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    Clinical Trial Results:
    Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore

    Summary
    EudraCT number
    2014-001713-26
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    14 Oct 2014

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

    Trial information

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    Trial identification
    Sponsor protocol code
    CYD28
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT00880893
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur SA
    Sponsor organisation address
    2, avenue Pont Pasteur, Lyon Cedex 07, France, 69367
    Public contact
    Director, Clinical Development, Sanofi Pasteur SA, 65 6431 2358, Anh.Wartel-Tram@sanofipasteur.com
    Scientific contact
    Director, Clinical Development, Sanofi Pasteur SA, 65 6431 2358, Anh.Wartel-Tram@sanofipasteur.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    EMEA-001201-PIP01-11
    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
    30 Mar 2015
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    14 Oct 2014
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    Safety and reactogenicity Humoral immune response to dengue before and after each vaccination with CYD dengue vaccine
    Protection of trial subjects
    Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.
    Background therapy
    Not applicable
    Evidence for comparator
    Not applicable
    Actual start date of recruitment
    07 Apr 2009
    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
    Singapore: 1198
    Worldwide total number of subjects
    1198
    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)
    316
    Adolescents (12-17 years)
    187
    Adults (18-64 years)
    695
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Study subjects were enrolled from 07 April 2009 to 08 October 2009 at 5 clinical sites in Singapore.

    Pre-assignment
    Screening details
    A total of 1198 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized.

    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Subject, Investigator, Monitor, Assessor
    Blinding implementation details
    An observer-design for the first vaccination and a single-blind design for the second and third vaccination were chosen to minimize the bias of the vaccine evaluation. The Investigator in charge of safety evaluation, the Sponsor, and the subjects/parents did not know which vaccine was administrated at the first visit. For the second and third vaccinations, the subjects/parents did not know which vaccine was administered.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    CYD Dengue vaccine group
    Arm description
    Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue vaccine
    Investigational medicinal product code
    323
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    0.5 mL, subcutaneous, 1 injection each at 0, 6, and 12 months.

    Arm title
    Control group
    Arm description
    All subjects received a placebo at first vaccination (Month 0). Subjects <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Subjects ≥12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Arm type
    Placebo

    Investigational medicinal product name
    Placebo (NaCl)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    0.5 mL, subcutaneous, 1 injection at Month 0.

    Investigational medicinal product name
    Hepatitis A vaccine (Havrix® pediatric formulation)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, subjects <12 years received hepatitis vaccine at second (Month 6) and third (Month 12) vaccinations.

    Investigational medicinal product name
    Influenza vaccine (split virion, inactivated) Northern and Southern hemispheres year 2009-2010 formulations (Vaxigrip®)
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Suspension for injection in pre-filled syringe
    Routes of administration
    Intramuscular use
    Dosage and administration details
    0.5 mL, intramuscular, subjects ≥12 years received 1 injection of the influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

    Number of subjects in period 1
    CYD Dengue vaccine group Control group
    Started
    898
    300
    Completed
    791
    255
    Not completed
    107
    45
         Protocol deviation
             13
             1
         Consent withdrawn by subject
             15
             11
         Lost to follow-up
             76
             33
         Serious adverse event
             3
             -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    CYD Dengue vaccine group
    Reporting group description
    Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

    Reporting group title
    Control group
    Reporting group description
    All subjects received a placebo at first vaccination (Month 0). Subjects <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Subjects ≥12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

    Reporting group values
    CYD Dengue vaccine group Control group Total
    Number of subjects
    898 300 1198
    Age categorical
    Units: Subjects
        In utero
    0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    0 0 0
        Newborns (0-27 days)
    0 0 0
        Infants and toddlers (28 days-23 months)
    0 0 0
        Children (2-11 years)
    236 80 316
        Adolescents (12-17 years)
    141 46 187
        Adults (18-64 years)
    521 174 695
        From 65-84 years
    0 0 0
        85 years and over
    0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    22.1 ± 11.97 21.7 ± 11.76 -
    Gender categorical
    Units: Subjects
        Female
    471 139 610
        Male
    427 161 588

    End points

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    End points reporting groups
    Reporting group title
    CYD Dengue vaccine group
    Reporting group description
    Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

    Reporting group title
    Control group
    Reporting group description
    All subjects received a placebo at first vaccination (Month 0). Subjects <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Subjects ≥12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

    Primary: Percentage of All Subjects Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

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    End point title
    Percentage of All Subjects Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine [1]
    End point description
    Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥5 cm. Grade 3 Solicited injection site reactions (adolescents and adults): Pain, Significant; prevents daily activity; Erythema and Swelling, >10 cm. Grade 3 Solicited systemic reactions: Fever, ≥39.0°C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 14 post-any and each injection
    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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    898
    300
    Units: Percentage of subjects
    number (not applicable)
        Injection site Pain; Post-Any Injection
    53.9
    66.7
        Grade 3 Injection site Pain; Post-Any Injection
    1
    2
        Injection site Erythema; Post-Any Injection
    7.2
    15.2
        Grade 3 Inj. site Erythema; Post-Any Inj.
    0
    0
        Injection site Swelling; Post-Any Injection
    4.1
    8.4
        Grade 3 Inj. site Swelling; Post-Any Inj.
    0
    0
        Injection site Pain; Post-Injection 1
    31.3
    21.9
        Grade 3 Injection site Pain; Post-Injection 1
    0.3
    0.7
        Injection site Erythema; Post-Injection 1
    2
    2
        Grade 3 Injection site Erythema; Post-Injection 1
    0
    0
        Injection site Swelling; Post-Injection 1
    1.1
    1.7
        Grade 3 Injection site Swelling; Post-Injection 1
    0
    0
        Injection site Pain; Post-Injection 2
    36.9
    54.4
        Grade 3 Injection site Pain; Post-Injection 2
    0.5
    0.7
        Injection site Erythema; Post-Injection 2
    3.4
    8.8
        Grade 3 Injection site Erythema; Post-Injection 2
    0
    0
        Injection site Swelling; Post-Injection 2
    1.4
    3.5
        Grade 3 Injection site Swelling; Post-Injection 2
    0
    0
        Injection site Pain; Post-Injection 3
    34.9
    50
        Grade 3 Injection site Pain; Post-Injection 3
    0.2
    0.7
        Injection site Erythema; Post-Injection 3
    3.8
    9.4
        Grade 3 Injection site Erythema; Post-Injection 3
    0
    0
        Injection site Swelling; Post-Injection 3
    2.6
    5.8
        Grade 3 Injection site Swelling; Post-Injection 3
    0
    0
        Fever; Post-Any Injection
    11.3
    7.4
        Grade 3 Fever; Post-Any Injection
    1.9
    1
        Headache; Post-Any Injection
    45.1
    38.4
        Grade 3 Headache; Post-Any Injection
    3.8
    2.7
        Malaise; Post-Any Injection
    41.8
    35.4
        Grade 3 Malaise; Post-Any Injection
    4.3
    2.7
        Myalgia; Post-Any Injection
    44.2
    43.8
        Grade 3 Myalgia; Post-Any Injection
    2.6
    2
        Asthenia; Post-Any Injection
    20.5
    17.5
        Grade 3 Asthenia; Post-Any Injection
    1.3
    0.7
        Fever; Post-Injection 1
    4.6
    2.7
        Grade 3 Fever; Post-Injection 1
    0.6
    0.7
        Headache; Post-Injection 1
    30
    27.3
        Grade 3 Headache; Post-Injection 1
    2.4
    1.3
        Malaise; Post-Injection 1
    25
    18.2
        Grade 3 Malaise; Post-Injection 1
    2
    0.7
        Myalgia; Post-Injection 1
    29.4
    19.2
        Grade 3 Myalgia; Post-Injection 1
    1.3
    1
        Asthenia; Post-Injection 1
    12.8
    6.1
        Grade 3 Asthenia; Post-Injection 1
    0.7
    0.3
        Fever; Post-Injection 2
    3.3
    2.8
        Grade 3 Fever; Post-Injection 2
    0.6
    0
        Headache; Post-Injection 2
    22.8
    21.8
        Grade 3 Headache; Post-Injection 2
    0.7
    1.1
        Malaise; Post-Injection 2
    19.1
    18.2
        Grade 3 Malaise; Post-Injection 2
    1.2
    1.1
        Myalgia; Post-Injection 2
    24
    29.5
        Grade 3 Myalgia; Post-Injection 2
    0.9
    0.7
        Asthenia; Post-Injection 2
    9.3
    10.2
        Grade 3 Asthenia; Post-Injection 2
    0.3
    0
        Fever; Post-Injection 3
    4.8
    2.9
        Grade 3 Fever; Post-Injection 3
    0.8
    0.4
        Headache; Post-Injection 3
    20.1
    19.8
        Grade 3 Headache; Post-Injection 3
    1
    0.4
        Malaise; Post-Injection 3
    18.2
    17.3
        Grade 3 Malaise; Post-Injection 3
    1.4
    1.1
        Myalgia; Post-Injection 3
    21.8
    26.3
        Grade 3 Myalgia; Post-Injection 3
    0.5
    0.7
        Asthenia; Post-Injection 3
    8.5
    9.4
        Grade 3 Asthenia; Post-Injection 3
    0.4
    0.4
    No statistical analyses for this end point

    Primary: Percentage of Subjects By Age Group Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

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    End point title
    Percentage of Subjects By Age Group Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine [2]
    End point description
    Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.
    End point type
    Primary
    End point timeframe
    Day 0 up to Day 14 post-each injection
    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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    898
    300
    Units: Percentage of subjects
    number (not applicable)
        2-11 years; Injection site Pain, Post-Injection 1
    33.9
    30
        2-11 years; Inj. site Erythema, Post-Inj. 1
    6.4
    7.5
        2-11 years; Inj. site Swelling, Post-Inj. 1
    3.8
    6.3
        12-17 years; Injection site Pain, Post-Injection 1
    28.4
    28.3
        12-17 years; Inj. site Erythema, Post-Inj. 1
    0
    0
        12-17 years; Inj. site Swelling, Post-Inj. 1
    0
    0
        18-45 years; Injection site Pain, Post-Injection 1
    30.9
    16.4
        18-45 years; Inj. site Erythema, Post-Inj. 1
    0.6
    0
        18-45 years; Inj. site Swelling, Post-Inj. 1
    0.2
    0
        2-11 years; Injection site Pain, Post-Injection 2
    38.3
    42.1
        2-11 years; Inj. site Erythema, Post-Inj. 2
    9.4
    5.3
        2-11 years; Inj. site Swelling, Post-Inj. 2
    4.7
    3.9
        12-17 years; Injection site Pain, Post-Injection 2
    29.4
    44.4
        12-17 years; Inj. site Erythema, Post-Inj. 2
    0
    0
        12-17 years; Inj. site Swelling, Post-Inj. 2
    0
    0
        18-45 years; Injection site Pain, Post-Injection 2
    38.3
    62.8
        18-45 years; Inj. site Erythema, Post-Inj. 2
    1.4
    12.8
        18-45 years; Inj. site Swelling, Post-Inj. 2
    0.2
    4.3
        2-11 years; Injection site Pain, Post-Injection 3
    32.6
    34.2
        2-11 years; Inj. site Erythema, Post-Inj. 3
    8.2
    6.6
        2-11 years; Inj. site Swelling, Post-Inj. 3
    6.4
    2.6
        12-17 years; Injection site Pain, Post-Injection 3
    26.7
    38.6
        12-17 years; Inj. site Erythema, Post-Inj. 3
    0
    0
        12-17 years; Inj. site Swelling, Post-Inj. 3
    0
    0
        18-45 years; Injection site Pain, Post-Injection 3
    38.5
    60.8
        18-45 years; Inj. site Erythema, Post-Inj. 3
    2.8
    13.3
        18-45 years; Inj. site Swelling, Post-Inj. 3
    1.5
    8.9
        2-11 years; Fever, Post-Injection 1
    8.1
    6.3
        2-11 years; Headache, Post-Injection 1
    25
    16.3
        2-11 years; Malaise, Post-Injection 1
    19.9
    13.8
        2-11 years; Myalgia, Post-Injection 1
    23.7
    16.3
        2-11 years; Asthenia, Post-Injection 1
    7.2
    3.8
        12-17 years; Fever, Post-Injection 1
    7.1
    2.2
        12-17 years; Headache, Post-Injection 1
    39.3
    39.1
        12-17 years; Malaise, Post-Injection 1
    29.3
    17.4
        12-17 years; Myalgia, Post-Injection 1
    32.1
    23.9
        12-17 years; Asthenia, Post-Injection 1
    13.6
    6.5
        18-45 years; Fever, Post-Injection 1
    2.3
    1.2
        18-45 years; Headache, Post-Injection 1
    29.7
    29.2
        18-45 years; Malaise, Post-Injection 1
    26.2
    20.5
        18-45 years; Myalgia, Post-Injection 1
    31.3
    19.3
        18-45 years; Asthenia, Post-Injection 1
    15.1
    7
        2-11 years; Fever, Post-Injection 2
    6.8
    6.6
        2-11 years; Headache, Post-Injection 2
    21.7
    15.8
        2-11 years; Malaise, Post-Injection 2
    21.7
    13.2
        2-11 years; Myalgia, Post-Injection 2
    24.7
    22.4
        2-11 years; Asthenia, Post-Injection 2
    7.7
    7.9
        12-17 years; Fever, Post-Injection 2
    4.4
    0
        12-17 years; Headache, Post-Injection 2
    19.9
    22.2
        12-17 years; Malaise, Post-Injection 2
    16.2
    20
        12-17 years; Myalgia, Post-Injection 2
    19.9
    28.9
        12-17 years; Asthenia, Post-Injection 2
    8.8
    6.7
        18-45 years; Fever, Post-Injection 2
    1.2
    1.8
        18-45 years; Headache, Post-Injection 2
    24.2
    24.4
        18-45 years; Malaise, Post-Injection 2
    18.6
    20.1
        18-45 years; Myalgia, Post-Injection 2
    24.8
    32.9
        18-45 years; Asthenia, Post-Injection 2
    10.2
    12.2
        2-11 years; Fever, Post-Injection 3
    8.2
    6.6
        2-11 years; Headache, Post-Injection 3
    17.6
    11.8
        2-11 years; Malaise, Post-Injection 3
    18.5
    14.5
        2-11 years; Myalgia, Post-Injection 3
    20.6
    17.1
        2-11 years; Asthenia, Post-Injection 3
    7.7
    3.9
        12-17 years; Fever, Post-Injection 3
    5.9
    2.3
        12-17 years; Headache, Post-Injection 3
    20.7
    20.5
        12-17 years; Malaise, Post-Injection 3
    18.5
    18.2
        12-17 years; Myalgia, Post-Injection 3
    14.8
    25
        12-17 years; Asthenia, Post-Injection 3
    5.9
    11.4
        18-45 years; Fever, Post-Injection 3
    2.8
    1.3
        18-45 years; Headache, Post-Injection 3
    21.2
    23.4
        18-45 years; Malaise, Post-Injection 3
    17.9
    18.4
        18-45 years; Myalgia, Post-Injection 3
    24.4
    31
        18-45 years; Asthenia, Post-Injection 3
    9.6
    11.4
    No statistical analyses for this end point

    Primary: Percentage of All Subjects Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of All Subjects Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine [3]
    End point description
    Seropositivity against each dengue virus serotype was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Primary
    End point timeframe
    Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
    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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    424
    140
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Pre-Injection 1
    14.6
    17.1
        CYD dengue Serotype 1; Post-Injection 1
    22.9
    11.6
        CYD dengue Serotype 1; Pre-Injection 2
    30.1
    16.7
        CYD dengue Serotype 1; Post-Injection 2
    54.9
    18.3
        CYD dengue Serotype 1; Pre-Injection 3
    45.8
    13.8
        CYD dengue Serotype 1; Post-Injection 3
    79.6
    22
        CYD dengue Serotype 2; Pre-Injection 1
    16.1
    15
        CYD dengue Serotype 2; Post-Injection 1
    39.5
    10.1
        CYD dengue Serotype 2; Pre-Injection 2
    39.3
    16.7
        CYD dengue Serotype 2; Post-Injection 2
    80.4
    15
        CYD dengue Serotype 2; Pre-Injection 3
    58.3
    13.8
        CYD dengue Serotype 2; Post-Injection 3
    88.1
    20.2
        CYD dengue Serotype 3; Pre-Injection 1
    19.7
    20.1
        CYD dengue Serotype 3; Post-Injection 1
    58.7
    21.7
        CYD dengue Serotype 3; Pre-Injection 2
    63.9
    31
        CYD dengue Serotype 3; Post-Injection 2
    87.4
    26.7
        CYD dengue Serotype 3; Pre-Injection 3
    77.8
    19
        CYD dengue Serotype 3; Post-Injection 3
    93.2
    24.8
        CYD dengue Serotype 4; Pre-Injection 1
    12.8
    12.9
        CYD dengue Serotype 4; Post-Injection 1
    67.3
    11.6
        CYD dengue Serotype 4; Pre-Injection 2
    69.1
    16.7
        CYD dengue Serotype 4; Post-Injection 2
    85.8
    16.9
        CYD dengue Serotype 4; Pre-Injection 3
    79.3
    8.6
        CYD dengue Serotype 4; Post-Injection 3
    93.7
    19.3
    No statistical analyses for this end point

    Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects By Age Group Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine [4]
    End point description
    Seropositivity against each dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Primary
    End point timeframe
    Pre-Injection 1 and Post-Injection 3
    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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    148
    47
    Units: Percentage of subjects
    number (not applicable)
        2-11 years, CYD dengue Serotype 1; Pre-Injection 1
    4.7
    8.5
        2-11 years, CYD dengue Serotype 1; Post-Inj. 3
    92.4
    10.8
        2-11 years, CYD dengue Serotype 2; Pre-Injection 1
    5.4
    2.1
        2-11 years, CYD dengue Serotype 2; Post-Inj. 3
    93.9
    16.2
        2-11 years, CYD dengue Serotype 3; Pre-Injection 1
    11.6
    10.6
        2-11 years, CYD dengue Serotype 3; Post-Inj. 3
    98.5
    13.5
        2-11 years, CYD dengue Serotype 4; Pre-Injection 1
    6.8
    6.4
        2-11 years, CYD dengue Serotype 4; Post-Inj. 3
    96.9
    18.9
        12-17 years, CYD dengue Serotype 1; Pre-Inj. 1
    5.7
    4.3
        12-17 years, CYD dengue Serotype 1; Post-Inj. 3
    68.3
    13.2
        12-17 years, CYD dengue Serotype 2; Pre-Inj. 1
    10
    4.3
        12-17 years, CYD dengue Serotype 2; Post-Inj. 3
    87
    10.5
        12-17 years, CYD dengue Serotype 3; Pre-Inj. 1
    11.5
    10.9
        12-17 years, CYD dengue Serotype 3; Post-Inj. 3
    88.5
    21.1
        12-17 years, CYD dengue Serotype 4; Pre-Inj. 1
    6.5
    2.2
        12-17 years, CYD dengue Serotype 4; Post-Inj. 3
    91.1
    10.5
        18-45 years, CYD dengue Serotype 1; Pre-Inj. 1
    34.6
    38.3
        18-45 years, CYD dengue Serotype 1; Post-Inj. 3
    76.5
    44.1
        18-45 years, CYD dengue Serotype 2; Pre-Inj. 1
    34.1
    38.3
        18-45 years, CYD dengue Serotype 2; Post-Inj. 3
    81.6
    35.3
        18-45 years, CYD dengue Serotype 3; Pre-Inj. 1
    37
    39.1
        18-45 years, CYD dengue Serotype 3; Post-Inj. 3
    91.8
    41.2
        18-45 years, CYD dengue Serotype 4; Pre-Inj. 1
    26.1
    30.4
        18-45 years, CYD dengue Serotype 4; Post-Inj. 3
    92.8
    29.4
    No statistical analyses for this end point

    Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects By Age Group Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine [5]
    End point description
    Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Primary
    End point timeframe
    Pre-Injection 1 and Post-Injection 3
    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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    148
    47
    Units: Percentage of subjects
    number (not applicable)
        2-11 yrs, CYD dengue ≥1 serotype; Pre-Inj. 1
    19.6
    27.7
        2-11 yrs, CYD dengue ≥1 serotype; Post-Inj. 3
    100
    56.8
        2-11 yrs, CYD dengue ≥2 serotypes; Pre-Inj. 1
    6.1
    0
        2-11 yrs, CYD dengue ≥2 serotypes; Post-Inj. 3
    99.2
    2.7
        2-11 yrs, CYD dengue ≥3 serotypes; Pre-Inj. 1
    2
    0
        2-11 yrs, CYD dengue ≥3 serotypes; Post-Inj. 3
    97
    0
        2-11 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1
    0.7
    0
        2-11 yrs, CYD dengue All 4 serotypes; Post-Inj. 3
    84.8
    0
        12-17 yrs, CYD dengue ≥1 serotype; Pre-Inj. 1
    13.6
    15.2
        12-17 yrs, CYD dengue ≥1 serotype; Post-Inj. 3
    98.4
    26.3
        12-17 yrs, CYD dengue ≥2 serotypes; Pre-Inj. 1
    7.9
    4.3
        12-17 yrs, CYD dengue ≥2 serotypes; Post-Inj. 3
    95.1
    10.5
        12-17 yrs, CYD dengue ≥3 serotypes; Pre-Inj. 1
    7.1
    2.2
        12-17 yrs, CYD dengue ≥3 serotypes; Post-Inj. 3
    81.3
    10.5
        12-17 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1
    5
    0
        12-17 yrs, CYD dengue All 4 serotypes; Post-Inj. 3
    59.3
    7.9
        18-45 yrs, CYD dengue ≥1 serotype; Pre-Inj. 1
    47.1
    53.2
        18-45 yrs, CYD dengue ≥1 serotype; Post-Inj. 3
    100
    55.9
        18-45 yrs, CYD dengue ≥2 serotypes; Pre-Inj. 1
    33.8
    38.3
        18-45 yrs, CYD dengue ≥2 serotypes; Post-Inj. 3
    96.9
    35.3
        18-45 yrs, CYD dengue ≥3 serotypes; Pre-Inj. 1
    27.9
    31.9
        18-45 yrs, CYD dengue ≥3 serotypes; Post-Inj. 3
    83.7
    32.4
        18-45 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1
    22.1
    21.3
        18-45 yrs, CYD dengue All 4 serotypes; Post-Inj. 3
    61.2
    26.5
    No statistical analyses for this end point

    Primary: Geometric Mean Titers (GMTs) of Antibodies In All Subjects Against Each Serotype with the Parental Dengue Virus Strain Before and Following Each Injection with CYD Dengue Vaccine

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    End point title
    Geometric Mean Titers (GMTs) of Antibodies In All Subjects Against Each Serotype with the Parental Dengue Virus Strain Before and Following Each Injection with CYD Dengue Vaccine [6]
    End point description
    Geometric mean titers against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
    End point type
    Primary
    End point timeframe
    Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3
    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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    424
    140
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        CYD dengue Serotype 1; Pre-Injection 1
    8.2 (7.2 to 9.33)
    8.23 (6.62 to 10.2)
        CYD dengue Serotype 1; Post-Injection 1
    10 (8.06 to 12.4)
    7.09 (5.48 to 9.18)
        CYD dengue Serotype 1; Pre-Injection 2
    12.9 (9.89 to 16.7)
    7.85 (5.79 to 10.6)
        CYD dengue Serotype 1; Post-Injection 2
    22.4 (17.1 to 29.3)
    7.91 (5.85 to 10.7)
        CYD dengue Serotype 1; Pre-Injection 3
    18 (14 to 23.2)
    7.4 (5.54 to 9.88)
        CYD dengue Serotype 1; Post-Injection 3
    46.6 (39 to 55.6)
    8.93 (7.08 to 11.3)
        CYD dengue Serotype 2; Pre-Injection 1
    9.06 (7.86 to 10.4)
    8.48 (6.69 to 10.8)
        CYD dengue Serotype 2; Post-Injection 1
    17.2 (13.3 to 22.2)
    7.39 (5.49 to 9.94)
        CYD dengue Serotype 2; Pre-Injection 2
    19.1 (14.3 to 25.5)
    9.79 (6.45 to 14.9)
        CYD dengue Serotype 2; Post-Injection 2
    50.3 (39 to 65)
    9.48 (6.22 to 14.4)
        CYD dengue Serotype 2; Pre-Injection 3
    24.4 (19.2 to 31.1)
    6.98 (5.38 to 9.07)
        CYD dengue Serotype 2; Post-Injection 3
    72.7 (61.6 to 85.8)
    8.88 (6.9 to 11.4)
        CYD dengue Serotype 3; Pre-Injection 1
    8.45 (7.54 to 9.47)
    8.93 (7.11 to 11.2)
        CYD dengue Serotype 3; Post-Injection 1
    28.2 (22 to 36.3)
    9.56 (6.72 to 13.6)
        CYD dengue Serotype 3; Pre-Injection 2
    29.7 (23.2 to 38)
    11.1 (7.6 to 16.3)
        CYD dengue Serotype 3; Post-Injection 2
    70.8 (56.8 to 88.2)
    10.5 (7.36 to 14.9)
        CYD dengue Serotype 3; Pre-Injection 3
    39.1 (31.2 to 48.9)
    8.23 (5.88 to 11.5)
        CYD dengue Serotype 3; Post-Injection 3
    100 (86.9 to 116)
    9.52 (7.41 to 12.2)
        CYD dengue Serotype 4; Pre-Injection 1
    6.93 (6.31 to 7.6)
    6.84 (5.86 to 7.99)
        CYD dengue Serotype 4; Post-Injection 1
    65.9 (49.1 to 88.3)
    6.31 (5.3 to 7.5)
        CYD dengue Serotype 4; Pre-Injection 2
    47.5 (36.5 to 61.8)
    7.91 (5.91 to 10.6)
        CYD dengue Serotype 4; Post-Injection 2
    90.2 (71.7 to 114)
    8 (5.89 to 10.9)
        CYD dengue Serotype 4; Pre-Injection 3
    47.1 (37.9 to 58.5)
    6.04 (5.09 to 7.17)
        CYD dengue Serotype 4; Post-Injection 3
    99.4 (87.4 to 113)
    7.66 (6.35 to 9.24)
    No statistical analyses for this end point

    Primary: Geometric Mean Titers (GMTs) of Antibodies By Age Groups Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

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    End point title
    Geometric Mean Titers (GMTs) of Antibodies By Age Groups Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine [7]
    End point description
    Geometric mean titers against each dengue virus serotype were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
    End point type
    Primary
    End point timeframe
    Pre-Injection 1 and Post-Injection 3
    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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    148
    47
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        2-11 years, CYD dengue Serotype 1; Pre-Injection 1
    5.33 (5.08 to 5.6)
    5.44 (5.01 to 5.92)
        2-11 years, CYD dengue Serotype 1; Post-Inj. 3
    60.7 (49.5 to 74.3)
    6.32 (4.92 to 8.13)
        2-11 years, CYD dengue Serotype 2; Pre-Injection 1
    5.85 (5.18 to 6.6)
    5.18 (4.82 to 5.57)
        2-11 years, CYD dengue Serotype 2; Post-Inj. 3
    95.9 (76.7 to 120)
    6.09 (5.18 to 7.16)
        2-11 years, CYD dengue Serotype 3; Pre-Injection 1
    6.24 (5.57 to 6.99)
    6.02 (5.04 to 7.17)
        2-11 years, CYD dengue Serotype 3; Post-Inj. 3
    138 (115 to 165)
    6.67 (5.11 to 8.71)
        2-11 years, CYD dengue Serotype 4; Pre-Injection 1
    5.64 (5.2 to 6.11)
    5.42 (4.92 to 5.97)
        2-11 years, CYD dengue Serotype 4; Post-Inj. 3
    101 (84.6 to 122)
    6.92 (5.47 to 8.76)
        12-17 years, CYD dengue Serotype 1; Pre-Inj. 1
    6.49 (5.31 to 7.92)
    5.47 (4.8 to 6.24)
        12-17 years, CYD dengue Serotype 1; Post-Inj. 3
    28.9 (21.5 to 38.7)
    6.56 (5.14 to 8.37)
        12-17 years, CYD dengue Serotype 2; Pre-Inj. 1
    7.47 (5.96 to 9.37)
    5.54 (4.69 to 6.56)
        12-17 years, CYD dengue Serotype 2; Post-Inj. 3
    54 (41.1 to 70.9)
    6.35 (5.03 to 8)
        12-17 years, CYD dengue Serotype 3; Pre-Inj. 1
    6.86 (5.82 to 8.09)
    6.83 (4.84 to 9.65)
        12-17 years, CYD dengue Serotype 3; Post-Inj. 3
    74.1 (57.5 to 95.5)
    8.32 (5.57 to 12.4)
        12-17 years, CYD dengue Serotype 4; Pre-Inj. 1
    5.83 (5.18 to 6.57)
    5.08 (4.92 to 5.23)
        12-17 years, CYD dengue Serotype 4; Post-Inj. 3
    80.4 (64.2 to 101)
    6.68 (4.87 to 9.15)
        18-45 years, CYD dengue Serotype 1; Pre-Inj. 1
    16.7 (12.2 to 22.8)
    18.5 (10.4 to 32.9)
        18-45 years, CYD dengue Serotype 1; Post-Inj. 3
    59.5 (38.7 to 91.6)
    18.3 (10.2 to 33)
        18-45 years, CYD dengue Serotype 2; Pre-Inj. 1
    17.8 (12.8 to 24.7)
    21.1 (11.3 to 39.2)
        18-45 years, CYD dengue Serotype 2; Post-Inj. 3
    72.7 (49.4 to 107)
    19.5 (9.69 to 39.1)
        18-45 years, CYD dengue Serotype 3; Pre-Inj. 1
    14.6 (11.2 to 19)
    17.5 (10.2 to 30)
        18-45 years, CYD dengue Serotype 3; Post-Inj. 3
    94.9 (69.4 to 130)
    16.3 (9.06 to 29.4)
        18-45 years, CYD dengue Serotype 4; Pre-Inj. 1
    10.4 (8.22 to 13.2)
    11.7 (7.65 to 17.9)
        18-45 years, CYD dengue Serotype 4; Post-Inj. 3
    127 (96 to 167)
    9.96 (6.47 to 15.3)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Seropositivity against each dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Pre-Injection 1
    4.7
    8
        CYD dengue Serotype 1; Post-Injection 3
    91
    8.9
        CYD dengue Serotype 1; 1st year follow up
    41.8
    6.8
        CYD dengue Serotype 1; 2nd year follow up
    27.1
    0
        CYD dengue Serotype 1; 3rd year follow up
    16.5
    0
        CYD dengue Serotype 1; 4th year follow up
    9.6
    0
        CYD dengue Serotype 2; Pre-Injection 1
    5.4
    2
        CYD dengue Serotype 2; Post-Injection 3
    94.4
    13.3
        CYD dengue Serotype 2; 1st year follow up
    59.6
    8.9
        CYD dengue Serotype 2; 2nd year follow up
    52.1
    11.6
        CYD dengue Serotype 2; 3rd year follow up
    34.3
    7
        CYD dengue Serotype 2; 4th year follow up
    36.9
    2.4
        CYD dengue Serotype 3; Pre-Injection 1
    11.6
    10
        CYD dengue Serotype 3; Post-Injection 3
    97.9
    13.6
        CYD dengue Serotype 3; 1st year follow up
    66
    9.1
        CYD dengue Serotype 3; 2nd year follow up
    74.4
    29.3
        CYD dengue Serotype 3; 3rd year follow up
    50
    4.7
        CYD dengue Serotype 3; 4th year follow up
    37.7
    2.4
        CYD dengue Serotype 4; Pre-Injection 1
    6.8
    6
        CYD dengue Serotype 4; Post-Injection 3
    97.2
    20.5
        CYD dengue Serotype 4; 1st year follow up
    75.2
    4.7
        CYD dengue Serotype 4; 2nd year follow up
    72.9
    4.7
        CYD dengue Serotype 4; 3rd year follow up
    60.6
    7
        CYD dengue Serotype 4; 4th year follow up
    49.3
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Seropositivity against each dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Pre-Injection 1
    5.7
    4.3
        CYD dengue Serotype 1; Post-Injection 3
    67.4
    11.6
        CYD dengue Serotype 1; 1st year follow up
    25.8
    7.3
        CYD dengue Serotype 1; 2nd year follow up
    19.5
    7.5
        CYD dengue Serotype 1; 3rd year follow up
    16.1
    5
        CYD dengue Serotype 1; 4th year follow up
    11.9
    5.4
        CYD dengue Serotype 2; Pre-Injection 1
    9.9
    4.3
        CYD dengue Serotype 2; Post-Injection 3
    83.7
    9.3
        CYD dengue Serotype 2; 1st year follow up
    44.3
    4.9
        CYD dengue Serotype 2; 2nd year follow up
    52.3
    10
        CYD dengue Serotype 2; 3rd year follow up
    35.5
    5
        CYD dengue Serotype 2; 4th year follow up
    36.2
    5.4
        CYD dengue Serotype 3; Pre-Injection 1
    11.4
    10.9
        CYD dengue Serotype 3; Post-Injection 3
    88.8
    20.9
        CYD dengue Serotype 3; 1st year follow up
    61.7
    5
        CYD dengue Serotype 3; 2nd year follow up
    56.3
    12.5
        CYD dengue Serotype 3; 3rd year follow up
    48.8
    5
        CYD dengue Serotype 3; 4th year follow up
    47.5
    5.4
        CYD dengue Serotype 4; Pre-Injection 1
    6.4
    2.2
        CYD dengue Serotype 4; Post-Injection 3
    91.1
    9.3
        CYD dengue Serotype 4; 1st year follow up
    73.5
    2.4
        CYD dengue Serotype 4; 2nd year follow up
    71.1
    10
        CYD dengue Serotype 4; 3rd year follow up
    66.7
    5
        CYD dengue Serotype 4; 4th year follow up
    61
    8.1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Seropositivity against each dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Pre-Injection 1
    33.1
    38.8
        CYD dengue Serotype 1; Post-Injection 3
    71.7
    39.5
        CYD dengue Serotype 1; 1st year follow up
    45.9
    31.8
        CYD dengue Serotype 1; 2nd year follow up
    43.6
    34.1
        CYD dengue Serotype 1; 3rd year follow up
    40.4
    30.8
        CYD dengue Serotype 1; 4th year follow up
    39.6
    31.6
        CYD dengue Serotype 2; Pre-Injection 1
    32.6
    38.8
        CYD dengue Serotype 2; Post-Injection 3
    80.3
    30.2
        CYD dengue Serotype 2; 1st year follow up
    66.4
    40.9
        CYD dengue Serotype 2; 2nd year follow up
    68.4
    34.1
        CYD dengue Serotype 2; 3rd year follow up
    55.3
    35.9
        CYD dengue Serotype 2; 4th year follow up
    55.2
    31.6
        CYD dengue Serotype 3; Pre-Injection 1
    36.9
    41.7
        CYD dengue Serotype 3; Post-Injection 3
    92.9
    34.9
        CYD dengue Serotype 3; 1st year follow up
    68.6
    38.6
        CYD dengue Serotype 3; 2nd year follow up
    77.8
    46.3
        CYD dengue Serotype 3; 3rd year follow up
    67.9
    35.9
        CYD dengue Serotype 3; 4th year follow up
    56.6
    29.7
        CYD dengue Serotype 4; Pre-Injection 1
    25
    31.3
        CYD dengue Serotype 4; Post-Injection 3
    93.7
    32.6
        CYD dengue Serotype 4; 1st year follow up
    86.9
    29.5
        CYD dengue Serotype 4; 2nd year follow up
    81.2
    24.4
        CYD dengue Serotype 4; 3rd year follow up
    79.8
    20.5
        CYD dengue Serotype 4; 4th year follow up
    77.6
    21.1
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue ≥1 serotype; Pre-Injection 1
    19.6
    26
        CYD dengue ≥1 serotype; Post-Injection 3
    100
    51.1
        CYD dengue ≥1 serotype; 1st year follow up
    92.3
    20
        CYD dengue ≥1 serotype; 2nd year follow up
    95
    34.9
        CYD dengue ≥1 serotype; 3rd year follow up
    76.9
    7
        CYD dengue ≥1 serotype; 4th year follow up
    72.1
    4.8
        CYD dengue ≥2 serotypes; Pre-Injection 1
    6.1
    0
        CYD dengue ≥2 serotypes; Post-Injection 3
    99.3
    4.4
        CYD dengue ≥2 serotypes; 1st year follow up
    66.2
    6.7
        CYD dengue ≥2 serotypes; 2nd year follow up
    70.7
    9.3
        CYD dengue ≥2 serotypes; 3rd year follow up
    48.5
    7
        CYD dengue ≥2 serotypes; 4th year follow up
    35.3
    0
        CYD dengue ≥3 serotypes; Pre-Injection 1
    2
    0
        CYD dengue ≥3 serotypes; Post-Injection 3
    96.5
    0
        CYD dengue ≥3 serotypes; 1st year follow up
    52.8
    2.2
        CYD dengue ≥3 serotypes; 2nd year follow up
    42.1
    0
        CYD dengue ≥3 serotypes; 3rd year follow up
    23.9
    4.7
        CYD dengue ≥3 serotypes; 4th year follow up
    16.2
    0
        CYD dengue All 4 serotypes; Pre-Injection 1
    0.7
    0
        CYD dengue All 4 serotypes; Post-Injection 3
    84
    0
        CYD dengue All 4 serotypes; 1st year follow up
    29.6
    0
        CYD dengue All 4 serotypes; 2nd year follow up
    15
    0
        CYD dengue All 4 serotypes; 3rd year follow up
    11.2
    0
        CYD dengue All 4 serotypes; 4th year follow up
    6.6
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue ≥1 Serotype; Pre-Injection 1
    13.5
    15.2
        CYD dengue ≥1 Serotype; Post-Injection 3
    97.8
    25.6
        CYD dengue ≥1 Serotype; 1st year follow up
    94.7
    7.3
        CYD dengue ≥1 Serotype; 2nd year follow up
    93
    15
        CYD dengue ≥1 Serotype; 3rd year follow up
    89.5
    5
        CYD dengue ≥1 serotype; 4th year follow up
    81.4
    8.1
        CYD dengue ≥2 Serotypes; Pre-Injection 1
    7.8
    4.3
        CYD dengue ≥2 Serotypes; Post-Injection 3
    94.8
    9.3
        CYD dengue ≥2 Serotypes; 1st year follow up
    60.2
    4.9
        CYD dengue ≥2 Serotypes; 2nd year follow up
    62.5
    10
        CYD dengue ≥2 Serotypes; 3rd year follow up
    45.2
    5
        CYD dengue ≥2 serotypes; 4th year follow up
    44.9
    5.4
        CYD dengue ≥3 Serotypes; Pre-Injection 1
    7.1
    2.2
        CYD dengue ≥3 Serotypes; Post-Injection 3
    80.7
    9.3
        CYD dengue ≥3 Serotypes; 1st year follow up
    33.1
    4.9
        CYD dengue ≥3 Serotypes; 2nd year follow up
    31.3
    7.5
        CYD dengue ≥3 Serotypes; 3rd year follow up
    22.6
    5
        CYD dengue ≥3 serotypes; 4th year follow up
    20.3
    5.4
        CYD dengue All 4 Serotypes; Pre-Injection 1
    5
    0
        CYD dengue All 4 Serotypes; Post-Injection 3
    57
    7
        CYD dengue All 4 Serotypes; 1st year follow up
    15.8
    2.4
        CYD dengue All 4 Serotypes; 2nd year follow up
    11.7
    7.5
        CYD dengue All 4 Serotypes; 3rd year follow up
    8.9
    5
        CYD dengue All 4 serotypes; 4th year follow up
    9.3
    5.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue ≥1 Serotype; Pre-Injection 1
    46.5
    55.1
        CYD dengue ≥1 Serotype; Post-Injection 3
    100
    53.5
        CYD dengue ≥1 Serotype; 1st year follow up
    96.7
    50
        CYD dengue ≥1 Serotype; 2nd year follow up
    96.6
    56.1
        CYD dengue ≥1 Serotype; 3rd year follow up
    93
    41
        CYD dengue ≥1 serotype; 4th year follow up
    92.5
    36.8
        CYD dengue ≥2 Serotypes; Pre-Injection 1
    32.4
    38.8
        CYD dengue ≥2 Serotypes; Post-Injection 3
    97.6
    32.6
        CYD dengue ≥2 Serotypes; 1st year follow up
    73.8
    38.6
        CYD dengue ≥2 Serotypes; 2nd year follow up
    76.9
    34.1
        CYD dengue ≥2 Serotypes; 3rd year follow up
    63.2
    33.3
        CYD dengue ≥2 serotypes; 4th year follow up
    54.2
    28.9
        CYD dengue ≥3 Serotypes; Pre-Injection 1
    26.8
    32.7
        CYD dengue ≥3 Serotypes; Post-Injection 3
    83.5
    27.9
        CYD dengue ≥3 Serotypes; 1st year follow up
    55.7
    34.1
        CYD dengue ≥3 Serotypes; 2nd year follow up
    56.4
    29.3
        CYD dengue ≥3 Serotypes; 3rd year follow up
    46.5
    30.8
        CYD dengue ≥3 serotypes; 4th year follow up
    43
    26.3
        CYD dengue All 4 Serotypes; Pre-Injection 1
    21.1
    22.4
        CYD dengue All 4 Serotypes; Post-Injection 3
    56.7
    23.3
        CYD dengue All 4 Serotypes; 1st year follow up
    41
    18.2
        CYD dengue All 4 Serotypes; 2nd year follow up
    41
    19.5
        CYD dengue All 4 Serotypes; 3rd year follow up
    39.5
    17.9
        CYD dengue All 4 serotypes; 4th year follow up
    37.4
    21.1
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 2 to 11 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

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    End point title
    Geometric Mean Titers (GMTs) of Antibodies In Subjects 2 to 11 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        CYD dengue Serotype 1; Pre-Injection 1
    5.33 (5.08 to 5.6)
    5.42 (5 to 5.86)
        CYD dengue Serotype 1; Post-Injection 3
    56.6 (46.5 to 68.9)
    6.06 (4.93 to 7.46)
        CYD dengue Serotype 1; 1st year follow up
    12.1 (9.92 to 14.7)
    5.52 (4.92 to 6.19)
        CYD dengue Serotype 1; 2nd year follow up
    8.89 (7.5 to 10.5)
    5 (5 to 5)
        CYD dengue Serotype 1; 3rd year follow up
    7.35 (6.22 to 8.67)
    5 (5 to 5)
        CYD dengue Serotype 1; 4th year follow up
    6.21 (5.51 to 7)
    5 (5 to 5)
        CYD dengue Serotype 2; Pre-Injection 1
    5.85 (5.18 to 6.6)
    5.17 (4.83 to 5.53)
        CYD dengue Serotype 2; Post-Injection 3
    101 (81.7 to 125)
    5.88 (5.15 to 6.72)
        CYD dengue Serotype 2; 1st year follow up
    21.1 (16.6 to 26.9)
    5.86 (4.79 to 7.16)
        CYD dengue Serotype 2; 2nd year follow up
    16.4 (12.9 to 20.9)
    6.11 (5.1 to 7.32)
        CYD dengue Serotype 2; 3rd year follow up
    11.7 (9.1 to 15.1)
    5.58 (4.86 to 6.41)
        CYD dengue Serotype 2; 4th year follow up
    14.2 (10.7 to 19)
    5.11 (4.89 to 5.32)
        CYD dengue Serotype 3; Pre-Injection 1
    6.24 (5.57 to 6.99)
    5.95 (5.04 to 7.02)
        CYD dengue Serotype 3; Post-Injection 3
    136 (114 to 162)
    6.54 (5.2 to 8.22)
        CYD dengue Serotype 3; 1st year follow up
    25.4 (20.1 to 32.1)
    5.87 (5 to 6.89)
        CYD dengue Serotype 3; 2nd year follow up
    29.9 (23.4 to 38.1)
    10.1 (6.68 to 15.2)
        CYD dengue Serotype 3; 3rd year follow up
    14.6 (11.7 to 18.3)
    5.43 (4.83 to 6.1)
        CYD dengue Serotype 3; 4th year follow up
    11.4 (9.22 to 14.1)
    5.09 (4.91 to 5.29)
        CYD dengue Serotype 4; Pre-Injection 1
    5.64 (5.2 to 6.11)
    5.39 (4.92 to 5.91)
        CYD dengue Serotype 4; Post-Injection 3
    104 (87.2 to 125)
    7.2 (5.74 to 9.05)
        CYD dengue Serotype 4; 1st year follow up
    31.8 (25.6 to 39.6)
    5.69 (4.7 to 6.89)
        CYD dengue Serotype 4; 2nd year follow up
    30.6 (24.2 to 38.6)
    5.68 (4.74 to 6.82)
        CYD dengue Serotype 4; 3rd year follow up
    22.3 (17.5 to 28.5)
    6.31 (4.84 to 8.24)
        CYD dengue Serotype 4; 4th year follow up
    16.5 (13.1 to 20.7)
    5 (5 to 5)
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 12 to 17 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

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    End point title
    Geometric Mean Titers (GMTs) of Antibodies In Subjects 12 to 17 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        CYD dengue Serotype 1; Pre-Injection 1
    6.47 (5.31 to 7.89)
    5.47 (4.8 to 6.24)
        CYD dengue Serotype 1; Post-Injection 3
    28.5 (21.4 to 37.9)
    6.36 (5.12 to 7.89)
        CYD dengue Serotype 1; 1st year follow up
    9.69 (7.53 to 12.5)
    5.69 (4.88 to 6.63)
        CYD dengue Serotype 1; 2nd year follow up
    8.31 (6.58 to 10.5)
    5.91 (4.8 to 7.27)
        CYD dengue Serotype 1; 3rd year follow up
    8.02 (6.3 to 10.2)
    5.54 (4.79 to 6.39)
        CYD dengue Serotype 1; 4th year follow up
    7.41 (5.85 to 9.38)
    5.51 (4.8 to 6.34)
        CYD dengue Serotype 2; Pre-Injection 1
    7.45 (5.95 to 9.33)
    5.54 (4.69 to 6.56)
        CYD dengue Serotype 2; Post-Injection 3
    48.7 (37.4 to 63.5)
    6.17 (5.03 to 7.58)
        CYD dengue Serotype 2; 1st year follow up
    16.6 (12.4 to 22.1)
    5.58 (4.78 to 6.52)
        CYD dengue Serotype 2; 2nd year follow up
    18.7 (14.1 to 24.7)
    6.38 (4.92 to 8.27)
        CYD dengue Serotype 2; 3rd year follow up
    13.3 (10.1 to 17.6)
    5.77 (4.71 to 7.07)
        CYD dengue Serotype 2; 4th year follow up
    14 (10.4 to 18.8)
    5.8 (4.68 to 7.17)
        CYD dengue Serotype 3; Pre-Injection 1
    6.84 (5.81 to 8.06)
    6.83 (4.84 to 9.65)
        CYD dengue Serotype 3; Post-Injection 3
    71.4 (56.3 to 90.7)
    8.1 (5.66 to 11.6)
        CYD dengue Serotype 3; 1st year follow up
    19.7 (15.1 to 25.6)
    6.27 (4.55 to 8.64)
        CYD dengue Serotype 3; 2nd year follow up
    20.5 (15.6 to 27.1)
    7.54 (5.16 to 11)
        CYD dengue Serotype 3; 3rd year follow up
    15.3 (11.8 to 19.9)
    6.17 (4.58 to 8.31)
        CYD dengue Serotype 3; 4th year follow up
    13.7 (10.7 to 17.6)
    6.47 (4.49 to 9.3)
        CYD dengue Serotype 4; Pre-Injection 1
    5.83 (5.17 to 6.56)
    5.08 (4.92 to 5.23)
        CYD dengue Serotype 4; Post-Injection 3
    79.2 (64.2 to 97.8)
    6.45 (4.89 to 8.53)
        CYD dengue Serotype 4; 1st year follow up
    30.8 (24.3 to 39)
    5.17 (4.84 to 5.52)
        CYD dengue Serotype 4; 2nd year follow up
    33.4 (25.6 to 43.6)
    6.18 (4.99 to 7.65)
        CYD dengue Serotype 4; 3rd year follow up
    23.1 (18.3 to 29.2)
    5.55 (4.79 to 6.42)
        CYD dengue Serotype 4; 4th year follow up
    20.8 (16.2 to 26.6)
    5.43 (4.92 to 6)
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 2 to 11 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 2 to 11 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects immune at baseline are defined as those subjects with titers ≥10 (1/dil) against at least one dengue serotype at baseline.
    End point type
    Secondary
    End point timeframe
    Post-Injection 3 and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    114
    47
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Post-Injection 3
    96.3
    0
        CYD dengue Serotype 1; 1st year follow up
    74.1
    7.7
        CYD dengue Serotype 1; 2nd year follow up
    55.6
    0
        CYD dengue Serotype 1; 3rd year follow up
    33.3
    0
        CYD dengue Serotype 1; 4th year follow up
    22.2
    0
        CYD dengue Serotype 2; Post-Injection 3
    100
    15.4
        CYD dengue Serotype 2; 1st year follow up
    85.2
    15.4
        CYD dengue Serotype 2; 2nd year follow up
    66.7
    16.7
        CYD dengue Serotype 2; 3rd year follow up
    48.1
    16.7
        CYD dengue Serotype 2; 4th year follow up
    48.1
    0
        CYD dengue Serotype 3; Post-Injection 3
    100
    23.1
        CYD dengue Serotype 3; 1st year follow up
    88.9
    7.7
        CYD dengue Serotype 3; 2nd year follow up
    81.5
    16.7
        CYD dengue Serotype 3; 3rd year follow up
    59.3
    8.3
        CYD dengue Serotype 3; 4th year follow up
    50
    0
        CYD dengue Serotype 4; Post-Injection 3
    100
    23.1
        CYD dengue Serotype 4; 1st year follow up
    88.9
    15.4
        CYD dengue Serotype 4; 2nd year follow up
    74.1
    0
        CYD dengue Serotype 4; 3rd year follow up
    70.4
    16.7
        CYD dengue Serotype 4; 4th year follow up
    70.4
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 2 to 11 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 2 to 11 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects naïve at baseline are defined as those subjects with titers <10 (1/dil) against all dengue serotypes at baseline.
    End point type
    Secondary
    End point timeframe
    Post-Injection 3 and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    313
    98
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Post-Injection 3
    89.6
    12.5
        CYD dengue Serotype 1; 1st year follow up
    33.6
    6.5
        CYD dengue Serotype 1; 2nd year follow up
    20.5
    0
        CYD dengue Serotype 1; 3rd year follow up
    12.4
    0
        CYD dengue Serotype 1; 4th year follow up
    6.5
    0
        CYD dengue Serotype 2; Post-Injection 3
    93
    12.5
        CYD dengue Serotype 2; 1st year follow up
    54
    6.3
        CYD dengue Serotype 2; 2nd year follow up
    49.1
    9.7
        CYD dengue Serotype 2; 3rd year follow up
    31.1
    3.2
        CYD dengue Serotype 2; 4th year follow up
    34.3
    3.3
        CYD dengue Serotype 3; Post-Injection 3
    97.4
    9.7
        CYD dengue Serotype 3; 1st year follow up
    60.2
    9.7
        CYD dengue Serotype 3; 2nd year follow up
    72.4
    34.5
        CYD dengue Serotype 3; 3rd year follow up
    47.2
    3.2
        CYD dengue Serotype 3; 4th year follow up
    34.3
    3.3
        CYD dengue Serotype 4; Post-Injection 3
    96.5
    19.4
        CYD dengue Serotype 4; 1st year follow up
    71.7
    0
        CYD dengue Serotype 4; 2nd year follow up
    73.2
    6.5
        CYD dengue Serotype 4; 3rd year follow up
    58.7
    3.2
        CYD dengue Serotype 4; 4th year follow up
    44.4
    0
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 12 to 17 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 12 to 17 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects immune at baseline are defined as those subjects with titers ≥10 (1/dil) against at least one dengue serotype at baseline.
    End point type
    Secondary
    End point timeframe
    Post-Injection 3 and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    114
    47
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Post-Injection 3
    94.4
    33.3
        CYD dengue Serotype 1; 1st year follow up
    58.8
    20
        CYD dengue Serotype 1; 2nd year follow up
    46.7
    16.7
        CYD dengue Serotype 1; 3rd year follow up
    43.8
    16.7
        CYD dengue Serotype 1; 4th year follow up
    42.9
    20
        CYD dengue Serotype 2; Post-Injection 3
    94.4
    16.7
        CYD dengue Serotype 2; 1st year follow up
    82.4
    20
        CYD dengue Serotype 2; 2nd year follow up
    73.3
    33.3
        CYD dengue Serotype 2; 3rd year follow up
    68.8
    16.7
        CYD dengue Serotype 2; 4th year follow up
    71.4
    20
        CYD dengue Serotype 3; Post-Injection 3
    100
    50
        CYD dengue Serotype 3; 1st year follow up
    76.5
    20
        CYD dengue Serotype 3; 2nd year follow up
    80
    50
        CYD dengue Serotype 3; 3rd year follow up
    68.8
    16.7
        CYD dengue Serotype 3; 4th year follow up
    71.4
    20
        CYD dengue Serotype 4; Post-Injection 3
    100
    33.3
        CYD dengue Serotype 4; 1st year follow up
    100
    20
        CYD dengue Serotype 4; 2nd year follow up
    100
    16.7
        CYD dengue Serotype 4; 3rd year follow up
    93.8
    16.7
        CYD dengue Serotype 4; 4th year follow up
    100
    20
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 12 to 17 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 12 to 17 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects naïve at baseline are defined as those subjects with titers <10 (1/dil) against all dengue serotypes at baseline.
    End point type
    Secondary
    End point timeframe
    Post-Injection 3 and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    313
    98
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Post-Injection 3
    62.9
    8.1
        CYD dengue Serotype 1; 1st year follow up
    20.9
    5.6
        CYD dengue Serotype 1; 2nd year follow up
    16.1
    5.9
        CYD dengue Serotype 1; 3rd year follow up
    12
    2.9
        CYD dengue Serotype 1; 4th year follow up
    7.7
    3.1
        CYD dengue Serotype 2; Post-Injection 3
    81.9
    8.1
        CYD dengue Serotype 2; 1st year follow up
    38.6
    2.8
        CYD dengue Serotype 2; 2nd year follow up
    49.1
    5.9
        CYD dengue Serotype 2; 3rd year follow up
    30.6
    2.9
        CYD dengue Serotype 2; 4th year follow up
    31.4
    3.1
        CYD dengue Serotype 3; Post-Injection 3
    87
    16.2
        CYD dengue Serotype 3; 1st year follow up
    59.5
    2.9
        CYD dengue Serotype 3; 2nd year follow up
    53.6
    5.9
        CYD dengue Serotype 3; 3rd year follow up
    45.8
    2.9
        CYD dengue Serotype 3; 4th year follow up
    44.2
    3.1
        CYD dengue Serotype 4; Post-Injection 3
    89.7
    5.4
        CYD dengue Serotype 4; 1st year follow up
    69.6
    0
        CYD dengue Serotype 4; 2nd year follow up
    67
    8.8
        CYD dengue Serotype 4; 3rd year follow up
    62.6
    2.9
        CYD dengue Serotype 4; 4th year follow up
    55.8
    6.3
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 18 to 45 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 18 to 45 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects immune at baseline are defined as those subjects with titers ≥10 (1/dil) against at least one dengue serotype at baseline.
    End point type
    Secondary
    End point timeframe
    Post-Injection 3 and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    114
    47
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Post-Injection 3
    89.3
    70
        CYD dengue Serotype 1; 1st year follow up
    77.8
    57.1
        CYD dengue Serotype 1; 2nd year follow up
    86.3
    65
        CYD dengue Serotype 1; 3rd year follow up
    80.8
    63.2
        CYD dengue Serotype 1; 4th year follow up
    84.8
    66.7
        CYD dengue Serotype 2; Post-Injection 3
    91.1
    65
        CYD dengue Serotype 2; 1st year follow up
    88.9
    71.4
        CYD dengue Serotype 2; 2nd year follow up
    92.2
    70
        CYD dengue Serotype 2; 3rd year follow up
    88.5
    68.4
        CYD dengue Serotype 2; 4th year follow up
    91.5
    66.7
        CYD dengue Serotype 3; Post-Injection 3
    98.2
    60
        CYD dengue Serotype 3; 1st year follow up
    90.7
    66.7
        CYD dengue Serotype 3; 2nd year follow up
    98
    70
        CYD dengue Serotype 3; 3rd year follow up
    94.2
    73.7
        CYD dengue Serotype 3; 4th year follow up
    91.5
    61.1
        CYD dengue Serotype 4; Post-Injection 3
    100
    65
        CYD dengue Serotype 4; 1st year follow up
    98.1
    47.6
        CYD dengue Serotype 4; 2nd year follow up
    96.1
    45
        CYD dengue Serotype 4; 3rd year follow up
    100
    42.1
        CYD dengue Serotype 4; 4th year follow up
    97.9
    44.4
    No statistical analyses for this end point

    Secondary: Percentage of Subjects Aged 18 to 45 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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    End point title
    Percentage of Subjects Aged 18 to 45 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects naïve at baseline are defined as those subjects with titers <10 (1/dil) against all dengue serotypes at baseline.
    End point type
    Secondary
    End point timeframe
    Post-Injection 3 and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    313
    98
    Units: Percentage of subjects
    number (not applicable)
        CYD dengue Serotype 1; Post-Injection 3
    59.4
    14.3
        CYD dengue Serotype 1; 1st year follow up
    21.3
    9.5
        CYD dengue Serotype 1; 2nd year follow up
    10.2
    5.3
        CYD dengue Serotype 1; 3rd year follow up
    7.1
    0
        CYD dengue Serotype 1; 4th year follow up
    5.6
    0
        CYD dengue Serotype 2; Post-Injection 3
    73.4
    0
        CYD dengue Serotype 2; 1st year follow up
    49.2
    14.3
        CYD dengue Serotype 2; 2nd year follow up
    50.8
    0
        CYD dengue Serotype 2; 3rd year follow up
    28.6
    5.6
        CYD dengue Serotype 2; 4th year follow up
    26.4
    0
        CYD dengue Serotype 3; Post-Injection 3
    87.5
    14.3
        CYD dengue Serotype 3; 1st year follow up
    48.3
    14.3
        CYD dengue Serotype 3; 2nd year follow up
    61
    21.1
        CYD dengue Serotype 3; 3rd year follow up
    46.3
    0
        CYD dengue Serotype 3; 4th year follow up
    28.3
    0
        CYD dengue Serotype 4; Post-Injection 3
    87.5
    4.8
        CYD dengue Serotype 4; 1st year follow up
    78.7
    14.3
        CYD dengue Serotype 4; 2nd year follow up
    71.2
    5.3
        CYD dengue Serotype 4; 3rd year follow up
    66.1
    0
        CYD dengue Serotype 4; 4th year follow up
    63
    0
    No statistical analyses for this end point

    Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 18 to 45 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

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    End point title
    Geometric Mean Titers (GMTs) of Antibodies In Subjects 18 to 45 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine
    End point description
    Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay.
    End point type
    Secondary
    End point timeframe
    Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up
    End point values
    CYD Dengue vaccine group Control group
    Number of subjects analysed
    438
    147
    Units: Titers (1/dil)
    geometric mean (confidence interval 95%)
        CYD dengue Serotype 1; Pre-Injection 1
    15.8 (11.7 to 21.5)
    19.2 (10.9 to 33.9)
        CYD dengue Serotype 1; Post-Injection 3
    48.7 (33.6 to 70.4)
    16.2 (9.77 to 27)
        CYD dengue Serotype 1; 1st year follow up
    26.3 (17.9 to 38.6)
    15.2 (8.76 to 26.3)
        CYD dengue Serotype 1; 2nd year follow up
    26.3 (17.7 to 38.9)
    16.3 (9.09 to 29.3)
        CYD dengue Serotype 1; 3rd year follow up
    24.1 (15.9 to 36.5)
    13.9 (7.89 to 24.6)
        CYD dengue Serotype 1; 4th year follow up
    23.5 (15.5 to 35.5)
    14.4 (8.03 to 25.6)
        CYD dengue Serotype 2; Pre-Injection 1
    16.9 (12.3 to 23.1)
    21 (11.5 to 38.2)
        CYD dengue Serotype 2; Post-Injection 3
    66.9 (47.9 to 93.5)
    15.2 (8.61 to 27)
        CYD dengue Serotype 2; 1st year follow up
    50.4 (34.5 to 73.7)
    19.3 (10.7 to 34.7)
        CYD dengue Serotype 2; 2nd year follow up
    66.5 (43.7 to 101)
    20 (10.2 to 39)
        CYD dengue Serotype 2; 3rd year follow up
    38.4 (25.8 to 57.2)
    17 (9.38 to 30.8)
        CYD dengue Serotype 2; 4th year follow up
    32.9 (22.4 to 48.2)
    15.5 (8.51 to 28.2)
        CYD dengue Serotype 3; Pre-Injection 1
    14.5 (11.2 to 18.7)
    19.4 (11.4 to 33.1)
        CYD dengue Serotype 3; Post-Injection 3
    88.4 (68.6 to 114)
    13.3 (8.22 to 21.7)
        CYD dengue Serotype 3; 1st year follow up
    45.2 (32.1 to 63.6)
    14.8 (8.96 to 24.3)
        CYD dengue Serotype 3; 2nd year follow up
    64.8 (46.8 to 89.7)
    19.9 (11.5 to 34.5)
        CYD dengue Serotype 3; 3rd year follow up
    48.3 (33 to 70.8)
    14.7 (8.46 to 25.7)
        CYD dengue Serotype 3; 4th year follow up
    28.6 (20.2 to 40.6)
    11.8 (7.18 to 19.3)
        CYD dengue Serotype 4; Pre-Injection 1
    10.1 (8.03 to 12.7)
    11.7 (7.74 to 17.6)
        CYD dengue Serotype 4; Post-Injection 3
    122 (96.5 to 155)
    10 (6.96 to 14.4)
        CYD dengue Serotype 4; 1st year follow up
    70.3 (53.6 to 92.2)
    9.87 (6.88 to 14.2)
        CYD dengue Serotype 4; 2nd year follow up
    52.6 (39.9 to 69.3)
    8.5 (6.07 to 11.9)
        CYD dengue Serotype 4; 3rd year follow up
    46.4 (35.5 to 60.6)
    8.39 (5.83 to 12.1)
        CYD dengue Serotype 4; 4th year follow up
    32.6 (25.2 to 42.3)
    7.54 (5.69 to 10)
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were collected from Day 0 (post-vaccination) up to the 4th year of follow up.
    Assessment type
    Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    11.0
    Reporting groups
    Reporting group title
    CYD Dengue vaccine group
    Reporting group description
    Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

    Reporting group title
    Control group
    Reporting group description
    Subjects received a placebo at first vaccination (Month 0). Subjects <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Subjects ≥12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

    Serious adverse events
    CYD Dengue vaccine group Control group
    Total subjects affected by serious adverse events
         subjects affected / exposed
    43 / 898 (4.79%)
    13 / 300 (4.33%)
         number of deaths (all causes)
    3
    0
         number of deaths resulting from adverse events
    0
    0
    Surgical and medical procedures
    Osteotomy
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Acute lymphocytic leukaemia
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian cancer metastatic
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Ovarian germ cell teratoma benign
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Papillary thyroid cancer
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ruptured ectopic pregnancy
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Adverse drug reaction
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Chest pain
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Depression
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Foot fracture
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand fracture
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intentional overdose
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Traumatic haematoma
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute coronary syndrome
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Asthma
         subjects affected / exposed
    2 / 898 (0.22%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchial hyperreactivity
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Rhinitis allergic
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Migraine
         subjects affected / exposed
    2 / 898 (0.22%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Radial nerve palsy
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Syncope vasovagal
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tension headache
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 898 (0.11%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gingivitis
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Back pain
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal pain
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid disorder
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    2 / 898 (0.22%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Conjunctivitis viral
         subjects affected / exposed
    2 / 898 (0.22%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Corneal infection
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Dengue fever
         subjects affected / exposed
    3 / 898 (0.33%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    2 / 898 (0.22%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 898 (0.11%)
    2 / 300 (0.67%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Groin abscess
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    2 / 898 (0.22%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpangina
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymph node tuberculosis
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Meningitis viral
         subjects affected / exposed
    0 / 898 (0.00%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis
         subjects affected / exposed
    1 / 898 (0.11%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pharyngitis bacterial
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Subcutaneous abscess
         subjects affected / exposed
    1 / 898 (0.11%)
    1 / 300 (0.33%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    2 / 898 (0.22%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 898 (0.11%)
    0 / 300 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    CYD Dengue vaccine group Control group
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    481 / 898 (53.56%)
    198 / 300 (66.00%)
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    42 / 898 (4.68%)
    15 / 300 (5.00%)
         occurrences all number
    48
    17
    Rhinorrhoea
         subjects affected / exposed
    42 / 898 (4.68%)
    15 / 300 (5.00%)
         occurrences all number
    47
    15
    Nervous system disorders
    Headache; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [1]
    402 / 891 (45.12%)
    114 / 297 (38.38%)
         occurrences all number
    402
    114
    General disorders and administration site conditions
    Injection site Pain; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [2]
    481 / 892 (53.92%)
    198 / 297 (66.67%)
         occurrences all number
    481
    198
    Injection site Erythema; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [3]
    64 / 891 (7.18%)
    45 / 297 (15.15%)
         occurrences all number
    64
    45
    Injection site Swelling; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [4]
    37 / 892 (4.15%)
    25 / 297 (8.42%)
         occurrences all number
    37
    25
    Fever; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [5]
    101 / 892 (11.32%)
    22 / 297 (7.41%)
         occurrences all number
    101
    22
    Malaise; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [6]
    372 / 891 (41.75%)
    105 / 297 (35.35%)
         occurrences all number
    372
    105
    Asthenia; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [7]
    183 / 891 (20.54%)
    52 / 297 (17.51%)
         occurrences all number
    183
    52
    Musculoskeletal and connective tissue disorders
    Myalgia; Post-Any Injection
    alternative assessment type: Systematic
         subjects affected / exposed [8]
    394 / 891 (44.22%)
    130 / 297 (43.77%)
         occurrences all number
    394
    130
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    72 / 898 (8.02%)
    27 / 300 (9.00%)
         occurrences all number
    77
    30
    Notes
    [1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 7 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 7 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 7 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
    [8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
    Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    05 Dec 2008
    Integrated comments from the Institutional Review Boards in the Protocol and Appendices.
    20 May 2009
    Modified the observer-blind design for the second vaccination into a single-blind design and modified the interim statistical analysis schedule to include an analysis at 24 and 36 months post-last vaccination to get supportive data regarding persistence of neutralizing antibodies.
    06 Dec 2010
    Changed from Pan Flavivirus reverse transcriptase-polymerase chain reaction (RT-PCR) to dengue screen RT-PCR to improve assay sensitivity, replaced the microneutralization assay by the plaque reduction neutralization test (PRNT) assay to determine dengue neutralizing antibodies to serotypes 1, 2, 3, and 4 in subjects, replaced the method of the assessment of the cross-reactivity (microneutralization assay) by a seroneutralization assay, added an observational objective regarding the cell mediated immunity and additional blood sample volumes were added at each visit during the 4-year follow up, and due to limited time between post-Injection 2 and 3 results the post-Injection 2 analysis of safety and immunogenicity was cancelled in order to analyze the results of post-Injection 2 and 3 samples obtained by PRNT at the same time; as a result, the blind was broken and subjects were informed about the vaccines after the database lock for statistical analyses.
    28 Mar 2012
    The Sponsor's Responsible Medical Officer for the study was replaced by T. Anh Wartel during the conduct of the long-term follow up and a new Principal Investigator (Low Chian Yong) was assigned to Center 004 from July 2011 following the resignation of the existing Principal Investigator.

    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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