Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or Without Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age

NCT03276962 | Completed Phase 2 Results

• 2 other identifiers: 2048892016-000290-20
• Study Type: interventional
• Target: 1,500
• Locations: 2 countries
• Sites: 2

Brief Summary

The study intends to establish proof of concept for a fractional dose schedule under conditions of natural exposure in children 5-17 months old at first vaccination. The study also aims to establish the role of third dose spacing in a fractional dose schedule, describe the effect of an earlier full fourth dose at Month 14 and describe the effect of multiple fractional or full yearly doses.

Conditions

Malaria

Keywords

falciparum, efficacy; RTS,S/AS01; malaria vaccine; safety; Malaria; immunogenicity; infants

Outcome Measures

Primary Outcomes (1)

• Incidence of Clinical Malaria Meeting the Primary Case Definition

  The primary case definition is: Plasmodium (P.) falciparum asexual parasitemia greater than (\>)5000 parasites/microliters (μl) and presence of fever (axillary temperature greater than or equal to \[≥\]37.5°C) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility. The incidence is expressed as a person year rate for each group (n/T), representing the number of events (n) reported over the risk period, which was counted in days and expressed as person years at risk (T). The objective of this endpoint was to demonstrate the superiority of a Fx012-14-mFxD Group compared to a standard schedule of RTS,S/AS01E with three full doses (R012-20+R012-14 Group) in terms of vaccine efficacy. This analysis was reported for the R012-20+R012-14 Group (Pooled group) because the interventional strategy (1st dose at Month 0, 2nd dose at Month 1, 3rd dose at Month 2) was the same for both the R012-20 group and the R012-14 group until Month 14.

  From Month 2.5 to Month 14

Secondary Outcomes (21)

• Incidence of Clinical Malaria Meeting the Primary and Secondary Case Definitions of the Fx012-14-mFxD Group Versus the R012-20 Group

  From Month 0 to Month 50

• Incidence of Clinical Malaria Meeting the Primary and Secondary Case Definitions of the Fx012-14-mFxD Group Versus the R012-14-mD Group

  From Month 0 to Month 50

• The Prevalence of P. Falciparum Infections Defined by Positive Blood Slide at Each Cross-sectional Survey

  Monthly from Month 0 to Month 20 and every 3 months thereafter until Study End (Month 50)

• Incidence of P. Falciparum Infections Defined by Positive Blood Slide

  Month 0 to Month 14

• Number of Seropositive Participants for Anti-circumsporozoite (Anti-CS) Antibodies

  Before Dose 1, one month post-Dose 2, before and one month post-Dose 3, before and one month after Dose 4, before and one month after each yearly dose and at Study End (Month 50)

Study Arms (5)

R012-20 Group

EXPERIMENTAL

Participants will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and at Month 20.

Biological: RTS,S/AS01E (Full dose)

R012-14-mD Group

EXPERIMENTAL

Participants will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and yearly full doses at Month 14, Month 26 and Month 38.

Biological: RTS,S/AS01E (Full dose)

Fx012-14-mFxD Group

EXPERIMENTAL

Participants will receive a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 2 and yearly fractional doses at Month 14, Month 26 and Month 38.

Biological: RTS,S/AS01E (Full dose); Biological: RTS,S/AS01E (1/5th dose)

Fx017-mFxD Group

EXPERIMENTAL

Participants will receive a full dose of RTS,S/AS01E at Month 0 and Month 1, and RTS,S/AS01E 1/5th dose at Month 7 and yearly fractional doses at Month 20 and Month 32.

Biological: RTS,S/AS01E (Full dose); Biological: RTS,S/AS01E (1/5th dose)

Control Group

EXPERIMENTAL

Participants will receive rabies vaccine at Month 0, Month 1 and Month 2.

Biological: Rabies vaccine

Interventions

RTS,S/AS01E (Full dose) BIOLOGICAL

Participants will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).

Fx012-14-mFxD Group; Fx017-mFxD Group; R012-14-mD Group; R012-20 Group

RTS,S/AS01E (1/5th dose) BIOLOGICAL

Participants will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).

