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    Clinical Trial Results:
    A Phase IIIb open-label, randomised, multi-centre primary immunization study to evaluate the immunogenicity and safety of GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine when administered intramuscularly according to alternative 2-dose schedules in 9 - 14 year old healthy females compared to the standard 3-dose schedule for GSK Biologicals’ HPV-16/18 L1 VLP AS04 vaccine in 15 - 25 year old healthy females

    Summary
    EudraCT number
    2011-000757-22
    Trial protocol
    DE   IT  
    Global end of trial date
    13 Nov 2014

    Results information
    Results version number
    v3(current)
    This version publication date
    04 Jun 2020
    First version publication date
    28 May 2015
    Other versions
    v1 (removed from public view) , v2
    Version creation reason

    Trial information

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    Trial identification
    Sponsor protocol code
    114700
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT01381575
    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
    07 Aug 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Jun 2012
    Global end of trial reached?
    Yes
    Global end of trial date
    13 Nov 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To demonstrate that the immunogenicity (as determined by [enzyme-linked immunosorbent assay] ELISA) of GSK Biologicals' HPV-16/18 L1 VLP AS04 vaccine administered according to a 2-dose schedule of 0,6 months in 9-14-year old females is non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25-year old females,1 month after the last dose of study vaccine.
    Protection of trial subjects
    As with all injectable vaccines, appropriate medical treatment was always readily available in case of anaphylactic reactions following the administration of the vaccine. For this reason, the vaccinee remained under medical supervision for 30 minutes after vaccination.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    29 Jun 2011
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    24 Months
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Canada: 190
    Country: Number of subjects enrolled
    Taiwan: 318
    Country: Number of subjects enrolled
    Thailand: 314
    Country: Number of subjects enrolled
    Germany: 325
    Country: Number of subjects enrolled
    Italy: 300
    Worldwide total number of subjects
    1447
    EEA total number of subjects
    625
    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)
    476
    Adolescents (12-17 years)
    628
    Adults (18-64 years)
    343
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    This study was conducted by 33 principal investigators in five countries (Canada, Germany, Italy, Taiwan and Thailand).

    Pre-assignment
    Screening details
    All 1447 subjects enrolled in the study were vaccinated and included in the Total vaccinated cohort (TVC).

    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
    Cervarix 1 Group
    Arm description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK Biologicals' HPV vaccine 580299
    Investigational medicinal product code
    Other name
    Cervarix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 2 doses of HPV vaccine administered intramuscularly.

    Arm title
    Cervarix 2 Group
    Arm description
    Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Day 0, at Month 1 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.
    Arm type
    Active comparator

    Investigational medicinal product name
    GSK Biologicals' HPV vaccine 580299
    Investigational medicinal product code
    Other name
    Cervarix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 3 doses of HPV vaccine administered intramuscularly.

    Arm title
    Cervarix 3 Group
    Arm description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 12, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.
    Arm type
    Experimental

    Investigational medicinal product name
    GSK Biologicals' HPV vaccine 580299
    Investigational medicinal product code
    Other name
    Cervarix
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Subjects received 2 doses of HPV vaccine administered intramuscularly.

    Number of subjects in period 1
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Started
    550
    482
    415
    Completed
    524
    443
    395
    Not completed
    26
    39
    20
         Protocol deviation
    -
    1
    1
         Migrated/moved from study area
    2
    12
    2
         Non-Serious Adverse Event
    -
    -
    1
         Consent withdrawn by subject
    15
    9
    7
         Serious Adverse Event
    1
    -
    -
         Lost to follow-up
    8
    17
    9

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cervarix 1 Group
    Reporting group description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Reporting group title
    Cervarix 2 Group
    Reporting group description
    Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Day 0, at Month 1 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Reporting group title
    Cervarix 3 Group
    Reporting group description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 12, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Reporting group values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group Total
    Number of subjects
    550 482 415 1447
    Age categorical
    Units: Subjects
        In utero
    0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0 0
        Newborns (0-27 days)
    0 0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0 0
        Children (2-11 years)
    264 0 212 476
        Adolescents (12-17 years)
    286 139 203 628
        Adults (18-64 years)
    0 343 0 343
        From 65-84 years
    0 0 0 0
        85 years and over
    0 0 0 0
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    11.6 ± 1.59 19.6 ± 3.05 11.4 ± 1.55 -
    Sex: Female, Male
    Units: Subjects
        Female
    550 482 415 1447
        Male
    0 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        African Heritage / African American
    6 3 6 15
        Asian - Central/South Asian Heritage
    1 1 4 6
        Asian - East Asian Heritage
    141 105 74 320
        Asian - South East Asian Heritage
    108 106 104 318
        White - Arabic / North African Heritage
    1 0 1 2
        White - Caucasian / European Heritage
    288 263 223 774
        Mixed origin
    5 4 3 12

    End points

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    End points reporting groups
    Reporting group title
    Cervarix 1 Group
    Reporting group description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Reporting group title
    Cervarix 2 Group
    Reporting group description
    Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Day 0, at Month 1 and at Month 6, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Reporting group title
    Cervarix 3 Group
    Reporting group description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Day 0 and at Month 12, respectively. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Primary: Number of seroconverted subjects for Anti- Human Papilloma virus 16 (Anti-HPV-16) and Anti-Human Papilloma Virus 18 (Anti-HPV-18) antibodies in Cervarix 1 Group and Cervarix 2 Group at Month 7

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    End point title
    Number of seroconverted subjects for Anti- Human Papilloma virus 16 (Anti-HPV-16) and Anti-Human Papilloma Virus 18 (Anti-HPV-18) antibodies in Cervarix 1 Group and Cervarix 2 Group at Month 7 [1]
    End point description
    Seroconversion was defined as the appearance of antibodies (anti-HPV-16 concentrations greater than or equal to (≥) 8 enzyme-linked immunosorbent assay (ELISA) units per milliliter (EL.U/mL) and anti-HPV-18 concentrations ≥ 7 EL.U/mL) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with anti-HPV-16/18 antibody concentration lower than (<) 8/7 EL.U/mL, respectively.
    End point type
    Primary
    End point timeframe
    At Month 7 (i.e. one month after the last dose of study vaccine)
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    493
    382
    Units: Subjects
        Anti-HPV-16 (N=488, 352)
    488
    352
        Anti-HPV-18 (N=493, 382)
    493
    382
    Statistical analysis title
    Immune response to anti-HPV-16 in terms of SCR
    Statistical analysis description
    Immune response to anti-HPV-16 in terms of seroconversion (SCR) rates: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule of 0,6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.
    Comparison groups
    Cervarix 1 Group v Cervarix 2 Group
    Number of subjects included in analysis
    875
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [2]
    Method
    Parameter type
    Difference in SCR
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1.08
         upper limit
    0.78
    Notes
    [2] - Non-inferiority with respect to seroconversion was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of the 95% Confidence Interval (CI) for the difference (Cervarix 2 Group minus Cervarix 1 Group) was below 5%.
    Statistical analysis title
    Immune response to anti-HPV-18 in terms of SCR
    Statistical analysis description
    Immune response to anti-HPV-18 in terms of seroconversion (SCR) rates: To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule of 0,6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.
    Comparison groups
    Cervarix 1 Group v Cervarix 2 Group
    Number of subjects included in analysis
    875
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [3]
    Method
    Parameter type
    Difference in SCR
    Point estimate
    0
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    -1
         upper limit
    0.77
    Notes
    [3] - Non-inferiority with respect to seroconversion was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of the 95% Confidence Interval (CI) for the difference (Cervarix 2 Group minus Cervarix 1 Group) was below 5%.

    Primary: Anti-HPV-16 and anti-HPV-18 antibody concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7

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    End point title
    Anti-HPV-16 and anti-HPV-18 antibody concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Month 7 [4]
    End point description
    Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EL.U/mL.
    End point type
    Primary
    End point timeframe
    At Month 7 (i.e. one month after the last dose of study vaccine)
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    493
    382
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-HPV-16 (N=488, 352)
    9400.1 (8818.3 to 10020.4)
    10234.5 (9258.3 to 11313.6)
        Anti-HPV-18 (N=493, 382)
    5909.1 (5508.9 to 6338.4)
    5002.6 (4572.6 to 5473.1)
    Statistical analysis title
    Immune response to anti-HPV-16 in terms of GMCs
    Statistical analysis description
    Immune response to anti-HPV-16 in terms of Geometric Mean Concentrations (GMCs): To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.
    Comparison groups
    Cervarix 1 Group v Cervarix 2 Group
    Number of subjects included in analysis
    875
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [5]
    Method
    Parameter type
    Geometric mean ratio
    Point estimate
    1.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.97
         upper limit
    1.22
    Notes
    [5] - Non-inferiority with respect to Geometric Mean Concentrations (GMCs) was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of 95% CI for the GMT ratio (Cervarix 2 Group divided by Cervarix 1 Group) was below 2.
    Statistical analysis title
    Immune response to anti-HPV-18 in terms of GMCs
    Statistical analysis description
    Immune response to anti-HPV-18 in terms of Geometric Mean Concentrations (GMCs): To evaluate sequentially if the immunogenicity (as determined by ELISA) of Cervarix vaccine administered according to a 2-dose schedule at 0, 6 months in 9-14 year old females was non-inferior to that administered according to the standard 3-dose schedule of 0,1,6 months in 15-25 year old females, 1 month after the last dose of study vaccine, in initially seronegative subjects.
    Comparison groups
    Cervarix 1 Group v Cervarix 2 Group
    Number of subjects included in analysis
    875
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority [6]
    Method
    Parameter type
    Geometric mean ratio
    Point estimate
    0.85
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.76
         upper limit
    0.95
    Notes
    [6] - Non-inferiority with respect to Geometric Mean Concentrations (GMCs) was demonstrated if, 1 month after the last dose, for both anti-HPV-16 and anti-HPV-18, the upper limit of 95% CI for the GMT ratio (Cervarix 2 Group divided by Cervarix 1 Group) was below 2.

    Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

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    End point title
    Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36 [7]
    End point description
    Seroconversion was defined as the appearance of antibodies (anti-HPV-16 concentrations ≥ 8 EL.U/mL and anti-HPV-18 concentrations ≥ 7 EL.U/mL [applicable for Day 0, Month 7 and Month 12 time points] and anti-HPV-16 concentrations ≥ 19 EL.U/mL and anti-HPV-18 concentrations ≥ 18 EL.U/mL [applicable for Month 18, Month 24 and Month 36 timepoints]) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with an anti-HPV-16/18 antibody concentration below (<) the aforementioned cut-offs. Note: In order to increase the ELISA precision, the assay cut-off value was changed from 8 EL.U/mL to 19 EL.U/mL for HPV-16 and from 7 EL.U/mL to 18 EL.U/mL for HPV-18 from Month 18 onwards.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 7, 12, 18, 24 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    462
    356
    Units: Subjects
        Anti-HPV-16, Day 0 (N=455, 330)
    0
    0
        Anti-HPV-16, Month 7 (N=455, 330)
    455
    330
        Anti-HPV-16, Month 12 (N=455, 330)
    455
    330
        Anti-HPV-16, Month 18 (N=453, 329)
    453
    329
        Anti-HPV-16, Month 24 (N=454, 326)
    454
    326
        Anti-HPV-16, Month 36 (N=455, 330)
    455
    330
        Anti-HPV-18, Day 0 (N=462, 356)
    0
    0
        Anti-HPV-18, Month 7 (N=462, 356)
    462
    356
        Anti-HPV-18, Month 12 (N=462, 356)
    462
    356
        Anti-HPV-18, Month 18 (N=459, 355)
    458
    355
        Anti-HPV-18, Month 24 (N=460, 352)
    459
    352
        Anti-HPV-18, Month 36 (N=462, 356)
    461
    355
    No statistical analyses for this end point

    Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36

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    End point title
    Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 1 Group and Cervarix 2 Group at Day 0 and at Months 7, 12, 18, 24 and 36 [8]
    End point description
    Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EL.U/mL.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 7, 12, 18, 24 and 36
    Notes
    [8] - 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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    462
    356
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-HPV-16, Day 0 (N=455, 330)
    4.0 (4.0 to 4.0)
    4.0 (4.0 to 4.0)
        Anti-HPV-16, Month 7 (N=455, 330)
    9402.9 (8792.4 to 10055.8)
    10120.2 (9162.7 to 11177.9)
        Anti-HPV-16, Month 12 (N=455, 330)
    2653.5 (2473.5 to 2846.6)
    3290.4 (2956.5 to 3662.0)
        Anti-HPV-16, Month 18 (N=453, 329)
    1730.7 (1608.6 to 1862.0)
    1931.2 (1735.4 to 2149.1)
        Anti-HPV-16, Month 24 (N=454, 326)
    1483.8 (1382.1 to 1592.9)
    1575.9 (1418.2 to 1751.2)
        Anti-HPV-16, Month 36 (N=455, 330)
    1210.2 (1124.8 to 1302.1)
    1326.4 (1193.9 to 1473.5)
        Anti-HPV-18, Day 0 (N=462, 356)
    3.5 (3.5 to 3.5)
    3.5 (3.5 to 3.5)
        Anti-HPV-18, Month 7 (N=462, 356)
    5935.6 (5519.4 to 6383.3)
    4984.2 (4543.9 to 5467.1)
        Anti-HPV-18, Month 12 (N=462, 356)
    1523.6 (1403.7 to 1653.7)
    1491.5 (1339.0 to 1661.4)
        Anti-HPV-18, Month 18 (N=459, 355)
    864.6 (793.1 to 942.7)
    830.6 (742.9 to 928.5)
        Anti-HPV-18, Month 24 (N=460, 352)
    715.5 (658.1 to 777.9)
    654.3 (582.9 to 734.5)
        Anti-HPV-18, Month 36 (N=462, 356)
    562.8 (516.4 to 613.4)
    552.6 (494.1 to 618.0)
    No statistical analyses for this end point

    Secondary: Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group

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    End point title
    Number of Seroconverted Subjects for Anti-HPV-16 and Anti-HPV-18 Antibodies in Cervarix 3 Group [9]
    End point description
    Seroconversion was defined as the appearance of antibodies (anti-HPV-16 concentrations ≥ 8 EL.U/mL and anti-HPV-18 concentrations ≥ 7 EL.U/mL [applicable for Day 0 and Month 13 time points] and anti-HPV-16 concentrations ≥ 19 EL.U/mL and anti-HPV-18 concentrations ≥ 18 EL.U/mL [applicable for Month 18, Month 24 and Month 36 timepoints]) in the serum of subjects seronegative before vaccination. A seronegative subject was a subject with an anti-HPV-16/18 antibody concentration below (<) the aforementioned cut-offs. Note: In order to increase the ELISA precision, the assay cut-off value was changed from 8 EL.U/mL to 19 EL.U/mL for HPV-16 and from 7 EL.U/mL to 18 EL.U/mL for HPV-18 from Month 18 onwards.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 13, 18, 24 and 36
    Notes
    [9] - 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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 3 Group
    Number of subjects analysed
    355
    Units: Subjects
        Anti-HPV-16, Day 0 (N=339)
    0
        Anti-HPV-16, Month 13 (N=339)
    339
        Anti-HPV-16, Month 18 (N=339)
    339
        Anti-HPV-16, Month 24 (N=337)
    337
        Anti-HPV-16, Month 36 (N=339)
    339
        Anti-HPV-18, Day 0 (N=355)
    0
        Anti-HPV-18, Month 13 (N=355)
    355
        Anti-HPV-18, Month 18 (N=355)
    355
        Anti-HPV-18, Month 24 (N=353)
    353
        Anti-HPV-18, Month 36 (N=355)
    355
    No statistical analyses for this end point

    Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group

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    End point title
    Anti-HPV-16 and Anti-HPV-18 Antibody Concentrations (by ELISA) in Cervarix 3 Group [10]
    End point description
    Antibody concentrations were assessed by ELISA and expressed as geometric mean concentrations (GMCs) in EL.U/mL.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 13, 18, 24 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 3 Group
    Number of subjects analysed
    355
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-HPV-16, Day 0 (N=339)
    4.0 (4.0 to 4.0)
        Anti-HPV-16, Month 13 (N=339)
    11329.4 (10509.3 to 12213.5)
        Anti-HPV-16, Month 18 (N=339)
    3248.2 (2974.2 to 3547.4)
        Anti-HPV-16, Month 24 (N=337)
    2191.0 (2003.9 to 2395.5)
        Anti-HPV-16, Month 36 (N=339)
    1559.3 (1431.2 to 1699.0)
        Anti-HPV-18, Day 0 (N=355)
    3.5 (3.5 to 3.5)
        Anti-HPV-18, Month 13 (N=355)
    6580.0 (6075.8 to 7126.0)
        Anti-HPV-18, Month 18 (N=355)
    1860.3 (1699.4 to 2036.4)
        Anti-HPV-18, Month 24 (N=353)
    1174.7 (1067.1 to 1293.2)
        Anti-HPV-18, Month 36 (N=355)
    804.0 (731.8 to 883.4)
    No statistical analyses for this end point

    Secondary: Anti-HPV-16 and Anti-HPV-18 antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a subset of subjects from Cervarix 3 Group

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    End point title
    Anti-HPV-16 and Anti-HPV-18 antibody Titers [by Pseudovirion-Based Neutralisation Assay (PBNA)] in a subset of subjects from Cervarix 3 Group [11]
    End point description
    Antibody titers were expressed as geometric mean titers (GMTs). The cut-off of the assay was 40 ED50 for both anti-HPV-16 and anti-HPV-18. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 13, 18, 24 and 36
    Notes
    [11] - 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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 3 Group
    Number of subjects analysed
    88
    Units: Titers
    geometric mean (confidence interval 95%)
        Anti-HPV-16, Day 0 (N=88)
    20.0 (20.0 to 20.0)
        Anti-HPV-16, Month 13 (N=88)
    74848.0 (60521.9 to 92565.1)
        Anti-HPV-16, Month 18 (N=88)
    16576.6 (13127.4 to 20932.0)
        Anti-HPV-16, Month 24 (N=87)
    10003.7 (8114.1 to 12333.4)
        Anti-HPV-16, Month 36 (N=88)
    9214.3 (7112.3 to 11937.5)
        Anti-HPV-18, Day 0 (N=88)
    20.0 (20.0 to 20.0)
        Anti-HPV-18, Month 13 (N=88)
    39994.7 (33327.2 to 47996.1)
        Anti-HPV-18, Month 18 (N=88)
    9495.4 (7744.4 to 11642.2)
        Anti-HPV-18, Month 24 (N=87)
    5464.1 (4377.8 to 6819.8)
        Anti-HPV-18, Month 36 (N=88)
    4046.4 (3278.0 to 4994.8)
    No statistical analyses for this end point

    Secondary: Anti-HPV-16 and Anti-HPV-18 Antibody Titers (by PBNA) in a Subset of Subjects From Cervarix 1 Group and Cervarix 2 Group

