Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine Given at 6, 7.5 and 9 Months of Age in Co-administration With Measles, Rubella and Yellow Fever (YF) Vaccines Followed by a Booster of the Malaria Vaccine.

• Sponsor: GlaxoSmithKline (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02699099
• Collaborator: (none)
• Enrollment: 699
• Locations: 2
• Arms: 3
• Actual Duration (Months): 40.9
• Patients Per Site: 349.5
• Patients Per Site Per Month: 8.5

Study Details

Study Description

Brief Summary

The purpose of this study is to assess the immunogenicity, safety, and reactogenicity of the SB257049 candidate malaria vaccine when co-administered with Vitamin A, measles, rubella and yellow fever vaccines to children aged 6 months at the first vaccination.

Condition or Disease	Intervention/Treatment	Phase
Malaria; Malaria Vaccines	Dietary Supplement: Vitamin A; Biological: Candidate Plasmodium falciparum malaria vaccine; Biological: MR-Vac; Biological: Stamaril	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 699 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety Study of GSK Biologicals' Candidate Malaria Vaccine (SB257049) Given at 6, 7.5 and 9 Months of Age in Co-administration With Measles, Rubella and Yellow Fever Vaccines Followed by a Booster of the Malaria Vaccine.
• Actual Study Start Date: May 10, 2017
• Actual Primary Completion Date: Mar 14, 2018
• Actual Study Completion Date: Oct 7, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Coad group Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Dietary Supplement: Vitamin A; Oral administration of Vitamin A (1 dose); Biological: Candidate Plasmodium falciparum malaria vaccine; Intramuscular administration of SB257049 vaccine (4 doses); Other Names: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine adjuvanted with GSK Biologicals' proprietary Adjuvant System AS01E (RTS,S/AS01E) ; Biological: MR-Vac; Subcutaneous injection of a combined measles and rubella vaccine (1 dose); Other Names: Live attenuated measles virus and rubella virus vaccine (MR-Vac) ; Biological: Stamaril; Intramuscular injection of a yellow fever (YF) vaccine (1 dose); Other Names: Yellow Fever (YF) Vaccine
Experimental: RTS,S group Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Dietary Supplement: Vitamin A; Oral administration of Vitamin A (1 dose); Biological: Candidate Plasmodium falciparum malaria vaccine; Intramuscular administration of SB257049 vaccine (4 doses); Other Names: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine adjuvanted with GSK Biologicals' proprietary Adjuvant System AS01E (RTS,S/AS01E) ; Biological: MR-Vac; Subcutaneous injection of a combined measles and rubella vaccine (1 dose); Other Names: Live attenuated measles virus and rubella virus vaccine (MR-Vac) ; Biological: Stamaril; Intramuscular injection of a yellow fever (YF) vaccine (1 dose); Other Names: Yellow Fever (YF) Vaccine
Experimental: Control group Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).	Dietary Supplement: Vitamin A; Oral administration of Vitamin A (1 dose); Biological: Candidate Plasmodium falciparum malaria vaccine; Intramuscular administration of SB257049 vaccine (4 doses); Other Names: GSK Biologicals' candidate Plasmodium falciparum malaria vaccine adjuvanted with GSK Biologicals' proprietary Adjuvant System AS01E (RTS,S/AS01E) ; Biological: MR-Vac; Subcutaneous injection of a combined measles and rubella vaccine (1 dose); Other Names: Live attenuated measles virus and rubella virus vaccine (MR-Vac) ; Biological: Stamaril; Intramuscular injection of a yellow fever (YF) vaccine (1 dose); Other Names: Yellow Fever (YF) Vaccine

Outcome Measures

Primary Outcome Measures

1. Anti-Circumsporozoite (Anti-CS) Antibody Concentrations, One Month Post Dose 3 of SB257049 (Primary Analysis) [At one month post Dose 3 of SB257049 (Month 4)]

   Concentrations were expressed as Geometric Mean Concentrations (GMCs) with the following unit of measure: Enzyme Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL). The 95% confidence intervals were calculated using the Analysis of Variance (ANOVA) model. The antibody response of anti-CS was assessed in the Coad Group and the RTS,S Group.

2. Anti-CS Antibody Concentrations, One Month Post Dose 3 of SB257049 (Study End Analysis) [At one month post Dose 3 of SB257049 (Month 4)]

   Concentrations were expressed as GMCs with the following unit of measure: EU/mL. The 95% confidence intervals were calculated using the ANOVA model. The antibody response of anti-CS was assessed in the Coad Group and the RTS,S Group. The analysis was re-evaluated and performed on the Per-Protocol set for immunogenicity defined at study end.

Secondary Outcome Measures

1. Anti-CS Antibody Concentrations, Pre-vaccination and One Month Post Dose 3 of SB257049 [At Day 0 and one month post Dose 3 of SB257049 (Month 4)]

   Concentrations were expressed as Geometric Mean Concentrations (GMCs) with the following unit of measure: ELISA units per milliliter (EU/mL). The 95% CI for the GMC was obtained by exponential transformation (base 10) of the 95% CI for the mean of the log transformed concentrations. The antibody response of anti-CS was assessed in the Coad Group and the RTS,S Group.

2. Number of Seropositive Subjects for Anti-CS Antibodies, Pre-vaccination and One Month Post Dose 3 of SB257049 [At Day 0 and one month post Dose 3 of SB257049 (Month 4)]

   A subject seropositive for anti-CS antibody was a subject whose antibody concentration was greater than or equal (≥) to the cut-off value (anti-CS ≥ 1.9 ELISA unit per milliliter [EU/mL]). Seropositivity was assessed in the Coad Group and the RTS,S Group.

3. Anti-hepatitis B (Anti-HBs) Antibody Concentrations, Pre-vaccination and One Month Post-Dose 3 of SB257049 [At Day 0 and one month post Dose 3 of SB257049 (Month 4)]

   Concentrations were expressed as GMCs with the following unit of measure: milli-international unit per milliliter (mIU/mL). The antibody response of anti-HB was assessed in the Coad Group and the RTS,S Group.

4. Number of Seroprotected Subjects for Anti-HB Antibodies, Pre-vaccination and One Month Post-Dose 3 of SB257049 [At Day 0 and one month post-Dose 3 of SB257049 (Month 4)]

   Seroprotection rate for anti-HBs antibody was defined as the percentage of subjects with antibody concentrations greater than or equal to an established cut-off value (anti-HBs ≥ 10 milli-international unit per milliliter [mIU/mL]). Seroprotection was assessed in the Coad Group and the RTS,S Group.

5. Number of Seroconverted Subjects for Anti-Measles (Anti-Me) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella (MeRu) Vaccine [At one month post-vaccination with the combined measles and rubella (MeRu) vaccine (Month 4)]

   Seroconversion was defined as number of subjects with an anti-Measles antibodies pre-vaccination concentration below 150 mIU/mL and a post-vaccination concentration ≥150 mIU/mL. Seroconversion was assessed in the Coad group and the Control group.

6. Anti-Me Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine [At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)]

   Concentrations were expressed in GMCs with the following unit of measure: milli-international unit per milliliter (mIU/mL). The antibody response of anti-Me was assessed in the Coad Group and the Control Group.

7. Number of Seropositive Subjects for Anti-Me Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine [At pre-vaccination (Month 3) and one month post-vaccination with the combined measles and rubella vaccine (Month 4)]

   A subject seropositive for anti-CS antibody was a subject whose antibody concentration was greater than or equal (≥) to the cut-off value (anti-Me ≥ 150 mIU/mL). Seropositivity was assessed in the Coad Group and the Control Group.

8. Number of Seroconverted Subjects for Anti-Rubella (Anti-Ru) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella Vaccine [At one month post-vaccination with combined measles and rubella vaccine (Month 4)]

   Seroconversion was defined as number of subjects with an anti-Ru pre-vaccination concentration less than (<) 4 IU/mL and a post-vaccination concentration ≥ 4 IU/mL. Seroconversion was assessed in the Coad group and Control group.

9. Anti-Ru Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine [At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)]

   Concentrations were expressed as GMCs with the following unit of measure: International unit per milliliter (IU/mL). The antibody response of anti-Ru was assessed in the Coad Group and Control Group.

10. Number of Seropositive Subjects for Anti-Ru Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine [At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)]

    A subject seropositive for anti-Ru antibody was a subject whose antibody concentration was greater than or equal (≥) to the cut-off value (anti-Ru ≥ 4 IU/mL). Seropositivity was assessed in the Coad Group and Control Group.

11. Number of Seropositive Subjects for Anti-Yellow Fever (Anti-YF) Antibodies, at One Month Post-vaccination With the YF Vaccine [At one month post-vaccination with the YF vaccine (Month 4)]

    Seropositivity was defined as number of subjects with anti-YF titers greater than or equal to (≥) 10 End point Dilution 50 (ED50). Seropositivity was assessed in the Coad group and Control group.

12. Anti-YF Antibody Titers One Month Post-vaccination With the YF Vaccine [At one month post-vaccination with the YF vaccine (Month 4)]

    Titers were expressed as Geometric Mean Titres (GMTs). The antibody response of anti-YF was assessed in the Coad Group and Control Group.

13. Number of Subjects With Any and Grade 3 Solicited Local Symptoms for Coad Group and RTS,S Group After Administration of Vitamin A and Study Vaccines at 6 Months of Age [During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A and SB257049 dose 1 (Day 0)]

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = subject crying when limb was moved /spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) at injection site.

14. Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Coad Group and RTS,S Group After Administration of Vitamin A and Study Vaccines at 6 Months of Age [During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A and SB257049 dose 1 (Day 0)]

    Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.

15. Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Control Group After Administration of Vitamin A at 6 Months of Age [During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A (Day 0)]

    Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.

16. Number of Subjects With Any and Grade 3 Solicited Local Symptoms for Coad Group and RTS,S Group After Dose of Study Vaccines Administered at 7.5 Months of Age [During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of SB257049 dose 2 (Month 1.5)]

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = subject crying when limb was moved /spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimetres (mm) at injection site.

17. Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Coad Group and RTS,S Group After Dose of Study Vaccines Administered at 7.5 Months of Age [During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of SB257049 dose 2 (Month 1.5)]

    Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 Fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.

18. Number of Subjects With Solicited General Symptoms for the Control Group, After Visit at 7.5 Months of Age [After visit at Month 1.5]

    Solicited symptoms were not analyzed for the Control Group after visit at Month 1.5 because no vaccination was administered at that visit.

19. Number of Subjects With Any and Grade 3 Solicited Local Symptoms for All Groups, After Dose of Study Vaccines Administered at 9 Months of Age [During a 14-day follow-up period (day of administration and 13 subsequent days) after administration of SB257049 dose 3 in Coad (and MeRu+YF) and RTS,S Groups and after MeRu+YF vaccines in Control Group (Month 3)]

    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = subject crying when limb was moved /spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) at injection site.

20. Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for All Groups, After Dose of Study Vaccines Administered at 9 Months of Age [During a 14-day follow-up period (day of administration and 13 subsequent days) after administration of SB257049 dose 3 in Coad (and MeRu+YF) and RTS,S Groups and after MeRu+YF vaccines in Control Group (Month 3)]

    Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 Fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.

21. Number of Subjects With Unsolicited Adverse Events (AEs) for All Groups, After Administration of Vitamin A and Study Vaccines at 6 Months of Age [Within 30-day (Days 0-29) period after dose 1 of SB257049 and Vitamin A- Coad and RTS,S Groups, and 30-day period after Vitamin A administration - Control Group]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

22. Number of Subjects With Unsolicited AEs for the Coad Group and RTS,S Group, After Dose of Study Vaccines at 7.5 Months of Age [Within 30-day (Day of vaccination and 29 subsequent days) period after dose 2 of SB257049 administered at Month 1.5 - Coad and RTS,S Groups]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

23. Number of Subjects With Unsolicited AEs for the Control Group, at Visit at 7.5 Months of Age [During the 30-day period (Day of the visit and 29 subsequent days) after the visit at Month 1.5]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

24. Number of Subjects With Unsolicited AEs for All Study Groups, After Dose of Study Vaccines Administered at 9 Months of Age [Within 42-day (vaccination day and 41 subsequent days) period after dose 3 of SB257049 in Coad (+MeRu+YF vaccines) and RTS,S groups, and 42-day period after MeRU+YF vaccination in Control group, administered at Month 3]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

25. Number of Subjects With Serious Adverse Events (SAEs): All, Fatal and Related, for All Study Groups, Following Each Administration at Day 0, Month1.5 and Month 3 [During 30-Days period (Day of vaccination and 29 subsequent days) following each administration at Day 0, Month1.5 and Month 3 for Coad and RTS,S groups and at Day 0 and Month 3 in the Control Group.]

    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

26. Number of Subjects With Any SAEs for All Study Groups, From Day 0 Until Month 4.5 [From Day 0 up to Month 4.5]

    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

27. Number of Subjects With Potential Immune-Mediated Disease (pIMDs) for All Study Groups From Day 0 Until Month 4.5 [From Day 0 up to Month 4.5]

    pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have an autoimmune etiology.

28. Number of Subjects With Meningitis for All Study Groups From Day 0 Until Month 4.5 [From Day 0 up to Month 4.5]

    Meningitis is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It was assessed by the investigator as specific to the treatment administration.

29. Number of Subjects With Seizures for All Groups, Post-vaccination for Vaccines Administered at 6, 7.5 or 9 Months of Age [Within 30 days post-vaccination for vaccine doses administered at Day 0, Month 1.5 or 42 days post-vaccination (doses given at Month 3 [Coad & Control Groups] or Month 4.5 [RTS,S Group]) vaccination period from Day 0 until Month 4.5]

    Seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It is assessed by the investigator as specific to the treatment administration.

30. Number of Subjects With Generalized Convulsive Seizure for All Study Groups, After Vaccines Administered at Day 0 and Month 1.5 (Coad and RTS,S Groups) and After Vaccines Administered at Month 3 (All Groups) [Within 7 days after vaccines administered at Day 0 and Month 1.5 for the Coad and RTS,S groups and 14 days after vaccines administered at Month 3 for all groups]

    Generalized convulsive seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It is assessed by the investigator as specific to the treatment administration.

31. Number of Subjects With Unsolicited AEs for the Coad Group and RTS,S Group, After the Booster Dose of Study Vaccine Administered at 27 Months of Age [During the 30-day period (Day of vaccination and 29 subsequent days) after booster dose administered at Month 21]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

32. Number of Subjects With Unsolicited AEs for the Control Group, After Dose of Study Vaccine Administered at 10.5, 11.5, 12.5 and 30 Months of Age [During the 30-Day Period (Day of vaccination and 29 subsequent days) after primary doses of study vaccine administered at Month 4.5, Month 5.5, Month 6.5 (across primary doses), and after booster dose administered at Month 24]

    An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

33. Number of Subjects With SAEs for All Study Groups From Day 0 Until Study End [During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)]

    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.

34. Number of Subjects With pIMDs for All Study Groups From Day 0 Until Study End [During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)]

    pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have an autoimmune etiology.

35. Number of Subjects With Meningitis for All Study Groups From Day 0 Until Study End [During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)]

    Meningitis is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It is assessed by the investigator as specific to the treatment administration.

36. Number of Subjects With Seizures for Vaccines Doses Administered at 6, 7.5, 27 Months of Age for Coad and RTS,S Groups; and at 9 Months of Age for Coad Group or 10.5 Months of Age for RTS,S Group [Within 30 days post-vaccination (doses given at Day 0, Month 1.5, Month 21) & 42 days post-vaccination (dose given at Month 3 [Coad Group] or Month 4.5 [RTS,S Group])]

    Seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It was assessed by the investigator as specific to the treatment administration. Results are presented across all doses for Coad and RTS,S Groups.

37. Number of Subjects With Seizures for Vaccines Doses Administered at 10.5, 11.5, 12.5, 30 and 9 Months of Age for Control Group [Within 30 days post-vaccination (doses given at Month 4.5, Month 5.5, Month 6.5, Month 24) & 42 days post-vaccination (dose given at Month 3)]

    Seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It was assessed by the investigator as specific to the treatment administration. Results are presented across all doses for the Control Group.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Months to 6 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subjects' parent(s)/Legally Acceptable Representative(s) (LAR[s]) who, in the opinion of the investigator, could and complied with the requirements of the protocol.

• A male or female 6 months of age (from the day the child becomes 6 months of age until the day before the child achieved 7 months of age) at the time of the first vaccination.

• Signed or thumb-printed informed consent obtained from the parent(s)/LAR(s) of the subject. Where parent(s)/LAR(s) were illiterate, the consent form was countersigned by an independent witness.

• Healthy subjects as established by medical history and clinical examination before entering into the study.

• Previously received three documented doses of diphtheria, tetanus, and whole-cell pertussis, hepatitis B vaccine (DTPwHepB), and a 3-dose course of oral polio vaccine and, if locally recommended, pneumococcal and rotavirus vaccines.

Exclusion Criteria:

• Child in care

• 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.

• Any medical condition that in the judgment of the investigator would make intramuscular injection unsafe.

• Chronic administration of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this meant prednisone≥ 0.5 mg/kg/day, or equivalent. Inhaled and topical steroids were allowed.

• Planned administration/administration of a vaccine not foreseen by the study protocol in the period starting seven days before the first dose of SB257049 measles, rubella and YF vaccines and ending 42 days after the last dose of vaccines given at 9 months of age (Visit 4), with the exception of oral polio vaccine which could be given for unforeseen public health threat.

• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product.

• Previous vaccination against measles, YF or rubella.

• Previous administration of Vitamin A.

• Moderate or severe malnutrition at screening defined as weight for age Z-score < -2.

• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.

• Family history of congenital or hereditary immunodeficiency.

• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine(s). See also Section 1.3.

• Major congenital defects or serious chronic illness.

• History of any neurological disorders or seizures.

• Acute disease and/or fever at the time of enrolment. Fever was defined as temperature ≥ 37.5°C /99.5°F for oral, axillary or tympanic route, or ≥ 38.0°C /100.4°F on rectal route. The preferred route for recording temperature in this study was axillary.

Subjects with a minor illness without fever might have been enrolled at the discretion of the investigator.

• Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.

• Same sex twin.

• Maternal death.

• Previous participation in any other malaria study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	GSK Investigational Site	Kintampo		Ghana
2	GSK Investigational Site	Kumasi		Ghana

Sponsors and Collaborators

• GlaxoSmithKline

Investigators

• Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

• Study Protocol - Aug 9, 2016
• Statistical Analysis Plan - Apr 9, 2018

More Information

Publications

None provided.

• Responsible Party: GlaxoSmithKline
• ClinicalTrials.gov Identifier: NCT02699099
• Other Study ID Numbers: 200596
• First Posted: Mar 4, 2016
• Last Update Posted: Sep 29, 2021
• Last Verified: Sep 1, 2021

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by GlaxoSmithKline: Children; Infants; SB257049; Malaria; Immunogenicity; Surveillance; Efficacy; Safety; Africa; Plasmodium falciparum
• Additional relevant MeSH terms: Malaria; Rubella; Yellow Fever; Vitamin A; Vaccines

Study Results

Participant Flow

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Period Title: Overall Study
STARTED	231	236	232
COMPLETED	223	233	226
NOT COMPLETED	8	3	6

Baseline Characteristics

Arm/Group Title	Coad Group	RTS,S Group	Control Group	Total
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).	Total of all reporting groups
Overall Participants	231	236	232	699
Age (Months) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Months]	6.3 (0.3)	6.3 (0.3)	6.3 (0.3)	6.3 (0.3)
Sex: Female, Male (Count of Participants)
Female	116 50.2%	119 50.4%	113 48.7%	348 49.8%
Male	115 49.8%	117 49.6%	119 51.3%	351 50.2%
Race/Ethnicity, Customized (Count of Participants)
BLACK OR AFRICAN AMERICAN	231 100%	236 100%	232 100%	699 100%

Outcome Measures

1. Primary Outcome

Title	Anti-Circumsporozoite (Anti-CS) Antibody Concentrations, One Month Post Dose 3 of SB257049 (Primary Analysis)
Description	Concentrations were expressed as Geometric Mean Concentrations (GMCs) with the following unit of measure: Enzyme Linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL). The 95% confidence intervals were calculated using the Analysis of Variance (ANOVA) model. The antibody response of anti-CS was assessed in the Coad Group and the RTS,S Group.
Time Frame	At one month post Dose 3 of SB257049 (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity defined for the primary analysis (Month 4.5), which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study. Subjects with incomplete vaccination course or blood sampling outside protocol windows were eliminated.

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	207	213
Geometric Mean (95% Confidence Interval) [EU/mL]	452.87	422.49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Coad Group, RTS,S Group
	Comments	Adjusted GMC ratios for anti-CS antibody: To demonstrate the non-inferiority of the antibody response to the CS antigen when SB257049 is co-administered with YF vaccine and a combined measles and rubella vaccine versus SB257049 administered alone.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority (1 month post-Dose 3 of SB257049) was defined as the upper limit (UL) of the 2-sided 95% confidence interval (CI) of the geometric mean concentration (GMC) ratio (RTS,S group/Coad group) for anti-CS, being below a limit of 2.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Anti-CS Antibody Concentrations, Pre-vaccination and One Month Post Dose 3 of SB257049
Description	Concentrations were expressed as Geometric Mean Concentrations (GMCs) with the following unit of measure: ELISA units per milliliter (EU/mL). The 95% CI for the GMC was obtained by exponential transformation (base 10) of the 95% CI for the mean of the log transformed concentrations. The antibody response of anti-CS was assessed in the Coad Group and the RTS,S Group.
Time Frame	At Day 0 and one month post Dose 3 of SB257049 (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity, defined at study end, which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	208	213
Anti-CS - Day 0	0.96	0.96
Anti-CS - Month 4	454.51	422.49

3. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-CS Antibodies, Pre-vaccination and One Month Post Dose 3 of SB257049
Description	A subject seropositive for anti-CS antibody was a subject whose antibody concentration was greater than or equal (≥) to the cut-off value (anti-CS ≥ 1.9 ELISA unit per milliliter [EU/mL]). Seropositivity was assessed in the Coad Group and the RTS,S Group.
Time Frame	At Day 0 and one month post Dose 3 of SB257049 (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity, defined at study end, which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	208	213
Anti-CS - Day 0	1 0.4%	2 0.8%
Anti-CS - Month 4	207 89.6%	213 90.3%

4. Secondary Outcome

Title	Anti-hepatitis B (Anti-HBs) Antibody Concentrations, Pre-vaccination and One Month Post-Dose 3 of SB257049
Description	Concentrations were expressed as GMCs with the following unit of measure: milli-international unit per milliliter (mIU/mL). The antibody response of anti-HB was assessed in the Coad Group and the RTS,S Group.
Time Frame	At Day 0 and one month post Dose 3 of SB257049 (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	205	210
Anti-HBs - Day 0	397.36	427.65
Anti-HBs - Month 4	42162.55	43261.19

5. Secondary Outcome

Title	Number of Seroprotected Subjects for Anti-HB Antibodies, Pre-vaccination and One Month Post-Dose 3 of SB257049
Description	Seroprotection rate for anti-HBs antibody was defined as the percentage of subjects with antibody concentrations greater than or equal to an established cut-off value (anti-HBs ≥ 10 milli-international unit per milliliter [mIU/mL]). Seroprotection was assessed in the Coad Group and the RTS,S Group.
Time Frame	At Day 0 and one month post-Dose 3 of SB257049 (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	205	210
Anti-HB - Day 0	196 84.8%	201 85.2%
Anti-HB - Month 4	205 88.7%	210 89%

6. Secondary Outcome

Title	Number of Seroconverted Subjects for Anti-Measles (Anti-Me) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella (MeRu) Vaccine
Description	Seroconversion was defined as number of subjects with an anti-Measles antibodies pre-vaccination concentration below 150 mIU/mL and a post-vaccination concentration ≥150 mIU/mL. Seroconversion was assessed in the Coad group and the Control group.
Time Frame	At one month post-vaccination with the combined measles and rubella (MeRu) vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	205	216
Count of Participants [Participants]	197 85.3%	212 89.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Coad Group, RTS,S Group
	Comments	Difference in seroconversion rates against measles antibodies: To demonstrate the non-inferiority of the antibody response to the measles vaccine antigen when YF vaccine and a combined measles and rubella vaccine are coadministered with SB257049 versus administration without SB257049.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was defined as the upper limit of the 95% confidence interval (CI) for the difference in seroconversion rate of the anti-measles antibody, being below 10% for the two groups (Control Group minus Coad Group).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	2.05
	Confidence Interval	(2-Sided) 95%; -1.29 to 5.89
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Anti-Me Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
Description	Concentrations were expressed in GMCs with the following unit of measure: milli-international unit per milliliter (mIU/mL). The antibody response of anti-Me was assessed in the Coad Group and the Control Group.
Time Frame	At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	208	220
Anti-Me - Month 3	75.00	75.00
Anti-Me - Month 4	565.81	572.09

8. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-Me Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
Description	A subject seropositive for anti-CS antibody was a subject whose antibody concentration was greater than or equal (≥) to the cut-off value (anti-Me ≥ 150 mIU/mL). Seropositivity was assessed in the Coad Group and the Control Group.
Time Frame	At pre-vaccination (Month 3) and one month post-vaccination with the combined measles and rubella vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	208	220
Anti-Me - Month 3	0 0%	0 0%
Anti-Me - Month 4	200 86.6%	213 90.3%

9. Secondary Outcome

Title	Number of Seroconverted Subjects for Anti-Rubella (Anti-Ru) Antibodies, One Month Post-vaccination With the Combined Measles and Rubella Vaccine
Description	Seroconversion was defined as number of subjects with an anti-Ru pre-vaccination concentration less than (<) 4 IU/mL and a post-vaccination concentration ≥ 4 IU/mL. Seroconversion was assessed in the Coad group and Control group.
Time Frame	At one month post-vaccination with combined measles and rubella vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	200	212
Count of Participants [Participants]	199 86.1%	212 89.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Coad Group, RTS,S Group
	Comments	Difference in seroconversion rates against Rubella antibodies: To demonstrate the non-inferiority of the antibody response to the rubella vaccine antigen when YF vaccine and a combined measles and rubella vaccine are coadministered. with SB257049 versus administration without SB257049.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was defined as the upper limit of the 95% confidence interval (CI) for the difference in seroconversion rates of the anti-rubella antibody, being below 10% for the two groups (Control Group minus Coad Group).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.50
	Confidence Interval	(2-Sided) 95%; -1.29 to 2.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Anti-Ru Antibody Concentrations, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
Description	Concentrations were expressed as GMCs with the following unit of measure: International unit per milliliter (IU/mL). The antibody response of anti-Ru was assessed in the Coad Group and Control Group.
Time Frame	At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	208	220
Anti-Ru - Month 3	2.08	2.09
Anti-Ru - Month 4	39.36	42.45

11. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-Ru Antibodies, Pre-vaccination and One Month Post-vaccination With the Combined Measles and Rubella Vaccine
Description	A subject seropositive for anti-Ru antibody was a subject whose antibody concentration was greater than or equal (≥) to the cut-off value (anti-Ru ≥ 4 IU/mL). Seropositivity was assessed in the Coad Group and Control Group.
Time Frame	At pre-vaccination (Month 3) and one month post-vaccination with combined measles and rubella vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	208	220
Anti-Ru - Month 3	5 2.2%	4 1.7%
Anti-Ru - Month 4	207 89.6%	217 91.9%

12. Secondary Outcome

Title	Number of Seropositive Subjects for Anti-Yellow Fever (Anti-YF) Antibodies, at One Month Post-vaccination With the YF Vaccine
Description	Seropositivity was defined as number of subjects with anti-YF titers greater than or equal to (≥) 10 End point Dilution 50 (ED50). Seropositivity was assessed in the Coad group and Control group.
Time Frame	At one month post-vaccination with the YF vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	207	217
Count of Participants [Participants]	203 87.9%	214 90.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Coad Group, RTS,S Group
	Comments	Difference in seropositivity rates against Yellow Fever antibodies: To demonstrate the non-inferiority of the antibody response to the YF vaccine antigen when YF vaccine and a combined measles and rubella vaccine are coadministered with SB257049 versus administration without SB257049.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was defined as the upper limit of the 95% confidence interval (CI) for the difference in seropositivity rates of the anti-yellow fever antibody , being below 10% for the two groups (Control Group minus Coad Group).
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in percentage
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; -2.30 to 3.65
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Anti-YF Antibody Titers One Month Post-vaccination With the YF Vaccine
Description	Titers were expressed as Geometric Mean Titres (GMTs). The antibody response of anti-YF was assessed in the Coad Group and Control Group.
Time Frame	At one month post-vaccination with the YF vaccine (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study, and who had available data concerning the outcome measure. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated.

Arm/Group Title	Coad Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	207	217
Geometric Mean (95% Confidence Interval) [Titers]	324.31	346.60

14. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms for Coad Group and RTS,S Group After Administration of Vitamin A and Study Vaccines at 6 Months of Age
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = subject crying when limb was moved /spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) at injection site.
Time Frame	During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A and SB257049 dose 1 (Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with the first dose of SB257049 and Vitamin A administered (Coad and RTS,S Groups).

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	231	236
Pain - Any	25 10.8%	16 6.8%
Pain - Grade 3	0 0%	1 0.4%
Redness - Any	7 3%	13 5.5%
Redness - Grade 3	0 0%	0 0%
Swelling - Any	8 3.5%	6 2.5%
Swelling - Grade 3	0 0%	0 0%

15. Secondary Outcome

Title	Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Coad Group and RTS,S Group After Administration of Vitamin A and Study Vaccines at 6 Months of Age
Description	Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.
Time Frame	During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A and SB257049 dose 1 (Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with the first dose of SB257049 and Vitamin A administered (Coad and RTS,S Groups).

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	231	235
Drowsiness - Any	4 1.7%	4 1.7%
Drowsiness - Grade 3	0 0%	0 0%
Drowsiness - Related	0 0%	0 0%
Drowsiness - Grade 3 related	0 0%	0 0%
Irritability/Fussiness - Any	14 6.1%	22 9.3%
Irritability/Fussiness - Grade 3	1 0.4%	1 0.4%
Irritability/Fussiness - Related	2 0.9%	1 0.4%
Irritability/Fussiness - Grade 3 related	0 0%	0 0%
Loss of appetite - Any	5 2.2%	7 3%
Loss of appetite - Grade 3	0 0%	0 0%
Loss of appetite - Related	0 0%	0 0%
Loss of appetite - Grade 3 related	0 0%	0 0%
Measles/Rubella-like rash - Any	0 0%	0 0%
Measles/Rubella-like rash - Grade 3	0 0%	0 0%
Measles/Rubella-like rash - Related	0 0%	0 0%
Measles/Rubella-like rash - Grade 3 related	0 0%	0 0%
Fever - Any	32 13.9%	30 12.7%
Fever - Grade 3	3 1.3%	1 0.4%
Fever - Related	10 4.3%	8 3.4%
Fever - Grade 3 related	1 0.4%	0 0%

16. Secondary Outcome

Title	Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Control Group After Administration of Vitamin A at 6 Months of Age
Description	Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.
Time Frame	During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of Vitamin A (Day 0)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with Vitamin A administered (Control group). In the Control Group, only solicited general symptoms were collected.

Arm/Group Title	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	232
Drowsiness - Any	1 0.4%
Drowsiness - Grade 3	0 0%
Drowsiness - Related	0 0%
Drowsiness - Grade 3 related	0 0%
Irritability/Fussiness - Any	6 2.6%
Irritability/Fussiness - Grade 3	1 0.4%
Irritability/Fussiness - Related	0 0%
Irritability/Fussiness - Grade 3 related	0 0%
Loss of appetite - Any	9 3.9%
Loss of appetite- Grade 3	0 0%
Loss of appetite- Related	0 0%
Loss of appetite- Grade 3 related	0 0%
Measles/Rubella-like rash - Any	0 0%
Measles/Rubella-like rash - Grade 3	0 0%
Measles/Rubella-like rash - Related	0 0%
Measles/Rubella-like rash - Grade 3 related	0 0%
Fever - Any	11 4.8%
Fever - Grade 3	0 0%
Fever - Related	1 0.4%
Fever - Grade 3 related	0 0%

17. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms for Coad Group and RTS,S Group After Dose of Study Vaccines Administered at 7.5 Months of Age
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = subject crying when limb was moved /spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimetres (mm) at injection site.
Time Frame	During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of SB257049 dose 2 (Month 1.5)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with the second dose of SB257049 administered (Coad and RTS,S Groups).

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	224	234
Pain - Any	3 1.3%	12 5.1%
Pain - Grade 3	0 0%	0 0%
Redness - Any	4 1.7%	2 0.8%
Redness - Grade 3	1 0.4%	0 0%
Swelling - Any	4 1.7%	6 2.5%
Swelling - Grade 3	0 0%	0 0%

18. Secondary Outcome

Title	Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for the Coad Group and RTS,S Group After Dose of Study Vaccines Administered at 7.5 Months of Age
Description	Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 Fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.
Time Frame	During a 7-day follow-up period (day of administration and 6 subsequent days) after administration of SB257049 dose 2 (Month 1.5)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with the second dose of SB257049 administered (Coad and RTS,S Groups).

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	224	234
Drowsiness - Any	6 2.6%	5 2.1%
Drowsiness - Grade 3	0 0%	0 0%
Drowsiness - Related	1 0.4%	2 0.8%
Drowsiness - Grade 3 related	0 0%	0 0%
Irritability/Fussiness - Any	11 4.8%	13 5.5%
Irritability/Fussiness - Grade 3	0 0%	1 0.4%
Irritability/Fussiness - Related	4 1.7%	2 0.8%
Irritability/Fussiness - Grade 3 related	0 0%	0 0%
Loss of appetite - Any	6 2.6%	11 4.7%
Loss of appetite - Grade 3	0 0%	0 0%
Loss of appetite - Related	1 0.4%	0 0%
Loss of appetite - Grade 3 related	0 0%	0 0%
Measles/Rubella-like rash - Any	0 0%	0 0%
Measles/Rubella-like rash - Grade 3	0 0%	0 0%
Measles/Rubella-like rash - Related	0 0%	0 0%
Measles/Rubella-like rash - Grade 3 related	0 0%	0 0%
Fever - Any	47 20.3%	47 19.9%
Fever - Grade 3	3 1.3%	3 1.3%
Fever - Related	11 4.8%	9 3.8%
Fever - Grade 3 related	1 0.4%	1 0.4%

19. Secondary Outcome

Title	Number of Subjects With Solicited General Symptoms for the Control Group, After Visit at 7.5 Months of Age
Description	Solicited symptoms were not analyzed for the Control Group after visit at Month 1.5 because no vaccination was administered at that visit.
Time Frame	After visit at Month 1.5

Outcome Measure Data

Analysis Population Description

Analysis was not performed. Solicited symptoms were not collected for the Control group after visit at Month 1.5 because no vaccination was administered.

Arm/Group Title	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	0

20. Secondary Outcome

Title	Number of Subjects With Any and Grade 3 Solicited Local Symptoms for All Groups, After Dose of Study Vaccines Administered at 9 Months of Age
Description	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = subject crying when limb was moved /spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 20 millimeters (mm) at injection site.
Time Frame	During a 14-day follow-up period (day of administration and 13 subsequent days) after administration of SB257049 dose 3 in Coad (and MeRu+YF) and RTS,S Groups and after MeRu+YF vaccines in Control Group (Month 3)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with SB257049 dose 3 for Coad (and MeRu+YF vaccines) and RTS,S Groups, and MeRU+YF vaccines for Control Group.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	221	228	225
Pain - Any	10 4.3%	10 4.2%	1 0.4%
Pain - Grade 3	0 0%	0 0%	0 0%
Redness - Any	0 0%	1 0.4%	2 0.9%
Redness - Grade 3	0 0%	0 0%	0 0%
Swelling - Any	3 1.3%	3 1.3%	1 0.4%
Swelling - Grade 3	0 0%	0 0%	0 0%

21. Secondary Outcome

Title	Number of Subjects With Any, Grade 3, Related, Grade 3 and Related Solicited General Symptoms for All Groups, After Dose of Study Vaccines Administered at 9 Months of Age
Description	Assessed solicited general symptoms were drowsiness, irritability/fussiness, loss of appetite, measles/rubella-like rash and fever. Any = occurrence of the symptom regardless of intensity grade. Any Fever = temperature greater than or equal to (≥) 37.5° C (axillary route). Grade 3 drowsiness= symptom that prevented normal activity; Grade 3 Irritability/Fussiness = Crying that couldn't be comforted/prevented normal activity; Grade 3 Loss of appetite = not eating at all; Grade 3 Measles /rubella rash = >150 lesions; Grade 3 Fever= temperature grater than (>) 39°C; Related = symptom assessed by the investigator as causally related to the vaccination.
Time Frame	During a 14-day follow-up period (day of administration and 13 subsequent days) after administration of SB257049 dose 3 in Coad (and MeRu+YF) and RTS,S Groups and after MeRu+YF vaccines in Control Group (Month 3)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with SB257049 dose 3 for Coad (and MeRu + YF vaccines) and RTS,S Groups, and MeRU+YF vaccines for Control Group.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	221	229	225
Drowsiness - Any	7 3%	6 2.5%	0 0%
Drowsiness - Grade 3	0 0%	0 0%	0 0%
Drowsiness - Related	4 1.7%	5 2.1%	0 0%
Drowsiness - Grade 3 related	0 0%	0 0%	0 0%
Irritability/Fussiness - Any	11 4.8%	8 3.4%	1 0.4%
Irritability/Fussiness - Grade 3	0 0%	0 0%	0 0%
Irritability/Fussiness - Related	4 1.7%	4 1.7%	0 0%
Irritability/Fussiness - Grade 3 related	0 0%	0 0%	0 0%
Loss of appetite - Any	8 3.5%	6 2.5%	2 0.9%
Loss of appetite - Grade 3	0 0%	0 0%	0 0%
Loss of appetite - Related	2 0.9%	2 0.8%	0 0%
Loss of appetite - Grade 3 related	0 0%	0 0%	0 0%
Measles/Rubella-like rash - Any	0 0%	0 0%	0 0%
Measles/Rubella-like rash - Grade 3	0 0%	0 0%	0 0%
Measles/Rubella-like rash - Related	0 0%	0 0%	0 0%
Measles/Rubella-like rash - Grade 3 related	0 0%	0 0%	0 0%
Fever - Any	54 23.4%	50 21.2%	17 7.3%
Fever - Grade 3	3 1.3%	2 0.8%	2 0.9%
Fever - Related	26 11.3%	23 9.7%	8 3.4%
Fever - Grade 3 related	1 0.4%	1 0.4%	1 0.4%

22. Secondary Outcome

Title	Number of Subjects With Unsolicited Adverse Events (AEs) for All Groups, After Administration of Vitamin A and Study Vaccines at 6 Months of Age
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame	Within 30-day (Days 0-29) period after dose 1 of SB257049 and Vitamin A- Coad and RTS,S Groups, and 30-day period after Vitamin A administration - Control Group

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with first dose of the study vaccine + Vitamin A (Coad and RTS,S Groups) or Vitamin A (Control Group).

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	116 50.2%	119 50.4%	111 47.8%

23. Secondary Outcome

Title	Number of Subjects With Unsolicited AEs for the Coad Group and RTS,S Group, After Dose of Study Vaccines at 7.5 Months of Age
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame	Within 30-day (Day of vaccination and 29 subsequent days) period after dose 2 of SB257049 administered at Month 1.5 - Coad and RTS,S Groups

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with the second dose of the study vaccine administered (Coad and RTS,S Groups).

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	225	234
Count of Participants [Participants]	107 46.3%	109 46.2%

24. Secondary Outcome

Title	Number of Subjects With Unsolicited AEs for the Control Group, at Visit at 7.5 Months of Age
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame	During the 30-day period (Day of the visit and 29 subsequent days) after the visit at Month 1.5

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects from the Control Group who completed the visit at Month 1.5.

Arm/Group Title	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	229
Count of Participants [Participants]	80 34.6%

25. Secondary Outcome

Title	Number of Subjects With Unsolicited AEs for All Study Groups, After Dose of Study Vaccines Administered at 9 Months of Age
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame	Within 42-day (vaccination day and 41 subsequent days) period after dose 3 of SB257049 in Coad (+MeRu+YF vaccines) and RTS,S groups, and 42-day period after MeRU+YF vaccination in Control group, administered at Month 3

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with the third dose of the study vaccine for Coad (+MeRu+YF vacines) and RTS,S Groups, or MeRU + YF vaccine for the Control Group.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	222	231	227
Count of Participants [Participants]	120 51.9%	121 51.3%	125 53.9%

26. Secondary Outcome

Title	Number of Subjects With Serious Adverse Events (SAEs): All, Fatal and Related, for All Study Groups, Following Each Administration at Day 0, Month1.5 and Month 3
Description	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	During 30-Days period (Day of vaccination and 29 subsequent days) following each administration at Day 0, Month1.5 and Month 3 for Coad and RTS,S groups and at Day 0 and Month 3 in the Control Group.

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Any SAEs	13 5.6%	8 3.4%	16 6.9%
Fatal SAEs	1 0.4%	0 0%	1 0.4%
Related SAEs	0 0%	0 0%	0 0%

27. Secondary Outcome

Title	Number of Subjects With Any SAEs for All Study Groups, From Day 0 Until Month 4.5
Description	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	From Day 0 up to Month 4.5

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccines or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	14 6.1%	12 5.1%	21 9.1%

28. Secondary Outcome

Title	Number of Subjects With Potential Immune-Mediated Disease (pIMDs) for All Study Groups From Day 0 Until Month 4.5
Description	pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have an autoimmune etiology.
Time Frame	From Day 0 up to Month 4.5

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	0 0%	0 0%	0 0%

29. Secondary Outcome

Title	Number of Subjects With Meningitis for All Study Groups From Day 0 Until Month 4.5
Description	Meningitis is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It was assessed by the investigator as specific to the treatment administration.
Time Frame	From Day 0 up to Month 4.5

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	0 0%	0 0%	0 0%

30. Secondary Outcome

Title	Number of Subjects With Seizures for All Groups, Post-vaccination for Vaccines Administered at 6, 7.5 or 9 Months of Age
Description	Seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It is assessed by the investigator as specific to the treatment administration.
Time Frame	Within 30 days post-vaccination for vaccine doses administered at Day 0, Month 1.5 or 42 days post-vaccination (doses given at Month 3 [Coad & Control Groups] or Month 4.5 [RTS,S Group]) vaccination period from Day 0 until Month 4.5

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	0 0%	0 0%	0 0%

31. Secondary Outcome

Title	Number of Subjects With Generalized Convulsive Seizure for All Study Groups, After Vaccines Administered at Day 0 and Month 1.5 (Coad and RTS,S Groups) and After Vaccines Administered at Month 3 (All Groups)
Description	Generalized convulsive seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It is assessed by the investigator as specific to the treatment administration.
Time Frame	Within 7 days after vaccines administered at Day 0 and Month 1.5 for the Coad and RTS,S groups and 14 days after vaccines administered at Month 3 for all groups

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	0 0%	0 0%	0 0%

32. Secondary Outcome

Title	Number of Subjects With Unsolicited AEs for the Coad Group and RTS,S Group, After the Booster Dose of Study Vaccine Administered at 27 Months of Age
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame	During the 30-day period (Day of vaccination and 29 subsequent days) after booster dose administered at Month 21

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with the booster dose of study vaccine administered at 27 months of age (Coad and RTS,S Groups)

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	216	209
Count of Participants [Participants]	62 26.8%	67 28.4%

33. Secondary Outcome

Title	Number of Subjects With Unsolicited AEs for the Control Group, After Dose of Study Vaccine Administered at 10.5, 11.5, 12.5 and 30 Months of Age
Description	An unsolicited adverse event is any adverse event (i.e. any untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.
Time Frame	During the 30-Day Period (Day of vaccination and 29 subsequent days) after primary doses of study vaccine administered at Month 4.5, Month 5.5, Month 6.5 (across primary doses), and after booster dose administered at Month 24

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of study vaccine administered at 10.5, 11.5, 12.5 and 30 months of age (Control Group).

Arm/Group Title	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	223
Across primary doses	160 69.3%
At Month 24	57 24.7%

34. Secondary Outcome

Title	Number of Subjects With SAEs for All Study Groups From Day 0 Until Study End
Description	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	During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	61 26.4%	62 26.3%	66 28.4%

35. Secondary Outcome

Title	Number of Subjects With pIMDs for All Study Groups From Day 0 Until Study End
Description	pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurological disorders of interest which may or may not have an autoimmune etiology.
Time Frame	During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	0 0%	1 0.4%	0 0%

36. Secondary Outcome

Title	Number of Subjects With Meningitis for All Study Groups From Day 0 Until Study End
Description	Meningitis is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It is assessed by the investigator as specific to the treatment administration.
Time Frame	During the entire study period (From Day 0 until Month 33 for Coad and RTS,S Groups and Month 36 for the Control Group)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	231	236	232
Count of Participants [Participants]	0 0%	1 0.4%	1 0.4%

37. Secondary Outcome

Title	Number of Subjects With Seizures for Vaccines Doses Administered at 6, 7.5, 27 Months of Age for Coad and RTS,S Groups; and at 9 Months of Age for Coad Group or 10.5 Months of Age for RTS,S Group
Description	Seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It was assessed by the investigator as specific to the treatment administration. Results are presented across all doses for Coad and RTS,S Groups.
Time Frame	Within 30 days post-vaccination (doses given at Day 0, Month 1.5, Month 21) & 42 days post-vaccination (dose given at Month 3 [Coad Group] or Month 4.5 [RTS,S Group])

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	231	236
Count of Participants [Participants]	0 0%	0 0%

38. Primary Outcome

Title	Anti-CS Antibody Concentrations, One Month Post Dose 3 of SB257049 (Study End Analysis)
Description	Concentrations were expressed as GMCs with the following unit of measure: EU/mL. The 95% confidence intervals were calculated using the ANOVA model. The antibody response of anti-CS was assessed in the Coad Group and the RTS,S Group. The analysis was re-evaluated and performed on the Per-Protocol set for immunogenicity defined at study end.
Time Frame	At one month post Dose 3 of SB257049 (Month 4)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Per-Protocol set for immunogenicity, defined at study end, which included all evaluable subjects meeting all eligibility criteria, complying with protocol defined procedures, with no elimination criteria during the study. Subjects with incomplete vaccination course or blood sampling performed outside protocol defined windows were eliminated. One subject that was eliminated at the primary analysis performed at Month 4.5 was included in this analysis.

Arm/Group Title	Coad Group	RTS,S Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).
Measure Participants	208	213
Geometric Mean (95% Confidence Interval) [EU/mL]	454.51	422.49

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Coad Group, RTS,S Group
	Comments	Adjusted GMC ratios for anti-CS antibody: To demonstrate the non-inferiority of the antibody response to the CS antigen when SB257049 is co-administered with YF vaccine and a combined measles and rubella vaccine versus SB257049 administered alone.
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority (1 month post-Dose 3 of SB257049) was defined as the upper limit (UL) of the 2-sided 95% confidence interval (CI) of the geometric mean concentration (GMC) ratio (RTS,S group/Coad group) for anti-CS, being below a limit of 2.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Geometric Mean Ratio
	Estimated Value	0.93
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.07
	Parameter Dispersion	Type: Value:
	Estimation Comments

39. Secondary Outcome

Title	Number of Subjects With Seizures for Vaccines Doses Administered at 10.5, 11.5, 12.5, 30 and 9 Months of Age for Control Group
Description	Seizure is an adverse event of specific interest (AESI). An AESI is defined as an AE including autoimmune diseases and other mediated inflammatory disorders. It was assessed by the investigator as specific to the treatment administration. Results are presented across all doses for the Control Group.
Time Frame	Within 30 days post-vaccination (doses given at Month 4.5, Month 5.5, Month 6.5, Month 24) & 42 days post-vaccination (dose given at Month 3)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the Exposed set which included all subjects with at least one dose of the study vaccine or Vitamin A administered.

Arm/Group Title	Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
Measure Participants	232
Count of Participants [Participants]	1 0.4%

Adverse Events

Time Frame	Solicited local & general AEs: Coad & RTS,S groups over 7-day follow-up period (FU) after vaccination at 6 & 7.5 Months of age (Mth-age); Control group at 6 Mth-age; all groups 14-Day FU after vaccination at 9 Mth-age. Unsolicited AEs: Coad & RTS,S groups over 30-Day FU after vaccination at 6, 7.5 & 27 Mth-age; Control group at 6, 10.5, 11.5, 12.5 & 30 Mth-age; all groups 42-Day FU after vaccination at 9 Mth-age. SAEs: Coad & RTS,S groups Day 0-Month 33; Control Group: Day 0-Month 36
Arm/Group Title	Coad Group		RTS,S Group		Control Group
Arm/Group Description	Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).		Children randomized received Vitamin A at 6 months of age, SB257049 vaccine at 6, 7.5 and 9 months of age, and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 10.5 months of age. Subjects received a booster dose of SB257049 vaccine at 18 months post Dose 3 (i.e. at 27 months of age).		Children randomized received Vitamin A at 6 months of age and Yellow Fever (YF) vaccine and a combined measles and rubella vaccine at 9 months of age. These children received SB257049 vaccine at 10.5, 11.5 and 12.5 months of age plus a booster dose 17.5 months post Dose 3 (i.e. at 30 months of age).
All Cause Mortality
	Coad Group		RTS,S Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/231 (0.9%)		0/236 (0%)		3/232 (1.3%)
Serious Adverse Events
	Coad Group		RTS,S Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/231 (26.4%)		62/236 (26.3%)		66/232 (28.4%)
Blood and lymphatic system disorders
Anaemia	0/231 (0%)	0	3/236 (1.3%)	3	4/232 (1.7%)	4
Haemolytic anaemia	1/231 (0.4%)	1	0/236 (0%)	0	1/232 (0.4%)	1
Sickle cell anaemia with crisis	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Congenital, familial and genetic disorders
Cerebral palsy	1/231 (0.4%)	1	0/236 (0%)	0	1/232 (0.4%)	1
Gastrointestinal disorders
Diarrhoea	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Intussusception	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Rectal prolapse	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Stomatitis	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
General disorders
Death	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Infections and infestations
Abscess neck	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Bronchiolitis	0/231 (0%)	0	3/236 (1.3%)	5	2/232 (0.9%)	2
Cellulitis	0/231 (0%)	0	1/236 (0.4%)	1	3/232 (1.3%)	3
Conjunctivitis	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Dermatitis infected	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Dysentery	0/231 (0%)	0	0/236 (0%)	0	2/232 (0.9%)	4
Gastroenteritis	16/231 (6.9%)	16	17/236 (7.2%)	18	13/232 (5.6%)	13
Gastroenteritis shigella	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
HIV infection	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Lower respiratory tract infection	3/231 (1.3%)	3	3/236 (1.3%)	3	1/232 (0.4%)	1
Malaria	6/231 (2.6%)	6	3/236 (1.3%)	3	11/232 (4.7%)	12
Meningitis pneumococcal	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Meningitis viral	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Otitis media	2/231 (0.9%)	2	5/236 (2.1%)	5	4/232 (1.7%)	4
Otitis media acute	1/231 (0.4%)	1	3/236 (1.3%)	3	1/232 (0.4%)	1
Plasmodium falciparum infection	21/231 (9.1%)	28	29/236 (12.3%)	35	21/232 (9.1%)	31
Pneumococcal sepsis	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Pneumonia	15/231 (6.5%)	17	12/236 (5.1%)	14	17/232 (7.3%)	22
Psoas abscess	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Respiratory tract infection	1/231 (0.4%)	1	0/236 (0%)	0	1/232 (0.4%)	1
Salmonella sepsis	2/231 (0.9%)	2	0/236 (0%)	0	0/232 (0%)	0
Sepsis	9/231 (3.9%)	9	2/236 (0.8%)	2	8/232 (3.4%)	8
Septic shock	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Skin bacterial infection	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Subcutaneous abscess	1/231 (0.4%)	1	1/236 (0.4%)	1	1/232 (0.4%)	1
Tracheobronchitis	0/231 (0%)	0	0/236 (0%)	0	2/232 (0.9%)	2
Upper respiratory tract infection	3/231 (1.3%)	3	1/236 (0.4%)	1	0/232 (0%)	0
Urinary tract infection	3/231 (1.3%)	3	2/236 (0.8%)	2	3/232 (1.3%)	3
Injury, poisoning and procedural complications
Accidental exposure to product by child	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Accidental poisoning	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Exposure to toxic agent	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Exposure via ingestion	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Foreign body ingestion	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Head injury	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Limb traumatic amputation	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Radius fracture	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Skin laceration	0/231 (0%)	0	1/236 (0.4%)	1	1/232 (0.4%)	1
Thermal burn	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Tibia fracture	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Metabolism and nutrition disorders
Kwashiorkor	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Malnutrition	0/231 (0%)	0	2/236 (0.8%)	2	0/232 (0%)	0
Musculoskeletal and connective tissue disorders
Dactylitis	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Musculoskeletal pain	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Torticollis	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lipoma	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Nervous system disorders
Febrile convulsion	3/231 (1.3%)	3	0/236 (0%)	0	2/232 (0.9%)	2
Renal and urinary disorders
Glomerulonephritis	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute chest syndrome	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Asthma	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Pneumonia aspiration	0/231 (0%)	0	2/236 (0.8%)	2	0/232 (0%)	0
Other (Not Including Serious) Adverse Events
	Coad Group		RTS,S Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	219/231 (94.8%)		221/236 (93.6%)		207/232 (89.2%)
Blood and lymphatic system disorders
Anaemia	2/231 (0.9%)	2	1/236 (0.4%)	1	3/232 (1.3%)	3
Lymphadenitis	1/231 (0.4%)	1	2/236 (0.8%)	2	2/232 (0.9%)	2
Microcytic anaemia	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Congenital, familial and genetic disorders
Sickle cell anaemia	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Ear and labyrinth disorders
Cerumen impaction	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Excessive cerumen production	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Eye disorders
Conjunctivitis allergic	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Vernal keratoconjunctivitis	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Gastrointestinal disorders
Aphthous ulcer	1/231 (0.4%)	1	0/236 (0%)	0	2/232 (0.9%)	2
Constipation	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Diarrhoea	14/231 (6.1%)	14	17/236 (7.2%)	17	22/232 (9.5%)	28
Enteritis	37/231 (16%)	42	42/236 (17.8%)	53	54/232 (23.3%)	77
Infantile colic	1/231 (0.4%)	1	1/236 (0.4%)	1	2/232 (0.9%)	2
Mouth ulceration	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Stomatitis	4/231 (1.7%)	4	2/236 (0.8%)	2	13/232 (5.6%)	14
Vomiting	2/231 (0.9%)	2	3/236 (1.3%)	3	4/232 (1.7%)	5
General disorders
Injection site erythema	11/231 (4.8%)	11	16/236 (6.8%)	16	2/232 (0.9%)	2
Injection site inflammation	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Injection site pain	38/231 (16.5%)	38	31/236 (13.1%)	38	1/232 (0.4%)	1
Injection site swelling	15/231 (6.5%)	16	15/236 (6.4%)	15	1/232 (0.4%)	1
Irritability postvaccinal	31/231 (13.4%)	36	37/236 (15.7%)	43	6/232 (2.6%)	7
Pyrexia	101/231 (43.7%)	138	95/236 (40.3%)	133	28/232 (12.1%)	31
Vessel puncture site swelling	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Infections and infestations
Abscess	1/231 (0.4%)	1	2/236 (0.8%)	2	1/232 (0.4%)	1
Abscess jaw	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Abscess limb	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Acarodermatitis	2/231 (0.9%)	2	3/236 (1.3%)	4	4/232 (1.7%)	4
Bacterial infection	1/231 (0.4%)	1	0/236 (0%)	0	3/232 (1.3%)	3
Body tinea	4/231 (1.7%)	4	5/236 (2.1%)	7	3/232 (1.3%)	3
Bronchiolitis	5/231 (2.2%)	5	7/236 (3%)	7	5/232 (2.2%)	5
Bullous impetigo	1/231 (0.4%)	1	1/236 (0.4%)	1	0/232 (0%)	0
Cellulitis	0/231 (0%)	0	3/236 (1.3%)	3	2/232 (0.9%)	2
Cellulitis orbital	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Conjunctivitis	26/231 (11.3%)	27	25/236 (10.6%)	29	31/232 (13.4%)	34
Conjunctivitis bacterial	2/231 (0.9%)	2	1/236 (0.4%)	1	0/232 (0%)	0
Conjunctivitis viral	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Cutaneous larva migrans	8/231 (3.5%)	9	6/236 (2.5%)	6	7/232 (3%)	8
Dermatitis infected	15/231 (6.5%)	16	23/236 (9.7%)	25	29/232 (12.5%)	37
Dermatophytosis	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Dysentery	12/231 (5.2%)	13	13/236 (5.5%)	13	15/232 (6.5%)	16
Ear infection	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Eczema infected	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Fungal skin infection	2/231 (0.9%)	2	0/236 (0%)	0	2/232 (0.9%)	2
Furuncle	14/231 (6.1%)	15	4/236 (1.7%)	5	9/232 (3.9%)	10
Gastroenteritis	103/231 (44.6%)	139	120/236 (50.8%)	162	119/232 (51.3%)	192
Gastroenteritis shigella	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Genital candidiasis	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Giardiasis	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Gingivitis	0/231 (0%)	0	0/236 (0%)	0	2/232 (0.9%)	2
Helminthic infection	3/231 (1.3%)	3	2/236 (0.8%)	2	4/232 (1.7%)	4
Hordeolum	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Impetigo	9/231 (3.9%)	10	4/236 (1.7%)	4	18/232 (7.8%)	20
Injection site abscess	1/231 (0.4%)	1	2/236 (0.8%)	2	1/232 (0.4%)	1
Lower respiratory tract infection	3/231 (1.3%)	3	3/236 (1.3%)	3	1/232 (0.4%)	2
Malaria	44/231 (19%)	60	51/236 (21.6%)	65	76/232 (32.8%)	129
Oral candidiasis	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Orchitis	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Otitis externa	1/231 (0.4%)	1	1/236 (0.4%)	1	3/232 (1.3%)	3
Otitis media	20/231 (8.7%)	21	26/236 (11%)	28	30/232 (12.9%)	32
Otitis media acute	2/231 (0.9%)	2	1/236 (0.4%)	1	0/232 (0%)	0
Pharyngitis	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Pneumonia	40/231 (17.3%)	42	33/236 (14%)	37	30/232 (12.9%)	34
Respiratory tract infection	67/231 (29%)	83	68/236 (28.8%)	88	84/232 (36.2%)	114
Rhinitis	17/231 (7.4%)	17	20/236 (8.5%)	22	21/232 (9.1%)	22
Sinusitis bacterial	2/231 (0.9%)	2	0/236 (0%)	0	0/232 (0%)	0
Skin bacterial infection	16/231 (6.9%)	18	16/236 (6.8%)	17	25/232 (10.8%)	35
Skin infection	1/231 (0.4%)	1	1/236 (0.4%)	1	1/232 (0.4%)	1
Staphylococcal skin infection	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Subcutaneous abscess	0/231 (0%)	0	1/236 (0.4%)	1	1/232 (0.4%)	1
Tinea capitis	3/231 (1.3%)	4	1/236 (0.4%)	1	3/232 (1.3%)	3
Tinea infection	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Tinea versicolour	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Tonsillitis	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Typhoid fever	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Upper respiratory tract infection	143/231 (61.9%)	246	149/236 (63.1%)	239	168/232 (72.4%)	314
Urinary tract infection	5/231 (2.2%)	5	3/236 (1.3%)	3	4/232 (1.7%)	4
Varicella	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Viral infection	14/231 (6.1%)	14	6/236 (2.5%)	6	5/232 (2.2%)	5
Viral rash	4/231 (1.7%)	4	1/236 (0.4%)	1	2/232 (0.9%)	2
Wound infection	0/231 (0%)	0	0/236 (0%)	0	2/232 (0.9%)	3
Injury, poisoning and procedural complications
Exposure to toxic agent	0/231 (0%)	0	1/236 (0.4%)	1	1/232 (0.4%)	1
Joint injury	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Lip injury	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Skin abrasion	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Thermal burn	1/231 (0.4%)	1	0/236 (0%)	0	4/232 (1.7%)	4
Vaccination complication	1/231 (0.4%)	1	0/236 (0%)	0	1/232 (0.4%)	1
Metabolism and nutrition disorders
Decreased appetite	19/231 (8.2%)	20	24/236 (10.2%)	27	15/232 (6.5%)	15
Failure to thrive	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Malnutrition	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Musculoskeletal and connective tissue disorders
Bone pain	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Costochondritis	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Musculoskeletal pain	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Nervous system disorders
Facial paralysis	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Intracranial pressure increased	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Somnolence	17/231 (7.4%)	17	14/236 (5.9%)	15	1/232 (0.4%)	1
Renal and urinary disorders
Dysuria	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Reproductive system and breast disorders
Gynaecomastia	0/231 (0%)	0	1/236 (0.4%)	1	0/232 (0%)	0
Respiratory, thoracic and mediastinal disorders
Adenoidal hypertrophy	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Rhinorrhoea	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Skin and subcutaneous tissue disorders
Blister	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Dermatitis	23/231 (10%)	27	25/236 (10.6%)	28	28/232 (12.1%)	30
Dermatitis allergic	2/231 (0.9%)	2	0/236 (0%)	0	3/232 (1.3%)	3
Dermatitis atopic	0/231 (0%)	0	0/236 (0%)	0	3/232 (1.3%)	3
Dermatitis contact	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Dermatitis diaper	4/231 (1.7%)	4	2/236 (0.8%)	2	0/232 (0%)	0
Eczema	1/231 (0.4%)	1	1/236 (0.4%)	1	0/232 (0%)	0
Miliaria	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0
Rash	1/231 (0.4%)	1	3/236 (1.3%)	3	1/232 (0.4%)	1
Rash macular	0/231 (0%)	0	0/236 (0%)	0	1/232 (0.4%)	1
Rash pruritic	1/231 (0.4%)	1	1/236 (0.4%)	1	1/232 (0.4%)	1
Urticaria	1/231 (0.4%)	1	0/236 (0%)	0	0/232 (0%)	0

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.