MalariaPhase 2NCT03276962
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
A Phase 2 study testing RTS,S/AS01E (Full dose), RTS,S/AS01E (1/5th dose) and Rabies vaccine in people with Malaria, run by GlaxoSmithKline at 2 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 5 to 17 monthsHealthy volunteers can take part
- Conditions the study is for
- Malaria
- What is being tested?
- RTS,S/AS01E (Full dose), RTS,S/AS01E (1/5th dose) and Rabies vaccine
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1,500 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 28 Sep 2017to 14 Nov 2022
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 to 17 months
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 23Show fewer
- 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).
- 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, be 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.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or With-out Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age
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.
Read the detailed description
The current study intends to establish proof of concept (POC) for a fractional dose schedule under conditions of natural exposure. The study will be conducted in children 5-17 months old at first vaccination living in areas of mid to high malaria transmission, in line with the age group recommended by the World Health Organization (WHO) for the implementation of the RTS,S/AS01E vaccine. Results from this study will be critical in informing future possibilities for the development of vaccine-based strategies which, in combination with other interventions, may contribute to the malaria elimination agenda.
- Conditions
- Malaria
- Being tested
- RTS,S/AS01E (Full dose), RTS,S/AS01E (1/5th dose), Rabies vaccine
- Keywords
- falciparum, efficacy, RTS,S/AS01, malaria vaccine, safety, Malaria, immunogenicity, infants
- Medical subject headings
- Malaria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RTS,S/AS01E (Full dose)Biological
Participants will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).
RTS,S/AS01E (1/5th dose)Biological
Participants will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).
Rabies vaccineBiological
Participants will receive intramuscular injection of rabies vaccine (0.1 ml).
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: 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. Receives: Biological: Rabies vaccine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
The primary case definition is P. falciparum asexual parasitemia > 5000 μl and presence of fever (axillary temperature ≥ 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 secondary case definition is P. falciparum asexual parasitemia > 0 and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation or history of fever within 24 hours of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility. The incidence of clinical malaria for primary and secondary case definition is expressed as n/T, representing the n reported over the risk period, which was counted in days and expressed as T.
Measured: 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
The primary case definition is P. falciparum asexual parasitemia > 5000 μl and presence of fever (axillary temperature ≥ 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 secondary case definition is P. falciparum asexual parasitemia > 0 and presence of fever (axillary temperature ≥ 37.5°C) at the time of presentation or history of fever within 24 hours of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility. The incidence of clinical malaria for primary and secondary case definition is expressed as n/T, representing the n reported over the risk period, which was counted in days and expressed as T.
Measured: From Month 0 to Month 50
The Prevalence of P. Falciparum Infections Defined by Positive Blood Slide at Each Cross-sectional Survey
Prevalence of P. falciparum infections of each RTS,S/AS01E schedule at cross-sectional visits. As specified in the statistical analysis plan, a graphical presentation of the prevalence over time was analyzed for this outcome measure and only the percentage values were reported to depict the prevalence of P. falciparum infections.
Measured: 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
The incidence of P. falciparum infections is expressed as n/T, representing the n reported over the risk period, which was counted in days and expressed as T.
Assessment of vaccine efficacy (VE) against first or only episodes of incident P. falciparum infections defined by positive blood slide over the entire study period (Month 0 to Month 50) was not done after the Month 21 Interim analysis since it was assumed that almost all children would have already contracted malaria at least once.
Measured: Month 0 to Month 14
Number of Seropositive Participants for Anti-circumsporozoite (Anti-CS) Antibodies
A seropositive participant is defined as a participant with antibody concentrations ≥ 0.5 ELISA units per milliliter (EU/mL).
Measured: 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)
Number of Seropositive Participants for Anti-hepatitis B (Anti-HB) Antibodies
A seropositive participant is defined as a participant with antibody concentrations ≥ 10 milli-international units per milliliter (mIU/mL).
Measured: 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)
Antibody Concentrations for Anti-CS
The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as EU/mL.
Measured: 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)
Antibody Concentrations for Anti-HB
The antibody concentrations were calculated as GMCs and expressed as mlU/mL.
