Efficacy of RTS,S/AS01 Vaccine Against Episodes of Malaria Due to P. Falciparum Infection in Children.

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00380393
• Collaborator: (none)
• Enrollment: 894
• Locations: 2
• Arms: 2
• Actual Duration (Months): 22.3
• Patients Per Site: 447
• Patients Per Site Per Month: 20.1

Study Details

Study Description

Brief Summary

This phase IIb trial is being done to find out if the RTS,S/AS01 vaccine helps to prevent children from falling ill with malaria and to evaluate vaccine safety.

The Protocol Posting has been updated in order to comply with the FDA Amendment Act, Sep 2007.

Condition or Disease	Intervention/Treatment	Phase
Malaria	Biological: GSK malaria vaccine 257049 Vaccine; Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 894 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: A Study of the Efficacy Against Episodes of Clinical Malaria Due to P. Falciparum Infection of GSK Biologicals Candidate Vaccine RTS,S/AS01, Administered According to a 0,1,2-months Schedule in Children Aged 5 to 17 Months Living in Tanzania & Kenya
• Actual Study Start Date: Jan 3, 2007
• Actual Primary Completion Date: Aug 15, 2008
• Actual Study Completion Date: Nov 11, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GSK257049 Group Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Biological: GSK malaria vaccine 257049 Vaccine; 3 dose intramuscular injection; Other Names: RTS S/AS01E vaccine
Active Comparator: Rabipur Group Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Biological: Sanofi-Pasteur's Human Diploid Cell Rabies Vaccine; 3 dose intramuscular injection

Outcome Measures

Primary Outcome Measures

1. Frequency of First Case of Malaria Meeting the Primary Case Definition [Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)]

   The first case of malaria meeting the primary case definition was defined as the first or only episodes with the presence of Plasmodium falciparum asexual parasitemia above (>) 2500 per microliter (μL) and the presence of fever greater than or equal to (≥) 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

Secondary Outcome Measures

1. Frequency of First Case Malaria Meeting the Secondary Case Definition [Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)]

   The first case of malaria meeting the secondary case definition was defined as the first or only episodes with the presence of P.falciparum asexual parasitemia > 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

2. Multiple Events of Malaria Meeting the Primary Case Definition [Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)]

   Multiple episodes of malaria meeting the primary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia > 25000 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of primary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

3. Multiple Events of Malaria Meeting the Secondary Case Definition [Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)]

   Multiple episodes of malaria meeting the secondary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia > 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of secondary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.

4. Number of Subjects Positive for P. Falciparum Parasitaemia [At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)]

5. Geometric Mean Density of Asexual P. Falciparum Parasite [At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)]

   Estimates of asexual P. falciparum parasite density were made at the investigator's sites according to laboratory standard operating procedures. Parasite density was presented as a geometric mean (GMean), expressed in parasite per microliters (μL).

6. Haemoglobin Values at Cross-Sectional Visit [At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)]

   Haemoglobin values are expressed in grams per deciliter (g/dL).

7. Number of Subjects With Any and Grade 3 Solicited Local Symptoms [During the 7-day (Days 0-6) post-vaccination period following each dose and across doses]

   Assessed solicited local symptoms were pain and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 20 millimeters (mm) of injection site.

8. Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms [During the 7-day (Days 0-6) post-vaccination period following each dose and across doses]

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

9. Number of Subjects With Any Unsolicited Adverse Events (AEs) [Within the 30-day (Days 0-29) post-vaccination follow-up period]

   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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.

10. Number of Subjects With Serious Adverse Events (SAEs) [Throughout the study period (Day 0 - Month 14)]

    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.

11. Number of Subjects With Hemoglobin Values Outside Normal Ranges With Toxicity Grades [At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)]

    Definitions for toxicity grading for hemoglobin were: Normal Hemoglobin = equal to or above (≥) 8.0 g/dL; Grade 1 Hemoglobin = under (<) 8.0 g/dL and above (>) 6.0 g/dL.; Grade 2 Hemoglobin = under (<) 6.0 g/dL.

12. Number of Subjects With White Blood Cell (WBC) Values Outside Normal Ranges With Toxicity Grades [At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)]

    Definitions for toxicity grading for WBC were: Normal WBC = ≥ 4.0 x 10^3 cells per microliters (cells/μL) or < 17 x 10^3 cells /μL; Grade 1 WBC = 2.5 to 4.0 x 10^3 cells/μL.

