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    Clinical Trial Results:
    Immunogenicity and Lot-to-Lot Consistency Study of a Quadrivalent Influenza Vaccine in Adult and Elderly Subjects

    Summary
    EudraCT number
    2014-000785-21
    Trial protocol
    DE   BE  
    Global end of trial date
    23 Oct 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    27 Mar 2016
    First version publication date
    27 Mar 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    GQM11
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    -
    WHO universal trial number (UTN)
    U1111-1143-8801
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur SA
    Sponsor organisation address
    2, avenue Pont Pasteur, Lyon Cedex 07, France, F-69367
    Public contact
    Director, Clinical Development , Sanofi Pasteur SA, 33 4 37 37 5850, stephanie.pepin@sanofipasteur.com
    Scientific contact
    Director, Clinical Development , Sanofi Pasteur SA, 33 4 37 37 5850, stephanie.pepin@sanofipasteur.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
    20 Jan 2016
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Oct 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    • Immunogenicity: Lot Consistency To demonstrate equivalence of immune response induced by the 3 different industrial lots of Quadrivalent Influenza Vaccine (QIV) for each strain • Immunogenicity: Non-inferiority To demonstrate the non-inferiority of immune response induced by QIV compared with Trivalent Influenza Vaccine (TIV) for each strain
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.
    Background therapy
    Not applicable
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    17 Sep 2014
    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
    Poland: 607
    Country: Number of subjects enrolled
    Belgium: 466
    Country: Number of subjects enrolled
    Germany: 587
    Country: Number of subjects enrolled
    France: 559
    Worldwide total number of subjects
    2219
    EEA total number of subjects
    2219
    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)
    1373
    From 65 to 84 years
    829
    85 years and over
    17

    Subject disposition

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    Recruitment
    Recruitment details
    The study subjects were enrolled from 17 September 2014 to 21 October 2014 at 3 clinic centers in Belgium, 3 in France, 4 in Germany, and 5 in Poland.

    Pre-assignment
    Screening details
    A total of 2225 subjects who met all of the inclusion and none of the exclusion criteria were randomized; however, 3 subjects were not injected and 3 subjects had no post-vaccination blood sample resulting in a total of 2219 patients.

    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, Assessor
    Blinding implementation details
    This was a double-blind study for subjects in the quadrivalent and trivalent influenza vaccine (TIV; Victoria) groups. The Investigator, the study staff, and the subject were blinded to study treatment. The study was a single-blind study up to Day 21 for all subjects included in the TIV (Yamagata) group. Immunogenicity was assessed in a blinded manner for all subjects. In the event of an emergency (i.e., serious adverse event), the code could be broken according to the code-breaking procedures.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    QIV S4456
    Arm description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.
    Arm type
    Experimental

    Investigational medicinal product name
    QIV (split-virion, inactivated)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

    Arm title
    QIV S4457
    Arm description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.
    Arm type
    Experimental

    Investigational medicinal product name
    QIV (split-virion, inactivated)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

    Arm title
    QIV S4458
    Arm description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.
    Arm type
    Experimental

    Investigational medicinal product name
    QIV (split-virion, inactivated)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

    Arm title
    TIV1
    Arm description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.
    Arm type
    Active comparator

    Investigational medicinal product name
    TIV1 (split-virion, inactivated) Victoria lineage
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

    Arm title
    TIV2
    Arm description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.
    Arm type
    Active comparator

    Investigational medicinal product name
    TIV2 (split-virion, inactivated) Yamagata lineage
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular in the deltoid muscle or deep subcutaneous, 1 injection on Day 0.

    Number of subjects in period 1
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Started
    553
    555
    558
    278
    275
    Completed
    552
    555
    555
    278
    274
    Not completed
    1
    0
    3
    0
    1
         Protocol deviation
             -
             -
             1
             -
             1
         Consent withdrawn by subject
             -
             -
             2
             -
             -
         Lost to follow-up
             1
             -
             -
             -
             -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    QIV S4456
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.

    Reporting group title
    QIV S4457
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.

    Reporting group title
    QIV S4458
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.

    Reporting group title
    TIV1
    Reporting group description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.

    Reporting group title
    TIV2
    Reporting group description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.

    Reporting group values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2 Total
    Number of subjects
    553 555 558 278 275 2219
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0 0 0
        Newborns (0-27 days)
    0 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0 0 0
        Children (2-11 years)
    0 0 0 0 0 0
        Adolescents (12-17 years)
    0 0 0 0 0 0
        Adults (18-64 years)
    344 330 350 176 172 1372
        From 65-84 years
    204 221 204 101 100 830
        85 years and over
    5 4 4 1 3 17
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    54.5 ± 18.1 54.8 ± 18.2 54.5 ± 18.1 55.6 ± 16.9 53.7 ± 18.6 -
    Gender categorical
    Units: Subjects
        Female
    309 304 282 152 151 1198
        Male
    244 251 276 126 124 1021
    History of influenza vaccination 2013/2014
    Number of subjects with a history of influenza vaccination by year
    Units: Subjects
        Influenza vaccination 2013/2014; Yes
    187 196 195 102 89 769
        Influenza vaccination 2013/2014; No
    366 355 362 175 186 1444
        Influenza vaccination 2013/2014; Unknown
    0 4 1 1 0 6
    History of influenza vaccination 2012/2013
    Units: Subjects
        Influenza vaccination 2012/2013; Yes
    177 199 199 105 97 777
        Influenza vaccination 2012/2013; No
    373 355 356 173 176 1433
        Influenza vaccination 2012/2013; Unknown
    3 1 3 0 2 9
    History of influenza vaccination 2011/2012
    Units: Subjects
        Influenza vaccination 2011/2012; Yes
    179 209 197 104 94 783
        Influenza vaccination 2011/2012; No
    369 344 356 170 179 1418
        Influenza vaccination 2011/2012; Unknown
    5 2 5 4 2 18
    Subject analysis sets

    Subject analysis set title
    Pooled QIV
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received a single dose of either quadrivalent influenza vaccine (QIV) Lot 1 S4456, Lot 2 S4457, or Lot 3 S4458.

    Subject analysis set title
    Pooled TIV
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received a single dose of either trivalent influenza vaccine (TIV) 1 from the Victoria lineage or TIV 2 from the Yamagata lineage.

    Subject analysis sets values
    Pooled QIV Pooled TIV
    Number of subjects
    1666
    553
    Age categorical
    Units: Subjects
        In utero
    0
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
    0
        Newborns (0-27 days)
    0
    0
        Infants and toddlers (28 days-23 months)
    0
    0
        Children (2-11 years)
    0
    0
        Adolescents (12-17 years)
    0
    0
        Adults (18-64 years)
    1024
    348
        From 65-84 years
    629
    201
        85 years and over
    13
    4
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    54.6 ± 18.1
    54.7 ± 17.8
    Gender categorical
    Units: Subjects
        Female
    895
    303
        Male
    771
    250
    History of influenza vaccination 2013/2014
    Number of subjects with a history of influenza vaccination by year
    Units: Subjects
        Influenza vaccination 2013/2014; Yes
    578
    191
        Influenza vaccination 2013/2014; No
    1083
    361
        Influenza vaccination 2013/2014; Unknown
    5
    1
    History of influenza vaccination 2012/2013
    Units: Subjects
        Influenza vaccination 2012/2013; Yes
    575
    202
        Influenza vaccination 2012/2013; No
    1084
    349
        Influenza vaccination 2012/2013; Unknown
    7
    2
    History of influenza vaccination 2011/2012
    Units: Subjects
        Influenza vaccination 2011/2012; Yes
    585
    198
        Influenza vaccination 2011/2012; No
    1069
    349
        Influenza vaccination 2011/2012; Unknown
    12
    6

    End points

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    End points reporting groups
    Reporting group title
    QIV S4456
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.

    Reporting group title
    QIV S4457
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.

    Reporting group title
    QIV S4458
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.

    Reporting group title
    TIV1
    Reporting group description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.

    Reporting group title
    TIV2
    Reporting group description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.

    Subject analysis set title
    Pooled QIV
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received a single dose of either quadrivalent influenza vaccine (QIV) Lot 1 S4456, Lot 2 S4457, or Lot 3 S4458.

    Subject analysis set title
    Pooled TIV
    Subject analysis set type
    Full analysis
    Subject analysis set description
    Subjects received a single dose of either trivalent influenza vaccine (TIV) 1 from the Victoria lineage or TIV 2 from the Yamagata lineage.

    Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in All Subjects

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    End point title
    Geometric Mean Titers (GMTs) of Influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in All Subjects
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 21 post-vaccination
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    830
    278
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        A/California/07/2009 (H1N1); 18 to 60 years
    612 (567 to 661)
    685 (587 to 800)
        A/California/07/2009 (H1N1); >60 years
    219 (198 to 241)
    268 (228 to 314)
        A/Texas/50/2012 (H3N2); 18 to 60 years
    501 (461 to 544)
    629 (543 to 728)
        A/Texas/50/2012 (H3N2); >60 years
    359 (329 to 391)
    410 (352 to 476)
        B/Brisbane/60/2008 (B Victoria); 18 to 60 years
    708 (660 to 760)
    735 (615 to 879)
        B/Brisbane/60/2008 (B Victoria); >60 years
    287 (265 to 312)
    301 (244 to 372)
        B/Massachusetts/02/2012 (B Yamagata); 18 to 60 yrs
    1713 (1604 to 1829)
    1735 (1490 to 2019)
        B/Massachusetts/02/2012 (B Yamagata); >60 yrs
    656 (612 to 703)
    697 (593 to 820)
    Statistical analysis title
    Non-inferiority (A/H1N1; GMT Ratio; Overall)
    Statistical analysis description
    Ratio of GMTs were assessed in the H1N1 strain between the pooled QIV and TIV groups to determine non-inferiority.
    Comparison groups
    Pooled QIV v Pooled TIV
    Number of subjects included in analysis
    1108
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [1]
    Method
    Parameter type
    Ratio of GMTs
    Point estimate
    0.855
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.757
         upper limit
    0.968
    Notes
    [1] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.
    Statistical analysis title
    Non-inferiority (A/H3N2; GMT Ratio; Overall)
    Statistical analysis description
    Ratio of GMTs were assessed in the H3N2 strain between the pooled QIV and TIV groups to determine non-inferiority.
    Comparison groups
    Pooled QIV v Pooled TIV
    Number of subjects included in analysis
    1108
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    Method
    Parameter type
    Ratio of GMTs
    Point estimate
    0.835
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.741
         upper limit
    0.941
    Notes
    [2] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.
    Statistical analysis title
    Non-inferiority (B/Brisbane; GMT Ratio; Overall)
    Statistical analysis description
    Ratio of GMTs were assessed in the H1N1 strain between the pooled QIV and TIV groups to determine non-inferiority.
    Comparison groups
    Pooled QIV v Pooled TIV
    Number of subjects included in analysis
    1108
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    Method
    Parameter type
    Ratio of GMTs
    Point estimate
    0.959
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.831
         upper limit
    1.11
    Notes
    [3] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.
    Statistical analysis title
    Non-inferiority (B/Massachusett; GMTR; Overall)
    Statistical analysis description
    Ratio of GMTs were assessed in the H3N2 strain between the pooled QIV and TIV groups to determine non-inferiority.
    Comparison groups
    Pooled QIV v Pooled TIV
    Number of subjects included in analysis
    1108
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [4]
    Method
    Parameter type
    Ratio of GMTs
    Point estimate
    0.964
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.85
         upper limit
    1.09
    Notes
    [4] - Non-inferiority was confirmed if the lower limit of the overall age-stratified two-sided 95% confidence interval of the ratio of geometric mean titers (GMTs) between groups (QIV/TIV) is >1/1.5 for each strain.

    Primary: Geometric Mean Titers (GMTs) of Influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

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    End point title
    Geometric Mean Titers (GMTs) of Influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years [5]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 post-vaccination
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    277
    276
    280
    140
    138
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        A/H1N1; Day 0
    59.7 (49.2 to 72.5)
    63.5 (52.3 to 77.1)
    63.6 (52.1 to 77.7)
    57.4 (43.7 to 75.4)
    77.6 (58.9 to 102)
        A/H1N1; Day 21
    603 (525 to 694)
    649 (567 to 743)
    575 (507 to 653)
    737 (586 to 926)
    637 (515 to 787)
        A/H3N2; Day 0
    47.5 (39 to 57.9)
    47.7 (38.9 to 58.6)
    50.5 (41.6 to 61.2)
    39.6 (30.3 to 51.8)
    44.9 (34.1 to 59.1)
        A/H3N2; Day 21
    526 (454 to 609)
    487 (422 to 562)
    484 (421 to 556)
    583 (468 to 725)
    680 (558 to 829)
        B/Brisbane; Day 0
    62.3 (52.3 to 74.2)
    61.8 (51.4 to 74.3)
    59.8 (50.4 to 71)
    64.5 (50.1 to 83)
    67.1 (52.5 to 85.8)
        B/Brisbane; Day 21
    711 (631 to 801)
    723 (640 to 818)
    692 (612 to 783)
    735 (615 to 879)
    204 (170 to 243)
        B/Massachusetts; Day 0
    213 (178 to 255)
    249 (206 to 300)
    240 (202 to 283)
    214 (166 to 276)
    285 (222 to 365)
        B/Massachusetts; Day 21
    1739 (1556 to 1944)
    1736 (1550 to 1945)
    1670 (1489 to 1874)
    689 (556 to 854)
    1735 (1490 to 2019)
    No statistical analyses for this end point

    Primary: Geometric Mean Titers (GMTs) of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

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    End point title
    Geometric Mean Titers (GMTs) of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older [6]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 post-vaccination
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    276
    277
    279
    138
    137
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        A/H1N1; Day 0
    42 (35.2 to 50)
    48 (39.9 to 57.9)
    43.3 (36 to 51.9)
    53.5 (40.7 to 70.5)
    36.7 (28.3 to 47.6)
        A/H1N1; Day 21
    222 (186 to 264)
    216 (184 to 254)
    219 (185 to 259)
    328 (265 to 406)
    218 (171 to 277)
        A/H3N2; Day 0
    59.3 (48.6 to 72.4)
    70.3 (58 to 85.1)
    63.2 (52.1 to 76.6)
    79.8 (58.4 to 109)
    62.6 (48.3 to 81.3)
        A/H3N2; Day 21
    362 (312 to 420)
    395 (341 to 456)
    324 (278 to 376)
    492 (395 to 612)
    340 (276 to 419)
        B/Brisbane; Day 0
    52.9 (44.3 to 63.1)
    70.2 (58.5 to 84.4)
    64.9 (54.8 to 76.9)
    65.4 (51.1 to 83.7)
    60.9 (47.9 to 77.4)
        B/Brisbane; Day 21
    272 (236 to 314)
    314 (273 to 360)
    277 (240 to 319)
    301 (244 to 372)
    121 (101 to 147)
        B/Massachusetts; Day 0
    140 (117 to 166)
    156 (134 to 182)
    186 (158 to 218)
    172 (138 to 214)
    170 (132 to 217)
        B/Massachusetts; Day 21
    595 (527 to 672)
    661 (588 to 744)
    712 (632 to 803)
    351 (294 to 420)
    697 (593 to 820)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route [7]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 post-vaccination
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    277
    276
    280
    140
    138
    Units: Percentage of subjects
    number (not applicable)
        A/H1N1; Day 0
    63.5
    64.9
    65.4
    65.7
    71
        A/H1N1; Day 21
    97.8
    97.8
    98.9
    97.1
    97.1
        A/H3N2; Day 0
    57.4
    55.6
    62.5
    56.4
    55.1
        A/H3N2; Day 21
    98.6
    98.2
    97.1
    97.9
    99.3
        B/Brisbane; Day 0
    62.5
    61.5
    61.8
    67.9
    65.2
        B/Brisbane; Day 21
    100
    99.3
    100
    100
    97.8
        B/Massachusetts; Day 0
    86.6
    86.5
    90.7
    87.1
    90.6
        B/Massachusetts; Day 21
    100
    100
    100
    99.3
    100
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 60 Years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination with a Quadrivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 60 Years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination with a Quadrivalent Influenza Vaccine Administered via the Intramuscular Route [8]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).
    End point type
    Primary
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 post-vaccination
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    276
    277
    279
    138
    137
    Units: Percentage of subjects
    number (not applicable)
        A/H1N1; Day 0
    57.6
    58.1
    57.3
    64.5
    54
        A/H1N1; Day 21
    89.1
    91.7
    91
    97.8
    91.2
        A/H3N2; Day 0
    64.5
    67
    65.9
    65.9
    69.9
        A/H3N2; Day 21
    96
    97.8
    94.6
    98.6
    97.1
        B/Brisbane; Day 0
    59.8
    69
    69.1
    70.3
    66.4
        B/Brisbane; Day 21
    96.4
    97.1
    96
    95.7
    85.4
        B/Massachusetts; Day 0
    81.9
    88
    88.9
    85.5
    86.9
        B/Massachusetts; Day 21
    100
    100
    100
    98.6
    100
    No statistical analyses for this end point

    Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

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    End point title
    Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years [9]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 21 post-vaccination/Day 0 (pre-vaccination)
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    277
    276
    280
    140
    138
    Units: Titer ratios (1/dil)
    geometric mean (confidence interval 95%)
        A/H1N1
    10.1 (8.28 to 12.3)
    10.2 (8.32 to 12.6)
    9.04 (7.37 to 11.1)
    12.8 (9.36 to 17.6)
    8.2 (6.27 to 10.7)
        A/H3N2
    11.1 (9.07 to 13.5)
    10.2 (8.32 to 12.5)
    9.58 (7.87 to 11.7)
    14.7 (10.9 to 19.8)
    15.1 (11.2 to 20.4)
        B/Brisbane
    11.4 (9.44 to 13.8)
    11.7 (9.66 to 14.2)
    11.6 (9.59 to 14)
    11.4 (8.66 to 15)
    3.03 (2.49 to 3.7)
        B/Massachusetts
    8.17 (6.87 to 9.72)
    6.97 (5.84 to 8.33)
    6.97 (5.91 to 8.23)
    3.22 (2.67 to 3.9)
    6.08 (4.79 to 7.72)
    No statistical analyses for this end point

    Primary: Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

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    End point title
    Geometric Mean Titer Ratios (GMTRs) of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older [10]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.
    End point type
    Primary
    End point timeframe
    Day 21 post-vaccination/Day 0 (pre-vaccination)
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    276
    277
    279
    138
    137
    Units: Titer ratios (1/dil)
    geometric mean (confidence interval 95%)
        A/H1N1
    5.29 (4.4 to 6.35)
    4.5 (3.81 to 5.33)
    5.06 (4.21 to 6.08)
    6.13 (4.51 to 8.33)
    5.94 (4.56 to 7.72)
        A/H3N2
    6.1 (5.01 to 7.43)
    5.61 (4.67 to 6.75)
    5.12 (4.24 to 6.18)
    6.16 (4.53 to 8.39)
    5.43 (4.22 to 6.99)
        B/Brisbane
    5.15 (4.33 to 6.13)
    4.47 (3.77 to 5.3)
    4.26 (3.61 to 5.03)
    4.6 (3.5 to 6.05)
    1.99 (1.7 to 2.34)
        B/Massachusetts
    4.26 (3.57 to 5.1)
    4.24 (3.62 to 4.97)
    3.83 (3.26 to 4.52)
    2.04 (1.71 to 2.43)
    4.11 (3.19 to 5.3)
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 18 to 60 Years Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 18 to 60 Years Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route [11]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroconversion was defined as the proportion of subjects with a pre-vaccination titer < 10 (1/dil) to a post-vaccination titer ≥ 40 (1/dil). Significant increase was defined as proportion of subjects with a pre-vaccination titer ≥ 10 (1/dil) and ≥ 4-fold increase of the titer.
    End point type
    Primary
    End point timeframe
    Day 21 post-vaccination/Day 0 (pre-vaccination)
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    277
    276
    280
    140
    138
    Units: Percentage of subjects
    number (not applicable)
        A/H1N1
    65
    65.6
    61.8
    63.6
    66.7
        A/H3N2
    70.8
    66.5
    61.4
    72.9
    73.9
        B/Brisbane
    71.5
    70.5
    70.7
    70
    38.4
        B/Massachusetts
    67.1
    61.1
    62.9
    42.1
    60.9
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 60 Years or Older Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 60 Years or Older Achieving Seroconversion or Significant increase Against Influenza Antigens after Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route [12]
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroconversion was defined as the proportion of subjects with a pre-vaccination titer < 10 (1/dil) to a post-vaccination titer ≥ 40 (1/dil). Significant increase was defined as proportion of subjects with a pre-vaccination titer ≥ 10 (1/dil) and ≥ 4-fold increase of the titer.
    End point type
    Primary
    End point timeframe
    Day 21 post-vaccination/Day 0 (pre-vaccination)
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    276
    277
    279
    138
    137
    Units: Percentage of subjects
    number (not applicable)
        A/H1N1
    49.3
    43
    44.4
    48.6
    51.8
        A/H3N2
    47.1
    50.7
    44.8
    47.1
    50
        B/Brisbane
    45.7
    46.6
    43.5
    43.5
    21.2
        B/Massachusetts
    42.8
    45.3
    40.1
    28.3
    38.7
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 18 to 60 years Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 18 to 60 years Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route [13]
    End point description
    Solicited injection site reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 Solicited injection site reactions: Pain, Significant; prevents daily activity; Erythema, Swelling, Induration, and Ecchymosis > 100 mm. Grade 3 Solicited systemic reactions: Fever, ≥ 39.0°C; Headache, Malaise, Myalgia, and Shivering, Significant; prevents daily activity.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 7 post-vaccination
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    277
    276
    280
    140
    138
    Units: Percentage of subjects
    number (not applicable)
        Injection site Pain
    53.1
    57.2
    53.9
    48.6
    61.6
        Grade 3 Injection site Pain
    0
    0.7
    0.4
    0
    0.7
        Injection site Erythema
    9
    6.9
    11.8
    5
    6.5
        Grade 3 Injection site Erythema
    0
    0
    0
    0
    0.7
        Injection site Swelling
    5.1
    6.5
    7.1
    2.9
    4.3
        Grade 3 Injection site Swelling
    0
    0
    0
    0
    0
        Injection site Induration
    4.3
    6.9
    8.2
    4.3
    6.5
        Grade 3 Injection site Induration
    0
    0
    0
    0
    0
        Injection site Ecchymosis
    0.7
    0.7
    0.7
    0.7
    0.7
        Grade 3 Injection site Ecchymosis
    0
    0
    0
    0
    0
        Fever
    0
    0.7
    1.4
    0
    0.7
        Grade 3 Fever
    0
    0
    0
    0
    0
        Headache
    26.4
    27.2
    26.4
    23.6
    30.4
        Grade 3 Headache
    0.7
    3.3
    1.1
    0.7
    1.4
        Malaise
    21.7
    16.3
    17.5
    20.7
    22.5
        Grade 3 Malaise
    1.1
    2.5
    0.7
    0.7
    0.7
        Myalgia
    24.5
    25.7
    28.6
    17.9
    23.9
        Grade 3 Myalgia
    0.4
    0.4
    0.7
    1.4
    0
        Shivering
    8.3
    8.3
    6.1
    7.1
    5.1
        Grade 3 Shivering
    0.7
    0.4
    0.7
    0
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 60 years and older Reporting Solicited Injection-site or Systemic Reaction After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route [14]
    End point description
    Solicited injection site reactions: Pain, Erythema, Swelling, Induration, and Ecchymosis. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Shivering. Grade 3 Solicited injection site reactions: Pain, Significant; prevents daily activity; Erythema, Swelling, Induration, and Ecchymosis > 100 mm. Grade 3 Solicited systemic reactions: Fever, ≥ 39.0°C; Headache, Malaise, Myalgia, and Shivering, Significant; prevents daily activity.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 7 post-vaccination
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    276
    278
    279
    139
    137
    Units: Percentage of subjects
    number (not applicable)
        Injection site Pain
    20.3
    25.3
    23.3
    25.2
    14.6
        Grade 3 Injection site Pain
    0
    0.4
    0
    0
    0
        Injection site Erythema
    8
    9.4
    5.4
    7.9
    5.8
        Grade 3 Injection site Erythema
    0
    0
    0
    0.7
    0.7
        Injection site Swelling
    3.3
    4.3
    2.2
    2.9
    3.6
        Grade 3 Injection site Swelling
    0
    0
    0
    0
    0
        Injection site Induration
    2.5
    2.9
    2.5
    2.9
    3.6
        Grade 3 Injection site Induration
    0
    0
    0
    0
    0
        Injection site Ecchymosis
    1.1
    0.4
    0
    0
    0.7
        Grade 3 Injection site Ecchymosis
    0
    0
    0
    0
    0
        Fever
    1.8
    0.7
    0.7
    0
    0.7
        Grade 3 Fever
    0.4
    0.4
    0
    0
    0
        Headache
    17
    12.2
    16.5
    12.2
    11.7
        Grade 3 Headache
    0.7
    0.4
    0.4
    0
    0.7
        Malaise
    12.7
    9.4
    9.3
    10.1
    12.4
        Grade 3 Malaise
    0
    1.1
    0.7
    0
    1.5
        Myalgia
    12
    12.6
    14
    10.1
    13.1
        Grade 3 Myalgia
    0
    0.7
    1.1
    0
    0
        Shivering
    3.3
    4.3
    5.7
    3.6
    4.4
        Grade 3 Shivering
    0.4
    0
    0.7
    0.7
    0
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 18 to 60 Years Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 18 to 60 Years Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route [15]
    End point description
    Reactions listed in the European Medicines Agency (EMA) Note for Guidance: Injection site induration ≥ 5 cm for at least 4 consecutive days; Injection site ecchymosis (injection site bruising); Pyrexia (recorded temperature > 38.0°C) for at least 1 day; Malaise; Shivering (Rigors).
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 3 post-vaccination
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    277
    276
    280
    140
    138
    Units: Percentage of subjects
    number (not applicable)
        Reaction listed in the EMA recommendations
    22.7
    19.9
    18.2
    20
    19.6
        Injection site Induration ≥ 5 cm for 4 days
    0
    0
    0
    0
    0
        Injection site Ecchymosis
    2.2
    2.2
    3.2
    2.1
    2.9
        Pyrexia (> 38.0°C) for at least 1 day
    0
    0.4
    1.1
    0
    0
        Malaise
    18.8
    14.5
    13.9
    17.1
    15.2
        Shivering (Rigors)
    7.2
    7.2
    5.7
    6.4
    3.6
    No statistical analyses for this end point

    Primary: Percentage of Subjects Aged 60 years and older Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days of Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 60 years and older Reporting Solicited Reactions Listed in the EMA Note for Guidance within 3 Days of Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Given via the Intramuscular Route [16]
    End point description
    Reactions listed in the European Medicines Agency (EMA) Note for Guidance: Injection site induration ≥ 5 cm for at least 4 consecutive days; Injection site ecchymosis (injection site bruising); Pyrexia (recorded temperature > 38.0°C) for at least 1 day; Malaise; Shivering (Rigors).
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 3 post-vaccination
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Number of subjects analysed
    276
    278
    279
    139
    137
    Units: Percentage of subjects
    number (not applicable)
        Reaction listed in the EMA recommendations
    13
    10.4
    11.5
    7.9
    11.7
        Injection site Induration ≥ 5 cm for 4 days
    0
    0
    0.4
    0
    0
        Injection site Ecchymosis
    2.5
    4
    1.1
    1.4
    2.9
        Pyrexia (> 38.0°C) for at least 1 day
    0.7
    0.7
    0.4
    0
    0
        Malaise
    10.5
    6.8
    7.5
    7.2
    8.8
        Shivering (Rigors)
    2.5
    4
    4.7
    2.2
    2.2
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 post-vaccination
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    833
    278
    Units: Percentage
    number (not applicable)
        A/H1N1; Day 0
    64.6
    68.3
        A/H1N1; Day 21
    98.2
    97.1
        A/H3N2; Day 0
    58.5
    55.8
        A/H3N2; Day 21
    98
    98.6
        B/Brisbane; Day 0
    61.9
    67.9
        B/Brisbane; Day 21
    99.8
    100
        B/Massachusetts; Day 0
    88
    90.6
        B/Massachusetts; Day 21
    100
    100
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

    Close Top of page
    End point title
    Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination) and Day 21 post-vaccination
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    832
    275
    Units: Percentage
    number (not applicable)
        A/H1N1; Day 0
    57.7
    59.3
        A/H1N1; Day 21
    90.6
    94.5
        A/H3N2; Day 0
    65.8
    67.9
        A/H3N2; Day 21
    96.1
    97.8
        B/Brisbane; Day 0
    65.9
    70.3
        B/Brisbane; Day 21
    96.5
    95.7
        B/Massachusetts; Day 0
    86.3
    86.9
        B/Massachusetts; Day 21
    100
    100
    No statistical analyses for this end point

    Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years.

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    End point title
    Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years.
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    145
    70
    Units: Geometric Mean Titers
    geometric mean (confidence interval 95%)
        A/H1N1; Day 0
    68.7 (52.2 to 90.5)
    65.2 (45.9 to 92.6)
        A/H1N1; Day 21
    658 (565 to 767)
    681 (501 to 925)
        A/H1N1; Day 180
    290 (244 to 345)
    253 (189 to 339)
        A/H1N1; Day 365
    250 (208 to 301)
    207 (151 to 285)
        A/H3N2; Day 0
    47.8 (36.8 to 62.1)
    42 (29.5 to 59.7)
        A/H3N2; Day 21
    470 (386 to 571)
    703 (517 to 955)
        A/H3N2; Day 180
    225 (185 to 274)
    275 (206 to 366)
        A/H3N2; Day 365
    184 (150 to 226)
    202 (149 to 273)
        B/Brisbane; Day 0
    58.7 (45.3 to 76.1)
    57.2 (33.2 to 98.6)
        B/Brisbane; Day 21
    675 (575 to 793)
    718 (462 to 1118)
        B/Brisbane; Day 180
    285 (235 to 346)
    271 (179 to 409)
        B/Brisbane; Day 365
    248 (199 to 309)
    217 (142 to 332)
        B/Massachusetts; Day 0
    197 (153 to 254)
    256 (175 to 374)
        B/Massachusetts; Day 21
    1731 (1492 to 2009)
    1759 (1341 to 2307)
        B/Massachusetts; Day 180
    830 (684 to 1007)
    873 (637 to 1197)
        B/Massachusetts; Day 365
    685 (558 to 840)
    764 (551 to 1059)
    No statistical analyses for this end point

    Other pre-specified: Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older.

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    End point title
    Geometric Mean Titers of influenza Antibodies Before and After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older.
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination.
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    145
    70
    Units: Geometric Mean Titers
    geometric mean (confidence interval 95%)
        A/H1N1; Day 0
    42.7 (33.4 to 54.4)
    45.5 (30.7 to 67.4)
        A/H1N1; Day 21
    204 (162 to 257)
    240 (176 to 327)
        A/H1N1; Day 180
    87.3 (68.8 to 111)
    120 (86.4 to 167)
        A/H1N1; Day 365
    77.4 (60.8 to 98.7)
    107 (75.5 to 153)
        A/H3N2; Day 0
    63.9 (48 to 85)
    79.6 (52.8 to 120)
        A/H3N2; Day 21
    392 (317 to 484)
    404 (293 to 557)
        A/H3N2; Day 180
    180 (144 to 225)
    221 (155 to 314)
        A/H3N2; Day 365
    144 (113 to 182)
    144 (101 to 205)
        B/Brisbane; Day 0
    64.5 (50.5 to 82.5)
    55.7 (33.5 to 92.7)
        B/Brisbane; Day 21
    281 (233 to 340)
    282 (161 to 493)
        B/Brisbane; Day 180
    132 (108 to 161)
    147 (85.2 to 253)
        B/Brisbane; Day 365
    118 (93.9 to 147)
    117 (73 to 188)
        B/Massachusetts; Day 0
    169 (135 to 212)
    182 (117 to 284)
        B/Massachusetts; Day 21
    667 (563 to 789)
    645 (497 to 836)
        B/Massachusetts; Day 180
    340 (284 to 407)
    334 (247 to 451)
        B/Massachusetts; Day 365
    324 (272 to 387)
    340 (249 to 463)
    No statistical analyses for this end point

    Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years

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    End point title
    Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 18 to 60 years
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    148
    78
    Units: Geometric Mean Titer Ratios
    geometric mean (confidence interval 95%)
        A/H1N1; Day 21/Day 0
    9.58 (7.21 to 12.7)
    10.4 (7.25 to 15)
        A/H1N1; Day 180/Day 21
    0.441 (0.388 to 0.5)
    0.373 (0.324 to 0.43)
        A/H1N1; Day 365/Day 21
    0.361 (0.31 to 0.421)
    0.324 (0.275 to 0.382)
        A/H3N2; Day 21/Day 0
    9.83 (7.62 to 12.7)
    16.7 (11.4 to 24.6)
        A/H3N2; Day 180/Day 21
    0.479 (0.414 to 0.555)
    0.377 (0.303 to 0.468)
        A/H3N2; Day 365/Day 21
    0.382 (0.328 to 0.446)
    0.277 (0.218 to 0.353)
        B/Brisbane; Day 21/Day 0
    11.5 (8.88 to 14.9)
    12.6 (6.81 to 23.1)
        B/Brisbane; Day 180/Day 21
    0.422 (0.38 to 0.47)
    0.366 (0.28 to 0.48)
        B/Brisbane; Day 365/Day 21
    0.352 (0.308 to 0.402)
    0.275 (0.201 to 0.377)
        B/Massachusetts; Day 21/Day 0
    8.79 (7.01 to 11)
    6.87 (4.85 to 9.74)
        Massachusetts; Day 180/Day 21
    0.479 (0.432 to 0.532)
    0.496 (0.415 to 0.594)
        Massachusetts; Day 365/Day 21
    0.407 (0.361 to 0.459)
    0.454 (0.362 to 0.569)
    No statistical analyses for this end point

    Other pre-specified: Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older

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    End point title
    Geometric Mean Titer Ratios of influenza Antibodies After Vaccination with Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route in Subjects Aged 60 years and older
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method.
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination.
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    145
    70
    Units: Geometric Mean Titer Ratios
    geometric mean (confidence interval 95%)
        A/H1N1; Day 21/Day 0
    4.77 (3.84 to 5.94)
    5.28 (3.57 to 7.8)
        A/H1N1; Day 180/Day 21
    0.431 (0.376 to 0.494)
    0.508 (0.403 to 0.64)
        A/H1N1; Day 365/Day 21
    0.358 (0.313 to 0.411)
    0.422 (0.317 to 0.56)
        A/H3N2; Day 21/Day 0
    6.14 (4.64 to 8.11)
    5.07 (3.48 to 7.39)
        A/H3N2; Day 180/Day 21
    0.46 (0.387 to 0.548)
    0.554 (0.423 to 0.724)
        A/H3N2; Day 365/Day 21
    0.359 (0.298 to 0.434)
    0.376 (0.288 to 0.493)
        B/Brisbane; Day 21/Day 0
    4.39 (3.55 to 5.44)
    5.07 (2.37 to 10.8)
        B/Brisbane; Day 180/Day 21
    0.465 (0.417 to 0.518)
    0.555 (0.388 to 0.793)
        B/Brisbane; Day 365/Day 21
    0.423 (0.373 to 0.481)
    0.443 (0.303 to 0.648)
        B/Massachusetts; Day 21/Day 0
    3.94 (3.15 to 4.94)
    3.54 (2.27 to 5.52)
        B/Massachusetts; Day 180/Day 21
    0.51 (0.454 to 0.573)
    0.518 (0.424 to 0.634)
        B/Massachusetts; Day 365/Day 21
    0.475 (0.416 to 0.542)
    0.53 (0.42 to 0.671)
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 18 to 60 years With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    148
    78
    Units: Percentage
    number (not applicable)
        A/H1N1; Day 0
    67.6
    70.5
        A/H1N1; Day 21
    98.6
    97.4
        A/H1N1; Day 180
    96.6
    90.9
        A/H1N1; Day 365
    94.5
    89.7
        A/H3N2; Day 0
    60.8
    60.3
        A/H3N2; Day 21
    97.3
    98.7
        A/H3N2; Day 180
    92.6
    93.5
        A/H3N2; Day 365
    91.4
    92.5
        B/Brisbane; Day 0
    58.1
    73.3
        B/Brisbane; Day 21
    100
    100
        B/Brisbane; Day 180
    97.3
    100
        B/Brisbane; Day 365
    95.3
    100
        B/Massachusetts; Day 0
    85.1
    91.7
        B/Massachusetts; Day 21
    100
    100
        B/Massachusetts; Day 180
    100
    100
        B/Massachusetts; Day 365
    99.2
    100
    No statistical analyses for this end point

    Other pre-specified: Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route

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    End point title
    Percentage of Subjects Aged 60 years and Older With Seroprotection Against Influenza Antigens Before and After Vaccination Either a Quadrivalent Influenza Vaccine or a Trivalent Influenza Vaccine Administered via the Intramuscular Route
    End point description
    Anti-hemagglutinin antibody titers were measured for each strain with the seroneutralization method. Seroprotection was defined as antibody titers ≥ 40 (1/dil).
    End point type
    Other pre-specified
    End point timeframe
    Day 0 (pre-vaccination); Day 21; Day 180 and Day 365 post-vaccination
    End point values
    Pooled QIV Pooled TIV
    Number of subjects analysed
    145
    70
    Units: Percentage
    number (not applicable)
        A/H1N1; Day 0
    57.9
    58.6
        A/H1N1; Day 21
    89.7
    94.3
        A/H1N1; Day 180
    76.2
    85.3
        A/H1N1; Day 365
    75
    80.3
        A/H3N2; Day 0
    65.5
    71.4
        A/H3N2; Day 21
    94.5
    97.1
        A/H3N2; Day 180
    89.5
    92.6
        A/H3N2; Day 365
    85.9
    83.6
        B/Brisbane; Day 0
    66.9
    72.7
        B/Brisbane; Day 21
    97.2
    100
        B/Brisbane; Day 180
    89.5
    95
        B/Brisbane; Day 365
    83.6
    95
        B/Massachusetts; Day 0
    86.2
    85.4
        B/Massachusetts; Day 21
    100
    100
        B/Massachusetts; Day 180
    100
    100
        B/Massachusetts; Day 365
    100
    100
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse event data were collected from Day 0 up to 12 months post-vaccination.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    14
    Reporting groups
    Reporting group title
    QIV S4456
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 1 S4456.

    Reporting group title
    QIV S4457
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 2 S4457.

    Reporting group title
    QIV S4458
    Reporting group description
    Subjects received a single dose of quadrivalent influenza vaccine (QIV) Lot 3 S4458.

    Reporting group title
    TIV1
    Reporting group description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 1 from the Victoria lineage.

    Reporting group title
    TIV2
    Reporting group description
    Subjects received a single dose of trivalent influenza vaccine (TIV) 2 from the Yamagata lineage.

    Serious adverse events
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Total subjects affected by serious adverse events
         subjects affected / exposed
    19 / 554 (3.43%)
    12 / 554 (2.17%)
    14 / 560 (2.50%)
    9 / 279 (3.23%)
    6 / 275 (2.18%)
         number of deaths (all causes)
    1
    1
    1
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Vascular disorders
    Aneurysm
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peripheral ischaemia
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Varicose vein
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Rotator cuff repair
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anaplastic astrocytoma
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast cancer
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic lymphocytic leukaemia
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometrial cancer
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    1 / 275 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal carcinoma
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lung neoplasm malignant
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metastatic neoplasm
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Prostate cancer
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thyroid neoplasm
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Hyperemesis gravidarum
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Completed suicide
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Confusional state
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Accident
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fall
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    1 / 279 (0.36%)
    1 / 275 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament sprain
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    1 / 275 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Meniscus lesion
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Angina unstable
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Arrhythmia
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial fibrillation
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrioventricular block complete
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiomyopathy
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coronary artery disease
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sick sinus syndrome
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tachycardia
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic obstructive pulmonary disease
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory failure
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Cerebrovascular accident
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Convulsion
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Transient ischaemic attack
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Maculopathy
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Deafness neurosensory
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Intestinal obstruction
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intestinal polyp
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis chronic
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis acute
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    1 / 275 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    2 / 560 (0.36%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lumbar spinal stenosis
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    2 / 554 (0.36%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Scleroderma
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypoglycaemia
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Erysipelas
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    1 / 279 (0.36%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    1 / 275 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 554 (0.00%)
    1 / 554 (0.18%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 554 (0.00%)
    0 / 554 (0.00%)
    0 / 560 (0.00%)
    0 / 279 (0.00%)
    1 / 275 (0.36%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 554 (0.18%)
    0 / 554 (0.00%)
    1 / 560 (0.18%)
    0 / 279 (0.00%)
    0 / 275 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    QIV S4456 QIV S4457 QIV S4458 TIV1 TIV2
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    147 / 554 (26.53%)
    158 / 554 (28.52%)
    151 / 560 (26.96%)
    68 / 279 (24.37%)
    85 / 275 (30.91%)
    Nervous system disorders
    Headache
    alternative assessment type: Systematic
         subjects affected / exposed [1]
    73 / 277 (26.35%)
    75 / 276 (27.17%)
    74 / 280 (26.43%)
    33 / 140 (23.57%)
    42 / 138 (30.43%)
         occurrences all number
    73
    75
    74
    33
    42
    General disorders and administration site conditions
    Injection site Pain
    alternative assessment type: Systematic
         subjects affected / exposed [2]
    147 / 277 (53.07%)
    158 / 276 (57.25%)
    151 / 280 (53.93%)
    68 / 140 (48.57%)
    85 / 138 (61.59%)
         occurrences all number
    147
    158
    151
    68
    85
    Injection site Erythema
    alternative assessment type: Systematic
         subjects affected / exposed [3]
    25 / 277 (9.03%)
    26 / 278 (9.35%)
    33 / 280 (11.79%)
    11 / 139 (7.91%)
    9 / 138 (6.52%)
         occurrences all number
    25
    26
    33
    11
    9
    Injection site Swelling
    alternative assessment type: Systematic
         subjects affected / exposed [4]
    14 / 277 (5.05%)
    18 / 276 (6.52%)
    20 / 280 (7.14%)
    4 / 140 (2.86%)
    6 / 138 (4.35%)
         occurrences all number
    14
    18
    20
    4
    6
    Injection site Induration
    alternative assessment type: Systematic
         subjects affected / exposed [5]
    12 / 277 (4.33%)
    19 / 276 (6.88%)
    23 / 280 (8.21%)
    6 / 140 (4.29%)
    9 / 138 (6.52%)
         occurrences all number
    12
    19
    23
    6
    9
    Malaise
    alternative assessment type: Systematic
         subjects affected / exposed [6]
    60 / 277 (21.66%)
    45 / 276 (16.30%)
    49 / 280 (17.50%)
    29 / 140 (20.71%)
    31 / 138 (22.46%)
         occurrences all number
    60
    45
    49
    29
    31
    Shivering
    alternative assessment type: Systematic
         subjects affected / exposed [7]
    23 / 277 (8.30%)
    23 / 276 (8.33%)
    17 / 280 (6.07%)
    10 / 140 (7.14%)
    7 / 138 (5.07%)
         occurrences all number
    23
    23
    17
    10
    7
    Musculoskeletal and connective tissue disorders
    Myalgia
    alternative assessment type: Systematic
         subjects affected / exposed [8]
    68 / 277 (24.55%)
    71 / 276 (25.72%)
    80 / 280 (28.57%)
    25 / 140 (17.86%)
    33 / 138 (23.91%)
         occurrences all number
    68
    71
    80
    25
    33
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed [9]
    19 / 552 (3.44%)
    19 / 554 (3.43%)
    16 / 560 (2.86%)
    11 / 279 (3.94%)
    9 / 275 (3.27%)
         occurrences all number
    19
    20
    17
    11
    9
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited adverse event recorded in a diary card within 7 days after vaccination; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was an unsolicited adverse event recorded in a diary card within 21 days after vaccination; the total number (N) reflects those subjects for which data were available for the event during the period.

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    21 Nov 2014
    Included an additional blood sample collection to be used to test the persistence of the immune response and the informed consent form was updated to inform the subjects of the observational subset, addition of a 4th visit, and to obtain their consent to continue in the study.

    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
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
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