Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register allows you to search for protocol and results information on:
  • interventional clinical trials that are conducted in the European Union (EU) and the European Economic Area (EEA);
  • clinical trials conducted outside the EU / EEA that are linked to European paediatric-medicine development.
  • Learn   more about the EU Clinical Trials Register   including the source of the information and the legal basis.


    The EU Clinical Trials Register currently displays   36366   clinical trials with a EudraCT protocol, of which   5991   are clinical trials conducted with subjects less than 18 years old.
    The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    Follow-up study to evaluate the long-term immunogenicity and safety of a HPV vaccine (580299) in healthy female subjects

    Summary
    EudraCT number
    2008-000369-44
    Trial protocol
    DE  
    Global end of trial date
    06 Jan 2015

    Results information
    Results version number
    v1(current)
    This version publication date
    11 May 2016
    First version publication date
    19 Jun 2015
    Other versions

    Trial information

    Close Top of page
    Trial identification
    Sponsor protocol code
    111375
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00877877
    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
    Interim
    Date of interim/final analysis
    21 Jan 2015
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    06 Jan 2015
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Jan 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the long-term immunogenicity of the HPV-16/18 vaccine by enzyme-linked immunosorbent assay (ELISA).
    Protection of trial subjects
    All subjects were supervised closely for at least 30 minutes following vaccination with appropriate medical treatment readily available. Vaccines were administered by qualified and trained personnel. Vaccines/products were administered only to eligible subjects that had no contraindications to any components of the vaccines. Subjects were followed-up from the time the subject consents to participate in the study until she/he is discharged.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    07 May 2008
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    10 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Colombia: 96
    Country: Number of subjects enrolled
    Germany: 208
    Country: Number of subjects enrolled
    Panama: 123
    Country: Number of subjects enrolled
    Taiwan: 103
    Country: Number of subjects enrolled
    Honduras: 102
    Worldwide total number of subjects
    632
    EEA total number of subjects
    208
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    632
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    Close Top of page
    Recruitment
    Recruitment details
    Subjects who participated in the primary study (NCT00196924) and received 3 doses of Cervarix.

    Pre-assignment
    Screening details
    Subjects enrolled in this study were primed with Cervarix vaccine as part of study NCT00196924. Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up phases. Actual enrollment differed depending on the rate of return for the follow-up study, so not all subjects enrolled came to each visit.

    Period 1
    Period 1 title
    Month 60
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Cervarix Month 60 Group
    Arm description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    Cervarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    All subjects received 3 doses of HPV vaccine intramuscularly into the deltoid region of the non-dominant arm.

    Number of subjects in period 1 [1]
    Cervarix Month 60 Group
    Started
    397
    Completed
    397
    Notes
    [1] - The number of subjects reported to be in the baseline period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up phases. Actual enrolment differed depending on the rate of return for the follow-up study, so not all enrolled subjects came to each visit.
    Period 2
    Period 2 title
    Month 72
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Cervarix Month 72 Group
    Arm description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    Cervarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    All subjects received 3 doses of HPV vaccine intramuscularly into the deltoid region of the non-dominant arm.

    Number of subjects in period 2
    Cervarix Month 72 Group
    Started
    397
    Completed
    529
    Joined
    132
         Subject inconsistency in coming to study visits
    132
    Period 3
    Period 3 title
    Month 84
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Cervarix Month 84 Group
    Arm description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    Cervarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    All subjects received 3 doses of HPV vaccine intramuscularly into the deltoid region of the non-dominant arm.

    Number of subjects in period 3 [2]
    Cervarix Month 84 Group
    Started
    523
    Completed
    523
    Notes
    [2] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up phases. Actual enrolment differed depending on the rate of return for the follow-up study, so not all enrolled subjects came to each visit.
    Period 4
    Period 4 title
    Month 96
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Cervarix Month 96 Group
    Arm description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    Cervarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    All subjects received 3 doses of HPV vaccine intramuscularly into the deltoid region of the non-dominant arm.

    Number of subjects in period 4 [3]
    Cervarix Month 96 Group
    Started
    522
    Completed
    522
    Notes
    [3] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up phases. Actual enrolment differed depending on the rate of return for the follow-up study, so not all enrolled subjects came to each visit.
    Period 5
    Period 5 title
    Month 108
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Cervarix Month 108 Group
    Arm description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    Cervarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    All subjects received 3 doses of HPV vaccine intramuscularly into the deltoid region of the non-dominant arm.

    Number of subjects in period 5 [4]
    Cervarix Month 108 Group
    Started
    507
    Completed
    507
    Notes
    [4] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up phases. Actual enrolment differed depending on the rate of return for the follow-up study, so not all enrolled subjects came to each visit.
    Period 6
    Period 6 title
    Month 120
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Not blinded

    Arms
    Arm title
    Cervarix Month 120 Group
    Arm description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Arm type
    Experimental

    Investigational medicinal product name
    Cervarix™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    All subjects received 3 doses of HPV vaccine intramuscularly into the deltoid region of the non-dominant arm.

    Number of subjects in period 6 [5]
    Cervarix Month 120 Group
    Started
    495
    Completed
    495
    Notes
    [5] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Subjects not returning for a specific visit were not withdrawn and could participate in the subsequent follow-up phases. Actual enrolment differed depending on the rate of return for the follow-up study, so not all enrolled subjects came to each visit.

    Baseline characteristics

    Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Month 60
    Reporting group description
    -

    Reporting group values
    Month 60 Total
    Number of subjects
    397 397
    Age categorical
    Units: Subjects
        In utero
    0
        Preterm newborn infants (gestational age < 37 wks)
    0
        Newborns (0-27 days)
    0
        Infants and toddlers (28 days-23 months)
    0
        Children (2-11 years)
    0
        Adolescents (12-17 years)
    0
        Adults (18-64 years)
    0
        From 65-84 years
    0
        85 years and over
    0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    17.1 ± 1.4 -
    Gender categorical
    Units: Subjects
        Female
    397 397
        Male
    0 0

    End points

    Close Top of page
    End points reporting groups
    Reporting group title
    Cervarix Month 60 Group
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Reporting group title
    Cervarix Month 72 Group
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Reporting group title
    Cervarix Month 84 Group
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Reporting group title
    Cervarix Month 96 Group
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Reporting group title
    Cervarix Month 108 Group
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.
    Reporting group title
    Cervarix Month 120 Group
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule.

    Primary: Number of seroconverted subjects with anti-HPV-16 antibody titers equal to or above 8 EL.U/mL

    Close Top of page
    End point title
    Number of seroconverted subjects with anti-HPV-16 antibody titers equal to or above 8 EL.U/mL [1]
    End point description
    Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.
    End point type
    Primary
    End point timeframe
    At Months 60, 72, 84, 96 and 108
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 96 Group Cervarix Month 84 Group Cervarix Month 72 Group Cervarix Month 60 Group Cervarix Month 108 Group
    Number of subjects analysed
    473
    475
    469
    353
    374
    Units: Subjects
        anti-HPV-16
    473
    475
    469
    353
    372
    No statistical analyses for this end point

    Primary: Number of seroconverted subjects with anti-HPV-18 antibody titers equal to or above 7 EL.U/mL

    Close Top of page
    End point title
    Number of seroconverted subjects with anti-HPV-18 antibody titers equal to or above 7 EL.U/mL [2]
    End point description
    Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer >= 8 or 7 EL.U/mL prior to vaccination.
    End point type
    Primary
    End point timeframe
    At Months 60, 72, 84, 96 and 108
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 96 Group Cervarix Month 84 Group Cervarix Month 72 Group Cervarix Month 60 Group Cervarix Month 108 Group
    Number of subjects analysed
    477
    473
    478
    358
    370
    Units: Subjects
        anti-HPV-18
    477
    473
    478
    358
    368
    No statistical analyses for this end point

    Primary: Anti-human papillomavirus-16 (anti-HPV-16) antibody titers

    Close Top of page
    End point title
    Anti-human papillomavirus-16 (anti-HPV-16) antibody titers [3]
    End point description
    Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
    End point type
    Primary
    End point timeframe
    At Months 60, 72, 84, 96 and 108
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 96 Group Cervarix Month 84 Group Cervarix Month 72 Group Cervarix Month 60 Group Cervarix Month 108 Group
    Number of subjects analysed
    499
    494
    502
    376
    392
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        anti-HPV-16
    1671 (1548.1 to 1803.7)
    1756.7 (1622.7 to 1901.7)
    1973.9 (1827.9 to 2131.6)
    2262.9 (2069.1 to 2475)
    1946.5 (1779.7 to 2128.9)
    No statistical analyses for this end point

    Primary: Anti-human papillomavirus-18 (anti-HPV-18) antibody titers

    Close Top of page
    End point title
    Anti-human papillomavirus-18 (anti-HPV-18) antibody titers [4]
    End point description
    Anti-HPV-16 and 18 antibody titers are given in Geometric Mean Titers (GMTs) in Enzyme-linked Immunosorbent Assay (ELISA) Units per milliliter (EL.U/mL).
    End point type
    Primary
    End point timeframe
    At months 60, 72, 84, 96 and 108
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 96 Group Cervarix Month 84 Group Cervarix Month 72 Group Cervarix Month 60 Group Cervarix Month 108 Group
    Number of subjects analysed
    499
    494
    502
    376
    391
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        anti-HPV-18
    679 (623.5 to 739.4)
    609.7 (559 to 664.9)
    762.8 (701 to 830.1)
    778.6 (703.1 to 862.1)
    754 (685.4 to 829.4)
    No statistical analyses for this end point

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

    Close Top of page
    End point title
    Number of subjects with serious adverse events (SAEs) [5]
    End point description
    SAEs assessed include medical occurrences that result in death, are life threatening, require hospitalization or prolongation of hospitalization, result in disability/incapacity or are a congenital anomaly/birth defect in the offspring of a study subject.
    End point type
    Primary
    End point timeframe
    From Month 48 to 60 (at Month 60), 60 to 72 (at Month 72), 72 to 84 (at Month 84), 84 to 96 (at Month 96), 96 to 108 (at Month 108), 108 to 120 (at Month 120).
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 96 Group Cervarix Month 84 Group Cervarix Month 72 Group Cervarix Month 60 Group Cervarix Month 108 Group Cervarix Month 120 Group
    Number of subjects analysed
    522
    523
    529
    397
    507
    495
    Units: Subjects
        SAEs
    8
    20
    20
    9
    15
    6
    No statistical analyses for this end point

    Primary: Anti-HPV-16 antibody titers

    Close Top of page
    End point title
    Anti-HPV-16 antibody titers [6]
    End point description
    Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer ≥8 or 7 EL.U/mL prior to vaccination.
    End point type
    Primary
    End point timeframe
    At Month 120
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 120 Group
    Number of subjects analysed
    416
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-HPV-16
    1607.9 (1480.8 to 1746.1)
    No statistical analyses for this end point

    Primary: Number of seroconverted subjects with HPV-16 antibody titers ≥8 EL.U/mL

    Close Top of page
    End point title
    Number of seroconverted subjects with HPV-16 antibody titers ≥8 EL.U/mL [7]
    End point description
    Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer ≥8 or 7 EL.U/mL prior to vaccination.
    End point type
    Primary
    End point timeframe
    At Month 120
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 120 Group
    Number of subjects analysed
    393
    Units: Subjects
        Anti-HPV-16
    393
    No statistical analyses for this end point

    Primary: Number of seroconverted subjects with HPV-18 antibody titers ≥7 EL.U/mL

    Close Top of page
    End point title
    Number of seroconverted subjects with HPV-18 antibody titers ≥7 EL.U/mL [8]
    End point description
    Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer ≥8 or 7 EL.U/mL prior to vaccination.
    End point type
    Primary
    End point timeframe
    At Month 120
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 120 Group
    Number of subjects analysed
    395
    Units: Subjects
        Anti-HPV-18
    395
    No statistical analyses for this end point

    Primary: Anti-HPV-18 antibody titers

    Close Top of page
    End point title
    Anti-HPV-18 antibody titers [9]
    End point description
    Anti-HPV-16 assay cut-off value was defined as 8 ELISA units per milliliter (EL.U/mL). Anti-HPV-18 assay cut-off value was defined as 7 EL.U/mL. Seroconversion was defined as the appearance of antibodies (i.e. titer greater than or equal to the cut-off value) in the serum of subjects seronegative before vaccination. A seronegative subject is a subject with antibody titer < 8 or 7 EL.U/mL prior to vaccination. A seropositive subject is a subject with antibody titer ≥8 or 7 EL.U/mL prior to vaccination.
    End point type
    Primary
    End point timeframe
    At Month 120
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: The scope of this primary endpoint was descriptive, no statistical analyses were conducted.
    End point values
    Cervarix Month 120 Group
    Number of subjects analysed
    415
    Units: EL.U/mL
    geometric mean (confidence interval 95%)
        Anti-HPV-18
    608 (552.5 to 669.1)
    No statistical analyses for this end point

    Adverse events

    Close Top of page
    Adverse events information [1]
    Timeframe for reporting adverse events
    Serious Adverse Events were assessed by time intervals: Months 48-60, Months 60-72, Months 72-84, Months 84-96, Months 96-108 and Months 108-120.
    Adverse event reporting additional description
    Other (non-serious) Adverse Events were not collected/assessed during this long-term follow-up study.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Cervarix Group from Month 48 until Month 60
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule and for whom serious adverse events were collected from Month 48 until Month 60.

    Reporting group title
    Cervarix Group from Month 60 until Month 72
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule and for whom serious adverse events were collected from Month 60 until Month 72.

    Reporting group title
    Cervarix Group from Month 72 to Month 84
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule and for whom serious adverse events were collected from Month 72 until Month 84.

    Reporting group title
    Cervarix Group from Month 84 to Month 96
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule and for whom serious adverse events were collected from Month 84 until Month 96.

    Reporting group title
    Cervarix Group from Month 96 to Month 108
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule and for whom serious adverse events were collected from Month 96 until Month 108.

    Reporting group title
    Cervarix Group from Month 108 to Month 120
    Reporting group description
    Subjects in the Cervarix Group of the primary study (NCT00196924), who had then received 3 doses of Cervarix™ vaccine intramuscularly into the deltoid region of the non-dominant arm according to a 0, 1, 6 month vaccination schedule and for whom serious adverse events were collected from Month 108 to Month 120.

    Notes
    [1] - There are no non-serious adverse events recorded for these results. It is expected that there will be at least one non-serious adverse event reported.
    Justification: Only serious adverse event were collected for this study.
    Serious adverse events
    Cervarix Group from Month 48 until Month 60 Cervarix Group from Month 60 until Month 72 Cervarix Group from Month 72 to Month 84 Cervarix Group from Month 84 to Month 96 Cervarix Group from Month 96 to Month 108 Cervarix Group from Month 108 to Month 120
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 397 (2.27%)
    20 / 529 (3.78%)
    20 / 523 (3.82%)
    8 / 522 (1.53%)
    15 / 507 (2.96%)
    6 / 495 (1.21%)
         number of deaths (all causes)
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    0
    0
    0
    Vascular disorders
    Circulatory collapse
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypertension
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypovolaemic shock
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Surgical and medical procedures
    Abortion induced
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Ovarian germ cell teratoma benign
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fibroadenoma of breast
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian neoplasm
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hodgkin’s disease
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    1 / 495 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous complete
         subjects affected / exposed
    1 / 397 (0.25%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion spontaneous incomplete
         subjects affected / exposed
    1 / 397 (0.25%)
    3 / 529 (0.57%)
    2 / 523 (0.38%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 3
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Threatened labour
         subjects affected / exposed
    1 / 397 (0.25%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pre-eclampsia
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Olygohydramnios
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    2 / 523 (0.38%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Foetal death
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cervical incompetence
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gestational diabetes
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion spontaneous
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ectopic pregnancy
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    1 / 495 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Premature baby
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stillbirth
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pain
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicide attempt
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Depression
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Drug abuse
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    1 / 397 (0.25%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ovarian cyst ruptured
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neonatal tachypnoea
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Inguinal hernia
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    1 / 495 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Alcohol poisoning
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Burns third degree
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Multiple injuries
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    2 / 523 (0.38%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Joint dislocation
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stab wound
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abdominal injury
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ligament rupture
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Contusion
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Excoriation
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Skull malformation
         subjects affected / exposed
    1 / 397 (0.25%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital megaureter
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Talipes
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Heart disease congenital
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary malformation
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Neonatal asphyxia
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neonatal respiratory distress syndrome
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Brain injury
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cerebral cyst
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Duodenal ulcer
         subjects affected / exposed
    1 / 397 (0.25%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Crohn’s disease
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diverticulum intestinal
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastritis
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Coeliac disease
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enteritis
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Irritable bowel syndrome
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    1 / 495 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Type 1 diabetes mellitus
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Abscess
         subjects affected / exposed
    1 / 397 (0.25%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 397 (0.25%)
    1 / 529 (0.19%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cystitis
         subjects affected / exposed
    1 / 397 (0.25%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 397 (0.25%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    0 / 397 (0.00%)
    2 / 529 (0.38%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pharyngeal abscess
         subjects affected / exposed
    0 / 397 (0.00%)
    2 / 529 (0.38%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Breast abscess
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Chronic sinusitis
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometritis
         subjects affected / exposed
    0 / 397 (0.00%)
    1 / 529 (0.19%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endometritis decidual
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    1 / 523 (0.19%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    2 / 522 (0.38%)
    0 / 507 (0.00%)
    1 / 495 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonsillar abscess
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    1 / 522 (0.19%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pilonidal cyst
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Postoperative wound infection
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    1 / 507 (0.20%)
    0 / 495 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    1 / 495 (0.20%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cervarix Group from Month 48 until Month 60 Cervarix Group from Month 60 until Month 72 Cervarix Group from Month 72 to Month 84 Cervarix Group from Month 84 to Month 96 Cervarix Group from Month 96 to Month 108 Cervarix Group from Month 108 to Month 120
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    0 / 397 (0.00%)
    0 / 529 (0.00%)
    0 / 523 (0.00%)
    0 / 522 (0.00%)
    0 / 507 (0.00%)
    0 / 495 (0.00%)

    More information

    Close Top of page

    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    02 Dec 2013
    The HPV-025 protocol was amended for the following reasons: 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 will be implemented for the testing of samples from Month 96 (Year 8) onwards. The number of subjects who were enrolled in the immunogenicity subset of the primary study HPV-013, received three doses of HPV vaccine and participated in the follow-up study Ext HPV-013 was erroneously mentioned as 626 subjects. This has now been corrected to 625 subjects. The total number of subjects in the Ext HPV-013 study was corrected to 1244 subjects.

    Interruptions (globally)

    Were there any global interruptions to the trial? No

    Limitations and caveats

    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    EU Clinical Trials Register Service Desk: https://servicedesk.ema.europa.eu
    European Medicines Agency © 1995-2020 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    Legal notice
    EMA HMA