13. Number of Subjects With Platelet Values Outside Normal Ranges With Toxicity Grades [At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)]

    Definitions for toxicity grading for platelets were: Normal Platelets = ≥ 75 x 10^3 cells/μL; Grade 1 Platelets = 50 to 74 x 10^3 /μL; Grade 2 Platelets = 25 to 49 x 10^3 /μL; Grade 3 Platelets = < 25 x 10^3 /μL.

14. Number of Subjects With Alanine Aminotransferase (ALT) Values Outside Normal Ranges With Toxicity Grades [At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)]

    Definition for toxicity grading for ALT were: Normal ALT = ≤ 60 international units per liter (IU/L); Grade 1 ALT = 1.1 to 2.5 x Upper Limit of Normal (ULN); Grade 2 ALT = 2.6 to 5.0 x ULN.

15. Number of Subjects With Creatinine Values Outside Normal Ranges With Toxicity Grades [At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)]

    Definition for toxicity grading for creatinine were: Normal Creatinine = ≤ 60 micromols per liter (μmol/L); Grade 1 Creatinine = 1.1 to 1.5 x ULN; Grade 2 Creatinine = 1.6 to 3.0 x ULN.

16. Concentration of Antibodies Against the P. Falciparum Circumsporozoite (CS) Repeat Domain (Anti-CS) [At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)]

    Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).

17. Concentration of Antibodies Against Hepatitis B Surface Antigen (Anti-HBs) [At Day 0 and at Month 3]

    Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).

18. Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells [Prior to vaccination (Day 0)]

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

19. Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells [Prior to vaccination (Day 0)]

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

20. Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells [At Month 3]

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

21. Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells [At Month 3]

    T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Months to 17 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• A male or female child of between 5 months and 17 months of age at the time of first vaccination.

• Written or oral, signed 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.

Exclusion Criteria:

• Acute disease at the time of enrolment.

• Serious acute or chronic illness determined by clinical or physical examination and laboratory screening tests.

• Laboratory screening tests for haemoglobin, total white cell count, platelets, ALT and creatinine out of acceptable limits.

• Planned administration/administration of a vaccine not foreseen by the study within 30 days of the first dose of vaccine(s) with the exception of tetanus toxoid or scheduled diphtheria, pertussis or measles vaccine.

• Use of any investigational or non-registered drug or vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.

• Administration of immunoglobulins, blood transfusions or other blood products within the three months preceding the first dose of study vaccine or planned administration during the study period.

• Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs within 6 months prior to the first vaccine dose

• Previous participation in any other malaria vaccine trial.

• Simultaneous participation in any other clinical trial.

• Same sex twin.

• History of allergic reactions (significant IgE-mediated events) or anaphylaxis to previous immunizations.

• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine.

• Any other findings that the investigator feels would increase the risk of having an adverse outcome from participation in the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Kilifi		Kenya	80108
2	GSK Investigational Site	Amani, Tanga		Tanzania

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

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

Publications

• Bejon P, Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Mshamu S, Lang T, Gould J, Dubois MC, Demoitié MA, Stallaert JF, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, von Seidlein L. Efficacy of RTS,S/AS01E vaccine against malaria in children 5 to 17 months of age. N Engl J Med. 2008 Dec 11;359(24):2521-32. doi: 10.1056/NEJMoa0807381. Epub 2008 Dec 8.
• Lang TA, Gould J, von Seidlein L, Lusingu JP, Mshamu S, Ismael S, Liheluka E, Kamuya D, Mwachiro D, Olotu A, Njuguna P, Bejon P, Marsh V, Molyneux C. Approaching the community about screening children for a multicentre malaria vaccine trial. Int Health. 2012 Mar;4(1):47-54. doi: 10.1016/j.inhe.2011.10.003.
• Lusingu J, Olotu A, Leach A, Lievens M, Vekemans J, Olivier A, Benns S, Olomi R, Msham S, Lang T, Gould J, Hallez K, Guerra Y, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Dekker D, Malle L, Ismael S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Ballou WR, Cohen J, Riley EM, Lemnge MM, Marsh K, Bejon P, von Seidlein L. Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children. PLoS One. 2010 Nov 29;5(11):e14090. doi: 10.1371/journal.pone.0014090. Erratum in: PLoS One. 2010; 5(12) doi: 10.1371/annotation/3b62fdef-4cdd-40cc-b69d-69afd2000c4f. PLoS One. 2010;5(12) doi: 10.1371/annotation/0543a689-83a6-4528-92a1-a0f978b47fcb.
• Olotu A, Lusingu J, Leach A, Lievens M, Vekemans J, Msham S, Lang T, Gould J, Dubois MC, Jongert E, Vansadia P, Carter T, Njuguna P, Awuondo KO, Malabeja A, Abdul O, Gesase S, Mturi N, Drakeley CJ, Savarese B, Villafana T, Lapierre D, Ballou WR, Cohen J, Lemnge MM, Peshu N, Marsh K, Riley EM, von Seidlein L, Bejon P. Efficacy of RTS,S/AS01E malaria vaccine and exploratory analysis on anti-circumsporozoite antibody titres and protection in children aged 5-17 months in Kenya and Tanzania: a randomised controlled trial. Lancet Infect Dis. 2011 Feb;11(2):102-9. doi: 10.1016/S1473-3099(10)70262-0. Epub 2011 Jan 13. Erratum in: Lancet Infect Dis. 2011 Mar;11(3):159.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT00380393
• Other Study ID Numbers: 106464
• First Posted: Sep 26, 2006
• Last Update Posted: Jul 3, 2018
• Last Verified: Nov 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by GlaxoSmithKline: Malaria; Plasmodium; RTS; S/AS01; Falciparum
• Additional relevant MeSH terms: Malaria; Vaccines

Study Results

Participant Flow

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Period Title: Month 8 (Cross-sectional Visit)
STARTED	447	447
COMPLETED	398	407
NOT COMPLETED	49	40
Period Title: Month 8 (Cross-sectional Visit)
STARTED	447	447
COMPLETED	390	391
NOT COMPLETED	57	56

Baseline Characteristics

Arm/Group Title	GSK257049 Group	Rabipur Group	Total
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Total of all reporting groups
Overall Participants	447	447	894
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	11.4 (3.6)	11.4 (3.4)	11.4 (3.5)
Sex: Female, Male (Count of Participants)
Female	229 51.2%	222 49.7%	451 50.4%
Male	218 48.8%	225 50.3%	443 49.6%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Frequency of First Case of Malaria Meeting the Primary Case Definition
Description	The first case of malaria meeting the primary case definition was defined as the first or only episodes with the presence of Plasmodium falciparum asexual parasitemia above (>) 2500 per microliter (μL) and the presence of fever greater than or equal to (≥) 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.
Time Frame	Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable for whom data concerning efficacy outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	415	420
With estimate of VE adjusted for covariates	244.77	238.51
With estimate of VE unadjusted for covariates	249.23	242.06

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy
	Estimated Value	52.9
	Confidence Interval	(2-Sided) 95%; 28.1 to 69.1
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was adjusted for site, age, bednet use, area and distance from health center.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine Efficacy
	Estimated Value	55.0
	Confidence Interval	(2-Sided) 95%; 31.4 to 70.4
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was not adjusted for site, age, bednet use, area or distance from health center.

2. Secondary Outcome

Title	Frequency of First Case Malaria Meeting the Secondary Case Definition
Description	The first case of malaria meeting the secondary case definition was defined as the first or only episodes with the presence of P.falciparum asexual parasitemia > 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of first case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.
Time Frame	Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable for whom data concerning efficacy outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	415	420
With estimate of VE adjusted for covariates	244.72	237.21
With estimate of VE unadjusted for covariates	249.17	240.76

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	54.6
	Confidence Interval	(2-Sided) 95%; 31.2 to 70.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was adjusted for site, age, bednet use, area and distance from health center.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	56.5
	Confidence Interval	(2-Sided) 95%; 34.2 to 71.2
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was not adjusted for site, age, bednet use, area or distance from health center.

3. Secondary Outcome

Title	Multiple Events of Malaria Meeting the Primary Case Definition
Description	Multiple episodes of malaria meeting the primary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia > 25000 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of primary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.
Time Frame	Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable for whom data concerning efficacy outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	415	420
With estimate of VE adjusted for covariates	253.69	255.36
With estimate of VE unadjusted for covariates	258.15	259.61

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0003
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	55.8
	Confidence Interval	(2-Sided) 95%; 31.0 to 71.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was adjusted for site, age, bednet use, area and distance from health center.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	57.9
	Confidence Interval	(2-Sided) 95%; 34.3 to 73.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was not adjusted for site, age, bednet use, area and distance from health center.

4. Secondary Outcome

Title	Multiple Events of Malaria Meeting the Secondary Case Definition
Description	Multiple episodes of malaria meeting the secondary case definition was defined as episodes with the presence of P.falciparum asexual parasitemia > 0 per μL and the presence of fever ≥ 37.5°C by active case detection (ACD) or passive case detection (PCD). Number of secondary case of malaria were assessed through estimate of vaccine efficacy (VE) adjusted or unadjusted for covariates, and are expressed in PYAR= number of episodes/Person Years at Risk.
Time Frame	Assessed over average of 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable for whom data concerning efficacy outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	415	420
With estimate of VE adjusted for covariates	253.62	255.06
With estimate of VE unadjusted for covariates	258.07	259.31

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	58.0
	Confidence Interval	(2-Sided) 95%; 34.8 to 73.0
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was adjusted for site, age, bednet use, area and distance from health center.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	GSK257049 Group, Rabipur Group
	Comments	Vaccine efficacy against P. falciparum.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Regression, Cox
	Comments
Method of Estimation	Estimation Parameter	Vaccine efficacy
	Estimated Value	59.5
	Confidence Interval	(2-Sided) 95%; 37.1 to 73.9
	Parameter Dispersion	Type: Value:
	Estimation Comments	Point estimate of VE was not adjusted for site, age, bednet use, area and distance from health center.

5. Secondary Outcome

Title	Number of Subjects Positive for P. Falciparum Parasitaemia
Time Frame	At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable for whom data concerning efficacy outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	380	390
Count of Participants [Participants]	7 1.6%	11 2.5%

6. Secondary Outcome

Title	Geometric Mean Density of Asexual P. Falciparum Parasite
Description	Estimates of asexual P. falciparum parasite density were made at the investigator's sites according to laboratory standard operating procedures. Parasite density was presented as a geometric mean (GMean), expressed in parasite per microliters (μL).
Time Frame	At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable for whom data concerning efficacy outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	380	390
Geometric Mean (95% Confidence Interval) [parasites/μL]	1020	3486

7. Secondary Outcome

Title	Haemoglobin Values at Cross-Sectional Visit
Description	Haemoglobin values are expressed in grams per deciliter (g/dL).
Time Frame	At the Cross-Sectional Visit that took place for each participant at on average 7.8 months post Dose 3 (range 4.3 to 10.3 months)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for efficacy, which included all evaluable for whom data concerning efficacy outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	379	388
Mean (Standard Deviation) [g/dL]	10.32 (1.01)	10.37 (1.03)

8. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms
Description	Assessed solicited local symptoms were pain and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 swelling = swelling spreading beyond 20 millimeters (mm) of injection site.
Time Frame	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available and who had their symptom sheets filled in.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Any Pain, Dose 1	51 11.4%	39 8.7%
Grade 3 Pain, Dose 1	0 0%	0 0%
Swelling Pain, Dose 1	20 4.5%	12 2.7%
Swelling 3 Pain, Dose 1	0 0%	0 0%
Any Pain, Dose 2	45 10.1%	38 8.5%
Grade 3 Pain, Dose 2	0 0%	0 0%
Swelling Pain, Dose 2	6 1.3%	3 0.7%
Swelling 3 Pain, Dose 2	1 0.2%	0 0%
Any Pain, Dose 3	76 17%	80 17.9%
Grade 3 Pain, Dose 3	0 0%	0 0%
Swelling Pain, Dose 3	8 1.8%	1 0.2%
Swelling 3 Pain, Dose 3	2 0.4%	0 0%
Any Pain, Across doses	143 32%	130 29.1%
Grade 3 Pain, Across doses	0 0%	0 0%
Swelling Pain, Across doses	30 6.7%	13 2.9%
Swelling 3 Pain, Across doses	3 0.7%	0 0%

9. Secondary Outcome

Title	Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms
Description	Assessed solicited general symptoms were drowsiness, fever [defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)], irritability and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever higher than (>) 39.0 °C. Related = symptom assessed by the investigator as related to the vaccination.
Time Frame	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available and who had their symptom sheets filled in.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Any Drowsiness, Dose 1	44 9.8%	28 6.3%
Grade 3 Drowsiness, Dose 1	0 0%	0 0%
Related Drowsiness, Dose 1	32 7.2%	27 6%
Any Fever, Dose 1	55 12.3%	138 30.9%
Grade 3 Fever, Dose 1	1 0.2%	2 0.4%
Related Fever, Dose 1	49 11%	133 29.8%
Any Irritability, Dose 1	26 5.8%	12 2.7%
Grade 3 Irritability, Dose 1	0 0%	0 0%
Related Irritability, Dose 1	17 3.8%	8 1.8%
Any Loss of appetite, Dose 1	34 7.6%	28 6.3%
Grade 3 Loss of appetite, Dose 1	0 0%	1 0.2%
Related Loss of appetite, Dose 1	14 3.1%	9 2%
Any Drowsiness, Dose 2	22 4.9%	25 5.6%
Grade 3 Drowsiness, Dose 2	0 0%	1 0.2%
Related Drowsiness, Dose 2	22 4.9%	23 5.1%
Any Fever, Dose 2	56 12.5%	159 35.6%
Grade 3 Fever, Dose 2	3 0.7%	8 1.8%
Related Fever, Dose 2	51 11.4%	156 34.9%
Any Irritability, Dose 2	16 3.6%	7 1.6%
Grade 3 Irritability, Dose 2	0 0%	0 0%
Related Irritability, Dose 2	14 3.1%	7 1.6%
Any Loss of appetite, Dose 2	24 5.4%	13 2.9%
Grade 3 Loss of appetite, Dose 2	0 0%	1 0.2%
Related Loss of appetite, Dose 2	12 2.7%	7 1.6%
Any Drowsiness, Dose 3	15 3.4%	11 2.5%
Grade 3 Drowsiness, Dose 3	0 0%	0 0%
Related Drowsiness, Dose 3	15 3.4%	10 2.2%
Any Fever, Dose 3	38 8.5%	112 25.1%
Grade 3 Fever, Dose 3	1 0.2%	2 0.4%
Related Fever, Dose 3	32 7.2%	107 23.9%
Any Irritability, Dose 3	17 3.8%	2 0.4%
Grade 3 Irritability, Dose 3	0 0%	0 0%
Related Irritability, Dose 3	13 2.9%	1 0.2%
Any Loss of appetite, Dose 3	6 1.3%	2 0.4%
Grade 3 Loss of appetite, Dose 3	0 0%	0 0%
Related Loss of appetite, Dose 3	3 0.7%	0 0%
Any Drowsiness, Across Doses	66 14.8%	59 13.2%
Grade 3 Drowsiness, Across Doses	0 0%	1 0.2%
Related Drowsiness, Across Doses	55 12.3%	56 12.5%
Any Fever, Across Doses	125 28%	268 60%
Grade 3 Fever, Across Doses	5 1.1%	12 2.7%
Related Fever, Across Doses	111 24.8%	262 58.6%
Any Irritability, Across Doses	45 10.1%	19 4.3%
Grade 3 Irritability, Across Doses	0 0%	0 0%
Related Irritability, Across Doses	33 7.4%	14 3.1%
Any Loss of appetite, Across Doses	54 12.1%	40 8.9%
Grade 3 Loss of appetite, Across Doses	0 0%	2 0.4%
Related Loss of appetite, Across Doses	28 6.3%	14 3.1%

10. Secondary Outcome

Title	Number of Subjects With Any Unsolicited Adverse Events (AEs)
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. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
Time Frame	Within the 30-day (Days 0-29) post-vaccination follow-up period

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Count of Participants [Participants]	349 78.1%	332 74.3%

11. Secondary Outcome

Title	Number of 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.
Time Frame	Throughout the study period (Day 0 - Month 14)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Count of Participants [Participants]	51 11.4%	88 19.7%

12. Secondary Outcome

Title	Number of Subjects With Hemoglobin Values Outside Normal Ranges With Toxicity Grades
Description	Definitions for toxicity grading for hemoglobin were: Normal Hemoglobin = equal to or above (≥) 8.0 g/dL; Grade 1 Hemoglobin = under (<) 8.0 g/dL and above (>) 6.0 g/dL.; Grade 2 Hemoglobin = under (<) 6.0 g/dL.
Time Frame	At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Normal	445 99.6%	446 99.8%
Grade 1	1 0.2%	1 0.2%
Grade 2	1 0.2%	0 0%
Missing	0 0%	0 0%
Normal	410 91.7%	413 92.4%
Grade 1	7 1.6%	10 2.2%
Grade 2	0 0%	0 0%
Missing	30 6.7%	24 5.4%
Normal	391 87.5%	397 88.8%
Grade 1	6 1.3%	8 1.8%
Grade 2	0 0%	0 0%
Missing	50 11.2%	42 9.4%

13. Secondary Outcome

Title	Number of Subjects With White Blood Cell (WBC) Values Outside Normal Ranges With Toxicity Grades
Description	Definitions for toxicity grading for WBC were: Normal WBC = ≥ 4.0 x 10^3 cells per microliters (cells/μL) or < 17 x 10^3 cells /μL; Grade 1 WBC = 2.5 to 4.0 x 10^3 cells/μL.
Time Frame	At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Normal	447 100%	447 100%
Grade 1	0 0%	0 0%
Missing	0 0%	0 0%
Normal	416 93.1%	422 94.4%
Grade 1	0 0%	1 0.2%
Missing	31 6.9%	24 5.4%
Normal	395 88.4%	405 90.6%
Grade 1	0 0%	0 0%
Missing	52 11.6%	42 9.4%

14. Secondary Outcome

Title	Number of Subjects With Platelet Values Outside Normal Ranges With Toxicity Grades
Description	Definitions for toxicity grading for platelets were: Normal Platelets = ≥ 75 x 10^3 cells/μL; Grade 1 Platelets = 50 to 74 x 10^3 /μL; Grade 2 Platelets = 25 to 49 x 10^3 /μL; Grade 3 Platelets = < 25 x 10^3 /μL.
Time Frame	At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Normal	445 99.6%	447 100%
Grade 1	1 0.2%	0 0%
Grade 2	0 0%	0 0%
Grade 3	0 0%	0 0%
Missing	1 0.2%	0 0%
Normal	414 92.6%	417 93.3%
Grade 1	1 0.2%	0 0%
Grade 2	2 0.4%	4 0.9%
Grade 3	0 0%	1 0.2%
Missing	30 6.7%	25 5.6%
Normal	386 86.4%	396 88.6%
Grade 1	4 0.9%	1 0.2%
Grade 2	1 0.2%	0 0%
Grade 3	0 0%	0 0%
Missing	56 12.5%	50 11.2%

15. Secondary Outcome

Title	Number of Subjects With Alanine Aminotransferase (ALT) Values Outside Normal Ranges With Toxicity Grades
Description	Definition for toxicity grading for ALT were: Normal ALT = ≤ 60 international units per liter (IU/L); Grade 1 ALT = 1.1 to 2.5 x Upper Limit of Normal (ULN); Grade 2 ALT = 2.6 to 5.0 x ULN.
Time Frame	At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Normal	446 99.8%	447 100%
Grade 1	1 0.2%	0 0%
Grade 2	0 0%	0 0%
Missing	0 0%	0 0%
Normal	413 92.4%	420 94%
Grade 1	1 0.2%	2 0.4%
Grade 2	0 0%	1 0.2%
Missing	33 7.4%	24 5.4%
Normal	393 87.9%	397 88.8%
Grade 1	5 1.1%	8 1.8%
Grade 2	0 0%	1 0.2%
Missing	49 11%	41 9.2%

16. Secondary Outcome

Title	Number of Subjects With Creatinine Values Outside Normal Ranges With Toxicity Grades
Description	Definition for toxicity grading for creatinine were: Normal Creatinine = ≤ 60 micromols per liter (μmol/L); Grade 1 Creatinine = 1.1 to 1.5 x ULN; Grade 2 Creatinine = 1.6 to 3.0 x ULN.
Time Frame	At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	447	447
Normal	447 100%	447 100%
Grade 1	0 0%	0 0%
Grade 2	0 0%	0 0%
Missing	0 0%	0 0%
Normal	415 92.8%	422 94.4%
Grade 1	0 0%	0 0%
Grade 2	0 0%	0 0%
Missing	32 7.2%	25 5.6%
Normal	397 88.8%	405 90.6%
Grade 1	1 0.2%	0 0%
Grade 2	0 0%	1 0.2%
Missing	49 11%	41 9.2%

17. Secondary Outcome

Title	Concentration of Antibodies Against the P. Falciparum Circumsporozoite (CS) Repeat Domain (Anti-CS)
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).
Time Frame	At Day 0, Month 3 and at Cross-sectional Visit (took place between 7 and 13 months post Dose 1, mean: 10 months, standard deviation: 1.29)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	411	419
At Day 0	0.3	0.3
At Month 3	539.6	0.3
At Cross-sectional Visit	71.9	0.3

18. Secondary Outcome

Title	Concentration of Antibodies Against Hepatitis B Surface Antigen (Anti-HBs)
Description	Concentrations are presented as geometric mean concentrations (GMCs), expressed in enzyme-linked immunosorbent assay (ELISA) units per milliliter (EU/mL).
Time Frame	At Day 0 and at Month 3

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	410	419
At Day 0	155.4	187.4
At Month 3	46776.3	168.0

19. Secondary Outcome

Title	Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells
Description	T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).
Time Frame	Prior to vaccination (Day 0)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	168	183
CD4-IFN-γ	15	14
CD4-IL-2	111	113
CD4-TNF-α	94	92

20. Secondary Outcome

Title	Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells
Description	T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).
Time Frame	Prior to vaccination (Day 0)

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	161	165
CD8-IFN-γ	1	37
CD8-IL-2	219	222
CD8-TNF-α	100	82

21. Secondary Outcome

Title	Frequency of Cluster of Differentiation 4 (CD4+) CS-specific T-cells
Description	T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).
Time Frame	At Month 3

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	156	169
CD4-IFN-γ	33	13
CD4-IL-2	648	139
CD4-TNF-α	416	172

22. Secondary Outcome

Title	Frequency of Cluster of Differentiation 8 (CD8+) CS-specific T-cells
Description	T-cells expressing at least one of the following cytokines are presented here: interleukin-2 [IL-2], tumor-necrosis factor-alpha [TNF-α] and interferon-gamma [IFN-γ]. Frequency is expressed in cells/million, as assessed by Intracellular Cytokine Assay (ICA).
Time Frame	At Month 3

Outcome Measure Data

Analysis Population Description

The analyses were performed on the According-To-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures were available.

Arm/Group Title	GSK257049 Group	Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
Measure Participants	143	156
CD8-IFN-γ	36	32
CD8-IL-2	248	219
CD8-TNF-α	201	185

