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 were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43865   clinical trials with a EudraCT protocol, of which   7286   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).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    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:
    An Immunogenicity and Safety Study of GARDASIL™ in Chinese Female Subjects Aged 9 to 45 Years and Male Subjects Aged 9 to 15 Years

    Summary
    EudraCT number
    		 2014-004581-16
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    28 Feb 2009

    Results information
    Results version number
    		 v1(current)
    This version publication date
    10 Feb 2016
    First version publication date
    25 Jul 2015
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    V501-030
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT00496626
    WHO universal trial number (UTN)
    		 -
    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 Feb 2009
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    28 Feb 2009
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Feb 2009
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    This is a China registration study. A randomized, double-blind, placebo-controlled immunogenicity and safety study in Chinese female participants aged 9 to 45 years and male participants aged 9 to 15 years. Approximately 600 participants will be randomized in a 1:1 ratio to receive either vaccine or aluminum-containing placebo. Each participant received one injection at each visit at Day 1, Month 2, and Month 6. Vaccine or placebo was given as a 0.5-mL intramuscular injection. Serum will be collected from all participants to evaluate immune response against anti-Human Papillomavirus (HPV) 6/11/16/18 with Luminex Assay. At Month 2, Month 6, Month 7, subjects will be evaluated for any new medical condition or health concerns and Serious Adverse Experiences throughout the study. The primary objective is to evaluate the vaccine-induced serum anti-HPV 6, 11, 16 and 18 antibody titers following 3-dose regimen of Gardasil® compared with placebo.
    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
    20 Jul 2008
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    China: 600
    Worldwide total number of subjects
    600
    EEA total number of subjects
    0
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    95
    Adolescents (12-17 years)
    122
    Adults (18-64 years)
    383
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Healthy Chinese participants aged 9 to 45 years (females) or 9 to 15 years (males) were enrolled. Additional inclusion and exclusion criteria applied.

    Pre-assignment
    Screening details
    		 A total of 610 participants were screened and 600 were enrolled.

    Period 1
    Period 1 title
    Vaccination and Follow-up (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Vaccine (GARDASIL™) Group
    Arm description
    		 Participants received 0.5 mL intramuscular injection of GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.
    Arm type
    		 Experimental

    Investigational medicinal product name
    GARDASIL™
    Investigational medicinal product code
    Other name
    Human Papillomavirus (HPV)(Type 6, 11, 16, 18) Recombinant Vaccine, V501
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL intramuscular injection of GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Arm title
    		 Placebo Group
    Arm description
    		 Participants received 0.5 mL intramuscular injection of placebo to GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo to GARDASIL™
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    Participants received 0.5 mL intramuscular injection of placebo to GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Number of subjects in period 1
    		Vaccine (GARDASIL™) Group Placebo Group
    Started
    302
    298
    Completed
    296
    292
    Not completed
    6
    6
         Consent withdrawn by subject
    5
    4
         Lost to follow-up
    -
    1
         Relocated
    -
    1
         Protocol deviation
    1
    -

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Vaccine (GARDASIL™) Group
    Reporting group description
    		 Participants received 0.5 mL intramuscular injection of GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Reporting group title
    Placebo Group
    Reporting group description
    		 Participants received 0.5 mL intramuscular injection of placebo to GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Reporting group values
    		 Vaccine (GARDASIL™) Group Placebo Group Total
    Number of subjects
    		 302 298 600
    Age categorical
    Units: Subjects
        9 to 15 years of age
    		 101 99 200
        16 to 26 years of age
    		 76 74 150
        27 to 34 years of age
    		 63 62 125
        35 to 45 years of age
    		 62 63 125
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 24.5 ± 10.9 24.8 ± 11 -
    Gender categorical
    Units: Subjects
        Female
    		 251 249 500
        Male
    		 51 49 100
    Body Temperature
    Units: ° C
        arithmetic mean (standard deviation)
    		 36.5 ± 0.31 36.5 ± 0.31 -
    Pulse Rate
    Units: Beats per minute
        arithmetic mean (standard deviation)
    		 74.4 ± 11.2 74.6 ± 11.2 -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Vaccine (GARDASIL™) Group
    Reporting group description
    		 Participants received 0.5 mL intramuscular injection of GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Reporting group title
    Placebo Group
    Reporting group description
    		 Participants received 0.5 mL intramuscular injection of placebo to GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Subject analysis set title
    Vaccine (GARDASIL™) Group Day 1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received 0.5 mL intramuscular injection of GARDASIL™ on Day 1, Month 2, and Month 6. This Subject Analysis Set is for Day 1 immunogenicity results.

    Subject analysis set title
    Vaccine (GARDASIL™) Group Month 7
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received 0.5 mL intramuscular injection of GARDASIL™ on Day 1, Month 2, and Month 6. This Subject Analysis Set is for Month 7 immunogenicity results.

    Subject analysis set title
    Placebo Group Day 1
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received 0.5 mL intramuscular injection of placebo to GARDASIL™ on Day 1, Month 2, and Month 6. This Subject Analysis Set is for Day 1 immunogenicity results.

    Subject analysis set title
    Placebo Group Month 7
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received 0.5 mL intramuscular injection of placebo to GARDASIL™ on Day 1, Month 2, and Month 6. This Subject Analysis Set is for Month 7 immunogenicity results.

    Primary: Geometric Mean Titer (GMT) of Anti-HPV 6, 11, 16, and 18

    		 Close Top of page
    End point title
    		 Geometric Mean Titer (GMT) of Anti-HPV 6, 11, 16, and 18
    End point description
    Measured GMT of anti-HPV 6, 11, 16 and 18 at Day 1 and Month 7 (1 month after completion of administration of a 6-month 3-dose regimen of vaccines). GMT at Day 1 was used to define per-protocol population. Antibody titers were tested with Luminex array (cLIA). The numeric values for the Day 1 (Vaccine and Placebo groups) and the Month 7 (Placebo groups) are the threshold of detection for the cLIA assays. The reported values are all below the lower limit of qualification, ([less than] <7, <8, <11, <10 respectively). Per-protocol population, defined as all participants who received all 3 dose vaccinations within acceptable day ranges, had at least 1 valid serology result after the third injection, and adhered to protocol guidelines. To be included in the immunogenicity analysis for given HPV type, participants must be seronegative to that HPV type at baseline.
    End point type
    Primary
    End point timeframe
    Day 1 before vaccination and Month 7
    End point values
    		 Vaccine (GARDASIL™) Group Day 1 Vaccine (GARDASIL™) Group Month 7 Placebo Group Day 1 Placebo Group Month 7
    Number of subjects analysed
    302
    302
    298
    298
    Units: milli Merck units/mL
    geometric mean (confidence interval 95%)
        Anti-HPV 6 (N=269, 269, 275, 275)
    7 (7 to 7)
    426 (369.5 to 491)
    7 (7 to 7)
    7 (7 to 7)
        Anti-HPV 11 (N=279, 279, 281, 281)
    8 (8 to 8)
    665 (589.4 to 750.3)
    8 (8 to 8)
    8 (8 to 8)
        Anti-HPV 16 (N=277, 277, 277, 277)
    11 (11 to 11)
    2336.9 (2023.1 to 2699.3)
    11 (11 to 11)
    11 (11 to 11)
        Anti-HPV 18 (N=287, 287, 282, 282)
    10 (10 to 10)
    535.6 (461.8 to 621.2)
    10 (10 to 10)
    10 (10 to 10)
    Statistical analysis title
    		 Superiority Analysis for All HPV Types: Month 7
    Statistical analysis description
    An Analysis of Covariance (ANCOVA) model was used for each HPV type, based on the pooled data from all age groups and genders. The natural-log-transformed titer was the response variable, and vaccination group, gender and age group were covariates. The null hypothesis was that the GMT ratio (Gardasil/Placebo) was equal to 1.
    Comparison groups
    Vaccine (GARDASIL™) Group Month 7 v Placebo Group Month 7
    Number of subjects included in analysis
    600
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.05
    Method
    		 ANCOVA
    Parameter type
    		 GMT Ratio (Gardasil/Placebo)
    Point estimate
    101.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 88.1
         upper limit
    		 117.2
    Notes
    [1] - Superiority of GARDASIL™ to placebo was claimed if, for each of the four HPV types, the lower bound of the two-sided 95% CI on the GMT ratio [GARDASIL™/placebo] being >1, or equivalently, the two-sided p-value <0.05. The ANCOVA models showed the lower bounds of two-sided 95% CI on the GMT ratio [GARDASIL™/placebo] were greater than 1 for each HPV type, so the null hypothesis was rejected. The CI reported is for HPV18, the type with the smallest CI lower bound.

    Secondary: Number of Participants Who Were Seronegative at Baseline and Developed Seropositive at Month 7

    		 Close Top of page
    End point title
    		 Number of Participants Who Were Seronegative at Baseline and Developed Seropositive at Month 7
    End point description
    Anti-HPV 6, 11, 16, 18 Seroconversion Rate, i.e., the Number of participants who were seronegative at baseline and developed seropositive at Month 7. Seroconversion for HPV 6, 11, 16, and 18 was defined as achieving an anti-HPV cLIA level of at least 20, 16, 20 and 24 mill Merck units/mL, respectively. Seroconversion rate = (number of participants with seronegative at baseline and developed seropositive at Month 7)/(number of participants with seronegative at baseline regardless relevant HPV serum status at Month 7). Measure serum anti-HPV 6, 11, 16, 18 titers at Day 1 prior to vaccination and at Month 7. Per-protocol population, defined as all participants who received all 3 dose vaccinations within acceptable day ranges, had at least 1 valid serology result after the third injection, and adhered to protocol guidelines. To be included in the immunogenicity analysis for given HPV type, participants must be seronegative to that HPV type at baseline.
    End point type
    Secondary
    End point timeframe
    Day 1 before vaccination and Month 7
    End point values
    		 Vaccine (GARDASIL™) Group Placebo Group
    Number of subjects analysed
    302
    298
    Units: Number of participants
        Anti-HPV 6 (N=269, 275)
    260
    2
        Anti-HPV 11 (N=279, 281)
    277
    2
        Anti-HPV 16 (N=277, 277)
    275
    0
        Anti-HPV 18 (N=287, 282)
    284
    3
    No statistical analyses for this end point

    Secondary: Number of Participants by Adverse Experience Categories

    		 Close Top of page
    End point title
    		 Number of Participants by Adverse Experience Categories
    End point description
    All adverse experiences were collected through 14 days following each vaccination. All participants were requested to record injection-site adverse experiences and monitor the participant's temperature daily on the Vaccination Report Card for Day 1 thereafter for 4 additional calendar days, and record all systemic adverse experiences that occurred during the 14-day period after each injection. Safety population, defined as all participants who were vaccinated with at least one dose and had safety follow-up data.
    End point type
    Secondary
    End point timeframe
    Serious adverse experiences and systemic adverse experiences: up to 14 days after each vaccination; injection-site adverse experiences: up to 5 days after each vaccination
    End point values
    		 Vaccine (GARDASIL™) Group Placebo Group
    Number of subjects analysed
    302
    298
    Units: Number of participants
        Clinical Adverse Experiences
    153
    131
        Injection-site Adverse Experiences
    66
    40
        Systemic Adverse Experiences
    129
    119
        Vaccine-related Adverse Experiences
    123
    100
        Vaccine-related Injection-site Adverse Experiences
    66
    40
        Vaccine-related Systemic Adverse Experiences
    87
    82
        Serious Adverse Experiences
    0
    1
        Vaccine-related Serious Adverse Experiences
    0
    0
        Adverse Experiences Leading to Discontinuation
    0
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Serious adverse experiences and systemic adverse experiences: up to 14 days after each vaccination; injection-site adverse experiences: up to 5 days after each vaccination
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 WHOART
    Dictionary version
    2000Q4
    Reporting groups
    Reporting group title
    Vaccine (GARDASIL™) Group
    Reporting group description
    		 Participants received 0.5 mL intramuscular injection of GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Reporting group title
    Placebo Group
    Reporting group description
    		 Participants received 0.5 mL intramuscular injection of placebo to GARDASIL™ on Day 1, Month 2, and Month 6. Immunogenicity was assessed on Day 1 and at Month 7 and safety was assessed through Month 7.

    Serious adverse events
    		 Vaccine (GARDASIL™) Group Placebo Group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    0 / 302 (0.00%)
    1 / 298 (0.34%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    Infections and infestations
    Acute suppurative tonsillitis
         subjects affected / exposed
    0 / 302 (0.00%)
    1 / 298 (0.34%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 1.25%
    Non-serious adverse events
    		 Vaccine (GARDASIL™) Group Placebo Group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    260 / 302 (86.09%)
    215 / 298 (72.15%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    16 / 302 (5.30%)
    18 / 298 (6.04%)
         occurrences all number
    20
    20
    General disorders and administration site conditions
    Allergic reaction
         subjects affected / exposed
    8 / 302 (2.65%)
    2 / 298 (0.67%)
         occurrences all number
    9
    2
    Fatigue
         subjects affected / exposed
    17 / 302 (5.63%)
    22 / 298 (7.38%)
         occurrences all number
    24
    25
    Fever
         subjects affected / exposed
    71 / 302 (23.51%)
    70 / 298 (23.49%)
         occurrences all number
    83
    85
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    9 / 302 (2.98%)
    10 / 298 (3.36%)
         occurrences all number
    11
    10
    Nausea
         subjects affected / exposed
    8 / 302 (2.65%)
    12 / 298 (4.03%)
         occurrences all number
    9
    14
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    11 / 302 (3.64%)
    10 / 298 (3.36%)
         occurrences all number
    12
    16
    Skin and subcutaneous tissue disorders
    Injection site redness
         subjects affected / exposed
    3 / 302 (0.99%)
    2 / 298 (0.67%)
         occurrences all number
    3
    2
    Injection site pain
         subjects affected / exposed
    61 / 302 (20.20%)
    39 / 298 (13.09%)
         occurrences all number
    94
    46
    Injection site induration
         subjects affected / exposed
    6 / 302 (1.99%)
    1 / 298 (0.34%)
         occurrences all number
    6
    1
    Injection site swelling
         subjects affected / exposed
    9 / 302 (2.98%)
    2 / 298 (0.67%)
         occurrences all number
    9
    3
    Injection site pruritus
         subjects affected / exposed
    12 / 302 (3.97%)
    2 / 298 (0.67%)
         occurrences all number
    16
    3
    Musculoskeletal and connective tissue disorders
    Myalgia
         subjects affected / exposed
    11 / 302 (3.64%)
    12 / 298 (4.03%)
         occurrences all number
    16
    12
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    18 / 302 (5.96%)
    13 / 298 (4.36%)
         occurrences all number
    21
    14

    More information

    		 Close Top of page

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

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

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
    For support, Contact us.
    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
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Fri Apr 26 19:24:31 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA