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    Clinical Trial Results:
    A Phase III, Observer-Blind, Randomized, Multi-center Study to Evaluate the Safety, Tolerability, and Immunogenicity of Fluad and Agriflu Compared to the Non Adjuvanted Trivalent Influenza Vaccine Fluzone in Children 6 to <72 Months of Age.

    Summary
    EudraCT number
    		 2014-005053-40
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    27 Jul 2012

    Results information
    Results version number
    		 v2(current)
    This version publication date
    29 Jul 2016
    First version publication date
    01 Apr 2015
    Other versions
    		 v1 (removed from public view)
    Version creation reason
    • Correction of full data set
    Required for the re-QC project because of the EudraCT system glitch and possible updates to results may be required. Moreover, a change in system user for this study is necessary.

    Trial information

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    Trial identification
    Sponsor protocol code
    V70_29
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01346592
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Novartis Vaccines and Diagnostic, S.r.l
    Sponsor organisation address
    Via Fiorentina 1, Siena, Italy, 53100
    Public contact
    Posting Director, Novartis Vaccines and Diagnostic, S.r.l, RegistryContactVaccinesUS@novartis.com
    Scientific contact
    Posting Director, Novartis Vaccines and Diagnostic, S.r.l, RegistryContactVaccinesUS@novartis.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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
    11 Jul 2013
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 Jul 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Jul 2012
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the noninferior immunogenicity of 2 intramuscular (IM) doses of Fluad to Agriflu and Fluzone (coprimary) in terms of both seroconversion1 and geometric mean titers (GMTs), as measured by hemagglutination inhibition (HI) assay in all 3 homologous strains in subjects aged 6 through <72 months. To demonstrate the noninferiority of 2 IM doses of Agriflu to Fluzone in terms of both seroconversion rates and GMTs, as measured by HI assay in all 3 homologous strains in subjects aged 6 through <36 months.
    Protection of trial subjects
    This clinical study was designated, implemented and reported in accordance with the International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for Good Clinical Practice (GCP), with applicable local regulations (including European Directive 2001/20/EC, US Code of Federal Regulations (CFR) Title 21, and Japanese Ministry of Health, Labor and Welfare), and with the ethical principles laid down in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    09 Apr 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 1 Years
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Philippines: 4513
    Country: Number of subjects enrolled
    South Africa: 834
    Country: Number of subjects enrolled
    Argentina: 552
    Country: Number of subjects enrolled
    Australia: 161
    Country: Number of subjects enrolled
    Chile: 40
    Worldwide total number of subjects
    6100
    EEA total number of subjects
    0
    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)
    1995
    Children (2-11 years)
    4105
    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
    		 A total of 5750 subjects were planned for this study. Overall, 6104 subjects were enrolled.

    Pre-assignment
    Screening details
    		 Subjects were assigned randomly to receive Fluad, Agriflu or Fluzone with allocation ratios 3:2:2 and 4:1:1 for age subgroups 6 to <36 and 36 to <72 months, respectively.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor
    Blinding implementation details
    During the study, unblinded designated qualified health care personnel were responsible for administering the study vaccines to the subjects, and were instructed not to reveal the identity of the study vaccines either to the subject or to the investigative site personnel (investigator, study nurse) involved in the monitoring or conduct of the study, except in an emergency.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 aTIV (6 to <72 Months)
    Arm description
    		 Subjects received an investigational MF59-adjuvanted trivalent influenza vaccine (aTIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.
    Arm type
    		 Experimental

    Investigational medicinal product name
    MF59-adjuvanted trivalent influenza vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single 0.25-mL or a 0.5 mL dose of relevant vaccine was to be administered intramuscularly in the deltoid muscle.

    Arm title
    		 Comparator TIV (6 to <72 Months)
    Arm description
    		 Subjects received a licensed comparator trivalent split influenza vaccine (comparator TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Licensed comparator Trivalent split influenza vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single 0.25-mL or a 0.5-mL dose of relevant vaccine was to be administered intramuscularly in the deltoid muscle.

    Arm title
    		 TIV (6 to <72 Months)
    Arm description
    		 Subjects received an investigational trivalent split influenza vaccine (TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Trivalent split influenza vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single 0.25-mL or a 0.5-mL dose of relevant vaccine was to be administered intramuscularly in the deltoid muscle.

    Number of subjects in period 1
    		aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Started
    3136
    1478
    1486
    Completed
    2983
    1389
    1408
    Not completed
    153
    89
    78
         Consent withdrawn by subject
    77
    51
    38
         Adverse Event
    -
    1
    -
         Death
    1
    3
    4
         Lost to follow-up
    62
    29
    29
         Unable to Classify
    7
    3
    6
         Inappropriate Enrollment
    3
    1
    1
         Administrative reason
    1
    -
    -
         Protocol deviation
    2
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    aTIV (6 to <72 Months)
    Reporting group description
    		 Subjects received an investigational MF59-adjuvanted trivalent influenza vaccine (aTIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Reporting group title
    Comparator TIV (6 to <72 Months)
    Reporting group description
    		 Subjects received a licensed comparator trivalent split influenza vaccine (comparator TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Reporting group title
    TIV (6 to <72 Months)
    Reporting group description
    		 Subjects received an investigational trivalent split influenza vaccine (TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Reporting group values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months) Total
    Number of subjects
    		 3136 1478 1486 6100
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 847 574 574 1995
        Children (2-11 years)
    		 2289 904 912 4105
        Adolescents (12-17 years)
    		 0 0 0 0
        Adults (18-64 years)
    		 0 0 0 0
        From 65-84 years
    		 0 0 0 0
        85 years and over
    		 0 0 0 0
    Age continuous
    Units: months
        arithmetic mean (standard deviation)
    		 37.1 ± 18.6 30 ± 16.9 30.2 ± 16.9 -
    Gender categorical
    Units: Subjects
        Female
    		 1545 745 731 3021
        Male
    		 1591 733 755 3079

    End points

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    End points reporting groups
    Reporting group title
    aTIV (6 to <72 Months)
    Reporting group description
    		 Subjects received an investigational MF59-adjuvanted trivalent influenza vaccine (aTIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Reporting group title
    Comparator TIV (6 to <72 Months)
    Reporting group description
    		 Subjects received a licensed comparator trivalent split influenza vaccine (comparator TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Reporting group title
    TIV (6 to <72 Months)
    Reporting group description
    		 Subjects received an investigational trivalent split influenza vaccine (TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Subject analysis set title
    FAS Population
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    All subjects in the Full analysis set who actually received a study vaccination, and provided at least one evaluable serum sample before and after vaccination (for subjects in the immunogenicity subset).

    Subject analysis set title
    PPS Population
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    All subjects in the FAS immunogenicity population who correctly received the vaccine, and provided evaluable serum samples at the relevant time points (for subjects in the immunogenicity subset), and had no major protocol violation as defined prior to unblinding.

    Subject analysis set title
    aTIV (6 to <36 Months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects received two doses (Day 1 & 29) of an investigational MF59-adjuvanted trivalent influenza vaccine (aTIV).

    Subject analysis set title
    Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    All subjects who had received at least one study vaccine and had postvaccination safety data were included in the safety analyses.

    Subject analysis set title
    Comparator TIV (6 to <36 Months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects received received two doses (Day 1 & 29) of a licensed comparator trivalent split influenza vaccine (comparator TIV).

    Subject analysis set title
    TIV (6 to <36 Months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects received two doses (Day 1 & 29) of an investigational trivalent split influenza vaccine (TIV).

    Subject analysis set title
    aTIV (36 to <72 Months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects received one dose (Day 1) of investigational MF59-adjuvanted trivalent influenza vaccine (aTIV).

    Subject analysis set title
    TIV (36 to <72 Months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects received one dose (Day1) of an investigational trivalent split influenza vaccine (TIV).

    Subject analysis set title
    Comparator TIV (36 to <72 Months)
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Subjects received one dose (Day 1) of a licensed comparator trivalent split influenza vaccine (comparator TIV).

    Subject analysis set title
    aTIV (6 to <24 Months)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received two doses of 0.25 mL each, of the investigational MF59-adjuvanted trivalent split influenza vaccine (aTIV), at Days 1 & 29.

    Subject analysis set title
    Comparator TIV (6 to <24 Months)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received two doses of 0.25 mL each, of the licensed comparator trivalent split influenza vaccine (comparator TIV), at Days 1 & 29.

    Subject analysis set title
    TIV (6 to <24 Months)
    Subject analysis set type
    		 Full analysis
    Subject analysis set description
    Subjects received two doses of 0.25 mL each, of the investigational trivalent split influenza vaccine (TIV), at Days 1 & 29.

    Primary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains
    End point description
    The non-inferiority of Hemagglutination Inhibition (HI) antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains.
    End point type
    Primary
    End point timeframe
    Day 1, Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    682
    757
    765
    Units: Titers
    geometric mean (confidence interval 95%)
        H1N1 - Day 1 (N=681,757,765)
    28 (24 to 33)
    24 (21 to 28)
    27 (23 to 31)
        H1N1 - Day 50 (N=681,757,765)
    1537 (1382 to 1709)
    629 (567 to 698)
    480 (433 to 532)
        H3N2 - Day 1
    40 (35 to 47)
    42 (36 to 49)
    44 (38 to 51)
        H3N2 - Day 50
    1908 (1785 to 2040)
    1012 (948 to 1080)
    803 (752 to 857)
        B strain Day 1
    9.87 (9.08 to 11)
    10 (9.41 to 11)
    10 (9.33 to 11)
        B strain Day 50
    492 (450 to 537)
    160 (147 to 175)
    157 (144 to 171)
    Statistical analysis title
    		 GMT ratio (H1N1 strain)
    Comparison groups
    Comparator TIV (6 to <72 Months) v aTIV (6 to <72 Months)
    Number of subjects included in analysis
    1439
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 GMT ratio (H1N1 strain)
    Point estimate
    2.44
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 2.06
         upper limit
    		 2.9
    Notes
    [1] - Noninferiority was established if the lower limit of the confidence interval of the day 50 ratio of GMTs was >0.667
    Statistical analysis title
    		 GMT ratio (H3N2 strain)
    Comparison groups
    Comparator TIV (6 to <72 Months) v aTIV (6 to <72 Months)
    Number of subjects included in analysis
    1439
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 GMT ratio (H3N2 strain)
    Point estimate
    1.89
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 1.69
         upper limit
    		 2.1
    Notes
    [2] - Noninferiority was established if the lower limit of the confidence interval of the day 50 ratio of GMTs was >0.667
    Statistical analysis title
    		 GMT ratio (B strain)
    Comparison groups
    Comparator TIV (6 to <72 Months) v aTIV (6 to <72 Months)
    Number of subjects included in analysis
    1439
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 GMT ratio (B strain)
    Point estimate
    3.07
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 2.66
         upper limit
    		 3.54
    Notes
    [3] - Noninferiority was established if the lower limit of the confidence interval of the day 50 ratio of GMTs was >0.667
    Statistical analysis title
    		 GMT ratio (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 GMT ratio (H1N1 strain)
    Point estimate
    3.2
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 2.7
         upper limit
    		 3.8
    Notes
    [4] - Noninferiority was established if the lower limit of the confidence interval of the day 50 ratio of GMTs was >0.667
    Statistical analysis title
    		 GMT ratio (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 GMT ratio (H3N2 strain)
    Point estimate
    2.38
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 2.14
         upper limit
    		 2.65
    Notes
    [5] - Noninferiority was established if the lower limit of the confidence interval of the day 50 ratio of GMTs was >0.667
    Statistical analysis title
    		 GMT ratio (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 GMT ratio (B strain)
    Point estimate
    3.14
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 2.72
         upper limit
    		 3.62
    Notes
    [6] - Noninferiority was established if the lower limit of the confidence interval of the day 50 ratio of GMTs was >0.667

    Primary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titers Against Homologous Strains

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titers Against Homologous Strains
    End point description
    The non-inferiority of HI antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of percentage of subjects achieving seroconversion or ≥4-fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains.
    End point type
    Primary
    End point timeframe
    Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    682
    757
    765
    Units: Percentage of subjects
    number (confidence interval 95%)
        H1N1 - (N=680,757,765)
    92.9 (90.8 to 94.8)
    84.5 (81.8 to 87.1)
    79.4 (76.3 to 82.2)
        H3N2
    96.5 (94.8 to 97.7)
    92.3 (90.2 to 94.1)
    89.4 (87 to 91.5)
        B strain
    98 (96.6 to 98.9)
    86 (83.3 to 88.4)
    84.6 (81.8 to 87.1)
    Statistical analysis title
    		 Group difference (H1N1 strain)
    Comparison groups
    Comparator TIV (6 to <72 Months) v aTIV (6 to <72 Months)
    Number of subjects included in analysis
    1439
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    9.09
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 5.48
         upper limit
    		 12.69
    Notes
    [7] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group difference was >-10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1439
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    4.07
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 1.58
         upper limit
    		 6.55
    Notes
    [8] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group difference was >-10%.
    Statistical analysis title
    		 Group difference (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1439
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    11.82
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 8.72
         upper limit
    		 14.92
    Notes
    [9] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group difference was >-10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [10]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    14.21
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 10.3
         upper limit
    		 18.13
    Notes
    [10] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    7.31
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 4.47
         upper limit
    		 10.14
    Notes
    [11] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1447
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [12]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    11.1
    Confidence interval
         level
    		 97.6%
         sides
    2-sided
         lower limit
    		 8.11
         upper limit
    		 14.1
    Notes
    [12] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group difference was > -10%.

    Primary: Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains (6 to <36 Months)

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    End point title
    		 Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Geometric Mean Titers (GMTs) Against Homologous Strains (6 to <36 Months)
    End point description
    The non-inferiority of HI antibody responses of TIV to that of comparator TIV, in subjects aged 6 to <36 Months, assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains.
    End point type
    Primary
    End point timeframe
    Day 1, Day 50
    End point values
    		 Comparator TIV (6 to <36 Months) TIV (6 to <36 Months)
    Number of subjects analysed
    635
    642
    Units: Titers
    geometric mean (confidence interval 95%)
        H1N1 - Day 1
    20 (17 to 23)
    23 (20 to 27)
        H1N1 - Day 50
    487 (431 to 551)
    370 (328 to 419)
        H3N2 - Day 1
    28 (24 to 33)
    29 (24 to 33)
        H3N2 - Day 50
    912 (849 to 980)
    698 (650 to 749)
        B strain Day 1
    9.42 (8.62 to 10)
    9.42 (8.63 to 10)
        B -strain Day 50
    152 (138 to 168)
    144 (130 to 159)
    Statistical analysis title
    		 GMT ratio (H1N1 strain)
    Comparison groups
    TIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1277
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [13]
    Method
    Parameter type
    		 GMT ratio (H1N1 strain)
    Point estimate
    0.76
    Confidence interval
         level
    		 97.4%
         sides
    2-sided
         lower limit
    		 0.62
         upper limit
    		 0.93
    Notes
    [13] - Non-inferiority was established if the lower bound of the confidence interval for day 50 GMT group ratios was >0.667
    Statistical analysis title
    		 GMT ratio (B strain)
    Comparison groups
    Comparator TIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1277
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [14]
    Method
    Parameter type
    		 GMT ratio (B strain)
    Point estimate
    0.94
    Confidence interval
         level
    		 97.4%
         sides
    2-sided
         lower limit
    		 0.8
         upper limit
    		 1.11
    Notes
    [14] - Non-inferiority was established if the lower bound of the confidence interval for day 50 GMT group ratios was >0.667
    Statistical analysis title
    		 GMT ratio (H3N2 strain)
    Comparison groups
    Comparator TIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1277
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [15]
    Method
    Parameter type
    		 GMT ratio (H3N2 strain)
    Point estimate
    0.77
    Confidence interval
         level
    		 97.4%
         sides
    2-sided
         lower limit
    		 0.68
         upper limit
    		 0.86
    Notes
    [15] - Non-inferiority was established if the lower bound of the confidence interval for day 50 GMT group ratios was >0.667

    Secondary: Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects 6 to <36 Months of Age

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    End point title
    		 Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects 6 to <36 Months of Age
    End point description
    The non-inferiority of HI antibody responses of TIV to that of the licensed comparator TIV assessed in terms of percentage of subjects achieving seroconversion or ≥4-fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains.
    End point type
    Secondary
    End point timeframe
    Day 50
    End point values
    		 Comparator TIV (6 to <36 Months) TIV (6 to <36 Months)
    Number of subjects analysed
    635
    642
    Units: Percentage of subjects
    number (confidence interval 95%)
        H1N1
    84.1 (81 to 86.9)
    78.8 (75.5 to 81.9)
        H3N2
    92.6 (90.3 to 94.5)
    89.9 (87.3 to 92.1)
        B Strain
    85.5 (82.5 to 88.2)
    82.7 (79.6 to 85.6)
    Statistical analysis title
    		 Group difference (H1N1 strain)
    Comparison groups
    Comparator TIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1277
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [16]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -5.3
    Confidence interval
         level
    		 97.4%
         sides
    2-sided
         lower limit
    		 -10.13
         upper limit
    		 -0.47
    Notes
    [16] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group differences was > -10%
    Statistical analysis title
    		 Group difference (H3N2 strain)
    Comparison groups
    Comparator TIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1277
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [17]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    -2.84
    Confidence interval
         level
    		 97.4%
         sides
    2-sided
         lower limit
    		 -6.16
         upper limit
    		 0.5
    Notes
    [17] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group differences was > -10%
    Statistical analysis title
    		 Group difference (B strain)
    Comparison groups
    Comparator TIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1277
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [18]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    -2.49
    Confidence interval
         level
    		 97.4%
         sides
    2-sided
         lower limit
    		 -7.01
         upper limit
    		 2
    Notes
    [18] - Non-inferiority was established if the lower bound of the confidence interval for day 50 vaccine group differences was > -10%

    Secondary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <24 Months)

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <24 Months)
    End point description
    Analysis was done on the Full Analysis Set.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 50
    End point values
    		 aTIV (6 to <24 Months) Comparator TIV (6 to <24 Months) TIV (6 to <24 Months)
    Number of subjects analysed
    266
    389
    387
    Units: Titers
    geometric mean (confidence interval 95%)
        H1N1 - Day 1
    12 (9.52 to 14)
    9.87 (8.36 to 12)
    12 (9.95 to 14)
        H1N1 - Day 50
    1080 (899 to 1297)
    298 (256 to 347)
    205 (176 to 238)
        H3N2 - Day 1
    15 (12 to 19)
    15 (12 to 18)
    17 (14 to 21)
        H3N2 - Day 50
    1709 (1536 to 1903)
    758 (694 to 828)
    552 (505 to 603)
        B strain Day 1
    7.75 (6.83 to 8.78)
    8.18 (7.37 to 9.07)
    7.92 (7.14 to 8.79)
        B strain Day 50
    616 (534 to 711)
    133 (118 to 149)
    112 (100 to 127)
    Statistical analysis title
    		 GMT ratio (H1N1 strain)
    Comparison groups
    aTIV (6 to <24 Months) v Comparator TIV (6 to <24 Months)
    Number of subjects included in analysis
    655
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [19]
    Method
    Parameter type
    		 GMT ratio (H1N1 strain)
    Point estimate
    3.63
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.86
         upper limit
    		 4.6
    Notes
    [19] - Superiority was concluded if the lower limit of the confidence interval for the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT ratio (H3N2 strain)
    Comparison groups
    aTIV (6 to <24 Months) v Comparator TIV (6 to <24 Months)
    Number of subjects included in analysis
    655
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [20]
    Method
    Parameter type
    		 GMT ratio (H3N2 strain)
    Point estimate
    2.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.96
         upper limit
    		 2.59
    Notes
    [20] - Superiority was concluded if the lower limit of the confidence interval for the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT ratio (B strain)
    Comparison groups
    aTIV (6 to <24 Months) v Comparator TIV (6 to <24 Months)
    Number of subjects included in analysis
    655
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [21]
    Method
    Parameter type
    		 GMT ratio (B strain)
    Point estimate
    4.64
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.86
         upper limit
    		 5.59
    Notes
    [21] - Superiority was concluded if the lower limit of the confidence interval for the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT ratio (H1N1 strain)
    Comparison groups
    aTIV (6 to <24 Months) v TIV (6 to <24 Months)
    Number of subjects included in analysis
    653
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [22]
    Method
    Parameter type
    		 GMT ratio (H1N1 strain)
    Point estimate
    5.28
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.16
         upper limit
    		 6.7
    Notes
    [22] - Superiority was concluded if the lower limit of the confidence interval for the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT ratio (H3N2 strain)
    Comparison groups
    aTIV (6 to <24 Months) v TIV (6 to <24 Months)
    Number of subjects included in analysis
    653
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [23]
    Method
    Parameter type
    		 GMT ratio (H3N2 strain)
    Point estimate
    3.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.69
         upper limit
    		 3.56
    Notes
    [23] - Superiority was concluded if the lower limit of the confidence interval for the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT ratio (B strain)
    Comparison groups
    aTIV (6 to <24 Months) v TIV (6 to <24 Months)
    Number of subjects included in analysis
    653
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [24]
    Method
    Parameter type
    		 GMT ratio (B strain)
    Point estimate
    5.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.55
         upper limit
    		 6.6
    Notes
    [24] - Superiority was concluded if the lower limit of the confidence interval for the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.

    Secondary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains (6 to <24 Months)

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains (6 to <24 Months)
    End point description
    Analysis was done on the FAS
    End point type
    Secondary
    End point timeframe
    Day 50
    End point values
    		 aTIV (6 to <24 Months) Comparator TIV (6 to <24 Months) TIV (6 to <24 Months)
    Number of subjects analysed
    266
    389
    387
    Units: Percentage of Subjects
    number (confidence interval 95%)
        H1N1
    95.5 (92.3 to 97.7)
    85.1 (81.2 to 88.5)
    77.8 (73.3 to 81.8)
        H3N2
    98.1 (95.7 to 99.4)
    95.6 (93.1 to 97.4)
    92.5 (89.4 to 94.9)
        B strain
    98.1 (95.7 to 99.4)
    85.4 (81.4 to 88.7)
    79.3 (75 to 83.3)
    Statistical analysis title
    		 Group difference (H1N1 strain)
    Comparison groups
    aTIV (6 to <24 Months) v Comparator TIV (6 to <24 Months)
    Number of subjects included in analysis
    655
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [25]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    10.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.1
         upper limit
    		 14.7
    Notes
    [25] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)
    Comparison groups
    aTIV (6 to <24 Months) v Comparator TIV (6 to <24 Months)
    Number of subjects included in analysis
    655
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [26]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.12
         upper limit
    		 5.1
    Notes
    [26] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (B strain)
    Comparison groups
    aTIV (6 to <24 Months) v Comparator TIV (6 to <24 Months)
    Number of subjects included in analysis
    655
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [27]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    12.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.9
         upper limit
    		 16.7
    Notes
    [27] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)
    Comparison groups
    aTIV (6 to <24 Months) v TIV (6 to <24 Months)
    Number of subjects included in analysis
    653
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [28]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    17.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.9
         upper limit
    		 22.6
    Notes
    [28] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)
    Comparison groups
    aTIV (6 to <24 Months) v TIV (6 to <24 Months)
    Number of subjects included in analysis
    653
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [29]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    5.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.5
         upper limit
    		 8.7
    Notes
    [29] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (B strain)
    Comparison groups
    aTIV (6 to <24 Months) v TIV (6 to <24 Months)
    Number of subjects included in analysis
    653
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [30]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    18.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 14.4
         upper limit
    		 23.1
    Notes
    [30] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.

    Secondary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <72 Months)-FAS

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains (6 to <72 Months)-FAS
    End point description
    Analysis was done on the FAS
    End point type
    Secondary
    End point timeframe
    Day 1, Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    747
    839
    849
    Units: Titers
    geometric mean (confidence interval 95%)
        H1N1 - Day 1 (N=746,839,849)
    29 (25 to 33)
    24 (21 to 28)
    27 (23 to 31)
        H1N1 - Day 50 (N=746,839,849)
    1519 (1372 to 1683)
    637 (577 to 704)
    473 (428 to 522)
        H3N2 - Day 1
    41 (36 to 48)
    42 (37 to 49)
    44 (38 to 50)
        H3N2 - Day 50
    1909 (1791 to 2035)
    1016 (954 to 1081)
    796 (748 to 847)
        B strain - Day 1
    9.97 (9.2 to 11)
    10 (9.49 to 11)
    10 (9.33 to 11)
        B strain-Day 50
    480 (441 to 523)
    164 (151 to 178)
    156 (144 to 169)
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1586
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [31]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.38
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.07
         upper limit
    		 2.75
    Notes
    [31] - Superiority was concluded if the lower limit of the confidence interval of the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1586
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [32]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.88
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.72
         upper limit
    		 2.06
    Notes
    [32] - Superiority was concluded if the lower limit of the confidence interval of the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT Ratio (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1586
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [33]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    2.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.6
         upper limit
    		 3.3
    Notes
    [33] - Superiority was concluded if the lower limit of the confidence interval of the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1596
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [34]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    3.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.79
         upper limit
    		 3.71
    Notes
    [34] - Superiority was concluded if the lower limit of the confidence interval of the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1596
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [35]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.19
         upper limit
    		 2.62
    Notes
    [35] - Superiority was concluded if the lower limit of the confidence interval of the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.
    Statistical analysis title
    		 GMT Ratio (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1596
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [36]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.73
         upper limit
    		 3.47
    Notes
    [36] - Superiority was concluded if the lower limit of the confidence interval of the day 50 vaccine group GMT ratios for at least 2 homologous strains was >1.5.

    Secondary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers Against Homologous Strains (6 to <72 Months)-FAS

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers Against Homologous Strains (6 to <72 Months)-FAS
    End point description
    The superiority of HI antibody responses, in subjects 6 to <24 months of age, of aTIV compared to TIV and comparator TIV assessed in terms of number of subjects achieving seroconversion ≥4 fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains.
    End point type
    Secondary
    End point timeframe
    Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    747
    839
    849
    Units: Percentage of Subjects
    number (confidence interval 95%)
        H1N1 (N=745, 849, 839)
    92.8 (90.7 to 94.5)
    83.7 (81 to 86.1)
    78.8 (75.9 to 81.5)
        H3N2
    96.4 (94.8 to 97.6)
    92.3 (90.2 to 94)
    89.8 (87.5 to 91.7)
        B strain
    97.5 (96.1 to 98.5)
    86.4 (83.9 to 88.7)
    84.5 (81.8 to 86.8)
    Statistical analysis title
    		 Group difference (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1586
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [37]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    9.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.3
         upper limit
    		 12.4
    Notes
    [37] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1586
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [38]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    3.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.8
         upper limit
    		 5.9
    Notes
    [38] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1586
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [39]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    10.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.1
         upper limit
    		 13.3
    Notes
    [39] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1596
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [40]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    14.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.1
         upper limit
    		 17.7
    Notes
    [40] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1596
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [41]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    6.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.5
         upper limit
    		 9.1
    Notes
    [41] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.
    Statistical analysis title
    		 Group difference (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1596
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [42]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    10.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.3
         upper limit
    		 13.4
    Notes
    [42] - Superiority was concluded if the lower limit of the confidence interval of day 50 vaccine group difference,for at least 2 homologous strains, was >10%.

    Secondary: The HI GMTs Against Homologous Strains, by Vaccine Group

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    End point title
    		 The HI GMTs Against Homologous Strains, by Vaccine Group
    End point description
    The HI antibody titers against the three homologous strains following vaccination with either aTIV, licensed comparator or TIV, at three weeks and at six months after vaccination are reported as GMTs.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 29, Day 50, Day 209
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    715
    822
    820
    Units: Titers
    geometric mean (confidence interval 95%)
        H1N1 - Day 1 (N=714,822,820)
    28 (24 to 32)
    24 (20 to 27)
    27 (23 to 31)
        H1N1 - Day 29
    647 (562 to 745)
    159 (139 to 182)
    170 (148 to 194)
        H1N1 - Day 50 (N=714,822,820)
    1507 (1358 to 1673)
    635 (575 to 702)
    475 (429 to 525)
        H1N1 - Day 209 (N=715,822,819)
    276 (246 to 311)
    97 (87 to 109)
    107 (96 to 120)
        H3N2 - Day 1
    42 (36 to 48)
    43 (37 to 49)
    43 (38 to 50)
        H3N2 - Day 29
    1087 (1004 to 1176)
    558 (517 to 602)
    453 (420 to 490)
        H3N2 - Day 50
    1920 (1799 to 2050)
    1013 (952 to 1079)
    810 (760 to 862)
        H3N2 - Day 209
    462 (423 to 505)
    277 (254 to 301)
    242 (222 to 263)
        B - Day 1
    10 (9.29 to 11)
    10 (9.57 to 11)
    10 (9.34 to 11)
        B - Day 29
    119 (106 to 134)
    58 (52 to 65)
    61 (54 to 68)
        B - Day 50
    488 (447 to 532)
    166 (153 to 180)
    159 (146 to 173)
        B- Day 209
    125 (114 to 136)
    57 (53 to 62)
    61 (56 to 66)
    No statistical analyses for this end point

    Secondary: Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains

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    End point title
    		 Geometric Mean Ratio (GMR) of Post- Versus Pre-vaccination HI Titers Against Homologous Strains
    End point description
    The GMR of post-vaccination versus pre-vaccination HI titers against homologous strains, three weeks (day 29/day 1; day 50/day 1) and six months (day 209/day 1) after vaccination with either aTIV, licensed comparator or TIV.
    End point type
    Secondary
    End point timeframe
    Day 29, Day 50, Day 209
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    715
    822
    820
    Units: Ratios
    geometric mean (confidence interval 95%)
        H1N1, Day 29:Day 1 (N=714,822,820)
    27 (23 to 31)
    6.81 (5.94 to 7.81)
    7.13 (6.22 to 8.18)
        H1N1, Day 50:Day 1 (N=713,822,820)
    58 (51 to 67)
    27 (24 to 31)
    19 (17 to 21)
        H1N1, Day 209:Day 1 (N=714,822,819)
    11 (9.79 to 13)
    4.15 (3.68 to 4.69)
    4.37 (3.87 to 4.94)
        H3N2, Day 29:Day 1
    29 (26 to 32)
    15 (14 to 16)
    12 (11 to 13)
        H3N2, Day 50:Day 1 (N=715,822,820)
    48 (43 to 54)
    25 (23 to 28)
    20 (18 to 22)
        H3N2, Day 209:Day 1
    12 (10 to 13)
    6.93 (6.14 to 7.83)
    6.02 (5.33 to 6.81)
        B strain, Day 29:Day 1
    12 (11 to 14)
    6.18 (5.49 to 6.95)
    6.38 (5.66 to 7.18)
        B strain, Day 50:Day 1
    49 (45 to 54)
    17 (15 to 18)
    16 (15 to 18)
        B strain, Day 209:Day 1
    13 (12 to 14)
    5.76 (5.26 to 6.3)
    6.15 (5.62 to 6.73)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects With HI Titers ≥40 Against Homologous Strains, by Vaccine Group

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    End point title
    		 Percentage of Subjects With HI Titers ≥40 Against Homologous Strains, by Vaccine Group
    End point description
    The percentage of subjects demonstrating HI titers ≥40,against homologous strains, at three weeks and six months after vaccination with aTIV or licensed comparator or TIV.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 29, Day 50, Day 209
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    715
    822
    820
    Units: Ratios
    geometric mean (confidence interval 95%)
        H1N1, Day 1 (N=714,822,820)
    40.6 (37 to 44.3)
    33.1 (29.9 to 36.4)
    36.3 (33 to 39.7)
        H1N1, Day 29
    89.8 (87.3 to 91.9)
    55 (51.5 to 58.4)
    57.9 (54.5 to 61.3)
        H1N1, Day 50 (N=714,822,820)
    99.3 (98.4 to 99.8)
    91.1 (89 to 93)
    88.2 (85.8 to 90.3)
        H1N1, Day 209 (N=715, 822,819)
    88.8 (86.3 to 91)
    59.5 (56 to 62.9)
    63.2 (59.8 to 66.6)
        H3N2, Day 1
    52.6 (48.9 to 56.3)
    45.5 (42.1 to 49)
    44.6 (41.2 to 48.1)
        H3N2, Day 29
    98.9 (97.8 to 99.5)
    95.9 (94.3 to 97.1)
    93.5 (91.6 to 95.1)
        H3N2, Day 50
    99.7 (99 to 100)
    99.5 (98.8 to 99.9)
    99.4 (98.6 to 99.8)
        H3N2, Day 209
    99.3 (98.4 to 99.8)
    94.3 (92.5 to 95.8)
    88.4 (86 to 90.5)
        B strain, Day 1
    22.1 (19.1 to 25.3)
    21.1 (18.3 to 24)
    20.5 (17.8 to 23.4)
        B strain, Day 29
    69 (65.4 to 72.3)
    48.2 (44.7 to 51.7)
    45.6 (42.2 to 49.1)
        B strain, Day 50
    98.9 (97.8 to 99.5)
    89.1 (86.7 to 91.1)
    87 (84.5 to 89.2)
        B strain, Day 209
    93.4 (91.4 to 95.1)
    67.9 (64.6 to 71.1)
    67 (63.6 to 70.2)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Homologous Strains

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    End point title
    		 Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Homologous Strains
    End point description
    The percentage of subjects achieving seroconversion ≥4 fold increase in HI titers from baseline, against homologous strains, at three weeks and six months after vaccination with ATIV or licensed comparator or TIV.
    End point type
    Secondary
    End point timeframe
    Day 29, Day 50, Day 209
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    715
    822
    820
    Units: Percentage of Subjects
    number (confidence interval 95%)
        H1N1, Day 29 (N=714,822,820)
    83.6 (80.7 to 86.3)
    48.5 (45.1 to 52)
    51.5 (48 to 54.9)
        H1N1, Day 50 (N=713,822,820)
    92.6 (90.4 to 94.4)
    83.9 (81.3 to 86.4)
    79 (76.1 to 81.8)
        H1N1, Day 209 (N=714,822,819)
    71.7 (68.3 to 75)
    39.5 (36.2 to 43)
    41.9 (38.5 to 45.3)
        H3N2, Day 29
    95.8 (94.1 to 97.2)
    90.3 (88 to 92.2)
    86.7 (84.2 to 89)
        H3N2, Day 50
    96.5 (94.9 to 97.7)
    92.1 (90 to 93.8)
    90 (87.7 to 92)
        H3N2, Day 209
    77.6 (74.4 to 80.6)
    62.5 (59.1 to 65.9)
    55.6 (52.1 to 59.1)
        B strain, Day 29
    68.4 (64.8 to 71.8)
    47 (43.5 to 50.4)
    44 (40.6 to 47.5)
        B strain, Day 50
    97.6 (96.2 to 98.6)
    86.6 (84.1 to 88.9)
    85 (82.4 to 87.4)
        B strain, Day 209
    87.3 (84.6 to 89.6)
    59.7 (56.3 to 63.1)
    61.5 (58 to 64.8)
    No statistical analyses for this end point

    Secondary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, Subjects at Risk/Not at Risk, by Age Subgroup

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, Subjects at Risk/Not at Risk, by Age Subgroup
    End point description
    The non-inferiority of Hemagglutination Inhibition (HI) antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains, in subjects with a defined set of underlying medical conditions (at risk) and healthy subjects (not at risk), by age sub group.
    End point type
    Secondary
    End point timeframe
    Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months) aTIV (6 to <36 Months) Comparator TIV (6 to <36 Months) TIV (6 to <36 Months) aTIV (36 to <72 Months) TIV (36 to <72 Months) Comparator TIV (36 to <72 Months)
    Number of subjects analysed
    660
    722
    739
    425
    612
    623
    235
    116
    110
    Units: Titers
    geometric mean (confidence interval 95%)
        H1N1nonrisk(N=659,722,739,425,612,623,234,110,116)
    1516 (1358 to 1692)
    566 (509 to 628)
    431 (388 to 478)
    1341 (1165 to 1544)
    478 (425 to 537)
    366 (326 to 411)
    2111 (1840 to 2423)
    879 (723 to 1068)
    1365 (1117 to 1668)
        H3N2nonrisk(N=660,722,739,425,612,623,235,110,116)
    1897 (1772 to 2030)
    1014 (950 to 1082)
    804 (754 to 857)
    1863 (1711 to 2028)
    912 (849 to 979)
    695 (648 to 746)
    2311 (2080 to 2568)
    1497 (1289 to 1739)
    1526 (1309 to 1780)
        B nonrisk(N=660,722,739,425,612,623,235,110,116)
    492 (450 to 539)
    162 (148 to 176)
    157 (144 to 170)
    559 (498 to 627)
    149 (136 to 164)
    141 (128 to 155)
    431 (380 to 488)
    254 (212 to 304)
    226 (188 to 272)
        H1N1 at risk(N=22,35,26,12,23,19,10,12,7)
    1706 (990 to 2939)
    772 (502 to 1185)
    631 (383 to 1041)
    1414 (658 to 3040)
    603 (350 to 1040)
    519 (283 to 950)
    2187 (956 to 5002)
    1030 (383 to 2767)
    1241 (583 to 2641)
        H3N2 at risk(N=22,35,26,12,23,19,10,12,7)
    2306 (1665 to 3194)
    941 (727 to 1220)
    709 (526 to 955)
    2323 (1407 to 3835)
    794 (552 to 1140)
    665 (447 to 988)
    2319 (1622 to 3315)
    826 (538 to 1267)
    1306 (940 to 1815)
        B at risk(N=22,35,26,12,23,19,10,12,7)
    495 (307 to 797)
    143 (98 to 209)
    179 (116 to 278)
    694 (367 to 1316)
    125 (79 to 199)
    132 (79 to 220)
    365 (184 to 724)
    312 (131 to 743)
    200 (108 to 372)
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [43]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.3
         upper limit
    		 3.12
    Notes
    [43] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [44]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.7
         upper limit
    		 2.05
    Notes
    [44] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [45]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.68
         upper limit
    		 3.44
    Notes
    [45] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [46]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.11
         upper limit
    		 4.42
    Notes
    [46] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [47]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.61
         upper limit
    		 3.72
    Notes
    [47] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [48]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.46
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.88
         upper limit
    		 6.34
    Notes
    [48] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [49]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    3.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.03
         upper limit
    		 4.1
    Notes
    [49] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [50]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.36
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.15
         upper limit
    		 2.59
    Notes
    [50] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    TIV (6 to <72 Months) v aTIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [51]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.78
         upper limit
    		 3.56
    Notes
    [51] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [52]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.28
         upper limit
    		 5.68
    Notes
    [52] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [53]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    3.25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.09
         upper limit
    		 5.06
    Notes
    [53] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [54]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    2.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.44
         upper limit
    		 5.3
    Notes
    [54] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [55]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.34
         upper limit
    		 3.37
    Notes
    [55] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [56]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.04
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.83
         upper limit
    		 2.28
    Notes
    [56] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [57]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.74
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.22
         upper limit
    		 4.34
    Notes
    [57] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [58]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.34
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 6
    Notes
    [58] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [59]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.93
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.57
         upper limit
    		 5.45
    Notes
    [59] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [60]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    5.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.52
         upper limit
    		 12
    Notes
    [60] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [61]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    3.66
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.05
         upper limit
    		 4.39
    Notes
    [61] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [62]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.4
         upper limit
    		 2.99
    Notes
    [62] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [63]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.97
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.42
         upper limit
    		 4.61
    Notes
    [63] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [64]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.72
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.02
         upper limit
    		 7.31
    Notes
    [64] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [65]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.85
         upper limit
    		 6.62
    Notes
    [65] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [66]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    5.26
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.32
         upper limit
    		 12
    Notes
    [66] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [67]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.55
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.21
         upper limit
    		 1.97
    Notes
    [67] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [68]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.51
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.26
         upper limit
    		 1.82
    Notes
    [68] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [69]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.52
         upper limit
    		 2.38
    Notes
    [69] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [70]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.57
         upper limit
    		 5.4
    Notes
    [70] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [71]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.09
         upper limit
    		 2.89
    Notes
    [71] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [72]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.73
         upper limit
    		 4.54
    Notes
    [72] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [73]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.89
         upper limit
    		 3.05
    Notes
    [73] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [74]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.29
         upper limit
    		 1.85
    Notes
    [74] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [75]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.36
         upper limit
    		 2.11
    Notes
    [75] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [76]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.58
         upper limit
    		 7.71
    Notes
    [76] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [77]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.17
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.37
         upper limit
    		 3.67
    Notes
    [77] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [78]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.81
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.61
         upper limit
    		 4.89
    Notes
    [78] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.

    Secondary: Comparison of Antibody Responses of aTIV Versus Comparator TIV and TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Subgroup

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    End point title
    		 Comparison of Antibody Responses of aTIV Versus Comparator TIV and TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Subgroup
    End point description
    The non-inferiority of HI antibody responses of aTIV to that of the licensed comparator TIV and to investigational TIV was assessed in terms of percentage of subjects achieving seroconversion or ≥4-fold increase in HI titers at three weeks after last vaccination against the three homologous vaccine strains in subjects with a defined set of underlying medical conditions (at risk) and in healthy subjects (not at risk) , by age sub group.
    End point type
    Secondary
    End point timeframe
    Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months) aTIV (6 to <36 Months) Comparator TIV (6 to <36 Months) TIV (6 to <36 Months) aTIV (36 to <72 Months) TIV (36 to <72 Months) Comparator TIV (36 to <72 Months)
    Number of subjects analysed
    660
    722
    739
    425
    612
    623
    235
    116
    110
    Units: Percentage of Subjects
    number (confidence interval 95%)
        H1N1 norisk(N=658,722,739,425,612,623,233,110,116)
    93 (91 to 95)
    85 (82 to 87)
    79 (76 to 82)
    95 (92 to 97)
    84 (81 to 87)
    78 (75 to 82)
    91 (86 to 94)
    83 (75 to 89)
    88 (81 to 94)
        H3N2 norisk(N=660,722,739,425,612,623,235,110,116)
    97 (95 to 98)
    93 (91 to 94)
    90 (87 to 92)
    98 (96 to 99)
    93 (91 to 95)
    90 (88 to 93)
    94 (91 to 97)
    86 (79 to 92)
    90 (83 to 95)
        B norisk(N=660,722,739,425,612,623,235,110,116)
    98 (96 to 99)
    86 (83 to 88)
    84 (82 to 87)
    98 (96 to 99)
    85 (82 to 88)
    83 (79 to 86)
    98 (95 to 99)
    94 (88 to 98)
    90 (83 to 95)
        H1N1 at risk (N=22,35,26,12,23,19,10,12,7)
    82 (60 to 95)
    83 (66 to 93)
    85 (65 to 96)
    92 (62 to 100)
    87 (66 to 97)
    89 (67 to 99)
    70 (35 to 93)
    71 (29 to 96)
    75 (43 to 95)
        H3N2 at risk(N=22,35,26,12,23,19,10,12,7)
    86 (65 to 97)
    86 (70 to 95)
    81 (61 to 93)
    83 (52 to 98)
    78 (56 to 93)
    74 (49 to 91)
    90 (55 to 100)
    100 (59 to 100)
    100 (74 to 100)
        B at risk(N=22,35,26,12,23,19,10,12,7)
    100 (85 to 100)
    86 (70 to 95)
    88 (70 to 98)
    100 (74 to 100)
    91 (72 to 99)
    84 (60 to 97)
    100 (69 to 100)
    100 (59 to 100)
    75 (43 to 95)
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [79]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.4
         upper limit
    		 12
    Notes
    [79] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [80]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.8
         upper limit
    		 6.6
    Notes
    [80] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [81]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24
         upper limit
    		 18.7
    Notes
    [81] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [82]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -21.2
         upper limit
    		 18.9
    Notes
    [82] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1382
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [83]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.6
         upper limit
    		 29.5
    Notes
    [83] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [84]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    14
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.7
         upper limit
    		 17.7
    Notes
    [84] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [85]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.6
         upper limit
    		 9.8
    Notes
    [85] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [86]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.7
         upper limit
    		 16.4
    Notes
    [86] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [87]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.5
         upper limit
    		 27.3
    Notes
    [87] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [88]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.1
         upper limit
    		 19.2
    Notes
    [88] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1399
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [89]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.4
         upper limit
    		 29.2
    Notes
    [89] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [90]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.2
         upper limit
    		 14.5
    Notes
    [90] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [91]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.6
         upper limit
    		 7.5
    Notes
    [91] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [92]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.5
         upper limit
    		 15.8
    Notes
    [92] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [93]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.7
         upper limit
    		 26.3
    Notes
    [93] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [94]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.9
         upper limit
    		 30.3
    Notes
    [94] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1037
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [95]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -16.9
         upper limit
    		 27.1
    Notes
    [95] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [96]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.4
         upper limit
    		 20.2
    Notes
    [96] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [97]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 5.1
         upper limit
    		 10.5
    Notes
    [97] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [98]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12
         upper limit
    		 18.6
    Notes
    [98] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [99]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -27.1
         upper limit
    		 25.5
    Notes
    [99] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [100]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -23.5
         upper limit
    		 37.2
    Notes
    [100] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1048
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [101]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -10.7
         upper limit
    		 38
    Notes
    [101] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [102]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -4.2
         upper limit
    		 10.4
    Notes
    [102] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [103]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.2
         upper limit
    		 11.9
    Notes
    [103] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [104]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.9
         upper limit
    		 15.1
    Notes
    [104] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [105]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.4
         upper limit
    		 32
    Notes
    [105] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [106]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    25
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.1
         upper limit
    		 53.9
    Notes
    [106] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    345
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [107]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    -10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.2
         upper limit
    		 16.6
    Notes
    [107] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [108]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1
         upper limit
    		 16.4
    Notes
    [108] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [109]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2
         upper limit
    		 16.1
    Notes
    [109] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [110]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 10
    Notes
    [110] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [111]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -42.1
         upper limit
    		 43
    Notes
    [111] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [112]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    -10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.5
         upper limit
    		 28.7
    Notes
    [112] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    351
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [113]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -29
         upper limit
    		 36.8
    Notes
    [113] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.

    Secondary: Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Sub Group-FAS

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    End point title
    		 Comparison of Antibody Responses of TIV Versus Comparator TIV in Terms of Percentage of Subjects Achieving Seroconversion or ≥4-fold Increase in HI Titer Against Homologous Strains in Subjects at Risk/Not at Risk, by Age Sub Group-FAS
    End point description
    The superiority of HI antibody responses of ATIV compared to TIV and comparator TIV assessed in terms of of percentage of subjects achieving seroconversion or ≥4-fold increase in HI Titer at three weeks after last vaccination against the three homologous vaccine strains in subjects with a defined set of underlying medical conditions (at risk) and healthy subjects (not at risk), by age sub group.
    End point type
    Secondary
    End point timeframe
    Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months) aTIV (6 to <36 Months) Comparator TIV (6 to <36 Months) TIV (6 to <36 Months) aTIV (36 to <72 Months) TIV (36 to <72 Months) Comparator TIV (36 to <72 Months)
    Number of subjects analysed
    719
    799
    814
    459
    673
    688
    260
    126
    126
    Units: Percentage of Subjects
    number (confidence interval 95%)
        H1N1 norisk(N=717,799,814,459,673,688,258,126,126)
    93 (91 to 95)
    84 (81 to 86)
    79 (76 to 81)
    95 (92 to 96)
    83 (80 to 86)
    78 (75 to 81)
    91 (87 to 94)
    81 (73 to 87)
    89 (82 to 94)
        H3N2 norisk(N=719,799,814,459,673,688,260,126,126)
    97 (95 to 98)
    93 (91 to 94)
    90 (88 to 92)
    98 (96 to 99)
    93 (91 to 95)
    91 (88 to 93)
    95 (91 to 97)
    87 (79 to 92)
    91 (85 to 96)
        B norisk(N=719,799,814,459,673,688,260,126,126)
    97 (96 to 99)
    86 (84 to 89)
    84 (82 to 87)
    98 (96 to 99)
    85 (83 to 88)
    83 (80 to 85)
    97 (95 to 99)
    94 (88 to 97)
    91 (85 to 96)
        H1N1 at risk(N=28,40,35,17,26,26,11,14,9)
    79 (59 to 92)
    83 (67 to 93)
    83 (66 to 93)
    82 (57 to 96)
    85 (65 to 96)
    85 (65 to 96)
    73 (39 to 94)
    78 (40 to 97)
    79 (49 to 95)
        H3N2 at risk(N=28,40,3517,26,26,11,14,9)
    89 (72 to 98)
    85 (70 to 94)
    83 (66 to 93)
    88 (64 to 99)
    77 (56 to 91)
    77 (56 to 91)
    91 (59 to 100)
    100 (66 to 100)
    100 (77 to 100)
        B at risk(N=28,40,35,17,26,26,11,14,9)
    96 (82 to 100)
    88 (73 to 96)
    89 (73 to 97)
    94 (71 to 100)
    92 (75 to 99)
    85 (65 to 96)
    100 (72 to 100)
    100 (66 to 100)
    79 (49 to 95)
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [114]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 6.4
         upper limit
    		 12.8
    Notes
    [114] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [115]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.8
         upper limit
    		 6.4
    Notes
    [115] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [116]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.6
         upper limit
    		 13.9
    Notes
    [116] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [117]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.7
         upper limit
    		 14.9
    Notes
    [117] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [118]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.8
         upper limit
    		 23.4
    Notes
    [118] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [119]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.4
         upper limit
    		 20.7
    Notes
    [119] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [120]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.3
         upper limit
    		 18.1
    Notes
    [120] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [121]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.2
         upper limit
    		 9.1
    Notes
    [121] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [122]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -25.3
         upper limit
    		 15.4
    Notes
    [122] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [123]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    13
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 10.5
         upper limit
    		 16.1
    Notes
    [123] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [124]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -12.7
         upper limit
    		 24.2
    Notes
    [124] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [125]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.8
         upper limit
    		 23.2
    Notes
    [125] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [126]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 8.2
         upper limit
    		 15.3
    Notes
    [126] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [127]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.5
         upper limit
    		 7.4
    Notes
    [127] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [128]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    12
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 9.2
         upper limit
    		 15.3
    Notes
    [128] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [129]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.5
         upper limit
    		 20.2
    Notes
    [129] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [130]
    Method
    Parameter type
    		 Group difference (H3N2H1N1 strain)
    Point estimate
    11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.9
         upper limit
    		 33.5
    Notes
    [130] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [131]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -20.7
         upper limit
    		 19.7
    Notes
    [131] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [132]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 12.6
         upper limit
    		 20.1
    Notes
    [132] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [133]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 4.6
         upper limit
    		 9.8
    Notes
    [133] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [134]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    15
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 11.9
         upper limit
    		 18.3
    Notes
    [134] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [135]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -28.5
         upper limit
    		 20.2
    Notes
    [135] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [136]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    11
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14.9
         upper limit
    		 33.5
    Notes
    [136] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [137]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -14
         upper limit
    		 29.3
    Notes
    [137] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [138]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.8
         upper limit
    		 9.5
    Notes
    [138] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [139]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.8
         upper limit
    		 10
    Notes
    [139] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [140]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.5
         upper limit
    		 12.5
    Notes
    [140] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [141]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -40.7
         upper limit
    		 27.9
    Notes
    [141] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [142]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    -9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.4
         upper limit
    		 14.3
    Notes
    [142] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [143]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    21
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.9
         upper limit
    		 48.1
    Notes
    [143] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [144]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    10
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3
         upper limit
    		 18.5
    Notes
    [144] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [145]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.2
         upper limit
    		 15.6
    Notes
    [145] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [146]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0
         upper limit
    		 9.6
    Notes
    [146] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [147]
    Method
    Parameter type
    		 Group difference (H1N1 strain)
    Point estimate
    -5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -41.7
         upper limit
    		 35
    Notes
    [147] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [148]
    Method
    Parameter type
    		 Group difference (H3N2 strain)
    Point estimate
    -9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -38.6
         upper limit
    		 23.4
    Notes
    [148] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.
    Statistical analysis title
    		 Group difference (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [149]
    Method
    Parameter type
    		 Group difference (B strain)
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -26.9
         upper limit
    		 31
    Notes
    [149] - Non-inferiority was established if the lower bound of confidence interval for day 50 vaccine group difference was > -10%.

    Secondary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, at Risk/Not at Risk, by Age Sub Group-FAS

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, at Risk/Not at Risk, by Age Sub Group-FAS
    End point description
    The superiority of HI antibody responses of aTIV compared to TIV and comparator TIV assessed in terms of post vaccination GMTs at three weeks after last vaccination against the three homologous vaccine strains, in subjects with a defined set of underlying medical conditions (at risk) and in healthy subjects (not at risk), by age sub group.
    End point type
    Secondary
    End point timeframe
    Day 50
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months) aTIV (6 to <36 Months) Comparator TIV (6 to <36 Months) TIV (6 to <36 Months) aTIV (36 to <72 Months) TIV (36 to <72 Months) Comparator TIV (36 to <72 Months)
    Number of subjects analysed
    719
    799
    814
    459
    673
    688
    260
    126
    126
    Units: Titers
    geometric mean (confidence interval 95%)
        H1N1 norisk(N=718,799,814,459,673,688,259,126,126)
    1509 (1357 to 1677)
    569 (515 to 629)
    422 (382 to 466)
    1336 (1166 to 1530)
    474 (424 to 530)
    365 (326 to 407)
    2077 (1815 to 2376)
    813 (670 to 986)
    1413 (1165 to 1713)
        H3N2 norisk(N=719,799,814,459,673,688,260,126,126)
    1894 (1775 to 2022)
    1015 (954 to 1080)
    794 (747 to 844)
    1851 (1705 to 2010)
    905 (845 to 968)
    686 (641 to 733)
    2343 (2120 to 2589)
    1475 (1278 to 1703)
    1582 (1370 to 1826)
        B norisk(N=719,814,799,459,673,688,260,126,126)
    484 (444 to 527)
    164 (151 to 178)
    155 (143 to 168)
    545 (487 to 608)
    150 (137 to 164)
    139 (127 to 152)
    432 (383 to 487)
    253 (212 to 300)
    243 (205 to 289)
        H1N1 at risk(N=28,40,35,17,26,26,11,14,9)
    1541 (948 to 2504)
    830 (553 to 1244)
    586 (380 to 905)
    1277 (674 to 2418)
    617 (370 to 1028)
    483 (289 to 808)
    1982 (929 to 4228)
    1028 (445 to 2372)
    1478 (756 to 2891)
        H3N2 at risk(N=28,40,35,17,26,26,11,14,9)
    2361 (1743 to 3197)
    960 (744 to 1237)
    763 (582 to 1001)
    2517 (1633 to 3881)
    820 (578 to 1164)
    705 (496 to 1000)
    2197 (1514 to 3187)
    929 (616 to 1399)
    1286 (925 to 1788)
        B at risk(N=28,40,35,17,26,26,11,14,9)
    399 (254 to 628)
    152 (104 to 222)
    183 (122 to 274)
    508 (274 to 939)
    140 (85 to 231)
    147 (89 to 242)
    319 (170 to 596)
    241 (118 to 493)
    197 (114 to 341)
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [150]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.29
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.91
         upper limit
    		 2.76
    Notes
    [150] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [151]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.35
         upper limit
    		 1.89
    Notes
    [151] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [152]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    2.92
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.57
         upper limit
    		 3.31
    Notes
    [152] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [153]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.53
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.6
         upper limit
    		 3.93
    Notes
    [153] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [154]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.02
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 4.61
    Notes
    [154] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1518
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [155]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    2.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.34
         upper limit
    		 4.67
    Notes
    [155] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [156]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    3.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.77
         upper limit
    		 4.01
    Notes
    [156] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [157]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.75
         upper limit
    		 2.45
    Notes
    [157] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [158]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.72
         upper limit
    		 3.49
    Notes
    [158] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [159]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.65
         upper limit
    		 4.5
    Notes
    [159] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [160]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    3.22
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.38
         upper limit
    		 7.51
    Notes
    [160] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1533
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [161]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    2.1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.1
         upper limit
    		 3.98
    Notes
    [161] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    Comparator TIV (6 to <36 Months) v aTIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [162]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.1
         upper limit
    		 3.21
    Notes
    [162] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [163]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.08
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.71
         upper limit
    		 2.52
    Notes
    [163] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [164]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.22
         upper limit
    		 4.33
    Notes
    [164] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [165]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 4.4
    Notes
    [165] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [166]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.86
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.94
         upper limit
    		 8.66
    Notes
    [166] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v Comparator TIV (6 to <36 Months)
    Number of subjects included in analysis
    1132
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [167]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 4.4
    Notes
    [167] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [168]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    3.67
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.97
         upper limit
    		 4.54
    Notes
    [168] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [169]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    2.78
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.29
         upper limit
    		 3.37
    Notes
    [169] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [170]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    4.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.46
         upper limit
    		 4.65
    Notes
    [170] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [171]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.45
         upper limit
    		 4.4
    Notes
    [171] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [172]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    4.32
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.43
         upper limit
    		 13
    Notes
    [172] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (6 to <36 Months) v TIV (6 to <36 Months)
    Number of subjects included in analysis
    1147
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [173]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    3.69
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.67
         upper limit
    		 8.15
    Notes
    [173] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [174]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.35
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.89
         upper limit
    		 2.04
    Notes
    [174] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [175]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.14
         upper limit
    		 2.22
    Notes
    [175] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [176]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.68
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.3
         upper limit
    		 2.15
    Notes
    [176] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [177]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    1.73
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.29
         upper limit
    		 10
    Notes
    [177] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [178]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.16
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.33
         upper limit
    		 4.01
    Notes
    [178] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v Comparator TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [179]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.45
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.53
         upper limit
    		 3.94
    Notes
    [179] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [180]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.24
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.48
         upper limit
    		 3.39
    Notes
    [180] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [181]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.76
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.26
         upper limit
    		 2.46
    Notes
    [181] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- No Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [182]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    1.59
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.24
         upper limit
    		 2.04
    Notes
    [182] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H1N1 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [183]
    Method
    Parameter type
    		 GMT Ratio (H1N1 strain)
    Point estimate
    2.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.34
         upper limit
    		 18
    Notes
    [183] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (H3N2 strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [184]
    Method
    Parameter type
    		 GMT Ratio (H3N2 strain)
    Point estimate
    1.98
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.49
         upper limit
    		 7.92
    Notes
    [184] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.
    Statistical analysis title
    		 GMT Ratio (B strain)- Risk
    Comparison groups
    aTIV (36 to <72 Months) v TIV (36 to <72 Months)
    Number of subjects included in analysis
    386
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [185]
    Method
    Parameter type
    		 GMT Ratio (B strain)
    Point estimate
    0.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 2.16
    Notes
    [185] - Noninferiority was concluded if the lower limit of the 2-sided 95% confidence interval of the postvaccination (day 50) ratio of GMTs was above 0.667.

    Secondary: The HI GMTs Against Heterologous Strains, by Vaccine Group (6 to <72 Months Age Group)

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    End point title
    		 The HI GMTs Against Heterologous Strains, by Vaccine Group (6 to <72 Months Age Group)
    End point description
    The HI antibody titers against the heterologous strains following vaccination with either aTIV, licensed comparator or TIV, at three weeks and at six months after vaccination are reported as GMTs.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 50, Day 209
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    380
    445
    431
    Units: Titers
    number (confidence interval 95%)
        H1N1/Jersey - Day 1 (N=380,445,430)
    10 (9.37 to 11)
    9.75 (8.85 to 11)
    10 (9.07 to 11)
        H1N1/Jersey - Day 50
    51 (45 to 58)
    29 (26 to 33)
    31 (27 to 36)
        H1N1/Jersey - Day 209
    21 (19 to 23)
    17 (16 to 19)
    18 (16 to 20)
        H3N2/Uruguay - Day 1 (N=380,445,430)
    17 (15 to 20)
    18 (16 to 20)
    17 (15 to 19)
        H3N2/Uruguay - Day 50
    184 (165 to 206)
    88 (79 to 98)
    71 (63 to 79)
        H3N2/Uruguay- Day 209
    42 (37 to 47)
    31 (28 to 34)
    27 (24 to 30)
        B strain - Day 1
    5.98 (5.72 to 6.25)
    5.8 (5.55 to 6.05)
    5.85 (5.6 to 6.11)
        B strain - Day 50
    99 (89 to 111)
    34 (31 to 38)
    35 (31 to 39)
        B strain Day 209
    20 (18 to 22)
    11 (9.86 to 12)
    11 (9.94 to 12)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Heterologous Strains

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    End point title
    		 Percentage of Subjects Achieving Seroconversion or ≥4 Fold Increase in HI Titers, Against Heterologous Strains
    End point description
    The percentage of subjects achieving seroconversion or ≥4 fold increase in HI titers from baseline, against heterologous strains, at three weeks and six months after last vaccination with aTIV or licensed comparator or TIV.
    End point type
    Secondary
    End point timeframe
    Day 50, Day 209
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    380
    445
    431
    Units: Percentage of Subjects
    number (confidence interval 95%)
        H1N1/Jersey, Day 50 (N=380,445,430)
    53.16 (48 to 58.26)
    36.85 (32.36 to 41.52)
    36.05 (31.5 to 40.78)
        H1N1/Jersey, Day 209 (N=380,445,430)
    33.95 (29.2 to 38.95)
    19.33 (15.76 to 23.31)
    20.7 (16.96 to 24.84)
        H3N2/Uruguay, Day 50 (N=380,445,430)
    91.84 (88.62 to 94.39)
    60.9 (56.19 to 65.46)
    53.26 (48.42 to 58.05)
        H3N2/Uruguay, Day 209 (N=380,445,430)
    40.26 (35.29 to 45.39)
    23.82 (19.94 to 28.06)
    19.07 (15.46 to 23.11)
        B strain, Day 50
    92.63 (89.53 to 95.05)
    53.71 (48.95 to 58.41)
    52.9 (48.07 to 57.69)
        B strain, Day 209
    30 (25.43 to 34.88)
    13.93 (10.85 to 17.5)
    17.63 (14.15 to 21.57)
    No statistical analyses for this end point

    Secondary: Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, After One Vaccination

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    End point title
    		 Comparison of Antibody Responses of aTIV With TIV and Comparator TIV in Terms of GMTs Against Homologous Strains, After One Vaccination
    End point description
    To demonstrate the GMTs at three weeks after one dose of aTIV are statistically significantly higher to the corresponding response's of comparator TIV and TIV.
    End point type
    Secondary
    End point timeframe
    Day 1, Day 29
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    715
    822
    820
    Units: Percentage of Subjects
    geometric mean (confidence interval 95%)
        H1N1- Day 1 (N=714,822,820)
    28 (24 to 32)
    24 (20 to 27)
    27 (23 to 31)
        H1N1- Day 29
    647 (562 to 745)
    159 (139 to 182)
    170 (148 to 194)
        H3N2 - Day 1
    42 (36 to 48)
    43 (37 to 49)
    43 (38 to 50)
        H3N2 - Day 29
    1087 (1004 to 1176)
    558 (517 to 602)
    453 (420 to 490)
        B strain Day 1
    10 (9.29 to 11)
    10 (9.57 to 11)
    10 (9.34 to 11)
        B strain Day 29
    119 (106 to 134)
    58 (52 to 65)
    61 (54 to 68)
    Statistical analysis title
    		 GMT ratio (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1537
    Analysis specification
    Pre-specified
    Analysis type
    		 other [186]
    Method
    Parameter type
    		 GMT ratio (H1N1 strain)
    Point estimate
    4.07
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.34
         upper limit
    		 4.95
    Notes
    [186] - GMTs were considered to be statistically significantly higher if the lower bound of the 95% confidence interval around the vaccine group ratio was >1.0.
    Statistical analysis title
    		 GMT ratio (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1537
    Analysis specification
    Pre-specified
    Analysis type
    		 other [187]
    Method
    Parameter type
    		 GMT ratio (H3N2 strain)
    Point estimate
    1.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.74
         upper limit
    		 2.18
    Notes
    [187] - GMTs were considered to be statistically significantly higher if the lower bound of the 95% confidence interval around the vaccine group ratio was >1.0.
    Statistical analysis title
    		 GMT ratio (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v Comparator TIV (6 to <72 Months)
    Number of subjects included in analysis
    1537
    Analysis specification
    Pre-specified
    Analysis type
    		 other [188]
    Method
    Parameter type
    		 GMT ratio (B strain)
    Point estimate
    2.03
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.73
         upper limit
    		 2.39
    Notes
    [188] - GMTs were considered to be statistically significantly higher if the lower bound of the 95% confidence interval around the vaccine group ratio was >1.0.
    Statistical analysis title
    		 GMT ratio (H1N1 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1535
    Analysis specification
    Pre-specified
    Analysis type
    		 other [189]
    Method
    Parameter type
    		 GMT ratio (H1N1 strain)
    Point estimate
    3.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.14
         upper limit
    		 4.64
    Notes
    [189] - GMTs were considered to be statistically significantly higher if the lower bound of the 95% confidence interval around the vaccine group ratio was >1.0.
    Statistical analysis title
    		 GMT ratio (H3N2 strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1535
    Analysis specification
    Pre-specified
    Analysis type
    		 other [190]
    Method
    Parameter type
    		 GMT ratio (H3N2 strain)
    Point estimate
    2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 2.15
         upper limit
    		 2.68
    Notes
    [190] - GMTs were considered to be statistically significantly higher if the lower bound of the 95% confidence interval around the vaccine group ratio was >1.0.
    Statistical analysis title
    		 GMT ratio (B strain)
    Comparison groups
    aTIV (6 to <72 Months) v TIV (6 to <72 Months)
    Number of subjects included in analysis
    1535
    Analysis specification
    Pre-specified
    Analysis type
    		 other [191]
    Method
    Parameter type
    		 GMT ratio (B strain)
    Point estimate
    1.95
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.65
         upper limit
    		 2.29
    Notes
    [191] - GMTs were considered to be statistically significantly higher if the lower bound of the 95% confidence interval around the vaccine group ratio was >1.0.

    Secondary: Number of Subjects Reporting Solicited Adverse Events After Vaccination

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    End point title
    		 Number of Subjects Reporting Solicited Adverse Events After Vaccination
    End point description
    The number of subjects reporting any solicited local and systemic adverse events (AEs), following vaccination with aTIV or licensed comparator or TIV.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 7 after any vaccination
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    3082
    1453
    1451
    Units: Percentage of Subjects
        Any local
    1082
    292
    311
        Injection site ecchymosis(N=3075,1450,1446)
    191
    72
    86
        Injection site erythema (N=3075,1450,1446)
    312
    109
    101
        Injection site induration (N=3075,1450,1446)
    258
    62
    67
        Injection site tenderness (N=1495,1025,1012)
    152
    70
    78
        Injection site swelling (N=3075,1450,1446)
    217
    1450
    1446
        Injection site pain (N=1580,422,429)
    1580
    422
    429
        Any systemic
    1487
    604
    569
        chills (N=1578,423,428)
    154
    23
    18
        Myalgia (N=1578,423,429)
    216
    43
    25
        Arthralgia (N=1578,423,429)
    125
    20
    16
        Headache (N=1578,423,429)
    282
    46
    38
        Fatigue (N=1578,423,430)
    204
    43
    31
        Eating Habit (N=3076,1450,1446)
    437
    196
    205
        Diarrhea (N=3075,1450,1447)
    423
    231
    220
        Irritability (N=1496,1024,1013)
    290
    164
    190
        Crying (N=1463,1001,990)
    186
    105
    122
        Sleepiness (N=1495,1024,1012)
    229
    150
    153
        Vomiting (N=3075,1451,1446)
    249
    100
    104
        Fever (≥38°C) (N=3074,1450,1446)
    748
    236
    224
        Any other
    1047
    310
    317
        Axillary Temperature (≥40°C) (N=3074,1450,1446)
    8
    4
    3
        Analgesic Antipyretic Med. used (N=3076,1448,1444)
    984
    285
    282
    No statistical analyses for this end point

    Secondary: Number of Subjects Reporting Unsolicited Adverse Events After Vaccination

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    End point title
    		 Number of Subjects Reporting Unsolicited Adverse Events After Vaccination
    End point description
    The number of subjects reporting any unsolicited adverse events (AEs) between Day 1 to Day 50, serious adverse events (SAEs), AE leading to withdrawal (WD), new onset of chronic disease(NOCD), adverse events of special interest following vaccination with aTIV or licensed comparator or TIV throughout the study (Day 1 to Day 394).
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 394
    End point values
    		 aTIV (6 to <72 Months) Comparator TIV (6 to <72 Months) TIV (6 to <72 Months)
    Number of subjects analysed
    3123
    1474
    1477
    Units: Percentage of Subjects
        Any AEs (Day 1 to Day 50)
    1541
    859
    808
        Possibly/probably related AEs(Day 1 to Day 50)
    158
    101
    84
        Any SAEs
    115
    64
    69
        Possibly/probably related SAE
    1
    0
    0
        AE leading to WD
    1
    5
    4
        NOCD
    48
    31
    24
        AESI
    1
    0
    0
        Deaths
    1
    3
    4
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited AEs collected from Day 1-7 after each vaccination, Unsolicited AEs, Adverse Events of Special Interest, New onset chronic disease, AEs leading to withdrawal and serious adverse events reported for through out the study (Day 1-Day 394).
    Adverse event reporting additional description
    Analysis was done on Full Safety Set - Subjects who received at least one study vaccination and provided postbaseline safety data.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    15.1
    Reporting groups
    Reporting group title
    Comparator TIV (6 to <72 Months)
    Reporting group description
    		 Subjects received a licensed comparator trivalent split influenza vaccine (comparator TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Reporting group title
    ATIV (6 to <72 Months)
    Reporting group description
    		 Subjects received an investigational MF59-adjuvanted trivalent influenza vaccine (aTIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Reporting group title
    TIV (6 to <72 Months)
    Reporting group description
    		 Subjects received an investigational trivalent split influenza vaccine (TIV), subjects aged between 6 to <36 months received two doses of 0.25 mL each, while subjects aged ≥36 months received two doses of 0.5 mL each, at Days 1 & 29.

    Serious adverse events
    		 Comparator TIV (6 to <72 Months) ATIV (6 to <72 Months) TIV (6 to <72 Months)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    64 / 1474 (4.34%)
    115 / 3123 (3.68%)
    69 / 1477 (4.67%)
         number of deaths (all causes)
    3
    1
    4
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute Lymphocytic Leukaemia
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    2 / 1477 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Cholesteatoma
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accidental Exposure
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Animal Bite
         subjects affected / exposed
    14 / 1474 (0.95%)
    22 / 3123 (0.70%)
    15 / 1477 (1.02%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 22
    0 / 15
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Animal Scratch
         subjects affected / exposed
    0 / 1474 (0.00%)
    3 / 3123 (0.10%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Craniocerebral Injury
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Eye Injury
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Femur Fracture
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Forearm Fracture
         subjects affected / exposed
    1 / 1474 (0.07%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Head Injury
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Humerus Fracture
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Multiple Injuries
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Radius Fracture
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skull Fracture
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subdural Haemorrhage
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thermal Burn
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Finger Amputation
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Convulsion
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    2 / 1477 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Febrile Convulsion
         subjects affected / exposed
    3 / 1474 (0.20%)
    13 / 3123 (0.42%)
    4 / 1477 (0.27%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 13
    0 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Drowning
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Immune system disorders
    Type III Immune Complex Mediated Reaction
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Coeliac Disease
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Gastrointestinal Disorder Hamorrage
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Adenoidal Hypertrophy
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 1474 (0.07%)
    4 / 3123 (0.13%)
    3 / 1477 (0.20%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 7
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Asthmatic Crisis
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Atelectasis
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchial Hyperreactivity
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchospasm
         subjects affected / exposed
    0 / 1474 (0.00%)
    3 / 3123 (0.10%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillary Hypertrophy
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Swelling Face
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Dermatitis Allergic
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    2 / 1477 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess Limb
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abscess Neck
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Amoebiasis
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 1474 (0.07%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Arthritis Bacterial
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bacterial Infection
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 1474 (0.07%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Bronchopneumonia
         subjects affected / exposed
    6 / 1474 (0.41%)
    4 / 3123 (0.13%)
    3 / 1477 (0.20%)
         occurrences causally related to treatment / all
    0 / 6
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dengue Fever
         subjects affected / exposed
    3 / 1474 (0.20%)
    5 / 3123 (0.16%)
    8 / 1477 (0.54%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 5
    0 / 8
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea Infectious
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dysentery
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Encephalitis Viral
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    12 / 1474 (0.81%)
    18 / 3123 (0.58%)
    10 / 1477 (0.68%)
         occurrences causally related to treatment / all
    0 / 13
    0 / 18
    0 / 13
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    Hepatitis A
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Lower Respiratory Tract Infection Viral
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Mastoiditis
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Measles
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Meningitis Pneumococcal
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis Media
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis Media Bacterial
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis Media Chronic
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Parasitic Gastroenteritis
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngotonsillitis
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    13 / 1474 (0.88%)
    26 / 3123 (0.83%)
    12 / 1477 (0.81%)
         occurrences causally related to treatment / all
    0 / 14
    0 / 28
    0 / 13
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Pneumonia Bacterial
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Viral
         subjects affected / exposed
    1 / 1474 (0.07%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis Acute
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory Syncytial Virus Infection
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory Tract Infection Viral
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Roseola
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    2 / 1474 (0.14%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    Septic Shock
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    Shigella Infection
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thypoid Fever
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    2 / 1477 (0.14%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 1474 (0.00%)
    2 / 3123 (0.06%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tooth Abscess
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    3 / 1474 (0.20%)
    4 / 3123 (0.13%)
    2 / 1477 (0.14%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 4
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Varicella
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    2 / 1474 (0.14%)
    2 / 3123 (0.06%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral Rash
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Hyponatraemia
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Malnutrition
         subjects affected / exposed
    0 / 1474 (0.00%)
    1 / 3123 (0.03%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolic Acidosis
         subjects affected / exposed
    0 / 1474 (0.00%)
    0 / 3123 (0.00%)
    1 / 1477 (0.07%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Tetany
         subjects affected / exposed
    1 / 1474 (0.07%)
    0 / 3123 (0.00%)
    0 / 1477 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Comparator TIV (6 to <72 Months) ATIV (6 to <72 Months) TIV (6 to <72 Months)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    917 / 1474 (62.21%)
    2106 / 3123 (67.44%)
    905 / 1477 (61.27%)
    Nervous system disorders
    Headache
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    40 / 1474 (2.71%)
    286 / 3123 (9.16%)
    48 / 1477 (3.25%)
         occurrences all number
    53
    342
    60
    Somnolence
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    153 / 1474 (10.38%)
    229 / 3123 (7.33%)
    150 / 1477 (10.16%)
         occurrences all number
    216
    316
    198
    General disorders and administration site conditions
    Crying
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    124 / 1474 (8.41%)
    186 / 3123 (5.96%)
    105 / 1477 (7.11%)
         occurrences all number
    162
    225
    139
    Fatigue
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    31 / 1474 (2.10%)
    204 / 3123 (6.53%)
    43 / 1477 (2.91%)
         occurrences all number
    45
    259
    57
    Injection site erythema
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    102 / 1474 (6.92%)
    312 / 3123 (9.99%)
    109 / 1477 (7.38%)
         occurrences all number
    122
    378
    130
    Injection site hemorrhage
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    86 / 1474 (5.83%)
    191 / 3123 (6.12%)
    72 / 1477 (4.87%)
         occurrences all number
    102
    215
    81
    Injection site induration
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    67 / 1474 (4.55%)
    258 / 3123 (8.26%)
    62 / 1477 (4.20%)
         occurrences all number
    78
    293
    71
    Injection site pain
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    189 / 1474 (12.82%)
    851 / 3123 (27.25%)
    177 / 1477 (11.98%)
         occurrences all number
    248
    1137
    220
    Injection site swelling
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    43 / 1474 (2.92%)
    217 / 3123 (6.95%)
    34 / 1477 (2.30%)
         occurrences all number
    47
    238
    36
    Gastrointestinal disorders
    Diarrhea
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    231 / 1474 (15.67%)
    445 / 3123 (14.25%)
    247 / 1477 (16.72%)
         occurrences all number
    307
    568
    318
    Vomiting
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    109 / 1474 (7.39%)
    257 / 3123 (8.23%)
    107 / 1477 (7.24%)
         occurrences all number
    127
    296
    129
    Pyrexia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    260 / 1474 (17.64%)
    795 / 3123 (25.46%)
    279 / 1477 (18.89%)
         occurrences all number
    330
    1003
    331
    Psychiatric disorders
    Irritability
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    191 / 1474 (12.96%)
    290 / 3123 (9.29%)
    165 / 1477 (11.17%)
         occurrences all number
    244
    396
    226
    Eating Disorder
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    206 / 1474 (13.98%)
    437 / 3123 (13.99%)
    197 / 1477 (13.34%)
         occurrences all number
    273
    541
    254
    Musculoskeletal and connective tissue disorders
    Myalgia
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    25 / 1474 (1.70%)
    216 / 3123 (6.92%)
    43 / 1477 (2.91%)
         occurrences all number
    35
    257
    50
    Infections and infestations
    Gastroenteritis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    84 / 1474 (5.70%)
    112 / 3123 (3.59%)
    70 / 1477 (4.74%)
         occurrences all number
    91
    117
    74
    Nasopharyngitis
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    175 / 1474 (11.87%)
    291 / 3123 (9.32%)
    151 / 1477 (10.22%)
         occurrences all number
    206
    349
    174
    Upper respiratory tract infection
    alternative dictionary used: MedDRA 17.1
         subjects affected / exposed
    246 / 1474 (16.69%)
    452 / 3123 (14.47%)
    237 / 1477 (16.05%)
         occurrences all number
    286
    533
    281

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? No

    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

    Online references
    http://www.ncbi.nlm.nih.gov/pubmed/25223266
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