The purpose of this study is to conduct long-term surveillance for efficacy, safety and immunogenicity of the GSK Biologicals RTS,S/AS01E candidate Plasmodium falciparum malaria vaccine in infants and children in Africa following a primary vaccination series (NCT00866619). No new subjects will be enrolled in this extension study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
3,084
Annual blood sampling (Year 1, Year 2 and Year 3) during the present study.
Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
GSK Investigational Site
Ouagadougou, Burkina Faso
GSK Investigational Site
Kisumu, Kenya
GSK Investigational Site
Tanga, Tanzania
Incidence of Severe Malaria Meeting Case Definition 1
Case definition 1 for severe malaria was defined as an episode of malaria with positive Plasmodium falciparum asexual parasitemia (within -1 to +3 days of admission) and with one or more marker of disease severity: Prostration, respiratory distress, Blantyre score equal to or less than (≤) 2, seizures 2 or more, hypoglycemia below (\<) 2.2 millimoles per liter (mmol/L), acidosis BE ≤ -10.0 mmol/L, lactate ≥ 5.0 mmol/L or anemia \< 5.0 grams per deciliter (g/dL). The incidence of severe malaria for case definition 1 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).
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Incidence of Severe Malaria Meeting Case Definition 2.
Case definition 2 for severe malaria was defined as an episode of malaria with positive Plasmodium falciparum asexual parasitemia (within -1 to +3 days of admission) and with one or more marker of disease severity: Prostration, respiratory distress, Blantyre score equal to or less than (≤) 2, seizures 2 or more, hypoglycemia below (\<) 2.2 millimoles per liter (mmol/L), acidosis BE ≤ -10.0 mmol/L, lactate ≥ 5.0 mmol/L or anemia \< 5.0 grams per deciliter (g/dL) or SAE report including preferred terms (Malaria, Plasmodium falciparum infection or Cerebral malaria) within -1 to +3 days of admission. The incidence of severe malaria for case definition 2 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).
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Incidence of Clinical Malaria Meeting Case Definition
Clinical malaria was defined as an episode of malaria with positive Plasmodium falciparum asexual parasitemia, accompanied by the 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 was unwell and brought for treatment to a healthcare facility. The incidence of clinical malaria for case definition 1 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 a t risk (T). Due to late protocol approvals and retrospective data collection the sites did not collect the data according to protocol and as such the case definition cannot be applied. For the final analysis, specific case definitions based on available data were developed.
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Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
Administered orally, during the MALARIA-055 study (NCT00866619).
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects With Malaria Hospitalization Meeting Case Definition 1.
Malaria hospitalization, case definition 1, was defined as a medical hospitalization with confirmed positive Plasmodium falciparum asexual parasitemia (excludes planned admissions for medical investigation/care or elective surgery and trauma).
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects With Malaria Hospitalization Meeting Case Definition 2.
Malaria hospitalization, case definition 2, was defined as a hospitalization for which, in the judgment of the principal investigator, Plasmodium falciparum infection was the sole or a major contributing factor to the presentation.
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects With Prevalent Parasitemia
Prevalent parasitemia (PP) was defined as a documented Plasmodium falciparum asexual parasite density greater than (\>) 0 parasites/µL, identified at an annual visit.
Time frame: At Years 1, 2 and 3
Number of Subjects With Prevalent Severe Anemia (Level of Hemoglobin <5g/dL)
Prevalent severe anemia (PSA) was defined as a documented hemoglobin lower than (\<) 5.0 grams per deciliter (g/dL), identified at an annual visit.
Time frame: At Years 1, 2 and 3
Number of Subjects With Prevalent Moderate Anemia (Level of Hemoglobin <8g/dL)
Prevalent moderate anemia (PMA) was defined as a documented hemoglobin \< 8.0 g/dL, identified at an annual visit.
Time frame: At Years 1, 2 and 3
Incidence of Severe Malaria Meeting Case Definition 1.
Case definition 1 for severe malaria was defined as an episode of malaria with positive Plasmodium falciparum asexual parasitemia (within -1 to +3 days of admission) and with one or more marker of disease severity: Prostration, respiratory distress, Blantyre score equal to or less than (≤) 2, seizures 2 or more, hypoglycemia below (\<) 2.2 millimoles per liter (mmol/L), acidosis BE ≤ -10.0 mmol/L, lactate ≥ 5.0 mmol/L or anemia \< 5.0 grams per deciliter (g/dL). The incidence of severe malaria for case definition 1 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).
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076)
Incidence of Severe Malaria Meeting Case Definition 2.
Case definition 2 for severe malaria was defined as an episode of malaria with positive Plasmodium falciparum asexual parasitemia (within -1 to +3 days of admission) and with one or more marker of disease severity: Prostration, respiratory distress, Blantyre score equal to or less than (≤) 2, seizures 2 or more, hypoglycemia below (\<) 2.2 millimoles per liter (mmol/L), acidosis BE ≤ -10.0 mmol/L, lactate ≥ 5.0 mmol/L or anemia \< 5.0 grams per deciliter (g/dL) or SAE report including preferred terms (Malaria, Plasmodium falciparum infection or Cerebral malaria) within -1 to +3 days of admission. The incidence of severe malaria for case definition 2 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).
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076)
Incidence of Clinical Malaria Meeting Case Definition
Clinical malaria was defined as an episode of malaria with positive Plasmodium falciparum asexual parasitemia, accompanied by the 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 was unwell and brought for treatment to a healthcare facility. The incidence of clinical malaria for case definition 1 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). Due to late protocol approvals and retrospective data collection the sites did not collect the data according to protocol and as such the case definition cannot be applied. For the final analysis, specific case definitions based on available data were developed.
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076)
Number of Subjects With Malaria Hospitalization Meeting Case Definition 1.
Malaria hospitalization, case definition 1, was defined as a medical hospitalization with confirmed positive Plasmodium falciparum asexual parasitemia (excludes planned admissions for medical investigation/care or elective surgery and trauma).
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076)
Number of Subjects With Malaria Hospitalization Meeting Case Definition 2.
Malaria hospitalization, case definition 2, was defined as a hospitalization for which, in the judgment of the principal investigator, Plasmodium falciparum infection was the sole or a major contributing factor to the presentation.
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076).
Number of Subjects With Cerebral Malaria Meeting Both Case Definitions.
Cerebral malaria was defined as a positive P. falciparum asexual parasitemia (within -1 to +3 days of admission), accompanied either by the presence of a marker of disease severity (a Blantyre score ≤ 2) or a SAE report with 'cerebral malaria' as preferred term.
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects With Fatal Malaria Meeting Case Definition 1.
Fatal malaria, case definition 1, was defined as a SAE report with preferred terms 'malaria', 'plasmodium falciparum infection', 'cerebral malaria' with confirmed positive Plasmodium falciparum asexual parasitemia associated with a fatal outcome (excludes planned admissions for medical investigation/care or elective surgery and trauma).
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects With Fatal Malaria Meeting Case Definition 2.
Fatal malaria, case definition 2, was defined as a SAE report with preferred terms 'malaria', 'plasmodium falciparum infection', 'cerebral malaria' associated with a fatal outcome.
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects With Cerebral Malaria
Cerebral malaria was defined as a positive P. falciparum asexual parasitemia (within -1 to +3 days of admission), accompanied either by the presence of a marker of disease severity (a Blantyre score ≤ 2) or a SAE report with 'cerebral malaria' as preferred term.
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076).
Number of Subjects With Fatal Malaria Meeting Case Definition 1.
Fatal malaria, case definition 1, was defined as a SAE report with preferred terms 'malaria', 'plasmodium falciparum infection', 'cerebral malaria' with confirmed positive Plasmodium falciparum asexual parasitemia associated with a fatal outcome (excludes planned admissions for medical investigation/care or elective surgery and trauma).
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076).
Number of Subjects With Fatal Malaria Meeting Case Definition 2.
Fatal malaria, case definition 2, was defined as a SAE report with preferred terms 'malaria', 'plasmodium falciparum infection', 'cerebral malaria' associated with a fatal outcome.
Time frame: From Month 0 (study start of Malaria-055) to Year 3 (study end of Malaria-076).
Number of Subjects Reporting Any, Related, Malaria and Fatal Serious Adverse Events (SAEs)
Malaria SAEs were defined as SAEs coded by MedDRA preferred term level as 'malaria', 'Plasmodium falciparum infection' or 'cerebral malaria". A serious adverse event was any untoward medical occurrence that: resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization or resulted in disability/incapacity. SAEs disclosed in this outcome are any SAEs , fatal SAEs, those that were related to vaccine administration in the primary study MALARIA-055 PRI (110021) and malaria hospitalization.
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects Reporting Any Potential Immune-mediated Disorders (pIMDs) SAEs
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 aetiology. Regardless of it being considered an AE or an SAE, it should have been reported per the SAE reporting rules.
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Number of Subjects With Meningitis SAEs
For the further evaluation of the safety signal of meningitis all the cases occurring during the study were reported as SAE. Meningitis is defined as an SAE coded at lowest level terms code, coded by MedDRA preferred term level as: 'meningitis', 'meningitis haemophilus', 'meningitis meningococcal', 'meningitis salmonella', 'meningitis pneumococcal', 'meningitis staphylococcal', 'meningitis tuberculous', 'meningitis herpes', 'meningitis candida', 'meningitis enterococcal', 'meningitis enteroviral', 'meningitis neonatal', 'meningitis toxoplasmal', 'meningitis mumps', 'meningitis cryptococcal', 'meningitis histoplasma', 'meningitis trypanosomal', 'Neurosyphilis', 'meningitis leptospiral', 'meningitis listeria', 'meningitis in sarcoidosis' (code in preferred term 'cerebral sarcoidosis'), 'meningitis bacterial', 'meningitis viral', 'meningitis aseptic', 'meningitis fungal'.
Time frame: From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Antibody Concentrations Against Against Plasmodium Falciparum Circumsporozoite (Anti-CS)
Antibody concentrations were assessed by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean titers (GMTs). Seropositivity anti-CS antibody cut-off was 0.5 EU/mL for Malaria-055 time points and 1.9 EU/mL for Malaria-076 time points.
Time frame: At screening, 1 month post Dose 3 (Month 3), 18 months post Dose 3 (Month 20), 1 month post Dose 4 (Month 21), 12 months post Dose 4 (Month 32) (of Malaria-055) and at Years 1, 2 and 3 (of Malaria-076)