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    Clinical Trial Results:
    A phase III long-term follow-up study to assess immunological memory induced following primary and booster vaccination with GSK Biologicals’ 10-valent pneumococcal conjugate vaccine (10Pn-PD-DiT), through evaluation of early antibody responses after an additional dose of 10Pn-PD-DiT at 40-48 months of age, to evaluate in the fourth year of life, the immunogenicity and safety of a 2-dose catch-up immunization course with the 10Pn-PD-DiT vaccine and the impact of pneumococcal vaccination on nasopharyngeal carriage.

    Summary
    EudraCT number
    		 2008-008104-41
    Trial protocol
    		 CZ  
    Global end of trial date
    29 Jul 2011

    Results information
    Results version number
    		 v3(current)
    This version publication date
    20 May 2023
    First version publication date
    02 Aug 2015
    Other versions
    		 v1 , v2
    Version creation reason
    • Correction of full data set
    Correction of full data set and alignment between registries.

    Trial information

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    Trial identification
    Sponsor protocol code
    112801
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00950833
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-000673-PIP01-09
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    19 Aug 2011
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    16 Sep 2010
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jul 2011
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the immunological memory induced following primary vaccination in study 10PN-PD-DIT-010 (107017) and booster vaccination in study 10PN-PD-DIT-014 (107137) with the 10Pn-PD-DiT vaccine, through evaluation of early antibody responses after an additional dose of 10Pn-PD-DiT at 40-48 months of age, compared to the unprimed group. Criteria for immune memory: The immune memory will be demonstrated if the lower limit of the 95% CI around the GMC ratios (pooled primed groups over unprimed group) is higher than 1 for all 10 vaccine serotypes.
    Protection of trial subjects
    The subjects were observed closely for at least 30 minutes following the administration of vaccine(s), with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    10 Aug 2009
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Czech Republic: 466
    Worldwide total number of subjects
    466
    EEA total number of subjects
    466
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    466
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Out of the 466 subjects enrolled in the study, 5 subjects were not included in the Total effective cohort as they did not meet eligibility criteria. Out of the 461 subjects enrolled in the Total effective cohort, 18 subjects were not included in the Total vaccinated cohort as these subjects withdrew before the first vaccination visit (Visit 2).

    Pre-assignment period milestones
    Number of subjects started
    		 466
    Number of subjects completed
    		 443

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Vaccine not administered: 5
    Reason: Number of subjects
    		 Consent withdrawn by subject: 18
    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Synflorix I Group
    Arm description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects received prophylactic antipyretic (AP) treatment with paracetamol.
    Arm type
    		 Experimental

    Investigational medicinal product name
    10-valent pneumococcal conjugate vaccine
    Investigational medicinal product code
    Other name
    10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose administered intramuscularly in the deltoid muscle at Month 9 (40-48 months of age).

    Arm title
    		 Synflorix II Group
    Arm description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects did not receive any prophylactic antipyretic (AP) treatment.
    Arm type
    		 Experimental

    Investigational medicinal product name
    10-valent Streptococcus pneumoniae conjugate vaccine
    Investigational medicinal product code
    Other name
    10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose administered intramuscularly in the deltoid region at Month 9 (40-48 months of age).

    Arm title
    		 Synflorix III Group
    Arm description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    10-valent Streptococcus pneumoniae conjugate vaccine
    Investigational medicinal product code
    Other name
    10Pn, 10Pn-PD-DiT, GlaxoSmithKline (GSK) Biologicals’ 10-valent pneumococcal conjugate vaccine, Synflorix, GlaxoSmithKline (GSK) Biologicals’ 1024850A vaccine
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Two doses administered intramuscularly in the deltoid muscle at Month 9 (40-48 months of age) and Month 11 (42-50 months of age).

    Number of subjects in period 1 [1]
    		Synflorix I Group Synflorix II Group Synflorix III Group
    Started
    112
    108
    223
    Completed
    112
    108
    223
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Out of the 466 subjects enrolled in the study, 5 subjects were not included in the Total effective cohort as they did not meet eligibility criteria. Out of the 461 subjects enrolled in the Total effective cohort, 18 subjects were not included in the Total vaccinated cohort as these subjects withdrew before the first vaccination visit (Visit 2).

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Synflorix I Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects received prophylactic antipyretic (AP) treatment with paracetamol.

    Reporting group title
    Synflorix II Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects did not receive any prophylactic antipyretic (AP) treatment.

    Reporting group title
    Synflorix III Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.

    Reporting group values
    		 Synflorix I Group Synflorix II Group Synflorix III Group Total
    Number of subjects
    		 112 108 223 443
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0
        Children (2-11 years)
    		 112 108 223 443
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 0 0 0 0
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 39.2 ± 1.53 39.1 ± 1.54 37.7 ± 3.36 -
    Gender categorical
    Units: Subjects
        Female
    		 60 48 99 207
        Male
    		 52 60 124 236
    Subject analysis sets

    Subject analysis set title
    Pooled primed Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.

    Subject analysis sets values
    		 Pooled primed Group
    Number of subjects
    220
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    220
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    39.15 ± 1.53
    Gender categorical
    Units: Subjects
        Female
    108
        Male
    112

    End points

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    End points reporting groups
    Reporting group title
    Synflorix I Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects received prophylactic antipyretic (AP) treatment with paracetamol.

    Reporting group title
    Synflorix II Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects did not receive any prophylactic antipyretic (AP) treatment.

    Reporting group title
    Synflorix III Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.

    Subject analysis set title
    Pooled primed Group
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    For the purpose of the analysis, subjects from Synflorix I Group and Synflorix II Group have been pooled into a sub-group.

    Primary: Antibody concentrations against vaccine pneumococcal serotypes

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    End point title
    		 Antibody concentrations against vaccine pneumococcal serotypes [1]
    End point description
    Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition enzyme linked immunosorbent assay (ELISA), presented as geometric mean concentrations (GMCs) and expressed in micrograms per milliliter (μg/mL). The seropositivity cut-off value of the assay was an antibody concentration greater than or equal to (≥) 0.05 μg/mL. The analysis was performed on the According-to-Protocol (ATP) cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Primary
    End point timeframe
    At 7-10 days after the first vaccine dose
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    204
    215
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Anti-1 (N=204;215)
    1.24 (1.07 to 1.42)
    7.63 (6.57 to 8.86)
        Anti-4 (N=204;215)
    4.52 (3.96 to 5.17)
    12.95 (11.37 to 14.75)
        Anti-5 (N=202;215)
    0.72 (0.63 to 0.84)
    9.76 (8.44 to 11.29)
        Anti-6B (N=203;215)
    0.27 (0.22 to 0.33)
    7.67 (6.7 to 8.78)
        Anti-7F (N=204;215)
    1.37 (1.19 to 1.58)
    6.51 (5.69 to 7.46)
        Anti-9V (N=202;213)
    0.69 (0.58 to 0.83)
    9.75 (8.46 to 11.24)
        Anti-14 (N=204;214)
    1.01 (0.8 to 1.27)
    23.07 (20.03 to 26.57)
        Anti-18C (N=204;214)
    3.25 (2.71 to 3.9)
    32.54 (28.15 to 37.61)
        Anti-19F (N=204;214)
    4.31 (3.59 to 5.17)
    39.84 (34.12 to 46.51)
        Anti-23F (N=204;215)
    0.25 (0.2 to 0.32)
    9.24 (7.86 to 10.86)
    Statistical analysis title
    		 Immune response non-inferiority - Anti-1
    Statistical analysis description
    To demonstrate the immunological memory induced for anti-pneumococcal serotype 1 following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    6.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.03
         upper limit
    		 7.58
    Notes
    [2] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 1.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-4
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 4 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    2.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.38
         upper limit
    		 3.45
    Notes
    [3] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled SynflorixI+II Group over Synflorix Group) was higher than 1 for pneumococcal serotype 4.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-5
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 6B induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    13.47
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.96
         upper limit
    		 16.55
    Notes
    [4] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 5.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-6B
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 6B induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    28.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 22.54
         upper limit
    		 36.81
    Notes
    [5] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 6B.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-7F
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 7F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    4.75
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.9
         upper limit
    		 5.78
    Notes
    [6] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 7F.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-9V
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 9V induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    14.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.21
         upper limit
    		 17.75
    Notes
    [7] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 9V.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-14
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 14 induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    22.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 17.51
         upper limit
    		 30
    Notes
    [8] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 14.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-18C
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 18C induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    10.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.95
         upper limit
    		 12.61
    Notes
    [9] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 18C.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-19F
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 19F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    9.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.29
         upper limit
    		 11.74
    Notes
    [10] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 19F.
    Statistical analysis title
    		 Immune response non-inferiority - Anti-23F
    Statistical analysis description
    To demonstrate the immunological memory for anti-pneumococcal serotype 23F induced following primary vaccination in study 107017 (NCT00370318) and booster vaccination in study 107137 (NCT00496015) with the Synflorix vaccine, through evaluation of early antibody responses after an additional dose of Synflorix vaccine at 40-48 months of age, compared to the Synflorix III Group.
    Comparison groups
    Synflorix III Group v Pooled primed Group
    Number of subjects included in analysis
    419
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    Parameter type
    		 GMC ratio
    Point estimate
    36.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 27.59
         upper limit
    		 48.34
    Notes
    [11] - The immune memory would be demonstrated if the lower limit (LL) of the 95% confidence interval (CI) around the geometric mean concentration (GMC) ratios (Pooled Synflorix I+II Group over Synflorix III Group) was higher than 1 for pneumococcal serotype 23F.

    Secondary: Antibody concentrations against vaccine pneumococcal serotypes

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    End point title
    		 Antibody concentrations against vaccine pneumococcal serotypes [12]
    End point description
    Antibody concentrations against pneumococcal serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F) have been assessed by 22F-inhibition ELISA, presented as GMCs and expressed in μg/mL. The seropositivity cut-off value of the assay was an antibody concentration ≥ 0.05 μg/mL. The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    Prior to the first study vaccine dose (At Day 0)
    Notes
    [12] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    209
    215
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Anti-1 (N=208;215)
    0.09 (0.08 to 0.11)
    0.27 (0.23 to 0.33)
        Anti-4 (N=206;213)
    0.05 (0.04 to 0.06)
    0.2 (0.17 to 0.23)
        Anti-5 (N=208;212)
    0.1 (0.09 to 0.11)
    0.41 (0.36 to 0.47)
        Anti-6B (N=202;212)
    0.1 (0.08 to 0.12)
    0.8 (0.61 to 1.05)
        Anti-7F (N=209;215)
    0.06 (0.05 to 0.07)
    0.48 (0.41 to 0.56)
        Anti-9V (N=203;211)
    0.07 (0.06 to 0.09)
    0.5 (0.41 to 0.61)
        Anti-14 (N=203;213)
    0.28 (0.22 to 0.36)
    1.21 (0.97 to 1.5)
        Anti-18C (N=205;215)
    0.09 (0.07 to 0.11)
    0.65 (0.54 to 0.79)
        Anti-19F (N=208;215)
    0.44 (0.32 to 0.59)
    2.35 (1.75 to 3.15)
        Anti-23F (N=207;215)
    0.08 (0.07 to 0.1)
    0.96 (0.72 to 1.29)
    No statistical analyses for this end point

    Secondary: Opsonophagocytic activity (OPA) titers against vaccine pneumococcal serotypes

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    End point title
    		 Opsonophagocytic activity (OPA) titers against vaccine pneumococcal serotypes [13]
    End point description
    Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    Prior to (Day 0/PRE) and 7-10 days after (POST) the first vaccine dose
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    191
    199
    Units: Titres
    geometric mean (confidence interval 95%)
        Opsono-1, PRE (N=191;199)
    5.4 (4.7 to 6.2)
    10.2 (8 to 12.9)
        Opsono-1, POST (N=182;194)
    632 (524.4 to 761.7)
    3106.5 (2670 to 3614.5)
        Opsono-4, PRE (N=174;189)
    9.1 (6.8 to 12.1)
    18.1 (13.1 to 24.9)
        Opsono-4, POST (N=187;195)
    13109.9 (11080.6 to 15510.7)
    27273.3 (22682.9 to 32792.6)
        Opsono-5, PRE (N=185;199)
    4 (4 to 4.1)
    8.9 (7.6 to 10.5)
        Opsono-5, POST (N=182;194)
    145.8 (111.7 to 190.3)
    1020 (874 to 1190.2)
        Opsono-6B, PRE (N=173;183)
    46.7 (29.8 to 73.3)
    163.5 (108.5 to 246.4)
        Opsono-6B, POST (N=184;192)
    1472.2 (1053.2 to 2057.8)
    5789.5 (4637.3 to 7227.9)
        Opsono-7F, PRE (N=167;187)
    973.4 (798.5 to 1186.6)
    1112.3 (951.4 to 1300.4)
        Opsono-7F, POST (N=186;191)
    13647.4 (11801.9 to 15781.3)
    19988.9 (16834.5 to 23734.2)
        Opsono-9V, PRE (N=156;171)
    268.2 (192.2 to 374.3)
    481.8 (394.6 to 588.1)
        Opsono-9V, POST (N=186;194)
    14668.8 (12476.1 to 17247)
    17952.5 (14699.2 to 21925.7)
        Opsono-14, PRE (N=166;184)
    145.3 (97.5 to 216.6)
    267.6 (196.9 to 363.8)
        Opsono-14, POST (N=187;195)
    4454.3 (3921.1 to 5059.9)
    16256.8 (13573 to 19471.4)
        Opsono-18C, PRE (N=169;186)
    5.7 (4.7 to 7)
    14.2 (10.6 to 19.2)
        Opsono-18C, POST (N=180;188)
    9092.2 (7381.2 to 11199.9)
    7413.8 (6072.3 to 9051.6)
        Opsono-19F, PRE (N=186;192)
    12.9 (9.6 to 17.2)
    79.5 (55.4 to 113.9)
        Opsono-19F, POST (N=190;192)
    902.5 (659.2 to 1235.6)
    6271.1 (4814.8 to 8168)
        Opsono-23F, PRE (N=166;189)
    220.6 (132 to 368.7)
    462.7 (292.9 to 730.9)
        Opsono-23F, POST (N=189;197)
    5776.5 (4686.8 to 7119.5)
    15613.5 (12386.9 to 19680.6)
    No statistical analyses for this end point

    Secondary: Antibody concentrations against vaccine pneumococcal cross-reactive serotypes 6A and 19A

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    End point title
    		 Antibody concentrations against vaccine pneumococcal cross-reactive serotypes 6A and 19A [14]
    End point description
    The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    Prior to (Day 0/PRe) and 7-10 days after (PI) the first vaccine dose
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    207
    215
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Anti-6A, PRE (N=207;214)
    0.11 (0.09 to 0.13)
    0.39 (0.3 to 0.5)
        Anti-6A, PI (N=203;215)
    0.2 (0.17 to 0.25)
    2.4 (2.01 to 2.85)
        Anti-19A, PRE (N=207;215)
    0.22 (0.18 to 0.28)
    0.52 (0.41 to 0.67)
        Anti-19A, PI (N=203;214)
    0.65 (0.52 to 0.82)
    6.75 (5.41 to 8.41)
    No statistical analyses for this end point

    Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A

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    End point title
    		 Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A [15]
    End point description
    Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (Opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs). The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    Prior to (Day 0/PRE) and 7-10 days after (PI) the first vaccine dose
    Notes
    [15] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    183
    191
    Units: Titres
    geometric mean (confidence interval 95%)
        Opsono-6A, PRE (N=167;178)
    49 (32.4 to 74)
    95.2 (65.3 to 138.7)
        Opsono-6A, PI (N=180;191)
    863.3 (619.3 to 1203.4)
    2408.4 (1815.7 to 3194.5)
        Opsono-19A, PRE (N=183;190)
    10.3 (7.9 to 13.4)
    15.9 (11.7 to 21.6)
        Opsono-19A, PI (N=175;191)
    880.5 (622.7 to 1245)
    2104.9 (1560.9 to 2838.7)
    No statistical analyses for this end point

    Secondary: Antibody concentrations against protein D (anti-PD)

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    End point title
    		 Antibody concentrations against protein D (anti-PD) [16]
    End point description
    Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL. The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against protein D were available after vaccination.
    End point type
    Secondary
    End point timeframe
    Prior to (Day 0/PRE) and 7-10 days after (PI) the first vaccine dose
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    204
    215
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-PD, PRE (N=198;210)
    105.6 (93.8 to 119)
    464.2 (401.6 to 536.5)
        Anti-PD, PI (N=204;215)
    374.3 (315.1 to 444.6)
    2673.7 (2359.1 to 3030.2)
    No statistical analyses for this end point

    Secondary: Memory B-cell detection for vaccine polysaccharides (PS)

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    End point title
    		 Memory B-cell detection for vaccine polysaccharides (PS)
    End point description
    B-cell detection for the pneumococcal serotype specific polysaccharides (1, 5, 6B, 18C, 19F, 23F and C) was tabulated for a subset of subjects from each group. The results are expressed as the frequencies of antigen-specific memory B-cells within the total memory B-cell population. The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    Prior to (Day 0/PRE) and 7-10 days after (POST) the first vaccine dose
    End point values
    		 Synflorix I Group Synflorix II Group Synflorix III Group
    Number of subjects analysed
    112
    107
    210
    Units: Memory B-cells
    arithmetic mean (standard deviation)
        1 PS, PRE (N=23;22;47)
    288.6 ± 352.5
    269.5 ± 432.2
    254.8 ± 368.4
        5 PS, PRE (N=26;27;42)
    139.4 ± 214.7
    141.9 ± 232.4
    81.5 ± 109.2
        6B PS, PRE (N=20;22;44)
    372 ± 545.5
    327.2 ± 554.4
    639.9 ± 846.5
        18C PS, PRE (N=26;26;42)
    537.7 ± 641.8
    530.9 ± 693.8
    135.2 ± 200.6
        19F PS, PRE (N=20;22;44)
    169.7 ± 415.3
    149.1 ± 194.4
    164.5 ± 343.4
        23F PS, PRE (N=23;22;45)
    112.6 ± 176.1
    285 ± 484.3
    185.6 ± 270.1
        C-PS, PRE (N=70;71;133)
    475.9 ± 682.3
    462.5 ± 704.5
    469.9 ± 639.2
        1 PS, POST (N=23;23;43)
    1488.8 ± 1584.2
    1017.4 ± 1309.9
    755.9 ± 1017.4
        5 PS, POST (N=28;23;37)
    233.5 ± 235.7
    406.6 ± 447.8
    152.6 ± 231
        6B PS, POST (N=16;24;42)
    629.1 ± 773.2
    1265.8 ± 1738.6
    526 ± 648.6
        18C PS, POST (N=28;23;36)
    3839 ± 5960.5
    8308.4 ± 7166.9
    2053.8 ± 2122.2
        19F PS, POST (N=16;23;42)
    1056.7 ± 1334
    1092.4 ± 1724.3
    708.2 ± 1609.4
        23F PS, POST (N=23;23;43)
    579.8 ± 632.5
    1123.7 ± 2095.4
    327.9 ± 470.5
        C-PS, POST (N=67;70;123)
    679.2 ± 885.8
    915.5 ± 1191.3
    762.6 ± 1039.4
    No statistical analyses for this end point

    Secondary: Antibody concentrations against vaccine pneumococcal serotypes

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    End point title
    		 Antibody concentrations against vaccine pneumococcal serotypes [17]
    End point description
    The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (anti-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). Antibody concentrations were measured by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs), expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    At Month 12, one month after the second vaccine dose
    Notes
    [17] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    209
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Anti-1 (N=209)
    2.33 (2.13 to 2.54)
        Anti-4 (N=209)
    6.26 (5.73 to 6.84)
        Anti-5 (N=209)
    2.69 (2.44 to 2.96)
        Anti-6B (N=209)
    0.84 (0.73 to 0.97)
        Anti-7F (N=208)
    3.63 (3.33 to 3.95)
        Anti-9V (N=209)
    1.73 (1.56 to 1.93)
        Anti-14 (N=209)
    5.21 (4.6 to 5.89)
        Anti-18C (N=209)
    13.59 (11.91 to 15.51)
        Anti-19F (N=209)
    11.83 (10.35 to 13.52)
        Anti-23F (N=209)
    0.99 (0.86 to 1.15)
    No statistical analyses for this end point

    Secondary: Opsonophagocytic activity (OPA) titers against vaccine pneumococcal serotypes

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    End point title
    		 Opsonophagocytic activity (OPA) titers against vaccine pneumococcal serotypes [18]
    End point description
    Seropositivity status was defined as the opsonophagocytic activity (OPA) against pneumococcal serotypes ≥ the value of 8, presented as geometric mean titers (GMTs). The vaccine pneumococcal serotypes assessed were 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F (Opsono-1, -4, -5, -6B, -7F, -9V, -14, -18C, -19F and -23F). The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    At Month 12, one month after the second vaccine dose
    Notes
    [18] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    201
    Units: Titres
    geometric mean (confidence interval 95%)
        Opsono-1 (N=201)
    125.6 (105 to 150.1)
        Opsono-4 (N=200)
    2451.2 (2203.6 to 2726.8)
        Opsono-5 (N=198)
    57.2 (47.3 to 69.1)
        Opsono-6B (N=196)
    1345 (1066.8 to 1695.7)
        Opsono-7F (N=198)
    6527.2 (5836.5 to 7299.6)
        Opsono-9V (N=197)
    6091.6 (5328.7 to 6963.8)
        Opsono-14 (N=197)
    4544.9 (4030.2 to 5125.4)
        Opsono-18C (N=196)
    3827.5 (3367.5 to 4350.4)
        Opsono-19F (N=201)
    1251 (1045.6 to 1496.8)
        Opsono-23F (N=198)
    4629.1 (3890.6 to 5507.8)
    No statistical analyses for this end point

    Secondary: Antibody concentrations against vaccine pneumococcal cross-reactive serotypes 6A and 19A

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    End point title
    		 Antibody concentrations against vaccine pneumococcal cross-reactive serotypes 6A and 19A [19]
    End point description
    The vaccine pneumococcal cross-reactive serotypes 6A and 19A have been assessed by 22F-inhibition ELISA, presented as geometric mean concentrations (GMCs) and expressed in μg/mL. The seropositivity cut-off of the assay was an antibody concentration ≥ 0.05 μg/mL. The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    At Month 12, one month after the second vaccine dose
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    209
    Units: μg/mL
    geometric mean (confidence interval 95%)
        Anti-6A
    0.51 (0.43 to 0.6)
        Anti-19A
    1.99 (1.68 to 2.36)
    No statistical analyses for this end point

    Secondary: Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A

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    End point title
    		 Opsonophagocytic activity (OPA) titers against pneumococcal cross-reactive serotypes 6A and 19A [20]
    End point description
    Seropositivity status was defined as the opsonophagocytic activity against pneumococcal cross-reactive serotypes 6A and 19A (opsono-16A and opsono-19A) ≥ the value of 8, presented as geometric mean titers (GMTs). The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against at least one pneumococcal vaccine serotype were available after vaccination.
    End point type
    Secondary
    End point timeframe
    At Month 12, one month after the second vaccine dose
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    196
    Units: Titres
    geometric mean (confidence interval 95%)
        Opsono-6A (N=193)
    918.6 (742.7 to 1136.1)
        Opsono-19A (N=196)
    597.6 (467.2 to 764.4)
    No statistical analyses for this end point

    Secondary: Antibody concentrations against protein D (anti-PD)

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    End point title
    		 Antibody concentrations against protein D (anti-PD) [21]
    End point description
    Anti-protein D (anti-PD) concentrations were presented as geometric mean concentrations (GMCs), expressed in ELISA units per milliliter (EL.U/mL). The seropositivity cut-off value of the assay was an antibody concentration ≥ 100 EL.U/mL. The analysis was performed on the ATP cohort for immunogenicity, which included all evaluable subjects for whom data concerning immunogenicity outcome measures and assay results for antibodies against protein D were available after vaccination.
    End point type
    Secondary
    End point timeframe
    At Month 12, one month after the second vaccine dose
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    209
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-PD
    785.9 (695.7 to 887.7)
    No statistical analyses for this end point

    Secondary: Rabbit complement-mediated serum bactericidal activity titers against Neisseria meningitidis serogroups (rSBA-Men)

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    End point title
    		 Rabbit complement-mediated serum bactericidal activity titers against Neisseria meningitidis serogroups (rSBA-Men) [22]
    End point description
    The Neisseria meningitidis serogroups assessed using rabbit complement were: A, C, W-135 and Y (rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY), presented as geometric mean titers (GMTs). The seropositivity cut-off of the assay was an antibody titer ≥ 8. The analysis was performed on the ATP cohort for antibody persistence, which included all subjects with the vaccine administration documented, for whom assay results were available for antibodies against each considered antigen for the blood sample taken before the administration of Synflorix vaccine.
    End point type
    Secondary
    End point timeframe
    At 25-36 months post-vaccination in previous 107137 (NCT00496015) study
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    83
    Units: Titres
    geometric mean (confidence interval 95%)
        rSBA-MenA (N=66)
    325.5 (243.9 to 434.5)
        rSBA-MenC (N=80)
    63.6 (41.2 to 98)
        rSBA-MenY (N=83)
    372.2 (270 to 513)
        rSBA-MenW-135 (N=83)
    247.6 (190.7 to 321.5)
    No statistical analyses for this end point

    Secondary: Number of subjects with any and grade 3 solicited local symptoms

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    End point title
    		 Number of subjects with any and grade 3 solicited local symptoms [23]
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the primed groups. The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix I Group and the Synflorix II Group.
    End point values
    		 Synflorix I Group Synflorix II Group
    Number of subjects analysed
    112
    108
    Units: Subjects
        Any pain
    75
    67
        Grade 3 pain
    7
    5
        Any redness
    58
    60
        Grade 3 redness
    13
    12
        Any swelling
    43
    41
        Grade 3 swelling
    11
    11
    No statistical analyses for this end point

    Secondary: Number of subjects with any and grade 3 solicited local symptoms

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    End point title
    		 Number of subjects with any and grade 3 solicited local symptoms [24]
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any local symptom regardless of intensity grade. Grade 3 pain = cried when limb was moved/spontaneously painful. Grade 3 redness/swelling = redness/swelling spreading beyond 30 millimeters (mm) of injection site. This outcome measure refers only to the unprimed group. The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    223
    Units: Subjects
        Any pain, D1 (N=223)
    150
        Grade 3 pain, D1 (N=223)
    13
        Any redness, D1 (N=223)
    102
        Grade 3 redness, D1 (N=223)
    23
        Any swelling, D1 (N=223)
    78
        Grade 3 swelling, D1 (N=223)
    14
        Any pain, D2 (N=222)
    121
        Grade 3 pain, D2 (N=222)
    12
        Any redness, D2 (N=222)
    93
        Grade 3 redness, D2 (N=222)
    12
        Any swelling, D2 (N=222)
    65
        Grade 3 swelling, D2 (N=222)
    3
        Any pain, Across (N=223)
    167
        Grade 3 pain, Across (N=223)
    23
        Any redness, Across (N=223)
    127
        Grade 3 redness, Across (N=223)
    29
        Any swelling, Across (N=223)
    101
        Grade 3 swelling, Across (N=223)
    16
    No statistical analyses for this end point

    Secondary: Number of subjects with any, grade 3 and related solicited general symptoms

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    End point title
    		 Number of subjects with any, grade 3 and related solicited general symptoms [25]
    End point description
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the primed groups. The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix I Group and the Synflorix II Group.
    End point values
    		 Synflorix I Group Synflorix II Group
    Number of subjects analysed
    112
    108
    Units: Subjects
        Any drowsiness
    41
    34
        Related drowsiness
    0
    0
        Grade 3 drowsiness
    26
    26
        Any Irritability
    33
    26
        Related Irritability
    1
    0
        Grade 3 Irritability
    21
    16
        Any loss of appetite
    23
    15
        Related loss of appetite
    1
    1
        Grade 3 loss of appetite
    13
    10
        Any fever (Axillary/37.5°C)
    12
    8
        Grade 3 fever (Axillary/39.5°C)
    0
    1
        Related fever
    10
    5
    No statistical analyses for this end point

    Secondary: Number of subjects with any, grade 3 and related solicited general symptoms

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    End point title
    		 Number of subjects with any, grade 3 and related solicited general symptoms [26]
    End point description
    Assessed solicited general symptoms were drowsiness, irritability, loss of appetite and fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)]. Any = occurrence of any general symptom regardless of intensity grade or relationship to vaccination. Grade 3 drowsiness = drowsiness that prevented normal activity. Grade 3 irritability = crying that could not be comforted/ prevented normal activity. Grade 3 loss of appetite = not eating at all. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as causally related to study vaccination. This outcome measure refers only to the unprimed group. The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period following each dose and across doses
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group.
    End point values
    		 Synflorix III Group
    Number of subjects analysed
    223
    Units: Subjects
        Any drowsiness, D1 (N=223)
    79
        Grade 3 drowsiness, D1 (N=223)
    1
        Related drowsiness, D1 (N=223)
    56
        Any Irritability, D1 (N=223)
    69
        Grade 3 Irritability, D1 (N=223)
    2
        Related irritability, D1 (N=223)
    49
        Any loss of appetite, D1 (N=223)
    47
        Grade 3 loss of appetite, D1 (N=223)
    5
        Related loss of appetite, D1 (N=223)
    32
        Any fever (Axillary/37.5°C), D1 (N=223)
    23
        Grade 3 fever (Axillary/39.5°C), D1 (N=223)
    1
        Related fever, D1 (N=223)
    15
        Any drowsiness, D2 (N=222)
    60
        Grade 3 drowsiness, D2 (N=222)
    1
        Related drowsiness, D2 (N=222)
    43
        Any Irritability, D2 (N=222)
    59
        Grade 3 Irritability, D2 (N=222)
    1
        Related irritability, D2 (N=222)
    44
        Any loss of appetite, D2 (N=222)
    26
        Grade 3 loss of appetite, D2 (N=222)
    1
        Related loss of appetite, D2 (N=222)
    16
        Any fever (Axillary/37.5°C), D2 (N=222)
    9
        Grade 3 fever (Axillary/39.5°C), D2 (N=222)
    1
        Related fever, D2 (N=222)
    5
        Any drowsiness, Across (N=223)
    102
        Grade 3 drowsiness, Across (N=223)
    2
        Related drowsiness, Across (N=223)
    73
        Any Irritability, Across (N=223)
    98
        Grade 3 Irritability, Across (N=223)
    3
        Related irritability, Across (N=223)
    74
        Any loss of appetite, Across (N=223)
    61
        Grade 3 loss of appetite, Across (N=223)
    6
        Related loss of appetite, Across (N=223)
    42
        Any fever (Axillary/37.5°C), Across (N=223)
    30
        Grade 3 fever (Axillary/39.5°C), Across (N=223)
    2
        Related fever, Across (N=223)
    19
    No statistical analyses for this end point

    Secondary: Number of subjects with any unsolicited adverse events (AEs)

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    End point title
    		 Number of subjects with any unsolicited adverse events (AEs)
    End point description
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
    End point type
    Secondary
    End point timeframe
    Within 31 days (Days 0-30) after each vaccination
    End point values
    		 Synflorix I Group Synflorix II Group Synflorix III Group
    Number of subjects analysed
    112
    108
    223
    Units: Subjects
        Any AE(s)
    24
    29
    73
    No statistical analyses for this end point

    Secondary: Number of subjects with serious adverse events (SAEs)

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    End point title
    		 Number of subjects with serious adverse events (SAEs)
    End point description
    Serious adverse events (SAEs) assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity. The analysis was performed on the Total Vaccinated Cohort, which included all vaccinated subjects.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Day 0 up to Month 10 or Month 12)
    End point values
    		 Synflorix I Group Synflorix II Group Synflorix III Group
    Number of subjects analysed
    112
    108
    223
    Units: Subjects
        Any SAE(s)
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of nasopharyngeal swabs with Streptococcus pneumoniae (vaccine serotypes)

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    End point title
    		 Number of nasopharyngeal swabs with Streptococcus pneumoniae (vaccine serotypes) [27]
    End point description
    Positive cultures of S. pneumoniae Synflorix vaccine serotypes identified in the nasopharynx were recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Swabs
        31-44 months (N=210;216)
    40
    21
        40-48 months (N=208;212)
    46
    20
    No statistical analyses for this end point

    Secondary: Number of nasopharyngeal swabs with S.pneumoniae (cross-reactive serotypes)

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    End point title
    		 Number of nasopharyngeal swabs with S.pneumoniae (cross-reactive serotypes) [28]
    End point description
    Positive cultures of S. pneumoniae cross- reactive serotypes identified in the nasopharynx were recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Swabs
        31-44 months (N=210;216)
    9
    13
        40-48 months (N=208;212)
    19
    18
    No statistical analyses for this end point

    Secondary: Number of nasopharyngeal swabs with S.pneumoniae (non-vaccine and non-cross-reactive serotypes)

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    End point title
    		 Number of nasopharyngeal swabs with S.pneumoniae (non-vaccine and non-cross-reactive serotypes) [29]
    End point description
    Positive cultures of S. pneumoniae non- Synflorix vaccine, non-cross-reactive serotypes identified in the nasopharynx were recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Swabs
        31-44 months (N=210;216)
    25
    34
        40-48 months (N=208;212)
    27
    35
    No statistical analyses for this end point

    Secondary: Number of nasopharyngeal swabs with Haemophilus influenzae

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    End point title
    		 Number of nasopharyngeal swabs with Haemophilus influenzae [30]
    End point description
    Positive cultures of H. influenzae identified in the nasopharynx were recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Swabs
        31-44 months (N=210;216)
    43
    54
        40-48 months (N=208;212)
    89
    74
    No statistical analyses for this end point

    Secondary: Number of subjects with new acquisition of S. pneumoniae (vaccine serotypes) in nasopharyngeal swabs

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    End point title
    		 Number of subjects with new acquisition of S. pneumoniae (vaccine serotypes) in nasopharyngeal swabs [31]
    End point description
    The number of subjects with new acquisition of S. pneumoniae (Synflorix vaccine serotypes) detected in nasopharyngeal swabs was recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [31] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Subjects
        31-44 months (N=210;216)
    39
    20
        40-48 months (N=208;212)
    41
    18
    No statistical analyses for this end point

    Secondary: Number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) in nasopharyngeal swabs

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    End point title
    		 Number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) in nasopharyngeal swabs [32]
    End point description
    The number of subjects with new acquisition of S. pneumoniae (cross-reactive serotypes) detected in nasopharyngeal swabs was recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [32] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Subjects
        31-44 months (N=210;216)
    9
    13
        40-48 months (N=208;212)
    18
    18
    No statistical analyses for this end point

    Secondary: Number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) in nasopharyngeal swabs

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    End point title
    		 Number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) in nasopharyngeal swabs [33]
    End point description
    The number of subjects with new acquisition of S. pneumoniae (non-vaccine and non-cross-reactive serotypes) detected in nasopharyngeal swabs was recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [33] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Subjects
        31-44 months (N=210;216)
    24
    32
        40-48 months (N=208;212)
    25
    33
    No statistical analyses for this end point

    Secondary: Number of subjects with new acquisition of H. influenzae in nasopharyngeal swabs

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    End point title
    		 Number of subjects with new acquisition of H. influenzae in nasopharyngeal swabs [34]
    End point description
    The number of subjects with new acquisition of H. influenzae detected in nasopharyngeal swabs was recorded. The analysis was performed on the ATP cohort for carriage, which included all evaluable subjects for whom carriage outcome measures were available after the swab time point.
    End point type
    Secondary
    End point timeframe
    At 31-44 months of age and prior to the first vaccine dose, at 40-48 months of age
    Notes
    [34] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: This endpoint is only reporting values for the Synflorix III Group and the Pooled primed Group.
    End point values
    		 Synflorix III Group Pooled primed Group
    Number of subjects analysed
    210
    216
    Units: Subjects
        31-44 months (N=210;216)
    35
    49
        40-48 months (N=208;212)
    70
    50
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited symptoms: during the 4-day (Days 0-3) follow-up periods after vaccination. Unsolicited AEs: within the 31-day (Days 0-30) follow-up periods after vaccination. SAEs: during the entire study period (from Day 0 up to Month 10/12).
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.0
    Reporting groups
    Reporting group title
    Synflorix I Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects received prophylactic antipyretic (AP) treatment with paracetamol.

    Reporting group title
    Synflorix II Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were previously given 3 primary vaccination doses of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107017 (NCT00370318) and one booster dose of Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study one dose of Synflorix vaccine at Month 9 (40-48 months of age), administered intramuscularly in the deltoid muscle. At the time of both primary and booster vaccinations, subjects did not receive any prophylactic antipyretic (AP) treatment.

    Reporting group title
    Synflorix III Group
    Reporting group description
    		 Healthy male or female subjects between and including 31 and 44 months of age at the time of enrolment, who were not previously primed with Synflorix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), but vaccinated with Nimenrix vaccine co-administered with Infanrix Hexa vaccine in study 107137 (NCT00496015), additionally received in the current study 2 doses of Synflorix vaccine at Month 9 (40-48 months of age) and at Month 11 (42-50 months of age), administered intramuscularly in the deltoid muscle.

    Serious adverse events
    		 Synflorix I Group Synflorix II Group Synflorix III Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 112 (0.00%)
    0 / 108 (0.00%)
    0 / 223 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Synflorix I Group Synflorix II Group Synflorix III Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    96 / 112 (85.71%)
    86 / 108 (79.63%)
    190 / 223 (85.20%)
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    75 / 112 (66.96%)
    67 / 108 (62.04%)
    167 / 223 (74.89%)
         occurrences all number
    75
    67
    167
    Redness
         subjects affected / exposed
    58 / 112 (51.79%)
    60 / 108 (55.56%)
    127 / 223 (56.95%)
         occurrences all number
    58
    60
    127
    Swelling
         subjects affected / exposed
    43 / 112 (38.39%)
    41 / 108 (37.96%)
    101 / 223 (45.29%)
         occurrences all number
    43
    41
    101
    Drowsiness
         subjects affected / exposed
    41 / 112 (36.61%)
    34 / 108 (31.48%)
    102 / 223 (45.74%)
         occurrences all number
    41
    34
    102
    Irritability
         subjects affected / exposed
    33 / 112 (29.46%)
    26 / 108 (24.07%)
    98 / 223 (43.95%)
         occurrences all number
    33
    26
    98
    Loss of appetite
         subjects affected / exposed
    23 / 112 (20.54%)
    15 / 108 (13.89%)
    61 / 223 (27.35%)
         occurrences all number
    23
    15
    61
    Fever/(Axillary ≥ 37.5°C)
         subjects affected / exposed
    12 / 112 (10.71%)
    8 / 108 (7.41%)
    30 / 223 (13.45%)
         occurrences all number
    12
    8
    30

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    29 Mar 2011
    The primary objective of the current study is to demonstrate the immunological memory induced following primary vaccination in study 10PN-PD-DIT-010 (107017) and booster vaccination in study 10PN-PD-DIT-014 (107137) with the 10Pn-PD-DiT vaccine, through evaluation of early antibody responses after an additional dose of 10Pn-PD-DiT at 40-48 months of age. In addition, as secondary objective, the antibody persistence 25-36 months following vaccination with GSK Biologicals’ MenACWYTT conjugate vaccine in study 10PN-PD-DIT-014 (107137) will be evaluated in terms of the percentage of subjects with N. meningitidis serogroup A, C, W-135 and Y titers ≥ 8 as measured by a serum bactericidal assay using rabbit complement (rSBA). In addition, to support the data obtained by rSBA testing, antibody concentrations against meningococcal polysaccharides are planned to be assessed by ELISA. However, the sponsor has decided not to perform the ELISA testing against meningococcal polysaccharides for this study for the following reasons: ● the World Health Organization (WHO) considers SBA the primary means of assessing immune response to meningococcal conjugate vaccines [WHO, 2006; WHO, 1999] ● circulating bactericidal antibodies are more critical for persistent protection against meningococcal disease than antibodies against meningococcal polysaccharides [CDC, 2011; WHO, 2006]. Although antibody concentrations will not be determined by ELISA, all subjects will be informed of their antibody titers measured by rSBA when statistical analyses have been completed.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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