Fx012-14-mFxD Group; Fx017-mFxD Group

Rabies vaccine BIOLOGICAL

Participants will receive intramuscular injection of rabies vaccine (0.1 ml).

Control Group

Eligibility Criteria

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

You may qualify if:

• Participants' parent(s)/LAR(s) who, in the opinion of the investigator, can and will comply 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) are illiterate, the consent form will be 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 make 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 will mean 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 will 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 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 (4)

• Westercamp N, Osei-Tutu L, Schuerman L, Kariuki SK, Bollaerts A, Lee CK, Samuels AM, Ockenhouse C, Bii DK, Adjei S, Oneko M, Lievens M, Attobrah Sarfo MA, Atieno C, Bakari A, Sang T, Kotoh-Mortty MF, Otieno K, Roman F, Buabeng PBY, Ntiamoah Y, Ansong D, Agbenyega T, Ofori-Anyinam O. Could Less Be More? Accounting for Fractional-Dose Regimens and Different Number of Vaccine Doses When Measuring the Impact of the RTS,S/AS01E Malaria Vaccine. J Infect Dis. 2024 Aug 16;230(2):e486-e495. doi: 10.1093/infdis/jiae075.

  PMID: 38438123 BACKGROUND

• Osei-Tutu L, Kariuki SK, Lee CK, Fabre R, Bii DK, Adjei S, Oneko M, Attobrah Sarfo MA, Ockenhouse CF, Schuerman L, Buabeng PBY, Bakari A, Atieno C, Kotoh-Mortty MF, Otieno K, Ntiamoah Y, Sang T, Bollaerts A, Westercamp N, Ansong D, Agbenyega T, Samuels AM, Ofori-Anyinam O; RTS,S study group. Sustained efficacy of the RTS,S/AS01E malaria vaccine over 50 months of follow-up when used in full-dose or fractional-dose regimens in young children in Ghana and Kenya: final results from an open-label, phase 2b, randomised controlled trial. Lancet Glob Health. 2025 Oct;13(10):e1723-e1736. doi: 10.1016/S2214-109X(25)00272-4.

  PMID: 40975080 DERIVED

• Juraska M, Early AM, Li L, Schaffner SF, Lievens M, Khorgade A, Simpkins B, Hejazi NS, Benkeser DA, 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. Baseline malaria infection status and RTS,S/AS01E malaria vaccine efficacy. medRxiv [Preprint]. 2023 Nov 23:2023.11.22.23298907. doi: 10.1101/2023.11.22.23298907.

  PMID: 38045387 DERIVED

• Samuels AM, Ansong D, Kariuki SK, Adjei S, Bollaerts A, Ockenhouse C, Westercamp N, Lee CK, Schuerman L, Bii DK, Osei-Tutu L, Oneko M, Lievens M, Attobrah Sarfo MA, Atieno C, Morelle D, Bakari A, Sang T, Jongert E, Kotoh-Mortty MF, Otieno K, Roman F, Buabeng PBY, Ntiamoah Y, Ofori-Anyinam O, Agbenyega T; RTS,S study group. Efficacy of RTS,S/AS01E malaria vaccine administered according to different full, fractional, and delayed third or early fourth dose regimens in children aged 5-17 months in Ghana and Kenya: an open-label, phase 2b, randomised controlled trial. Lancet Infect Dis. 2022 Sep;22(9):1329-1342. doi: 10.1016/S1473-3099(22)00273-0. Epub 2022 Jun 23.

  PMID: 35753316 DERIVED

MeSH Terms

Conditions

Malaria

Interventions

RTS malaria vaccine; Rabies Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

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: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2017
• First Posted: September 8, 2017
• Study Start: September 28, 2017
• Primary Completion: November 4, 2019
• Study Completion: November 14, 2022
• Last Updated: May 21, 2024
• Results First Posted: May 21, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the 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 can be granted, when justified, for up to another 12 months.

Locations

GH (1); KE (1)