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    End point title
    Anti-HPV-16 and Anti-HPV-18 Antibody Titers (by PBNA) in a Subset of Subjects From Cervarix 1 Group and Cervarix 2 Group [12]
    End point description
    Antibody titers were expressed as GMTs. The cut-off of the assay was 40 ED50 for both anti-HPV-16 and anti-HPV-18. The assay was performed on a subset of 100 subjects per study group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and Months 7, 12, 18, 24 and 36
    Notes
    [12] - 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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    96
    92
    Units: Titers
    geometric mean (confidence interval 95%)
        Anti-HPV-16, Day 0 (N=96, 92)
    21.3 (18.8 to 24.2)
    23.5 (20.7 to 26.6)
        Anti-HPV-16, Month 7 (N=96, 92)
    82975.9 (67377.4 to 102185.6)
    31407.6 (24181.5 to 40793.0)
        Anti-HPV-16, Month 12 (N=96, 92)
    14872.1 (12025.5 to 18392.4)
    15801.8 (12069.8 to 20687.8)
        Anti-HPV-16, Month 18 (N=95, 92)
    7393.6 (5986.6 to 9131.1)
    8246.4 (6224.6 to 10925.0)
        Anti-HPV-16, Month 24 (N=96, 92)
    6216.5 (5111.0 to 7561.1)
    7267.5 (5423.4 to 9738.6)
        Anti-HPV-16, Month 36 (N=96, 92)
    7762.7 (6218.6 to 9690.1)
    5063.7 (3800.4 to 6746.9)
        Anti-HPV-18, Day 0 (N=96, 92)
    21.0 (19.0 to 23.5)
    22.4 (20.4 to 24.5)
        Anti-HPV-18, Month 7 (N=96, 92)
    24833.1 (20777.0 to 29681.1)
    13935.6 (10991.0 to 17669.0)
        Anti-HPV-18, Month 12 (N=96, 92)
    5914.5 (4756.0 to 7355.4)
    5066.5 (3818.9 to 6721.7)
        Anti-HPV-18, Month 18 (N=95, 92)
    3961.2 (3153.8 to 4975.4)
    2958.2 (2213.9 to 3952.6)
        Anti-HPV-18, Month 24 (N=96, 92)
    2849.4 (2276.0 to 3567.2)
    2524.3 (1860.4 to 3425.2)
        Anti-HPV-18, Month 36 (N=95, 92)
    2416.4 (1905.9 to 3063.5)
    1956.2 (1488.5 to 2570.7)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T cell-mediated immune response (CMI) for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-16 specific T cell-mediated immune response (CMI) for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects [13]
    End point description
    The CMI response represents the measure of the cytokines production [i.e. interleukin-2 (IL-2), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and the cluster of differentiation 40 Ligand (CD40L)] by HPV-antigen specific T lymphocytes and measured by intracellular cytokine staining (ICS) assay for HPV-16. The frequency was presented as number of cytokine-positive cluster of differentiation (CD)4 i.e. CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles = T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and Months 7, 12, 24 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    84
    70
    Units: cells/million T cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-16, CD4 all doubles, S-, Day 0 (N=81, 68)
    88.0 (62.0 to 152.0)
    120.0 (67.0 to 185.5)
        Anti-HPV-16, CD4 all doubles, S-, Mth 7 (N=69, 50)
    3953.0 (1866.0 to 7025.0)
    3426.0 (1889.0 to 5214.0)
        Anti-HPV-16,CD4 all doubles, S-, Mth 12 (N=84, 70)
    2491.0 (1387.5 to 5543.5)
    2278.5 (1225.0 to 3363.0)
        Anti-HPV-16,CD4 all doubles, S-, Mth 24 (N=78, 67)
    2698.0 (1231.0 to 5147.0)
    2401 (1231.0 to 3641.0)
        Anti-HPV-16,CD4 all doubles, S-, Mth 36 (N=75, 57)
    1951.0 (1085.0 to 5130.0)
    2073.0 (1012.0 to 2836.0)
        Anti-HPV-16, CD4 all doubles, S+, Day 0 (N=8, 14)
    77.5 (57.0 to 192.0)
    100.0 (60.0 to 269.0)
        Anti-HPV-16, CD4 all doubles, S+, Mth 7 (N=8, 13)
    5019.5 (1353.0 to 7343.0)
    1820.0 (1311.0 to 3021.0)
        Anti-HPV-16, CD4 all doubles, S+, Mth 12 (N=9, 14)
    2603.0 (1003.0 to 3350.0)
    1423.5 (876.0 to 3747.0)
        Anti-HPV-16,CD4 all doubles, S+, Mth 24 (N=9, 12)
    2552.0 (1156.0 to 3963.0)
    1404.0 (1050.0 to 2856.5)
        Anti-HPV-16,CD4 all doubles, S+, Mth 36 (N=7, 12)
    2180.0 (1293.0 to 3383.0)
    1310.0 (939.0 to 2614.5)
        Anti-HPV-16, CD4-d-CD40L, S-, Day 0 (N=81, 68)
    70.0 (42.0 to 130.0)
    97.0 (49.0 to 144.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Month 7 (N=69, 50)
    3531.0 (1676.0 to 6528.0)
    3196.0 (1692.0 to 4771.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Month 12 (N=84, 70)
    2439.5 (1342.5 to 5376.0)
    2255.5 (1185.0 to 3290.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Month 24 (N=78, 67)
    2443.0 (1111.0 to 4922.0)
    2344.0 (1031.0 to 3323.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Month 36 (N=75, 57)
    1935.0 (1048.0 to 5061.0)
    2027.0 (978.0 to 2806.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Day 0 (N=8, 14)
    57.5 (39.5 to 162.0)
    72.5 (40.0 to 186.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Month 7 (N=8, 13)
    4979.5 (1290.5 to 7001.5)
    1655.0 (1050.0 to 2440.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Month 12 (N=9, 14)
    2587.0 (975.0 to 3305.0)
    1412.5 (832.0 to 3677.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Month 24 (N=9, 12)
    2456.0 (945.0 to 3931.0)
    1285.0 (962.5 to 1953.5)
        Anti-HPV-16, CD4-d-CD40L, S+, Month 36 (N=7, 12)
    2109.0 (1178.0 to 3343.0)
    1279.0 (928.0 to 2496.5)
        Anti-HPV-16, CD4-d-IFNγ, S-, Day 0 (N=81, 68)
    44.0 (19.0 to 67.0)
    39.5 (19.5 to 72.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Month 7 (N=69, 50)
    840.0 (503.0 to 1538.0)
    657.0 (474.0 to 1185.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Month 12 (N=84, 70)
    546.0 (176.5 to 1007.5)
    362.0 (202.0 to 644.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Month 24 (N=78, 67)
    644.5 (294.0 to 1318.0)
    449.0 (204.0 to 884.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Month 36 (N=75, 57)
    562.0 (273.0 to 1334.0)
    391.0 (215.0 to 824.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Day 0 (N=8, 14)
    38.5 (26.5 to 86.0)
    50.5 (31.0 to 75.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Month 7 (N=8, 13)
    881.5 (462.5 to 2704.0)
    489.0 (244.0 to 814.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Month 12 (N=9, 14)
    533.0 (336.0 to 827.0)
    329.0 (183.0 to 481.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Month 24 (N=9, 12)
    579.0 (398.0 to 897.0)
    310.5 (221.5 to 595.5)
        Anti-HPV-16, CD4-d-IFNγ, S+, Month 36 (N=7, 12)
    651.0 (520.0 to 998.0)
    564.0 (185.5 to 714.5)
        Anti-HPV-16, CD4-d-IL-2, S-, Day 0 (N=81, 68)
    59.0 (35.0 to 103.0)
    85.5 (43.5 to 143.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Month 7 (N=69, 50)
    3808.0 (1728.0 to 6787.0)
    3212.5 (1788.0 to 5010.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Month 12 (N=84, 70)
    2402.5 (1308.5 to 5242.0)
    2184.5 (1156.0 to 3238.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Month 24 (N=78, 67)
    2477.0 (1140.0 to 4680.0)
    2282.0 (1138.0 to 3392.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Month 36 (N=75, 57)
    1881.0 (958.0 to 4912.0)
    1922.0 (892.0 to 2708.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Day 0 (N=8, 14)
    68.0 (23.0 to 147.5)
    77.5 (39.0 to 229.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Month 7 (N=8, 13)
    4886.0 (1162.5 to 6906.0)
    1573.0 (1202.0 to 2924.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Month 12 (N=9, 14)
    2339.0 (877.0 to 3166.0)
    1372.0 (868.0 to 3692.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Month 24 (N=9, 12)
    2454.0 (1026.0 to 3931.0)
    1226.5 (969.0 to 2392.5)
        Anti-HPV-16, CD4-d-IL-2, S+, Month 36 (N=7, 12)
    2135.0 (1221.0 to 3291.0)
    1243.0 (910.5 to 2382.5)
        Anti-HPV-16, CD4-d-TNFα, S-, Day 0 (N=81, 68)
    59.0 (37.0 to 93.0)
    68.0 (29.5 to 110.5)
        Anti-HPV-16, CD4-d-TNFα, S-, Month 7 (N=69, 50)
    2474.0 (1311.0 to 4800.0)
    2575.5 (1224.0 to 3675.0)
        Anti-HPV-16, CD4-d-TNFα, S-, Month 12 (N=84, 70)
    1944.0 (814.5 to 4150.0)
    1726.0 (919.0 to 2481.0)
        Anti-HPV-16, CD4-d-TNFα, S-, Month 24 (N=78, 67)
    2181.5 (886.0 to 4177.0)
    1970.0 (773.0 to 2758.0)
        Anti-HPV-16, CD4-d-TNFα, S-, Month 36 (N=75, 57)
    1595.0 (700.0 to 3836.0)
    1390.0 (672.0 to 2092.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Day 0 (N=8, 14)
    47.0 (32.0 to 131.0)
    64.0 (49.0 to 120.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Month 7 (N=8, 13)
    2058.5 (1047.0 to 3933.0)
    1273.0 (949.0 to 2372.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Month 12 (N=9, 14)
    1826.0 (875.0 to 2703.0)
    1171.0 (733.0 to 2828.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Month 24 (N=9, 12)
    1851.0 (1039.0 to 2259.0)
    1061.5 (878.5 to 2421.5)
        Anti-HPV-16, CD4-d-TNFα, S+, Month 36 (N=7, 12)
    1138.0 (1031.0 to 2506.0)
    1057.0 (732.0 to 2009.0)
        Anti-HPV-16, CD8-all doubles, S-, Day 0 (N=81, 68)
    11.0 (11.0 to 41.0)
    11.0 (11.0 to 44.0)
        Anti-HPV-16, CD8-all doubles, S-, Mth 7 (N=69, 50)
    11.0 (11.0 to 41.0)
    11.0 (11.0 to 36.0)
        Anti-HPV-16,CD8 all doubles, S-, Mth 12 (N=84, 70)
    30.5 (11.0 to 45.5)
    29.5 (11.0 to 50.0)
        Anti-HPV-16,CD8-all doubles, S-, Mth 24 (N=78, 67)
    11.0 (11.0 to 53.0)
    11.0 (11.0 to 54.0)
        Anti-HPV-16,CD8-all doubles, S-, Mth 36 (N=75, 57)
    37.0 (11.0 to 72.0)
    35.0 (11.0 to 59.0)
        Anti-HPV-16, CD8-all doubles, S+, Day 0 (N=8, 14)
    11.0 (11.0 to 49.0)
    35.5 (26.0 to 41.0)
        Anti-HPV-16, CD8-all doubles, S+, Mth 7 (N=8, 13)
    11.0 (11.0 to 30.5)
    33.0 (11.0 to 43.0)
        Anti-HPV-16,CD8 all doubles, S+, Mth 12 (N=9, 14)
    52.0 (49.0 to 77.0)
    29.0 (11.0 to 57.0)
        Anti-HPV-16,CD8-all doubles, S+, Mth 24 (N=9, 12)
    49.0 (12.0 to 63.0)
    11.0 (11.0 to 56.0)
        Anti-HPV-16,CD8-all doubles, S+, Mth 36 (N=7, 12)
    27.0 (11.0 to 123.0)
    11.0 (11.0 to 49.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Day 0 (N=81, 68)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Month 7 (N=69, 50)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Month 12 (N=84, 70)
    7.0 (7.0 to 32.0)
    7.0 (7.0 to 37.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Month 24 (N=78, 68)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 31.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Month 36 (N=75, 57)
    11.0 (7.0 to 52.0)
    7.0 (7.0 to 32.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Day 0 (N=8, 14)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Month 7 (N=8, 13)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 22.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Month 12 (N=9, 14)
    45.0 (7.0 to 48.0)
    15.0 (7.0 to 37.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Month 24 (N=9, 12)
    7.0 (7.0 to 46.0)
    7.0 (7.0 to 17.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Month 36 (N=7, 12)
    7.0 (7.0 to 27.0)
    7.0 (7.0 to 15.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Day 0 (N=81, 68)
    7.0 (7.0 to 32.0)
    7.0 (7.0 to 37.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Month 7 (N=69, 50)
    7.0 (7.0 to 35.0)
    7.0 (7.0 to 26.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Month 12 (N=84, 70)
    7.0 (7.0 to 38.0)
    7.0 (7.0 to 46.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Month 24 (N=78, 67)
    7.0 (7.0 to 37.0)
    7.0 (7.0 to 42.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Month 36 (N=75, 57)
    11.0 (7.0 to 44.0)
    25.0 (7.0 to 44.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Day 0 (N=8, 14)
    7.0 (7.0 to 45.0)
    31.5 (22.0 to 37.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Month 7 (N=8, 13)
    7.0 (7.0 to 7.0)
    22.0 (7.0 to 30.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Month 12 (N=9, 14)
    46.0 (31.0 to 54.0)
    15.0 (7.0 to 40.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Month 24 (N=9, 12)
    8.0 (7.0 to 46.0)
    7.0 (7.0 to 23.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Month 36 (N=7, 12)
    7.0 (7.0 to 63.0)
    7.0 (7.0 to 45.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Day 0 (N=81, 68)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Month 7 (N=69, 50)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Month 12 (N=84, 70)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Month 24 (N=78, 67)
    7.0 (7.0 to 30.0)
    7.0 (7.0 to 30.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Month 36 (N=75, 57)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Day 0 (N=8, 14)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Month 7 (N=8, 13)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 28.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Month 12 (N=9, 14)
    7.0 (7.0 to 31.0)
    7.0 (7.0 to 23.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Month 24 (N=9, 12)
    7.0 (7.0 to 45.0)
    7.0 (7.0 to 13.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Month 36 (N=7, 12)
    7 (7.0 to 23.0)
    7 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Day 0 (N=81, 68)
    7.0 (7.0 to 29.0)
    7.0 (7.0 to 28.5)
        Anti-HPV-16, CD8-d-TNFα, S-, Month 7 (N=69, 50)
    7.0 (7.0 to 33.0)
    7.0 (7.0 to 32.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Month 12 (N=84, 70)
    7.0 (7.0 to 38.0)
    7.0 (7.0 to 33.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Month 24 (N=78, 67)
    7.0 (7.0 to 37.0)
    7.0 (7.0 to 24.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Month 36 (N=75, 57)
    7 (7.0 to 36.0)
    7 (7.0 to 32.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Day 0 (N=8, 14)
    7.0 (7.0 to 30.5)
    14.5 (7.0 to 31.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Month 7 (N=8, 13)
    7.0 (7.0 to 26.5)
    22.0 (7.0 to 30.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Month 12 (N=9, 14)
    8.0 (7.0 to 54.0)
    23.0 (7.0 to 30.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Month 24 (N=9, 12)
    8.0 (7.0 to 42.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Month 36 (N=7, 12)
    7.0 (7.0 to 119.0)
    7.0 (7.0 to 7.0)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects [14]
    End point description
    The CMI response represents the measure of the cytokines production [IL-2, IFN-γ, TNF-α, and CD40L] by HPV-antigen specific T lymphocytes and measured by ICS assay for HPV-18. The frequency was presented as a number of cytokine-producing CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles = T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < the cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and Months 7, 12, 24 and 36
    Notes
    [14] - 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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    83
    72
    Units: cells/million T cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-18, CD4 all doubles, S-, Day 0 (N=77, 69)
    86.0 (61.0 to 129.0)
    112.0 (75.0 to 177)
        Anti-HPV-18, CD4 all doubles, S-,Mth 7 (N=65, 53)
    2780.0 (1606.0 to 4289.0)
    1864.0 (1158.0 to 2565.0)
        Anti-HPV-18,CD4 all doubles, S-,Mth 12 (N=83, 72)
    2039.0 (1053.0 to 3481.0)
    1246.5 (814.0 to 2045.5)
        Anti-HPV-18,CD4 all doubles, S-,Mth 24 (N=76, 68)
    1815.5 (877.5 to 3193.0)
    1355.0 (638.5 to 2106.0)
        Anti-HPV-18,CD4 all doubles, S-,Mth 36 (N= 72, 56)
    1609.0 (716.0 to 3322.0)
    1246.0 (676.5 to 1751.0)
        Anti-HPV-18, CD4 all doubles, S+, Day 0 (N=11, 14)
    125.0 (61.0 to 227.0)
    128.0 (71.0 to 153.0)
        Anti-HPV-18, CD4 all doubles, S+, Mth 7 (N=11, 11)
    1593.0 (786.0 to 4012.0)
    1498.0 (808.0 to 2727.0)
        Anti-HPV-18,CD4 all doubles, S+, Mth 12 (N=10, 13)
    868.0 (576.0 to 2069.0)
    787.0 (597.0 to 1771.0)
        Anti-HPV-18,CD4 all doubles, S+, Mth 24 (N=10, 12)
    710.5 (523.0 to 2329.0)
    885.0 (475.5 to 2147.5)
        Anti-HPV-18,CD4 all doubles, S+, Mth 36 (N=10, 13)
    808.5 (624.0 to 1764.0)
    598.0 (367.0 to 1414.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Day 0 (N=77, 69)
    62.0 (35.0 to 105.0)
    88.0 (49.0 to 155.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Month 7 (N=65, 53)
    2634.0 (1331.0 to 3748.0)
    1700.0 (993.0 to 2324.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Month 12 (N=83, 72)
    1967.0 (1019.0 to 3362.0)
    1206.5 (797.5 to 2006.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Month 24 (N=76, 68)
    1632.0 (807.0 to 3133.0)
    1290.5 (600.5 to 1911.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Month 36 (N=72, 56)
    1543.0 (686.0 to 3258.0)
    1222.0 (670.0 to 1665.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Day 0 (N=11, 14)
    121.0 (50.0 to 223.0)
    110.5 (44.0 to 142.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Month 7 (N=11, 11)
    1419.0 (729.0 to 3704.0)
    1377.0 (703.0 to 2511.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Month 12 (N=10, 13)
    830.0 (572.0 to 2008.0)
    767.0 (539.0 to 1724.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Month 24 (N=10, 12)
    652.0 (475.0 to 2151.0)
    867.0 (431.0 to 1963.5)
        Anti-HPV-18, CD4-d-CD40L, S+, Month 36 (N=10, 13)
    794.0 (604.0 to 1721.0)
    594.0 (350.0 to 1356.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Day 0 (N=77, 69)
    32.0 (19.0 to 55.0)
    32.0 (19.0 to 68.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Month 7 (N=65, 53)
    562.0 (220.0 to 952.0)
    350.0 (192.0 to 554.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Month 12 (N=83, 72)
    354.0 (132.0 to 669.0)
    216.5 (111.5 to 390.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Month 24 (N=76, 68)
    326.5 (166.5 to 799.5)
    205.5 (108.5 to 538.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Month 36 (N=72, 56)
    304.5 (168.5 to 757.0)
    233.5 (114.5 to 485.5)
        Anti-HPV-18, CD4-d-IFNγ, S+, Day 0 (N=11, 14)
    55.0 (19.0 to 70.0)
    28.0 (19.0 to 48.0)
        Anti-HPV-18, CD4-d-IFNγ, S+, Month 7 (N=11, 11)
    628.0 (186.0 to 1186.0)
    376.0 (234.0 to 580.0)
        Anti-HPV-18, CD4-d-IFNγ, S+, Month 12 (N=10, 13)
    244.5 (120.0 to 535.0)
    161.0 (85.0 to 344.0)
        Anti-HPV-18, CD4-d-IFNγ, S+, Month 24 (N=10, 12)
    295.5 (108.0 to 636.0)
    270.5 (94.5 to 455.5)
        Anti-HPV-18, CD4-d-IFNγ, S+, Month 36 (N=10, 13)
    356.0 (278.0 to 417.0)
    239.0 (102.0 to 422.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Day 0 (N=77, 69)
    57.0 (30.0 to 96.0)
    81.0 (36.0 to 127.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Month 7 (N=65, 53)
    2611.0 (1452.0 to 3953.0)
    1725.0 (1026.0 to 2329.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Month 12 (N=83, 72)
    1959.0 (1009.0 to 3269.0)
    1172.5 (755.5 to 1916.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Month 24 (N=76, 68)
    1638.5 (851.5 to 3084.0)
    1306.0 (589.0 to 1977.5)
        Anti-HPV-18, CD4-d-IL-2, S-, Month 36 (N=72, 56)
    1495.0 (661.0 to 3065.0)
    1183.5 (586.5 to 1684.5)
        Anti-HPV-18, CD4-d-IL-2, S+, Day 0 (N=11, 14)
    65.0 (31.0 to 137.0)
    96.5 (48.0 to 102.0)
        Anti-HPV-18, CD4-d-IL-2, S+, Month 7 (N=11, 11)
    1470.0 (691.0 to 3887.0)
    1231.0 (690.0 to 2313.0)
        Anti-HPV-18, CD4-d-IL-2, S+, Month 12 (N=10, 13)
    847.5 (556.0 to 2022.0)
    783.0 (514.0 to 1650.0)
        Anti-HPV-18, CD4-d-IL-2, S+, Month 24 (N=10, 12)
    652.5 (448.0 to 2269.0)
    705.5 (433.0 to 2041.5)
        Anti-HPV-18, CD4-d-IL-2, S+, Month 36 (N=10, 13)
    777.0 (589.0 to 1669.0)
    554.0 (333.0 to 1370.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Day 0 (N=77, 69)
    49.0 (31.0 to 72.0)
    73.0 (27.0 to 138.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Month 7 (N=65, 53)
    1699.0 (979.0 to 2832.0)
    1394.0 (824.0 to 2060.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Month 12 (N=83, 72)
    1573.0 (715.0 to 2662.0)
    991.0 (599.0 to 1617.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Month 24 (N=76, 68)
    1434.0 (637.5 to 2506.0)
    1102.5 (543.0 to 1580.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Month 36 (N=72, 56)
    1268.0 (473.5 to 2130.0)
    868.5 (520.0 to 1296.5)
        Anti-HPV-18, CD4-d-TNFα, S+, Day 0 (N=11, 14)
    51.0 (44.0 to 159.0)
    68.0 (32.0 to 137.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Month 7 (N=11, 11)
    1337.0 (437.0 to 3141.0)
    1137.0 (648.0 to 2211.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Month 12 (N=10, 13)
    604.0 (391.0 to 1696.0)
    684.0 (443.0 to 1284.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Month 24 (N=10, 12)
    601.0 (462.0 to 2122.0)
    768.5 (370.5 to 1673.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Month 36 (N=10, 13)
    652.5 (489.0 to 1590.0)
    444.0 (294.0 to 996.0)
        Anti-HPV-18, CD8-all doubles, S-, Day 0 (N=77, 69)
    11.0 (11.0 to 36.0)
    11.0 (11.0 to 33.0)
        Anti-HPV-18, CD8-all doubles, S-, Mth 7 (N=65, 53)
    11.0 (11.0 to 37.0)
    11.0 (11.0 to 32.0)
        Anti-HPV-18,CD8 all doubles, S-, Mth 12 (N=83, 72)
    28.0 (11.0 to 47.0)
    37.0 (11.0 to 51.5)
        Anti-HPV-18,CD8-all doubles, S-, Mth 24 (N=76, 68)
    11.0 (11.0 to 51.0)
    11.0 (11.0 to 43.0)
        Anti-HPV-18,CD8-all doubles, S-, Mth 36 (N=72, 56)
    32.0 (11.0 to 45.5)
    29.0 (11.0 to 51.0)
        Anti-HPV-18, CD8-all doubles, S+, Day 0 (N=11, 14)
    11.0 (11.0 to 27.0)
    11.0 (11.0 to 34.0)
        Anti-HPV-18, CD8-all doubles, S+, Mth 7 (N=11, 11)
    11.0 (11.0 to 78.0)
    11.0 (11.0 to 73.0)
        Anti-HPV-18,CD8 all doubles, S+, Mth 12 (N=10, 13)
    44.0 (11.0 to 73.0)
    11.0 (11.0 to 33.0)
        Anti-HPV-18,CD8-all doubles, S+, Mth 24 (N=10, 12)
    19.5 (11.0 to 47.0)
    11.0 (11.0 to 36.0)
        Anti-HPV-18,CD8-all doubles, S+, Mth 36 (N=10, 13)
    45.0 (11.0 to 85.0)
    34.0 (11.0 to 50.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Day 0 (N=77, 69)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Month 7 (N=65, 53)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Month 12 (N=83, 72)
    7.0 (7.0 to 32.0)
    7.0 (7.0 to 36.5)
        Anti-HPV-18, CD8-d-CD40L, S-, Month 24 (N=76, 68)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Month 36 (N=72, 56)
    7.0 (7.0 to 35.5)
    7.0 (7.0 to 37.5)
        Anti-HPV-18, CD8-d-CD40L, S+, Day 0 (N=11, 14)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Month 7 (N=11, 11)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 27.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Month 12 (N=10, 13)
    34.5 (7.0 to 48.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Month 24 (N=10, 12)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Month 36 (N=10, 13)
    25.0 (7.0 to 61.0)
    7.0 (7.0 to 30.0)
        Anti-HPV-18, CD8-d-IFNγ, S-, Day 0 (N=77, 69)
    7.0 (7.0 to 29.0)
    7.0 (7.0 to 24.0)
        Anti-HPV-18, CD8-d-IFNγ, S-, Month 7 (N=65, 53)
    7.0 (7.0 to 26.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IFNγ, S-, Month 12 (N=83, 72)
    7.0 (7.0 to 34.0)
    7.0 (7.0 to 39.5)
        Anti-HPV-18, CD8-d-IFNγ, S-, Month 24 (N=76, 68)
    7.0 (7.0 to 29.5)
    7.0 (7.0 to 33.5)
        Anti-HPV-18, CD8-d-IFNγ, S-, Month 36 (N=72, 56)
    7.0 (7.0 to 40.5)
    7.0 (7.0 to 34.5)
        Anti-HPV-18, CD8-d-IFNγ, S+, Day 0 (N=11, 14)
    7.0 (7.0 to 23.0)
    7.0 (7.0 to 30.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Month 7 (N=11, 11)
    7.0 (7.0 to 74.0)
    7.0 (7.0 to 39.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Month 12 (N=10, 13)
    16.0 (7.0 to 38.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Month 24 (N=10, 12)
    7.0 (7.0 to 9.0)
    7.0 (7.0 to 32.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Month 36 (N=10, 13)
    7.0 (7.0 to 39.0)
    7.0 (7.0 to 40.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Day 0 (N=77, 69)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Month 7 (N=65, 53)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Month 12 (N=83, 72)
    7.0 (7.0 to 26.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Month 24 (N=76, 68)
    7.0 (7.0 to 27.0)
    7.0 (7.0 to 14.5)
        Anti-HPV-18, CD8-d-IL-2, S-, Month 36 (N=72, 56)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Day 0 (N=11, 14)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Month 7 (N=11, 11)
    7.0 (7.0 to 24.0)
    7.0 (7.0 to 34.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Month 12 (N=10, 13)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 23.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Month 24 (N=10, 12)
    7.0 (7.0 to 24.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Month 36 (N=10, 13)
    7.0 (7.0 to 39.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Day 0 (N=77, 69)
    7.0 (7.0 to 7.0)
    7.0 (7.0 to 8.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Month 7 (N=65, 53)
    7.0 (7.0 to 31.0)
    7.0 (7.0 to 27.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Month 12 (N=83, 72)
    7.0 (7.0 to 31.0)
    7.0 (7.0 to 35.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Month 24 (N=76, 68)
    7.0 (7.0 to 32.5)
    7.0 (7.0 to 33.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Month 36 (N=72, 56)
    7.0 (7.0 to 32.0)
    7.0 (7.0 to 35.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Day 0 (N=11, 14)
    7.0 (7.0 to 23.0)
    7.0 (7.0 to 30.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Month 7 (N=11, 11)
    7.0 (7.0 to 74.0)
    7.0 (7.0 to 62.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Month 12 (N=10, 13)
    7.0 (7.0 to 38.0)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Month 24 (N=10, 12)
    7.0 (7.0 to 31.0)
    7.0 (7.0 to 16.5)
        Anti-HPV-18, CD8-d-TNFα, S+, Month 36 (N=10, 13)
    17.0 (7.0 to 57.0)
    7.0 (7.0 to 29.0)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-16 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects [15]
    End point description
    The CMI response was the measure of the cytokines production (IL-2, IFN-γ, TNF-α, and CD40L) by HPV-antigen specific T lymphocytes and measured by ICS assay for HPV-16. The frequency was presented as a number of cytokine-positive cluster of differentiation (CD)4 i.e.CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles= T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 13, 18 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 3 Group
    Number of subjects analysed
    77
    Units: cells/million T cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-16, CD4 all doubles, S-, Day 0 (N=77)
    96.0 (61.0 to 170.0)
        Anti-HPV-16, CD4 all doubles, S-, Month 13 (N=73)
    2399.0 (1514.0 to 4223.0)
        Anti-HPV-16, CD4 all doubles, S-, Month 18 (N=73)
    1879.0 (1124.0 to 3449.0)
        Anti-HPV-16, CD4 all doubles, S-, Month 36 (N=70)
    1786.5 (1064.0 to 3285.0)
        Anti-HPV-16, CD4 all doubles, S+, Day 0 (N=7)
    169.0 (77.0 to 277.0)
        Anti-HPV-16, CD4 all doubles, S+, Month 13 (N=6)
    2507.5 (1067.0 to 4212.0)
        Anti-HPV-16, CD4 all doubles, S+, Month 18 (N=6)
    2717.5 (1597.0 to 4103.0)
        Anti-HPV-16, CD4 all doubles, S+, Month 36 (N=7)
    1521.0 (297.0 to 3794.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Day 0 (N=77)
    89.0 (48.0 to 133.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Month 13 (N=73)
    2356.0 (1510.0 to 4165.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Month 18 (N=73)
    1831.0 (1070.0 to 3272.0)
        Anti-HPV-16, CD4-d-CD40L, S-, Month 36 (N=70)
    1763.0 (1048.0 to 3239.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Day 0 (N=7)
    141.0 (73.0 to 261.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Month 13 (N=6)
    2450.5 (1036.0 to 4139.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Month 18 (N=6)
    2614.5 (1580.0 to 3862.0)
        Anti-HPV-16, CD4-d-CD40L, S+, Month 36 (N=7)
    1426.0 (280.0 to 3697.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Day 0 (N=77)
    35.0 (20.0 to 60.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Month 13 (N=73)
    651.0 (328.0 to 1356.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Month 18 (N=73)
    405.0 (208.0 to 821.0)
        Anti-HPV-16, CD4-d-IFNγ, S-, Month 36 (N=70)
    646.0 (276.0 to 1282.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Day 0 (N=7)
    68.0 (33.0 to 203.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Month 13 (N=6)
    644.0 (204.0 to 1163.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Month 18 (N=6)
    708.5 (361.0 to 1218.0)
        Anti-HPV-16, CD4-d-IFNγ, S+, Month 36 (N=7)
    310.0 (72.0 to 1783.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Day 0 (N=77)
    63.0 (34.0 to 111.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Month 13 (N=73)
    2220.0 (1406.0 to 4107.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Month 18 (N=73)
    1830.0 (1084.0 to 3221.0)
        Anti-HPV-16, CD4-d-IL-2, S-, Month 36 (N=70)
    1670.5 (1009.0 to 3169.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Day 0 (N=7)
    121.0 (47.0 to 191.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Month 13 (N=6)
    2442.0 (835.0 to 4006.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Month 18 (N=6)
    2659.5 (1510.0 to 3870.0)
        Anti-HPV-16, CD4-d-IL-2, S+, Month 36 (N=7)
    1028.0 (267.0 to 3629.0)
        Anti-HPV-16, CD4-d-TNFα, S-, Day 0 (N=77)
    63.0 (37.0 to 99.0)
        Anti-HPV-16, CD4-d-TNFα, S-, Month 13 (N=73)
    1643.0 (907.0 to 2988.0)
        Anti-HPV-16, CD4-d-TNFα, S-, Month 18 (N=73)
    1326.0 (807.0 to 2627.0)
        Anti-HPV-16, CD4-d-TNFα, S-, Month 36 (N=70)
    1300.5 (693.0 to 2267.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Day 0 (N=7)
    140.0 (32.0 to 164.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Month 13 (N=6)
    1843.0 (584.0 to 2657.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Month 18 (N=6)
    2085.0 (1380.0 to 2700.0)
        Anti-HPV-16, CD4-d-TNFα, S+, Month 36 (N=7)
    1202.0 (169.0 to 2745.0)
        Anti-HPV-16, CD8-all doubles, S-, Day 0 (N=77)
    27.0 (11.0 to 54.0)
        Anti-HPV-16, CD8-all doubles, S-, Month 13 (N=73)
    11.0 (11.0 to 43.0)
        Anti-HPV-16, CD8-all doubles, S-, Month 18 (N=73)
    11.0 (11.0 to 53.0)
        Anti-HPV-16, CD8-all doubles, S-, Month 36 (N=70)
    21.5 (11.0 to 52.0)
        Anti-HPV-16, CD8-all doubles, S+, Day 0 (N=7)
    33.0 (11.0 to 59.0)
        Anti-HPV-16, CD8-all doubles, S+, Month 13 (N=6)
    43.0 (11.0 to 57.0)
        Anti-HPV-16, CD8-all doubles, S+, Month 18 (N=6)
    27.0 (11.0 to 52.0)
        Anti-HPV-16, CD8-all doubles, S+, Month 36 (N=7)
    11.0 (11.0 to 89.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Day 0 (N=77)
    7.0 (7.0 to 35.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Month 13 (N=73)
    7.0 (7.0 to 29.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Month 18 (N=73)
    7.0 (7.0 to 34.0)
        Anti-HPV-16, CD8-d-CD40L, S-, Month 36 (N=70)
    7.0 (7.0 to 30.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Day 0 (N=7)
    7.0 (7.0 to 35.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Month 13 (N=6)
    7.0 (7.0 to 34.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Month 18 (N=6)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-CD40L, S+, Month 36 (N=7)
    7.0 (7.0 to 46.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Day 0 (N=77)
    7.0 (7.0 to 44.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Month 13 (N=73)
    7.0 (7.0 to 35.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Month 18 (N=73)
    7.0 (7.0 to 37.0)
        Anti-HPV-16, CD8-d-IFNγ, S-, Month 36 (N=70)
    7.0 (7.0 to 38.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Day 0 (N=7)
    29.0 (7.0 to 55.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Month 13 (N=6)
    25.5 (7.0 to 53.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Month 18 (N=6)
    7.0 (7.0 to 33.0)
        Anti-HPV-16, CD8-d-IFNγ, S+, Month 36 (N=7)
    7.0 (7.0 to 46.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Day 0 (N=77)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Month 13 (N=73)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Month 18 (N=73)
    7.0 (7.0 to 29.0)
        Anti-HPV-16, CD8-d-IL-2, S-, Month 36 (N=70)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Day 0 (N=7)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Month 13 (N=6)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Month 18 (N=6)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-IL-2, S+, Month 36 (N=7)
    7.0 (7.0 to 46.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Day 0 (N=77)
    7.0 (7.0 to 27.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Month 13 (N=73)
    7.0 (7.0 to 29.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Month 18 (N=73)
    7.0 (7.0 to 41.0)
        Anti-HPV-16, CD8-d-TNFα, S-, Month 36 (N=70)
    7.0 (7.0 to 38.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Day 0 (N=7)
    7.0 (7.0 to 7.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Month 13 (N=6)
    20.5 (7.0 to 44.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Month 18 (N=6)
    20.0 (7.0 to 39.0)
        Anti-HPV-16, CD8-d-TNFα, S+, Month 36 (N=7)
    7.0 (7.0 to 7.0)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-18 specific T CMI response for Cervarix 3 Group in a sub-cohort of subjects [16]
    End point description
    The CMI response was the measure of the cytokines production (IL-2, IFN-γ, TNF-α, and CD40L) by HPV-antigen specific T lymphocytes and measured by ICS assay for HPV-18. The frequency was presented as a number of cytokine-producing CD4+/CD8+ cells per million CD4+/CD8+ cells. All doubles= T cell expressing at least 2 cytokines. Results were tabulated by the pre-vaccination status of the subjects, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination. S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 13, 18 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 3 Group
    Number of subjects analysed
    82
    Units: cells/million T-cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-18, CD4 all doubles, S-, Day 0 (N=82)
    99.0 (61.0 to 149.0)
        Anti-HPV-18, CD4 all doubles, S-, Month 13 (N=77)
    1499.0 (1033.0 to 2928.0)
        Anti-HPV-18, CD4 all doubles, S-, Month 18 (N=77)
    1222.0 (796.0 to 2116.0)
        Anti-HPV-18, CD4 all doubles, S-, Month 36 (N=75)
    1158.0 (606.0 to 2185.0)
        Anti-HPV-18, CD4 all doubles, S+, Day 0 (N=2)
    107.5 (69.0 to 146.0)
        Anti-HPV-18, CD4 all doubles, S+, Month 13 (N=2)
    1968.5 (1753.0 to 2184.0)
        Anti-HPV-18, CD4 all doubles, S+, Month 18 (N=2)
    1250.0 (1156.0 to 1344.0)
        Anti-HPV-18, CD4 all doubles, S+, Month 36 (N=2)
    1399.5 (1004.0 to 1795.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Day 0 (N=82)
    82.5 (42.0 to 125.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Month 13 (N=77)
    1472.0 (1003.0 to 2880.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Month 18 (N=77)
    1199.0 (748.0 to 2098.0)
        Anti-HPV-18, CD4-d-CD40L, S-, Month 36 (N=75)
    1154.0 (563.0 to 2157.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Day 0 (N=2)
    103.5 (65.0 to 142.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Month 13 (N=2)
    1904.5 (1656.0 to 2153.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Month 18 (N=2)
    1174.5 (1110.0 to 1239.0)
        Anti-HPV-18, CD4-d-CD40L, S+, Month 36 (N=2)
    1320.0 (918.0 to 1722.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Day 0 (N=82)
    35.0 (23.0 to 61.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Month 13 (N=77)
    349.0 (173.0 to 1221.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Month 18 (N=77)
    226.0 (108.0 to 575.0)
        Anti-HPV-18, CD4-d-IFNγ, S-, Month 36 (N=75)
    318.0 (140.0 to 766.0)
        Anti-HPV-18, CD4-d-IFNγ, S+, Day 0 (N=2)
    33.5 (24.0 to 43.0)
        Anti-HPV-18, CD4-d-IFNγ, S+, Month 13 (N=2)
    378.0 (307.0 to 449.0)
        Anti-HPV-18, CD4-d-IFNγ, S+, Month 18 (N=2)
    157.5 (136.0 to 179.0)
        Anti-HPV-18, CD4-d-IFNγ, S+, Month 36 (N=2)
    389.0 (231.0 to 547.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Day 0 (N=82)
    58.5 (32.0 to 98.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Month 13 (N=77)
    1398.0 (812.0 to 2743.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Month 18 (N=77)
    1102.0 (719.0 to 1924.0)
        Anti-HPV-18, CD4-d-IL-2, S-, Month 36 (N=75)
    1086.0 (535.0 to 1974.0)
        Anti-HPV-18, CD4-d-IL-2, S+, Day 0 (N=2)
    46.5 (33.0 to 60.0)
        Anti-HPV-18, CD4-d-IL-2, S+, Month 13 (N=2)
    1845.0 (1544.0 to 2146.0)
        Anti-HPV-18, CD4-d-IL-2, S+, Month 18 (N=2)
    1151.0 (1078.0 to 1224.0)
        Anti-HPV-18, CD4-d-IL-2, S+, Month 36 (N=2)
    1160.0 (827.0 to 1493.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Day 0 (N=82)
    60.5 (34.0 to 97.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Month 13 (N=77)
    1029.0 (649.0 to 2051.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Month 18 (N=77)
    921.0 (539.0 to 1783.0)
        Anti-HPV-18, CD4-d-TNFα, S-, Month 36 (N=75)
    812.0 (384.0 to 1545.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Day 0 (N=2)
    66.5 (29.0 to 104.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Month 13 (N=2)
    1449.5 (1317.0 to 1582.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Month 18 (N=2)
    954.5 (873.0 to 1036.0)
        Anti-HPV-18, CD4-d-TNFα, S+, Month 36 (N=2)
    1127.0 (847.0 to 1407.0)
        Anti-HPV-18, CD8-all doubles, S-, Day 0 (N=82)
    11.0 (11.0 to 47.0)
        Anti-HPV-18, CD8-all doubles, S-, Month 13 (N=77)
    32.0 (11.0 to 49.0)
        Anti-HPV-18, CD8-all doubles, S-, Month 18 (N=77)
    34.0 (11.0 to 50.0)
        Anti-HPV-18, CD8-all doubles, S-, Month 36 (N=75)
    33.0 (11.0 to 56.0)
        Anti-HPV-18, CD8-all doubles, S+, Day 0 (N=2)
    29.0 (11.0 to 47.0)
        Anti-HPV-18, CD8-all doubles, S+, Month 13 (N=2)
    63.5 (39.0 to 88.0)
        Anti-HPV-18, CD8-all doubles, S+, Month 18 (N=2)
    11.0 (11.0 to 11.0)
        Anti-HPV-18, CD8-all doubles, S+, Month 36 (N=2)
    45.0 (11.0 to 79.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Day 0 (N=82)
    7.0 (7.0 to 30.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Month 13 (N=77)
    7.0 (7.0 to 38.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Month 18 (N=77)
    7.0 (7.0 to 34.0)
        Anti-HPV-18, CD8-d-CD40L, S-, Month 36 (N=75)
    7.0 (7.0 to 38.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Day 0 (N=82)
    25.0 (7.0 to 43.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Month 13 (N=2)
    21.0 (7.0 to 35.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Month 18 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-CD40L, S+, Month 36 (N=2)
    41.0 (7.0 to 75.0)
        Anti-HPV-18, CD8-d-IFNγ, S-, Day 0 (N=82)
    7.0 (7.0 to 41.0)
        Anti-HPV-18, CD8-d-IFNγ, S-, Month 13 (N=77)
    7.0 (7.0 to 40.0)
        Anti-HPV-18, CD8-d-IFNγ, S-, Month 18 (N=77)
    7.0 (7.0 to 37.0)
        Anti-HPV-18, CD8-d-IFNγ, S-, Month 36 (N=75)
    7.0 (7.0 to 44.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Day 0 (N=2)
    25.0 (7.0 to 43.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Month 13 (N=2)
    59.5 (35.0 to 84.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Month 18 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IFNγ, S+, Month 36 (N=2)
    41.0 (7.0 to 75.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Day 0 (N=82)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Month 13 (N=77)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Month 18 (N=77)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S-, Month 36 (N=75)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Day 0 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Month 13 (N=2)
    45.5 (7.0 to 84.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Month 18 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-IL-2, S+, Month 36 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Day 0 (N=72)
    7.0 (7.0 to 38.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Month 13 (N=77)
    7.0 (7.0 to 30.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Month 18 (N=77)
    7.0 (7.0 to 40.0)
        Anti-HPV-18, CD8-d-TNFα, S-, Month 36 (N=75)
    7.0 (7.0 to 35.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Day 0 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Month 13 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Month 18 (N=2)
    7.0 (7.0 to 7.0)
        Anti-HPV-18, CD8-d-TNFα, S+, Month 36 (N=2)
    7.0 (7.0 to 7.0)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects [17]
    End point description
    The CMI response was assessed as being the frequency of B-cell memory of HPV-16 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and Months 7, 12, 24 and 36
    Notes
    [17] - 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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    75
    63
    Units: cells/million B-cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-16, S-, Day 0 (N=74, 63)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        Anti-HPV-16, S-, Month 7 (N=70, 46)
    2155.0 (886.0 to 5421.0)
    1510.0 (799.0 to 3114.0)
        Anti-HPV-16, S-, Month 12 (N=55, 42)
    801.0 (361.0 to 2648.0)
    1145.0 (371.0 to 3215.0)
        Anti-HPV-16, S-, Month 24 (N=75, 60)
    318.0 (95.0 to 697.0)
    594.5 (147.5 to 1133.5)
        Anti-HPV-16, S-, Month 36 (N=70, 53)
    560.5 (157.0 to 1012.0)
    448.0 (219.0 to 821.0)
        Anti-HPV-16, S+, Day 0 (N=8, 13)
    1.0 (1.0 to 16.0)
    1.0 (1.0 to 51.0)
        Anti-HPV-16, S+, Month 7 (N=7, 11)
    4838.0 (1513.0 to 11824.0)
    477.0 (139.0 to 4928.0)
        Anti-HPV-16, S+, Month 12 (N=2, 9)
    5056.0 (5018.0 to 5094.0)
    539.0 (340.0 to 2111.0)
        Anti-HPV-16, S+, Month 24 (N=8, 12)
    621.0 (324.5 to 1751.5)
    568.5 (50.0 to 1955.0)
        Anti-HPV-16, S+, Month 36 (N=6, 13)
    475.0 (414.0 to 822.0)
    107.0 (1.0 to 1275.0)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 1 Group and Cervarix 2 Group in a sub-cohort of subjects [18]
    End point description
    The cell-mediated immune response was assessed as being the frequency of B-cell memory of HPV-18 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects per study group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 7, 12, 24 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 1 Group Cervarix 2 Group
    Number of subjects analysed
    72
    63
    Units: cells/million B-cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-18, S-, Day 0 (N=72, 63)
    1.0 (1.0 to 1.0)
    1.0 (1.0 to 1.0)
        Anti-HPV-18, S-, Month 7 (N=67, 48)
    958.0 (386.0 to 2500.0)
    817.5 (368.0 to 1894.5)
        Anti-HPV-18, S-, Month 24 (N=72, 61)
    236.0 (61.5 to 710.0)
    274.0 (71.0 to 829.0)
        Anti-HPV-18, S-, Month 36 (N=67, 54)
    269.0 (62.0 to 732.0)
    284.5 (90.0 to 582.0)
        Anti-HPV-18, S+, Day 0 (N=10, 14)
    1.0 (1.0 to 44.0)
    1.0 (1.0 to 22.0)
        Anti-HPV-18, S+, Month 7 (N=10, 10)
    2016.5 (423.0 to 2797.0)
    439.5 (31.0 to 1779.0)
        Anti-HPV-18, S+, Month 24 (N=11, 12)
    299.0 (117.0 to 643.0)
    338.5 (174.0 to 786.0)
        Anti-HPV-18, S+, Month 36 (N=9, 12)
    154.0 (141.0 to 427.0)
    93.0 (18.0 to 762.0)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-16 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects [19]
    End point description
    The cell-mediated immune response was assessed as being the frequency of B-cell memory of HPV-16 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 13, 18 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 3 Group
    Number of subjects analysed
    68
    Units: cells/million B-cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-16, S-, Day 0 (N=66)
    1.0 (1.0 to 7.0)
        Anti-HPV-16, S-, Month 13 (N=68)
    2809.5 (1402.5 to 5045.5)
        Anti-HPV-16, S-, Month 18 (N=60)
    766.0 (412.0 to 1946.5)
        Anti-HPV-16, S-, Month 36 (N=67)
    613.0 (322.0 to 1301.0)
        Anti-HPV-16, S+, Day 0 (N=5)
    1.0 (1.0 to 20.0)
        Anti-HPV-16, S+, Month 13 (N=5)
    5996.0 (919.0 to 7353.0)
        Anti-HPV-16, S+, Month 18 (N=5)
    2130.0 (808.0 to 2271.0)
        Anti-HPV-16, S+, Month 36 (N=6)
    425.0 (102.0 to 714.0)
    No statistical analyses for this end point

    Secondary: Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects

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    End point title
    Cell-mediated immunogenicity related to anti-HPV-18 specific B CMI response for Cervarix 3 Group in a sub-cohort of subjects [20]
    End point description
    The cell-mediated immune response was assessed as being the frequency of B-cell memory of HPV-18 antigen-specific memory B-cells per million memory B-cells in subjects with detectable B-cells. The results are presented by pre-vaccination status, where S- = seronegative subjects (antibody concentration < cut-off value) prior to vaccination and S+ = seropositive subjects (antibody concentration ≥ cut-off value) prior to vaccination. The assay was performed on a subset of 100 subjects from Cervarix 3 Group.
    End point type
    Secondary
    End point timeframe
    At Day 0 and at Months 13, 18 and 36
    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: As Group Cervarix 3 received the last vaccination dose at Month 12, results were presented separately for Groups Cervarix 3 and for Cervarix 1 and 2.
    End point values
    Cervarix 3 Group
    Number of subjects analysed
    72
    Units: cells/million B-cells
    median (inter-quartile range (Q1-Q3))
        Anti-HPV-18, S-, Day 0 (N=70)
    1.0 (1.0 to 1.0)
        Anti-HPV-18, S-, Month 13 (N=71)
    1165.0 (602.0 to 1660.0)
        Anti-HPV-18, S-, Month 18 (N=64)
    561.5 (132.0 to 1213.5)
        Anti-HPV-18, S-, Month 36 (N=72)
    361.0 (112.0 to 724.0)
        Anti-HPV-18, S+, Day 0 (N=1)
    48.0 (48.0 to 48.0)
        Anti-HPV-18, S+, Month 13 (N=2)
    758.0 (114.0 to 1402.0)
        Anti-HPV-18, S+, Month 18 (N=1)
    938.0 (938.0 to 938.0)
        Anti-HPV-18, S+, Month 36 (N=1)
    1231.0 (1231.0 to 1231.0)
    No statistical analyses for this end point

    Secondary: Number of subjects with any and grade 3 solicited local symptoms

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    End point title
    Number of subjects with any and grade 3 solicited local symptoms
    End point description
    Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of any solicited local symptom regardless of their intensity grade. Grade 3 pain = significant pain at rest, that prevented normal every day activity. Grade 3 redness/swelling = redness/swelling above 50 millimeters (mm). Subjects from Cervarix 1 and Cervarix 3 Groups received only 2 doses of vaccine, therefore data are presented up to Dose 2.
    End point type
    Secondary
    End point timeframe
    During the 7 day period (Days 0-6) after each vaccine dose and across doses
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    550
    480
    413
    Units: Subjects
        Any Pain - Dose 1 (N=549, 480, 411)
    461
    439
    354
        Grade 3 Pain - Dose 1 (N=549, 480, 411)
    24
    21
    21
        Any Pain - Dose 2 (N=544, 470, 404)
    446
    377
    323
        Grade 3 Pain - Dose 2 (N=544, 470, 404)
    33
    25
    31
        Any Pain - Dose 3 (N=0, 464, 0)
    0
    358
    0
        Grade 3 Pain - Dose 3 (N=0, 464, 0)
    0
    20
    0
        Any Pain - Across doses (N=550, 480, 413)
    499
    461
    381
        Grade 3 Pain - Across doses (N=550, 480, 413)
    50
    53
    48
        Any Redness - Dose 1 (N=549, 480, 411)
    167
    135
    126
        Grade 3 Redness - Dose 1 (N=549, 480, 411)
    0
    2
    2
        Any Redness - Dose 2 (N=544, 470, 404)
    180
    143
    153
        Grade 3 Redness - Dose 2 (N=544, 470, 404)
    4
    5
    1
        Any Redness - Dose 3 (N=0, 464, 0)
    0
    142
    0
        Grade 3 Redness - Dose 3 (N=0, 464, 0)
    0
    5
    0
        Any Redness - Across doses (N=550, 480, 413)
    247
    212
    197
        Grade 3 Redness - Across doses (N=550, 480, 413)
    4
    10
    3
        Any Swelling - Dose 1 (N=549, 480, 411)
    141
    105
    101
        Grade 3 Swelling - Dose 1 (N=549, 480, 411)
    3
    1
    4
        Any Swelling - Dose 2 (N=544, 470, 404)
    166
    131
    135
        Grade 3 Swelling - Dose 2 (N=544, 470, 404)
    2
    4
    2
        Any Swelling - Dose 3 (N=0, 464, 0)
    0
    136
    0
        Grade 3 Swelling - Dose 3 (N=0, 464, 0)
    0
    3
    0
        Any Swelling - Across doses (N=550, 480, 413)
    225
    204
    171
        Grade 3 Swelling - Across doses (N=550, 480, 413)
    5
    6
    6
    No statistical analyses for this end point

    Secondary: Number of subjects with any, grade 3 and related solicited general symptoms

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    End point title
    Number of subjects with any, grade 3 and related solicited general symptoms
    End point description
    Assessed solicited general symptoms were arthralgia, fatigue, gastrointestinal symptoms, headache, myalgia, rash, fever and urticaria. Any = occurrence of any solicited general symptom regardless of intensity grade or relationship to vaccination. Any Fever = axillary temperature ≥ 37.5 degrees Celsius (°C). Grade 3 symptom = symptom that prevented normal activity. Grade 3 fever = fever greater than (>) 39.0 °C. Related = general symptom assessed by the investigator as causally related to the vaccination. Subjects from Cervarix 1 and Cervarix 3 Groups received only 2 doses of vaccine, therefore data are presented up to Dose 2.
    End point type
    Secondary
    End point timeframe
    During the 7-day period (Days 0-6) after each vaccine dose and across doses
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    550
    480
    413
    Units: Subjects
        Any Artharlgia - Dose 1 (N=549, 480, 411)
    61
    53
    52
        Grade 3 Arthralgia - Dose 1 (N=549, 480, 411)
    8
    3
    3
        Related Arthralgia - Dose 1 (N=549, 480, 411)
    56
    50
    45
        Any Artharlgia - Dose 2 (N=544, 470, 404)
    71
    56
    64
        Grade 3 Arthralgia - Dose 2 (N=544, 470, 404)
    2
    1
    3
        Related Arthralgia - Dose 2 (N=544, 470, 404)
    64
    50
    57
        Any Artharlgia - Dose 3 (N=0, 464, 0)
    0
    49
    0
        Grade 3 Arthralgia - Dose 3 (N=0, 464, 0)
    0
    3
    0
        Related Arthralgia - Dose 3 (N=0, 464, 0)
    0
    42
    0
        Any Artharlgia - Across doses (N=550, 480, 413)
    111
    107
    93
        Grade 3 Arthralgia -Across doses (N=550, 480, 413)
    9
    6
    6
        Related Arthralgia -Across doses (N=550, 480, 413)
    105
    102
    83
        Any Fatigue - Dose 1 (N=549, 480, 411)
    181
    238
    156
        Grade 3 Fatigue - Dose 1 (N=549, 480, 411)
    7
    9
    10
        Related Fatigue - Dose 1 (N=549, 480, 411)
    153
    205
    129
        Any Fatigue - Dose 2 (N=544, 470, 404)
    167
    168
    144
        Grade 3 Fatigue - Dose 2 (N=544, 470, 404)
    9
    11
    14
        Related Fatigue - Dose 2 (N=544, 470, 404)
    149
    142
    119
        Any Fatigue - Dose 3 (N=0, 464, 0)
    0
    177
    0
        Grade 3 Fatigue - Dose 3 (N=0, 464, 0)
    0
    12
    0
        Related Fatigue - Dose 3 (N=0, 464, 0)
    0
    161
    0
        Any Fatigue - Across doses (N=550, 480, 413)
    247
    310
    215
        Grade 3 Fatigue - Across doses (N=550, 480, 413)
    14
    25
    21
        Related Fatigue - Across doses (N=550, 480, 413)
    221
    294
    185
        Any Gastrointestinal - Dose 1 (N=549, 480, 411)
    59
    88
    44
        Grade 3 Gastrointestinal -Dose 1 (N=549, 480, 411)
    1
    2
    3
        Related Gastrointestinal -Dose 1 (N=549, 480, 411)
    49
    67
    32
        Any Gastrointestinal - Dose 2 (N=544, 470, 404)
    51
    50
    48
        Grade 3 Gastrointestinal -Dose 2 (N=544, 470, 404)
    6
    2
    4
        Related Gastrointestinal -Dose 2 (N=544, 470, 404)
    34
    36
    40
        Any Gastrointestinal - Dose 3 (N=0, 464, 0)
    0
    45
    0
        Grade 3 Gastrointestinal -Dose 3 (N=0, 464, 0)
    0
    7
    0
        Related Gastrointestinal -Dose 3 (N=0, 464, 0)
    0
    35
    0
        Any Gastrointestinal -Across doses (N=550,480,413)
    98
    134
    77
        Grade 3 Gastroint. -Across doses (N=550, 480, 413)
    7
    11
    7
        Related Gastroint. -Across doses (N=550, 480, 413)
    77
    106
    62
        Any Headache - Dose 1 (N=549, 480, 411)
    133
    161
    128
        Grade 3 Headache - Dose 1 (N=549, 480, 411)
    9
    10
    10
        Related Headache - Dose 1 (N=549, 480, 411)
    104
    136
    104
        Any Headache - Dose 2 (N=544, 470, 404)
    128
    129
    130
        Grade 3 Headache - Dose 2 (N=544, 470, 404)
    14
    5
    6
        Related Headache - Dose 2 (N=544, 470, 404)
    107
    108
    100
        Any Headache - Dose 3 (N=0, 464, 0)
    0
    124
    0
        Grade 3 Headache - Dose 3 (N=0, 464, 0)
    0
    11
    0
        Related Headache - Dose 3 (N=0, 464, 0)
    0
    106
    0
        Any Headache - Across doses (N=550, 480, 413)
    204
    246
    185
        Grade 3 Headache - Across doses (N=550, 480, 413)
    19
    26
    16
        Related Headache - Across doses (N=550, 480, 413)
    176
    219
    148
        Any Myalgia - Dose 1 (N=549, 480, 411)
    206
    236
    160
        Grade 3 Myalgia - Dose 1 (N=549, 480, 411)
    16
    12
    8
        Related Myalgia - Dose 1 (N=549, 480, 411)
    191
    223
    140
        Any Myalgia - Dose 2 (N=544, 470, 404)
    196
    182
    150
        Grade 3 Myalgia - Dose 2 (N=544, 470, 404)
    13
    11
    10
        Related Myalgia - Dose 2 (N=544, 470, 404)
    182
    171
    136
        Any Myalgia - Dose 3 (N=0, 464, 0)
    0
    158
    0
        Grade 3 Myalgia - Dose 3 (N=0, 464, 0)
    0
    8
    0
        Related Myalgia - Dose 3 (N=0, 464, 0)
    0
    150
    0
        Any Myalgia - Across doses (N=550, 480, 413)
    278
    295
    221
        Grade 3 Myalgia - Across doses (N=550, 480, 413)
    24
    25
    15
        Related Myalgia - Across doses (N=550, 480, 413)
    265
    285
    201
        Any Rash - Dose 1 (N=549, 480, 411)
    17
    8
    15
        Grade 3 Rash - Dose 1 (N=549, 480, 411)
    1
    0
    0
        Related Rash - Dose 1 (N=549, 480, 411)
    13
    5
    13
        Any Rash - Dose 2 (N=544, 470, 404)
    17
    11
    16
        Grade 3 Rash - Dose 2 (N=544, 470, 404)
    1
    0
    0
        Related Rash - Dose 2 (N=544, 470, 404)
    13
    10
    16
        Any Rash - Dose 3 (N=0, 464, 0)
    0
    8
    0
        Grade 3 Rash - Dose 3 (N=0, 464, 0)
    0
    0
    0
        Related Rash - Dose 3 (N=0, 464, 0)
    0
    5
    0
        Any Rash - Across doses (N=550, 480, 413)
    33
    25
    29
        Grade 3 Rash - Across doses (N=550, 480, 413)
    2
    0
    0
        Related Rash - Across doses (N=550, 480, 413)
    26
    18
    28
        Any Fever - Dose 1 (N=549, 480, 411)
    24
    17
    18
        Grade 3 Fever - Dose 1 (N=549, 480, 411)
    1
    0
    0
        Related Fever - Dose 1 (N=549, 480, 411)
    15
    12
    15
        Any Fever - Dose 2 (N=544, 470, 404)
    21
    15
    25
        Grade 3 Fever - Dose 2 (N=544, 470, 404)
    1
    3
    1
        Related Fever - Dose 2 (N=544, 470, 404)
    17
    12
    18
        Any Fever - Dose 3 (N=0, 464, 0)
    0
    29
    0
        Grade 3 Fever - Dose 3 (N=0, 464, 0)
    0
    0
    0
        Related Fever - Dose 3 (N=0, 464, 0)
    0
    25
    0
        Any Fever - Across doses (N=550, 480, 413)
    41
    48
    42
        Grade 3 Fever - Across doses (N=550, 480, 413)
    2
    3
    1
        Related Fever - Across doses (N=550, 480, 413)
    29
    39
    32
        Any Urticaria - Dose 1 (N=549, 480, 411)
    9
    7
    4
        Grade 3 Urticaria - Dose 1 (N=549, 480, 411)
    1
    1
    0
        Related Urticaria - Dose 1 (N=549, 480, 411)
    7
    3
    4
        Any Urticaria - Dose 2 (N=544, 470, 404)
    7
    9
    9
        Grade 3 Urticaria - Dose 2 (N=544, 470, 404)
    0
    0
    0
        Related Urticaria - Dose 2 (N=544, 470, 404)
    6
    7
    8
        Any Urticaria - Dose 3 (N=0, 464, 0)
    0
    5
    0
        Grade 3 Urticaria - Dose 3 (N=0, 464, 0)
    0
    0
    0
        Related Urticaria - Dose 3 (N=0, 464, 0)
    0
    3
    0
        Any Urticaria - Across doses (N=550, 480, 413)
    15
    15
    13
        Grade 3 Urticaria - Across doses (N=550, 480, 413)
    1
    1
    0
        Related Urticaria - Across doses (N=550, 480, 413)
    13
    11
    12
    No statistical analyses for this end point

    Secondary: Number of subjects with any, grade 3 and related unsolicited adverse events (AEs)

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    End point title
    Number of subjects with any, grade 3 and related 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 = any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 = unsolicited AE preventing normal activity. Related = unsolicited AE assessed by the investigator as causally related to the study vaccination.
    End point type
    Secondary
    End point timeframe
    During the 30-day (Days 0-29) post-vaccination period
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    550
    482
    415
    Units: Subjects
        Any unsolicited AEs
    97
    167
    74
        Grade 3 unsolicited AEs
    2
    17
    6
        Related unsolicited AEs
    11
    24
    13
    No statistical analyses for this end point

    Secondary: Number of subjects with any potential Immune-Mediated Diseases (pIMDs)

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    End point title
    Number of subjects with any potential Immune-Mediated Diseases (pIMDs)
    End point description
    pIMDs are a subset of AEs that include both clearly autoimmune diseases and also other inflammatory and/or neurologic disorders which may or may not have an autoimmune etiology. The data for Cervarix 1 and 2 Groups are only presented up to Month 13, as the data were only collected up to Month 13 for those 2 groups.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 13 (for Cervarix 1 Group and Cervarix 2 Group) and from Day 0 up to Month 18 (for Cervarix 3 Group)
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    550
    482
    415
    Units: Subjects
        Any pIMDs,from Day 0 up to Month 13(N=550,482,415)
    2
    2
    2
        Any pIMDs, from Day 0 up to Month 18 (N=0, 0, 415)
    0
    0
    2
    No statistical analyses for this end point

    Secondary: Number of subjects with Medically Significant Conditions (MSCs)

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    End point title
    Number of subjects with Medically Significant Conditions (MSCs)
    End point description
    MSC include AEs prompting emergency room or physician visits that are not related to common diseases or routine visits for physical examination or vaccination, or serious adverse events (SAEs) that are not related to common diseases. Common diseases include upper respiratory infections, sinusitis, pharyngitis, gastroenteritis, urinary tract infections, cervico-vaginal yeast infections, menstrual cycle abnormalities and injury.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 36 (throughout the study period)
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    550
    482
    415
    Units: Subjects
    134
    153
    87
    No statistical analyses for this end point

    Secondary: Number of subjects with any, related and fatal serious adverse events (SAEs)

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    End point title
    Number of subjects with any, related and fatal serious adverse events (SAEs)
    End point description
    SAEs assessed include medical occurrences that resulted in death, were life-threatening, required hospitalization or prolongation of hospitalization or resulted in disability/incapacity or were a congenital anomaly/birth defect in the offspring of a study subject. Any = any SAE regardless of intensity grade or relation to vaccination. Related = SAE assessed by the investigator as causally related to the study vaccination.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 36 (throughout the study period)
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    550
    482
    415
    Units: Subjects
        Any SAEs
    20
    28
    24
        Related SAEs
    0
    0
    1
        Fatal SAEs
    0
    0
    0
    No statistical analyses for this end point

    Secondary: Number of subjects reporting pregnancies and outcomes of reported pregnancies

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    End point title
    Number of subjects reporting pregnancies and outcomes of reported pregnancies
    End point description
    Outcomes of reported pregnancies were: Ectopic pregnancy, Elective termination NO apparent congenital anomaly (ACA), Live Infant NO ACA, Stillbirth NO ACA.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 36 (throughout the study period)
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    1
    34
    1
    Units: Subjects
        Ectopic pregnancy
    0
    1
    0
        Elective termination NO ACA
    0
    2
    0
        Live Infant NO ACA
    1
    30
    1
        Stillbirth NO ACA
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Number of subjects completing the vaccination course

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    End point title
    Number of subjects completing the vaccination course
    End point description
    The number of subjects completing the vaccination course was assessed as the number of subjects with at least one dose received during the study.
    End point type
    Secondary
    End point timeframe
    From Day 0 up to Month 13
    End point values
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Number of subjects analysed
    550
    482
    415
    Units: Subjects
    550
    482
    415
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Solicited symptoms were collected during the 7-day period (Days 0-6) after vaccination. Unsolicited AEs were collected during the 30-day period (Days 0-29) after vaccination. SAEs were collected from Day 0 to Month 36.
    Adverse event reporting additional description
    The occurrence of reported AEs (all/related) was not available and encoded as equal to the number of subjects affected. For the systematically assessed other (non-serious) adverse events, the number of exposed subjects included those from Total Vaccinated cohort who had the symptom sheet completed.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Cervarix 1 Group
    Reporting group description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Months 0 and 6. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Reporting group title
    Cervarix 2 Group
    Reporting group description
    Female subjects aged 15 to 25 years at the time of the first vaccination, who received 3 doses of the Cervarix vaccine at Months 0, 1 and 6. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Reporting group title
    Cervarix 3 Group
    Reporting group description
    Female subjects aged 9 to 14 years at the time of the first vaccination, who received 2 doses of the Cervarix vaccine at Months 0 and 12. The vaccine was administered intramuscularly into the deltoid muscle of the non-dominant arm.

    Serious adverse events
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    20 / 550 (3.64%)
    28 / 482 (5.81%)
    24 / 415 (5.78%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Ectopic pregnancy termination
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Medulloblastoma
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cholesteatoma
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Synovial sarcoma
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine leiomyoma
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Drug hypersensitivity
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anaphylactic reaction
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Hyperemesis gravidarum
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Premature baby
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abortion threatened
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Postpartum haemorrhage
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Stillbirth
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Psychotic disorder
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Schizoaffective disorder
         subjects affected / exposed
    0 / 550 (0.00%)
    2 / 482 (0.41%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst ruptured
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Forearm fracture
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Carbon monoxide poisoning
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Road traffic accident
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Traumatic intracranial haemorrhage
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Alcohol poisoning
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Lymphadenitis
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Transient tachypnoea of the newborn
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory disorder
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillar hypertrophy
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Seizure
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    VIIth nerve paralysis
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Strabismus
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal strangulated hernia
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal pain lower
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Anal haemorrhage
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Constipation
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Dyspepsia
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Faecaloma
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Chronic gastritis
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    IgA nephropathy
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Synovial cyst
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Autoimmune thyroiditis
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypovolaemia
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Type 1 diabetes mellitus
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Dengue fever
         subjects affected / exposed
    1 / 550 (0.18%)
    4 / 482 (0.83%)
    3 / 415 (0.72%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis bacterial
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 550 (0.18%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tubo-ovarian abscess
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 550 (0.18%)
    1 / 482 (0.21%)
    2 / 415 (0.48%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media chronic
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infectious mononucleosis
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic inflammatory disease
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salpingitis
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Salpingo-oophoritis
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Otitis media acute
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pelvic infection
         subjects affected / exposed
    0 / 550 (0.00%)
    1 / 482 (0.21%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 550 (0.18%)
    0 / 482 (0.00%)
    0 / 415 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    0 / 550 (0.00%)
    0 / 482 (0.00%)
    1 / 415 (0.24%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    0 / 550 (0.00%)
    3 / 482 (0.62%)
    5 / 415 (1.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 3
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 550 (0.36%)
    1 / 482 (0.21%)
    2 / 415 (0.48%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cervarix 1 Group Cervarix 2 Group Cervarix 3 Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    513 / 550 (93.27%)
    466 / 482 (96.68%)
    387 / 415 (93.25%)
    General disorders and administration site conditions
    Pain
         subjects affected / exposed [1]
    499 / 550 (90.73%)
    461 / 480 (96.04%)
    381 / 413 (92.25%)
         occurrences all number
    499
    461
    381
    Redness
         subjects affected / exposed [2]
    247 / 550 (44.91%)
    212 / 480 (44.17%)
    197 / 413 (47.70%)
         occurrences all number
    247
    212
    197
    Swelling
         subjects affected / exposed [3]
    225 / 550 (40.91%)
    204 / 480 (42.50%)
    171 / 413 (41.40%)
         occurrences all number
    225
    204
    171
    Arthralgia
         subjects affected / exposed [4]
    111 / 550 (20.18%)
    107 / 480 (22.29%)
    93 / 413 (22.52%)
         occurrences all number
    111
    107
    93
    Fatigue
         subjects affected / exposed [5]
    247 / 550 (44.91%)
    310 / 480 (64.58%)
    215 / 413 (52.06%)
         occurrences all number
    247
    310
    215
    Gastrointestinal symptoms
         subjects affected / exposed [6]
    98 / 550 (17.82%)
    134 / 480 (27.92%)
    77 / 413 (18.64%)
         occurrences all number
    98
    134
    77
    Headache
         subjects affected / exposed [7]
    204 / 550 (37.09%)
    246 / 480 (51.25%)
    185 / 413 (44.79%)
         occurrences all number
    204
    246
    185
    Myalgia
         subjects affected / exposed [8]
    278 / 550 (50.55%)
    295 / 480 (61.46%)
    221 / 413 (53.51%)
         occurrences all number
    278
    295
    221
    Rash
         subjects affected / exposed [9]
    33 / 550 (6.00%)
    25 / 480 (5.21%)
    29 / 413 (7.02%)
         occurrences all number
    33
    25
    29
    Fever
         subjects affected / exposed [10]
    41 / 550 (7.45%)
    48 / 480 (10.00%)
    42 / 413 (10.17%)
         occurrences all number
    41
    48
    42
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    22 / 550 (4.00%)
    27 / 482 (5.60%)
    14 / 415 (3.37%)
         occurrences all number
    22
    27
    14
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [9] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.
    [10] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: The analysis was performed on the Total vaccinated cohort, only on subjects with their symptom sheet completed.

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    26 Nov 2013
    The HPV-070 protocol is being amended for the following reason: The assay used to measure anti-HPV-16/-18 antibody concentrations at the designated laboratory was improved to increase the assay precision by changing the assay cut-off value from 8 EL.U/mL to 19 EL.U/mL for HPV-16 and from 7 EL.U/mL to 18 EL.U/mL for HPV-18. This change in the assay was implemented for the testing of samples from Month 18 onwards.

    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
    As of 1.2.2020, the UK is no longer an EU Member State. However, EU law still applies to the UK during the transition period
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