Study to Assess the Vaccine Efficacy Against Malaria Infection, in Children Immunized With the Primary and Yearly Booster of the RTS,S/AS01E Vaccine, as Part of Their Participation in the Malaria-094 (204889/NCT03276962) Study.

NCT ID: NCT03281291

Last Updated: 2025-01-23

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 1500 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2018-11-19
• Study Completion Date: 2023-10-23

Brief Summary

The aim of this study was to evaluate the effectiveness of the RTS,S/AS01E malaria vaccine against both clinical and asymptomatic malaria infections by detecting Plasmodium falciparum (P. falciparum) parasites in blood samples collected from children who received the primary and yearly booster doses of the RTS,S/AS01E vaccine, as part of their participation in the Malaria-094 parent clinical study. The genomic analysis was conducted on parasites found in blood spot samples from children aged 5-17 months, who were vaccinated according to different dosage and schedule regimens as part of the Malaria-094 parent clinical study.

Detailed Description

This genotyping study of malaria parasites, collected from serial blood samples following RTS,S/AS01E immunization, assessed vaccine efficacy using molecular genetic data. The study aimed to identify the first infections post-vaccination and distinguish new infections from existing ones through an amplicon sequencing-based strategy. This involved deep sequencing of small, highly variable regions of the parasite genome, enabling both: 1. Highly sensitive detection of parasitemia (similar to conventional polymerase chain reaction [PCR]-based detection), and 2. Identification of genetically distinct parasite populations within or between affected individuals.

Conditions

Malaria

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

R012-20 Group

Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and Month 20 of study NCT03276962.

No interventions assigned to this group

R012-14-mD Group

Participants received a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.

No interventions assigned to this group

Fx012-14-mFxD Group

Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26 and Month 38 of study NCT03276962.

No interventions assigned to this group

Fx017-mFxD Group

Participants received a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7, Month 20 and Month 32 of study NCT03276962.

No interventions assigned to this group

Control Group

Participants received rabies vaccine at Month 0, Month 1 and Month 2 of study NCT03276962.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Participants' parent(s)/LAR(s) who, in the opinion of the investigator, complied with the requirements of the protocol (e.g. return for follow-up visits).
• Signed or thumb-printed and witnessed informed consent obtained from the parent(s)/LAR(s) of the participant prior to performance of any study specific procedure. Where parent(s)/LAR(s) were illiterate, the consent form was countersigned by an independent witness.
• A male or female between, and including, five and 17 months of age at the time of the first vaccination.
• Healthy participants as established by medical history and clinical examination before entering into the study.
• Previously received three documented doses of diphtheria, tetanus, pertussis, hepatitis B vaccine (DTPHepB), and at least three doses of oral polio vaccine.

Exclusion Criteria

• Child in care.
• Use of a drug or vaccine that is not approved for that indication (by one of the following regulatory authorities: Food and Drug Administration [FDA; USA] or European Union member state or WHO [with respect to prequalification]) other than the study vaccines during the period starting 30 days before the first dose of study vaccines (Day -29 to Day 0), or planned use during the study period.
• Any medical condition that in the judgment of the investigator would have made the intramuscular injection unsafe.

Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine dose. For corticosteroids, this meant prednisone (0.5 mg/kg/day (for pediatric participants) or equivalent. Inhaled and topical steroids are allowed.

• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before each dose and ending seven days after each dose of vaccine administration.
• Concurrently participating in another clinical study, at any time during the study period, in which the participant has been or was to be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required).
• Family history of congenital or hereditary immunodeficiency.
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccines.
• History of anaphylaxis post-vaccination.
• History of any, or documented, serious adverse reaction to rabies vaccination.
• Contraindication to rabies vaccination (Rabipur is contraindicated in participants with a history of a severe hypersensitivity to any of the ingredients in the vaccine. Note that the vaccine contains polygeline and residues of chicken proteins, and may contain traces of neomycin, chlortetracycline and amphotericin B).
• Major congenital defects.
• Serious chronic illness.
• Children with a past history of a neurological disorder or atypical febrile seizure (a febrile seizure is atypical if it meets one of the following criteria: not associated with fever; lasts > 5 minutes; focal (not generalized); followed by transient or persistent neurological abnormality; occurs in a child < 6 months of age).
• Acute disease and/or fever at the time of enrolment.
• Fever is defined as temperature ≥ 37.5°C/99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C/100.4°F for rectal route.
• Participants with a minor illness (such as mild diarrhea, mild upper respiratory infection) without fever may have been enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/or any blood products during the period starting three months before the first dose of study vaccine or planned administration during the study period.
• Moderate or severe malnutrition at screening defined as weight for age or weight for height Z-score < -2.
• Hemoglobin concentration < 8 g/dl at screening.
• Same sex twins (to avoid misidentification).
• Maternal death.
• Prior receipt of an investigational malaria vaccine.

• Minimum Eligible Age: 5 Months
• Maximum Eligible Age: 17 Months
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Kumasi, , Ghana

GSK Investigational Site

Kisumu, , Kenya

Countries

Ghana; Kenya

References

Juraska M, Early AM, Li L, Schaffner SF, Lievens M, Khorgade A, Simpkins B, Hejazi NS, Benkeser D, Wang Q, Mercer LD, Adjei S, Agbenyega T, Anderson S, Ansong D, Bii DK, Buabeng PBY, English S, Fitzgerald N, Grimsby J, Kariuki SK, Otieno K, Roman F, Samuels AM, Westercamp N, Ockenhouse CF, Ofori-Anyinam O, Lee CK, MacInnis BL, Wirth DF, Gilbert PB, Neafsey DE. Genotypic analysis of RTS,S/AS01E malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial. Lancet Infect Dis. 2024 Sep;24(9):1025-1036. doi: 10.1016/S1473-3099(24)00179-8. Epub 2024 May 6.

Reference Type: BACKGROUND

PMID: 38723650 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

206213

Identifier Type: -

Identifier Source: org_study_id