Measured: 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)
Number of Participants With Any, Fatal and Related Serious Adverse Events (SAEs)
SAEs assessed included any untoward medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Related SAEs= Any SAE related to investigational vaccine or related to study participation or to a GSK concomitant medication/vaccine as assessed by the investigator. Fatal SAEs= Any SAEs leading to death.
Measured: From Day 0 to Month 50
Number of Participants With Any Adverse Events (AEs) and SAEs Leading to Withdrawal From Further Vaccination
An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Measured: From Day 0 to Month 50
Number of Participants With Cerebral Malaria and Severe Malaria
Cerebral malaria is defined as Severe P. falciparum malaria with coma (Blantyre coma score less than [<] 3); and if malaria with seizure: coma persisting for > 30 min after the seizure. Other treatable causes of coma should be excluded before diagnosing cerebral malaria (e.g. hypoglycaemia, bacterial meningitis).
Severe malaria is defined as P. falciparum parasitemia > 0 detected by microscopy and/or rapid diagnostic test (RDT) and one or more of the following, occurring in the absence of an identified alternative cause: Impaired consciousness, Prostration, Multiple convulsions, Acidosis, Hypoglycemia, Severe malarial anemia, Renal impairment, Jaundice, Pulmonary edema, Significant bleeding: including recurrent or prolonged bleeding from the nose, gums or venipuncture sites, hematemesis or melaena, Shock, Hyperparasitemia.
Measured: From Day 0 to Month 50
Number of Participants With Potential Immune Mediated Diseases (pIMDs)
Potential immune-mediated diseases (pIMDs) are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune etiology.
Measured: From Day 0 to Month 50
Number of Participants With Meningitis
Meningitis is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders.
Measured: From Day 0 to Month 50
Number of Participants With Seizures
Seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders.
Measured: During the 30-day (Day 0 to Day 29) follow-up period after any dose of study vaccine
Number of Participants With Generalized Convulsive Seizures
Generalized convulsive seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders.
Measured: During the 7-day (Day 0 to Day 6) follow-up period after any dose of study vaccine
Number of Participants With Any Unsolicited AEs
An unsolicited AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
Measured: During the 30-day (Day 0 to Day 29) follow-up period following the 1st 3 doses and post dose 4, 5 and 6 of study vaccine
Number of Participants With Grade 4 Hematology and Biochemical Toxicities Before Dose 3
The assessed parameters (alanine aminotransferase [ALT], creatinine, haemoglobin, white blood cells [WBC], platelets) were summarized according to DAIDS, 2004 (Division of AIDS). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling. Data are presented for those participants who experienced Grade 4 toxicities. Grade 4 hematological toxicities included ALT: > 10.0 x ULN (Upper limit of normal), creatine: > 6.0 x ULN or requires dialysis, WBC: < 1.0 x 103 per microliter, platelets: < 25 x 103/μl and clinical signs of bleeding, and hemoglobin: < 5.0 grams/deciliter and clinical signs of heart failure.
Measured: Before Dose 3 (at Month 2)
Number of Participants With Grade 4 Hematology and Biochemical Toxicities at 7 Days Post-Dose 3
The assessed parameters (ALT, creatinine, haemoglobin, WBC, platelets) were summarized according to DAIDS, 2004 (Division of AIDS). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling. Data are presented for those participants who experienced Grade 4 toxicities. Grade 4 hematological toxicities included ALT: > 10.0 x ULN, creatine: > 6.0 x ULN or requires dialysis, WBC: < 1.0 x 103 per microliter, platelets: < 25 x 103/μl and clinical signs of bleeding, and hemoglobin: < 5.0 grams/deciliter and clinical signs of heart failure.
Measured: At 7 days post-Dose 3
Number of Participants With Grade 4 Hematology and Biochemical Toxicities at 30 Days Post-Dose 3
The assessed parameters (ALT, creatinine, haemoglobin, WBC, platelets) were summarized according to DAIDS, 2004 (Division of AIDS). Grade 1, mild; Grade 2, moderate; Grade 3, severe; Grade 4, life-threatening or disabling. Data are presented for those participants who experienced Grade 4 toxicities. Grade 4 hematological toxicities included ALT: > 10.0 x ULN, creatine: > 6.0 x ULN or requires dialysis, WBC: < 1.0 x 103 per microliter, platelets: < 25 x 103/μl and clinical signs of bleeding, and hemoglobin: < 5.0 grams/deciliter and clinical signs of heart failure.
Measured: At 30 days post-Dose 3
Number of Participants With Any Solicited Local Symptoms
Assessed solicited local AEs are: redness, pain and swelling. Any = occurrence of the adverse event regardless of intensity grade. Any redness and swelling = adverse event reported with a surface diameter > 0 millimeters.
Measured: During the 4-day (Day 0 to Day 3) follow-up period after Dose 3, Dose 4, Dose 5 and Dose 6 of study vaccination
Number of Participants With Any Solicited General Symptoms
Assessed solicited general AEs are: drowsiness, irritability/fussiness and loss of appetite. Any = occurrence of the adverse event regardless of intensity grade or relation to study vaccination.
Measured: During the 4-day (Day 0 to Day 3) follow-up period after Dose 3, Dose 4, Dose 5 and Dose 6 of study vaccination
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2017
- Study start28 Sep 2017
- Primary completion4 Nov 2019
- Study completion14 Nov 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for MalariaStudies of the same condition, open and under way.
- More trials run by GlaxoSmithKlineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1,500 participants (actual)
Sponsor and investigators
- Lead sponsor
- GlaxoSmithKline
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03276962
- Sponsor's protocol ID
- 204889
- Other IDs
- 2016-000290-20, 2016
- Status last verified
- May 2024
- First submitted
- 7 Sep 2017
- Last updated
- 21 May 2024
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD for this study will be made available via the Clinical Study Data Request site.
Publications
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.
PubMed 38438123Osei-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.
PubMed 40975080Juraska 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.
PubMed 38723650Juraska 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.
PubMed 38045387Samuels 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.
PubMed 35753316
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy, Safety and Immunogenicity Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Evaluating Schedules With or With-out Fractional Doses, Early Dose 4 and Yearly Doses, in Children 5-17 Months of Age
- ClinicalTrials.gov ID
- NCT03276962
- Acronym / sponsor ID
- 204889
- Conditions
- Malaria
- Keywords
- falciparum, efficacy, RTS,S/AS01, malaria vaccine, safety, Malaria, immunogenicity, infants
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,500 participants (actual)
- Lead sponsor
- GlaxoSmithKlineIndustry (pharma, biotech, devices)
- Study start
- 28 Sep 2017 (actual)
- Primary completion
- 4 Nov 2019 (actual)
- Study completion
- 14 Nov 2022 (actual)
- First posted
- 8 Sep 2017 (actual)
- Results
- Posted 21 May 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The current study intends to establish proof of concept (POC) for a fractional dose schedule under conditions of natural exposure. The study will be conducted in children 5-17 months old at first vaccination living in areas of mid to high malaria transmission, in line with the age group recommended by the World Health Organization (WHO) for the implementation of the RTS,S/AS01E vaccine. Results from this study will be critical in informing future possibilities for the development of vaccine-based strategies which, in combination with other interventions, may contribute to the malaria elimination agenda.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| R012-20 Group | Experimental | Biological: RTS,S/AS01E (Full dose)Participants will receive a full dose of RTS,S/AS01E at Month 0, Month 1, Month 2 and at Month 20. |
| R012-14-mD Group | Experimental | Biological: RTS,S/AS01E (Full dose)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. |
| Fx012-14-mFxD Group | Experimental | Biological: RTS,S/AS01E (Full dose), Biological: RTS,S/AS01E (1/5th dose)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. |
| Fx017-mFxD Group | Experimental | Biological: RTS,S/AS01E (Full dose), Biological: RTS,S/AS01E (1/5th dose)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. |
| Control Group | Experimental | Biological: Rabies vaccineParticipants will receive rabies vaccine at Month 0, Month 1 and Month 2. |
Who may qualify
- Ages
- 5 to 17 months
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (23 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RTS,S/AS01E (Full dose)Participants will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml). | Biological | Fx012-14-mFxD Group, Fx017-mFxD Group, R012-14-mD Group, R012-20 Group |
| RTS,S/AS01E (1/5th dose)Participants will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml). | Biological | Fx012-14-mFxD Group, Fx017-mFxD Group |
| Rabies vaccineParticipants will receive intramuscular injection of rabies vaccine (0.1 ml). | Biological | Control Group |
Primary outcome
Incidence of Clinical Malaria Meeting the Primary Case Definition
Time frame: From Month 2.5 to Month 14
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.
