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.

NCT03281291 | Completed Results

• 1 other identifier: 206213
• Study Type: observational
• Target: 1,500
• Locations: 2 countries
• Sites: 2

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.

Conditions

Malaria

Keywords

malaria vaccine; infants; malaria; RTS,S/AS01; falciparum; genomics; efficacy

Outcome Measures

Primary Outcomes (8)

• Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 20 Study Visit

  The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  Up to 20 months post Dose 1

• Time From First Vaccination to the Detection of the First New Malaria Infection From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3

  The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  From Month 2.5 to Month 14 for the R012-20 + R012-14-mD Pooled Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 19 for the Fx017-mFxD Group

• Time From First Vaccination to the Detection of the First New Malaria Infection Through to the Month 32 Study Visit

  The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  Up to 32 months post Dose 1

• Time From First Vaccination to the Detection of the First New Malaria Infection From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3

  The number of days from the time origin in each analysis to the visit date associated with the first molecular detection of a new malaria infection. A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  From Month 2.5 to Month 26 for the R012-20 Group, the R012-14-mD Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 31 for the Fx017-mFxD Group

• Number of Molecularly Confirmed New Malaria Infections Through to the Month 20 Study Visit

  A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  Up to 20 months post Dose 1

• Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 12 Months Post-Dose 3

  A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  From Month 2.5 to Month 14 for the R012-20 + R012-14-mD Pooled Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 19 for the Fx017-mFxD Group

• Number of Molecularly Confirmed New Malaria Infections Through to the Month 32 Study Visit

  A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  Up to 32 months post Dose 1

• Number of Molecularly Confirmed New Malaria Infections From 14 Days Post-Dose 3 Through to 24 Months Post-Dose 3

  A new molecularly confirmed malaria infection was defined by a detected new infection from genomic analysis of dried blood spot samples originating either from active monthly screening for infection or from unscheduled visits intended for the assessment of clinical malaria.

  From Month 2.5 to Month 26 for the R012-20 Group, the R012-14-mD Group, the Fx012-14-mFxD Group and the Control Group, and from Month 7.5 to Month 31 for the Fx017-mFxD Group

Study Arms (5)

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.

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.

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.

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.

Control Group

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

Eligibility Criteria

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

Study Population

Community sample

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (2)

GSK Investigational Site

Kumasi, Ghana

Location

GSK Investigational Site

Kisumu, 40100, Kenya

Location

Related Publications (1)

• 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.

  PMID: 38723650 BACKGROUND

MeSH Terms

Conditions

Malaria

Condition Hierarchy (Ancestors)

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

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: September 11, 2017
• First Posted: September 13, 2017
• Study Start: November 19, 2018
• Primary Completion: April 22, 2022
• Study Completion: October 23, 2023
• Last Updated: January 23, 2025
• Results First Posted: January 23, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GH (1); KE (1)