Phase 3
Completed N=15,459
Efficacy of GSK Biologicals' Candidate Malaria Vaccine 257049 Against Malaria Disease in Infants and Children in Africa
Source: ClinicalTrials.gov NCT00866619 ↗Enrolled (actual)
15,459
Serious AEs
26.7%
Results posted
Oct 2019
Primary outcomePrimary: 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) — 0.435; 0.833 events per person-year — p=<0.0001
◆ Published Evidence
Emerging
12citations · ~3 / year
Transcriptional correlates of malaria in RTS,S/AS01-vaccinated African children: a matched case-control study.
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.
Linked Publications (5)
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Transcriptional correlates of malaria in RTS,S/AS01-vaccinated African children: a matched case-control study.
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Potential effect modification of RTS,S/AS01 malaria vaccine efficacy by household socio-economic status.
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Understanding the role of serological and clinical data on assessing the dynamic of malaria transmission: a case study of Bagamoyo district, Tanzania.
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Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials?
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Can incorporating genotyping data into efficacy estimators improve efficiency of early phase malaria vaccine trials?
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 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) |
0.435; 0.833 | <0.0001 sig |
| PRIMARY Rate of First or Only Clinical Episode of P. Falciparum Malaria Infection (CPFMI), or Clinical Malaria Episode of Primary Case Definition (CPFMI-PCD) |
0.367; 0.484 | <0.0001 sig |
| SECONDARY 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 |
0.735; 0.639; 1.468; 0.908; 1.224; 0.989 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, Overall and by Center |
0.56; 0.64; 1.16; 0.79; 0.1; 0.08 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of SCD1, SCD2 and SCD3 (Overall) |
1.09; 1.09; 1.78; 1.42; 0.78; 0.81 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Centers and Across Centers |
0.02; 0.03; 0.08; 0.06; 0.04; 0.04 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1), Across Centers |
1.26; 1.41; 1.81; 1.29; 1.43; 1.61 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1), Across Centers |
0.87; 1.03; 1.1; 1.01; 1.21; 1.23 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD and SCD1, Across Centers |
1.01; 1.1; 1.1; 1.18; 1.31; 1.29 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of PCD, by Center and Across Centers |
0.03; 0.04; 0.09; 0.06; 0.04; 0.05 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Secondary Case Definition 1 (SCD1) |
1.1; 1.24; 1.78; 1.19; 1.33; 1.54 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD) and Secondary Case Definition 1 (SCD1) |
0.72; 0.96; 1.1; 0.91; 1.15; 1.2 | — |
| SECONDARY Percentage of Subjects With Severe PFMI (SPFMI) of PCD, SCD1, SCD2 and SCD3, Across Centers |
0.019; 0.03; 0.023; 0.036; 0.023; 0.034 | — |
| SECONDARY Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1 |
0.04; 0.06; 0.06; 0.04; 0.04; 0.05 | — |
| SECONDARY Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1 |
0.04; 0.06; 0.06; 0.04; 0.04; 0.05 | — |
| SECONDARY Percentage of Subjects With Severe PFMI (SPFMI) of PCD and SCD1 |
0.04; 0.06; 0.06; 0.04; 0.04; 0.05 | — |
| SECONDARY Percentage of Subjects With Incident Severe Anaemia (ISA) and Malaria Hospitalization (MH) for Case Definitions (CD) Considered |
0.01; 0.01; 0.01; 0.01; 0.05; 0.04 | — |
| SECONDARY Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered |
0.01; 0.01; 0.01; 0.1; 0.01; 0.01 | — |
| SECONDARY Percentage of Subjects With Incident Severe Anaemia (ISA), Malaria Hospitalization (MH) and Fatal Malaria (FM) for Case Definitions (CD) Considered |
0.01; 0.01; 0.01; 0.1; 0.01; 0.01 | — |
| SECONDARY Percentage of Subjects With Prevalent Parasitemia, Prevalent Gametocytemia and Prevalent Severe and Moderate Anemia |
0.07; 0.07; 0.11; 0.08; 0; 0 | — |
| SECONDARY Percentage of Subjects With Prevalent Parasitemia and Prevalent Severe and Moderate Anemia |
0.09; 0.1; 0.14; 0.09; 0.11; 0.1 | — |
| SECONDARY Percentage of Subjects With Pneumonia, All-cause Hospitalization and Sepsis, as Per Case Definitions Assessed |
0.03; 0.04; 0.03; 0.04; 0.01; 0.01 | — |
| SECONDARY Percentage of Subjects With Fatal Malaria (FM) and All-cause Mortality (ACM) as Per Case Definitions Assessed |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Subjects With Pneumonia, All-cause Hospitalization/Mortality and Sepsis, as Per Case Definitions Assessed |
0.21; 0.22; 0.24; 0.23; 0.23; 0.24 | — |
| SECONDARY Percentage of Subjects With Blood Transfusion, as Per Case Definition Assessed |
0.03; 0.03; 0.04; 0.03; 0.03; 0.04 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Gender and Overall |
0.72; 0.8; 1.11; 0.76; 0.79; 1.06 | — |
| SECONDARY Height, Weight and Mid Upper Arm Circumference for Age Z-score (HAZ, WAZ and MUACZ) |
-1.3; -1.4; -1.4; -1.5; -1.4; -1.5 | — |
| SECONDARY Height, Weight and Mid Upper Arm Circumference for Age Z-score (HAZ, WAZ and MUACZ) |
-1.3; -1.4; -1.4; -1.5; -1.4; -1.5 | — |
| SECONDARY Antibody Concentrations Against Plasmodium Falciparum Circumsporozoite (Anti-CS) |
0.3; 0.4; 0.3; 0.4; 621; 210.5 | — |
| SECONDARY Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS) |
27.7; 17.9; 0.3; 23.2; 17.2; 0.3 | — |
| SECONDARY Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS) |
27.7; 17.9; 0.3; 23.2; 17.2; 0.3 | — |
| SECONDARY Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS) |
27.7; 17.9; 0.3; 23.2; 17.2; 0.3 | — |
| SECONDARY Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile |
138.15; 47.99; 311.35; 194.85; 675.24; 479.44 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile |
0.68; 1.21; 0.99; 0.94; 0.68; 1.21 | — |
| SECONDARY Antibody Concentrations Against P. Falciparum Circumsporozoite (Anti-CS), by Tertile |
138.15; 47.99; 311.35; 194.85; 675.24; 479.44 | — |
| SECONDARY Rate of All Episodes of Clinical P. Falciparum Malaria Infection (CPFMI) of Primary Case Definition (PCD), by Tertile |
0.68; 1.21; 0.99; 0.94; 0.68; 1.21 | — |
| SECONDARY Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) |
5068.5; 1532.5; 95206.4; 116458.1 | — |
| SECONDARY Antibody Concentrations Against Hepatitis B Surface Antigen |
98.6; 7.5; 63.6; 5; 37476.5; 1996.2 | — |
| SECONDARY Antibody Concentrations Against Hepatitis B Surface Antigen (Anti-HBs) |
5068.5; 1532.5; 95206.4; 116458.1 | — |
| SECONDARY Antibody Titers Against Poliomyelitis (Anti-polio) Type 1, 2 and 3 |
47.4; 43.3; 334.9; 417.6; 38.6; 40.3 | — |
| SECONDARY Number of Subjects With Any and Grade 3 Solicited Local Symptoms |
109; 45; 41; 59; 29; 25 | — |
| SECONDARY Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms |
55; 22; 21; 33; 19; 15 | — |
| SECONDARY Number of Subjects With Any and Grade 3 Solicited Local Symptoms |
109; 45; 41; 59; 29; 25 | — |
| SECONDARY Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms |
55; 22; 21; 33; 19; 15 | — |
| SECONDARY Number of Doses With Seizures by Diagnostic Certainty Level |
1; 1; 0; 1; 0; 0 | — |
| SECONDARY Number of Subjects Reporting Mucocutaneous Changes (All Levels) |
64; 47; 59 | — |
| SECONDARY Number of Subjects Reporting Any Meningitis and Encephalitis Serious Adverse Events (SAEs) |
15; 12; 5; 7; 8; 7 | — |
| SECONDARY Number of Subjects Reporting Any Meningitis and Encephalitis SAEs |
4; 4; 0; 0; 2; 3 | — |
| SECONDARY Number of Subjects Reporting Any Potential Immune-mediated Disorders (pIMDs) |
5; 1; 4; 3; 1; 2 | — |
| SECONDARY Number of Subjects With Any Unsolicited Adverse Events (AEs) |
1273; 1161; 626; 600 | — |
| SECONDARY Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal |
13; 0; 0; 3; 0; 2 | — |
| SECONDARY Number of Subjects With Any Unsolicited AEs |
232; 205; 215; 231; 239; 240 | — |
| SECONDARY Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal |
13; 0; 0; 3; 0; 2 | — |
| SECONDARY Number of Subjects With Unsolicited AEs Related to or Leading to Vaccination Withdrawal in the Low-weight (LW) and Very Low-weight (VLW) Category |
68; 38; 21; 17; 27; 24 | — |
| SECONDARY Number of Subjects With Unsolicited AEs Related to Vaccination in the Low-weight (LW) and Very Low-weight (VLW) Category |
4; 1; 0; 2; 0; 0 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) |
43; 39; 36; 47; 46; 42 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) |
43; 39; 36; 47; 46; 42 | — |
| SECONDARY Number of Subjects With Serious Adversee Events (SAEs) |
1108; 959; 676; 503 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) |
43; 39; 36; 47; 46; 42 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) |
43; 39; 36; 47; 46; 42 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) |
43; 39; 36; 47; 46; 42 | — |
| SECONDARY Number of Subjects With Serious Adverse Events (SAEs) |
43; 39; 36; 47; 46; 42 | — |
| SECONDARY Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs) |
32; 40; 38; 34; 21; 24 | — |
| SECONDARY Number of Low-weight (LW) Subjects With Serious Adverse Events (SAEs) |
32; 40; 38; 34; 21; 24 | — |
| SECONDARY Number of Very Low-weight (VLW) Subjects With Serious Adverse Events (SAEs) |
55; 48; 28; 17 | — |
| SECONDARY Number of Very Low-weight Subjects With Serious Adverse Events (SAEs) |
5; 8; 11; 6; 9; 15 | — |
| SECONDARY Number of Subjects With Fatal Outcomes, by Gender |
27; 20; 14; 20; 24; 13 | — |
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
Data sourced from ClinicalTrials.gov (NCT00866619) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.