A Study to Assess the Safety and Immunogenicity of a Vaccine Against Malaria in Healthy Children Aged 5-60 Months

A Phase 2a, Open Label, Randomized, Interventional Study to Assess the Safety and Immunogenicity of Alternative Vaccination Regimens and Reduced Antigen Doses of RTS,S/AS01E Vaccine in Healthy Children Aged 5-60 Months in a Malaria-endemic Area

The purpose of this study is to evaluate the safety and immunogenicity of reduced antigen doses and alternative vaccination regimes for RTS,S/AS01E in healthy children aged 5-60 months in a malaria-endemic area.

Study Overview

• Status: Recruiting
• Conditions: Malaria
• Intervention / Treatment: Biological: RTS,S/AS01E vaccine

• Study Type: Interventional
• Enrollment (Estimated): 238
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
• Study Contact Backup: Name: EU GSK Clinical Trials Call Center; Phone Number: +44 (0) 20 89904466; Email: GSKClinicalSupportHD@gsk.com

Study Locations

• Rwanda
  • Kigali, Rwanda
    • Recruiting
    • GSK Investigational Site
    • Contact: US GSK Clinical Trials Call Center; Phone Number: 877-379-3718; Email: GSKClinicalSupportHD@gsk.com
    • Contact: EU GSK Clinical Trials Call Centre; Phone Number: +44 (0) 20 8990 4466; Email: GSKClinicalSupportHD@gsk.com
    • Principal Investigator: Mossi Nzeyimana

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male or female participants aged 5 to 60 months at the time of the first vaccination, who have previously completed the World Health Organization (WHO) Expanded Programme on Immunization (EPI) vaccinations or for younger infants have received all required vaccinations at point of recruitment according to the schedule for the country where the study is conducted.
2. Participants' parent(s)/Legally Acceptable Representative(s) (LAR), in the opinion of the investigator, can and will comply with the requirements of the protocol (eg, completion of the diaries, returning for follow-up visits).
3. Written or witnessed/thumb-printed informed consent obtained from the participant's parent(s)/LAR prior to performance of any study-specific procedure.
4. Healthy, as established by medical history and clinical examination.
5. Negative for human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV).
6. With hemoglobin levels >8 g/dL.
7. Born after a gestation period of ≥37 weeks.

Exclusion Criteria:

1. Progressive, unstable, or uncontrolled clinical conditions.
2. History (known or suspected) of any reaction or hypersensitivity likely to be exacerbated by any component of the study vaccine.
3. Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
4. Clinical conditions representing a contraindication to IM vaccination or blood draws.
5. Any behavioral or cognitive impairment or psychiatric disease that, in the opinion of the investigator, may interfere with the participant's ability to participate in the study.
6. Recurrent history of or uncontrolled neurological disorders or seizures.
7. Undernutrition, defined as WHO Z-score less than -2 standard deviation.
8. Any other clinical condition that, in the opinion of the investigator, might pose additional risk to the participant as a result of participation in the study, for example, any major congenital defects.
9. Acute or chronic clinically significant pulmonary, cardiovascular, hepatic, or renal functional abnormality, as determined by physical examination and medical history.
10. Administration of long-acting immune-modifying drugs (eg, infliximab) during the study period starting 3 months before the first dose of study vaccine or planned administration during the study period.
11. Prior receipt of a malaria vaccine (registered or experimental).

12. Use of any investigational or non-registered product (drug, vaccine, or medical device)* other than the study vaccine during the period starting 30 days before the first dose of study vaccine (Day -30 to Day 1), or planned use during the study period.

    *Use of herbs and traditional treatments is not considered an exclusion criterion.

13. Planned administration of a vaccine not foreseen by the study protocol or the country EPI in the period starting 14 days before each dose and ending 28 days after the last dose of study vaccine administration*, with the exception of flu vaccines and vaccines administered as part of a public health vaccination campaign*.

    *If emergency mass vaccination for an unforeseen public health threat (eg, a pandemic) is organized by public health authorities outside the routine immunization program, the time period described above can be reduced, provided the vaccination is used according to the local governmental recommendations and the Sponsor is notified.

    Under such circumstances, a participant may be considered eligible for study enrollment and/or study vaccine administration after the appropriate window for delay has passed, if the participant is confirmed to be eligible after inclusion/exclusion criteria have been re checked.

