; Vaccine effectiveness; Sub-Saharan Africa; Active surveillance

Outcome Measures

Primary Outcomes (2)

• Incidence rates of adverse events of special interest (AESI)

  AESI are predefined list of adverse events that have historically been associated with vaccines other than RTS,S/AS01E, or may hypothetically be associated with RTS,S/AS01E due to the fact that this vaccine has components which are new compared to current widely used vaccines. The incidence rate will be calculated by dividing the number of study participants reporting at least one event over the follow-up period by the total person-time. The person-time for an event of interest will be calculated as the time between the reference date (date of first RTS,S/AS01E vaccination for the vaccinated study participants and virtual vaccination corresponding to the week before first visit for the unvaccinated study participants) and the end of the at-risk period or the earliest of the followings: Date of first diagnosis of event of interest, Date of end of study period, Date when child reaches 5 years, Date of last contact or Date of death.

  During the entire study period (From Day 0 up to Month 62)

• Incidence rates of aetiology-confirmed meningitis

  Incidence rate of aetiology confirmed meningitis is analyzed with an at-risk period of 12 months. At the site level, a suspected meningitis case based on clinical symptoms and/or signs is defined as: * A child with sudden onset of fever (\> 38.0°C rectal or 37.5°C axillary) and one or more of the following signs: neck stiffness, altered consciousness with no other alternative diagnosis, or other meningeal sign such as bulging fontanelle in children under one year of age. If a Cerebrospinal fluid (CSF) sample is available and any known aetiologic agent (bacterial or not) has been identified, it is defined as an aetiology confirmed meningitis. The incidence rate will be calculated by dividing the number of study participants reporting at least one event over the follow-up period by the total person-time.

  During the entire study period (From Day 0 up to Month 62)

Secondary Outcomes (8)

• Incidence rate of probable meningitis (final classification)

  During the entire study period (From Day 0 up to Month 62)

• Incidence rates of clinically suspected meningitis (final classification)

  During the entire study period (From Day 0 up to Month 62)

• Number of meningitis cases identified at site level (first line laboratory)

  During the entire study period (From Day 0 up to Month 62)

• Incidence rates of cerebral malaria (diagnosed by Rapid Diagnostic Test [RDT] and/or microscopy)

  During the entire study period (From Day 0 up to Month 62)

• Incidence rates of malaria episodes diagnosed by RDT and/or microscopy

  During the entire study period (From Day 0 up to Month 62)

Study Arms (3)

Active surveillance (DTP sub-Group)

Children enrolled in the active surveillance (AS), \<18 months of age who were identified at any administration of DTP/HepB/Hib (usually given at 6, 10 and 14 weeks of age) or at hospitalisation before administration of 3rd dose of DTP/HepB/Hib and vaccinated with at least one dose of DTP/HepB/Hib; including both RTS,S/AS01E vaccinated and unvaccinated children (from exposed or unexposed clusters), living in the HDSS area are eligible for enrolment in the DTP sub-group of active surveillance.

Procedure: Whole blood sample

Active surveillance (Catch-up sub-Group)

Children enrolled in the active surveillance (AS), \<18 months of age who were identified at 1st RTS,S/AS01E dose administration and 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; including only RTS,S/AS01E vaccinated children from exposed clusters who could not be recruited at the time of DTP/HepB/Hib administration because the study had not yet started, living in the HDSS area are eligible for enrolment in the Catch-up sub-group of active surveillance.

Procedure: Whole blood sample

Enhanced Hospitalisation Surveillance Group

Children at least 6 weeks and \<5 years of age, within the study areas in both exposed and unexposed clusters, not already enrolled in the active surveillance (because parents/ Legally Acceptable Representative (LARs) declined enrolment in active surveillance or because recruitment had been completed) or not eligible for active surveillance at the time of hospitalisation, living in the HDSS area are eligible for enrolment in the Enhanced Hospital Surveillance (EHS) group.