Adverse Events

Time Frame	Solicited local/general symptoms: during the 7-day post-vaccination period (Days 0-6), Unsolicited AEs: during the 30-day post-vaccination period(Days 0-29), SAEs: during the entire study period (Day 0 - Month 14).
Arm/Group Title	GSK257049 Group		Rabipur Group
Arm/Group Description	Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of GSK257049 vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.		Male or female subjects between 5 and 17 months of age at the time of first vaccination received 3 doses of Rabipur vaccine administered intramuscularly in the left deltoid muscle at Days 0, 30 and 60.
All Cause Mortality
	GSK257049 Group		Rabipur Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/447 (0.2%)		0/447 (0%)
Serious Adverse Events
	GSK257049 Group		Rabipur Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	51/447 (11.4%)		88/447 (19.7%)
Blood and lymphatic system disorders
Anaemia	5/447 (1.1%)	5	11/447 (2.5%)	12
Cardiac disorders
Mitral valve disease	1/447 (0.2%)	1	0/447 (0%)	0
Congenital, familial and genetic disorders
Sickle cell anaemia	0/447 (0%)	0	1/447 (0.2%)	1
Sickle cell anaemia with crisis	0/447 (0%)	0	1/447 (0.2%)	1
Ventricular septal defect	1/447 (0.2%)	1	0/447 (0%)	0
Eye disorders
Conjunctivitis	0/447 (0%)	0	1/447 (0.2%)	1
Gastrointestinal disorders
Rectal prolapse	0/447 (0%)	0	2/447 (0.4%)	2
General disorders
Pyrexia	1/447 (0.2%)	1	0/447 (0%)	0
Infections and infestations
Abscess	1/447 (0.2%)	1	0/447 (0%)	0
Acarodermatitis	0/447 (0%)	0	1/447 (0.2%)	1
Bronchiolitis	1/447 (0.2%)	1	3/447 (0.7%)	3
Bronchitis	1/447 (0.2%)	1	1/447 (0.2%)	1
Cellulitis	1/447 (0.2%)	1	1/447 (0.2%)	1
Cerebral malaria	0/447 (0%)	0	3/447 (0.7%)	3
Cholera	1/447 (0.2%)	1	2/447 (0.4%)	2
Dysentery	2/447 (0.4%)	2	1/447 (0.2%)	1
Escherichia sepsis	1/447 (0.2%)	1	0/447 (0%)	0
Extrapulmonary tuberculosis	0/447 (0%)	0	1/447 (0.2%)	1
Gastroenteritis	10/447 (2.2%)	10	22/447 (4.9%)	22
Impetigo	0/447 (0%)	0	1/447 (0.2%)	1
Lower respiratory tract infection	1/447 (0.2%)	1	1/447 (0.2%)	1
Otitis media	0/447 (0%)	0	1/447 (0.2%)	1
Otitis media acute	1/447 (0.2%)	1	0/447 (0%)	0
Plasmodium falciparum infection	8/447 (1.8%)	8	25/447 (5.6%)	25
Pneumococcal sepsis	0/447 (0%)	0	1/447 (0.2%)	1
Pneumonia	16/447 (3.6%)	18	26/447 (5.8%)	28
Rhinitis	0/447 (0%)	0	1/447 (0.2%)	1
Schistosomiasis	1/447 (0.2%)	1	0/447 (0%)	0
Skin infection	0/447 (0%)	0	1/447 (0.2%)	1
Streptococcal sepsis	0/447 (0%)	0	1/447 (0.2%)	1
Subcutaneous abscess	1/447 (0.2%)	1	1/447 (0.2%)	1
Tinea capitis	1/447 (0.2%)	1	0/447 (0%)	0
Tonsillitis	0/447 (0%)	0	1/447 (0.2%)	1
Upper respiratory tract infection	8/447 (1.8%)	8	4/447 (0.9%)	5
Urinary tract infection	3/447 (0.7%)	3	0/447 (0%)	0
Varicella	1/447 (0.2%)	1	0/447 (0%)	0
Injury, poisoning and procedural complications
Burns first degree	0/447 (0%)	0	1/447 (0.2%)	1
Drug toxicity	0/447 (0%)	0	1/447 (0.2%)	1
Femur fracture	0/447 (0%)	0	1/447 (0.2%)	1
Petroleum distillate poisoning	0/447 (0%)	0	2/447 (0.4%)	2
Thermal burn	0/447 (0%)	0	2/447 (0.4%)	2
Metabolism and nutrition disorders
Kwashiorkor	0/447 (0%)	0	1/447 (0.2%)	2
Malnutrition	1/447 (0.2%)	1	2/447 (0.4%)	2
Marasmus	0/447 (0%)	0	2/447 (0.4%)	2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant mesenchymoma	0/447 (0%)	0	1/447 (0.2%)	1
Nervous system disorders
Convulsion	3/447 (0.7%)	3	2/447 (0.4%)	2
Epilepsy	0/447 (0%)	0	1/447 (0.2%)	1
Febrile convulsion	14/447 (3.1%)	17	20/447 (4.5%)	24
Respiratory, thoracic and mediastinal disorders
Asthma	2/447 (0.4%)	2	1/447 (0.2%)	1
Bronchial hyperreactivity	0/447 (0%)	0	2/447 (0.4%)	2
Foreign body aspiration	1/447 (0.2%)	1	0/447 (0%)	0
Vascular disorders
Shock	0/447 (0%)	0	1/447 (0.2%)	1
Other (Not Including Serious) Adverse Events
	GSK257049 Group		Rabipur Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	385/447 (86.1%)		396/447 (88.6%)
General disorders
Pain	143/447 (32%)	172	130/447 (29.1%)	157
Pyrexia	125/447 (28%)	149	268/447 (60%)	409
Swelling	30/447 (6.7%)	34	14/447 (3.1%)	17
Infections and infestations
Gastroenteritis	101/447 (22.6%)	120	81/447 (18.1%)	90
Impetigo	27/447 (6%)	28	19/447 (4.3%)	20
Lower respiratory tract infection	27/447 (6%)	27	28/447 (6.3%)	28
Pneumonia	149/447 (33.3%)	195	141/447 (31.5%)	188
Rhinitis	27/447 (6%)	28	18/447 (4%)	20
Upper respiratory tract infection	81/447 (18.1%)	96	56/447 (12.5%)	59
Metabolism and nutrition disorders
Decreased appetite	54/447 (12.1%)	64	40/447 (8.9%)	43
Nervous system disorders
Somnolence	66/447 (14.8%)	81	59/447 (13.2%)	64
Psychiatric disorders
Irritability	45/447 (10.1%)	59	19/447 (4.3%)	21

Limitations/Caveats

[Not Specified]

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Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial.