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    Clinical Trial Results:
    A Phase III, Randomized, International, Placebo-Controlled, Double-Blind Clinical Trial to Study the Tolerability and Immunogenicity of V503, a Multivalent Human Papillomavirus (HPV) L1 Virus- Like Particle (VLP) Vaccine, Given to Females 12-26 Years of Age Who Have Previously Received GARDASIL™

    Summary
    EudraCT number
    		 2009-015500-26
    Trial protocol
    		 SE   DK   Outside EU/EEA  
    Global end of trial date
    28 Nov 2015

    Results information
    Results version number
    		 v1(current)
    This version publication date
    04 Jun 2016
    First version publication date
    04 Jun 2016
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    V503-006
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT01047345
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Merck Registration Number: 2010_504
    Sponsors
    Sponsor organisation name
    Merck Sharp & Dohme Corp.
    Sponsor organisation address
    2000 Galloping Hill Road, Kenilworth, NJ, United States, 07033
    Public contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.com
    Scientific contact
    Clinical Trials Disclosure, Merck Sharp & Dohme Corp., ClinicalTrialsDisclosure@merck.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
    28 Nov 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Nov 2015
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This study will evaluate whether V503 (9vHPV vaccine) is well tolerated in girls and women between 12 and 26 years old who have previously been vaccinated with GARDASIL™. Participants will receive vaccination with 9vHPV vaccine or placebo on Day 1, Month 2, and Month 6 of the Base Study. Participants who receive placebo in the Base Study will be eligible to receive vaccination with 9vHPV vaccine on Day 1, Month 2, and Month 6 of the Extension Study.
    Protection of trial subjects
    This study was conducted in conformance with Good Clinical Practice standards and applicable country and/or local statutes and regulations regarding ethical committee review, informed consent, and the protection of human subjects participating in biomedical research.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    24 Feb 2010
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Canada: 70
    Country: Number of subjects enrolled
    Colombia: 151
    Country: Number of subjects enrolled
    Denmark: 303
    Country: Number of subjects enrolled
    Hong Kong: 46
    Country: Number of subjects enrolled
    Mexico: 20
    Country: Number of subjects enrolled
    Puerto Rico: 12
    Country: Number of subjects enrolled
    Sweden: 105
    Country: Number of subjects enrolled
    United States: 214
    Worldwide total number of subjects
    924
    EEA total number of subjects
    408
    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)
    331
    Adults (18-64 years)
    593
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 -

    Pre-assignment
    Screening details
    		 Healthy female participants Age 12 to 26 who received a 3-dose regimen of marketed GARDASIL™ within a 1 year period and the last dose of GARDASIL™ was at least 1 year from study day 1. Other inclusion and exclusion criteria applied.

    Period 1
    Period 1 title
    Base Study
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 9vHPV Vaccine- Base Study
    Arm description
    		 9vHPV vaccine (V503) 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study. Participants will not continue to the Extension Study
    Arm type
    		 Experimental

    Investigational medicinal product name
    9vHPV Vaccine
    Investigational medicinal product code
    Other name
    V503
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study

    Arm title
    		 Placebo - Base Study
    Arm description
    		 0.5 mL intramuscular injection of saline placebo at Day 1, Month 2, and Month 6 of the Base Study. After completion of the Base Study, participants will be eligible to receive 9vHPV 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Extension Study.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study

    Number of subjects in period 1
    		9vHPV Vaccine- Base Study Placebo - Base Study
    Started
    618
    306
    Vaccination 1
    615
    306
    Vaccination 2
    604
    304
    Vaccination 3
    597
    300
    Completed
    596
    300
    Not completed
    22
    6
         Consent withdrawn by subject
    12
    4
         Adverse event, non-fatal
    3
    -
         Lost to follow-up
    4
    1
         Protocol deviation
    3
    1
    Period 2
    Period 2 title
    Extension
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 9vHPV Vaccine -Extension
    Arm description
    		 Participants who received placebo in base study and elected to have 9vHPV vaccination in extension.
    Arm type
    		 Experimental

    Investigational medicinal product name
    9vHPV Vaccine
    Investigational medicinal product code
    Other name
    V503
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Extension

    Number of subjects in period 2 [1]
    		9vHPV Vaccine -Extension
    Started
    102
    Vaccination 4
    102
    Vaccination 5
    99
    Vaccination 6
    95 [2]
    Completed
    96
    Not completed
    6
         Consent withdrawn by subject
    1
         Lost to follow-up
    5
    Notes
    [1] - 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: Participation in the extension was voluntary. Not all eligible participants elected to enter the extension.
    [2] - The number of subjects at this milestone seems inconsistent with the number of subjects in the arm. It is expected that the number of subjects will be greater than, or equal to the number that completed, minus those who left.
    Justification: One participant received 3rd 9vHPV vaccination outside the context of the study and therefore was not eligible to receive 3rd dose as part of the study. Participant remained in the study, was followed for safety to study completion.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    9vHPV Vaccine- Base Study
    Reporting group description
    		 9vHPV vaccine (V503) 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study. Participants will not continue to the Extension Study

    Reporting group title
    Placebo - Base Study
    Reporting group description
    		 0.5 mL intramuscular injection of saline placebo at Day 1, Month 2, and Month 6 of the Base Study. After completion of the Base Study, participants will be eligible to receive 9vHPV 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Extension Study.

    Reporting group values
    		 9vHPV Vaccine- Base Study Placebo - Base Study Total
    Number of subjects
    		 618 306 924
    Age Categorical
    Units: Subjects
        12 to 15 years
    		 122 60 182
        16 to 26 years
    		 496 246 742
    Gender Categorical
    Units: Subjects
        Female
    		 618 306 924
        Male
    		 0 0 0

    End points

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    End points reporting groups
    Reporting group title
    9vHPV Vaccine- Base Study
    Reporting group description
    		 9vHPV vaccine (V503) 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study. Participants will not continue to the Extension Study

    Reporting group title
    Placebo - Base Study
    Reporting group description
    		 0.5 mL intramuscular injection of saline placebo at Day 1, Month 2, and Month 6 of the Base Study. After completion of the Base Study, participants will be eligible to receive 9vHPV 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Extension Study.
    Reporting group title
    9vHPV Vaccine -Extension
    Reporting group description
    		 Participants who received placebo in base study and elected to have 9vHPV vaccination in extension.

    Subject analysis set title
    9vHPV Vaccine - Efficacy
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants who received all 3 vaccinations within an acceptable day range, had Month 7 serology sample collected within an acceptable range and had no other protocol violations that could interfere with the immune response to the vaccine.

    Subject analysis set title
    Placebo - Efficacy
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants who received all 3 vaccinations within an acceptable day range, had Month 7 serology sample collected within an acceptable range and had no other protocol violations that could interfere with the immune response to the vaccine.

    Primary: Percentage of Participants Who Experience an Injection-site Adverse Event (AE) – Base Study

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    End point title
    		 Percentage of Participants Who Experience an Injection-site Adverse Event (AE) – Base Study [1]
    End point description
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. The percentage of participants who reported an AE that was associated with the injection site such as redness, swelling, and pain/tenderness/soreness was summarized. Analysis population included all participants who received at least 1 vaccination and had follow-up safety data.
    End point type
    Primary
    End point timeframe
    up to 5 days after any vaccination - Base Study
    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: No statistical analysis was planned or performed for this endpoint.
    End point values
    		 9vHPV Vaccine- Base Study Placebo - Base Study
    Number of subjects analysed
    608
    305
    Units: Percentage of Participants
        number (not applicable)
    91.1
    43.9
    No statistical analyses for this end point

    Primary: Percentage of Participants with Body Temperature ≥100.0°F (≥37.8ºC) – Base Study

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    End point title
    		 Percentage of Participants with Body Temperature ≥100.0°F (≥37.8ºC) – Base Study
    End point description
    Participants collected their oral body temperature in the evening of their vaccination day and at the same time each day thereafter for 4 days. The maximum body temperature obtained within 5 days of any of the 3 vaccinations was recorded. Analysis population included all participants who received at least 1 vaccination and had follow-up safety data.
    End point type
    Primary
    End point timeframe
    up to 5 days after any vaccination - Base Study
    End point values
    		 9vHPV Vaccine- Base Study Placebo - Base Study
    Number of subjects analysed
    604
    304
    Units: Percentage of Participants
        number (not applicable)
    6.5
    3
    Statistical analysis title
    		 Comparison of Difference in Percentages
    Statistical analysis description
    Comparison based on Miettinen & Nurminen method
    Comparison groups
    9vHPV Vaccine- Base Study v Placebo - Base Study
    Number of subjects included in analysis
    908
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.026
    Method
    		 Miettinen & Nurminen
    Parameter type
    		 Difference in Percentages
    Point estimate
    3.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.5
         upper limit
    		 6.2

    Primary: Percentage of Participants Who Experience a Systemic AE – Base Study

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    End point title
    		 Percentage of Participants Who Experience a Systemic AE – Base Study
    End point description
    An AE is defined as any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the use of the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Systemic AEs were those not categorized as injection-site AEs. Analysis population included all participants who received at least 1 vaccination and had follow-up safety data.
    End point type
    Primary
    End point timeframe
    up to 14 days after any vaccination - Base Study
    End point values
    		 9vHPV Vaccine- Base Study Placebo - Base Study
    Number of subjects analysed
    608
    305
    Units: Percentage of Participants
        number (not applicable)
    59.7
    55.7
    Statistical analysis title
    		 Comparison of Difference in Percentages
    Statistical analysis description
    Analysis was performed based on Miettinen & Nurminen method
    Comparison groups
    9vHPV Vaccine- Base Study v Placebo - Base Study
    Number of subjects included in analysis
    913
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    4
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.8
         upper limit
    		 10.8

    Primary: Percentage of Participants Who Experience a Serious Adverse Event (SAE) Within 15 Days of any Vaccination – Base Study

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    End point title
    		 Percentage of Participants Who Experience a Serious Adverse Event (SAE) Within 15 Days of any Vaccination – Base Study
    End point description
    An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention. Analysis population included all participants who received at least 1 vaccination and had follow-up safety data.
    End point type
    Primary
    End point timeframe
    up to 14 days after any vaccination - Base Study
    End point values
    		 9vHPV Vaccine- Base Study Placebo - Base Study
    Number of subjects analysed
    608
    305
    Units: Percentage of Participants
        number (not applicable)
    0.3
    0.3
    Statistical analysis title
    		 Comparison of Difference in Percentages
    Statistical analysis description
    Analysis was performed based on Miettinen & Nurminen method
    Comparison groups
    9vHPV Vaccine- Base Study v Placebo - Base Study
    Number of subjects included in analysis
    913
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    0
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 0.9

    Primary: Percentage of Participants Who Experience a Vaccine-related SAE Any Time During Study– Base Study

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    End point title
    		 Percentage of Participants Who Experience a Vaccine-related SAE Any Time During Study– Base Study
    End point description
    An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention. An SAE that is judged by the Investigator to be “definitely related,” “probably related,” or “possibly related” is defined as a vaccine-related SAE. Analysis population included all participants who received at least 1 vaccination and had follow-up safety data.
    End point type
    Primary
    End point timeframe
    up to 7 months - Base Study
    End point values
    		 9vHPV Vaccine- Base Study Placebo - Base Study
    Number of subjects analysed
    608
    305
    Units: Percentage of Participants
        number (not applicable)
    0.2
    0.3
    Statistical analysis title
    		 Comparison of Difference in Percentages
    Statistical analysis description
    Analysis was performed based on Miettinen & Nurminen method
    Comparison groups
    9vHPV Vaccine- Base Study v Placebo - Base Study
    Number of subjects included in analysis
    913
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    -0.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.7
         upper limit
    		 0.6

    Primary: Percentage of Participants Who Experience a Severe Injection-site AE – Base Study

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    End point title
    		 Percentage of Participants Who Experience a Severe Injection-site AE – Base Study
    End point description
    An AE is any unfavorable and unintended change in the structure, function, or chemistry of the body temporally associated with the use of the study vaccine, whether or not considered related to the vaccine. Any worsening of a preexisting condition which is temporally associated with the use of the study vaccine is also an AE. Participants were instructed to estimate the severity of AEs such as pain at injection site as mild (awareness of symptom, but easily tolerated), moderate (discomfort enough to cause interference with usual activities), or severe (incapacitating with inability to work or do usual activity). Additionally, participants were instructed to measure any swelling and/or erythema at its greatest width. Swelling or erythema with diameter >2 inches (>5 cm) was recorded as severe. All AEs associated with the injection site and reported as severe were summarized. Analysis population included all participants who received at least 1 vaccination and had follow-up safety data.
    End point type
    Primary
    End point timeframe
    up to 5 days after any vaccination - Base Study
    End point values
    		 9vHPV Vaccine- Base Study Placebo - Base Study
    Number of subjects analysed
    608
    305
    Units: Percentage of Participants
        number (not applicable)
    11.2
    1
    Statistical analysis title
    		 Comparison of Difference in Percentages
    Statistical analysis description
    Comparison based on Miettinen & Nurminen method
    Comparison groups
    9vHPV Vaccine- Base Study v Placebo - Base Study
    Number of subjects included in analysis
    913
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    Method
    Parameter type
    		 Difference in Percentages
    Point estimate
    10.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 7.5
         upper limit
    		 13.1

    Secondary: Percentage of Participants who Seroconvert to Each of the HPV Types Contained in the Vaccine - Base Study

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    End point title
    		 Percentage of Participants who Seroconvert to Each of the HPV Types Contained in the Vaccine - Base Study
    End point description
    Serum antibody titers for HPV virus-like particles (VLPs), Types 6, 11, 16, 18, 31, 33, 45, 52 and 58 were determined 4 weeks post-vaccination 3 using competitive luminex immunoassay (cLIA). The serostatus cutoffs (milli Merck U/mL) for HPV types were as follows: HPV Type 6: ≥30, HPV Type 11: ≥16; HPV Type 16: ≥20, HPV Type 18: ≥24, HPV Type 31: ≥10, HPV Type 33: ≥8, HPV Type 45: ≥8, HPV Type 52: ≥8, and HPV Type 58: ≥8. Analysis population included all participants that received all 3 vaccinations within an acceptable day range, had Month 7 serology sample collected within an acceptable range and had no other protocol violations that could interfere with the immune response to the vaccine.
    End point type
    Secondary
    End point timeframe
    4 weeks post-vaccination 3 (Month 7; End of Base Study)
    End point values
    		 9vHPV Vaccine - Efficacy Placebo - Efficacy
    Number of subjects analysed
    515
    261
    Units: Percentage of Participants
    number (confidence interval 95%)
        Anti-HPV 6 (n=511; n=251)
    100 (99.3 to 100)
    100 (98.5 to 100)
        Anti-HPV 11 (n=515; n=261)
    100 (99.3 to 100)
    99.6 (97.9 to 100)
        Anti-HPV 16 (n=515; n=261)
    100 (99.3 to 100)
    100 (98.6 to 100)
        Anti-HPV 18 (n=515; n=261)
    100 (99.3 to 100)
    85.4 (80.6 to 89.5)
        Anti-HPV 31 (n=515; n=261)
    99.8 (98.9 to 100)
    23.8 (18.7 to 29.4)
        Anti-HPV 33 (n=515; n=261)
    99.8 (98.9 to 100)
    8 (5 to 12)
        Anti-HPV 45 (n=515; n=261)
    98.3 (96.7 to 99.2)
    3.4 (1.6 to 6.4)
        Anti-HPV 52 (n=515; n=261)
    99.6 (98.6 to 100)
    3.8 (1.9 to 6.9)
        Anti-HPV 58 (n=515; n=261)
    99.8 (98.9 to 100)
    9.2 (6 to 13.4)
    No statistical analyses for this end point

    Other pre-specified: Percentage of Participants Who Experience an SAE- Extension Study

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    End point title
    		 Percentage of Participants Who Experience an SAE- Extension Study
    End point description
    An SAE is one that results in death, disability/incapacity, or hospitalization or is life threatening, a congenital anomaly or birth defect, cancer, an overdose, or otherwise jeopardizes the participant and may require medical intervention.
    End point type
    Other pre-specified
    End point timeframe
    up to Month 7 - Extension Study
    End point values
    		 9vHPV Vaccine -Extension
    Number of subjects analysed
    99
    Units: Percentage of Participants
        number (not applicable)
    2
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 5 days after any vaccination (Non-serious injection site AEs); up to 15 days after any vaccination (Non-serious systemic AEs) and up to 7 months (Serious AEs) - Base Study; up to 7 months-Extension
    Adverse event reporting additional description
    Population included all participants who received at least 1 vaccination and had available follow-up data. Only SAEs were collected systematically in the extension. Although some unsolicited non-serious AEs were reported, none exceeded the 5% cut-off.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    14.0
    Reporting groups
    Reporting group title
    9vHPV Vaccine- Base Study
    Reporting group description
    		 9vHPV vaccine (V503) 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Base Study. Participants will not continue to the Extension Study

    Reporting group title
    9vHPV Vaccine- Extension
    Reporting group description
    		 Participants who received placebo in base study and elected to have 9vHPV vaccination in extension.

    Reporting group title
    Placebo - Base Study
    Reporting group description
    		 0.5 mL intramuscular injection of saline placebo at Day 1, Month 2, and Month 6 of the Base Study. After completion of the Base Study, participants will be eligible to receive 9vHPV 0.5 mL intramuscular injection at Day 1, Month 2, and Month 6 of the Extension Study.

    Serious adverse events
    		 9vHPV Vaccine- Base Study 9vHPV Vaccine- Extension Placebo - Base Study
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 608 (0.49%)
    2 / 99 (2.02%)
    3 / 305 (0.98%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Injury, poisoning and procedural complications
    Lumbar vertebral fracture
         subjects affected / exposed
    0 / 608 (0.00%)
    0 / 99 (0.00%)
    1 / 305 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Thoracic vertebral fracture
         subjects affected / exposed
    0 / 608 (0.00%)
    0 / 99 (0.00%)
    1 / 305 (0.33%)
         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
    Abortion induced
         subjects affected / exposed
    0 / 608 (0.00%)
    0 / 99 (0.00%)
    1 / 305 (0.33%)
         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
    Migraine
         subjects affected / exposed
    0 / 608 (0.00%)
    0 / 99 (0.00%)
    1 / 305 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    1 / 608 (0.16%)
    0 / 99 (0.00%)
    0 / 305 (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 pain
         subjects affected / exposed
    0 / 608 (0.00%)
    1 / 99 (1.01%)
    0 / 305 (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
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 608 (0.16%)
    0 / 99 (0.00%)
    0 / 305 (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 / 608 (0.16%)
    0 / 99 (0.00%)
    0 / 305 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    0 / 608 (0.00%)
    1 / 99 (1.01%)
    0 / 305 (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
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 9vHPV Vaccine- Base Study 9vHPV Vaccine- Extension Placebo - Base Study
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    566 / 608 (93.09%)
    0 / 99 (0.00%)
    197 / 305 (64.59%)
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    31 / 608 (5.10%)
    0 / 99 (0.00%)
    6 / 305 (1.97%)
         occurrences all number
    34
    0
    8
    Headache
         subjects affected / exposed
    190 / 608 (31.25%)
    0 / 99 (0.00%)
    81 / 305 (26.56%)
         occurrences all number
    318
    0
    150
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    258 / 608 (42.43%)
    0 / 99 (0.00%)
    26 / 305 (8.52%)
         occurrences all number
    420
    0
    33
    Injection site pain
         subjects affected / exposed
    549 / 608 (90.30%)
    0 / 99 (0.00%)
    117 / 305 (38.36%)
         occurrences all number
    1392
    0
    182
    Injection site pruritus
         subjects affected / exposed
    48 / 608 (7.89%)
    0 / 99 (0.00%)
    4 / 305 (1.31%)
         occurrences all number
    68
    0
    5
    Injection site swelling
         subjects affected / exposed
    298 / 608 (49.01%)
    0 / 99 (0.00%)
    18 / 305 (5.90%)
         occurrences all number
    558
    0
    27
    Pyrexia
         subjects affected / exposed
    42 / 608 (6.91%)
    0 / 99 (0.00%)
    10 / 305 (3.28%)
         occurrences all number
    50
    0
    10
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    52 / 608 (8.55%)
    0 / 99 (0.00%)
    12 / 305 (3.93%)
         occurrences all number
    67
    0
    13
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    40 / 608 (6.58%)
    0 / 99 (0.00%)
    12 / 305 (3.93%)
         occurrences all number
    46
    0
    14
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    47 / 608 (7.73%)
    0 / 99 (0.00%)
    19 / 305 (6.23%)
         occurrences all number
    55
    0
    20

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Jan 2014
    Amendment 2: Added extension study. Participants who received placebo in the base study could elect to receive the 9vHPV vaccine in the extension.

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

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