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    Clinical Trial Results:
    Phase IIIa, observer-blind, randomized study to evaluate non-inferiority of second dose of GSK Biologicals' measles-mumps-rubella vaccine vs second dose of Merck & Co., Inc.'s MMR vaccine when administered with and without diphtheria, tetanus, acellular pertussis and inactivated polio (DTaP-IPV) vaccine and varicella vaccine (VV) to healthy children 4 to 6 years of age

    Summary
    EudraCT number
    		 2011-004638-32
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    09 Nov 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    30 Aug 2017
    First version publication date
    30 Aug 2017
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    115158
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01621802
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 44 2089904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Jul 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Jul 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Nov 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    - To demonstrate the non-inferiority of Priorix vaccine to M-M-R II (M-M-R Vax Pro) vaccine, when administered with VV and DTaP-IPV vaccines in terms of seroresponse rates to measles, mumps and rubella viruses at Day 42. - To demonstrate the non-inferiority of Priorix vaccine to M-M-R II (M-M-R Vax Pro) vaccine, when administered with VV and DTaP-IPV vaccines in terms of antibody concentrations to measles, mumps and rubella viruses at Day 42. - To demonstrate the non-inferiority of Priorix vaccine to M-M-R II (M-M-R Vax Pro) vaccine, when administered without VV and DTaP-IPV vaccines in terms of seroresponse rates to measles, mumps and rubella viruses at Day 42. - To demonstrate the non-inferiority of Priorix vaccine to M-M-R II (M-M-R Vax Pro) vaccine, when administered without VV and DTaP-IPV vaccines in terms of antibody concentrations to measles, mumps and rubella viruses at Day 42.
    Protection of trial subjects
    The subjects were observed closely for at least 30 minutes following the administration of vaccine(s), with appropriate medical treatment readily available in case of a rare anaphylactic reaction.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    21 Jun 2012
    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
    Korea, Republic of: 359
    Country: Number of subjects enrolled
    Taiwan: 968
    Country: Number of subjects enrolled
    United States: 2684
    Worldwide total number of subjects
    4011
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    4011
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects were enrolled in 3 sub-cohorts. Sub-cohort 1: Inv_MMR_CO and Com_MMR_CO (Lot 1 or Lot 2), Sub-cohort 2: Inv_MMR_I and Com_MMR_I (Lot 1 or Lot 2) and Sub-cohort 3: Inv_MMR_S and Com_MMR_S (Lot 1 or Lot 2).

    Pre-assignment
    Screening details
    		 During the screening the following steps occurred: check for inclusion/exclusion criteria, contraindications/precautions, medical history of the subjects and signing informed consent forms.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Data analyst, Carer, Assessor
    Blinding implementation details
    Data were collected in an observer-blind manner. By observer-blind, it is meant that during the course of the study, the vaccine recipient and those responsible for the evaluation of any study endpoint (e.g. safety, reactogenicity, and immunogenicity) will all be unaware of which vaccine was administered.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Inv_MMR_CO Group
    Arm description
    		 Subjects received one dose of the study vaccine Priorix along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Priorix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the right arm.

    Investigational medicinal product name
    Kinrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose administered by deep intramuscular injection in the upper left deltoid.

    Investigational medicinal product name
    ProQuad
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the left arm.

    Arm title
    		 Com_MMR_CO Group
    Arm description
    		 Subjects received one dose of the licensed vaccine M-M-R II (also known as M-M-R Vax Pro) Lot 1 or Lot 2 along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    ProQuad
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the left arm.

    Investigational medicinal product name
    Kinrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    One dose administered by deep intramuscular injection in the upper left deltoid.

    Investigational medicinal product name
    M-M-R II
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the right arm.

    Arm title
    		 Inv_MMR_I Group
    Arm description
    		 Subjects received one dose of Priorix at Visit 1 (Day 0).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Priorix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the right arm.

    Arm title
    		 Com_MMR_I Group
    Arm description
    		 Subjects received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    M-M-R II
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the right arm.

    Arm title
    		 Inv_MMR_S Group
    Arm description
    		 Subjects in this safety cohort received one dose of Priorix at Visit 1 (Day 0).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Priorix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the right arm.

    Arm title
    		 Com_MMR_S Group
    Arm description
    		 Subjects in this safety cohort received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).
    Arm type
    		 Active comparator

    Investigational medicinal product name
    M-M-R II
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    One dose administered subcutaneously in the triceps region of the right arm.

    Number of subjects in period 1 [1]
    		Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Started
    802
    298
    796
    303
    1319
    489
    Completed
    755
    275
    763
    292
    1284
    477
    Not completed
    47
    23
    33
    11
    35
    12
         Consent withdrawn by subject
    8
    4
    4
    2
    2
    -
         Others
    3
    3
    3
    2
    1
    -
         Migrated/moved from study area
    -
    -
    2
    -
    1
    -
         Lost to follow-up
    36
    16
    24
    7
    31
    11
         Protocol deviation
    -
    -
    -
    -
    -
    1
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: While 4011 subjects were enrolled in the study, only 4007 eligible subjects received a study vaccination.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Inv_MMR_CO Group
    Reporting group description
    		 Subjects received one dose of the study vaccine Priorix along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_CO Group
    Reporting group description
    		 Subjects received one dose of the licensed vaccine M-M-R II (also known as M-M-R Vax Pro) Lot 1 or Lot 2 along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).

    Reporting group title
    Inv_MMR_I Group
    Reporting group description
    		 Subjects received one dose of Priorix at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_I Group
    Reporting group description
    		 Subjects received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).

    Reporting group title
    Inv_MMR_S Group
    Reporting group description
    		 Subjects in this safety cohort received one dose of Priorix at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_S Group
    Reporting group description
    		 Subjects in this safety cohort received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).

    Reporting group values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group Total
    Number of subjects
    		 802 298 796 303 1319 489
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 4.1 ± 0.3 4.1 ± 0.3 4.4 ± 0.6 4.3 ± 0.6 4.4 ± 0.6 4.4 ± 0.6 -
    Gender categorical
    Units: Subjects
        Female
    		 398 134 361 153 632 225 1903
        Male
    		 404 164 435 150 687 264 2104
    Race/Ethnicity, Customized
    Units: Subjects
        African Heritage / African American
    		 96 39 48 19 94 32 328
        American Indian or Alaskan Native
    		 130 38 15 3 4 0 190
        Asian - Central/South Asian Heritage
    		 12 5 7 1 8 0 33
        Asian - East Asian Heritage
    		 28 6 384 146 565 209 1338
        Asian - Japanese Heritage
    		 3 0 0 1 1 0 5
        Asian - South East Asian Heritage
    		 49 25 11 4 16 8 113
        Native Hawaiian or Other Pacific Islander
    		 4 2 2 0 3 0 11
        Other
    		 112 45 35 9 52 22 275
        White - Arabic / North African Heritage
    		 5 3 3 3 1 0 15
        White - Caucasian / European Heritage
    		 363 135 291 117 575 218 1699

    End points

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    End points reporting groups
    Reporting group title
    Inv_MMR_CO Group
    Reporting group description
    		 Subjects received one dose of the study vaccine Priorix along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_CO Group
    Reporting group description
    		 Subjects received one dose of the licensed vaccine M-M-R II (also known as M-M-R Vax Pro) Lot 1 or Lot 2 along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).

    Reporting group title
    Inv_MMR_I Group
    Reporting group description
    		 Subjects received one dose of Priorix at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_I Group
    Reporting group description
    		 Subjects received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).

    Reporting group title
    Inv_MMR_S Group
    Reporting group description
    		 Subjects in this safety cohort received one dose of Priorix at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_S Group
    Reporting group description
    		 Subjects in this safety cohort received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).

    Primary: Number of subjects with anti-measles virus antibody concentration equal to or above the cut-off-value

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    End point title
    		 Number of subjects with anti-measles virus antibody concentration equal to or above the cut-off-value [1]
    End point description
    Seroresponse was defined as post-vaccination anti-measles virus antibody concentration equal to or above (≥) 200 milli-international Units per milliliter (mIU/mL). Analysis was done in sub-cohorts 1 and 2 only.
    End point type
    Primary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, with and without co-administration with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO, Com_MMR_CO, Inv_MMR_I and Com_MMR_I Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group
    Number of subjects analysed
    697
    249
    736
    283
    Units: Subjects
        Anti-measles
    697
    249
    736
    281
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Power obtained using PASS 2005 (Likelihood Score [Miettienen and Nurminen approach]), one-sided non-inferiority test for the difference of two independent proportions, under the alternative associated to the reference value & alpha=1.25%. The global power to reach all non-inferiority objectives of Priorix vs. M-M-R II in sub-cohort 1 should be at least 94.04% (=100%- the sum of type II errors associated to cohort 1.
    Comparison groups
    Inv_MMR_CO Group v Com_MMR_CO Group
    Number of subjects included in analysis
    946
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [2]
    Method
    Parameter type
    		 Difference in seroresponse rate (%)
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.72
         upper limit
    		 1.98
    Notes
    [2] - Non-inferiority criterion for sub cohort 1: Lower limit (LL) of the 2-sided 97.5% confidence interval (CI) for group difference (Inv_MMR_CO Group minus pooled Com_MMR_CO Group) in seroresponse rates to measles, mumps and rubella viruses is ≥ -5%.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Power obtained using PASS 2005 (Likelihood Score [Miettienen and Nurminen approach]), one-sided non-inferiority test for the difference of two independent proportions, under the alternative associated to the reference value & alpha=1.25%. The global power to reach all non-inferiority objectives of Priorix vs. M-M-R II in sub-cohort 2 should be at least 98.88% (=100%- the sum of type II error associated to cohort 2.
    Comparison groups
    Inv_MMR_I Group v Com_MMR_I Group
    Number of subjects included in analysis
    1019
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [3]
    Method
    Parameter type
    		 Difference in Seroresponse rate (%)
    Point estimate
    0.71
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 0.02
         upper limit
    		 2.97
    Notes
    [3] - Non-inferiority criterion for sub cohort 2: The LL of the 2-sided 97.5% CI for group difference (Inv_MMR_I group minus pooled Com_MMR_I group) in seroresponse rates to measles, mumps and rubella viruses was ≥ -5%.

    Primary: Number of subjects with anti-mumps virus antibody concentration equal to or above the cut-off-value

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    End point title
    		 Number of subjects with anti-mumps virus antibody concentration equal to or above the cut-off-value [4]
    End point description
    Seroresponse was defined as post-vaccination anti-mumps virus antibody concentration ≥ 10 ELISA Units per milliliter (EU/mL). Analysis was done in sub-cohorts 1 and 2 only.
    End point type
    Primary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, with and without co-administration with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO, Com_MMR_CO, Inv_MMR_I and Com_MMR_I Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group
    Number of subjects analysed
    698
    250
    736
    283
    Units: Subjects
        Anti-mumps
    698
    250
    736
    283
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Power obtained using PASS 2005 (Likelihood Score [Miettienen and Nurminen approach]), one-sided non-inferiority test for the difference of two independent proportions, under the alternative associated to the reference value & alpha =1.25%. The global power to reach all non-inferiority objectives of Priorix vs. M-M-R II in sub-cohort 1 should be at least 94.04% (=100%- the sum of type II errors associated to cohort 1.
    Comparison groups
    Inv_MMR_CO Group v Com_MMR_CO Group
    Number of subjects included in analysis
    948
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [5]
    Method
    Parameter type
    		 Difference in seroresponse rate (%)
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.72
         upper limit
    		 1.97
    Notes
    [5] - Non-inferiority criterion for sub cohort 1: The LL of the 2-sided 97.5% CI for group difference (Inv_MMR_CO Group minus pooled Com_MMR_CO Group) in seroresponse rates to measles, mumps and rubella viruses was ≥ -5%.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Power obtained using PASS 2005 (Likelihood Score [Miettienen and Nurminen approach]), one-sided non-inferiority test for the difference of two independent proportions, under the alternative associated to the reference value & alpha=1.25%. The global power to reach all non-inferiority objectives of Priorix vs. M-M-R II in sub-cohort 2 should be at least 98.88% (=100%- the sum of type II error associated to cohort 2.
    Comparison groups
    Inv_MMR_I Group v Com_MMR_I Group
    Number of subjects included in analysis
    1019
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [6]
    Method
    Parameter type
    		 Difference in Seroresponse rate (%)
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.68
         upper limit
    		 1.75
    Notes
    [6] - Non-inferiority criterion for sub cohort 2: The LL of the 2-sided 97.5% CI for group difference (Inv_MMR_I group minus pooled Com_MMR_I group) in seroresponse rates to measles, mumps and rubella viruses was ≥ -5%.

    Primary: Number of subjects with anti-rubella virus antibody concentration equal to or above the cut-off-value

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    End point title
    		 Number of subjects with anti-rubella virus antibody concentration equal to or above the cut-off-value [7]
    End point description
    Seroresponse was defined as post-vaccination anti-rubella virus antibody concentration ≥ 10 International Units per milliliter (IU/mL). Analysis was done in sub-cohorts 1 and 2 only.
    End point type
    Primary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [7] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, with and without co-administration with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO, Com_MMR_CO, Inv_MMR_I and Com_MMR_I Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group
    Number of subjects analysed
    697
    249
    736
    283
    Units: Subjects
        Anti-rubella
    696
    249
    736
    283
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Power obtained using PASS 2005 (Likelihood Score [Miettienen and Nurminen approach]), one-sided non-inferiority test for the difference of two independent proportions, under the alternative associated to the reference value & alpha =1.25%. The global power to reach all non-inferiority objectives of Priorix vs. M-M-R II in sub-cohort 1 should be at least 94.04% (=100%- the sum of type II errors associated to cohort 1.
    Comparison groups
    Inv_MMR_CO Group v Com_MMR_CO Group
    Number of subjects included in analysis
    946
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [8]
    Method
    Parameter type
    		 Difference in seroresponse rate (%)
    Point estimate
    -0.14
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.98
         upper limit
    		 1.84
    Notes
    [8] - Non-inferiority criterion for sub cohort 1: The LL of the 2-sided 97.5% CI for group difference (Inv_MMR_CO group minus pooled Com_MMR_CO group) in seroresponse rates to measles, mumps and rubella viruses was ≥ -5%.
    Statistical analysis title
    		 Statistical analysis 2
    Statistical analysis description
    Power obtained using PASS 2005 (Likelihood Score [Miettienen and Nurminen approach]), one-sided non-inferiority test for the difference of two independent proportions, under the alternative associated to the reference value & alpha=1.25%. The global power to reach all non-inferiority objectives of Priorix vs. M-M-R II in sub-cohort 2 should be at least 98.88% (=100%- the sum of type II error associated to cohort 2.
    Comparison groups
    Inv_MMR_I Group v Com_MMR_I Group
    Number of subjects included in analysis
    1019
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [9]
    Method
    Parameter type
    		 Difference in seroresponse rate (%)
    Point estimate
    0
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 -0.68
         upper limit
    		 1.75
    Notes
    [9] - Non-inferiority criterion for sub cohort 2: The LL of the 2-sided 97.5% CI for group difference (Inv_MMR_I group minus pooled Com_MMR_I group) in seroresponse rates to measles, mumps and rubella viruses was ≥ -5%.

    Primary: Evaluation of immunogenicity in terms of anti-measles virus antibody concentrations

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    End point title
    		 Evaluation of immunogenicity in terms of anti-measles virus antibody concentrations [10]
    End point description
    Antibody concentrations were expressed as Geometric Mean Concentrations (GMCs) in mIU/mL. Analysis was done in sub-cohorts 1 and 2 only.
    End point type
    Primary
    End point timeframe
    42 days after vaccination (At Day 42)
    Notes
    [10] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, with and without co-administration with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO, Com_MMR_CO, Inv_MMR_I and Com_MMR_I Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group
    Number of subjects analysed
    697
    249
    736
    283
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Anti-measles
    4335 (4089.7 to 4594.9)
    4215.6 (3806.7 to 4668.4)
    3646.6 (3453.5 to 3850.4)
    3503.9 (3174.6 to 3867.4)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Inv_MMR_CO Group v Com_MMR_CO Group
    Number of subjects included in analysis
    946
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [11]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMC ratio
    Point estimate
    0.99
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 0.92
         upper limit
    		 1.06
    Notes
    [11] - Non-inferiority criterion for sub cohort 1: The LL of the 2-sided 97.5% CI for the adjusted GMC ratio (Inv_MMR_CO group divided by pooled Com_MMR_CO group) was ≥ 0.67 for antibodies to measles, mumps and rubella viruses.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Inv_MMR_I Group v Com_MMR_I Group
    Number of subjects included in analysis
    1019
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [12]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMC ratio
    Point estimate
    1.03
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 0.96
         upper limit
    		 1.1
    Notes
    [12] - Non-inferiority criterion for sub cohort 2: The LL of the 2-sided 97.5% CI for the adjusted GMC ratio (Inv_MMR_I group divided by pooled Com_MMR_I group) was ≥ 0.67 for antibodies to measles, mumps and rubella viruses.

    Primary: Evaluation of immunogenicity in terms of anti-mumps virus antibody concentrations

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    End point title
    		 Evaluation of immunogenicity in terms of anti-mumps virus antibody concentrations [13]
    End point description
    Antibody concentrations were expressed as GMCs in EU/mL. Analysis was done in sub-cohorts 1 and 2 only.
    End point type
    Primary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [13] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, with and without co-administration with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO, Com_MMR_CO, Inv_MMR_I and Com_MMR_I Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group
    Number of subjects analysed
    698
    250
    736
    283
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-mumps
    170.5 (161.6 to 179.9)
    190.1 (174.7 to 206.8)
    167.2 (158.6 to 176.3)
    176.2 (161.5 to 192.2)
    Statistical analysis title
    		 Statistical analysis 1
    Comparison groups
    Inv_MMR_CO Group v Com_MMR_CO Group
    Number of subjects included in analysis
    948
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [14]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMC ratio
    Point estimate
    0.91
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 0.83
         upper limit
    		 1
    Notes
    [14] - The LL of the 2-sided 97.5% CI for the adjusted GMC ratio (Inv_MMR_CO group divided by pooled Com_MMR_CO group) was ≥ 0.67 for antibodies to measles, mumps and rubella viruses.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Inv_MMR_I Group v Com_MMR_I Group
    Number of subjects included in analysis
    1019
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [15]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMC ratio
    Point estimate
    0.96
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 0.87
         upper limit
    		 1.06
    Notes
    [15] - The LL of the 2-sided 97.5% CI for the adjusted GMC ratio (Inv_MMR_I group divided by pooled Com_MMR_I group) was ≥ 0.67 for antibodies to measles, mumps and rubella viruses.

    Primary: Evaluation of immunogenicity in terms of anti-rubella virus antibody concentrations

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    End point title
    		 Evaluation of immunogenicity in terms of anti-rubella virus antibody concentrations [16]
    End point description
    Antibody concentrations were expressed as GMCs in IU/mL. Analysis was done in sub-cohorts 1 and 2 only.
    End point type
    Primary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [16] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, with and without co-administration with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO, Com_MMR_CO, Inv_MMR_I and Com_MMR_I Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group
    Number of subjects analysed
    697
    249
    736
    283
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-rubella
    96.4 (92.6 to 100.4)
    96 (89.5 to 103)
    98.9 (95.3 to 102.8)
    98.7 (93.2 to 104.5)
    Statistical analysis title
    		 Statistical analysis 1
    Statistical analysis description
    Adjusted geometric mean concentration (GMC) ratio (Inv_MMR_CO group divided by Com_MMR_CO group) for antibodies to rubella virus.
    Comparison groups
    Inv_MMR_CO Group v Com_MMR_CO Group
    Number of subjects included in analysis
    946
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [17]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMC ratio
    Point estimate
    1.03
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 0.97
         upper limit
    		 1.09
    Notes
    [17] - Non-inferiority criterion for sub cohort 1: The LL of the 2-sided 97.5% CI for the adjusted GMC ratio (Inv_MMR_CO group divided by pooled Com_MMR_CO group) was ≥ 0.67 for antibodies to measles, mumps and rubella viruses.
    Statistical analysis title
    		 Statistical analysis 2
    Comparison groups
    Inv_MMR_I Group v Com_MMR_I Group
    Number of subjects included in analysis
    1019
    Analysis specification
    Pre-specified
    Analysis type
    		 non-inferiority [18]
    Method
    		 ANCOVA
    Parameter type
    		 Adjusted GMC ratio
    Point estimate
    1.01
    Confidence interval
         level
    		 97.5%
         sides
    2-sided
         lower limit
    		 0.95
         upper limit
    		 1.07
    Notes
    [18] - Non-inferiority criterion for sub cohort 2: The LL of the 2-sided 97.5% CI for the adjusted GMC ratio (Inv_MMR_I group divided by pooled Com_MMR_I group) was ≥ 0.67 for antibodies to measles, mumps and rubella viruses.

    Secondary: Number of subjects with anti-varicella zoster virus (VZV) antibody concentration equal to or above the cut-off-value

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    End point title
    		 Number of subjects with anti-varicella zoster virus (VZV) antibody concentration equal to or above the cut-off-value [19]
    End point description
    Seroresponse was defined as post-vaccination anti-VZV antibody concentration ≥ 75 mIU/mL. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [19] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    695
    247
    Units: Subjects
        Anti-VZV
    693
    247
    No statistical analyses for this end point

    Secondary: Evaluation of immunogenicity in terms of anti-VZV antibody concentrations

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    End point title
    		 Evaluation of immunogenicity in terms of anti-VZV antibody concentrations [20]
    End point description
    Antibody concentrations were expressed as GMCs in mIU/mL. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [20] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    695
    247
    Units: mIU/mL
    geometric mean (confidence interval 95%)
        Anti-VZV
    887.7 (834.3 to 944.4)
    820.4 (749.3 to 898.3)
    No statistical analyses for this end point

    Secondary: Number of subjects with antibody booster response to diphtheria toxin (anti-D) and tetanus toxin (anti-T)

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    End point title
    		 Number of subjects with antibody booster response to diphtheria toxin (anti-D) and tetanus toxin (anti-T) [21]
    End point description
    Booster response was defined as: For subjects with pre-vaccination antibody concentration less than (<) 0.1 IU/mL, antibody concentration ≥ 0.4 IU/ml at Day 42. For subjects with pre-vaccination antibody concentration ≥ 0.1 IU/mL: antibody concentration at Day 42 ≥ 4 fold the pre-vaccination antibody concentration. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [21] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    661
    234
    Units: Subjects
        Anti-D (N=659;233)
    657
    233
        Anti-T (N=661;234)
    621
    224
    No statistical analyses for this end point

    Secondary: Number of subjects with antibody booster response to pertussis toxin (PT)

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    End point title
    		 Number of subjects with antibody booster response to pertussis toxin (PT) [22]
    End point description
    Booster response was defined as: For initially seronegative subjects, antibody concentration ≥ 10.772 IU/mL at Day 42. For initially seropositive subjects with pre-vaccination antibody concentration < 10.772 IU/mL: antibody concentration at Day 42 ≥ 4 fold the pre-vaccination antibody concentration. For initially seropositive subjects with pre-vaccination antibody concentration ≥ 10.772 IU/mL: antibody concentration at Day 42 ≥ 2 fold the pre-vaccination antibody concentration. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [22] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    659
    233
    Units: Subjects
        Anti-PT
    643
    225
    No statistical analyses for this end point

    Secondary: Number of subjects with antibody booster response to filamentous hemagglutinin (FHA)

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    End point title
    		 Number of subjects with antibody booster response to filamentous hemagglutinin (FHA) [23]
    End point description
    Booster response was defined as: For initially seronegative subjects, antibody concentration ≥ 8.184 IU/ml at Day 42. For initially seropositive subjects with pre-vaccination antibody concentration < 8.184 IU/mL: antibody concentration at Day 42 ≥ 4 fold the pre-vaccination antibody concentration. For initially seropositive subjects with pre-vaccination antibody concentration ≥ 8.184 IU/mL: antibody concentration at Day 42 ≥ 2 fold the pre-vaccination antibody concentration. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [23] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    659
    234
    Units: Subjects
        Anti-FHA
    620
    221
    No statistical analyses for this end point

    Secondary: Number of subjects with antibody booster response to pertactin (PRN)

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    End point title
    		 Number of subjects with antibody booster response to pertactin (PRN) [24]
    End point description
    Booster response was defined as: For initially seronegative subjects, antibody concentration ≥ 8.748 IU/mL at Day 42. For initially seropositive subjects with pre-vaccination antibody concentration < 8.748 IU/mL: antibody concentration at Day 42 ≥ 4 fold the pre-vaccination antibody concentration. For initially seropositive subjects with pre-vaccination antibody concentration ≥ 8.748 IU/mL: antibody concentration at Day 42 ≥ 2 fold the pre-vaccination antibody concentration. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [24] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    660
    234
    Units: Subjects
        Anti-PRN
    657
    233
    No statistical analyses for this end point

    Secondary: Evaluation of immunogenicity in terms of anti-D and anti-T antibody concentrations

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    End point title
    		 Evaluation of immunogenicity in terms of anti-D and anti-T antibody concentrations [25]
    End point description
    Antibody concentrations were expressed as GMCs in IU/mL. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [25] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    684
    243
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-D
    17.2 (16.2 to 18.1)
    17.8 (16.1 to 19.6)
        Anti-T
    7.4 (6.9 to 7.8)
    8.4 (7.6 to 9.3)
    No statistical analyses for this end point

    Secondary: Evaluation of immunogenicity in terms of anti-PT, anti-FHA and anti-PRN antibody concentrations

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    End point title
    		 Evaluation of immunogenicity in terms of anti-PT, anti-FHA and anti-PRN antibody concentrations [26]
    End point description
    Antibody concentrations were expressed as GMCs in EU/mL. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [26] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    684
    243
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-PT (N=684;243)
    76.6 (71.6 to 82)
    73.9 (66.2 to 82.4)
        Anti-FHA (N=684;243)
    316.2 (299.4 to 334)
    319.3 (293.1 to 347.9)
        Anti-PRN (N=682;243)
    402.2 (370.4 to 436.8)
    427.3 (377.6 to 483.4)
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL

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    End point title
    		 Number of subjects with anti-D and anti-T antibody concentrations ≥ 0.1 IU/mL [27]
    End point description
    Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [27] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    684
    243
    Units: Subjects
        Anti-D
    684
    243
        Anti-T
    684
    243
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-D and anti-T antibody concentrations ≥ 1.0 IU/mL

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    End point title
    		 Number of subjects with anti-D and anti-T antibody concentrations ≥ 1.0 IU/mL [28]
    End point description
    Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [28] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    684
    243
    Units: Subjects
        Anti-D
    683
    242
        Anti-T
    678
    243
    No statistical analyses for this end point

    Secondary: Evaluation of immunogenicity in terms of anti-polio virus types 1, 2 and 3 antibody titers

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    End point title
    		 Evaluation of immunogenicity in terms of anti-polio virus types 1, 2 and 3 antibody titers [29]
    End point description
    Antibody titers were expressed as Geometric Mean Titers (GMTs) in ED50. Analysis was done in sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    42 days post vaccination (At Day 42)
    Notes
    [29] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    669
    238
    Units: ED50
    geometric mean (confidence interval 95%)
        Anti-Polio 1 (N=669;238)
    1618.7 (1499.8 to 1747)
    1587.3 (1387.3 to 1816.1)
        Anti-Polio 2 (N=653;233)
    2026.4 (1881.2 to 2182.7)
    2206.1 (1955.2 to 2489.3)
        Anti-Polio 3 (N=590;214)
    2753.5 (2512.4 to 3017.6)
    3040.6 (2613 to 3538.1)
    No statistical analyses for this end point

    Secondary: Number of subjects with solicited local symptoms

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    End point title
    		 Number of subjects with solicited local symptoms
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 Pain = Cried when limb was moved/spontaneously painful. Grade 3 redness and swelling = greater than 50 millimeters (m m ) i.e . > 50mm.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    727
    267
    766
    289
    1289
    480
    Units: Subjects
        Any Pain
    295
    109
    152
    64
    278
    123
        Grade 3 Pain
    22
    4
    6
    2
    5
    2
        Any Redness
    157
    69
    146
    53
    242
    90
        Grade 3 Redness
    9
    4
    0
    0
    0
    0
        Any Swelling
    82
    28
    64
    23
    108
    42
        Grade 3 Swelling
    3
    3
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with solicited general symptoms

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    End point title
    		 Number of subjects with solicited general symptoms [30]
    End point description
    Assessed solicited general symptoms were drowsiness and loss of appetite. Any = occurrence of the symptom regardless of intensity grade. Grade 3 Drowsiness = Drowsiness that prevented normal activity, Grade 3 Loss of appetite = Not eating at all. Related = symptom assessed by the investigator as causally related to study vaccination. Analysis was done for sub-cohort 1 only.
    End point type
    Secondary
    End point timeframe
    During the 4-day (Days 0-3) post-vaccination period
    Notes
    [30] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: The end point was aimed at assessing non-inferiority of Priorix vaccine to M-M-R II vaccine, when co-administered with Kinrix and ProQuad vaccines. This endpoint therefore presents the results for groups applicable for this analysis (i.e., Inv_MMR_CO and Com_MMR_CO Groups).
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group
    Number of subjects analysed
    731
    268
    Units: Subjects
        Any Drowsiness
    199
    72
        Grade 3 Drowsiness
    10
    3
        Related Drowsiness
    180
    63
        Any Loss of appetite
    154
    59
        Grade 3 Loss of appetite
    2
    2
        Related Loss of appetite
    135
    56
    No statistical analyses for this end point

    Secondary: Number of subjects reporting fever

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    End point title
    		 Number of subjects reporting fever
    End point description
    Any fever = fever ≥ 38°C. Grade 3 fever = fever > 39.5°C. Related = fever assessed by the investigator as causally related to study vaccination.
    End point type
    Secondary
    End point timeframe
    During the 43-day (Days 0-42) post-vaccination period
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    731
    268
    767
    291
    1291
    481
    Units: Subjects
        Any fever
    177
    67
    146
    58
    257
    96
        Grade 3 fever
    7
    6
    14
    9
    21
    8
        Related fever
    100
    32
    27
    11
    52
    25
    No statistical analyses for this end point

    Secondary: Number of subjects reporting MMR specific solicited general symptoms

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    End point title
    		 Number of subjects reporting MMR specific solicited general symptoms
    End point description
    Assessed MMR specific symptoms were parotid gland swelling and any suspected signs of meningism including febrile convulsions. Any = occurrence of any general symptoms regardless of their intensity grade or relationship to vaccination. Grade 3 Parotid/salivary gland swelling = Swelling accompanied with general symptoms. Grade 3 Sign of meningism (any suspected signs including febrile convulsions) = An event which prevented normal, everyday activities. Related = symptom assessed by the investigator as causally related to study vaccination.
    End point type
    Secondary
    End point timeframe
    During the 43-day (Days 0-42) post-vaccination period
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    731
    268
    767
    291
    1291
    481
    Units: Subjects
        Any Sign of meningism
    0
    2
    1
    0
    0
    0
        Grade 3 Sign of meningism
    0
    0
    0
    0
    0
    0
        Related Sign of meningism
    0
    2
    0
    0
    0
    0
        Any Parotid gland swelling
    0
    0
    0
    1
    1
    1
        Grade 3 Parotid gland swelling
    0
    0
    0
    0
    0
    0
        Related Parotid gland swelling
    0
    0
    0
    1
    1
    1
    No statistical analyses for this end point

    Secondary: Number of subjects reporting investigator-confirmed rash

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    End point title
    		 Number of subjects reporting investigator-confirmed rash
    End point description
    Assessed any rash, varicella-like rash, measles/rubella-like rash, Grade 3, related. Any= occurrence of rash regardless of their intensity grade. Grade 3 measles/rubella/varicella-like rash = Rash with more than 150 lesions. Other Grade 3 Rash = Rash that prevented normal, everyday activities. Related= Rash assessed by the investigator as causally related to study vaccination.
    End point type
    Secondary
    End point timeframe
    During the 43-day (Days 0-42) post-vaccination period
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    731
    268
    767
    291
    1291
    481
    Units: Subjects
        Any localized or generalized
    61
    28
    37
    12
    56
    23
        Any with fever
    11
    7
    5
    1
    6
    1
        Any Varicella like
    4
    3
    0
    0
    0
    0
        Any Measles/Rubella like
    14
    5
    3
    2
    4
    2
        Any grade 3
    3
    0
    1
    0
    3
    0
        Any related
    25
    11
    2
    2
    8
    3
        Localized any
    50
    24
    27
    9
    42
    19
        Localized administration site
    9
    2
    1
    0
    8
    0
        Localized other site
    41
    22
    26
    9
    36
    19
        Localized with fever
    8
    6
    4
    0
    4
    1
        Localized Varicella like
    2
    2
    0
    0
    0
    0
        Localized Measles/Rubella like
    12
    4
    3
    2
    4
    1
        Localized Grade 3
    2
    0
    1
    0
    0
    0
        Localized related
    18
    10
    2
    2
    7
    2
        Generalized any
    12
    4
    10
    3
    15
    4
        Generalized with fever
    3
    1
    1
    1
    2
    0
        Generalized Varicella like
    2
    1
    0
    0
    0
    0
        Generalized Measles/Rubella like
    2
    1
    0
    0
    0
    1
        Generalized Grade 3
    1
    0
    0
    0
    3
    0
        Generalized Related
    7
    1
    0
    0
    1
    1
    No statistical analyses for this end point

    Secondary: Number of subjects with new onset chronic diseases (NOCDs)

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    End point title
    		 Number of subjects with new onset chronic diseases (NOCDs)
    End point description
    NOCDs include autoimmune disorders, asthma, type I diabetes, allergies.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Day 0 up to Day 180)
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    802
    298
    796
    303
    1319
    489
    Units: Subjects
        Any NOCD(s)
    8
    4
    6
    0
    11
    3
    No statistical analyses for this end point

    Secondary: Number of subjects reporting adverse events resulting in Emergency Room (ER) visits

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    End point title
    		 Number of subjects reporting adverse events resulting in Emergency Room (ER) visits
    End point description
    The number of subjects reporting adverse events resulting in Emergency Room (ER) visits is reported.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Day 0 up to Day 180)
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    802
    298
    796
    303
    1319
    489
    Units: Subjects
        Any AE(s) with ER visits
    61
    29
    64
    22
    102
    36
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects with unsolicited adverse events (AEs)
    End point description
    An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination.
    End point type
    Secondary
    End point timeframe
    During the 43-day (Days 0-42) post-vaccination period
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    802
    298
    796
    303
    1319
    489
    Units: Subjects
        Any AE(s)
    276
    90
    314
    112
    508
    186
    No statistical analyses for this end point

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

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    End point title
    		 Number of subjects with serious adverse events (SAEs)
    End point description
    Serious adverse events (SAEs) assessed included medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity. Any SAE = occurrence of SAE regardless of intensity grade or relation to vaccination.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Day 0 up to Day 180)
    End point values
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Number of subjects analysed
    802
    298
    796
    303
    1319
    489
    Units: Subjects
        Any SAE(s)
    4
    0
    14
    1
    25
    9
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited local symptoms: during the 4-day (Days 0-3) post-vaccination period; Solicited general symptoms and Unsolicited AEs: during the 43-day (Days 0-42) post-vaccination period; SAEs: during the entire study period (from Day 0 up to Day 180).
    Adverse event reporting additional description
    Drowsiness and loss of appetite symptoms were collected during the 4-day (Days 0-3) post-vaccination period.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    20.0
    Reporting groups
    Reporting group title
    Inv_MMR_CO Group
    Reporting group description
    		 Subjects received one dose of the study vaccine Priorix along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_CO Group
    Reporting group description
    		 Subjects received one dose of the licensed vaccine M-M-R II (also known as M-M-R Vax Pro) Lot 1 or Lot 2 along with Kinrix and ProQuad vaccines at Visit 1 (Day 0).

    Reporting group title
    Inv_MMR_I Group
    Reporting group description
    		 Subjects received one dose of Priorix at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_I Group
    Reporting group description
    		 Subjects received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).

    Reporting group title
    Inv_MMR_S Group
    Reporting group description
    		 Subjects in this safety cohort received one dose of Priorix at Visit 1 (Day 0).

    Reporting group title
    Com_MMR_S Group
    Reporting group description
    		 Subjects in this safety cohort received one dose of M-M-R II (also known as M-M-R Vax Pro) vaccine from Lot 1 or Lot 2 at Visit 1 (Day 0).

    Serious adverse events
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 802 (0.50%)
    0 / 298 (0.00%)
    14 / 796 (1.76%)
    1 / 303 (0.33%)
    25 / 1319 (1.90%)
    9 / 489 (1.84%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Accidental exposure to product
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Concussion
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    1 / 489 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Injury
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Nervous system disorders
    Febrile convulsion
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Blood and lymphatic system disorders
    Thrombocytopenia
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    1 / 489 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    1 / 802 (0.12%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Cyclic vomiting syndrome
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    2 / 1319 (0.15%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 4
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ileus
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    1 / 489 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Hepatobiliary disorders
    Hepatic function abnormal
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Adenoidal hypertrophy
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    2 / 1319 (0.15%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    2 / 802 (0.25%)
    0 / 298 (0.00%)
    4 / 796 (0.50%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    2 / 489 (0.41%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 4
    0 / 0
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 802 (0.12%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sleep apnoea syndrome
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Status asthmaticus
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Skin and subcutaneous tissue disorders
    Eczema vesicular
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Rash generalised
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Infections and infestations
    Adenovirus infection
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    1 / 489 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Appendicitis perforated
         subjects affected / exposed
    1 / 802 (0.12%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    1 / 489 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    2 / 796 (0.25%)
    0 / 303 (0.00%)
    5 / 1319 (0.38%)
    1 / 489 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 5
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Herpangina
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    3 / 489 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    2 / 1319 (0.15%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    2 / 1319 (0.15%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    2 / 796 (0.25%)
    1 / 303 (0.33%)
    0 / 1319 (0.00%)
    3 / 489 (0.61%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 1
    0 / 0
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia bacterial
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Tonsillitis
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    2 / 1319 (0.15%)
    1 / 489 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    0 / 796 (0.00%)
    0 / 303 (0.00%)
    2 / 1319 (0.15%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Viral upper respiratory tract infection
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    2 / 1319 (0.15%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemia
         subjects affected / exposed
    0 / 802 (0.00%)
    0 / 298 (0.00%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    1 / 1319 (0.08%)
    0 / 489 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    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
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Inv_MMR_CO Group Com_MMR_CO Group Inv_MMR_I Group Com_MMR_I Group Inv_MMR_S Group Com_MMR_S Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    544 / 802 (67.83%)
    198 / 298 (66.44%)
    410 / 796 (51.51%)
    156 / 303 (51.49%)
    702 / 1319 (53.22%)
    279 / 489 (57.06%)
    Nervous system disorders
    Somnolence
         subjects affected / exposed
    199 / 802 (24.81%)
    73 / 298 (24.50%)
    1 / 796 (0.13%)
    0 / 303 (0.00%)
    0 / 1319 (0.00%)
    0 / 489 (0.00%)
         occurrences all number
    199
    73
    1
    0
    0
    0
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    170 / 802 (21.20%)
    73 / 298 (24.50%)
    147 / 796 (18.47%)
    53 / 303 (17.49%)
    242 / 1319 (18.35%)
    90 / 489 (18.40%)
         occurrences all number
    173
    75
    147
    53
    242
    90
    Injection site pain
         subjects affected / exposed
    309 / 802 (38.53%)
    118 / 298 (39.60%)
    153 / 796 (19.22%)
    64 / 303 (21.12%)
    278 / 1319 (21.08%)
    123 / 489 (25.15%)
         occurrences all number
    321
    125
    153
    64
    278
    123
    Injection site swelling
         subjects affected / exposed
    97 / 802 (12.09%)
    31 / 298 (10.40%)
    64 / 796 (8.04%)
    23 / 303 (7.59%)
    108 / 1319 (8.19%)
    42 / 489 (8.59%)
         occurrences all number
    97
    32
    64
    23
    108
    42
    Pyrexia
         subjects affected / exposed
    177 / 802 (22.07%)
    67 / 298 (22.48%)
    146 / 796 (18.34%)
    58 / 303 (19.14%)
    257 / 1319 (19.48%)
    96 / 489 (19.63%)
         occurrences all number
    177
    67
    146
    58
    257
    96
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    38 / 802 (4.74%)
    16 / 298 (5.37%)
    37 / 796 (4.65%)
    8 / 303 (2.64%)
    47 / 1319 (3.56%)
    21 / 489 (4.29%)
         occurrences all number
    41
    17
    41
    8
    50
    22
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    61 / 802 (7.61%)
    28 / 298 (9.40%)
    37 / 796 (4.65%)
    12 / 303 (3.96%)
    56 / 1319 (4.25%)
    23 / 489 (4.70%)
         occurrences all number
    61
    28
    37
    12
    56
    23
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    25 / 802 (3.12%)
    3 / 298 (1.01%)
    77 / 796 (9.67%)
    28 / 303 (9.24%)
    112 / 1319 (8.49%)
    45 / 489 (9.20%)
         occurrences all number
    27
    3
    100
    32
    143
    57
    Upper respiratory tract infection
         subjects affected / exposed
    27 / 802 (3.37%)
    11 / 298 (3.69%)
    55 / 796 (6.91%)
    27 / 303 (8.91%)
    92 / 1319 (6.97%)
    21 / 489 (4.29%)
         occurrences all number
    28
    11
    66
    35
    107
    22
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    156 / 802 (19.45%)
    61 / 298 (20.47%)
    2 / 796 (0.25%)
    1 / 303 (0.33%)
    3 / 1319 (0.23%)
    0 / 489 (0.00%)
         occurrences all number
    159
    61
    2
    1
    3
    0

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

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
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