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    Clinical Trial Results:
    Immunogenicity and safety study of GSK Biologicals’ meningococcal vaccine 134612 with or without co-administration of Cervarix and Boostrix in female adolescents and young adults at 9-25 years of age

    Summary
    EudraCT number
    2012-001876-13
    Trial protocol
    EE  
    Global end of trial date
    29 Apr 2014

    Results information
    Results version number
    v3(current)
    This version publication date
    25 Jan 2018
    First version publication date
    17 Jun 2017
    Other versions
    v1 , v2
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    113823
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01755689
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    GlaxoSmithKline Biologicals
    Sponsor organisation address
    Rue de l’Institut 89, Rixensart, Belgium, B-1330
    Public contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Scientific contact
    Clinical Trials Call Center, GlaxoSmithKline Biologicals, 044 2089-904466, GSKClinicalSupportHD@gsk.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    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
    25 May 2017
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Apr 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate the non-inferiority of MenACWY-TT conjugate vaccine co-administered with HPV-16/18 L1 AS04 compared to MenACWY-TT alone with respect to Serum Bactericidal Assay using rabbit complement (rSBA) geometric mean titres (GMTs) for serogroups A, C, W-135 and Y one month after vaccination. To demonstrate the non-inferiority of HPV-16/18 L1 AS04 co-administered with MenACWY-TT compared to HPV-16/18 L1 AS04 alone in terms of HPV16 and HPV18 GMTs as measured by ELISA one month after the third dose of HPV-16/18 L1 AS04. To demonstrate the non-inferiority of MenACWY-TT co-administered with HPV-16/18 L1 AS04 and Tdap compared to MenACWY-TT alone with respect to rSBA GMTs for serogroups A, C, W-135 and Y one month after vaccination. To demonstrate the non-inferiority of HPV-16/18 L1 AS04 co-administered with MenACWY-TT and Tdap compared to HPV-16/18 L1 AS04 co-administered with Tdap in terms of HPV16 and HPV18 GMTs as measured by ELISA one month after the third dose of HPV-16
    Protection of trial subjects
    All subjects were supervised after vaccination/product administration with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines were administered only to eligible subjects that had no contraindications to any components of the vaccines.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    01 Nov 2013
    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
    Dominican Republic: 435
    Country: Number of subjects enrolled
    Estonia: 435
    Country: Number of subjects enrolled
    Thailand: 430
    Worldwide total number of subjects
    1300
    EEA total number of subjects
    435
    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)
    153
    Adolescents (12-17 years)
    606
    Adults (18-64 years)
    541
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    -

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

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    Nimenrix+Cervarix (1,2,7-Month) Group
    Arm description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 1, Month 2 and Month 7. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Arm type
    Experimental

    Investigational medicinal product name
    Nimenrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose of Nimenrix vaccine at Month 0, administered intramuscularly (IM) in the deltoid region of the arm.

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6/7, administered intramuscularly (IM) in the deltoid region of the arm.

    Arm title
    Nimenrix+Cervarix (0,1,6-Month) Group
    Arm description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Arm type
    Experimental

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6/7, administered intramuscularly (IM) in the deltoid region of the arm.

    Investigational medicinal product name
    Nimenrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose of Nimenrix vaccine at Month 0, administered intramuscularly (IM) in the deltoid region of the arm.

    Arm title
    Cervarix Group
    Arm description
    Subjects in this group received 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6, administered intramuscularly (IM) in the deltoid region of the arm.
    Arm type
    Active comparator

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6/7, administered intramuscularly (IM) in the deltoid region of the arm.

    Arm title
    Nimenrix+Cervarix+Boostrix Group
    Arm description
    Subjects in this group received 1 dose each of Nimenrix and Boostrix vaccines at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. All vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Arm type
    Experimental

    Investigational medicinal product name
    Nimenrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose of Nimenrix vaccine at Month 0, administered intramuscularly (IM) in the deltoid region of the arm.

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6/7, administered intramuscularly (IM) in the deltoid region of the arm.

    Investigational medicinal product name
    Boostrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose of Boostrix vaccine at Month 0, administered intramuscularly (IM) in the deltoid region of the arm.

    Arm title
    Boostrix+Cervarix Group
    Arm description
    Subjects in this group received 1 dose of Boostrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.
    Arm type
    Active comparator

    Investigational medicinal product name
    Boostrix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    1 dose of Boostrix vaccine at Month 0, administered intramuscularly (IM) in the deltoid region of the arm.

    Investigational medicinal product name
    Cervarix
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6/7, administered intramuscularly (IM) in the deltoid region of the arm.

    Number of subjects in period 1
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Started
    259
    259
    261
    260
    261
    Completed
    256
    254
    255
    254
    255
    Not completed
    3
    5
    6
    6
    6
         Migrated/moved from study area
    -
    1
    1
    1
    1
         Pregnancy
    1
    1
    2
    4
    2
         Consent withdrawn by subject
    1
    3
    2
    1
    1
         Lost to follow-up
    1
    -
    1
    -
    2

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Nimenrix+Cervarix (1,2,7-Month) Group
    Reporting group description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 1, Month 2 and Month 7. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Nimenrix+Cervarix (0,1,6-Month) Group
    Reporting group description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Cervarix Group
    Reporting group description
    Subjects in this group received 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6, administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Nimenrix+Cervarix+Boostrix Group
    Reporting group description
    Subjects in this group received 1 dose each of Nimenrix and Boostrix vaccines at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. All vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Boostrix+Cervarix Group
    Reporting group description
    Subjects in this group received 1 dose of Boostrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group Total
    Number of subjects
    259 259 261 260 261
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    16.3 ± 4.6 16.6 ± 4.4 16.6 ± 4.6 16.6 ± 4.6 16.6 ± 4.5 -
    Gender categorical
    Units:
        Male
    0 0 0 0 0 0
        Female
    259 259 261 260 261 1300
    Race/Ethnicity, Customized
    Units: Subjects
        African Heritage / African American
    0 0 0 1 0 1
        Asian - South East Asian Heritage
    86 86 86 86 86 430
        White - Caucasian / European Heritage
    87 86 87 87 88 435
        Other
    86 87 88 86 87 434

    End points

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    End points reporting groups
    Reporting group title
    Nimenrix+Cervarix (1,2,7-Month) Group
    Reporting group description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 1, Month 2 and Month 7. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Nimenrix+Cervarix (0,1,6-Month) Group
    Reporting group description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Cervarix Group
    Reporting group description
    Subjects in this group received 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6, administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Nimenrix+Cervarix+Boostrix Group
    Reporting group description
    Subjects in this group received 1 dose each of Nimenrix and Boostrix vaccines at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. All vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Boostrix+Cervarix Group
    Reporting group description
    Subjects in this group received 1 dose of Boostrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Primary: Anti-Meningitis antibody titers by serum bactericidal assay using rabbit complement (rSBA)

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    End point title
    Anti-Meningitis antibody titers by serum bactericidal assay using rabbit complement (rSBA) [1]
    End point description
    The analysis was performed for the serogroups -MenA, -MenC -MenW-135 and -MenY. Antibody titers, tabulated as geometric mean titers (GMTs), were obtained by serum bactericidal assay using rabbit complement. This analysis was only performed on groups receiving Nimenrix vaccine.
    End point type
    Primary
    End point timeframe
    At one month after vaccination with Nimenrix (Month 1)
    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 analysis was performed only on the groups receiving Nimenrix vaccine.
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Nimenrix+Cervarix+Boostrix Group
    Number of subjects analysed
    256
    255
    257
    Units: Titers
    geometric mean (confidence interval 95%)
        rSBA-MenA
    5517.1 (4791.4 to 6352.6)
    5523.5 (4913.2 to 6209.6)
    4649.6 (4022.8 to 5374.0)
        rSBA-MenC
    4277.3 (3604.3 to 5076.1)
    5091.0 (4338.6 to 5973.8)
    3598.6 (3004.2 to 4310.7)
        rSBA-MenW-135
    14782.1 (12254.2 to 17831.5)
    18068.3 (15381.6 to 21224.4)
    11663.6 (9336.8 to 14570.2)
        rSBA-MenY
    11871.0 (10542.3 to 13367.2)
    12758.9 (11569.6 to 14070.5)
    11201.2 (9678.7 to 12963.1)
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix+Boostrix Group in terms of rSBA-MenA titers.
    Comparison groups
    Nimenrix+Cervarix+Boostrix Group v Nimenrix+Cervarix (1,2,7-Month) Group
    Number of subjects included in analysis
    513
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.99
         upper limit
    1.43
    Notes
    [2] - The non-inferiority criteria: the upper limit (UL) of the 2-sided standardised asymptotic 95% confidence interval (CI) for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix Group in terms of rSBA-MenA titers.
    Comparison groups
    Nimenrix+Cervarix (1,2,7-Month) Group v Nimenrix+Cervarix (0,1,6-Month) Group
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.01
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.84
         upper limit
    1.21
    Notes
    [3] - The non-inferiority criteria: the UL of the 2-sided standardised asymptotic 95% CI for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix+Boostrix Group in terms of rSBA-MenC titers.
    Comparison groups
    Nimenrix+Cervarix+Boostrix Group v Nimenrix+Cervarix (1,2,7-Month) Group
    Number of subjects included in analysis
    513
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [4]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.93
         upper limit
    1.51
    Notes
    [4] - The non-inferiority criteria: the UL of the 2-sided standardised asymptotic 95% CI for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix Group in terms of rSBA-MenC titers.
    Comparison groups
    Nimenrix+Cervarix (1,2,7-Month) Group v Nimenrix+Cervarix (0,1,6-Month) Group
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [5]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    0.83
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.66
         upper limit
    1.06
    Notes
    [5] - The non-inferiority criteria: the UL of the 2-sided standardised asymptotic 95% CI for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 5
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix+Boostrix Group in terms of rSBA-MenW-135 titers.
    Comparison groups
    Nimenrix+Cervarix+Boostrix Group v Nimenrix+Cervarix (1,2,7-Month) Group
    Number of subjects included in analysis
    513
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [6]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.26
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.97
         upper limit
    1.64
    Notes
    [6] - The non-inferiority criteria: the UL of the 2-sided standardised asymptotic 95% CI for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 6
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix Group in terms of rSBA-MenW-135 titers.
    Comparison groups
    Nimenrix+Cervarix (1,2,7-Month) Group v Nimenrix+Cervarix (0,1,6-Month) Group
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [7]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    0.82
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.63
         upper limit
    1.07
    Notes
    [7] - The non-inferiority criteria: the UL of the 2-sided standardised asymptotic 95% CI for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 7
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix+Boostrix Group in terms of rSBA-MenY titers.
    Comparison groups
    Nimenrix+Cervarix+Boostrix Group v Nimenrix+Cervarix (1,2,7-Month) Group
    Number of subjects included in analysis
    513
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [8]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.89
         upper limit
    1.24
    Notes
    [8] - The non-inferiority criteria: the UL of the 2-sided standardised asymptotic 95% CI for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 8
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix Group versus Nimenrix+Cervarix Group in terms of rSBA-MenY titers.
    Comparison groups
    Nimenrix+Cervarix (1,2,7-Month) Group v Nimenrix+Cervarix (0,1,6-Month) Group
    Number of subjects included in analysis
    511
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [9]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    0.95
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.8
         upper limit
    1.12
    Notes
    [9] - The non-inferiority criteria: the UL of the 2-sided standardised asymptotic 95% CI for the ratio of rSBA GMTs had to be below the pre-defined limit of 2.

    Primary: Anti-HPV-16 and anti-HPV-18 concentrations

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    End point title
    Anti-HPV-16 and anti-HPV-18 concentrations [10]
    End point description
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as Enzyme-linked Immunosorbent Assay (ELISA) units per milliliter (EU/mL).
    End point type
    Primary
    End point timeframe
    At one month after vaccination with Cervarix (Month 7)
    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 analysis was performed only on the groups receiving Cervarix vaccine.
    End point values
    Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    248
    249
    244
    247
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-HPV-16
    12124.9 (10564.5 to 13915.7)
    11672.1 (10173.5 to 13391.4)
    9563.8 (8262.0 to 11070.7)
    11470.7 (10018.5 to 13133.5)
        Anti-HPV-18
    5234.1 (4573.9 to 5989.6)
    5655.0 (4978.5 to 6423.4)
    4306.2 (3748.3 to 4947.1)
    5110.0 (4487.0 to 5819.6)
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Adjusted GMT ratio of the Cervarix Group versus Nimenrix+Cervarix (0,1,6-Month) Group in terms of HPV-16 titers.
    Comparison groups
    Cervarix Group v Nimenrix+Cervarix (0,1,6-Month) Group
    Number of subjects included in analysis
    497
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [11]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT
    Point estimate
    0.97
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.81
         upper limit
    1.15
    Notes
    [11] - For HPV-16, one month after the third dose of Cervarix, the UL of the two-sided standardized asymptotic 95% CI on the group GMT ratio had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Adjusted GMT ratio of the Cervarix Group versus Nimenrix+Cervarix (0,1,6-Month) Group in terms of HPV-18 titers.
    Comparison groups
    Cervarix Group v Nimenrix+Cervarix (0,1,6-Month) Group
    Number of subjects included in analysis
    497
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [12]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT
    Point estimate
    1.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.92
         upper limit
    1.29
    Notes
    [12] - For HPV-18, one month after the third dose of Cervarix, the UL of the two-sided standardized asymptotic 95% CI on the group GMT ratio had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Adjusted GMT ratio of the Boostrix+Cervarix Group versus Nimenrix+Cervarix+Boostrix Group in terms of HPV-16 titers.
    Comparison groups
    Boostrix+Cervarix Group v Nimenrix+Cervarix+Boostrix Group
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [13]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT
    Point estimate
    1.2
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.01
         upper limit
    1.43
    Notes
    [13] - For HPV-16, one month after the third dose of Cervarix, the UL of the two-sided standardized asymptotic 95% CI on the group GMT ratio had to be below the pre-defined limit of 2.
    Statistical analysis title
    Statistical analysis 4
    Statistical analysis description
    Adjusted GMT ratio of the Boostrix+Cervarix Group versus Nimenrix+Cervarix+Boostrix Group in terms of HPV-18 titers.
    Comparison groups
    Boostrix+Cervarix Group v Nimenrix+Cervarix+Boostrix Group
    Number of subjects included in analysis
    491
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [14]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT
    Point estimate
    1.19
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1
         upper limit
    1.41
    Notes
    [14] - For HPV-18, one month after the third dose of Cervarix, the UL of the two-sided standardized asymptotic 95% CI on the group GMT ratio had to be below the pre-defined limit of 2.

    Primary: Number of subjects with anti-diphteria (anti-D) and anti-tetanus (anti-T) concentrations equal to or above (≥) 1.0 IU/mL

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    End point title
    Number of subjects with anti-diphteria (anti-D) and anti-tetanus (anti-T) concentrations equal to or above (≥) 1.0 IU/mL [15]
    End point description
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as International Units per milliliter (IU/mL). This analysis was only performed in the groups receiving Boostrix vaccine.
    End point type
    Primary
    End point timeframe
    At one month after Boostrix vaccination (Month 1)
    Notes
    [15] - 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 analysis was performed only on the groups receiving Boostrix vaccine.
    End point values
    Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    250
    256
    Units: Participants
        Anti-D
    235
    248
        Anti-T
    249
    256
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    The group difference of the Nimenrix+Cervarix+Boostrix Group and Boostrix +Cervarix Group in terms of Anti-D titers.
    Comparison groups
    Boostrix+Cervarix Group v Nimenrix+Cervarix+Boostrix Group
    Number of subjects included in analysis
    506
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [16]
    Method
    Parameter type
    Difference between groups
    Point estimate
    -2.88
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -6.9
         upper limit
    0.81
    Notes
    [16] - For anti-D the LL of the 2-sided standardised asymptotic 95% CI for the group difference (Nimenrix+Cervarix+Boostrix Group minus Boostrix +Cervarix Group) had to be greater than or equal to the pre-defined limit of -10%.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    The group difference of the Nimenrix+Cervarix+Boostrix Group and Boostrix+Cervarix Group in terms of Anti-T titers.
    Comparison groups
    Boostrix+Cervarix Group v Nimenrix+Cervarix+Boostrix Group
    Number of subjects included in analysis
    506
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [17]
    Method
    Parameter type
    Difference between groups
    Point estimate
    -0.4
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -2.23
         upper limit
    1.08
    Notes
    [17] - For anti-T the LL of the 2-sided standardised asymptotic 95% CI for the group difference (Nimenrix+Cervarix+Boostrix Group minus Boostrix +Cervarix Group) had to be greater than or equal to the pre-defined limit of -10%.

    Primary: Anti-Pertussis Toxoid(anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations

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    End point title
    Anti-Pertussis Toxoid(anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibody concentrations [18]
    End point description
    The antibody concentrations were tabulated as GMCs and expressed as IU/mL. GMCs were only analyzed in subjects receiving Boostrix vaccination.
    End point type
    Primary
    End point timeframe
    At one month after Boostrix vaccination (Month 1)
    Notes
    [18] - 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 analysis was performed only on the groups receiving Boostrix vaccine.
    End point values
    Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    247
    256
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-PT, (N=245;254)
    52.9 (46.4 to 60.4)
    73.2 (65.0 to 82.5)
        Anti-FHA, (N=247;256)
    278.7 (249.5 to 311.2)
    472.4 (419.7 to 531.8)
        Anti-PRN, (N=246;256)
    193.4 (159.0 to 235.1)
    318.6 (262.4 to 386.8)
    Statistical analysis title
    Statistical analysis 1
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix+Cervarix+Boostrix Group versus Boostrix+ Cervarix Group in terms of anti-PRN titers.
    Comparison groups
    Boostrix+Cervarix Group v Nimenrix+Cervarix+Boostrix Group
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [19]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.53
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.25
         upper limit
    1.87
    Notes
    [19] - For anti-PRN the UL of the 2-sided standardised asymptotic 95% CI for the adjusted group ratio of GMCs (Nimenrix+Cervarix+Boostrix Group/Boostrix+Cervarix Group) had to be less than or equal to the pre-defined limit of 1.5.
    Statistical analysis title
    Statistical analysis 2
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix+Cervarix Group versus Boostrix+ Cervarix Group in terms of anti-FHA titers.
    Comparison groups
    Boostrix+Cervarix Group v Nimenrix+Cervarix+Boostrix Group
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [20]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.65
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.42
         upper limit
    1.93
    Notes
    [20] - For anti-FHA the UL of the 2-sided standardised asymptotic 95% CI for the adjusted group ratio of GMCs (Nimenrix+Cervarix+Boostrix Group/Boostrix+Cervarix Group) had to be less than or equal to the pre-defined limit of 1.5.
    Statistical analysis title
    Statistical analysis 3
    Statistical analysis description
    Adjusted GMT ratio of the Nimenrix+Cervarix Group versus Boostrix+ Cervarix Group in terms of anti-PT titers.
    Comparison groups
    Boostrix+Cervarix Group v Nimenrix+Cervarix+Boostrix Group
    Number of subjects included in analysis
    503
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [21]
    Method
    ANCOVA
    Parameter type
    Adjusted GMT Ratio
    Point estimate
    1.39
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    1.2
         upper limit
    1.61
    Notes
    [21] - For anti-PT the UL of the 2-sided standardised asymptotic 95% CI for the adjusted group ratio of GMCs (Nimenrix+Cervarix+Boostrix Group/Boostrix+Cervarix Group) had to be less than or equal to the pre-defined limit of 1.5.

    Secondary: Number of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titres ≥ 1:8 and ≥ 1:128

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    End point title
    Number of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titres ≥ 1:8 and ≥ 1:128 [22]
    End point description
    The number of subjects with rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY antibody titers ≥ 1:8 and ≥ 1:128 prior to and one month after vaccination with Nimenrix vaccine.
    End point type
    Secondary
    End point timeframe
    Prior to and one month after vaccination with Nimenrix (Months 0 and 1)
    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 analysis was performed only on the groups receiving Nimenrix vaccine.
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Nimenrix+Cervarix+Boostrix Group
    Number of subjects analysed
    256
    255
    257
    Units: Participants
        rSBA-MenA ≥1:8, Month 0 (N=256;255;255)
    112
    118
    129
        rSBA-MenC ≥1:8, Month 0 (N=255;255;255)
    34
    29
    40
        rSBA-MenW-135 ≥1:8, Month 0 (N=256;255;256)
    23
    24
    22
        rSBA-MenY ≥1:8, Month 0 (N=255;255;256)
    86
    102
    80
        rSBA-MenA ≥1:128, Month 0 (N=256;255;255)
    78
    86
    82
        rSBA-MenC ≥1:128, Month 0 (N=255;255;255)
    20
    10
    23
        rSBA-MenW-135 ≥1:128, Month 0 (N=256;255;256)
    22
    23
    20
        rSBA-MenY ≥1:128, Month 0 (N=255;255;256)
    84
    99
    74
        rSBA-MenA ≥1:8, Month 1 (N=256;255;257)
    255
    255
    255
        rSBA-MenC ≥1:8, Month 1 (N=256;255;257)
    254
    253
    253
        rSBA-MenW-135 ≥1:8, Month 1 (N=256;255;257)
    253
    255
    250
        rSBA-MenY ≥1:8, Month 1 (N=256;255;257)
    256
    255
    255
        rSBA-MenA ≥1:128, Month 1 (N=256;255;257)
    255
    255
    255
        rSBA-MenC ≥1:128, Month 1 (N=256;255;257)
    254
    252
    252
        rSBA-MenW-135 ≥1:128, Month 1 (N=256;255;257)
    253
    255
    250
        rSBA-MenY ≥1:128, Month 1 (N=256;255;257)
    256
    255
    255
    No statistical analyses for this end point

    Secondary: rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY vaccine response

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    End point title
    rSBA-MenA, rSBA-MenC, rSBA-MenW-135 and rSBA-MenY vaccine response [23]
    End point description
    rSBA vaccine response for serogroups A, C, W-135 and Y was defined as: • For initially seronegative subjects (pre-vaccination titre below the cut-off of 1:8): number of subjects with rSBA antibody titres ≥ 1:32 one month after vaccination. • For initially seropositive subjects (pre-vaccination titre ≥ 1:8): number of subjects with rSBA antibody titres at least four times the pre-vaccination antibody titres, one month after vaccination.
    End point type
    Secondary
    End point timeframe
    At one month after Nimenrix vaccination (Month 1)
    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 analysis was performed only on the groups receiving Nimenrix vaccine.
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Nimenrix+Cervarix+Boostrix Group
    Number of subjects analysed
    256
    255
    256
    Units: Participants
        rSBA-MenA, (N=256;255;255)
    240
    235
    230
        rSBA-MenC, (N=255;255;255)
    250
    251
    246
        rSBA-MenW-135, (N=256;255;256)
    252
    255
    248
        rSBA-MenY, (N=255;255;256)
    245
    253
    251
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-T antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL

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    End point title
    Number of subjects with anti-T antibody concentrations ≥ 0.1 IU/mL and ≥ 1.0 IU/mL [24]
    End point description
    The antibody concentrations were tabulated as GMCs and expressed as IU/mL, only for the Nimenrix+Cervarix (1,2,7-Month) Group.
    End point type
    Secondary
    End point timeframe
    Prior to and one month after vaccination with Nimenrix (Months 0 and 1)
    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 analysis was performed only on the groups receiving Boostrix vaccine.
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group
    Number of subjects analysed
    255
    Units: Participants
        Anti-T ≥ 0.1 IU/mL, Month 0
    236
        Anti-T ≥ 0.1 IU/mL, Month 1
    255
        Anti-T ≥ 1 IU/mL, Month 0
    151
        Anti-T ≥ 1 IU/mL, Month 1
    253
    No statistical analyses for this end point

    Secondary: Anti-T antibody concentrations

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    End point title
    Anti-T antibody concentrations [25]
    End point description
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL). This analysis was only performed for the Nimenrix+Cervarix (1,2,7-Month) Group.
    End point type
    Secondary
    End point timeframe
    Prior to and one month after vaccination with Nimenrix (Months 0 and 1)
    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 analysis was performed only on the Nimenrix+Cervarix (1,2,7-Month) Group.
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group
    Number of subjects analysed
    255
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-T, Month 0
    1.2 (1.0 to 1.4)
        Anti-T, Month 1
    25.4 (22.8 to 28.3)
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-HPV-16 concentrations ≥ 19 EU/mL and anti-HPV-18 concentrations ≥ 18 EU/mL

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    End point title
    Number of subjects with anti-HPV-16 concentrations ≥ 19 EU/mL and anti-HPV-18 concentrations ≥ 18 EU/mL [26]
    End point description
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as ELISA units per milliliter (EU/mL).
    End point type
    Secondary
    End point timeframe
    Prior to the first dose and one month after the third dose of Cervarix [Month 0 and Month 7/Month 8 in Nimenrix+Cervarix (1,2,7-Month) Group]
    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 analysis was performed only on the groups receiving Cervarix vaccine.
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Boostrix+Cervarix Group
    Number of subjects analysed
    246
    248
    249
    247
    Units: Participants
        Anti-HPV-16, Month 0
    17
    29
    32
    22
        Anti-HPV-16, Month 7/Month 8
    245
    248
    249
    247
        Anti-HPV-18, Month 0
    11
    12
    17
    14
        Anti-HPV-18, Month 7/Month 8
    245
    248
    249
    247
    No statistical analyses for this end point

    Secondary: Number of subjects seroconverted for anti-HPV-16 and anti-HPV-18 antibodies

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    End point title
    Number of subjects seroconverted for anti-HPV-16 and anti-HPV-18 antibodies
    End point description
    Seroconversion rate is defined as the appearance of antibodies (i.e. titers greater than or equal to the cut-off value) in the serum of subjects who are seronegative before vaccination. The antibody concentrations were calculated as GMCs and expressed as EU/mL.
    End point type
    Secondary
    End point timeframe
    Prior to and one month after the third dose of Cervarix (Month 0 and Month 7/Month 8)
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    235
    236
    232
    230
    233
    Units: Participants
        Anti-HPV-16, Month 0, (N=229;219;217;215;225)
    0
    0
    0
    0
    0
        Anti-HPV-16, Month 7/8, (N=229;219;217;215;225)
    228
    219
    217
    215
    225
        Anti-HPV-18, Month 0, (N=235;236;232;230;233)
    0
    0
    0
    0
    0
        Anti-HPV-18, Month 7/8. (N=235;236;232;230;233)
    234
    236
    232
    230
    233
    No statistical analyses for this end point

    Secondary: Anti-HPV-16 and anti-HPV-18 concentrations

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    End point title
    Anti-HPV-16 and anti-HPV-18 concentrations [27]
    End point description
    The antibody concentrations were calculated as GMCs and expressed as EU/mL, only for the Nimenrix+Cervarix (1,2,7-Month) Group.
    End point type
    Secondary
    End point timeframe
    Prior to and one month after the third dose of Cervarix (Months 0 and 8)
    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 analysis was performed only on the Nimenrix+Cervarix (1,2,7-Month) Group.
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group
    Number of subjects analysed
    246
    Units: EU/mL
    geometric mean (confidence interval 95%)
        Anti-HPV-16, Month 0
    10.9 (10.2 to 11.6)
        Anti-HPV-16, Month 8
    11128.2 (9471.8 to 13074.4)
        Anti-HPV-18, Month 0
    9.8 (9.3 to 10.4)
        Anti-HPV-18, Month 8
    5357.0 (4550.2 to 6306.9)
    No statistical analyses for this end point

    Secondary: Booster responses for anti-PT, anti-FHA and anti-PRN antibodies

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    End point title
    Booster responses for anti-PT, anti-FHA and anti-PRN antibodies [28]
    End point description
    Booster responses to the PT, FHA and PRN antigens were defined as: -For initially seronegative subjects (antibody concentrations: < 2.046 IU/ml for anti-FHA, < 2.187 IU/ml for anti-PRN, < 2.693 IU/ml for anti-PT), antibody concentration ≥ 4*cut_off IU/ml at Month 1 post-vaccination; -For initially seropositive subjects (antibody concentrations: ≥ 2.046 IU/ml for anti-FHA, ≥ 2.187 IU/ml for anti-PRN, ≥ 2.693 IU/ml for anti-PT) with pre-vaccination antibody concentration < 4*cut_off IU/ml : antibody concentration at Month 1 ≥ 4 fold the pre-vaccination antibody concentration; -For initially seropositive subjects (antibody concentrations: ≥ 2.046 IU/ml for anti-FHA, ≥ 2.187 IU/ml for anti-PRN, ≥ 2.693 IU/ml for anti-PT) with pre-vaccination antibody concentration ≥ 4*cut_off IU/ml : antibody concentration at Month 1 ≥ 2 fold the pre-vaccination antibody concentration.
    End point type
    Secondary
    End point timeframe
    At one month after Boostrix vaccination (Month 1)
    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 analysis was performed only on the groups receiving Boostrix vaccine.
    End point values
    Boostrix+Cervarix Group
    Number of subjects analysed
    256
    Units: Participants
        Anti-PT, (N=245;254)
    235
        Anti-FHA, (N=247;256)
    247
        Anti-PRN, (N=246;256)
    248
    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 [29]
    End point description
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL).
    End point type
    Secondary
    End point timeframe
    Prior to and one month after Boostrix vaccination (Month 0 and Month 1)
    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 analysis was performed only on the groups receiving Boostrix vaccine.
    End point values
    Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    251
    256
    Units: Participants
        Anti-D, Month 0, (N=249;254)
    214
    223
        Anti-D, Month 1, (N=250;256)
    250
    256
        Anti-T, Month 0, (N=251;256)
    239
    248
        Anti-T, Month 1, (N=250;256)
    250
    256
    No statistical analyses for this end point

    Secondary: Anti-D and anti-T antibody concentrations

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    End point title
    Anti-D and anti-T antibody concentrations [30]
    End point description
    The antibody concentrations were calculated as geometric mean concentrations (GMCs) and expressed as international units per milliliter (IU/mL).
    End point type
    Secondary
    End point timeframe
    Prior to and one month after Boostrix vaccination (Months 0 and 1)
    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 analysis was performed only on the groups receiving Boostrix vaccine.
    End point values
    Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    251
    256
    Units: IU/mL
    geometric mean (confidence interval 95%)
        Anti-D, Month 0, (N=249;254)
    0.5 (0.4 to 0.5)
    0.5 (0.4 to 0.6)
        Anti-D, Month 1, (N=250;256)
    4.7 (4.2 to 5.2)
    6.6 (5.9 to 7.4)
        Anti-T, Month 0, (N=251;256)
    1.3 (1.1 to 1.5)
    1.3 (1.1 to 1.5)
        Anti-T, Month 1, (N=250;256)
    25.9 (23.4 to 28.8)
    15.4 (14.1 to 16.9)
    No statistical analyses for this end point

    Secondary: Number of subjects with anti-PT, anti-FHA and anti-PRN antibody concentrations equal to or above the cut-off value

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    End point title
    Number of subjects with anti-PT, anti-FHA and anti-PRN antibody concentrations equal to or above the cut-off value [31]
    End point description
    The antibody concentrations were calculated as GMCs and expressed as IU/mL. Anti-PT assay cut-off=2.693 IU/mL, anti-FHA assay cut-off=2.046 IU/mL, anti-PRN assay cut-off=2.187 IU/mL.
    End point type
    Secondary
    End point timeframe
    Prior to and one month after Boostrix vaccination (Months 0 and 1)
    Notes
    [31] - 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 analysis was performed only on the groups receiving Boostrix vaccine.
    End point values
    Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    251
    256
    Units: Participants
        Anti-PT, Month 0, (N=249;254)
    156
    153
        Anti-PT, Month 1, (N=245;254)
    240
    252
        Anti-FHA, Month 0, (N=251;256)
    235
    244
        Anti-FHA, Month 1, (N=247;256)
    247
    256
        Anti-PRN, Month 0, (N=250;256)
    218
    229
        Anti-PRN, Month 1, (N=246;256)
    246
    256
    No statistical analyses for this end point

    Secondary: Number of subjects reporting solicited local symptoms

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    End point title
    Number of subjects reporting 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 (Gr. 3) pain = significant pain at rest, pain that prevented normal every day activities. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site. Symptoms were presented by vaccination site. Some groups do not have results for “Dose 2” because solicited local symptoms were not collected for these subjects at the Dose 2 timepoint.
    End point type
    Secondary
    End point timeframe
    During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    259
    259
    261
    260
    261
    Units: Participants
        Any Pain (Nimenrix), Dose 1, (N=259;257;0;260;0)
    152
    140
    0
    156
    0
        Gr.3 Pain (Nimenrix),Dose 1, (N=259;257;0;260;0)
    4
    3
    0
    7
    0
        Any Pain (Boostrix), Dose 1, (N=0;0;0;260;261)
    0
    0
    0
    189
    200
        Gr. 3 Pain (Boostrix), Dose 1, (N=0;0;0;260;261)
    0
    0
    0
    21
    15
        Any Pain (Cervarix), Dose 1, (N=0;257;259;260;261)
    0
    213
    205
    217
    221
        Gr.3 Pain (Cervarix), Dose 1,(N=0;257;259;260;261)
    0
    8
    11
    23
    18
        Any Redness (Nimenrix), Dose 1,(N=259;257;0;260;0)
    57
    42
    0
    54
    0
        Gr.3 Redness (Nimenrix),Dose 1,(N=259;257;0;260;0)
    4
    2
    0
    0
    0
        Any Redness (Boostrix), Dose 1, (N=0;0;0;260;261)
    0
    0
    0
    73
    53
        Gr. 3 Redness (Boostrix),Dose 1, (N=0;0;0;260;261)
    0
    0
    0
    2
    4
        Any Redness(Cervarix),Dose 1,(N=0;257;259;260;261)
    0
    56
    54
    62
    48
        Gr.3 Redness(Cervarix),Dose1,(N=0;257;259;260;261)
    0
    0
    0
    1
    0
        Any Swelling (Nimenrix),Dose 1,(N=259;257;0;260;0)
    40
    34
    0
    58
    0
        Gr.3 Swelling(Nimenrix),Dose 1,(N=259;257;0;260;0)
    1
    1
    0
    5
    0
        Any Swelling (Boostrix), Dose 1, (N=0;0;0;260;261)
    0
    0
    0
    79
    58
        Gr.3 Swelling (Boostrix),Dose 1,(N=0;0;0;260;261)
    0
    0
    0
    5
    7
        Any Swelling (Cerv.),Dose 1,(N=0;257;259;260;261)
    0
    42
    37
    64
    55
        Gr.3 Swelling (Cerv.),Dose 1,(N=0;257;259;260;261)
    0
    1
    1
    1
    5
        Any Pain (Cervarix), Dose 2, (N=258;0;0;0;0)
    193
    0
    0
    0
    0
        Gr. 3 Pain (Cervarix), Dose 2, (N=258;0;0;0;0)
    15
    0
    0
    0
    0
        Any Redness (Cervarix), Dose 2, (N=258;0;0;0;0)
    43
    0
    0
    0
    0
        Gr. 3 Redness (Cervarix), Dose 2,(N=258;0;0;0;0)
    0
    0
    0
    0
    0
        Any Swelling (Cervarix), Dose 2, (N=258;0;0;0;0)
    41
    0
    0
    0
    0
        Gr. 3 Swelling (Cervarix), Dose 2, (N=258;0;0;0;0)
    1
    0
    0
    0
    0
        Any Pain (Nimenrix), Across, (N=259;257;0;260;0)
    152
    140
    0
    156
    0
        Gr. 3 Pain (Nimenrix), Across, (N=259;257;0;260;0)
    4
    3
    0
    7
    0
        Any Pain (Boostrix), Across, (N=0;0;0;260;261)
    0
    0
    0
    189
    200
        Gr. 3 Pain (Boostrix), Across, (N=0;0;0;260;261)
    0
    0
    0
    21
    15
        Any Pain (Cervarix),Across,(N=258;257;259;260;261)
    193
    213
    205
    217
    221
        Gr.3 Pain (Cervarix),Across,(N=258;257;259;260;261
    15
    8
    11
    23
    18
        Any Redness (Nimenrix), Across,(N=259;257;0;260;0)
    57
    42
    0
    54
    0
        Gr.3 Redness (Nimenrix),Across,(N=259;257;0;260;0)
    4
    2
    0
    0
    0
        Any Redness (Boostrix), Across, (N=0;0;0;260;261)
    0
    0
    0
    73
    53
        Gr. 3 Redness (Boostrix), Across,(N=0;0;0;260;261)
    0
    0
    0
    2
    4
        Any Redness(Cerv.),Across,(N=258;257;259;260;261)
    43
    56
    54
    62
    48
        Gr.3 Redness(Cerv.),Across,(N=258;257;259;260;261)
    0
    0
    0
    1
    0
        Any Swelling (Nimenrix),Across,(N=259;257;0;260;0)
    40
    34
    0
    58
    0
        Gr.3 Swelling(Nimenrix),Across,(N=259;257;0;260;0)
    1
    1
    0
    5
    0
        Any Swelling (Boostrix), Across, (N=0;0;0;260;261)
    0
    0
    0
    79
    58
        Gr.3 Swelling (Boostrix),Across,(N=0;0;0;260;261)
    0
    0
    0
    5
    7
        Any Swelling(Cerv.),Across,(N=258;257;259;260;261)
    41
    42
    37
    64
    55
        Gr.3 Swelling(Cerv.),Across,(N=258;257;259;260;261
    1
    1
    1
    1
    5
    No statistical analyses for this end point

    Secondary: Number of subjects reporting solicited general symptoms

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    End point title
    Number of subjects reporting solicited general symptoms
    End point description
    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms (gastro.), headache, myalgia, rash, fever [defined as axillary temperature equal to or above 37.5 degrees Celsius (°C)] and urticaria. Any = occurrence of the symptom regardless of intensity grade. Grade 3 symptom (Gr. 3) = symptom that prevented normal activity. Grade 3 fever = fever > 39.5 °C. Related = symptom assessed by the investigator as related to the vaccination. Some groups do not have results for “Dose 2” because solicited local symptoms were not collected for these subjects at the Dose 2 timepoint.
    End point type
    Secondary
    End point timeframe
    During the 7-day (Days 0-6) post-vaccination period following each dose and across doses
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    259
    257
    259
    260
    261
    Units: Participants
        Any Arthralgia, Dose 1, (N=259;257;259;260;261)
    23
    18
    13
    36
    23
        Grade 3 Arthralgia, Dose 1,(N=259;257;259;260;261)
    0
    1
    1
    1
    4
        Related Arthralgia, Dose 1,(N=259;257;259;260;261)
    23
    18
    13
    34
    23
        Any Fatigue, Dose 1, (N=259;257;259;260;261)
    87
    95
    85
    110
    101
        Grade 3 Fatigue, Dose 1, (N=259;257;259;260;261)
    2
    4
    2
    8
    5
        Related Fatigue, Dose 1, (N=259;257;259;260;261)
    82
    92
    79
    103
    99
        Any Gastro., Dose 1, (N=259;257;259;260;261)
    21
    27
    23
    29
    22
        Grade 3 Gastro., Dose 1, (N=259;257;259;260;261)
    1
    1
    0
    2
    0
        Related Gastro., Dose 1, (N=259;257;259;260;261)
    19
    27
    21
    26
    20
        Any Headache, Dose 1, (N=259;257;259;260;261)
    82
    94
    78
    99
    95
        Grade 3 Headache, Dose 1, (N=259;257;259;260;261)
    5
    3
    5
    5
    4
        Related Headache, Dose 1, (N=259;257;259;260;261)
    81
    89
    73
    92
    85
        Any Myalgia, Dose 1, (N=259;257;259;260;261)
    65
    83
    85
    96
    101
        Grade 3 Myalgia, Dose 1, (N=259;257;259;260;261)
    0
    4
    6
    9
    9
        Related Myalgia, Dose 1, (N=259;257;259;260;261)
    60
    81
    82
    92
    100
        Any Rash, Dose 1, (N=259;257;259;260;261)
    4
    8
    8
    6
    6
        Grade 3 Rash, Dose 1, (N=259;257;259;260;261)
    0
    0
    0
    0
    0
        Related Rash, Dose 1, (N=259;257;259;260;261)
    1
    6
    7
    6
    4
        Any Fever, Dose 1, (N=259;257;259;260;261)
    24
    32
    15
    38
    27
        Grade 3 Fever, Dose 1, (N=259;257;259;260;261)
    0
    0
    0
    0
    0
        Related Fever, Dose 1, (N=259;257;259;260;261)
    21
    31
    14
    37
    25
        Any Urticaria, Dose 1, (N=259;257;259;260;261)
    0
    4
    4
    5
    5
        Grade 3 Urticaria, Dose 1, (N=259;257;259;260;261)
    0
    0
    0
    0
    0
        Related Urticaria, Dose 1, (N=259;257;259;260;261)
    0
    3
    4
    5
    3
        Any Arthralgia, Dose 2, (N=258;0;0;0;0)
    18
    0
    0
    0
    0
        Grade 3 Arthralgia, Dose 2, (N=258;0;0;0;0)
    0
    0
    0
    0
    0
        Related Arthralgia, Dose 2, (N=258;0;0;0;0)
    18
    0
    0
    0
    0
        Any Fatigue, Dose 2, (N=258;0;0;0;0)
    61
    0
    0
    0
    0
        Grade 3 Fatigue, Dose 2, (N=258;0;0;0;0)
    2
    0
    0
    0
    0
        Related Fatigue, Dose 2, (N=258;0;0;0;0)
    58
    0
    0
    0
    0
        Any Gastro., Dose 2, (N=258;0;0;0;0)
    10
    0
    0
    0
    0
        Grade 3 Gastro., Dose 2, (N=258;0;0;0;0)
    1
    0
    0
    0
    0
        Related Gastro., Dose 2, (N=258;0;0;0;0)
    8
    0
    0
    0
    0
        Any Headache, Dose 2, (N=258;0;0;0;0)
    58
    0
    0
    0
    0
        Grade 3 Headache, Dose 2, (N=258;0;0;0;0)
    3
    0
    0
    0
    0
        Related Headache, Dose 2, (N=258;0;0;0;0)
    55
    0
    0
    0
    0
        Any Myalgia, Dose 2, (N=258;0;0;0;0)
    73
    0
    0
    0
    0
        Grade 3 Myalgia, Dose 2, (N=258;0;0;0;0)
    4
    0
    0
    0
    0
        Related Myalgia, Dose 2, (N=258;0;0;0;0)
    72
    0
    0
    0
    0
        Any Rash, Dose 2, (N=258;0;0;0;0)
    3
    0
    0
    0
    0
        Grade 3 Rash, Dose 2, (N=258;0;0;0;0)
    0
    0
    0
    0
    0
        Related Rash, Dose 2, (N=258;0;0;0;0)
    3
    0
    0
    0
    0
        Any Fever, Dose 2, (N=258;0;0;0;0)
    11
    0
    0
    0
    0
        Grade 3 Fever, Dose 2, (N=258;0;0;0;0)
    0
    0
    0
    0
    0
        Related Fever, Dose 2, (N=258;0;0;0;0)
    10
    0
    0
    0
    0
        Any Urticaria, Dose 2, (N=258;0;0;0;0)
    2
    0
    0
    0
    0
        Grade 3 Urticaria, Dose 2, (N=258;0;0;0;0)
    0
    0
    0
    0
    0
        Related Urticaria, Dose 2, (N=258;0;0;0;0)
    2
    0
    0
    0
    0
        Any Arthralgia, Across, (N=259;257;259;260;261)
    34
    18
    13
    36
    23
        Grade 3 Arthralgia, Across,(N=259;257;259;260;261)
    0
    1
    1
    1
    4
        Related Arthralgia, Across,(N=259;257;259;260;261)
    34
    18
    13
    34
    23
        Any Fatigue, Across, (N=259;257;259;260;261)
    105
    95
    85
    110
    101
        Grade 3 Fatigue, Across, (N=259;257;259;260;261)
    4
    4
    2
    8
    5
        Related Fatigue, Across, (N=259;257;259;260;261)
    98
    92
    79
    103
    99
        Any Gastro., Across, (N=259;257;259;260;261)
    26
    27
    23
    29
    22
        Grade 3 Gastro., Across, (N=259;257;259;260;261)
    2
    1
    0
    2
    0
        Related Gastro., Across, (N=259;257;259;260;261)
    23
    27
    21
    26
    20
        Any Headache, Across, (N=259;257;259;260;261)
    101
    94
    78
    99
    95
        Grade 3 Headache, Across, (N=259;257;259;260;261)
    8
    3
    5
    5
    4
        Related Headache, Across, (N=259;257;259;260;261)
    99
    89
    73
    92
    85
        Any Myalgia, Across, (N=259;257;259;260;261)
    95
    83
    85
    96
    101
        Grade 3 Myalgia, Across, (N=259;257;259;260;261)
    4
    4
    6
    9
    9
        Related Myalgia, Across, (N=259;257;259;260;261)
    91
    81
    82
    92
    100
        Any Rash, Across, (N=259;257;259;260;261)
    7
    8
    8
    6
    6
        Grade 3 Rash, Across, (N=259;257;259;260;261)
    0
    0
    0
    0
    0
        Related Rash, Across, (N=259;257;259;260;261)
    4
    6
    7
    6
    4
        Any Fever, Across, (N=259;257;259;260;261)
    34
    32
    15
    38
    27
        Grade 3 Fever, Across, (N=259;257;259;260;261)
    0
    0
    0
    0
    0
        Related Fever, Across, (N=259;257;259;260;261)
    30
    31
    14
    37
    25
        Any Urticaria, Across, (N=259;257;259;260;261)
    2
    4
    4
    5
    5
        Grade 3 Urticaria, Across, (N=259;257;259;260;261)
    0
    0
    0
    0
    0
        Related Urticaria, Across, (N=259;257;259;260;261)
    2
    3
    4
    5
    3
    No statistical analyses for this end point

    Secondary: Number of subjects with unsolicited adverse events AE(s)

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    End point title
    Number of subjects with unsolicited adverse events AE(s)
    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. Grade 3 AE = an AE which prevented normal, everyday activities. Related = AE assessed by the investigator as related to the vaccination.
    End point type
    Secondary
    End point timeframe
    During the 31-day (Days 0-30) period following vaccination with Nimenrix, Boostrix or the first dose of Cervarix
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    259
    259
    261
    260
    261
    Units: Participants
        Participants
    37
    35
    35
    42
    39
    No statistical analyses for this end point

    Secondary: Number of subjects with serious adverse events SAE(s)

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    End point title
    Number of subjects with serious adverse events SAE(s)
    End point description
    SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Month 0 to Month 8)
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    259
    259
    261
    260
    261
    Units: Participants
        Participants
    3
    2
    5
    7
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with potential immune-mediated diseases (pIMDs)

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    End point title
    Number of subjects with potential immune-mediated diseases (pIMDs)
    End point description
    pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Month 0 to Month 8)
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    259
    259
    261
    260
    261
    Units: Participants
        Participants
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects with new onset chronic illnesses (NOCIs)

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    End point title
    Number of subjects with new onset chronic illnesses (NOCIs)
    End point description
    NOCIs include autoimmune disorders, asthma, type I diabetes, allergies.
    End point type
    Secondary
    End point timeframe
    During the entire study period (from Month 0 to Month 8)
    End point values
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Number of subjects analysed
    259
    259
    261
    260
    261
    Units: Participants
        Participants
    3
    0
    1
    0
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited local and general symptoms: during the 7-day (Days 0-6) period following each vaccination, Unsolicited AEs: during the 31-day (Days 0-30) period following each vaccination; SAEs: throughout the whole study period (from Month 0 up to Month 8).
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    17.0
    Reporting groups
    Reporting group title
    Nimenrix+Cervarix (1,2,7-Month) Group
    Reporting group description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 1, Month 2 and Month 7. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Nimenrix+Cervarix (0,1,6-Month) Group
    Reporting group description
    Subjects in this group received 1 dose of Nimenrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Cervarix Group
    Reporting group description
    Subjects in this group received 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6, administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Nimenrix+Cervarix+Boostrix Group
    Reporting group description
    Subjects in this group received 1 dose each of Nimenrix and Boostrix vaccines at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. All vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Reporting group title
    Boostrix+Cervarix Group
    Reporting group description
    Subjects in this group received 1 dose of Boostrix vaccine at Month 0 and 3 doses of Cervarix vaccine at Month 0, Month 1 and Month 6. Both vaccines were administered intramuscularly (IM) in the deltoid region of the arm.

    Serious adverse events
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 259 (1.16%)
    2 / 259 (0.77%)
    5 / 261 (1.92%)
    7 / 260 (2.69%)
    6 / 261 (2.30%)
         number of deaths (all causes)
    0
    0
    0
    0
    1
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    Injury, poisoning and procedural complications
    Stab wound
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    1 / 261 (0.38%)
         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
    Congenital, familial and genetic disorders
    Atrial septal defect
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    1 / 260 (0.38%)
    0 / 261 (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
    Respiratory, thoracic and mediastinal disorders
    Neonatal respiratory distress syndrome
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    1 / 261 (0.38%)
         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 / 1
    Nervous system disorders
    Migraine
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    1 / 261 (0.38%)
         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
    Pregnancy, puerperium and perinatal conditions
    Premature baby
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    1 / 261 (0.38%)
         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 / 1
    Abortion incomplete
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    1 / 260 (0.38%)
    0 / 261 (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
    Abortion spontaneous
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    1 / 261 (0.38%)
    0 / 260 (0.00%)
    0 / 261 (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
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    1 / 261 (0.38%)
         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
    Pelvic pain
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    1 / 261 (0.38%)
         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
    Skin and subcutaneous tissue disorders
    Dermatitis atopic
         subjects affected / exposed
    1 / 259 (0.39%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    0 / 261 (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
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    1 / 260 (0.38%)
    0 / 261 (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
    Metabolism and nutrition disorders
    Underweight
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    1 / 261 (0.38%)
         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 / 1
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    2 / 259 (0.77%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    1 / 260 (0.38%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
    2 / 261 (0.77%)
    2 / 260 (0.77%)
    0 / 261 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    0 / 261 (0.00%)
    1 / 260 (0.38%)
    1 / 261 (0.38%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    1 / 261 (0.38%)
    0 / 260 (0.00%)
    0 / 261 (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
    Pelvic inflammatory disease
         subjects affected / exposed
    0 / 259 (0.00%)
    0 / 259 (0.00%)
    1 / 261 (0.38%)
    0 / 260 (0.00%)
    0 / 261 (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
    Pharyngitis
         subjects affected / exposed
    0 / 259 (0.00%)
    1 / 259 (0.39%)
    0 / 261 (0.00%)
    0 / 260 (0.00%)
    0 / 261 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Nimenrix+Cervarix (1,2,7-Month) Group Nimenrix+Cervarix (0,1,6-Month) Group Cervarix Group Nimenrix+Cervarix+Boostrix Group Boostrix+Cervarix Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    232 / 259 (89.58%)
    228 / 259 (88.03%)
    222 / 261 (85.06%)
    236 / 260 (90.77%)
    243 / 261 (93.10%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    103 / 259 (39.77%)
    98 / 259 (37.84%)
    78 / 261 (29.89%)
    102 / 260 (39.23%)
    98 / 261 (37.55%)
         occurrences all number
    147
    99
    78
    107
    101
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    105 / 259 (40.54%)
    95 / 259 (36.68%)
    85 / 261 (32.57%)
    110 / 260 (42.31%)
    101 / 261 (38.70%)
         occurrences all number
    148
    95
    85
    110
    101
    Pain
         subjects affected / exposed
    217 / 259 (83.78%)
    220 / 259 (84.94%)
    205 / 261 (78.54%)
    228 / 260 (87.69%)
    233 / 261 (89.27%)
         occurrences all number
    345
    220
    205
    228
    233
    Pyrexia
         subjects affected / exposed
    35 / 259 (13.51%)
    33 / 259 (12.74%)
    16 / 261 (6.13%)
    39 / 260 (15.00%)
    28 / 261 (10.73%)
         occurrences all number
    36
    34
    16
    39
    28
    Swelling
         subjects affected / exposed
    62 / 259 (23.94%)
    54 / 259 (20.85%)
    37 / 261 (14.18%)
    98 / 260 (37.69%)
    70 / 261 (26.82%)
         occurrences all number
    81
    54
    37
    98
    70
    Gastrointestinal disorders
    Gastrointestinal disorder
         subjects affected / exposed
    26 / 259 (10.04%)
    27 / 259 (10.42%)
    23 / 261 (8.81%)
    29 / 260 (11.15%)
    22 / 261 (8.43%)
         occurrences all number
    31
    27
    23
    29
    22
    Skin and subcutaneous tissue disorders
    Erythema
         subjects affected / exposed
    78 / 259 (30.12%)
    68 / 259 (26.25%)
    54 / 261 (20.69%)
    90 / 260 (34.62%)
    64 / 261 (24.52%)
         occurrences all number
    100
    68
    54
    90
    64
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    34 / 259 (13.13%)
    18 / 259 (6.95%)
    13 / 261 (4.98%)
    36 / 260 (13.85%)
    23 / 261 (8.81%)
         occurrences all number
    41
    18
    13
    36
    23
    Myalgia
         subjects affected / exposed
    95 / 259 (36.68%)
    83 / 259 (32.05%)
    85 / 261 (32.57%)
    96 / 260 (36.92%)
    101 / 261 (38.70%)
         occurrences all number
    139
    83
    85
    96
    101

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? No

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

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