21 secondary outcomes
Incidence of Clinical Malaria Meeting the Primary and Secondary Case Definitions of the Fx012-14-mFxD Group Versus the R012-20 Group
Time frame: 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
Time frame: From Month 0 to Month 50
The Prevalence of P. Falciparum Infections Defined by Positive Blood Slide at Each Cross-sectional Survey
Time frame: 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
Time frame: Month 0 to Month 14
Number of Seropositive Participants for Anti-circumsporozoite (Anti-CS) Antibodies
Time frame: 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)
Number of Seropositive Participants for Anti-hepatitis B (Anti-HB) Antibodies
Time frame: 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)
Antibody Concentrations for Anti-CS
Time frame: 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)
Antibody Concentrations for Anti-HB
Time frame: 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)
Number of Participants With Any, Fatal and Related Serious Adverse Events (SAEs)
Time frame: From Day 0 to Month 50
Number of Participants With Any Adverse Events (AEs) and SAEs Leading to Withdrawal From Further Vaccination
Time frame: From Day 0 to Month 50
Number of Participants With Cerebral Malaria and Severe Malaria
Time frame: From Day 0 to Month 50
Number of Participants With Potential Immune Mediated Diseases (pIMDs)
Time frame: From Day 0 to Month 50
Number of Participants With Meningitis
Time frame: From Day 0 to Month 50
Number of Participants With Seizures
Time frame: During the 30-day (Day 0 to Day 29) follow-up period after any dose of study vaccine
Number of Participants With Generalized Convulsive Seizures
Time frame: During the 7-day (Day 0 to Day 6) follow-up period after any dose of study vaccine
Number of Participants With Any Unsolicited AEs
Time frame: During the 30-day (Day 0 to Day 29) follow-up period following the 1st 3 doses and post dose 4, 5 and 6 of study vaccine
Number of Participants With Grade 4 Hematology and Biochemical Toxicities Before Dose 3
Time frame: Before Dose 3 (at Month 2)
Number of Participants With Grade 4 Hematology and Biochemical Toxicities at 7 Days Post-Dose 3
Time frame: At 7 days post-Dose 3
Number of Participants With Grade 4 Hematology and Biochemical Toxicities at 30 Days Post-Dose 3
Time frame: At 30 days post-Dose 3
Number of Participants With Any Solicited Local Symptoms
Time frame: During the 4-day (Day 0 to Day 3) follow-up period after Dose 3, Dose 4, Dose 5 and Dose 6 of study vaccination
Number of Participants With Any Solicited General Symptoms
Time frame: During the 4-day (Day 0 to Day 3) follow-up period after Dose 3, Dose 4, Dose 5 and Dose 6 of study vaccination
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 May 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 38438123Westercamp 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.
- Derived from this study: PubMed 40975080Osei-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.
- Derived from this study: PubMed 38723650Juraska 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.
- Derived from this study: PubMed 38045387Juraska 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.
- Derived from this study: PubMed 35753316Samuels 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.
- Individual participant dataSharing planned: Yes. IPD for this study will be made available via the Clinical Study Data Request site.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
GSK Clinical Trials study director
GlaxoSmithKline
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing RTS,S/AS01E (Full dose), RTS,S/AS01E (1/5th dose) and Rabies vaccine in people with Malaria, run by GlaxoSmithKline at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Ghana, Kenya. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Clinical Malaria Meeting the Primary Case Definition (time frame: From Month 2.5 to Month 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03276962, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 May 2024; AzTrials last refreshed its copy on 7 Nov 2026.