Back to resultsAn Extension to Study MALARIA-055 PRI (NCT00866619) to Evaluate the Long-term Efficacy, Safety and Immunogenicity of GSK Biologicals' Candidate Malaria Vaccine in Infants and Children in Africa
Primary Purpose
Malaria
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Blood sampling
Malaria Vaccine 257049 (MALARIA-055 PRI)
Meningococcal C Conjugate Vaccine (MALARIA-055 PRI)
Cell-culture rabies vaccine (MALARIA-055 PRI)
TritanrixHepB/Hib (MALARIA-055 PRI)
Polio Sabin Oral Polio Vaccine (GSK) (MALARIA-055 PRI)
Sponsored by
About this trial
This is an interventional prevention trial for Malaria focused on measuring Infants, Efficacy, Children, Malaria, Plasmodium falciparum, Safety, Surveillance, Immunogenicity, RTS,S/AS01E, Africa
Eligibility Criteria
Inclusion Criteria:
- Subjects' parent(s)/ Legally Acceptable Representative (LARs) who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
- Subjects who were enrolled and who received at least one vaccine dose in the primary study MALARIA-055 PRI NCT00866619 and who did not withdraw consent (except those who moved away from the area) during the primary study MALARIA-055 PRI NCT00866619.
- Written informed consent obtained from the parent(s)/LAR(s) of the subject.
Exclusion Criteria:
- Child in care.
- Use of any investigational or non-registered product or planned use during the study period.
Sites / Locations
- GSK Investigational Site
- GSK Investigational Site
- GSK Investigational Site
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
GSK257049 Group
GSK257049 Comparator Group
VeroRab/Menjugate Comparator Group
Arm Description
Male or female infants (between and including 6 to 12 weeks of age)/children (between and including 5 to 17 months of age) received 3 doses of GSK257049 malaria vaccine (co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, for the infants subgroup) on a 0-1-2-month schedule, and a booster dose of GSK257049 malaria vaccine (co-administered with Polio Sabin, for the infants subgroup) at Month 20 during the primary study MALARIA-055 PRI (NCT00866619). Vaccines were administered intramuscularly: in the anterolateral left thigh (GSK257049 vaccine); left deltoid (GSK257049 booster dose); anterolateral right thigh (Tritanrix HepB/Hib vaccine); orally: Polio Sabin vaccine. No vaccination was administered during this study.
Male or female infants (between and including 6 to 12 weeks of age)/children (between and including 5 to 17 months of age) received 3 doses of GSK257049 malaria vaccine (co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, for the infants subgroup) on 0-1-2-month schedule, and a booster dose of Menjugate vaccine (co-administered with Polio Sabin, for the infants subgroup) at Month 20 during the primary study MALARIA-055 PRI (NCT00866619). Vaccines were administered intramuscularly: in the anterolateral left thigh (GSK257049 vaccine); anterolateral right thigh (Tritanrix HepB/Hib vaccine); orally: Polio Sabin vaccine. No vaccination was administered during this study.
Male or female infants (between and including 6 to 12 weeks of age)/children (between and including 5 to 17 months of age) received 3 doses of VeroRab vaccine (children subgroup) or Menjugate vaccine (co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, for the infants subgroup) on 0-1-2-month schedule, and a booster dose of Menjugate vaccine (co-administered with Polio Sabin, for the infants subgroup) at Month 20 during the primary study MALARIA-055 PRI (NCT00866619). Vaccines were administered intramuscularly: left deltoid (VeroRab vaccine and Menjugate vaccine); anterolateral right thigh (Tritanrix HepB/Hib vaccine); orally: Polio Sabin vaccine. No vaccination was administered during this study.
Outcomes
Primary Outcome Measures
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).
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).
Secondary Outcome Measures
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.
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).
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.
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.
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.
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.
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).
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).
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.
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).
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.
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.
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).
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.
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.
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).
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.
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.
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.
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'.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02207816
Brief Title
An Extension to Study MALARIA-055 PRI (NCT00866619) to Evaluate the Long-term Efficacy, Safety and Immunogenicity of GSK Biologicals' Candidate Malaria Vaccine in Infants and Children in Africa
Official Title
Extension to Study MALARIA-055 PRI (NCT00866619) for Evaluation of Long-term Efficacy, Safety and Immunogenicity of GSK Biologicals' Candidate Malaria Vaccine (SB257049) in Infants and Children in Africa
Study Type
Interventional
2. Study Status
Record Verification Date
November 2019
Overall Recruitment Status
Completed
Study Start Date
September 18, 2014 (Actual)
Primary Completion Date
January 31, 2017 (Actual)
Study Completion Date
January 31, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
GlaxoSmithKline
4. Oversight
5. Study Description
Brief Summary
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Malaria
Keywords
Infants, Efficacy, Children, Malaria, Plasmodium falciparum, Safety, Surveillance, Immunogenicity, RTS,S/AS01E, Africa
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
3084 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GSK257049 Group
Arm Type
Experimental
Arm Description
Male or female infants (between and including 6 to 12 weeks of age)/children (between and including 5 to 17 months of age) received 3 doses of GSK257049 malaria vaccine (co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, for the infants subgroup) on a 0-1-2-month schedule, and a booster dose of GSK257049 malaria vaccine (co-administered with Polio Sabin, for the infants subgroup) at Month 20 during the primary study MALARIA-055 PRI (NCT00866619). Vaccines were administered intramuscularly: in the anterolateral left thigh (GSK257049 vaccine); left deltoid (GSK257049 booster dose); anterolateral right thigh (Tritanrix HepB/Hib vaccine); orally: Polio Sabin vaccine. No vaccination was administered during this study.
Arm Title
GSK257049 Comparator Group
Arm Type
Active Comparator
Arm Description
Male or female infants (between and including 6 to 12 weeks of age)/children (between and including 5 to 17 months of age) received 3 doses of GSK257049 malaria vaccine (co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, for the infants subgroup) on 0-1-2-month schedule, and a booster dose of Menjugate vaccine (co-administered with Polio Sabin, for the infants subgroup) at Month 20 during the primary study MALARIA-055 PRI (NCT00866619). Vaccines were administered intramuscularly: in the anterolateral left thigh (GSK257049 vaccine); anterolateral right thigh (Tritanrix HepB/Hib vaccine); orally: Polio Sabin vaccine. No vaccination was administered during this study.
Arm Title
VeroRab/Menjugate Comparator Group
Arm Type
Active Comparator
Arm Description
Male or female infants (between and including 6 to 12 weeks of age)/children (between and including 5 to 17 months of age) received 3 doses of VeroRab vaccine (children subgroup) or Menjugate vaccine (co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, for the infants subgroup) on 0-1-2-month schedule, and a booster dose of Menjugate vaccine (co-administered with Polio Sabin, for the infants subgroup) at Month 20 during the primary study MALARIA-055 PRI (NCT00866619). Vaccines were administered intramuscularly: left deltoid (VeroRab vaccine and Menjugate vaccine); anterolateral right thigh (Tritanrix HepB/Hib vaccine); orally: Polio Sabin vaccine. No vaccination was administered during this study.
Intervention Type
Procedure
Intervention Name(s)
Blood sampling
Intervention Description
Annual blood sampling (Year 1, Year 2 and Year 3) during the present study.
Intervention Type
Biological
Intervention Name(s)
Malaria Vaccine 257049 (MALARIA-055 PRI)
Intervention Description
Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
Intervention Type
Biological
Intervention Name(s)
Meningococcal C Conjugate Vaccine (MALARIA-055 PRI)
Other Intervention Name(s)
Menjugate
Intervention Description
Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
Intervention Type
Biological
Intervention Name(s)
Cell-culture rabies vaccine (MALARIA-055 PRI)
Other Intervention Name(s)
VeroRab
Intervention Description
Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
Intervention Type
Biological
Intervention Name(s)
TritanrixHepB/Hib (MALARIA-055 PRI)
Intervention Description
Administered intramuscularly into the left deltoid, during the MALARIA-055 study (NCT00866619).
Intervention Type
Biological
Intervention Name(s)
Polio Sabin Oral Polio Vaccine (GSK) (MALARIA-055 PRI)
Intervention Description
Administered orally, during the MALARIA-055 study (NCT00866619).
Primary Outcome Measure Information:
Title
Incidence of Severe Malaria Meeting Case Definition 1
Description
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)
Title
Incidence of Severe Malaria Meeting Case Definition 2.
Description
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)
Secondary Outcome Measure Information:
Title
Incidence of Clinical Malaria Meeting Case Definition
Description
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.
Time Frame
From Year 0 to Year 3 (Starting January 2014 and ending December 2016)
Title
Number of Subjects With Malaria Hospitalization Meeting Case Definition 1.
Description
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)
Title
Number of Subjects With Malaria Hospitalization Meeting Case Definition 2.
Description
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)
Title
Number of Subjects With Prevalent Parasitemia
Description
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
Title
Number of Subjects With Prevalent Severe Anemia (Level of Hemoglobin <5g/dL)
Description
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
Title
Number of Subjects With Prevalent Moderate Anemia (Level of Hemoglobin <8g/dL)
Description
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
Title
Incidence of Severe Malaria Meeting Case Definition 1.
Description
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)
Title
Incidence of Severe Malaria Meeting Case Definition 2.
Description
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)
Title
Incidence of Clinical Malaria Meeting Case Definition
Description
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)
Title
Number of Subjects With Malaria Hospitalization Meeting Case Definition 1.
Description
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)
Title
Number of Subjects With Malaria Hospitalization Meeting Case Definition 2.
Description
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).
Title
Number of Subjects With Cerebral Malaria Meeting Both Case Definitions.
Description
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)
Title
Number of Subjects With Fatal Malaria Meeting Case Definition 1.
Description
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)
Title
Number of Subjects With Fatal Malaria Meeting Case Definition 2.
Description
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)
Title
Number of Subjects With Cerebral Malaria
Description
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).
Title
Number of Subjects With Fatal Malaria Meeting Case Definition 1.
Description
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).
Title
Number of Subjects With Fatal Malaria Meeting Case Definition 2.
Description
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).
Title
Number of Subjects Reporting Any, Related, Malaria and Fatal Serious Adverse Events (SAEs)
Description
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)
Title
Number of Subjects Reporting Any Potential Immune-mediated Disorders (pIMDs) SAEs
Description
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)
Title
Number of Subjects With Meningitis SAEs
Description
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)
Title
Antibody Concentrations Against Against Plasmodium Falciparum Circumsporozoite (Anti-CS)
Description
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)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
42 Months
Maximum Age & Unit of Time
9 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Subjects' parent(s)/ Legally Acceptable Representative (LARs) who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
Subjects who were enrolled and who received at least one vaccine dose in the primary study MALARIA-055 PRI NCT00866619 and who did not withdraw consent (except those who moved away from the area) during the primary study MALARIA-055 PRI NCT00866619.
Written informed consent obtained from the parent(s)/LAR(s) of the subject.
Exclusion Criteria:
Child in care.
Use of any investigational or non-registered product or planned use during the study period.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
GSK Clinical Trials
Organizational Affiliation
GlaxoSmithKline
Official's Role
Study Director
Facility Information:
Facility Name
GSK Investigational Site
City
Ouagadougou
Country
Burkina Faso
Facility Name
GSK Investigational Site
City
Kisumu
Country
Kenya
Facility Name
GSK Investigational Site
City
Tanga
Country
Tanzania
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing Time Frame
IPD is available via the Clinical Study Data Request site (click on the link provided below)
IPD Sharing 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.
IPD Sharing URL
https://clinicalstudydatarequest.com/Posting.aspx?ID=20045
Citations:
PubMed Identifier
31300331
Citation
Tinto H, Otieno W, Gesase S, Sorgho H, Otieno L, Liheluka E, Valea I, Sing'oei V, Malabeja A, Valia D, Wangwe A, Gvozdenovic E, Guerra Mendoza Y, Jongert E, Lievens M, Roman F, Schuerman L, Lusingu J. Long-term incidence of severe malaria following RTS,S/AS01 vaccination in children and infants in Africa: an open-label 3-year extension study of a phase 3 randomised controlled trial. Lancet Infect Dis. 2019 Aug;19(8):821-832. doi: 10.1016/S1473-3099(19)30300-7. Epub 2019 Jul 9.
Results Reference
background
Learn more about this trial
An Extension to Study MALARIA-055 PRI (NCT00866619) to Evaluate the Long-term Efficacy, Safety and Immunogenicity of GSK Biologicals' Candidate Malaria Vaccine in Infants and Children in Africa
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