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    Clinical Trial Results:
    Estudio de fase IIIB, abierto, multinacional, aleatorizado y controlado para demostrar la no inferioridad de la respuesta inmunitaria a la vacuna antimeningocócica (serogrupos A, C, W-135 e Y) conjugada (MenACWY-TT) de GSK Biologicals, administrada por vía intramuscular a los 2, 4 y 12 meses de edad o a los 2, 3, 4 y 12 meses de edad, en comparación con dos vacunas MenC conjugadas y autorizadas, administradas por vía intramuscular a los 2, 4 y 12 meses de edad.

    Summary
    EudraCT number
    		 2009-016841-24
    Trial protocol
    		 ES   DE   EE  
    Global end of trial date
    10 Sep 2013

    Results information
    Results version number
    		 v1
    This version publication date
    22 Apr 2016
    First version publication date
    05 Jun 2015
    Other versions
    		 v2 , v3

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    113369
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01144663
    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-000429-PIP01-08
    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
    03 Jun 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Jun 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    10 Sep 2013
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Demostrar, a los 5 meses de edad: 1.la no inferioridad del esquema de 3 dosis de la vacuna MenACWY-TT conjugada en comparación con el esquema de 2 dosis de la vacuna MenC-CRM197 conjugada 2.la no inferioridad del esquema de 3 dosis de la vacuna MenACWY-TT conjugada, frente al esquema de 2 dosis de la vacuna MenC-TT conjugada 3.la no inferioridad del esquema de 2 dosis de la vacuna MenACWY-TT conjugada frente al esquema de 2 dosis de la vacuna MenC-CRM197 conjugada 4.la no inferioridad del esquema de 2 dosis de la vacuna MenACWY-TT conjugada, frente al esquema de 2 dosis de la vacuna MenC-TT conjugada
    Protection of trial subjects
    All subjects were supervised for 30 min after vaccination/product administration with appropriate medical treatment readily available. Vaccines/products were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines/products. Subjects were followed-up for 30 days after the last vaccination/product administration.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Jul 2010
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Estonia: 34
    Country: Number of subjects enrolled
    Spain: 1559
    Country: Number of subjects enrolled
    Germany: 502
    Worldwide total number of subjects
    2095
    EEA total number of subjects
    2095
    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)
    2095
    Children (2-11 years)
    0
    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
    		 During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

    Period 1
    Period 1 title
    Primary Vaccination
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK134612A 3-dose Group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nimenrix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2, 3 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2, 3, 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2, 3, 4 and 12 months of age.

    Arm title
    		 GSK134612A 2-dose Group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nimenrix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Arm title
    		 Menjugate Group
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Menjugate®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Arm title
    		 NeisVac-C Group
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    NeisVac-CTM
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Number of subjects in period 1
    		GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Started
    528
    524
    516
    527
    Completed
    508
    517
    508
    509
    Not completed
    20
    7
    8
    18
         Other (please specify)
    20
    7
    8
    18
    Period 2
    Period 2 title
    Booster Phase
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GSK134612A 3-dose Group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nimenrix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2, 3 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2, 3, 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2, 3, 4 and 12 months of age.

    Arm title
    		 GSK134612A 2-dose Group
    Arm description
    		 -
    Arm type
    		 Experimental

    Investigational medicinal product name
    Nimenrix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Arm title
    		 Menjugate Group
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Menjugate®
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Arm title
    		 NeisVac-C Group
    Arm description
    		 -
    Arm type
    		 Active comparator

    Investigational medicinal product name
    NeisVac-CTM
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 and 4 months of age and 1 booster dose at 12 months of age.

    Investigational medicinal product name
    Infanrix™ hexa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Investigational medicinal product name
    Synflorix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single dose intramuscular injection at 2 4 and 12 months of age.

    Number of subjects in period 2 [1]
    		GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Started
    497
    511
    503
    506
    Completed
    494
    509
    498
    505
    Not completed
    3
    2
    5
    1
         Consent withdrawn by subject
    -
    -
    1
    1
         Migrated/moved from study area
    1
    1
    1
    -
         Lost to follow-up
    2
    1
    3
    -
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up study. Actual enrolment differed depending on the rate of return for the follow-up study, so not all enrolled subjects came to each visit.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GSK134612A 3-dose Group
    Reporting group description
    		 -

    Reporting group title
    GSK134612A 2-dose Group
    Reporting group description
    		 -

    Reporting group title
    Menjugate Group
    Reporting group description
    		 -

    Reporting group title
    NeisVac-C Group
    Reporting group description
    		 -

    Reporting group values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group Total
    Number of subjects
    		 528 524 516 527 2095
    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)
    		 0
        Adolescents (12-17 years)
    		 0
        Adults (18-64 years)
    		 0
        From 65-84 years
    		 0
        85 years and over
    		 0
    Age continuous
    Units: weeks
        arithmetic mean (standard deviation)
    		 8.7 ± 1.54 8.6 ± 1.52 8.7 ± 1.53 8.6 ± 1.49 -
    Gender categorical
    Units: Subjects
        Female
    		 255 273 264 251 1043
        Male
    		 273 251 252 276 1052

    End points

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    End points reporting groups
    Reporting group title
    GSK134612A 3-dose Group
    Reporting group description
    		 -

    Reporting group title
    GSK134612A 2-dose Group
    Reporting group description
    		 -

    Reporting group title
    Menjugate Group
    Reporting group description
    		 -

    Reporting group title
    NeisVac-C Group
    Reporting group description
    		 -
    Reporting group title
    GSK134612A 3-dose Group
    Reporting group description
    		 -

    Reporting group title
    GSK134612A 2-dose Group
    Reporting group description
    		 -

    Reporting group title
    Menjugate Group
    Reporting group description
    		 -

    Reporting group title
    NeisVac-C Group
    Reporting group description
    		 -

    Primary: Number of subjects with meningococcal polysaccharide C serum bactericidal assay, using baby rabbit complement (rSBA-MenC) titres ≥ 1:8

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    End point title
    		 Number of subjects with meningococcal polysaccharide C serum bactericidal assay, using baby rabbit complement (rSBA-MenC) titres ≥ 1:8 [1]
    End point description
    End point type
    Primary
    End point timeframe
    One month after vaccination.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    0 [2]
    0 [3]
    0 [4]
    0 [5]
    Units: Subjects
    Notes
    [2] - These results were not available at the time of posting. The record will be updated.
    [3] - These results were not available at the time of posting. The record will be updated.
    [4] - These results were not available at the time of posting. The record will be updated.
    [5] - These results were not available at the time of posting. The record will be updated.
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and grade 3 solicited local symptom.

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    End point title
    		 Number of subjects reporting any and grade 3 solicited local symptom.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after each primary vaccine dose.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    518
    523
    509
    518
    Units: Subjects
        Any Pain, D1 (N=518; 523; 509; 517)
    247
    243
    243
    233
        Grade 3 Pain, D1 (N=518; 523; 509; 517)
    32
    33
    28
    34
        Any Redness, D1 (N=518; 523; 509; 517)
    241
    229
    236
    230
        Grade 3 Redness, D1 (N=518; 523; 509; 517)
    9
    5
    9
    5
        Any Swelling, D1 (N=518; 523; 509; 517)
    188
    182
    179
    188
        Grade 3 Swelling, D1 (N=518; 523; 509; 517)
    6
    4
    14
    6
        Any Pain, D2 (N=511; 517; 509; 513)
    212
    210
    230
    214
        Grade 3 Pain, D2 (N=511; 517; 509; 513)
    23
    37
    23
    29
        Any Redness, D2 (N=511; 517; 509; 513)
    261
    271
    283
    284
        Grade 3 Redness, D2 (N=511; 517; 509; 513)
    3
    5
    10
    2
        Any Swelling, D2 (N=511; 517; 509; 513)
    211
    206
    225
    210
        Grade 3 Swelling, D2 (N=511; 517; 509; 513)
    3
    6
    14
    10
        Any Pain, D3 (N=505; 517; 507; 508)
    168
    180
    180
    193
        Grade 3 Pain, D3 (N=505; 517; 507; 508)
    13
    18
    15
    22
        Any Redness, D3 (N=505; 517; 507; 508)
    247
    265
    308
    274
        Grade 3 Redness, D3 (N=505; 517; 507; 508)
    9
    6
    13
    9
        Any Swelling, D3 (N=505; 517; 507; 508)
    210
    216
    252
    218
        Grade 3 Swelling, D3 (N=505; 517; 507; 508)
    8
    6
    11
    13
        Any Pain, Overall (N=518; 523; 509; 518)
    319
    332
    344
    327
        Grade 3 Pain, Overall (N=518; 523; 509; 518)
    54
    67
    48
    69
        Any Redness, Overall (N=518; 523; 509; 518)
    363
    369
    391
    371
        Grade 3 Redness, Overall (N=518; 523; 509; 518)
    18
    15
    24
    15
        Any Swelling, Overall (N=518; 523; 509; 518)
    326
    318
    343
    317
        Grade 3 Swelling, Overall (N=518; 523; 509; 518)
    15
    11
    27
    24
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and grade 3 solicited local symptom post meningococcal vaccination.

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    End point title
    		 Number of subjects reporting any and grade 3 solicited local symptom post meningococcal vaccination.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after each primary vaccine dose.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    518
    523
    509
    518
    Units: Subjects
        Any Pain, D1 (N=518; 523; 509; 517)
    161
    155
    158
    157
        Grade 3 Pain, D1 (N=518; 523; 509; 517)
    18
    17
    12
    24
        Any Redness, D1 (N=518; 523; 509; 517)
    132
    128
    138
    140
        Grade 3 Redness, D1 (N=518; 523; 509; 517)
    2
    1
    2
    1
        Any Swelling, D1 (N=518; 523; 509; 517)
    68
    62
    87
    82
        Grade 3 Swelling, D1 (N=518; 523; 509; 517)
    1
    0
    3
    0
        Any Pain, D2 (N=510; 0; 0; 0)
    125
    0
    0
    0
        Grade 3 Pain, D2 (N=510; 0; 0; 0)
    9
    0
    0
    0
        Any Redness, D2 (N=510; 0; 0; 0)
    131
    0
    0
    0
        Grade 3 Redness, D2 (N=510; 0; 0; 0)
    0
    0
    0
    0
        Any Swelling, D2 (N=510; 0; 0; 0)
    77
    0
    0
    0
        Grade 3 Swelling, D2 (N=510; 0; 0; 0)
    0
    0
    0
    0
        Any Pain, D3 (N=505; 516; 507; 508)
    106
    124
    130
    143
        Grade 3 Pain, D3 (N=505; 516; 507; 508)
    7
    11
    9
    12
        Any Redness, D3 (N=505; 516; 507; 508)
    162
    169
    214
    197
        Grade 3 Redness, D3 (N=505; 516; 507; 508)
    0
    0
    0
    1
        Any Swelling, D3 (N=505; 516; 507; 508)
    104
    115
    137
    130
        Grade 3 Swelling, D3 (N=505; 516; 507; 508)
    0
    1
    0
    4
        Any Pain, Overall (N=518; 523; 509; 518)
    229
    202
    213
    213
        Grade 3 Pain, Overall (N=518; 523; 509; 518)
    29
    26
    19
    33
        Any Redness, Overall (N=518; 523; 509; 518)
    233
    206
    255
    233
        Grade 3 Redness, Overall (N=518; 523; 509; 518)
    2
    1
    2
    2
        Any Swelling, Overall (N=518; 523; 509; 518)
    154
    136
    175
    164
        Grade 3 Swelling, Overall (N=518; 523; 509; 518)
    1
    1
    3
    4
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Infanrix hexa.

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    End point title
    		 Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Infanrix hexa.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after each primary vaccine dose.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    518
    523
    509
    517
    Units: Subjects
        Any Pain, D1 (N=518; 523; 509; 517)
    212
    202
    208
    210
        Grade 3 Pain, D1 (N=518; 523; 509; 517)
    28
    28
    25
    32
        Any Redness, D1 (N=518; 523; 509; 517)
    201
    190
    191
    192
        Grade 3 Redness, D1 (N=518; 523; 509; 517)
    7
    3
    6
    2
        Any Swelling, D1 (N=518; 523; 509; 517)
    148
    148
    128
    147
        Grade 3 Swelling, D1 (N=518; 523; 509; 517)
    6
    4
    13
    4
        Any Pain, D2 (N=511; 517; 509; 513)
    184
    200
    219
    198
        Grade 3 Pain, D2 (N=511; 517; 509; 513)
    18
    34
    22
    27
        Any Redness, D2 (N=511; 517; 509; 513)
    232
    250
    264
    265
        Grade 3 Redness, D2 (N=511; 517; 509; 513)
    1
    5
    10
    2
        Any Swelling, D2 (N=511; 517; 509; 513)
    182
    185
    208
    195
        Grade 3 Swelling, D2 (N=511; 517; 509; 513)
    1
    3
    13
    10
        Any Pain, D3 (N=505; 517; 507; 508)
    144
    159
    153
    175
        Grade 3 Pain, D3 (N=505; 517; 507; 508)
    9
    14
    11
    19
        Any Redness, D3 (N=505; 517; 507; 508)
    228
    243
    272
    247
        Grade 3 Redness, D3 (N=505; 517; 507; 508)
    5
    4
    11
    7
        Any Swelling, D3 (N=505; 517; 507; 508)
    191
    200
    227
    197
        Grade 3 Swelling, D3 (N=505; 517; 507; 508)
    6
    4
    11
    11
        Any Pain, Overall (N=518; 523; 509; 518)
    289
    311
    314
    310
        Grade 3 Pain, Overall (N=518; 523; 509; 518)
    44
    58
    43
    63
        Any Redness, Overall (N=518; 523; 509; 518)
    336
    344
    358
    349
        Grade 3 Redness, Overall (N=518; 523; 509; 518)
    13
    11
    19
    10
        Any Swelling, Overall (N=518; 523; 509; 518)
    297
    292
    308
    294
        Grade 3 Swelling, Overall (N=518; 523; 509; 518)
    12
    7
    25
    21
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Synflorix.

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    End point title
    		 Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Synflorix.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after each primary vaccine dose.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    518
    523
    509
    518
    Units: Subjects
        Any Pain, D1 (N=518; 523; 509; 517)
    218
    201
    217
    195
        Grade 3 Pain, D1 (N=518; 523; 509; 517)
    29
    26
    26
    32
        Any Redness, D1 (N=518; 523; 509; 517)
    209
    184
    196
    183
        Grade 3 Redness, D1 (N=518; 523; 509; 517)
    4
    2
    5
    4
        Any Swelling, D1 (N=518; 523; 509; 517)
    135
    136
    130
    120
        Grade 3 Swelling, D1 (N=518; 523; 509; 517)
    4
    1
    10
    4
        Any Pain, D2 (N=511; 517; 509; 513)
    179
    186
    203
    189
        Grade 3 Pain, D2 (N=511; 517; 509; 513)
    20
    31
    19
    25
        Any Redness, D2 (N=511; 517; 509; 513)
    197
    216
    225
    235
        Grade 3 Redness, D2 (N=511; 517; 509; 513)
    2
    1
    5
    1
        Any Swelling, D2 (N=511; 517; 509; 513)
    154
    162
    156
    155
        Grade 3 Swelling, D2 (N=511; 517; 509; 513)
    3
    4
    8
    5
        Any Pain, D3 (N=505; 517; 507; 508)
    129
    152
    132
    150
        Grade 3 Pain, D3 (N=505; 517; 507; 508)
    10
    13
    10
    18
        Any Redness, D3 (N=505; 517; 507; 508)
    173
    213
    227
    209
        Grade 3 Redness, D3 (N=505; 517; 507; 508)
    4
    4
    6
    2
        Any Swelling, D3 (N=505; 517; 507; 508)
    136
    152
    164
    146
        Grade 3 Swelling, D3 (N=505; 517; 507; 508)
    3
    4
    6
    5
        Any Pain, Overall (N=518; 523; 509; 518)
    285
    304
    312
    291
        Grade 3 Pain, Overall (N=518; 523; 509; 518)
    46
    54
    41
    61
        Any Redness, Overall (N=518; 523; 509; 518)
    297
    322
    331
    316
        Grade 3 Redness, Overall (N=518; 523; 509; 518)
    8
    7
    12
    7
        Any Swelling, Overall (N=518; 523; 509; 518)
    247
    259
    262
    237
        Grade 3 Swelling, Overall (N=518; 523; 509; 518)
    9
    7
    16
    13
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and grade 3 solicited local symptom post meningococcal vaccination.

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    End point title
    		 Number of subjects reporting any and grade 3 solicited local symptom post meningococcal vaccination.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after booster vaccination.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    491
    510
    496
    503
    Units: Subjects
        Any Pain
    191
    203
    203
    181
        Grade 3 Pain
    24
    23
    31
    18
        Any Redness
    186
    221
    213
    228
        Grade 3 Redness
    3
    6
    5
    4
        Any Swelling
    133
    152
    158
    165
        Grade 3 Swelling
    1
    2
    2
    5
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Infanrix hexa.

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    End point title
    		 Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Infanrix hexa.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after booster vaccination.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    491
    510
    495
    504
    Units: Subjects
        Any Pain
    240
    241
    242
    221
        Grade 3 Pain
    35
    33
    39
    23
        Any Redness
    259
    286
    282
    280
        Grade 3 Redness
    29
    24
    32
    22
        Any Swelling
    212
    226
    244
    240
        Grade 3 Swelling
    20
    18
    17
    14
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Synflorix.

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    End point title
    		 Number of subjects reporting any and grade 3 solicited local symptom post vaccination with Synflorix.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after booster vaccination.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    491
    510
    495
    504
    Units: Subjects
        Any Pain
    212
    215
    227
    205
        Grade 3 Pain
    36
    33
    33
    26
        Any Redness
    219
    243
    242
    251
        Grade 3 Redness
    14
    9
    20
    9
        Any Swelling
    173
    174
    189
    195
        Grade 3 Swelling
    5
    5
    4
    10
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any, grade 3 and related solicited general symptom.

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    End point title
    		 Number of subjects reporting any, grade 3 and related solicited general symptom.
    End point description
    Symptoms were abbreviated as follows: D=Drowsiness; I=Irritability/Fussiness; L=Loss of appetite ; T=Temperature, while vaccine doses were D1=Dose 1, D2 = Dose2, D3 = Dose 3 and Overall = Across doses.
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after each primary vaccine dose.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    518
    523
    509
    518
    Units: Subjects
        Any D, D1 (N=518; 523; 508; 517)
    298
    282
    285
    297
        Grade 3 D, D1 (N=518; 523; 508; 517)
    22
    22
    17
    34
        Related D, D1 (N=518; 523; 508; 517)
    163
    167
    163
    178
        Any I, D1 (N=518; 523; 508; 517)
    329
    337
    355
    364
        Grade 3 I, D1 (N=518; 523; 508; 517)
    54
    41
    45
    54
        Related I, D1 (N=518; 523; 508; 517)
    199
    206
    213
    235
        Any L, D1 (N=518; 523; 508; 517)
    188
    208
    196
    219
        Grade 3 L, D1 (N=518; 523; 508; 517)
    12
    11
    9
    8
        Related L, D1 (N=518; 523; 508; 517)
    95
    106
    111
    117
        Any T, D1 (N=518; 523; 508; 517)
    166
    162
    170
    183
        Grade 3 T, D1 (N=518; 523; 508; 517)
    0
    0
    0
    0
        Related T, D1 (N=518; 523; 508; 517)
    128
    119
    122
    144
        Any D, D2 (N=511; 515; 509; 512)
    232
    210
    231
    211
        Grade 3 D, D2 (N=511; 515; 509; 512)
    20
    20
    17
    12
        Related D, D2 (N=511; 515; 509; 512)
    133
    123
    137
    132
        Any I, D2 (N=511; 515; 509; 512)
    328
    312
    319
    320
        Grade 3 I, D2 (N=511; 515; 509; 512)
    52
    35
    44
    48
        Related I, D2 (N=511; 515; 509; 512)
    208
    198
    194
    212
        Any L, D2 (N=511; 515; 509; 512)
    164
    185
    183
    179
        Grade 3 L, D2 (N=511; 515; 509; 512)
    10
    6
    6
    7
        Related L, D2 (N=511; 515; 509; 512)
    95
    103
    93
    106
        Any T, D2 (N=511; 515; 509; 512)
    146
    145
    158
    144
        Grade 3 T, D2 (N=511; 515; 509; 512)
    1
    0
    1
    1
        Related T, D2 (N=511; 515; 509; 512)
    107
    105
    116
    110
        Any D, D3 (N=505; 516; 505; 507)
    181
    194
    197
    193
        Grade 3 D, D3 (N=505; 516; 505; 507)
    21
    7
    13
    14
        Related D, D3 (N=505; 516; 505; 507)
    112
    115
    109
    112
        Any I, D3 (N=505; 516; 505; 507)
    259
    279
    271
    262
        Grade 3 I, D3 (N=505; 516; 505; 507)
    37
    30
    32
    39
        Related I, D3 (N=505; 516; 505; 507)
    165
    178
    164
    174
        Any L, D3 (N=505; 516; 505; 507)
    149
    176
    159
    154
        Grade 3 L, D3 (N=505; 516; 505; 507)
    14
    11
    10
    9
        Related L, D3 (N=505; 516; 505; 507)
    88
    94
    83
    90
        Any T, D3 (N=505; 516; 505; 507)
    106
    127
    112
    114
        Grade 3 T, D3 (N=505; 516; 505; 507)
    0
    2
    2
    1
        Related T, D3 (N=505; 516; 505; 507)
    71
    88
    79
    89
        Any D, Overall (N=518; 523; 509; 518)
    376
    365
    370
    377
        Grade 3 D, Overall (N=518; 523; 509; 518)
    45
    41
    40
    47
        Related D, Overall (N=518; 523; 509; 518)
    235
    231
    235
    237
        Any I, Overall (N=518; 523; 509; 518)
    419
    436
    439
    441
        Grade 3 I, Overall (N=518; 523; 509; 518)
    109
    83
    86
    104
        Related I, Overall (N=518; 523; 509; 518)
    302
    304
    311
    325
        Any L, Overall (N=518; 523; 509; 518)
    295
    325
    307
    312
        Grade 3 L, Overall (N=518; 523; 509; 518)
    28
    23
    22
    22
        Related L, Overall (N=518; 523; 509; 518)
    180
    194
    186
    182
        Any T, Overall (N=518; 523; 509; 518)
    272
    274
    277
    275
        Grade 3 T, Overall (N=518; 523; 509; 518)
    1
    2
    3
    2
        Related T, Overall (N=518; 523; 509; 518)
    203
    208
    208
    220
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any, grade 3 and related solicited general symptom.

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    End point title
    		 Number of subjects reporting any, grade 3 and related solicited general symptom.
    End point description
    End point type
    Secondary
    End point timeframe
    Within 8 days (days 0 to 7) after booster vaccination.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    491
    510
    496
    504
    Units: Subjects
        Any Drowsiness
    198
    206
    208
    202
        Grade 3 Drowsiness
    14
    13
    21
    18
        Related Drowsiness
    125
    129
    119
    125
        Any Irritability
    284
    296
    284
    297
        Grade 3 Irritability
    41
    37
    37
    45
        Related Irritability
    180
    197
    181
    186
        Any Loss of appetite
    189
    193
    198
    195
        Grade 3 Loss of appetite
    12
    21
    23
    27
        Related Loss of appetite
    118
    114
    114
    121
        Any Temperature (Rectally)
    187
    180
    186
    170
        Grade 3 Temperature (Rectally)
    2
    2
    3
    7
        Related Temperature (Rectally)
    133
    132
    122
    125
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects reporting any unsolicited adverse events (AEs).
    End point description
    End point type
    Secondary
    End point timeframe
    Within 31 days (days 0 to 30) after each primary vaccine dose.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    528
    524
    516
    527
    Units: Subjects
        Any AE(s)
    293
    273
    291
    280
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects reporting any unsolicited adverse events (AEs).
    End point description
    End point type
    Secondary
    End point timeframe
    Within 31 days (days 0 to 30) after booster vaccination.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    497
    511
    503
    506
    Units: Subjects
        Any AE(s)
    179
    185
    164
    167
    No statistical analyses for this end point

    Secondary: Number of subjects reporting serious adverse events (SAEs).

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    End point title
    		 Number of subjects reporting serious adverse events (SAEs).
    End point description
    End point type
    Secondary
    End point timeframe
    Throughout the entire primary study (Day 0 - Month 16).
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    528
    524
    516
    527
    Units: Subjects
        Any SAE(s)
    1
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects reporting serious adverse events (SAEs).

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    End point title
    		 Number of subjects reporting serious adverse events (SAEs).
    End point description
    End point type
    Secondary
    End point timeframe
    Throughout the entire booster study.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    497
    511
    503
    506
    Units: Subjects
        Any SAE(s)
    26
    31
    25
    25
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any specific AEs of new onset of chronic illnesses (NOCIs).

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    End point title
    		 Number of subjects reporting any specific AEs of new onset of chronic illnesses (NOCIs).
    End point description
    End point type
    Secondary
    End point timeframe
    During the 31 days (Days 0-30) post-each primary vaccination dose.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    528
    524
    516
    527
    Units: Subjects
        Any NOCI(s)
    11
    6
    5
    5
    No statistical analyses for this end point

    Secondary: Number of subjects reporting any specific AEs of new onset of chronic illnesses (NOCIs).

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    End point title
    		 Number of subjects reporting any specific AEs of new onset of chronic illnesses (NOCIs).
    End point description
    End point type
    Secondary
    End point timeframe
    From booster vaccination up to ESFU contact.
    End point values
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Number of subjects analysed
    497
    511
    503
    506
    Units: Subjects
        Any NOCI(s)
    2
    2
    7
    5
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    - Solicited local and general symptoms: during the 8 day - (Day 0-Day 7) after each vaccination - Unsolicited adverse events: during the 31 day (Day 0 - Day 30) after each vaccination - SAEs: throughout the entire study (Day 0 – Month 1)
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    16.0
    Reporting groups
    Reporting group title
    GSK134612A 3-dose Group
    Reporting group description
    		 -

    Reporting group title
    GSK134612A 2-dose Group
    Reporting group description
    		 -

    Reporting group title
    Menjugate Group
    Reporting group description
    		 -

    Reporting group title
    NeisVac-C Group
    Reporting group description
    		 -

    Serious adverse events
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    54 / 528 (10.23%)
    56 / 524 (10.69%)
    45 / 516 (8.72%)
    52 / 527 (9.87%)
         number of deaths (all causes)
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cerebral haemangioma (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral haemangioma (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Kawasaki’s disease (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Kawasaki’s disease (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    5 / 524 (0.95%)
    0 / 516 (0.00%)
    3 / 527 (0.57%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 5
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Milk allergy (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Milk allergy (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Balanoposthitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Testicular retraction (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Balanoposthitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Testicular retraction (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Bronchial hyperreactivity (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngospasm (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinitis allergic (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial hyperreactivity (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Apparent life threatening event
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asphyxia
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngospasm (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rhinitis allergic (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Breath holding
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    4 / 516 (0.78%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal burn (Booster)
         subjects affected / exposed
    2 / 528 (0.38%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Near drowning (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Concussion (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    4 / 516 (0.78%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal burn (Primary)
         subjects affected / exposed
    2 / 528 (0.38%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Near drowning (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Overdose
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skull fracture (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Laryngomalacia
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Plagiocephaly
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Wolff-Parkinson-White syndrome
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Epilepsy (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile convulsion (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain injury (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Febrile convulsion (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain injury (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypotonia
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphadenitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Conjunctivitis allergic (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis allergic (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Vomiting (Booster)
         subjects affected / exposed
    2 / 528 (0.38%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphthous stomatitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    2 / 524 (0.38%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia, obstructive (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    3 / 524 (0.57%)
    1 / 516 (0.19%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting (Primary)
         subjects affected / exposed
    2 / 528 (0.38%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aphthous stomatitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    2 / 524 (0.38%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematemesis
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia, obstructive (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rash
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urticaria
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Haematuria (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haematuria (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle spasms (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sacroiliitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Torticollis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Muscle spasms (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arthritis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sacroiliitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Torticollis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Bronchitis (Booster)
         subjects affected / exposed
    5 / 528 (0.95%)
    4 / 524 (0.76%)
    1 / 516 (0.19%)
    4 / 527 (0.76%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 4
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis (Booster)
         subjects affected / exposed
    4 / 528 (0.76%)
    2 / 524 (0.38%)
    4 / 516 (0.78%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    2 / 524 (0.38%)
    1 / 516 (0.19%)
    3 / 527 (0.57%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    2 / 524 (0.38%)
    0 / 516 (0.00%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia (booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    3 / 516 (0.58%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media (Booster)
         subjects affected / exposed
    3 / 528 (0.57%)
    0 / 524 (0.00%)
    2 / 516 (0.39%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    2 / 524 (0.38%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenovirus infection (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial pyelonephritis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis bacterial (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Exanthema subitum (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis bacterial (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital candidiasis (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotavirus infection (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection (Booster)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral rash (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchiolitis (Primary)
         subjects affected / exposed
    12 / 528 (2.27%)
    10 / 524 (1.91%)
    9 / 516 (1.74%)
    14 / 527 (2.66%)
         occurrences causally related to treatment / all
    0 / 12
    0 / 10
    0 / 9
    0 / 14
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis (Primary)
         subjects affected / exposed
    9 / 528 (1.70%)
    4 / 524 (0.76%)
    1 / 516 (0.19%)
    8 / 527 (1.52%)
         occurrences causally related to treatment / all
    0 / 9
    0 / 4
    0 / 1
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis (Primary)
         subjects affected / exposed
    6 / 528 (1.14%)
    3 / 524 (0.57%)
    5 / 516 (0.97%)
    3 / 527 (0.57%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 3
    0 / 5
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia (Primary)
         subjects affected / exposed
    3 / 528 (0.57%)
    3 / 524 (0.57%)
    2 / 516 (0.39%)
    4 / 527 (0.76%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 3
    0 / 2
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection (Primary)
         subjects affected / exposed
    4 / 528 (0.76%)
    2 / 524 (0.38%)
    2 / 516 (0.39%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 4
    0 / 2
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus (Primary)
         subjects affected / exposed
    2 / 528 (0.38%)
    2 / 524 (0.38%)
    1 / 516 (0.19%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    1 / 524 (0.19%)
    1 / 516 (0.19%)
    4 / 527 (0.76%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus bronchiolitis
         subjects affected / exposed
    2 / 528 (0.38%)
    3 / 524 (0.57%)
    2 / 516 (0.39%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 3
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    4 / 516 (0.78%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 4
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media (Primary)
         subjects affected / exposed
    3 / 528 (0.57%)
    0 / 524 (0.00%)
    2 / 516 (0.39%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection (Primary)
         subjects affected / exposed
    3 / 528 (0.57%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    1 / 524 (0.19%)
    1 / 516 (0.19%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacterial pyelonephritis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    2 / 524 (0.38%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    2 / 527 (0.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Laryngitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral candidiasis
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection (Primary)
         subjects affected / exposed
    2 / 528 (0.38%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abscess (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Adenovirus infection (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal abscess (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atypical pneumonia (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bacteraemia (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Conjunctivitis bacterial (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Croup infectious
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Encephalitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Epstein-Barr virus infection
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Exanthema subitum (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis bacterial (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis norovirus (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis salmonella (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Genital candidiasis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    H1N1 influenza
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    1 / 516 (0.19%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes simplex (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral discitis (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung infection (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Oral herpes (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteomyelitis
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pertussis
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory syncytial virus infection
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rotavirus infection (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis (Primary)
         subjects affected / exposed
    1 / 528 (0.19%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral rash (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    1 / 524 (0.19%)
    0 / 516 (0.00%)
    0 / 527 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Decreased appetite (Booster)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Decreased appetite (Primary)
         subjects affected / exposed
    0 / 528 (0.00%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    1 / 527 (0.19%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 GSK134612A 3-dose Group GSK134612A 2-dose Group Menjugate Group NeisVac-C Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    419 / 528 (79.36%)
    436 / 524 (83.21%)
    439 / 516 (85.08%)
    441 / 527 (83.68%)
    General disorders and administration site conditions
    Pain
    alternative assessment type: Systematic
         subjects affected / exposed
    319 / 528 (60.42%)
    332 / 524 (63.36%)
    344 / 516 (66.67%)
    327 / 527 (62.05%)
         occurrences all number
    319
    332
    344
    327
    Redness
    alternative assessment type: Systematic
         subjects affected / exposed
    363 / 528 (68.75%)
    369 / 524 (70.42%)
    391 / 516 (75.78%)
    371 / 527 (70.40%)
         occurrences all number
    363
    369
    391
    371
    Swelling
    alternative assessment type: Systematic
         subjects affected / exposed
    326 / 528 (61.74%)
    318 / 524 (60.69%)
    343 / 516 (66.47%)
    317 / 527 (60.15%)
         occurrences all number
    326
    318
    343
    317
    Drowsiness
    alternative assessment type: Systematic
         subjects affected / exposed
    376 / 528 (71.21%)
    365 / 524 (69.66%)
    370 / 516 (71.71%)
    377 / 527 (71.54%)
         occurrences all number
    376
    365
    370
    377
    Irritability
    alternative assessment type: Systematic
         subjects affected / exposed
    419 / 528 (79.36%)
    436 / 524 (83.21%)
    439 / 516 (85.08%)
    441 / 527 (83.68%)
         occurrences all number
    419
    436
    439
    441
    Loss of appetite
    alternative assessment type: Systematic
         subjects affected / exposed
    295 / 528 (55.87%)
    325 / 524 (62.02%)
    307 / 516 (59.50%)
    312 / 527 (59.20%)
         occurrences all number
    295
    325
    307
    312
    Temperature/(Rectally ≥38.0°C)
    alternative assessment type: Systematic
         subjects affected / exposed
    272 / 528 (51.52%)
    274 / 524 (52.29%)
    277 / 516 (53.68%)
    275 / 527 (52.18%)
         occurrences all number
    272
    274
    277
    275
    Respiratory, thoracic and mediastinal disorders
    Rhinitis
         subjects affected / exposed
    32 / 528 (6.06%)
    27 / 524 (5.15%)
    33 / 516 (6.40%)
    0 / 527 (0.00%)
         occurrences all number
    32
    27
    33
    0
    Infections and infestations
    Upper respiratory tract infection (post-primary)
         subjects affected / exposed
    82 / 528 (15.53%)
    86 / 524 (16.41%)
    80 / 516 (15.50%)
    74 / 527 (14.04%)
         occurrences all number
    82
    86
    80
    74
    Nasopharyngitis
         subjects affected / exposed
    43 / 528 (8.14%)
    34 / 524 (6.49%)
    46 / 516 (8.91%)
    36 / 527 (6.83%)
         occurrences all number
    43
    34
    46
    36
    Bronchiolitis
         subjects affected / exposed
    41 / 528 (7.77%)
    34 / 524 (6.49%)
    33 / 516 (6.40%)
    44 / 527 (8.35%)
         occurrences all number
    41
    34
    33
    44
    Bronchitis
         subjects affected / exposed
    34 / 528 (6.44%)
    0 / 524 (0.00%)
    0 / 516 (0.00%)
    31 / 527 (5.88%)
         occurrences all number
    34
    0
    0
    31
    Upper respiratory tract infection (post-booster)
         subjects affected / exposed
    38 / 528 (7.20%)
    54 / 524 (10.31%)
    53 / 516 (10.27%)
    44 / 527 (8.35%)
         occurrences all number
    38
    54
    53
    44

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    06 Dec 2010
    An inconsistency between inclusion criteria and Table 5 was noticed and Table 5 has been corrected according to inclusion criteria. The age for administration of the booster dose has been clarified. Procedure for reporting Guillain Barre syndrome (GBS) has been added. New cold chain deviation wording has been incorporated.
    25 May 2011
    The sample size of the study population is increased by approximately 50%, i.e., 680 additional subjects will be enrolled in the study to reach the target samples size of 1650 evaluable subjects to demonstrate the co-primary objectives of this study. The serum bactericidal assay (SBA) is a functional measure of the ability of antibodies in conjunction with complement to kill bacteria and is considered the assay of choice for measurement of functional anti-meningococcal antibodies in vitro. It is well known that, as there is no standardized SBA testing, the inter-laboratory variability could have an important impact on the measured bactericidal titers. Depending on the laboratory where the SBA testing is to be performed, differences around 1% in the percentage of subjects with seroprotective titers may occur. It has been estimated that 50% sample size increase would be necessary to demonstrate all the sequential co-primary objectives regardless of the laboratory where the testing is performed. The primary endpoint of the current study is to assess the immunogenicity induced by the components of the investigational vaccine in terms of rSBA titres ≥ 1:8 for each of the four serogroups (A, C, W-135 and Y) in all subjects, one month after the final priming vaccination. In addition, rSBA titres ≥ 1:8 and ≥ 1:128 will also be assessed at any blood sampling time point during the study in a subset of subjects in all vaccine groups as secondary endpoints. To support the data obtained by rSBA testing, hSBA testing will also be performed and in addition antibody concentrations against meningococcal polysaccharides (PS) are planned to be assessed by ELISA (anti-PS testing). Now, GSK Biologicals decided not to perform anti-PS testing at any blood sampling time point 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].
    30 Jul 2012
    A measles outbreak in Spain impacted 2 centers participating in the study and the local authorities recommended vaccinating subjects from 9 months old onwards. The protocol is amended to allow administration of Measles, Mumps, Rubella (MMR) or Measles, Mumps, Rubella and Varicella (MMRV) vaccine throughout the study in line with local governmental recommendations. It is preferable that the vaccine not be given within 30 days prior or after a dose of study vaccine (with the day of vaccination considered Day 0). The introduction was updated with the current licensing status of MenACWY-TT and competitor vaccines. Several sections were updated to clarify that the Immune Mediated Disease (IMD) report should only be used in case of Guillain-Barre syndrome (GBS).

    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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