Procedure: Whole blood sample

Interventions

Whole blood sample PROCEDURE

Whole blood samples will be collected from all enrolled children hospitalised and suspected of having an AESI or meningitis.

Active surveillance (Catch-up sub-Group); Active surveillance (DTP sub-Group); Enhanced Hospitalisation Surveillance Group

Eligibility Criteria

• Age: Up to 5 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

The target population for the introduction of the RTS,S/AS01E vaccine are children living in the SSA.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (6)

GSK Investigational Site

Kintampo, Ghana

Location

GSK Investigational Site

Navrongo, Ghana

Location

GSK Investigational Site

Kisumu, 4 0100, Kenya

Location

GSK Investigational Site

Kisumu, 40100, Kenya

Location

GSK Investigational Site

Chikwawa, Malawi

Location

GSK Investigational Site

Mangochi, Malawi

Location

Related Publications (2)

• Ndeketa L, Haine V, Debois M, Asante KP, Agyapong PD, Kaali S, Devadiga R, Harrison SBE, Boahen O, French N, Kayan K, Ogutu B, Adeniji E, Kariuki S, Owusu-Agyei S, Olewe F, Jere TM, Maleta K, Mategula D, Mzanga P, Phiri VK, Ansah PO, Orimbo J, Ansah NA, Orsini M, Ong'echa JM, Oduro AR, Sifuna PM, Azongo DK, Otieno W, Bangre O, Kaburise MB, Ababio LO, Oyieko JN, Sing'oei V, Amoit SK, Nyangulu W, Schuerman L, Awuni D, Ochieng BO, Onyango I, Odera-Ojwang P, Oguk EA, Mendoza YG, Cherop RY, Okoth GO, Cravcenco C, Chipatala R, Roman F, Oneko M, Savic M; RTS,S Epidemiology EPI-MAL-003 Study Group. Effectiveness of the RTS,S/AS01E malaria vaccine in a real-world setting over 1 year of follow-up after the three-dose primary schedule: an interim analysis of a phase 4 study in Ghana, Kenya, and Malawi. Lancet Glob Health. 2026 Jan;14(1):e61-e69. doi: 10.1016/S2214-109X(25)00415-2. Epub 2025 Nov 6.

  PMID: 41207319 DERIVED

• Haine V, Oneko M, Debois M, Ndeketa L, Agyapong PD, Boahen O, Harrison SBE, Adeniji E, Kaali S, Kayan K, Owusu-Agyei S, French N, Kariuki S, Devadiga R, Ogutu B, Ansah NA, Orsini M, Ansah PO, Maleta K, Ong'echa JM, Phiri VK, Mzanga P, Jere TM, Azongo DK, Mategula D, Orimbo J, Oduro AR, Otieno W, Kaburise MB, Ababio LO, Sifuna PM, Amoit SK, Olewe F, Oyieko JN, Achieng Oguk E, Guerra Mendoza Y, Awuni D, Sing'oei V, Onyango I, Schuerman L, Ochieng BO, Okoth GO, Nyangulu W, Cherop RY, Odera-Ojwang P, Cravcenco C, Chipatala R, Roman F, Savic M, Asante KP. Safety of RTS,S/AS01E malaria vaccine up to 1 year after the third dose in Ghana, Kenya, and Malawi (EPI-MAL-003): a phase 4 cohort event monitoring study. Lancet Glob Health. 2025 Jun;13(6):e995-e1005. doi: 10.1016/S2214-109X(25)00096-8. Epub 2025 Apr 24.

  PMID: 40288377 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood, Cerebrospinal fluid

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline (for GlaxoSmithKline; Human Genome Sciences Inc., a GSK Company; Sirtris, a GSK Company; Stiefel, a GSK Company; ViiV Healthcare)

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 25, 2019
• First Posted: February 27, 2019
• Study Start: March 21, 2019
• Primary Completion: August 7, 2025
• Study Completion: August 7, 2025
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

GH (2); MA (2); KE (2)