14. Administration of immunoglobulins and/or any blood products or plasma derivatives, or bone marrow transplantation, during the period starting 3 months before the first dose of study vaccine or planned administration during the study period.
15. Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 3 months prior to the first vaccine dose or planned administration during the study period. For corticosteroids, this means prednisone ≥0.5 mg/kg/day or 20 mg/day, whichever is the maximum dose for pediatric participants. Inhaled and topical steroids are allowed.
16. Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or will be exposed to an investigational or a non-investigational intervention (drug or invasive medical device).
17. Any study personnel's immediate dependents, family, or household members.
18. Child in care.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Groups 1 to 3; Participants receive 3 doses of RTS,S/AS01E vaccine on Day 1, Month 1, and Month 2.	Biological: RTS,S/AS01E vaccine; RTS,S/AS01E vaccine will be administered intramuscularly.; Other Names: Mosquirix
Experimental: Groups 4 and 5; Participants receive 3 doses of RTS,S/AS01E vaccine on Day 1, Month 1, and Month 7.	Biological: RTS,S/AS01E vaccine; RTS,S/AS01E vaccine will be administered intramuscularly.; Other Names: Mosquirix
Experimental: Groups 6 and 7; Participants receive 3 doses of RTS,S/AS01E vaccine on Day 1, Month 2, and Month 7.	Biological: RTS,S/AS01E vaccine; RTS,S/AS01E vaccine will be administered intramuscularly.; Other Names: Mosquirix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Geometric Mean Concentrations (GMCs) of anti-NANP immunoglobulin G (IgG) antibodies	12 months post-Dose 3 (Month 14 for Groups 1 to 3 and Month 19 for Groups 4 and 5 and Groups 6 and 7)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the curve (AUC) of anti-NANP IgG antibodies		At Month 7 and 19
GMC of anti-NANP IgG antibodies		At Month 0, 1, 2, 3, 7, 8, 14, and 19
Number of participants with a greater than or equal to (>=) 2-fold and a (>=) 4-fold increase from pre-Dose 1 in IgG antibody concentration		At Month 0, 1, 2, 3, 7, 8, 14, and 19
Number of participants with solicited administration site events	Solicited administration site events include pain, redness, and swelling at administration site.	Up to 7 days after each vaccine administration (vaccine administered on Day 1, Month 1, Month 2, and Month 7)
Number of participants with solicited systemic events	Solicited systemic events include fever, irritability/fussiness, loss of appetite, sleepiness/drowsiness, and vomiting.	Up to 7 days after each vaccine administration (vaccine administered on Day 1, Month 1, Month 2, and Month 7)
Number of participants with unsolicited adverse events (AEs)	An unsolicited AE is an AE that is either not included in the list of solicited events or could be included in the list of solicited events but with an onset outside the specified period of follow-up for solicited events.	Within 30 days after each study vaccine administration (vaccine administered on Day 1, Month 1, Month 2, and Month 7)
Number of participants with serious adverse events (SAEs)	An SAE is defined as any untoward medical occurrence that results in death, is life threatening, requires hospitalization or prolongs existing hospitalization, results in disability/incapacity, or other medically significant events.	From first study vaccine administration (Day 1) to the end of the study (Month 19)
Number of participants with SAEs		From first study vaccine administration (Day 1) to 12 months after the last study vaccine administration (Month 14 for Groups 1 to 3 and Month 19 for Groups 4 and 5 and Groups 6 and 7)
Number of participants with adverse events of special interest (AESIs)	AESIs include febrile convulsion that are defined as seizures that occur in febrile children between the ages of 6 and 60 months who do not have an intracranial infection, metabolic disturbance, or history of afebrile seizures.	Up to 7 days after each vaccine administration (vaccine administered on Day 1, Month 1, Month 2, and Month 7)
Number of participants with AEs/SAEs leading to withdrawal from the study and/or discontinuation of study vaccine		From first study vaccine administration (Day 1) to the end of the study (Month 19)
GMC of anti-hepatitis B surface antigens (HBs) antibody concentrations (IgG)		At Month 0, 1, 2, 3, 7, 8, 14, and 19
Number of participants achieving anti-HBs IgG levels above 6.2 International Units per liter (IU/L) and 10.0 IU/L		At Month 0, 1, 2, 3, 7, 8, 14, and 19
Geometric mean fold increase over pre-Dose 1 for anti-HBs IgG		At Month 0, 1, 2, 3, 7, 8, 14, and 19

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Investigators: Principal Investigator: Julien M Nyombayire, MD, MSc, Center for Family Health Research; Principal Investigator: Mossi Nzeyimana, MD, Rinda Ubuzima Gatenga Medicalized Health Center University of Rwanda

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2025
• Primary Completion (Estimated): April 23, 2027
• Study Completion (Estimated): April 23, 2027

Study Registration Dates

• First Submitted: June 16, 2025
• First Submitted That Met QC Criteria: June 16, 2025
• First Posted (Actual): June 25, 2025

Study Record Updates

• Last Update Posted (Estimated): September 29, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Safety; Malaria; Plasmodium falciparum; Immunogenicity; Healthy children; Parasitic disease
• Additional Relevant MeSH Terms: Vector Borne Diseases; Mosquito-Borne Diseases; Infections; Protozoan Infections; Malaria; Malaria, Falciparum; Parasitic Diseases; RTS,S-AS01E vaccine; RTS malaria vaccine
• Other Study ID Numbers: 223247; 2024-000563-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No