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.

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.