- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03276962
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
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
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Subjects' 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 subject 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 subjects 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 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 subjects) 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 subject 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 subjects with an 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.
Subjects 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: R012-20 Group
Subjects will receive full doses of RTS,S/AS01E at Month 0, Month 1, Month 2 and a full dose at Month 20.
|
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).
|
Experimental: R012-14-mD Group
Subjects 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, Month 38.
|
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).
|
Experimental: Fx012-14-mFxD Group
Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 2, Month 14, Month 26, Month 38.
|
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).
Subjects will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).
|
Experimental: Fx017-mFxD Group
Subjects will receive a full dose of RTS,S/AS01E at Month 0, Month 1 and RTS,S/AS01E 1/5th dose at Month 7, Month 20, Month 32.
|
Subjects will receive intramuscular injection of RTS,S/AS01E (full dose: 0.5 ml).
Subjects will receive intramuscular injection of RTS,S/AS01E (1/5th dose: 0.1 ml).
|
Experimental: Control Group
Subjects will receive rabies vaccine at Month 0, Month 1, Month 2.
|
Subjects will receive intramuscular injection of rabies vaccine (0.1 ml).
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The occurrence of clinical malaria meeting the primary case definition
Time Frame: From Month 2.5 up to Month 14
|
The primary case definition will be P. falciparum asexual parasitemia greater than (>) 5000 parasites/microliters (μl) and presence of fever (axillary temperature greater than or equal to [≥] 37.5 degrees Celsius [°C]) at the time of presentation and occurring in a child who is unwell and brought for treatment to a healthcare facility.
|
From Month 2.5 up to Month 14
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
The occurrence of clinical malaria meeting the primary and secondary case definitions
Time Frame: From Day 0 up to Month 50
|
The primary case definition will be P. falciparum asexual parasitemia > 5000 parasites/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 will be 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. |
From Day 0 up to Month 50
|
The occurrence of incident P. falciparum infections
Time Frame: From Day 0 to Month 50
|
Vaccine efficacy against incident P. falciparum infections defined by positive blood slide.
|
From Day 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 0-20 and every three months thereafter till study end (Month 50)
|
Prevalence of P. falciparum infections of each RTS,S/AS01E schedule at cross-sectional visits.
|
Monthly from Month 0-20 and every three months thereafter till study end (Month 50)
|
Number of seropositive subjects for anti-circumsporozoite (anti-CS) antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site)
Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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)
|
A seropositive subject is defined as a subject with antibody concentrations ≥ 0.5 ELISA units per milliliter (EU/mL).
|
Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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 subjects for anti-hepatitis B (anti-HB) antibodies (in a sub-cohort of first 25 subjects enrolled in each group per site)
Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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)
|
A seropositive subject is defined as a subject with antibody concentrations ≥ 10 milli-international units per milliliter (mIU/mL).
|
Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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 (in a sub-cohort of first 25 subjects enrolled in each group per site)
Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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)
|
Concentrations are expressed as geometric mean concentrations (GMC).
|
Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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 (in a sub-cohort of first 25 subjects enrolled in each group per site)
Time Frame: Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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).
|
Concentrations are expressed as geometric mean concentrations (GMC).
|
Before Dose 1, one month post-Dose 2 (group Fx017-mFxD only), 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 subjects with any, fatal and related serious adverse events (SAEs)
Time Frame: From Day 0 to Month 50
|
SAEs include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
|
From Day 0 to Month 50
|
Number of subjects with any adverse events (AEs) and serious adverse events (SAEs) leading to withdrawal from further vaccination
Time Frame: From Day 0 to Month 50
|
An adverse event (AE) is any untoward medical occurrence in a clinical investigation subject, 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. |
From Day 0 to Month 50
|
Number of subjects with severe malaria and cerebral malaria
Time Frame: From Day 0 to Month 50
|
Cerebral malaria is defined as Severe P. falciparum malaria with coma (Blantyre coma score 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. |
From Day 0 to Month 50
|
Number of subjects with potential Immune mediated diseases (pIMDs)
Time Frame: From Day 0 to Month 50
|
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.
|
From Day 0 to Month 50
|
Number of subjects with meningitis
Time Frame: From Day 0 to Month 50
|
The number of subjects with meningitis per study group.
|
From Day 0 to Month 50
|
Number of subjects with seizures
Time Frame: During the 30-day (Days 0-29) follow-up period after each dose of study vaccine
|
The number of subjects with seizures per study group.
|
During the 30-day (Days 0-29) follow-up period after each dose of study vaccine
|
Number of subjects with generalized convulsive seizures
Time Frame: During the 7-day (Days 0-6) follow-up period after each dose of study vaccine
|
The number of subjects with generalized convulsive seizures per study group.
|
During the 7-day (Days 0-6) follow-up period after each dose of study vaccine
|
Number of subjects with any unsolicited adverse events (AEs)
Time Frame: During the 30-day (Days 0-29) follow-up period after each dose of study vaccine
|
An unsolicited AE is any untoward medical occurrence in a clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product.
|
During the 30-day (Days 0-29) follow-up period after each dose of study vaccine
|
Number of subjects with abnormal laboratory values (in a sub-cohort of first 25 subjects enrolled in each group per site)
Time Frame: Before Dose 3, seven days post-Dose 3 and 30 days post-Dose 3
|
The assessed parameters (alanine aminotransferase [ALT], creatinine, haemoglobin, white blood cells [WBC], platelets) will be summarised by toxicity grading scales and by group.
|
Before Dose 3, seven days post-Dose 3 and 30 days post-Dose 3
|
Number of subjects with any solicited local symptoms (in the reactogenicity sub-cohort of first 25 subjects enrolled per site)
Time Frame: During the 4-day (Days 0-3) follow-up period after each vaccination
|
Solicited local symptoms assessed will be pain, redness and swelling.
|
During the 4-day (Days 0-3) follow-up period after each vaccination
|
Number of subjects with any solicited general symptoms (in the reactogenicity sub-cohort of first 25 subjects enrolled per site)
Time Frame: During the 4-day (Days 0-3) follow-up period after each vaccina-tion
|
Solicited general symptoms assessed will be drowsiness, fever, irritability/fussiness and loss of appetite.
|
During the 4-day (Days 0-3) follow-up period after each vaccina-tion
|
Collaborators and Investigators
Sponsor
Investigators
- Study Director: GSK Clinical Trials, GlaxoSmithKline
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 204889
- 2016-000290-20 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
- CSR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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