A Surveillance Study of Diseases Specified as Adverse Events of Special Interest, of Other Adverse Events Leading to Hospitalisation or Death, and of Meningitis in Children in Africa Prior to Implementation of the RTS,S/AS01E Candidate Vaccine

NCT02374450 | Completed Results

• 1 other identifier: 115055
• Study Type: observational
• Target: 36,366
• Locations: 3 countries
• Sites: 5

Brief Summary

The purpose of this pre-licensure cohort study was to estimate the incidence of adverse events of special interest (AESI), other adverse events (AE) leading to hospitalisation or death, meningitis and malaria in sub-Saharan African children under 5 years of age. The outcomes of this study provide the baseline data for the post-licensure EPI-MALARIA-003 (115056) study that evaluated the safety, effectiveness and impact of the RTS,S/AS01E vaccine. An interim analysis was performed on a sub-group of study participants enrolled in active surveillance from sites where the vaccine was implemented, having 6 months of follow-up after the administration of dose 3 of DTP/HepB/Hib vaccine (6-12 weeks group), or 6 months after Visit 3 (mimicking the RTS,S/AS01E primary vaccination schedule) for the 5-17 months group; corresponding to Visit 5. The interim analysis concerned primary safety endpoints and the main secondary endpoints.

Conditions

Malaria

Keywords

Malaria; Surveillance study; Adverse Events of Specific Interest (AESI); Children; Infants; Adverse events (AE) leading to hospitalisation or death; Meningitis; Epidemiology; Africa

Outcome Measures

Primary Outcomes (3)

• Number of Participants With at Least One Adverse Events of Specific Interest (AESI) From Month 0 to Month 79

  AESI were a predefined list of adverse events historically associated with vaccines other than RTS,S/AS01E or potentially associated with RTS,S/AS01E. This was because the RTS,S/AS01E vaccine contained new components not present in widely used vaccines at the time.

  During the entire study period (From Month 0 up to Month 79)

• Number of Participants With at Least One Adverse Event (AE) Leading to Hospitalization or Death From Month 0 to Month 79

  AEs assessed in children \<5 years old, included in active or enhanced hospitalization surveillance, prior to implementation of RTS,S/AS01E.

  During the entire study period (From Month 0 up to Month 79)

• Number of Participants With at Least One Aetiology Confirmed Meningitis From Month 0 to Month 79

  Aetiology-confirmed meningitis was defined by the presence of symptoms and/or signs of meningitis and the identification of any known aetiologic agent (bacterial or not) in the Cerebrospinal Fluid (CSF).

  During the entire study period (From Month 0 up to Month 79)

Secondary Outcomes (10)

• Number of Participants With at Least One Confirmed Meningitis Case From Month 0 to Month 79 (Final Classification)

  During the entire study period (From Month 0 up to Month 79)

• Number of Participants With at Least One Confirmed Meningitis Case Identified at Site Level From Month 0 to Month 79 (First Line Laboratory)

  During the entire study period (From Month 0 up to Month 79)

• Number of Participants With Risk Factors for AESI, Meningitis and Malaria Among Hospitalized Participants

  During the entire study period (From Month 0 up to Month 79)

• Incidence Rates of Death After the Virtual Secondary Schedule (Secondary Dose of DTP/HepB/Hib Administered at Day 31) for the Active Surveillance 6-12 Weeks and Active Surveillance 5-17 Weeks Groups

  Day 31 to approximately Month 13 (Within an at-risk period of 12 months after virtual secondary schedule)

• Number of Participants Hospitalized With Causes (Including Those Attributed to an AESI, Other AE, Meningitis, or Malaria) From Month 0 to Month 79

  During the entire study period (From Month 0 up to Month 79)

Study Arms (3)

Active surveillance 6-12 weeks

Children were identified at the first administration of Diphtheria-tetanus-whole- cell pertussis-hepatitis B- Haemophilus influenza type b pentavalent (DTP/HepB/Hib) vaccine (usually given at 6weeks of age) and home visits were conducted according to DTP/HepB/Hib vaccine schedule.

Procedure: Blood collection

Active surveillance 5-17 months

Children who were either identified at the first administration of the DTP/HepB/Hib vaccine (usually given at 6 weeks of age), with home visits scheduled from 5 months of age onwards or identified at first encounter with the study staff, with home visits started within one week of the first encounter with study staff.

Procedure: Blood collection

Enhanced hospitalization surveillance

All children under the age of 5 years within the study areas, who were not already enrolled in active surveillance were eligible for enrolment in enhanced hospitalization surveillance during any hospitalizations throughout the entire study period.

Procedure: Blood collection

Interventions

Blood collection PROCEDURE

For all hospitalised children suspected of having an AESI or meningitis, a sample of 5 ml of whole blood was collected and the serum was stored.

Active surveillance 5-17 months; Active surveillance 6-12 weeks; Enhanced hospitalization surveillance

Eligibility Criteria

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

Study Population

The study population was defined as those children living in the study areas who are \< 5 years old.

You may qualify if:

• All subjects must satisfy ALL the following criteria at study entry:
• Subjects' parent(s)/Legally Acceptable Representative(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 subject.
• Subject living in the Health and Demographic Surveillance System (HDSS) area.
• For enrolment in active surveillance: children must be \<18 months of age. OR
• For enrolment in enhanced hospitalisation surveillance: children must be \<5 years of age and hospitalised at any time during the study.

You may not qualify if:

• Child in care.

Sponsors & Collaborators

• GlaxoSmithKline: lead
• PATH: collaborator
• Agence de Médecine Préventive, France: collaborator
• Réseau en Afrique Francophone pour la Télémédecine,: collaborator
• Iqvia Pty Ltd: collaborator
• Parexel: collaborator
• Clinical Laboratory Services: collaborator

Study Sites (5)

GSK Investigational Site

Ouagadougou, Burkina Faso

Location

GSK Investigational Site

PO BOX 02 Nouna, Burkina Faso

Location

GSK Investigational Site

Kintampo, Ghana

Location

GSK Investigational Site

Navrongo, Ghana

Location

GSK Investigational Site

Kisumu, 40102, Kenya

Location

Related Publications (1)

• RTS,S Epidemiology EPI-MAL-002 Study Group. Baseline incidence of meningitis, malaria, mortality and other health outcomes in infants and young sub-Saharan African children prior to the introduction of the RTS,S/AS01E malaria vaccine. Malar J. 2021 Apr 26;20(1):197. doi: 10.1186/s12936-021-03670-w.

  PMID: 33902599 DERIVED

MeSH Terms

Conditions

Malaria; Death; Meningitis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroinflammatory Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Limitations and Caveats

The study limitations included influences on case detection and ascertainment due to factors such as medical supply shortages, limited investigational capacities, and reduced availability of medical personnel during strikes and elections. Despite efforts to improve case detection, a "study effect" could still be anticipated. Modifications in malaria case definition and occasional missed home visits for a small number of participants might have had a minimal impact on interpretation of study.

Results Point of Contact

• Title: GSK Response Center
• Organization: GlaxoSmithKline

GSKClinicalSupportHD@gsk.com

866-435-7343

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: January 12, 2015
• First Posted: February 27, 2015
• Study Start: October 5, 2015
• Primary Completion: August 2, 2022
• Study Completion: August 2, 2022
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

BU (2); GH (2); KE (1)