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Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa

Primary Purpose

Malaria

Status

Completed

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Malaria Vaccine 257049

Meningococcal C Conjugate Vaccine

Cell-culture rabies vaccine

TritanrixHepB/Hib

Polio Sabin Oral Polio Vaccine (GSK)

About this trial

This is an interventional prevention trial for Malaria

Eligibility Criteria

6 Weeks - 17 Months (Child)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

All subjects must satisfy the following criteria at study entry:

A male or female child of:5-17 months (inclusive) of age at time of first vaccination,or between 6-12 weeks of age at time of first vaccination and NOT have already received a dose of vaccine against diphtheria, tetanus or pertussis or Hemophilus influenzae type B and must be > 28 days of age at screening.
Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child.
Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.

All subjects must satisfy the following criteria at the start of the extension phase:

Subjects who were enrolled and who received at least one vaccine dose in the primary trial phase.
Subjects who were present for Visit 35 on or before 30 September 2013.
Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study.

Exclusion Criteria:

The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study:

Acute disease at the time of enrollment.
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality.
Anemia associated with clinical signs or symptoms of decompensation or hemoglobin ≥ 5.0 g/dL.
Major congenital defects.
History of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunizations.
Children with a past history of a neurological disorder or atypical febrile seizure.
Children with malnutrition requiring hospital admission.
Children currently meeting the criteria for HIV disease of Stage III or Stage IV severity as defined by the World Health Organization.
History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to a drug or vaccine that is not licensed for that indication with the exception of studies with the objective of improving the drug treatment or clinical management of severe malaria disease.
Use of a drug or vaccine that is not approved for that indication other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Previous participation in any other malaria vaccine trial.
Receipt of a vaccine within the preceding 7 days.
Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.
Any other findings that the investigator feels would result in data collected being incomplete or of poor quality

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Active Comparator

Experimental

Arm Label

GSK257049 [5-17M] Group

GSK257049 [6-12W] Group

VeroRab Comparator [5-17M] Group

Menjugate Comparator [6-12W] Group

Arm Description

Male or female children between and including 5 to 17 months of age [5-17M], who received a 3-dose primary vaccination course of the GSK257049 malaria vaccine, according to a 0-1-2 Month schedule, followed by either a booster dose of the same GSK257049 vaccine or a dose of Menjugate vaccine, at Month 20. Both vaccines have been administered intramuscularly into the left deltoid.

Male or female children between and including 6 to 12 weeks of age [6-12W], who received a 3-dose primary vaccination course of the GSK257049 malaria vaccine co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, according to a 0-1-2 Month schedule, followed by either a booster dose of the GSK257049 and Polio Sabin vaccines or a booster dose of Menjugate and Polio Sabin vaccines, at Month 20. All vaccines have been administered intramuscularly in the interolateral left thigh (GSK257049 vaccine); left deltoid (GSK257049 booster dose); left thigh for children under 1 year and left deltoid for children above 1 year of age (Menjugate vaccine); anterolateral right thigh (Tritanrix HepB/Hib vaccine), except for the Polio Sabin vaccine, which has been given orally.

Male or female children between and including 5 to 17 months of age [5-17M], who received a 3-dose primary vaccination course of the VeroRab vaccine, according to a 0-1-2 Month schedule, followed by a booster dose of Menjugate vaccine, at Month 20. Both vaccines have been administered intramuscularly into the left deltoid.

Male or female children between and including 6 to 12 weeks of age [6-12W], who received a 3-dose primary vaccination course of Menjugate vaccine co-administered with Polio Sabin and Tritanrix HepB/Hib vaccines, according to a 0-1-2 Month schedule, followed by a booster dose of Menjugate and Polio Sabin vaccines, at Month 12. All vaccines have been administered intramuscularly in the left thigh for children under 1 year and left deltoid for children above 1 year of age (Menjugate vaccine); anterolateral right thigh (Tritanrix HepB/Hib vaccine), except for the Polio Sabin vaccine, which has been given orally.

Outcomes

Primary Outcome Measures

Rate of First or Only Clinical Episode of Plasmodium Falciparum (P. Falciparum) Malaria Infection (CPFMI), or Clinical Malaria Episode of Primary Case Definition (CPFMI-PCD)

A CPFMI-PCD was defined as an episode of malaria for which P. falciparum asexual parasitemia was greater than (>) 5000 parasites per microliter (µL) accompanied by the 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 OR a case of malaria meeting the primary case definition of severe malaria disease. The time to first or only CPFMI-PCD is expressed in terms of rate of first or only CPFMI (RfoCPFMI), that is person-year rate in each group (n/T). Analysis for this outcome was solely performed on subjects in the 5-17 months age category.

Rate of First or Only Clinical Episode of P. Falciparum Malaria Infection (CPFMI), or Clinical Malaria Episode of Primary Case Definition (CPFMI-PCD)

A CPFMI-PCD was defined as an episode of malaria for which P. falciparum asexual parasitemia > 5000 parasites/µL was accompanied by the 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 OR a case of malaria meeting the primary case definition of severe malaria disease. The time to first or only CPFMI-PCD is expressed in terms of rate of first or only CPFMI (RfoCPFMI), that is, person-year rate in each group (n/T). Analysis for this outcome was solely performed on subjects in the 6-12 weeks (6-12W) age category.

