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    Clinical Trial Results:
    A Phase 3, Randomized, Observer-blind, Controlled, Multicenter, Clinical Study to Evaluate Immunogenicity and Safety of an MF59-adjuvanted Quadrivalent Subunit Inactivated Influenza Vaccine in Comparison with a Licensed Quadrivalent Influenza Vaccine, in Adults 50 to 64 Years of Age

    Summary
    EudraCT number
    		 2021-001721-40
    Trial protocol
    		 DE   EE  
    Global end of trial date
    14 Oct 2022

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Oct 2023
    First version publication date
    14 Oct 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    V118_23
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05044195
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Seqirus UK Limited
    Sponsor organisation address
    The Point, 29 Market Street, Maidenhead, United Kingdom, SL6 8AA
    Public contact
    Clinical Trial Disclosures Manager, Seqirus UK Limited, Seqirus.ClinicalTrials@Seqirus.com
    Scientific contact
    Clinical Trial Disclosures Manager, Seqirus UK Limited, Seqirus.ClinicalTrials@Seqirus.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    09 Dec 2022
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    18 Jan 2022
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Oct 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Primary Immunogenicity Objectives: 1. To demonstrate immunological noninferiority of aQIV versus a nonadjuvanted quadrivalent influenza comparator (QIV) in subjects 50-64 years of age, as measured by hemagglutination inhibition (HI) geometric mean titers (GMTs) and seroconversion rates (SCRs) for each vaccine strain, at 3 weeks after vaccination. 2. To demonstrate that aQIV induces a superior immune response compared with QIV in subjects 50-64 years of age as measured by HI GMTs at 3 weeks after vaccination for at least 2 of the 4 vaccine strains.
    Protection of trial subjects
    This clinical study was designed, implemented, and reported in accordance with the ICH Harmonised Tripartite Guidelines for Good Clinical Practice (ICH E6(R2)), with applicable local regulations European Directive 2001/20/EC, United States (US) Code of Federal Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare, Seqirus codes on protection of human rights, and with the ethical principles laid down in the Declaration of Helsinki.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    15 Sep 2021
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Estonia: 787
    Country: Number of subjects enrolled
    Germany: 513
    Country: Number of subjects enrolled
    United States: 744
    Worldwide total number of subjects
    2044
    EEA total number of subjects
    1300
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    2044
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects were enrolled from 6 centers in Estonia, 11 centers in Germany, and 12 centers in the US.

    Pre-assignment
    Screening details
    		 All enrolled subjects were randomized in the study.

    Period 1
    Period 1 title
    overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Monitor, Data analyst, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 aQIV
    Arm description
    		 Adjuvanted QIV containing 2 influenza type A strains and 2 influenza type B strains
    Arm type
    		 Experimental

    Investigational medicinal product name
    Adjuvanted Quadrivalent Influenza Vaccine (aQIV)
    Investigational medicinal product code
    Other name
    Fluad Tetra
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single intramuscular injection (0.5 mL dose) on Day 1

    Arm title
    		 Comparator QIV
    Arm description
    		 Non-adjuvanted comparator QIV containing 2 influenza type A strains and 2 influenza type B strains
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Non-adjuvanted Quadrivalent Influenza Vaccine (QIV)
    Investigational medicinal product code
    Other name
    Fluarix Quadrivalent
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Single intramuscular injection (0.5 mL dose) on Day 1

    Number of subjects in period 1
    		aQIV Comparator QIV
    Started
    1027
    1017
    Completed
    982
    989
    Not completed
    45
    28
         Adverse event, serious fatal
    1
    -
         Consent withdrawn by subject
    6
    8
         Adverse event, non-fatal
    -
    1
         Other
    3
    2
         Lost to follow-up
    35
    17

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    aQIV
    Reporting group description
    		 Adjuvanted QIV containing 2 influenza type A strains and 2 influenza type B strains

    Reporting group title
    Comparator QIV
    Reporting group description
    		 Non-adjuvanted comparator QIV containing 2 influenza type A strains and 2 influenza type B strains

    Reporting group values
    		 aQIV Comparator QIV Total
    Number of subjects
    		 1027 1017 2044
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 0 0 0
        Adolescents (12-17 years)
    		 0 0 0
        Adults (18-64 years)
    		 1027 1017 2044
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.8 ± 4.17 57.8 ± 4.21 -
    Gender categorical
    Units: Subjects
        Female
    		 635 615 1250
        Male
    		 392 402 794
    Age group
    Units: Subjects
        50 to 59 years
    		 609 596 1205
        60 to 64 years
    		 418 421 839
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 14 12 26
        Not Hispanic or Latino
    		 1013 1001 2014
        Unknown or Not Reported
    		 0 4 4
    Race
    Units: Subjects
        American Indian or Alaska Native
    		 2 3 5
        Asian
    		 2 4 6
        Black or African American
    		 39 36 75
        Native Hawaiian or Other Pacific Islander
    		 1 1 2
        White
    		 982 972 1954
        Other
    		 1 1 2
    Country
    Units: Subjects
        Estonia
    		 391 396 787
        Germany
    		 259 254 513
        United States
    		 377 367 744
    Received an influenza vaccination in the previous 3 influenza seasons
    Units: Subjects
        Yes
    		 586 598 1184
        No
    		 441 419 860
    Comorbidity Risk Score
    A subject's comorbidity risk score was obtained by adding scores for each applicable characteristic: age (<70; 70-74; 75-79; 80-89; ≥90 years); sex (female; male); number of outpatient visits during the previous year (0; 1-6; 7-12; ≥13); previous hospitalization due to pneumonia or influenza (no; yes); pre-existing comorbidity (pulmonary disease; heart disease; renal disease or renal transplant; dementia or stroke; nonhematological and hematological cancer). A cut-off score ≥50 defines higher probability of hospitalization due to pneumonia/influenza or death (Hak et al, J Infect Dis 2004).
    Units: Subjects
        <50
    		 912 919 1831
        ≥50
    		 115 98 213

    End points

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    End points reporting groups
    Reporting group title
    aQIV
    Reporting group description
    		 Adjuvanted QIV containing 2 influenza type A strains and 2 influenza type B strains

    Reporting group title
    Comparator QIV
    Reporting group description
    		 Non-adjuvanted comparator QIV containing 2 influenza type A strains and 2 influenza type B strains

    Subject analysis set title
    FAS Immunogenicity
    Subject analysis set type
    		 Modified intention-to-treat
    Subject analysis set description
    The Full Analysis Set (FAS) Immunogenicity is defined as all enrolled subjects who were randomized, received study vaccination and provided immunogenicity data at any time point.

    Subject analysis set title
    PPS Immunogenicity
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    The Per Protocol Set (PPS) Immunogenicity is defined as all subjects in the FAS Immunogenicity who: had both Day 1 and Day 22 immunogenicity assessment; correctly received the vaccine (ie, received the vaccine to which the subjects were randomized and at the scheduled time points); had no protocol deviations leading to exclusion as defined prior to unblinding/analysis; were not excluded due to other reasons defined prior to unblinding or analysis.

    Subject analysis set title
    Solicited Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Solicited Safety Set is defined as all exposed subjects with any solicited AE data including temperature measurements or use of analgesics/antipyretics.

    Subject analysis set title
    Unsolicited Safety Set
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    The Unsolicited Safety Set is defined as all exposed subjects who provided unsolicited AE data.

    Primary: Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio of Hemagglutination Inhibition (HI) Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (PPS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: Geometric Mean Titer (GMT) and GMT Ratio of Hemagglutination Inhibition (HI) Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (PPS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Adjusted GMTs are presented.
    End point type
    Primary
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    983
    985
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1
    731.90 (689.39 to 777.04)
    586.85 (552.83 to 622.96)
        A/H3N2
    347.89 (324.78 to 372.64)
    313.16 (292.42 to 335.36)
        B/Yamagata
    154.40 (146.80 to 162.40)
    145.74 (138.57 to 153.27)
        B/Victoria
    144.41 (136.97 to 152.26)
    143.32 (135.97 to 151.07)
    Statistical analysis title
    		 GMT Ratio / A/H1N1
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H1N1 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [1]
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.802
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.738
         upper limit
    		 0.871
    Notes
    [1] - Non-inferiority criteria for the GMT ratio: upper limit (UL) of the 95% confidence interval (CI) for the inter-group GMT ratio is ≤1.5 for each vaccine strain
    Statistical analysis title
    		 GMT Ratio / A/H3N2
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H3N2 vaccine strain
    Comparison groups
    Comparator QIV v aQIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.819
         upper limit
    		 0.989
    Notes
    [2] - Non-inferiority criteria for the GMT ratio: UL of the 95% CI for the inter-group GMT ratio is ≤1.5 for each vaccine strain
    Statistical analysis title
    		 GMT Ratio / B/Yamagata
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Yamagata vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.944
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.012
    Notes
    [3] - Non-inferiority criteria for the GMT ratio: UL of the 95% CI for the inter-group GMT ratio is ≤1.5 for each vaccine strain
    Statistical analysis title
    		 GMT Ratio / B/Victoria
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Victoria vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [4]
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.992
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.923
         upper limit
    		 1.067
    Notes
    [4] - Non-inferiority criteria for the GMT ratio: UL of the 95% CI for the inter-group GMT ratio is ≤1.5 for each vaccine strain

    Primary: Immunogenicity Endpoint: Seroconversion Rate (SCR) and SCR Difference for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (PPS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: Seroconversion Rate (SCR) and SCR Difference for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (PPS Immunogenicity)
    End point description
    The SCR defined as the percentage of subjects with either a prevaccination HI titer <1:10 and a postvaccination (Day 22) HI titer ≥1:40, or with either a prevaccination HI titer ≥1:10 and a ≥4-fold increase in postvaccination HI titer. The SCR difference is defined as the Comparator QIV SCR minus the aQIV SCR.
    End point type
    Primary
    End point timeframe
    Day 1 to Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    983
    985
    Units: percentage of participants
    number (confidence interval 95%)
        A/H1N1
    81.2 (78.57 to 83.58)
    76.8 (74.04 to 79.42)
        A/H3N2
    63.6 (60.46 to 66.63)
    61.8 (58.61 to 64.82)
        B/Yamagata
    43.4 (40.27 to 46.60)
    41.0 (37.92 to 44.19)
        B/Victoria
    44.5 (41.39 to 47.74)
    40.6 (37.52 to 43.76)
    Statistical analysis title
    		 SCR Difference / A/H1N1
    Statistical analysis description
    SCR difference at Day 22 for the A/H1N1 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 SCR difference
    Point estimate
    -4.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -7.97
         upper limit
    		 -0.74
    Notes
    [5] - Non-inferiority criteria for the SCR difference: UL of the 95% CI for the difference in SCR is ≤10% for each vaccine strain
    Statistical analysis title
    		 SCR Difference / A/H3N2
    Statistical analysis description
    SCR difference at Day 22 for the A/H3N2 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 SCR difference
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.14
         upper limit
    		 2.48
    Notes
    [6] - Non-inferiority criteria for the SCR difference: UL of the 95% CI for the difference in SCR is ≤10% for each vaccine strain
    Statistical analysis title
    		 SCR Difference / B/Yamagata
    Statistical analysis description
    SCR difference at Day 22 for the B/Yamagata vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [7]
    Method
    Parameter type
    		 SCR difference
    Point estimate
    -2.4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -6.77
         upper limit
    		 2
    Notes
    [7] - Non-inferiority criteria for the SCR difference: UL of the 95% CI for the difference in SCR is ≤10% for each vaccine strain
    Statistical analysis title
    		 SCR Difference / B/Victoria
    Statistical analysis description
    SCR difference at Day 22 for the B/Victoria vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1968
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 SCR difference
    Point estimate
    -3.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -8.31
         upper limit
    		 0.45
    Notes
    [8] - Non-inferiority criteria for the SCR difference: UL of the 95% CI for the difference in SCR is ≤10% for each vaccine strain

    Primary: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Adjusted GMTs are presented.
    End point type
    Primary
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1
    729.17 (687.51 to 773.36)
    589.07 (555.25 to 624.94)
        A/H3N2
    347.09 (324.44 to 371.33)
    315.69 (295.04 to 337.79)
        B/Yamagata
    155.19 (147.67 to 163.09)
    146.89 (139.74 to 154.40)
        B/Victoria
    143.73 (136.44 to 151.42)
    143.74 (136.42 to 151.45)
    Statistical analysis title
    		 GMT Ratio / A/H1N1
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H1N1 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.808
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.745
         upper limit
    		 0.876
    Statistical analysis title
    		 GMT Ratio / A/H3N2
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H3N2 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.91
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.829
         upper limit
    		 0.998
    Statistical analysis title
    		 GMT Ratio / B/Yamagata
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Yamagata vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.947
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.884
         upper limit
    		 1.014
    Statistical analysis title
    		 GMT Ratio / B/Victoria
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Victoria vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    1
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.931
         upper limit
    		 1.075

    Secondary: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Adjusted GMTs are presented.
    End point type
    Secondary
    End point timeframe
    Day 181
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1
    351.73 (331.61 to 373.06)
    306.11 (288.62 to 324.66)
        A/H3N2
    165.17 (155.85 to 175.05)
    157.34 (148.48 to 166.73)
        B/Yamagata
    83.42 (79.81 to 87.20)
    84.53 (80.87 to 88.36)
        B/Victoria
    79.51 (75.81 to 83.40)
    81.73 (77.92 to 85.72)
    Statistical analysis title
    		 GMT Ratio / A/H1N1
    Statistical analysis description
    GMT ratio of HI antibodies at Day 181 for the A/H1N1 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.87
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.803
         upper limit
    		 0.944
    Statistical analysis title
    		 GMT Ratio / A/H3N2
    Statistical analysis description
    GMT ratio of HI antibodies at Day 181 for the A/H3N2 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.953
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.88
         upper limit
    		 1.032
    Statistical analysis title
    		 GMT Ratio / B/Yamagata
    Statistical analysis description
    GMT ratio of HI antibodies at Day 181 for the B/Yamagata vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    1.013
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.953
         upper limit
    		 1.077
    Statistical analysis title
    		 GMT Ratio / B/Victoria
    Statistical analysis description
    GMT ratio of HI antibodies at Day 181 for the B/Victoria vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    2043
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    1.028
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.963
         upper limit
    		 1.098

    Secondary: Immunogenicity Endpoint: GMT of HI Antibodies on Day 1, Day 22, and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT of HI Antibodies on Day 1, Day 22, and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)
    End point description
    GMTs on Day 1 (prior to vaccination), Day 22 (3 weeks after vaccination), and Day 181 (6 months after vaccination) as determined by HI assay against each of the four vaccine strains. Unadjusted GMTs are presented.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 181
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1 Day 1 GMT
    54.37 (49.71 to 59.47)
    50.41 (46.13 to 55.09)
        A/H1N1 Day 22 GMT
    708.36 (666.39 to 752.98)
    553.70 (519.14 to 590.56)
        A/H1N1 Day 181 GMT
    330.76 (308.44 to 354.70)
    276.24 (257.32 to 296.56)
        A/H3N2 Day 1 GMT
    45.97 (42.06 to 50.25)
    46.54 (42.63 to 50.81)
        A/H3N2 Day 22 GMT
    323.40 (300.77 to 347.73)
    292.50 (271.72 to 314.88)
        A/H3N2 Day 181 GMT
    151.92 (141.27 to 163.37)
    143.80 (133.33 to 155.09)
        B/Yamagata Day 1 GMT
    38.50 (35.83 to 41.38)
    38.33 (35.68 to 41.18)
        B/Yamagata Day 22 GMT
    144.30 (136.02 to 153.08)
    134.15 (126.31 to 142.48)
        B/Yamagata Day 181 GMT
    76.87 (72.33 to 81.70)
    77.34 (72.72 to 82.25)
        B/Victoria Day 1 GMT
    36.24 (33.78 to 38.87)
    37.06 (34.56 to 39.73)
        B/Victoria Day 22 GMT
    134.45 (126.24 to 143.21)
    132.45 (124.32 to 141.10)
        B/Victoria Day 181 GMT
    74.17 (69.66 to 78.97)
    75.99 (71.42 to 80.85)
    No statistical analyses for this end point

    Secondary: Immunogenicity Endpoint: Geometric Mean Fold Increase (GMFI) for Day 22/Day 1 and Day 181/Day 1 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: Geometric Mean Fold Increase (GMFI) for Day 22/Day 1 and Day 181/Day 1 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)
    End point description
    The GMFI is defined as the geometric mean of the fold increase of postvaccination HI titer over the prevaccination HI titer.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 181
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: fold increase
    geometric mean (confidence interval 95%)
        A/H1N1 Fold increase Day 22 HI Titer
    13.07 (11.92 to 14.34)
    11.00 (10.07 to 12.02)
        A/H1N1 Fold increase Day 181 HI Titer
    6.22 (5.71 to 6.76)
    5.47 (5.03 to 5.95)
        A/H3N2 Fold increase Day 22 HI Titer
    7.09 (6.43 to 7.83)
    6.31 (5.78 to 6.89)
        A/H3N2 Fold increase Day 181 HI Titer
    3.29 (3.04 to 3.56)
    3.08 (2.86 to 3.31)
        B/Yamagata Fold increase Day 22 HI Titer
    3.77 (3.50 to 4.07)
    3.50 (3.25 to 3.77)
        B/Yamagata Fold increase Day 181 HI Titer
    2.03 (1.91 to 2.16)
    2.01 (1.89 to 2.14)
        B/Victoria Fold increase Day 22 HI Titer
    3.73 (3.45 to 4.02)
    3.60 (3.33 to 3.88)
        B/Victoria Fold increase Day 181 HI Titer
    2.06 (1.93 to 2.19)
    2.05 (1.92 to 2.20)
    No statistical analyses for this end point

    Secondary: Immunogenicity Endpoint: The Percentage of Subjects With a Titer ≥1:40 at Day 1, Day 22, and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: The Percentage of Subjects With a Titer ≥1:40 at Day 1, Day 22, and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)
    End point description
    Percentage of subjects with a titer ≥1:40 on Day 1, Day 22, and Day 181 as determined by HI assay against each of the four vaccine strains
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 181
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: percentage of participants
    number (confidence interval 95%)
        A/H1N1 HI Titer ≥1:40 at Day 1
    65.2 (62.20 to 68.15)
    64.2 (61.14 to 67.15)
        A/H1N1 HI Titer ≥1:40 at Day 22
    99.7 (99.14 to 99.94)
    99.2 (98.44 to 99.66)
        A/H1N1 HI Titer ≥1:40 at Day 181
    98.2 (97.13 to 98.92)
    96.3 (94.89 to 97.36)
        A/H3N2 HI Titer ≥1:40 at Day 1
    60.3 (57.16 to 63.30)
    61.7 (58.61 to 64.72)
        A/H3N2 HI Titer ≥1:40 at Day 22
    97.5 (96.39 to 98.40)
    97.3 (96.12 to 98.23)
        A/H3N2 HI Titer ≥1:40 at Day 181
    92.0 (90.08 to 93.59)
    89.9 (87.81 to 91.68)
        B/Yamagata HI Titer ≥1:40 at Day 1
    60.8 (57.77 to 63.87)
    61.9 (58.81 to 64.90)
        B/Yamagata HI Titer ≥1:40 at Day 22
    95.9 (94.47 to 97.01)
    94.6 (93.05 to 95.94)
        B/Yamagata HI Titer ≥1:40 at Day 181
    83.9 (81.48 to 86.17)
    84.0 (81.60 to 86.28)
        B/Victoria HI Titer ≥1:40 at Day 1
    58.5 (55.42 to 61.57)
    60.4 (57.30 to 63.43)
        B/Victoria HI Titer ≥1:40 at Day 22
    94.4 (92.79 to 95.72)
    93.3 (91.63 to 94.81)
        B/Victoria HI Titer ≥1:40 at Day 181
    83.4 (80.90 to 85.66)
    84.3 (81.84 to 86.48)
    No statistical analyses for this end point

    Secondary: Immunogenicity Endpoint: SCR at Day 22 and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: SCR at Day 22 and Day 181 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains (FAS Immunogenicity)
    End point description
    The SCR defined as the percentage of subjects with either a prevaccination HI titer <1:10 and a postvaccination (Day 22 or Day 181) HI titer ≥1:40, or with either a prevaccination HI titer ≥1:10 and a ≥4-fold increase in postvaccination HI titer.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 181
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: percentage of participants
    number (confidence interval 95%)
        A/H1N1 Day 22 SCR
    80.8 (78.24 to 83.20)
    77.1 (74.34 to 79.65)
        A/H1N1 Day 181 SCR
    64.5 (61.46 to 67.55)
    56.1 (52.94 to 59.24)
        A/H3N2 Day 22 SCR
    63.4 (60.35 to 66.42)
    61.8 (58.65 to 64.79)
        A/H3N2 Day 181 SCR
    39.4 (36.28 to 42.54)
    38.6 (35.51 to 41.72)
        B/Yamagata Day 22 SCR
    42.9 (39.82 to 46.02)
    41.1 (37.99 to 44.19)
        B/Yamagata Day 181 SCR
    22.4 (19.82 to 25.16)
    22.4 (19.86 to 25.19)
        B/Victoria Day 22 SCR
    43.9 (40.86 to 47.08)
    40.6 (37.50 to 43.68)
        B/Victoria Day 181 SCR
    24.3 (21.64 to 27.13)
    23.6 (20.97 to 26.38)
    No statistical analyses for this end point

    Secondary: Safety Endpoint: Solicited Local and Systemic AEs for 7 Days Following Vaccination (Solicited Safety Set)

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    End point title
    		 Safety Endpoint: Solicited Local and Systemic AEs for 7 Days Following Vaccination (Solicited Safety Set)
    End point description
    Percentage of subjects with solicited local and systemic AEs occurring for 7 days following vaccination
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 7
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1020
    1008
    Units: percentage of subjects
    number (not applicable)
        Any Solicited AEs
    65.9
    53.7
        Any Solicited Local AEs
    49.8
    30.4
        Any Solicited Systemic AEs
    45.3
    40.0
        Analgesic/Antipyretic Use
    12.9
    9.6
    No statistical analyses for this end point

    Secondary: Safety Endpoint: All Unsolicited AEs for 21 Days Following Vaccination (Unsolicited Safety Set)

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    End point title
    		 Safety Endpoint: All Unsolicited AEs for 21 Days Following Vaccination (Unsolicited Safety Set)
    End point description
    The percentage of subjects with at least one unsolicited AE occurring 21 days following vaccination The severity of AEs is based on the maximum severity associated with a Preferred Term for a reported AE. Related AEs include possibly related AEs, probably related AEs and AEs with missing relatedness assessment. The severity and relatedness of AEs were determined by the investigator. For the any AE summary by severity, a subject with multiple AEs is counted according to the highest severity of their reported AEs.
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: percentage of subjects
    number (not applicable)
        Any AE
    16.5
    16.9
        Any AE (Mild)
    11.3
    11.3
        Any AE (Moderate)
    5.0
    4.9
        Any AE (Severe)
    0.2
    0.7
        Related AE
    3.2
    3.1
    No statistical analyses for this end point

    Secondary: Safety Endpoint: Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Withdrawal From the Study, and Adverse Events of Special Interest (AESIs)

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    End point title
    		 Safety Endpoint: Serious Adverse Events (SAEs), Adverse Events (AEs) Leading to Withdrawal From the Study, and Adverse Events of Special Interest (AESIs)
    End point description
    The percentage of subjects with any SAE, AE leading to withdrawal, or AESI during the study period
    End point type
    Secondary
    End point timeframe
    Day 1 through Day 271
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    1027
    1016
    Units: percentage of subjects
    number (not applicable)
        SAE
    3.0
    3.1
        Related SAE
    0
    0.1
        AE leading to study withdrawal
    0
    0.1
        AESI
    0.2
    0
        Death
    0.1
    0
    No statistical analyses for this end point

    Other pre-specified: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Age (Subgroup Analysis: 50 to 59 years) (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Age (Subgroup Analysis: 50 to 59 years) (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Subgroup analysis by age (50 to 59 years; 60 to 64 years). Adjusted GMTs for the 50 to 59 years age subgroup are presented.
    End point type
    Other pre-specified
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    609
    595
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1 (50 to 59 years)
    674.25 (622.70 to 730.07)
    565.33 (521.77 to 612.53)
        A/H3N2 (50 to 59 years)
    345.83 (317.55 to 376.63)
    319.55 (293.19 to 348.27)
        B/Yamagata (50 to 59 years)
    161.27 (150.98 to 172.25)
    149.36 (139.72 to 159.67)
        B/Victoria (50 to 59 years)
    167.60 (156.68 to 179.27)
    165.81 (154.92 to 177.47)
    Statistical analysis title
    		 GMT Ratio / A/H1N1 (50 to 59 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H1N1 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.838
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.751
         upper limit
    		 0.936
    Statistical analysis title
    		 GMT Ratio / A/H3N2 (50 to 59 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H3N2 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.924
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.821
         upper limit
    		 1.04
    Statistical analysis title
    		 GMT Ratio / B/Yamagata (50 to 59 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Yamagata vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.926
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.845
         upper limit
    		 1.015
    Statistical analysis title
    		 GMT Ratio / B/Victoria (50 to 59 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Victoria vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1204
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.989
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.901
         upper limit
    		 1.087

    Other pre-specified: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Age (Subgroup Analysis: 60 to 64 years) (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Age (Subgroup Analysis: 60 to 64 years) (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Subgroup analysis by age (50 to 59 years; 60 to 64 years). Adjusted GMTs for the 60 to 64 years age subgroup are presented.
    End point type
    Other pre-specified
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    418
    421
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1 (60 to 64 years)
    806.65 (740.51 to 878.70)
    618.90 (567.97 to 674.41)
        A/H3N2 (60 to 64 years)
    348.59 (312.82 to 388.45)
    310.23 (278.52 to 345.54)
        B/Yamagata (60 to 64 years)
    148.20 (137.62 to 159.59)
    144.34 (134.10 to 155.36)
        B/Victoria (60 to 64 years)
    119.64 (110.33 to 129.75)
    121.16 (111.79 to 131.32)
    Statistical analysis title
    		 GMT Ratio / A/H1N1 (60 to 64 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H1N1 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    839
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.767
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.681
         upper limit
    		 0.864
    Statistical analysis title
    		 GMT Ratio / A/H3N2 (60 to 64 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H3N2 vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    839
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.89
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.766
         upper limit
    		 1.033
    Statistical analysis title
    		 GMT Ratio / B/Yamagata (60 to 64 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Yamagata vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    839
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.974
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.879
         upper limit
    		 1.079
    Statistical analysis title
    		 GMT Ratio / B/Victoria (60 to 64 years)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Victoria vaccine strain
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    839
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    1.013
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.905
         upper limit
    		 1.133

    Other pre-specified: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Influenza Vaccination History (Subgroup Analysis: yes) (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Influenza Vaccination History (Subgroup Analysis: yes) (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Subgroup analysis by influenza vaccination history (received at least one influenza vaccination within the previous 3 influenza seasons: yes; no). Adjusted GMTs for subjects who received at least one influenza vaccination within the previous 3 influenza seasons (yes) are presented.
    End point type
    Other pre-specified
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    586
    598
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1 (previous influenza vaccination - yes)
    648.75 (601.45 to 699.78)
    547.54 (508.79 to 589.24)
        A/H3N2 (previous influenza vaccination - yes)
    279.61 (257.70 to 303.38)
    282.44 (260.95 to 305.71)
        B/Yamagata (previous influenza vaccination - yes)
    116.48 (110.62 to 122.65)
    110.37 (104.98 to 116.04)
        B/Victoria (previous influenza vaccination - yes)
    101.89 (96.50 to 107.59)
    101.59 (96.39 to 107.07)
    Statistical analysis title
    		 GMT Ratio / A/H1N1 (yes)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H1N1 vaccine strain (previous influenza vaccination - yes)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1184
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.844
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.761
         upper limit
    		 0.935
    Statistical analysis title
    		 GMT Ratio / A/H3N2 (yes)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H3N2 vaccine strain (previous influenza vaccination - yes)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1184
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.904
         upper limit
    		 1.128
    Statistical analysis title
    		 GMT Ratio / B/Yamagata (yes)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Yamagata vaccine strain (previous influenza vaccination - yes)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1184
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.948
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.883
         upper limit
    		 1.016
    Statistical analysis title
    		 GMT Ratio / B/Victoria (yes)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Victoria vaccine strain (previous influenza vaccination - yes)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1184
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.997
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.926
         upper limit
    		 1.073

    Other pre-specified: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Influenza Vaccination History (Subgroup Analysis: no) (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Influenza Vaccination History (Subgroup Analysis: no) (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Subgroup analysis by influenza vaccination history (received at least one influenza vaccination within the previous 3 influenza seasons: yes; no). Adjusted GMTs for subjects who did not receive at least one influenza vaccination within the previous 3 influenza seasons (no) are presented.
    End point type
    Other pre-specified
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    441
    418
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1 (previous influenza vaccination - no)
    755.46 (688.45 to 829.00)
    582.90 (529.83 to 641.28)
        A/H3N2 (previous influenza vaccination - no)
    389.77 (347.94 to 436.63)
    312.38 (277.97 to 351.06)
        B/Yamagata (previous influenza vaccination - no)
    188.78 (172.28 to 206.85)
    178.45 (162.38 to 196.12)
        B/Victoria (previous influenza vaccination - no)
    185.31 (168.62 to 203.65)
    186.65 (169.30 to 205.78)
    Statistical analysis title
    		 GMT Ratio / A/H1N1 (no)
    Statistical analysis description
    GMT ratio of HI Antibodies at Day 22 for the A/H1N1 vaccine strain (previous influenza vaccination - no)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    859
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.772
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.677
         upper limit
    		 0.88
    Statistical analysis title
    		 GMT Ratio / A/H3N2 (no)
    Statistical analysis description
    GMT ratio of HI Antibodies at Day 22 for the A/H3N2 vaccine strain (previous influenza vaccination - no)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    859
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.801
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.683
         upper limit
    		 0.941
    Statistical analysis title
    		 GMT Ratio / B/Yamagata (no)
    Statistical analysis description
    GMT ratio of HI Antibodies at Day 22 for the B/Yamagata vaccine strain (previous influenza vaccination - no)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    859
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.945
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.831
         upper limit
    		 1.076
    Statistical analysis title
    		 GMT Ratio / B/Victoria (no)
    Statistical analysis description
    GMT ratio of HI Antibodies at Day 22 for the B/Victoria vaccine strain (previous influenza vaccination - no)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    859
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    1.007
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.881
         upper limit
    		 1.151

    Other pre-specified: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Comorbidity Risk Score (Subgroup Analysis: <50) (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Comorbidity Risk Score (Subgroup Analysis: <50) (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Subgroup analysis by comorbidity risk score (<50; ≥50). Adjusted GMTs for subjects with a comorbidity risk score <50 are presented.
    End point type
    Other pre-specified
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    912
    918
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1 (Comorbidity Risk Score <50)
    715.26 (671.75 to 761.60)
    586.42 (550.95 to 624.16)
        A/H3N2 (Comorbidity Risk Score <50)
    337.43 (314.06 to 362.53)
    314.75 (293.14 to 337.96)
        B/Yamagata (Comorbidity Risk Score <50)
    150.17 (142.37 to 158.40)
    145.98 (138.44 to 153.93)
        B/Victoria (Comorbidity Risk Score <50)
    139.76 (132.15 to 147.82)
    141.58 (133.93 to 149.68)
    Statistical analysis title
    		 GMT Ratio / A/H1N1 (<50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H1N1 vaccine strain (Comorbidity Risk Score <50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1830
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.82
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.752
         upper limit
    		 0.894
    Statistical analysis title
    		 GMT Ratio / A/H3N2 (<50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H3N2 vaccine strain (Comorbidity Risk Score <50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1830
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.933
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.846
         upper limit
    		 1.029
    Statistical analysis title
    		 GMT Ratio / B/Yamagata (<50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Yamagata vaccine strain (Comorbidity Risk Score <50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1830
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.972
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.904
         upper limit
    		 1.046
    Statistical analysis title
    		 GMT Ratio / B/Victoria (<50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Victoria vaccine strain (Comorbidity Risk Score <50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    1830
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    1.013
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.938
         upper limit
    		 1.094

    Other pre-specified: Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Comorbidity Risk Score (Subgroup Analysis: ≥50) (FAS Immunogenicity)

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    End point title
    		 Immunogenicity Endpoint: GMT and GMT Ratio of HI Antibodies at Day 22 for the A/H1N1, A/H3N2, B/Yamagata, and B/Victoria Vaccine Strains by Comorbidity Risk Score (Subgroup Analysis: ≥50) (FAS Immunogenicity)
    End point description
    The GMT ratio is defined as the geometric mean of the postvaccination HI titer for Comparator QIV over the geometric mean of the postvaccination HI titer for aQIV. Subgroup analysis by comorbidity risk score (<50; ≥50). Adjusted GMTs for subjects with a comorbidity risk score ≥50 are presented.
    End point type
    Other pre-specified
    End point timeframe
    Day 22
    End point values
    		 aQIV Comparator QIV
    Number of subjects analysed
    115
    98
    Units: titer
    geometric mean (confidence interval 95%)
        A/H1N1 (Comorbidity Risk Score ≥50)
    812.59 (681.59 to 968.76)
    573.86 (473.11 to 696.06)
        A/H3N2 (Comorbidity Risk Score ≥50)
    453.60 (368.59 to 558.20)
    333.16 (265.15 to 418.62)
        B/Yamagata (Comorbidity Risk Score ≥50)
    198.10 (172.89 to 227.00)
    153.05 (131.91 to 177.58)
        B/Victoria (Comorbidity Risk Score ≥50)
    174.79 (151.43 to 201.74)
    158.12 (135.26 to 184.85)
    Statistical analysis title
    		 GMT Ratio / A/H1N1 (≥50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H1N1 vaccine strain (Comorbidity Risk Score ≥50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.706
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.553
         upper limit
    		 0.902
    Statistical analysis title
    		 GMT Ratio / A/H3N2 (≥50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the A/H3N2 vaccine strain (Comorbidity Risk Score ≥50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.734
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.549
         upper limit
    		 0.982
    Statistical analysis title
    		 GMT Ratio / B/Yamagata (≥50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Yamagata vaccine strain (Comorbidity Risk Score ≥50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.773
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.638
         upper limit
    		 0.935
    Statistical analysis title
    		 GMT Ratio / B/Victoria (≥50)
    Statistical analysis description
    GMT ratio of HI antibodies at Day 22 for the B/Victoria vaccine strain (Comorbidity Risk Score ≥50)
    Comparison groups
    aQIV v Comparator QIV
    Number of subjects included in analysis
    213
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 GMT ratio
    Point estimate
    0.905
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.739
         upper limit
    		 1.107

    Adverse events

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    Adverse events information [1]
    Timeframe for reporting adverse events
    SAEs: Day 1 through Day 271; nonserious unsolicited AEs: Day 1 through Day 22
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    aQIV
    Reporting group description
    		 Adjuvanted QIV containing 2 influenza type A strains and 2 influenza type B strains

    Reporting group title
    Comparator QIV
    Reporting group description
    		 Non-adjuvanted comparator QIV containing 2 influenza type A strains and 2 influenza type B strains

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: No nonserious unsolicited AEs were reported at a frequency >5% in either vaccine group during the study.
    Serious adverse events
    		 aQIV Comparator QIV
    Total subjects affected by serious adverse events
         subjects affected / exposed
    31 / 1027 (3.02%)
    31 / 1016 (3.05%)
         number of deaths (all causes)
    1
    0
         number of deaths resulting from adverse events
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    B-cell lymphoma
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder cancer
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endometrial adenocarcinoma
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Follicular lymphoma
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic neoplasm
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Huerthle cell carcinoma
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lip and/or oral cavity cancer
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Pancreatic carcinoma
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Plasmacytoma
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Deep vein thrombosis
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypertensive crisis
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 1027 (0.10%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hernia pain
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Immune system disorders
    Allergy to metals
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug hypersensitivity
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vaginal prolapse
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Haemothorax
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pulmonary thrombosis
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conversion disorder
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric decompensation
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Alcohol poisoning
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ankle fracture
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bladder injury
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Clavicle fracture
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Femoral neck fracture
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Limb crushing injury
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radius fracture
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Scapula fracture
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    2 / 1027 (0.19%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Angina pectoris
         subjects affected / exposed
    1 / 1027 (0.10%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Aortic valve stenosis
         subjects affected / exposed
    1 / 1027 (0.10%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac failure congestive
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 1027 (0.00%)
    2 / 1016 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebellar stroke
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cerebral infarction
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Status epilepticus
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subarachnoid haemorrhage
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Middle ear adhesions
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulum
         subjects affected / exposed
    2 / 1027 (0.19%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastritis erosive
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intestinal obstruction
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Large intestine polyp
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Bile duct stenosis
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 1027 (0.10%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hypothyroidism
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis
         subjects affected / exposed
    2 / 1027 (0.19%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Spondylolisthesis
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Abscess limb
         subjects affected / exposed
    1 / 1027 (0.10%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    3 / 1027 (0.29%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Device related infection
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rectal abscess
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Staphylococcal sepsis
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Streptococcal sepsis
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 1027 (0.00%)
    1 / 1016 (0.10%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Ketoacidosis
         subjects affected / exposed
    1 / 1027 (0.10%)
    0 / 1016 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 aQIV Comparator QIV
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 1027 (0.00%)
    0 / 1016 (0.00%)

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    18 Nov 2021
    Version 1.0 to Version 2.0 The main reasons for the protocol amendment were the following: 1. Updating of the CI for secondary objectives 2a and 2b to reflect the correct alpha. 2. Conducting database lock and unblinding in two stages to allow expedited CSR reporting. A Blinding Maintenance Plan was prepared to ensure blinding of relevant laboratory and statistical personnel was maintained until their activities had been completed. 3. Clarification of Exclusion Criteria #7b and #9, based on regulatory agency feedback. 4. Clarifications of reporting requirements for solicited AEs that start during Day 1-7 and continue beyond Day 14. 5. Correction of how the FAS would be analyzed in case of vaccination errors, based on regulatory agency feedback.
    11 Jul 2022
    Version 2.0 to Version 3.0 The main reasons for the protocol amendment were the following: 1. Reclassification of the secondary objective of immunogenicity persistence at 9 months after vaccination (Day 271) as an exploratory objective in order to expedite the primary and secondary immunogenicity results and report them with the complete safety data to support timely license applications in different regions. 2. Improvement in the definition of previous influenza vaccination as a stratification factor to consider subjects who had received an influenza vaccination in the previous 3 influenza seasons as previously vaccinated subjects (Yes) in order to acknowledge variability in timing of the annual influenza vaccination campaigns. 3. Correction of an inconsistency in the assessment and reporting of local solicited reactions to consider local events as being present if they measured ≥25 mm to ensure consistency with the approved labeling information for aQIV (Fluad Quadrivalent/Quad/Tetra).

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

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