Secondary Outcome Measures

Rate of All Episodes of P. Falciparum Clinical Malaria Infection (CPFMI) of PCD and of Secondary Case Definitions (SCD) 1, SCD 2 and SCD 3

PCD=malaria episode with P. falciparum asexual parasitemia (PFAP) > 5000 parasites/µL accompanied by fever and occurring in a child unwell brought for treatment to a healthcare facility or a case of malaria meeting the PCD of severe malaria disease. SCD1=malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. SCD2=malaria episode with PFAP > 500 parasites/μL and fever at time of presentation in a subject unwell brought for treatment to a healthcare facility. SCD3=malaria episode with PFAP > 20.000 parasites/μL and fever at time of presentation in a subject unwell and brought for treatment to a healthcare facility. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are uncorrected for double enrollment of 1 subject receiving GSK257049 vaccine.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, Overall and by Center

PCD = malaria episode with PFAP > 5000 parasites/µL accompanied by fever and occurring in a child unwell brought for treatment to a healthcare facility or a case of malaria meeting the PCD of severe malaria disease (see below endpoints on severe malaria for details). Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are by center and across centers, and are uncorrected for double enrollment of 1 subject receiving GSK257049 vaccine.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of SCD1, SCD2 and SCD3 (Overall)

SCD1 = malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. SCD2 = malaria episode with PFAP > 500 parasites/μL and fever at time of presentation in a subject unwell brought for treatment to a healthcare facility. SCD3 = malaria episode with PFAP > 20.000 parasites/μL and fever at time of presentation in a subject unwell and brought for treatment to a healthcare facility. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are across centers, and are uncorrected for double enrollment of 1 subject receiving GSK257049 vaccine.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Centers and Across Centers

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1), Across Centers

CPFMI of SCD1 = malaria episode with PFAP >0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are presented across centers.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1), Across Centers

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. CPFMI of SCD1 = malaria episode with PFAP >0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are presented across centers.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD and SCD1, Across Centers

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. CPFMI of SCD1 = malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are presented across centers.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, by Center and Across Centers

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are presented by center and across centers.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1)

CPFMI of SCD1 = malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T).

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1)

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. CPFMI of SCD1 = malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T).

Percentage of Subjects With Severe PFMI (SPFMI) of PCD, SCD1, SCD2 and SCD3, Across Centers

SPFMI of PCD = PFMI > 5000 parasites/μL, at least one severity marker and no co-morbidity diagnosis. SPFMI of SCD1 = PFMI >5000 parasites/μL and with one or more severity marker. SPFMI of SCD2 = PFMI >0 with one or more severity marker and without co-morbidity diagnosis. SPFMI of SCD3 = PFMI >5000 parasites/μL, with one or more severity marker, and without co-morbidity or HIV. Severity markers = prostration; respiratory distress; Blantyre score ≤ 2; ≥ 2 seizures in 24 h prior to admission, emergency room and hospitalisation; hypoglycaemia < 2.2 mmol/L; acidosis BE ≤ -10.0 mmol/L,l < 5.0 mmol/L; anaemia<5.0 g/dL. Comorbidities = radiographically proven pneumonia; meningitis; positive blood culture on a blood culture taken within 72 h of admission; gastroenteritis with dehydration. Analysis was performed in a pooled manner across age categories. Results presented are uncorrected for double enrollment of one subject in 5-17 months age category receiving GSK257049 vaccine.

Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1

SPFMI of PCD = PFMI>5000 parasites/μL, at least one severity marker and no co-morbidity diagnosis. SPFMI of SCD1 = PFMI>5000 parasites/μL and with one or more severity marker. Severity markers = prostration; respiratory distress; Blantyre score ≤ 2; ≥ 2 seizures in 24h prior to admission, emergency room and hospitalisation; hypoglycaemia<2.2 mmol/L; acidosis BE ≤ -10.0 mmol/L,l ≥ 5.0 mmol/L; anaemia<5.0 g/dL. Comorbidities = radiographically proven pneumonia; meningitis; positive blood culture on a blood culture taken within 72h of admission; gastroenteritis with dehydration. SPFMI of SCD1 = PFMI>5000 parasites/μL and with one or more severity marker. Severity markers = prostration; respiratory distress; Blantyre score ≤ 2; ≥ 2 seizures in 24h prior to admission, emergency room and hospitalisation; hypoglycaemia<2.2 mmol/L; acidosis BE ≤ -10.0 mmol/L,l ≥ 5.0 mmol/L; anaemia<5.0 g/dL. Results presented are uncorrected for double enrollment of one subject in 5-17 months age category.

Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1

SPFMI of PCD = PFMI >5000 parasites/μL, at least one severity marker and no co-morbidity diagnosis. SPFMI of SCD1 = PFMI >5000 parasites/μL and with one or more severity marker. Severity markers = prostration; respiratory distress; Blantyre score ≤ 2; ≥ 2 seizures in 24 h prior to admission, emergency room and hospitalisation; hypoglycaemia<2.2 mmol/L; acidosis BE ≤ -10.0 mmol/L,l ≥ 5.0 mmol/L; anaemia<5.0 g/dL. Comorbidities = radiographically proven pneumonia; meningitis; positive blood culture on a blood culture taken within 72 h of admission; gastroenteritis with dehydration. SPFMI of SCD1 = PFMI >5000 parasites/μL and with one or more severity marker. Severity markers = prostration; respiratory distress; Blantyre score ≤ 2; ≥ 2 seizures in 24 h prior to admission, emergency room and hospitalisation; hypoglycaemia<2.2 mmol/L; acidosis BE ≤ -10.0 mmol/L,l ≥ 5.0 mmol/L; anaemia<5.0 g/dL.

Percentage of Subjects With Incident Severe Anaemia (ISA) and Malaria Hospitalization (MH) for Case Definitions (CD) Considered

CD considered were CD1 for ISA and CD1 and CD2 for MH. ISA of CD1 was defined as a documented hemoglobin < 5.0 g/dL identified at clinical presentation to morbidity surveillance system in association with a P. falciparum parasitemia > 5000 parasites/μL. MH of CD1 was defined as a medical hospitalization with confirmed P. falciparum > 5000 parasites/μL. MH of CD2 was defined as a hospitalization which, in the judgment of the principal investigator, P. falciparum infection was the sole or a major contributing factor to the presentation. Results presented are uncorrected for double enrollment of one subject in 5-17 months age category receiving GSK257049 vaccine.

Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered

ISA CD considered were CD1, CD2 and CD3 (definitions mentioned in the previous outcome measure). MH CD considered were CD1 and CD2 (definitions mentioned in the previous outcome measure).FM CD considered were primary CD (PCD) and sedondary CDs 1 and 4 (SCD1 and SCD4). FM of PCD was defined as a case of severe malaria meeting the primary case definition of severe malaria disease with a fatal outcome. FM of SCD1 was defined as a case of severe malaria meeting the secondary case definition 1 severe malaria disease with a fatal outcome. FM of SCD4 was defined as a fatal case associated with International Classification Disease (ICD10) codes B50, B53 and/or B54. Code B50 corresponds to P. falciparum malaria including mixed infections of P. falciparum with any other Plasmodium species; Code B53 corresponds to other parasitologically confirmed malaria; Code B54 corresponds to unspecified malaria including clinically diagnosed malaria without parasitological confirmation.

Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered

Percentage of Subjects With Prevalent Parasitemia, Prevalent Gametocytemia and Prevalent Severe and Moderate Anemia

Prevalent parasitemia (PP) was defined as a documented P. falciparum asexual parasite density > 0 identified at timing of assessment. Prevalent gametocytemia (PG) was defined as a documented P. falciparum gametocyte density > 0 identified at a cross sectional survey. Prevalent severe anemia (PSA) was defined as a documented hemoglobin < 5.0 g/dL identified at timing of assessment. Prevalent moderate anemia (PMA) was defined as a documented hemoglobin < 8.0 g/dL identified at at timing of assessment. Results presented are uncorrected for the double enrollment of one subject receiving RTS,S/AS01.

Percentage of Subjects With Prevalent Parasitemia and Prevalent Severe and Moderate Anemia

Prevalent parasitemia (PP) was defined as a documented P. falciparum asexual parasite density > 0 identified at timing of assessment. Prevalent severe anemia (PSA) was defined as a documented hemoglobin < 5.0 g/dL identified at timing of assessment. Prevalent moderate anemia (PMA) was defined as a documented hemoglobin < 8.0 g/dL identified at timing of assessment. Analysis was performed on subjects aged 5-17 months at enrollment. Study End (Early) corresponds to children whose Month 32 visit took place after 30 June 2012 and who had one cross-sectional visit at study end. These children's last study visit was relatively earlier, with a median follow-up time of 14 months post Month 32. Study End (Late) corresponds to children whose Month 32 visit took place before (and including) 30 June 2012, and who had 2 cross-sectional visits after Month 32. These children's last study visit was relatively later, with a median follow-up time of 17 months post Month 32).

Percentage of Subjects With Pneumonia, All-cause Hospitalization and Sepsis, as Per Case Definitions Assessed

Pneumonia case definitions assessed are PCD and SCD 1, 2 and 3. Pneumonia of PCD was defined as cough or difficulty breathing AND tachypnea (≥ 50 breaths per minute < 1 year, ≥ 40 breaths per minute ≥ 1year) AND lower chest wall indrawing. Pneumonia of SCD1 was defined as pneumonia of PCD accompanied by chest X-ray (CXR) consolidation or pleural effusion on x-ray taken within 72 h of admission. Pneumonia of SCD2 was defined as pneumonia of PCD accompanied by consolidation or pleural effusion or other infiltrates on a chest x-ray taken within 72 h of admission. Pneumonia of SCD3 was defined as pneumonia of PCD accompanied by an oxygen saturation < 90%. All-cause hospitalization of PCD was defined as a medical hospitalization of any cause (excludes planned admissions for medical investigation/care or elective surgery and trauma). Sepsis cases were defined as a child with positive blood culture (CD1) or salmonella blood culture (CD2).

Percentage of Subjects With Fatal Malaria (FM) and All-cause Mortality (ACM) as Per Case Definitions Assessed

Fatal malaria case definitions assessed were PCD and SCD1. Fatal malaria of PCD was defined as a case of severe malaria meeting the primary case definition of severe malaria disease (defined in a previous outcome measure) with a fatal outcome. Fatal malaria of SCD1 was defined as a case of severe malaria meeting the secondary case definition 1 severe malaria disease (defined previously) with a fatal outcome. All-cause mortality case definitions assessed were the case definitions (CD) 1 and 2. All-cause mortality of CD1 was defined as a fatality (of any cause) (including mortality in the community and in hospital). All-cause mortality of CD2 was defined as a fatality (medical cause) (including mortality in the community and in hospital), at the exclusion of trauma which may be diagnosed by verbal autopsy. Results presented are uncorrected for double enrollment of one subject in 5-17 months age category receiving GSK257049 vaccine.

Percentage of Subjects With Pneumonia, All-cause Hospitalization/Mortality and Sepsis, as Per Case Definitions Assessed

Pneumonia of PCD was defined as cough or difficulty breathing (on history) AND tachypnea (>= 50 breaths per minute < 1 year, >= 40 breaths per minute >= 1year) AND lower chest wall indrawing,SCD1 was defined as pneumonia of PCD accompanied by chest X-ray (CXR) consolidation or pleural effusion on x-ray taken within 72 h of admission,SCD2 was defined as pneumonia of PCD accompanied by consolidation or pleural effusion or other infiltrates on a chest x-ray taken within 72 h of admission,SCD3 was defined as pneumonia of PCD accompanied by an oxygen saturation less than 90%.All-cause hospitalization of PCD was defined as a medical hospitalization of any cause (excluding planned admissions for medical investigation/care or elective surgery and trauma).All-cause mortality of CD1 was defined as a fatality (of any cause),of CD2 defined as a fatality (medical cause).Sepsis of CD1 was defined as a child with positive blood culture;CD2 defined as a child with positive salmonella blood culture.

Percentage of Subjects With Blood Transfusion, as Per Case Definition Assessed

Blood transfusion case definition assessed was the case definition 1 (CD1). Blood transfusion of CD1 was defined as a child with inpatient admission with documented blood transfusion.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Gender and Overall

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T). Analysis was performed on subjects aged 5-17 months and 6-12 weeks at enrollment. Results were presented by gender and overall.

Height, Weight and Mid Upper Arm Circumference for Age Z-score (HAZ, WAZ and MUACZ)

Anthropometry consisted of length/height for age z-score [HAZ] (children < 2 years length measure and children ≥ 2 years standing height measure), weight for age z-score [WAZ] and mid-upper arm circumference for age z-score [MUACZ] measurements, where a HAZ < -1,5 z-score, indicates growth deficit, while a HAZ between -1,0 and ± 1,0 z-score, indicates normal height. A WAZ ≤ -3 z-score indicates a very low weight for age, a WAZ > -3 and ≤ -2 z-score indicates a low weight for age, a WAZ > - 2 z-score indicates normal weight. A MUACZ < -2 z-score indicates children that are wasted, a MUACZ < - 3 z-score indicates severely wasted children. Note: The early study end refers to children whose last visit in the primary study phase (Month 32) was after 30 June 2012 and who by protocol had one cross-sectional study end and to late study end refers to children whose last visit in the primary study phase (Month 32) was after 30 June 2012 and who by protocol had one cross-sectional study end.

Antibody Concentrations Against Plasmodium Falciparum Circumsporozoite (Anti-CS)

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off for the endpoint was a GMC value ≥ 0.5 EL.U/mL. Results were assessed for the first 200 subjects enrolled in each study center.

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS)

Anti-CS antibody concentrations were determined by ELISA and presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. The seropositivity cut-off for the endpoint was a GMC value ≥ 0.5 EL.U/mL. Results were assessed for the first 200 HIV-infected subjects enrolled in each study center. HIV infection was confirmed if present at screening or identified by morbidity surveillance, not infection confirmed by antibody testing after 18 months of age or by PCR, by the time of the analysis of results up to the Month 14 time point for the respective 5-17 months and 6-12 weeks age categories.

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS)

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile

Anti-CS antibody concentrations were determined by ELISA and presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. The seropositivity cut-off for the endpoint was a GMC value ≥ 0.5 EL.U/mL. Results were presented by tertiles of anti-CS responses in the first 200 participants per site, based on subjects assessed for vaccine efficacy results.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T). RaCPFMI was calculated by tertile of anti-CS response post primary vaccination pooled across sites, on subjects in GSK257049-Menjugate Groups (5-17M; 6-12W) and Comparator Groups (5-17M; 6-12W), taking into account the first 200 participants per site.

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile

Anti-CS antibody concentrations were determined by ELISA and presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. The seropositivity cut-off for the endpoint was a GMC value ≥ 0.5 EL.U/mL. Results were presented by tertiles of anti-CS responses in the first 200 participants per site, based on subjects assessed for vaccine efficacy results.

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T). RaCPFMI was calculated by tertile of anti-CS response post booster vaccination pooled across sites, on subjects in R3R (5-17M; 6-12W) (or R3R below) and C3C (5-17M; 6-12W) (or C3C below) groups taking into account the first 200 participants per site.

Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)

Antibody concentrations assessed by ELISA, were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The seropositivity and seroprotection cut-offs were ≥ 10 and 100 mIU/mL, respectively. Results were assessed for the first 200 subjects in each center.

Antibody Concentrations Against Hepatitis B Surface Antigen

Antibody concentrations as assessed by ELISA, were presented as geometric mean concentrations (GMCs), and expressed in mIU/mL. The seropositivity and seroprotection cut-offs were ≥ 10 and 100 mIU/mL, respectively. Results were assessed for the first 200 HIV-infected subjects enrolled in each study center. HIV infection was confirmed if present at screening or identified by morbidity surveillance, not infection confirmed by antibody testing after 18 months of age or by PCR, by the time of the analysis of results up to the Month 14 time point for the respective 5-17 months and 6-12 weeks age categories.

Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)

Antibody Titers Against Poliomyelitis (Anti-polio) Type 1, 2 and 3

Anti-Polio 1, 2 and 3 antibody titers were presented as geometric mean titers (GMTs). The seroprotection cut-off for the assay was an antibody titer ≥ 1:8.

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Assessed solicited local symptoms included pain, redness and swelling. Any = the incidence of a particular symptom, regardless of intensity grade. Grade 3 pain = cried when limb was moved, spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) of injection site.

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Assessed solicited general symptoms were drowsiness, irritability, loss of appetite, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)]. Any = occurrence of the symptom regardless of intensity grade or relationship to vaccination. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever > 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Number of Doses With Seizures by Diagnostic Certainty Level

Diagnostic certainty levels included: Level 1- Witnessed sudden loss of consciousness and generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations; Level 2- History of unconsciousness and generalized, tonic, clonic, tonic-clonic, or atonic motor manifestations; Level 3- History of unconsciousness and other generalized motor manifestations; Level 4- Reported generalized convulsive seizure with insufficient evidence to meet the case definition; Level 5- Not a case of generalized convulsive seizure.

Number of Subjects Reporting Mucocutaneous Changes (All Levels)

Levels of mucocutaneous changes reported were: cutaneous and mucosal change; cutaneous only change; mucosal only change; cutaneous change focused on the nappy/diaper area. Mucocutaneous changes results calculated based on the first 200 subjects in the 6-12 weeks age category in each study center were enrolled, and with available data (i.e. who received a booster dose).

Number of Subjects Reporting Any Meningitis and Encephalitis Serious Adverse Events (SAEs)

Meningitis and encephalitis SAEs included: meningitis/encephalitis; meningitis/encephalitis viral; meningism; meningitis haemophilus; meningitis meningococcal; meningitis pneumococcal; meningitis tuberculous; encephalomyelitis.

Number of Subjects Reporting Any Meningitis and Encephalitis SAEs

Meningitis and encephalitis SAEs included: meningitis/encephalitis; meningitis haemophilus; meningitis meningococcal; meningitis tuberculous; encephalomyelitis.

Number of Subjects Reporting Any Potential Immune-mediated Disorders (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 aetiology.

Number of Subjects With Any Unsolicited Adverse Events (AEs)

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal

Number of Subjects With Any Unsolicited AEs

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = AE assessed by the investigator as related to the vaccination. Unsolicited AEs were calculated based on the subgroup of the first 200 subjects enrolled in each study center, who were reported with HIV infected status ((HIV status either as per general medical history taken at screening or as identified by morbidity surveillance).

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal in the Low-weight (LW) and Very Low-weight (VLW) Category

Number of Subjects With Unsolicited AEs Related to Vaccination in the Low-weight (LW) and Very Low-weight (VLW) Category

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = AE assessed by the investigator as related to the vaccination. Unsolicited AEs were calculated based on the subgroup of the first 200 subjects enrolled in each study center. Low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was > -3 and ≤ -2. Very low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was ≤ -3.

Number of Subjects With Serious Adverse Events (SAEs)

Number of Subjects With Serious Adversee Events (SAEs)

Number of Subjects With Serious Adverse Events (SAEs)

Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs)

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was > -3 and ≤ -2.

Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs)

Number of Very Low-weight (VLW) Subjects With Serious Adverse Events (SAEs)

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Very low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was ≤ -3.

Number of Very Low-weight Subjects With Serious Adverse Events (SAEs)

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Very low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was ≤ -3.

Number of Subjects With Fatal Outcomes, by Gender

Mortality was presented as overall mortality (up to Month 20 and up to study end), mortality due to severe malaria as per secondary case definition(SCD), cerebral malaria as per secondary case definition (SCD), meningitis, fatal all-cause traumas and fatal malaria. SCD= Plasmodium falciparum malaria > 5000 parasites/mcL and 1 or more markers of severe malaria (prostration, respiratory distress, Blantyre score ≤ 2, seizures 2 or more, hypoglycemia < 2.2 mmol/L, acidosis BE ≤ -10.0 mmol/L,lactate ≥ 5.0 mmol/L, anemia < 5.0 g/dL.

Full Information

NCT ID

NCT00866619

First Posted

March 19, 2009

Last Updated

September 19, 2019

Sponsor

GlaxoSmithKline

Collaborators

The PATH Malaria Vaccine Initiative (MVI)

1. Study Identification

Unique Protocol Identification Number

NCT00866619

Brief Title

Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa

Official Title

Efficacy of GSK Biologicals' Candidate Malaria Vaccine (257049) Against Malaria Disease Caused by P. Falciparum Infection in Infants and Children in Africa

Study Type

Interventional

2. Study Status

Record Verification Date

September 2019

Overall Recruitment Status

Completed

Study Start Date

March 27, 2009 (Actual)

Primary Completion Date

March 1, 2011 (Actual)

Study Completion Date

January 31, 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

GlaxoSmithKline

Collaborators

The PATH Malaria Vaccine Initiative (MVI)

4. Oversight

5. Study Description

Brief Summary

The purpose of this observer-blind study is to gather key efficacy, safety, and immunogenicity information on GSK's candidate malaria vaccine in infants and children.

Detailed Description

The protocol posting document has been updated due to a protocol amendment dated 23 January 2012. An analysis time point has been added at Month 20. No changes have been made to the protocol endpoints or statistical methods but protocol endpoints will be analysed on data collected up to Month 20 once these data are available. The rationale is to have the full scope of protocol defined efficacy and safety endpoints related to a primary schedule without booster in both age categories followed up for 20 months earlier than at the initially planned study end time point (Visit 34 or Month 32 time point). The protocol posting document was updated due to a protocol amendment dated 10 December 2010 to extend the study until December 2013 for all enrolled subjects (interval: Nov 2013-Jan 2014). Including the extension, the mean follow-up time for subjects from 5-17 months will be during 49 months post dose 1 (range: 41-55), while for subjects from 6-12 weeks, it will be during 41 months post dose 1 (range: 32-48). This study is double-blind during the first part and single-blind during the extension part. An analysis will be conducted at the end of the extension including an evaluation of safety and efficacy against clinical malaria, severe malaria and prevalent parasitemia. The protocol posting document has been updated following the posting of results of the study (January 2015): The study remained double-blind until the end of the extension phase, and the analyses of Month 32 (initial end of study now becoming end of the first part of the study or primary study phase) and of the extension phase were conducted together.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Malaria

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

15459 (Actual)

8. Arms, Groups, and Interventions

Arm Title

GSK257049 [5-17M] Group

Arm Type

Experimental

Arm Description

Arm Title

GSK257049 [6-12W] Group

Arm Type

Experimental

Arm Description

Arm Title

VeroRab Comparator [5-17M] Group

Arm Type

Active Comparator

Arm Description

Arm Title

Menjugate Comparator [6-12W] Group

Arm Type

Experimental

Arm Description

Intervention Type

Biological

Intervention Name(s)

Malaria Vaccine 257049

Intervention Description

administered intramuscularly into the left deltoid.

Intervention Type

Biological

Intervention Name(s)

Meningococcal C Conjugate Vaccine

Other Intervention Name(s)

Menjugate

Intervention Description

administered intramuscularly into the left deltoid.

Intervention Type

Biological

Intervention Name(s)

Cell-culture rabies vaccine

Other Intervention Name(s)

VeroRab

Intervention Description

administered intramuscularly into the left deltoid.

Intervention Type

Biological

Intervention Name(s)

TritanrixHepB/Hib

Intervention Description

administered intramuscularly into the left deltoid.

Intervention Type

Biological

Intervention Name(s)

Polio Sabin Oral Polio Vaccine (GSK)

Intervention Description

administered orally.

Primary Outcome Measure Information:

Title

Rate of First or Only Clinical Episode of Plasmodium Falciparum (P. Falciparum) Malaria Infection (CPFMI), or Clinical Malaria Episode of Primary Case Definition (CPFMI-PCD)

Description

Time Frame

From Month 2.5 to Month 14

Title

Rate of First or Only Clinical Episode of P. Falciparum Malaria Infection (CPFMI), or Clinical Malaria Episode of Primary Case Definition (CPFMI-PCD)

Description

Time Frame

From Month 2.5 to Month 14

Secondary Outcome Measure Information:

Title

Rate of All Episodes of P. Falciparum Clinical Malaria Infection (CPFMI) of PCD and of Secondary Case Definitions (SCD) 1, SCD 2 and SCD 3

Description

Time Frame

From Month 2.5 to Month 14

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, Overall and by Center

Description

Time Frame

From Month 2.5 to Month 20

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of SCD1, SCD2 and SCD3 (Overall)

Description

Time Frame

From Month 2.5 to Month 20

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Centers and Across Centers

Description

Time Frame

From Month 2.5 up to study End (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1), Across Centers

Description

Time Frame

From Month 2.5 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1), Across Centers

Description

Time Frame

From Booster at Month 20 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD and SCD1, Across Centers

Description

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. CPFMI of SCD1 = malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are presented across centers.

Time Frame

From Month 33 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, by Center and Across Centers

Description

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. Time to all CPFMI episodes is expressed as person-year rate in each group (n/T). Results are presented by center and across centers.

Time Frame

From Month 2.5 to Month 32

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1)

Description

CPFMI of SCD1 = malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T).

Time Frame

From Month 2.5 to Month 32

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1)

Description

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. CPFMI of SCD1 = malaria episode with PFAP > 0 and fever at time of presentation or history of fever within 24h of presentation in a subject unwell brought for treatment to a healthcare facility. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T).

Time Frame

From Booster at Month 20 up to Month 32

Title

Percentage of Subjects With Severe PFMI (SPFMI) of PCD, SCD1, SCD2 and SCD3, Across Centers

Description

Time Frame

From Month 2.5 up to the time when 250 subjects were diagnosed with severe malaria of PCD, SCD1, SCD2 and SCD3 (up to the Month 14 time point for each age category or date of booster dose, whichever occurred first)

Title

Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1

Description

Time Frame

From Month 2.5 to Month 14

Title

Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1

Description

Time Frame

From Month 2.5 to Month 20 at Booster

Title

Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1

Description

SPFMI of PCD = PFMI >5000 parasites/μL, at least one severity marker and no co-morbidity diagnosis. SPFMI of SCD1 = PFMI >5000 parasites/μL and with one or more severity marker. Severity markers = prostration; respiratory distress; Blantyre score ≤ 2; ≥ 2 seizures in 24 h prior to admission, emergency room and hospitalisation; hypoglycaemia<2.2 mmol/L; acidosis BE ≤ -10.0 mmol/L,l ≥ 5.0 mmol/L; anaemia<5.0 g/dL. Comorbidities = radiographically proven pneumonia; meningitis; positive blood culture on a blood culture taken within 72 h of admission; gastroenteritis with dehydration. SPFMI of SCD1 = PFMI >5000 parasites/μL and with one or more severity marker. Severity markers = prostration; respiratory distress; Blantyre score ≤ 2; ≥ 2 seizures in 24 h prior to admission, emergency room and hospitalisation; hypoglycaemia<2.2 mmol/L; acidosis BE ≤ -10.0 mmol/L,l ≥ 5.0 mmol/L; anaemia<5.0 g/dL.

Time Frame

From Month 2.5, from Month 20(booster), from Month 33 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17M age category and of 38 months post-Dose 1 for 6-12W age category) and from Month 2.5 to Month 32 and from Month 20 to Month 32

Title

Percentage of Subjects With Incident Severe Anaemia (ISA) and Malaria Hospitalization (MH) for Case Definitions (CD) Considered

Description

Time Frame

From Month 2.5 to Month 20

Title

Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered

Description

Time Frame

From Month 2.5 to up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Title

Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered

Description

Time Frame

From Month 2.5 to Month 32

Title

Percentage of Subjects With Prevalent Parasitemia, Prevalent Gametocytemia and Prevalent Severe and Moderate Anemia

Description

Time Frame

At Month 20 (Booster)

Title

Percentage of Subjects With Prevalent Parasitemia and Prevalent Severe and Moderate Anemia

Description

Time Frame

At Months 32, 44, at study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category) (early and late)

Title

Percentage of Subjects With Pneumonia, All-cause Hospitalization and Sepsis, as Per Case Definitions Assessed

Description

Time Frame

From Month 2.5 to Month 20

Title

Percentage of Subjects With Fatal Malaria (FM) and All-cause Mortality (ACM) as Per Case Definitions Assessed

Description

Time Frame

From Month 2.5 to Month 20

Title

Percentage of Subjects With Pneumonia, All-cause Hospitalization/Mortality and Sepsis, as Per Case Definitions Assessed

Description

Time Frame

From Month 2.5 up to study end (with a median follow-up time post-Dose 1 of 48 months for 5-17M groups and 38 months for 6-12W groups)

Title

Percentage of Subjects With Blood Transfusion, as Per Case Definition Assessed

Description

Blood transfusion case definition assessed was the case definition 1 (CD1). Blood transfusion of CD1 was defined as a child with inpatient admission with documented blood transfusion.

Time Frame

From Month 2.5 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Gender and Overall

Description

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by the presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T). Analysis was performed on subjects aged 5-17 months and 6-12 weeks at enrollment. Results were presented by gender and overall.

Time Frame

From Month 2.5 to Month 32

Title

Height, Weight and Mid Upper Arm Circumference for Age Z-score (HAZ, WAZ and MUACZ)

Description

Time Frame

At Month 20 (Booster)

Title

Height, Weight and Mid Upper Arm Circumference for Age Z-score (HAZ, WAZ and MUACZ)

Description

Time Frame

At Months 32, 44, at study end (early and late) (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Antibody Concentrations Against Plasmodium Falciparum Circumsporozoite (Anti-CS)

Description

Time Frame

At Day 0 and at Month 3

Title

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS)

Description

Time Frame

At Day 0 and at Month 3

Title

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS)

Description

Time Frame

At Months 20, 21 and 32

Title

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS)

Description

Time Frame

At Month 44 and at study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile

Description

Anti-CS antibody concentrations were determined by ELISA and presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. The seropositivity cut-off for the endpoint was a GMC value ≥ 0.5 EL.U/mL. Results were presented by tertiles of anti-CS responses in the first 200 participants per site, based on subjects assessed for vaccine efficacy results.

Time Frame

At Month 3

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile

Description

Time Frame

From Month 2.5 to Month 32

Title

Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile

Description

Anti-CS antibody concentrations were determined by ELISA and presented as geometric mean concentrations (GMCs), expressed in EL.U/mL. The seropositivity cut-off for the endpoint was a GMC value ≥ 0.5 EL.U/mL. Results were presented by tertiles of anti-CS responses in the first 200 participants per site, based on subjects assessed for vaccine efficacy results.

Time Frame

At Month 21

Title

Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile

Description

CPFMI of PCD = episode of malaria for which PFAP > 5000 parasites/µL accompanied by presence of fever (axillary temperature ≥ 37.5°C at time of presentation) AND occurring in a child unwell brought for treatment to a healthcare facility OR a case of malaria meeting the PCD of severe malaria disease. Time to all episodes of CPFMI is expressed as a rate of all CPFMI (RaCPFMI), that is, person-year rate in each group (n/T). RaCPFMI was calculated by tertile of anti-CS response post booster vaccination pooled across sites, on subjects in R3R (5-17M; 6-12W) (or R3R below) and C3C (5-17M; 6-12W) (or C3C below) groups taking into account the first 200 participants per site.

Time Frame

From Booster at Month 20 to Month 32

Title

Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)

Description

Time Frame

At Day 0 and at Month 3

Title

Antibody Concentrations Against Hepatitis B Surface Antigen

Description

Time Frame

At Day 0 and at Month 3

Title

Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs)

Description

Time Frame

At Months 20 and 21

Title

Antibody Titers Against Poliomyelitis (Anti-polio) Type 1, 2 and 3

Description

Anti-Polio 1, 2 and 3 antibody titers were presented as geometric mean titers (GMTs). The seroprotection cut-off for the assay was an antibody titer ≥ 1:8.

Time Frame

At Day 0 and at Month 3

Title

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Description

Time Frame

During the 7-day (Days 0-6) post-primary vaccination period following each dose and across doses

Title

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Description

Time Frame

During the 7-day (Days 0-6) post-primary vaccination period following each dose and across doses

Title

Number of Subjects With Any and Grade 3 Solicited Local Symptoms

Description

Time Frame

During the 7-day (Days 0-6) post-booster vaccination period

Title

Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms

Description

Time Frame

During the 7-day (Days 0-6) post-booster vaccination period

Title

Number of Doses With Seizures by Diagnostic Certainty Level

Description

Time Frame

During the 7-day (Days 0-6) post-booster vaccination period, at Month 20 + 7 Day (Days 0-6)

Title

Number of Subjects Reporting Mucocutaneous Changes (All Levels)

Description

Time Frame

During the 30-day (Days 0-29) post-booster vaccination

Title

Number of Subjects Reporting Any Meningitis and Encephalitis Serious Adverse Events (SAEs)

Description

Time Frame

At Month 0 until study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Number of Subjects Reporting Any Meningitis and Encephalitis SAEs

Description

Meningitis and encephalitis SAEs included: meningitis/encephalitis; meningitis haemophilus; meningitis meningococcal; meningitis tuberculous; encephalomyelitis.

Time Frame

From Booster up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Number of Subjects Reporting Any Potential Immune-mediated Disorders (pIMDs)

Description

Time Frame

From Month 0 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Number of Subjects With Any Unsolicited Adverse Events (AEs)

Description

Time Frame

Within the 30-day (Days 0-29) post-primary vaccination period

Title

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal

Description

Time Frame

Within the 30-day (Days 0-29) post-primary vaccination period

Title

Number of Subjects With Any Unsolicited AEs

Description

Time Frame

Within the 30-day (days 0-29) post-booster vaccination period

Title

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal

Description

Time Frame

Within the 30-day (Days 0-29) post-primary and post-booster vaccination period in HIV-infected children

Title

Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal in the Low-weight (LW) and Very Low-weight (VLW) Category

Description

Time Frame

Within the 30-day (Days 0-29) post-primary vaccination period in HIV-infected children

Title

Number of Subjects With Unsolicited AEs Related to Vaccination in the Low-weight (LW) and Very Low-weight (VLW) Category

Description

An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Related = AE assessed by the investigator as related to the vaccination. Unsolicited AEs were calculated based on the subgroup of the first 200 subjects enrolled in each study center. Low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was > -3 and ≤ -2. Very low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was ≤ -3.

Time Frame

Within the 30-day (Days 0-29) post-booster vaccination period

Title

Number of Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

From Month 0 up to Month 14

Title

Number of Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

During the 30-day (Days 0-29) post-primary vaccination period

Title

Number of Subjects With Serious Adversee Events (SAEs)

Description

Time Frame

From Month 0 up to Month 20

Title

Number of Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

From Booster (at Month 20) up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Number of Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

From Month 0 up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Number of Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

Within the 30-day (Days 0-29) post-booster vaccination period

Title

Number of Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

From Month 0 up to Booster (Month 20), from Month 0 up to study end and from Month 20 up to study end

Title

Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

From Month 0 up to Month 20

Title

Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs)

Description

Time Frame

From Booster (Month 20) up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

Title

Number of Very Low-weight (VLW) Subjects With Serious Adverse Events (SAEs)

Description

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Very low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was ≤ -3.

Time Frame

From Month 0 up to Month 20

Title

Number of Very Low-weight Subjects With Serious Adverse Events (SAEs)

Description

Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. Very low-weight subjects were defined as subjects whose weight for age z-score (WAZ) was ≤ -3.

Time Frame

From Booster (Month 20) up to study end (median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)]

Title

Number of Subjects With Fatal Outcomes, by Gender

Description

Time Frame

From Month 0 up to study end (SE - median follow-up time of 48 months post-Dose 1 for 5-17 months age category and of 38 months post-Dose 1 for 6-12 weeks age category)

10. Eligibility

Sex

All

Minimum Age & Unit of Time

6 Weeks

Maximum Age & Unit of Time

17 Months

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: All subjects must satisfy the following criteria at study entry: A male or female child of:5-17 months (inclusive) of age at time of first vaccination,or between 6-12 weeks of age at time of first vaccination and NOT have already received a dose of vaccine against diphtheria, tetanus or pertussis or Hemophilus influenzae type B and must be > 28 days of age at screening. Signed informed consent or thumb-printed and witnessed informed consent obtained from the parent(s)/guardian(s) of the child. Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol. All subjects must satisfy the following criteria at the start of the extension phase: Subjects who were enrolled and who received at least one vaccine dose in the primary trial phase. Subjects who were present for Visit 35 on or before 30 September 2013. Subjects who the investigator believes that their parents/guardians can and will comply with the requirements of the protocol (e.g. return for follow-up visits) should be enrolled in the study. Exclusion Criteria: The following criteria should be checked at the time of study entry. If any apply, the subject must not be included in the study: Acute disease at the time of enrollment. Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality. Anemia associated with clinical signs or symptoms of decompensation or hemoglobin ≥ 5.0 g/dL. Major congenital defects. History of allergic reactions, significant IgE-mediated events or anaphylaxis to previous immunizations. Children with a past history of a neurological disorder or atypical febrile seizure. Children with malnutrition requiring hospital admission. Children currently meeting the criteria for HIV disease of Stage III or Stage IV severity as defined by the World Health Organization. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine. Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to a drug or vaccine that is not licensed for that indication with the exception of studies with the objective of improving the drug treatment or clinical management of severe malaria disease. Use of a drug or vaccine that is not approved for that indication other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period. Previous participation in any other malaria vaccine trial. Receipt of a vaccine within the preceding 7 days. Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial. Any other findings that the investigator feels would result in data collected being incomplete or of poor quality

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

Lambaréné

Country

Gabon

Facility Name

GSK Investigational Site

City

Kintampo

Country

Ghana

Facility Name

GSK Investigational Site

City

Kumasi

Country

Ghana

Facility Name

GSK Investigational Site

City

Kilifi

ZIP/Postal Code

80108

Country

Kenya

Facility Name

GSK Investigational Site

City

Kisumu

Country

Kenya

Facility Name

GSK Investigational Site

City

Lilongwe

Country

Malawi

Facility Name

GSK Investigational Site

City

Maputo

Country

Mozambique

Facility Name

GSK Investigational Site

City

Dar-es-Salaam

Country

Tanzania

Facility Name

GSK Investigational Site

City

Tanga

Country

Tanzania

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

IPD for this study will be made available via the Clinical Study Data Request site.

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

http://clinicalstudydatarequest.com

Citations:

PubMed Identifier

23136909

Citation

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22007715

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Links:

URL

https://www.clinicalstudydatarequest.com

Description

Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Available IPD and Supporting Information:

Available IPD/Information Type

Informed Consent Form

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

110021

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Individual Participant Data Set

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

110021

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Study Protocol

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

110021

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Dataset Specification

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

110021

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Clinical Study Report

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

110021

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Available IPD/Information Type

Statistical Analysis Plan

Available IPD/Information URL

https://www.clinicalstudydatarequest.com

Available IPD/Information Identifier

110021

Available IPD/Information Comments

For additional information about this study please refer to the GSK Clinical Study Register

Learn more about this trial

Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa

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Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa

Malaria

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial