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    Clinical Trial Results:
    Immunogenicity and Safety of Tetravalent Dengue Vaccine Given in 1-, 2-, or 3-Dose Schedules (STAGE I) Followed by a Single Booster Injection of the Same Vaccine (STAGE II) 1 or 2 Years after the Last Primary Dose in Healthy Subjects 9 to 50 Years of Age in Colombia and the Philippines

    Summary
    EudraCT number
    2020-002854-25
    Trial protocol
    Outside EU/EEA  
    Global end of trial date
    29 Apr 2020

    Results information
    Results version number
    v1(current)
    This version publication date
    12 Nov 2020
    First version publication date
    12 Nov 2020
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CYD65
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT02628444
    WHO universal trial number (UTN)
    U1111-1161-3242
    Sponsors
    Sponsor organisation name
    Sanofi Pasteur
    Sponsor organisation address
    14, Espace Henry Vallée, Lyon, France, 69007
    Public contact
    Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
    Scientific contact
    Trial Transparency Team, Sanofi Pasteur, Contact-US@sanofi.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    12 Aug 2020
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Apr 2020
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    STAGE1: •To demonstrate non-inferiority (NI) of immune response elicited against each dengue serotype by CYD dengue vaccine given as 2-dose schedule (Group 2) compared to immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in subjects seropositive at Baseline, 28 days post-final injection, and 1 year after last injection, both in terms of geometric mean ratio (GMR). STAGE2: •To demonstrate NI of immune response elicited against each dengue serotype by CYD dengue vaccine, in subjects seropositive at baseline, 28 days after administration of booster dose of CYD dengue vaccine, in terms of geometric mean of titer ratio (GMTR, within a group) or GMR (between groups): Booster Dose at 1 Year •Post-Year 1 booster Group 1/post-Dose-3 Group 1 (GMTR) •Post-Year 1 booster Group 2/post-Dose 3 Group 1 (GMR) Booster Dose at 2 Years •Post-Year 2 booster Group 1/post-Dose 3 Group 1 (GMTR) •Post-Year 2 booster Group 2/post-Dose 3 Group 1 (GMR)
    Protection of trial subjects
    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
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    02 May 2016
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    Safety
    Long term follow-up duration
    2 Years
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Colombia: 525
    Country: Number of subjects enrolled
    Philippines: 525
    Worldwide total number of subjects
    1050
    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)
    162
    Adolescents (12-17 years)
    173
    Adults (18-64 years)
    715
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    The study was conducted at 6 active centers in 2 countries. A total of 1050 subjects were enrolled from 02 May 2016 to 16 September 2016.

    Pre-assignment
    Screening details
    Subjects were enrolled and randomised in 1:1:1 ratio to 1 of 3 treatment arms in STAGE-I. After STAGE-I, subjects identified as seropositive at Baseline were randomised in ratio 1:1 to 1 of 2 subgroups (a [1a,2a,3a] or b: [1b,2b,3b]) and received one CYD booster vaccine in STAGE-II at either 12 months (Subgroup a) or 24 months (Subgroup b).

    Period 1
    Period 1 title
    STAGE-I (24 Months)
    Is this the baseline period?
    Yes
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    STAGE-I Group 1: CYD Dengue Vaccine
    Arm description
    Subjects received 3 doses of CYD dengue vaccine 0.5 millilitres (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received 0.5 mL, SC injection at Day 0, Month 6, and Month 12, respectively, in the deltoid region of the upper arm.

    Arm title
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
    Arm description
    Subjects received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, SC injection at Month 6 and Month 12, respectively, in the deltoid region of the upper arm.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL placebo matched to CYD vaccine, SC injection at Day 0 in the deltoid region of the upper arm.

    Arm title
    STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Arm description
    Subjects received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, SC injection at Month 12, in the deltoid region of the upper arm.

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL placebo matched to CYD vaccine, SC injection at Day 0 and Month 6, in the deltoid region of the upper arm.

    Number of subjects in period 1
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Started
    350
    348
    352
    Vaccinated subjects
    348
    348
    352
    Full analysis set
    333
    328
    332
    Completed
    314
    309
    310
    Not completed
    36
    39
    42
         Adverse event (AE) intensity less than (<) Grade 1
    1
    -
    -
         Serious AE (SAE)
    -
    4
    3
         Voluntary withdrawal not due to AE
    21
    16
    25
         Non-compliance with protocol
    9
    16
    9
         Lost to follow-up
    5
    3
    5
    Period 2
    Period 2 title
    STAGE-II (18 Months)
    Is this the baseline period?
    No
    Allocation method
    Randomised - controlled
    Blinding used
    Double blind
    Roles blinded
    Carer, Assessor, Subject, Investigator, Monitor, Data analyst

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)
    Arm description
    Subjects from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, booster SC injection after 1 year (or 12 months) post last dose in STAGE-I, in the deltoid region of the upper arm.

    Arm title
    STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)
    Arm description
    Subjects from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, booster SC injection after 1 year (or 12 months) post last dose in STAGE-I, in the deltoid region of the upper arm.

    Arm title
    STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)
    Arm description
    Subjects from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, booster SC injection after 1 year (or 12 months) post last dose in STAGE-I, in the deltoid region of the upper arm.

    Arm title
    STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)
    Arm description
    Subjects from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, booster SC injection after 2 years (or 24 months) post last dose in STAGE-I, in the deltoid region of the upper arm.

    Arm title
    STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)
    Arm description
    Subjects from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, booster SC injection after 2 years (or 24 months) post last dose in STAGE-I, in the deltoid region of the upper arm.

    Arm title
    STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Arm description
    Subjects from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
    Arm type
    Experimental

    Investigational medicinal product name
    CYD Dengue Vaccine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Powder and solvent for suspension for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subject received 0.5 mL, booster SC injection after 2 years (or 24 months) post last dose in STAGE-I, in the deltoid region of the upper arm.

    Number of subjects in period 2 [1]
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Started
    145
    152
    157
    149
    152
    151
    Vaccinated
    55
    59
    62
    53
    54
    52
    Completed
    55
    59
    62
    53
    54
    52
    Not completed
    90
    93
    95
    96
    98
    99
         Other AE
    1
    -
    -
    -
    -
    -
         Non-compliance with protocol
    83
    83
    83
    81
    84
    85
         Voluntary withdrawal not due to AE
    5
    6
    10
    12
    11
    9
         SAE
    -
    3
    -
    -
    2
    3
         Lost to follow-up
    1
    1
    2
    3
    1
    2
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: Started indicates the number of subjects who had completed STAGE-I and were seropositive at Baseline.

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    STAGE-I Group 1: CYD Dengue Vaccine
    Reporting group description
    Subjects received 3 doses of CYD dengue vaccine 0.5 millilitres (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3).

    Reporting group title
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
    Reporting group description
    Subjects received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).

    Reporting group title
    STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Reporting group description
    Subjects received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).

    Reporting group values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) Total
    Number of subjects
    350 348 352 1050
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    30.8 ± 14.42 31.3 ± 14.47 31.1 ± 14.62 -
    Gender categorical
    Units: Subjects
        Female
    190 197 185 572
        Male
    160 151 167 478
    Race
    Units: Subjects
        American Indian or Alaska Native
    171 172 169 512
        Asian
    174 172 177 523
        Black or African American
    5 3 6 14
        Native Hawaiian or Other Pacific Islander
    0 0 0 0
        White
    0 1 0 1
        Not Reported
    0 0 0 0
    Dengue Baseline Status
    Baseline dengue seropositive subjects were defined as subjects with greater than equal to (>=) 10 (1/dilution [dil]) for at least 1 serotype with parental dengue virus strain. Baseline dengue seronegative subjects were defined as subjects with valid titer less than (<) 10 (1/dil) for all serotypes with parental dengue virus strains. Baseline dengue status was evaluated for subjects in full analysis set (FAS) that included subjects who had received either at least 1 injection of either CYD dengue vaccine or placebo and had at least 1 blood sample drawn and valid post-injection serology results.
    Units: Subjects
        Seropositive subjects
    281 288 291 860
        Seronegative subjects
    52 40 41 133
        Undetermined
    17 20 20 57

    End points

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    End points reporting groups
    Reporting group title
    STAGE-I Group 1: CYD Dengue Vaccine
    Reporting group description
    Subjects received 3 doses of CYD dengue vaccine 0.5 millilitres (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3).

    Reporting group title
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
    Reporting group description
    Subjects received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).

    Reporting group title
    STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Reporting group description
    Subjects received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
    Reporting group title
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)
    Reporting group description
    Subjects from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).

    Reporting group title
    STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)
    Reporting group description
    Subjects from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).

    Reporting group title
    STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)
    Reporting group description
    Subjects from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).

    Reporting group title
    STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)
    Reporting group description
    Subjects from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).

    Reporting group title
    STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)
    Reporting group description
    Subjects from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).

    Reporting group title
    STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Reporting group description
    Subjects from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).

    Subject analysis set title
    Group 1: 28 days Post-dose 3 in STAGE-I
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects who received 3 doses of CYD dengue vaccine in STAGE-I, and were seropositive at Baseline were assessed 28 days after third CYD vaccine in STAGE-I.

    Subject analysis set title
    Group 1a: 28 days post 12 month Booster dose
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects from Group 1 (STAGE-I) who were seropositive at Baseline and received a booster dose at 1 year (or 12 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.

    Subject analysis set title
    Group 1b: 28 days post 24 month Booster dose
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects from Group 1 (STAGE-I) who were seropositive at Baseline and received a booster dose at 2 years (or 24 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.

    Subject analysis set title
    Group 2a: 28 days post 12 month Booster dose
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects from Group 2 (STAGE-I) who were seropositive at Baseline and received a booster dose at 1 year (or 12 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.

    Subject analysis set title
    Group 2b: 28 days post 24 month Booster dose
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Subjects from Group 2 (STAGE-I) who were seropositive at Baseline and received a booster dose at 2 years (or 24 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.

    Primary: STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline

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    End point title
    STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline [1]
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using plaque reduction neutralisation test (PRNT) assay method. Dengue seropositive subjects at Baseline: subjects with titers >=10 (1/dil) for at least 1 serotype with parental dengue virus strains. Analysis performed on per-protocol analysis set (PPAS): all subjects who had no protocol violations; and who met any of following study violations were excluded from PPAS (STAGE I/II): had not met all protocol-specified inclusion/exclusion criteria, had not received correct doses or injections, received vaccine other than randomised schedule, did not receive the vaccination in proper time window, had not provided post-dose serology sample in proper time window, received protocol-restricted medication, therapy, or vaccine. Here, 'Number of subject analysed'=subjects with available data for this endpoint.
    End point type
    Primary
    End point timeframe
    28 days after last CYD dengue vaccination
    Notes
    [1] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was not planned to be collected and analysed for Group 3, as pre-specified in protocol.
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
    Number of subjects analysed
    265
    272
    Units: titers
    geometric mean (confidence interval 95%)
        Serotype 1
    822 (700 to 964)
    899 (752 to 1075)
        Serotype 2
    875 (770 to 995)
    869 (754 to 1002)
        Serotype 3
    610 (535 to 694)
    599 (524 to 685)
        Serotype 4
    531 (470 to 601)
    510 (453 to 575)
    Statistical analysis title
    Group 2/Group 1: Serotype 1
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% confidence interval (CI) of the ratio of GMTs between groups (Group 2/Group 1) was greater than (>) 1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    537
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    Ratio
    Point estimate
    1.09
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.862
         upper limit
    1.39
    Statistical analysis title
    Group 2/Group 1: Serotype 2
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    537
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    Ratio
    Point estimate
    0.993
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.82
         upper limit
    1.2
    Statistical analysis title
    Group 2/Group 1: Serotype 3
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    537
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    Ratio
    Point estimate
    0.983
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.816
         upper limit
    1.18
    Statistical analysis title
    Group 2/Group 1: Serotype 4
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    537
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    Ratio
    Point estimate
    0.96
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.809
         upper limit
    1.14

    Primary: STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline

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    End point title
    STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline [2]
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Analysis was performed on PPAS. Here, 'Number of subject analysed' = subjects with available data for this endpoint.
    End point type
    Primary
    End point timeframe
    1 year after last CYD dengue vaccination
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data for this endpoint was not planned to be collected and analysed for Group 3, as pre-specified in protocol.
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
    Number of subjects analysed
    185
    190
    Units: titers
    geometric mean (confidence interval 95%)
        Serotype 1
    490 (398 to 604)
    504 (403 to 630)
        Serotype 2
    821 (704 to 957)
    737 (611 to 888)
        Serotype 3
    477 (405 to 561)
    437 (368 to 519)
        Serotype 4
    270 (235 to 310)
    238 (205 to 277)
    Statistical analysis title
    Group 2/Group 1: Serotype 1
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    375
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    1.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.757
         upper limit
    1.4
    Statistical analysis title
    Group 2/Group 1: Serotype 2
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    375
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.897
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.705
         upper limit
    1.14
    Statistical analysis title
    Group 2/Group 1: Serotype 3
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    375
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.917
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.724
         upper limit
    1.16
    Statistical analysis title
    Group 2/Group 1: Serotype 4
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    375
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.884
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.72
         upper limit
    1.09

    Primary: STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline

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    End point title
    STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days after post-dose 3 in STAGE-I) and Group 1a (28 days post 12 month Booster dose) was reported and compared in this endpoint. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1a: 28 days post 12 months booster dose by Group 1: 28 days Post-dose 3 in STAGE-I. Analysis was performed on PPAS. Here, 'Number of subject analysed'=subjects with available data for this endpoint.
    End point type
    Primary
    End point timeframe
    Group 1: 28 days Post-dose 3 in STAGE-I, Group 1a: 28 days post 12 month booster dose
    End point values
    Group 1: 28 days Post-dose 3 in STAGE-I Group 1a: 28 days post 12 month Booster dose
    Number of subjects analysed
    53
    53
    Units: titers
    geometric mean (confidence interval 98.75%)
        Serotype 1
    853 (526 to 1384)
    483 (281 to 832)
        Serotype 2
    1186 (809 to 1738)
    884 (602 to 1300)
        Serotype 3
    696 (483 to 1002)
    722 (458 to 1140)
        Serotype 4
    592 (400 to 876)
    383 (269 to 545)
    Statistical analysis title
    Group 1a Booster/Group 1 Post-dose 3: Serotype 1
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1a: 28 days post 12 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    0.567
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.399
         upper limit
    0.805
    Statistical analysis title
    Group 1a Booster/Group 1 Post-dose 3: Serotype 2
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1a: 28 days post 12 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    0.746
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.55
         upper limit
    1.01
    Statistical analysis title
    Group 1a Booster/Group 1 Post-dose 3: Serotype 3
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1a: 28 days post 12 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    1.04
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.686
         upper limit
    1.57
    Statistical analysis title
    Group 1a Booster/Group 1 Post-dose 3: Serotype 4
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1a: 28 days post 12 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    0.647
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.434
         upper limit
    0.963

    Primary: STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline

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    End point title
    STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dil. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2a (28 days post 12 months Booster dose) was reported and compared in this endpoint. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2a: 28 days post 12 months booster dose by Group 1: 28 days Post-dose 3 in STAGE-I. Analysis was performed on PPAS. Here, 'Number of subject analysed' = subjects with available data for this endpoint.
    End point type
    Primary
    End point timeframe
    Group 1: 28 days Post-dose 3 in STAGE-I, Group 2a: 28 days post 12 month booster dose
    End point values
    Group 1: 28 days Post-dose 3 in STAGE-I Group 2a: 28 days post 12 month Booster dose
    Number of subjects analysed
    112
    58
    Units: titers
    geometric mean (confidence interval 98.75%)
        Serotype 1
    875 (614 to 1248)
    549 (331 to 911)
        Serotype 2
    1023 (771 to 1356)
    828 (569 to 1203)
        Serotype 3
    568 (433 to 745)
    676 (436 to 1049)
        Serotype 4
    540 (418 to 697)
    270 (200 to 364)
    Statistical analysis title
    Group 2a Booster/Group 1 Post-dose 3: Serotype 1
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was to be demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 2a: 28 days post 12 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.627
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.342
         upper limit
    1.15
    Statistical analysis title
    Group 2a Booster/Group 1 Post-dose 3: Serotype 2
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was to be demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 2a: 28 days post 12 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.809
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.505
         upper limit
    1.3
    Statistical analysis title
    Group 2a Booster/Group 1 Post-dose 3: Serotype 3
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was to be demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 2a: 28 days post 12 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    1.19
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.732
         upper limit
    1.94
    Statistical analysis title
    Group 2a Booster/Group 1 Post-dose 3: Serotype 4
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was to be demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1: 28 days Post-dose 3 in STAGE-I v Group 2a: 28 days post 12 month Booster dose
    Number of subjects included in analysis
    170
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.499
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.331
         upper limit
    0.754

    Primary: STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1b and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline

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    End point title
    STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1b and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dil. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days Post-dose 3 in STAGE-I) and Group 1b (28 days post 24 month booster dose) was reported and compared in this endpoint. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1b: 28 days post 24 months booster dose by Group 1: 28 days Post-dose 3 in STAGE-I. Analysis was performed on PPAS. Here, 'Number of subject analysed'=subjects with available data for this endpoint.
    End point type
    Primary
    End point timeframe
    Group 1: 28 days Post-dose 3 in STAGE-I, Group 1b: 28 days post 24 month booster dose
    End point values
    Group 1: 28 days Post-dose 3 in STAGE-I Group 1b: 28 days post 24 month Booster dose
    Number of subjects analysed
    48
    48
    Units: titers
    geometric mean (confidence interval 98.75%)
        Serotype 1
    1017 (592 to 1746)
    700 (401 to 1220)
        Serotype 2
    838 (554 to 1269)
    730 (497 to 1071)
        Serotype 3
    486 (333 to 708)
    559 (395 to 792)
        Serotype 4
    556 (400 to 774)
    364 (260 to 510)
    Statistical analysis title
    Group 1b Booster/Group 1 Post-dose 3: Serotype 1
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    0.688
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.479
         upper limit
    0.989
    Statistical analysis title
    Group 1b Booster/Group 1 Post-dose 3: Serotype 2
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    0.871
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.673
         upper limit
    1.13
    Statistical analysis title
    Group 1b Booster/Group 1 Post-dose 3: Serotype 3
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    1.15
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.887
         upper limit
    1.49
    Statistical analysis title
    Group 1b Booster/Group 1 Post-dose 3: Serotype 4
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 1b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    96
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT paired ratio
    Point estimate
    0.655
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.471
         upper limit
    0.911

    Primary: STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2b and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline

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    End point title
    STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2b and Group 1 After the Third Dose of CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2b (28 days post 12 months Booster dose) was reported and compared in this endpoint. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2b: 28 days post 24 months booster dose by Group 1: 28 days Post-dose 3 in STAGE-I. Analysis was performed on PPAS. Here, 'Number of subject analysed'=subjects with available data for this endpoint.
    End point type
    Primary
    End point timeframe
    Group 1: 28 days Post-dose 3 in STAGE-I, Group 2b: 28 days post 24 month Booster dose
    End point values
    Group 1: 28 days Post-dose 3 in STAGE-I Group 2b: 28 days post 24 month Booster dose
    Number of subjects analysed
    112
    50
    Units: titers
    geometric mean (confidence interval 98.75%)
        Serotype 1
    875 (614 to 1248)
    778 (429 to 1414)
        Serotype 2
    1023 (771 to 1356)
    692 (430 to 1116)
        Serotype 3
    568 (433 to 745)
    517 (365 to 733)
        Serotype 4
    540 (418 to 697)
    379 (261 to 551)
    Statistical analysis title
    Group 2b Booster/Group 1 Post-dose 3: Serotype 1
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 2b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.889
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.462
         upper limit
    1.71
    Statistical analysis title
    Group 2b Booster/Group 1 Post-dose 3: Serotype 2
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 2b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.677
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.402
         upper limit
    1.14
    Statistical analysis title
    Group 2b Booster/Group 1 Post-dose 3: Serotype 3
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 2b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.911
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.573
         upper limit
    1.45
    Statistical analysis title
    Group 2b Booster/Group 1 Post-dose 3: Serotype 4
    Statistical analysis description
    The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
    Comparison groups
    Group 2b: 28 days post 24 month Booster dose v Group 1: 28 days Post-dose 3 in STAGE-I
    Number of subjects included in analysis
    162
    Analysis specification
    Pre-specified
    Analysis type
    non-inferiority
    Method
    Parameter type
    GMT ratio
    Point estimate
    0.702
    Confidence interval
         level
    98.75%
         sides
    2-sided
         lower limit
    0.447
         upper limit
    1.1

    Secondary: STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline

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    End point title
    STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After CYD Dengue Vaccination in Subjects Who Were Seropositive at Baseline [3]
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Analysis was performed on FAS that included the subjects who had received either at least one injection of CYD dengue vaccine or placebo; and had at least one blood sample drawn and valid post-injection serology results. Here, 'Number of subject analysed'=subjects with available data for this endpoint and 'n' = subjects with available data for each specified category. Here, 'vacc.' in categories indicates 'vaccination'.
    End point type
    Secondary
    End point timeframe
    28 days and 1 year after last CYD dengue vaccination
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Data were collected and analysed for the applicable arms only.
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
    Number of subjects analysed
    281
    288
    Units: titers
    geometric mean (confidence interval 95%)
        28 days after last vacc.:Serotype 1 (n=274,282)
    834 (713 to 975)
    877 (737 to 1043)
        28 days after last vacc.:Serotype 2 (n=274, 282)
    879 (775 to 997)
    870 (758 to 1000)
        28 days after last vacc.:Serotype 3 (n=274, 282)
    620 (545 to 704)
    602 (529 to 686)
        28 days after last vacc.:Serotype 4 (n=274, 282)
    527 (467 to 595)
    507 (451 to 570)
        1 year after last vacc.:Serotype 1 (n=192, 197)
    498 (406 to 611)
    512 (411 to 638)
        1 year after last vacc.:Serotype 2 (n=192, 197)
    815 (702 to 947)
    747 (622 to 897)
        1 year after last vacc.:Serotype 3 (n=192, 197)
    477 (407 to 558)
    444 (376 to 525)
        1 year after last vacc.:Serotype 4 (n=192, 197)
    263 (230 to 302)
    241 (208 to 279)
    Statistical analysis title
    Group2/Group1: Serotype 1(28days after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    1.05
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.833
         upper limit
    1.33
    Statistical analysis title
    Group2/Group1: Serotype2 (28days after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.99
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.821
         upper limit
    1.19
    Statistical analysis title
    Group2/Group1: Serotype3 (28days after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.972
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.81
         upper limit
    1.17
    Statistical analysis title
    Group2/Group1: Serotype4 (28days after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.963
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.814
         upper limit
    1.14
    Statistical analysis title
    Group2/Group1: Serotype1 (1 year after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    1.03
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.762
         upper limit
    1.39
    Statistical analysis title
    Group2/Group1: Serotype2 (1 year after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.917
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.724
         upper limit
    1.16
    Statistical analysis title
    Group2/Group1: Serotype3 (1 year after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.933
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.742
         upper limit
    1.17
    Statistical analysis title
    Group2/Group1: Serotype4 (1 year after last vacc.)
    Comparison groups
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) v STAGE-I Group 1: CYD Dengue Vaccine
    Number of subjects included in analysis
    569
    Analysis specification
    Pre-specified
    Analysis type
    superiority
    Method
    Parameter type
    GMT Ratio
    Point estimate
    0.916
    Confidence interval
         level
    95%
         sides
    2-sided
         lower limit
    0.75
         upper limit
    1.12

    Secondary: STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Subjects

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    End point title
    STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Subjects
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (parental strains) were assessed using the PRNT assay method. Analysis was performed on FAS. Here, 'n' = subjects with available data for each specified category. Here, 'vacc.' in categories indicates 'vaccination'.
    End point type
    Secondary
    End point timeframe
    Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    333
    328
    332
    Units: titers
    geometric mean (confidence interval 95%)
        Serotype 1: Baseline (n=333,328,332)
    131 (103 to 165)
    187 (147 to 237)
    198 (157 to 250)
        Serotype 1: 28 days post vacc. 3 (n=326,322,324)
    497 (410 to 602)
    586 (482 to 714)
    735 (589 to 916)
        Serotype 1: 1 year post vacc. 3 (n=231,232,230)
    259 (200 to 336)
    279 (213 to 365)
    331 (252 to 435)
        Serotype 2: Baseline (n=333,328,332)
    172 (138 to 214)
    202 (163 to 252)
    181 (147 to 222)
        Serotype 2: 28 days post vacc.3 (n=326,322,324)
    567 (482 to 666)
    628 (532 to 741)
    734 (614 to 878)
        Serotype 2: 1 year post vacc. 3 (n=231,232,230)
    470 (380 to 582)
    457 (364 to 574)
    500 (402 to 623)
        Serotype 3: Baseline (n=333,328,332)
    163 (131 to 202)
    180 (145 to 222)
    169 (138 to 207)
        Serotype 3: 28 days post vacc.3 (n=326,322,324)
    432 (373 to 500)
    446 (383 to 519)
    505 (428 to 595)
        Serotype 3: 1 year post vacc. 3 (n=231,232,230)
    294 (240 to 361)
    288 (235 to 354)
    258 (213 to 312)
        Serotype 4: Baseline (n=333,328,332)
    86.7 (71.4 to 105)
    83.8 (69.9 to 100)
    81.2 (67.7 to 97.4)
        Serotype 4: 28 days post vacc.3 (n=326,322,324)
    429 (380 to 484)
    441 (392 to 496)
    546 (475 to 629)
        Serotype 4: 1 year post vacc. 3 (n=231,232,230)
    203 (176 to 235)
    192 (164 to 226)
    177 (150 to 210)
    No statistical analyses for this end point

    Secondary: STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains (by Baseline Dengue Status) in Subjects Who Were Seropositive and Seronegative at Baseline

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    End point title
    STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains (by Baseline Dengue Status) in Subjects Who Were Seropositive and Seronegative at Baseline
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using the PRNT assay. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Dengue seronegative subjects at Baseline were defined as the subjects with valid titer <0 (1/dil) for all serotypes with parental dengue virus strains. Titers were measured in terms of 1/dil. Analysis was performed on FAS. Here, ‘number of subjects analysed’=subjects evaluable for this endpoint and 'n'=subjects with available data for each specified category. Here, 'vacc.' in categories indicates 'vaccination'; ‘SP’ and ‘SN’ in categories indicates ‘seropositive’ and ‘seronegative’, respectively; '99999' is used as space filler and specify that the 95% CI was not computable as the standard deviation of the sample was 0, since all subjects had the same value.
    End point type
    Secondary
    End point timeframe
    Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    281
    288
    291
    Units: titers
    geometric mean (confidence interval 95%)
        SP- Serotype1: Baseline (n=281,288,291)
    239 (194 to 295)
    304 (244 to 379)
    328 (267 to 404)
        SP- Serotype1: 28 days post inj. 3 (n=274,282,285)
    834 (713 to 975)
    877 (737 to 1043)
    1201 (1007 to 1431)
        SP- Serotype1: 1 year post inj. 3 (n=192,197,197)
    498 (406 to 611)
    512 (411 to 638)
    618 (500 to 764)
        SP- Serotype2: Baseline (n=281,288,291)
    331 (279 to 394)
    326 (271 to 393)
    293 (247 to 347)
        SP- Serotype2: 28 days post inj. 3 (n=274,282,285)
    879 (775 to 997)
    870 (758 to 1000)
    1046 (912 to 1201)
        SP- Serotype2: 1 year post inj. 3 (n=192,197,197)
    815 (702 to 947)
    747 (622 to 897)
    798 (676 to 942)
        SP- Serotype3: Baseline (n=281,288,291)
    310 (263 to 367)
    290 (241 to 349)
    269 (227 to 319)
        SP- Serotype3: 28 days post inj. 3 (n=274,282,285)
    620 (545 to 704)
    602 (529 to 686)
    694 (604 to 797)
        SP- Serotype3: 1 year post inj. 3 (n=192,197,197)
    477 (407 to 558)
    444 (376 to 525)
    390 (338 to 450)
        SP- Serotype4: Baseline (n=281,288,291)
    147 (124 to 174)
    123 (104 to 144)
    118 (100 to 140)
        SP- Serotype4: 28 days post inj. 3 (n=274,282,285)
    527 (467 to 595)
    507 (451 to 570)
    581 (507 to 666)
        SP- Serotype4: 1 year post inj. 3 (n=192,197,197)
    263 (230 to 302)
    241 (208 to 279)
    227 (194 to 265)
        SN- Serotype1: Baseline (n=52,40,41)
    5.00 (-99999 to 99999)
    5.57 (4.65 to 6.67)
    5.49 (4.75 to 6.34)
        SN- Serotype1: 28 days post inj. 3 (n=52,40,39)
    32.4 (23.1 to 45.6)
    34.3 (23.8 to 49.4)
    20.2 (12.0 to 34.1)
        SN- Serotype1: 1 year post inj. 3 (n=39,35,33)
    10.4 (7.12 to 15.1)
    9.01 (6.30 to 12.9)
    8.04 (5.86 to 11.0)
        SN- Serotype2: Baseline (n=52,40,41)
    5.00 (-99999 to 99999)
    6.47 (4.43 to 9.45)
    5.86 (4.99 to 6.89)
        SN- Serotype2: 28 days post inj. 3 (n=52,40,39)
    56.2 (40.1 to 78.7)
    63.0 (37.5 to 106)
    55.2 (27.8 to 110)
        SN- Serotype2: 1 year post inj. 3 (n=39,35,33)
    31.3 (20.2 to 48.6)
    28.7 (17.3 to 47.7)
    30.9 (17.5 to 54.5)
        SN- Serotype3: Baseline (n=52,40,41)
    5.00 (-99999 to 99999)
    5.69 (4.86 to 6.66)
    6.09 (5.05 to 7.34)
        SN- Serotype3: 28 days post inj. 3 (n=52,40,39)
    64.2 (48.6 to 84.9)
    53.7 (36.1 to 80.0)
    49.5 (30.1 to 81.5)
        SN- Serotype3: 1 year post inj. 3 (n=39,35,33)
    27.5 (17.4 to 43.5)
    25.3 (15.8 to 40.3)
    21.8 (13.6 to 35.0)
        SN- Serotype4: Baseline (n=52,40,41)
    5.00 (-99999 to 99999)
    5.41 (4.61 to 6.35)
    5.64 (4.90 to 6.50)
        SN- Serotype4: 28 days post inj. 3 (n=52,40,39)
    145 (112 to 187)
    164 (114 to 237)
    349 (189 to 646)
        SN- Serotype4: 1 year post inj. 3 (n=39,35,33)
    57.1 (42.5 to 76.8)
    53.8 (32.0 to 90.5)
    40.8 (24.9 to 66.8)
    No statistical analyses for this end point

    Secondary: STAGE-I: Percentage of Subjects With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Subjects

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    End point title
    STAGE-I: Percentage of Subjects With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Subjects
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay. Analysis was performed on FAS. Here, 'n' = subjects with available data for each specified category. Here, 'vacc.' in categories indicates 'vaccination'.
    End point type
    Secondary
    End point timeframe
    Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    333
    328
    332
    Units: percentage of subjects
    number (confidence interval 95%)
        Serotype 1: Baseline (n=333,328,332)
    77.8 (72.9 to 82.1)
    80.5 (75.8 to 84.6)
    83.4 (79.0 to 87.3)
        Serotype 1: 28 days post vacc.3 (n=326,322,324)
    96.3 (93.7 to 98.1)
    97.2 (94.8 to 98.7)
    94.1 (91.0 to 96.4)
        Serotype 1: 1 year post vacc.3 (n=231,232,230)
    88.3 (83.5 to 92.2)
    87.5 (82.5 to 91.5)
    88.3 (83.4 to 92.1)
        Serotype 2: Baseline (n=333,328,332)
    82.6 (78.1 to 86.5)
    83.8 (79.4 to 87.7)
    85.2 (81.0 to 88.9)
        Serotype 2: 28 days post vacc.3 (n=326,322,324)
    98.2 (96.0 to 99.3)
    96.6 (94.0 to 98.3)
    96.0 (93.2 to 97.8)
        Serotype 2: 1 year post vacc.3 (n=231,232,230)
    95.7 (92.2 to 97.9)
    94.4 (90.6 to 97.0)
    94.8 (91.1 to 97.3)
        Serotype 3: Baseline (n=333,328,332)
    82.6 (78.1 to 86.5)
    84.1 (79.7 to 87.9)
    87.0 (83.0 to 90.5)
        Serotype 3: 28 days post vacc.3 (n=326,322,324)
    98.5 (96.5 to 99.5)
    98.1 (96.0 to 99.3)
    97.5 (95.2 to 98.9)
        Serotype 3: 1 year post vacc.3 (n=231,232,230)
    95.7 (92.2 to 97.9)
    95.7 (92.2 to 97.9)
    94.3 (90.5 to 97.0)
        Serotype 4: Baseline (n=333,328,332)
    79.6 (74.8 to 83.8)
    81.4 (76.8 to 85.5)
    81.6 (77.0 to 85.6)
        Serotype 4: 28 days post vacc.3 (n=326,322,324)
    99.7 (98.3 to 100.0)
    99.4 (97.8 to 99.9)
    98.8 (96.9 to 99.7)
        Serotype 4: 1 year post vacc.3 (n=231,232,230)
    99.1 (96.9 to 99.9)
    96.6 (93.3 to 98.5)
    95.7 (92.1 to 97.9)
    No statistical analyses for this end point

    Secondary: STAGE-II: Percentage of Subjects With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Subjects Seropositive at Baseline

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    End point title
    STAGE-II: Percentage of Subjects With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Subjects Seropositive at Baseline
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Analysis was performed on FAS. Here, 'Number of subject analysed'=subjects with available data for this endpoint and 'n' = subjects with available data for each specified category. Here, 'vacc.' in categories indicates 'vaccination'; 28d indicates 28 days and 1yr indicates 1 year.
    End point type
    Secondary
    End point timeframe
    Baseline, 28 days post vaccination 3, and 1 year post vaccination 3
    End point values
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Number of subjects analysed
    141
    144
    147
    140
    144
    144
    Units: percentage of subjects
    number (confidence interval 95%)
        Serotype1: Baseline (n=141,144,147,140,144,144)
    92.2 (86.5 to 96.0)
    90.3 (84.2 to 94.6)
    91.8 (86.2 to 95.7)
    92.1 (86.4 to 96.0)
    91.7 (85.9 to 95.6)
    97.2 (93.0 to 99.2)
        Serotype1:28dpostvacc.3(n=137,140,145,137,142,140)
    100.0 (97.3 to 100.0)
    99.3 (96.1 to 100.0)
    100.0 (97.5 to 100.0)
    99.3 (96.0 to 100.0)
    99.3 (96.1 to 100.0)
    100.0 (97.4 to 100.0)
        Serotype1:1yrpostvacc.3(n=137,138,143,128,130,131)
    100.0 (97.3 to 100.0)
    99.3 (96.0 to 100.0)
    99.3 (96.2 to 100.0)
    100.0 (97.2 to 100.0)
    96.9 (92.3 to 99.2)
    98.5 (94.6 to 99.8)
        Serotype2: Baseline(n=141,144,147,140,144,144)
    99.3 (96.1 to 100.0)
    94.4 (89.3 to 97.6)
    94.6 (89.6 to 97.6)
    96.4 (91.9 to 98.8)
    94.4 (89.3 to 97.6)
    97.2 (93.0 to 99.2)
        Serotype2:28dpostvacc.3(n=137,140,145,137,142,140)
    100.0 (97.3 to 100.0)
    99.3 (96.1 to 100.0)
    100.0 (97.5 to 100.0)
    100.0 (97.3 to 100.0)
    99.3 (96.1 to 100.0)
    100.0 (97.4 to 100.0)
        Serotype2:1yrpostvacc.3(n=137,138,143,128,130,131)
    100.0 (97.3 to 100.0)
    99.3 (96.0 to 100.0)
    100.0 (97.5 to 100.0)
    100.0 (97.2 to 100.0)
    98.5 (94.6 to 99.8)
    100.0 (97.2 to 100.0)
        Serotype3: Baseline(n=141,144,147,140,144,144)
    98.6 (95.0 to 99.8)
    96.5 (92.1 to 98.9)
    95.2 (90.4 to 98.1)
    97.1 (92.8 to 99.2)
    93.1 (87.6 to 96.6)
    100.0 (97.5 to 100.0)
        Serotype3:28dpostvacc.3(n=137,140,145,137,142,140)
    100.0 (97.3 to 100.0)
    100.0 (97.4 to 100.0)
    100.0 (97.5 to 100.0)
    99.3 (96.0 to 100.0)
    100.0 (97.4 to 100.0)
    100.0 (97.4 to 100.0)
        Serotype3:1yrpostvacc.3(n=137,138,143,128,130,131)
    100.0 (97.3 to 100.0)
    99.3 (96.0 to 100.0)
    99.3 (96.2 to 100.0)
    100.0 (97.2 to 100.0)
    100.0 (97.2 to 100.0)
    100.0 (97.2 to 100.0)
        Serotype4: Baseline(n=141,144,147,140,144,144)
    93.6 (88.2 to 97.0)
    93.1 (87.6 to 96.6)
    89.8 (83.7 to 94.2)
    95.0 (90.0 to 98.0)
    91.7 (85.9 to 95.6)
    94.4 (89.3 to 97.6)
        Serotype4:28dpostvacc.3(n=137,140,145,137,142,140)
    100.0 (97.3 to 100.0)
    100.0 (97.4 to 100.0)
    100.0 (97.5 to 100.0)
    100.0 (97.3 to 100.0)
    100.0 (97.4 to 100.0)
    100.0 (97.4 to 100.0)
        Serotype4:1yrpostvacc.3(n=137,138,143,128,130,131)
    100.0 (97.3 to 100.0)
    99.3 (96.0 to 100.0)
    98.6 (95.0 to 99.8)
    100.0 (97.2 to 100.0)
    98.5 (94.6 to 99.8)
    100.0 (97.2 to 100.0)
    No statistical analyses for this end point

    Secondary: STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Subjects Seropositive at Baseline

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    End point title
    STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Subjects Seropositive at Baseline
    End point description
    GMTs of antibodies against each of the 4 dengue virus serotype (1, 2, 3, or 4) were assessed using the PRNT assay. Dengue seropositive subjects at Baseline were defined as subjects with titers >=10 (1/dil) for at least one serotype with the parental dengue virus strains. Titers were measured in terms of 1/dilution. Analysis was performed on FAS. Here, 'Number of subject analysed' = subjects with available data for this endpoint and 'n' = subjects with available data for each specified category. Here, 'vacc.' in categories indicates 'vaccination'.
    End point type
    Secondary
    End point timeframe
    Baseline, 28 days post vaccination-3, and 28 days post booster dose
    End point values
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Number of subjects analysed
    141
    144
    147
    140
    144
    144
    Units: titers
    geometric mean (confidence interval 95%)
        Serotype1: Baseline (n=141,144,147,140,144,144)
    246 (183 to 331)
    283 (207 to 385)
    309 (227 to 421)
    231 (171 to 313)
    327 (239 to 447)
    350 (265 to 462)
        Serotype1:28daypostvacc3(n=137,140,145,137,142,140
    828 (671 to 1022)
    933 (730 to 1192)
    1111 (868 to 1423)
    840 (664 to 1061)
    824 (644 to 1056)
    1301 (1011 to 1675)
        Serotype1:28daypostboosterdose(n=55,59,62,53,54,52
    505 (335 to 763)
    552 (375 to 812)
    861 (572 to 1297)
    707 (472 to 1057)
    749 (465 to 1207)
    1199 (755 to 1902)
        Serotype2:Baseline(n=141,144,147,140,144,144)
    370 (295 to 466)
    335 (258 to 437)
    283 (221 to 363)
    296 (228 to 385)
    318 (244 to 413)
    303 (241 to 382)
        Serotype2:28daypostvacc3(n=137,140,145,137,142,140
    986 (834 to 1166)
    897 (735 to 1096)
    1018 (850 to 1218)
    783 (648 to 947)
    844 (695 to 1025)
    1077 (871 to 1331)
        Serotype2:28daypostboosterdose(n=55,59,62,53,54,52
    856 (638 to 1147)
    858 (639 to 1152)
    867 (640 to 1174)
    813 (600 to 1100)
    655 (461 to 931)
    967 (697 to 1343)
        Serotype3:Baseline(n=141,144,147,140,144,144)
    363 (285 to 462)
    399 (308 to 519)
    287 (222 to 371)
    266 (211 to 335)
    210 (164 to 271)
    253 (201 to 317)
        Serotype3:28daypostvacc3(n=137,140,145,137,142,140
    733 (617 to 871)
    659 (547 to 794)
    725 (607 to 865)
    524 (434 to 631)
    551 (459 to 661)
    663 (534 to 823)
        Serotype3:28daypostboosterdose(n=55,59,62,53,54,52
    721 (511 to 1018)
    667 (477 to 933)
    743 (557 to 992)
    586 (455 to 754)
    477 (364 to 626)
    506 (370 to 691)
        Serotype4:Baseline(n=141,144,147,140,144,144)
    147 (114 to 190)
    142 (113 to 178)
    115 (89.6 to 146)
    147 (117 to 183)
    106 (84.5 to 133)
    122 (97.3 to 153)
        Serotype4:28daypostvacc3(n=137,140,145,137,142,140
    512 (433 to 605)
    536 (456 to 631)
    570 (463 to 701)
    543 (456 to 647)
    480 (406 to 568)
    593 (495 to 711)
        Serotype4:28daypostboosterdose(n=55,59,62,53,54,52
    380 (292 to 495)
    265 (210 to 334)
    300 (223 to 405)
    368 (290 to 466)
    360 (273 to 474)
    413 (297 to 574)
    No statistical analyses for this end point

    Secondary: STAGE-I: Number of Subjects With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)

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    End point title
    STAGE-I: Number of Subjects With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
    End point description
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the electronic case report form (eCRF) in terms of diagnosis and/or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after any vaccination. Analysis was performed on safety analysis set (SafAS) that included subjects who had received at least one injection of either CYD dengue vaccine or placebo.
    End point type
    Secondary
    End point timeframe
    Within 30 minutes after any vaccination (1, 2, or 3)
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    348
    348
    352
    Units: subjects
    0
    3
    0
    No statistical analyses for this end point

    Secondary: STAGE-II: Number of Subjects With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine

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    End point title
    STAGE-II: Number of Subjects With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
    End point description
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of diagnosis and / or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after vaccination. Analysis was performed on SafAS.
    End point type
    Secondary
    End point timeframe
    Within 30 minutes after CYD booster vaccination
    End point values
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Number of subjects analysed
    55
    59
    62
    53
    56
    53
    Units: subjects
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Secondary: STAGE-I: Number of Subjects With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)

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    End point title
    STAGE-I: Number of Subjects With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
    End point description
    Adverse reaction (AR) was defined as all noxious and unintended responses to a medicinal product related to any dose. A Solicited Reaction (SR) was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Within 7 days after any vaccination (1, 2, or 3)
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    348
    348
    352
    Units: subjects
        Pain (n=347,347,352)
    109
    114
    97
        Erythema (n=347,347,352)
    4
    3
    3
        Swelling (n=347,347,352)
    2
    5
    5
    No statistical analyses for this end point

    Secondary: STAGE-I: Number of Subjects With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)

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    End point title
    STAGE-I: Number of Subjects With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
    End point description
    AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Within 7 days after each vaccination (1, 2, and 3)
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    348
    348
    352
    Units: subjects
        Post-vacc. 1: Pain (n=347,347,352)
    61
    61
    61
        Post-vacc. 1: Erythema (n=347,347,352)
    3
    3
    2
        Post vacc. 1: Swelling (n=347,347,352)
    0
    2
    2
        Post-vacc. 2: Pain (n=332,328,332)
    50
    53
    50
        Post-vacc. 2: Erythema (n=332,328,332)
    1
    0
    1
        Post-vacc. 2: Swelling (n=332,328,332)
    1
    1
    2
        Post-vacc. 3: Pain (n=325,321,324)
    43
    49
    35
        Post-vacc. 3: Erythema (n=325,321,324)
    0
    0
    1
        Post-vacc. 3: Swelling (n=325,321,324)
    1
    2
    2
    No statistical analyses for this end point

    Secondary: STAGE-I: Number of Subjects With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)

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    End point title
    STAGE-I: Number of Subjects With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
    End point description
    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Systemic AEs were all AEs that were not injection site reactions. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Within 14 days after any vaccination (1, 2, or 3)
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    348
    348
    352
    Units: subjects
        Fever (n=347,347,352)
    29
    21
    31
        Headache (n=347,347,352)
    129
    122
    124
        Malaise (n=347,347,352)
    114
    98
    102
        Myalgia (n=347,347,352)
    110
    92
    86
        Asthenia (n=347,347,352)
    98
    80
    71
    No statistical analyses for this end point

    Secondary: STAGE-I: Number of Subjects With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)

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    End point title
    STAGE-I: Number of Subjects With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
    End point description
    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Within 14 days after each vaccination (1, 2, and 3)
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    348
    348
    352
    Units: subjects
        Post-vacc. 1: Fever (n=347,347,352)
    10
    8
    13
        Post-vacc. 1: Headache (n=347,347,352)
    90
    83
    84
        Post-vacc. 1: Malaise (n=347,347,352)
    74
    60
    61
        Post-vacc. 1: Myalgia (n=347,347,352)
    67
    55
    48
        Post-vacc. 1: Asthenia (n=347,347,352)
    63
    52
    45
        Post-vacc. 2: Fever (n=332,327,330)
    12
    7
    12
        Post-vacc. 2: Headache (n=332,328,332)
    54
    55
    53
        Post-vacc. 2: Malaise (n=332,328,332)
    50
    44
    47
        Post-vacc. 2: Myalgia (n=332,328,332)
    49
    33
    35
        Post-vacc. 2: Asthenia (n=332,328,332)
    40
    30
    33
        Post-vacc. 3: Fever (n=324,317,317)
    9
    8
    9
        Post-vacc. 3: Headache (n=325,321,324)
    55
    47
    47
        Post-vacc. 3: Malaise (n=325,321,324)
    46
    41
    39
        Post-vacc. 3: Myalgia (n=325,321,324)
    26
    37
    38
        Post-vacc. 3: Asthenia (n=325,321,324)
    29
    32
    21
    No statistical analyses for this end point

    Secondary: STAGE-II: Number of Subjects With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine

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    End point title
    STAGE-II: Number of Subjects With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine
    End point description
    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Within 7 days after CYD booster vaccination
    End point values
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Number of subjects analysed
    55
    59
    62
    53
    56
    53
    Units: subjects
        Pain (n=55,59,62,53,54,52)
    6
    7
    11
    7
    12
    10
        Erythema (n=55,59,62,53,54,52)
    0
    0
    0
    0
    1
    0
        Swelling (n=55,59,62,53,54,52)
    0
    0
    0
    0
    1
    1
    No statistical analyses for this end point

    Secondary: STAGE-II: Number of Subjects With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine

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    End point title
    STAGE-II: Number of Subjects With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine
    End point description
    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia. Analysis was performed on SafAS. Here, 'n' = subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Within 14 days after CYD booster vaccination
    End point values
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Number of subjects analysed
    55
    59
    62
    53
    56
    53
    Units: subjects
        Fever (n=55,59,62,53,54,51)
    1
    0
    1
    2
    2
    0
        Headache (n=55,59,62,53,54,52)
    5
    11
    6
    7
    11
    7
        Malaise (n=55,59,62,53,54,52)
    5
    9
    7
    7
    9
    5
        Myalgia (n=55,59,62,53,54,52)
    5
    8
    9
    9
    12
    6
        Asthenia (n=55,59,62,53,54,52)
    4
    6
    6
    7
    9
    3
    No statistical analyses for this end point

    Secondary: STAGE-I: Number of Subjects Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo

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    End point title
    STAGE-I: Number of Subjects Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo
    End point description
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination. Analysis was performed on SafAS.
    End point type
    Secondary
    End point timeframe
    Within 28 days after any vaccination (1, 2, or 3)
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    348
    348
    352
    Units: subjects
    73
    94
    75
    No statistical analyses for this end point

    Secondary: STAGE-II: Number of Subjects Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine

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    End point title
    STAGE-II: Number of Subjects Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
    End point description
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination. Analysis was performed on SafAS.
    End point type
    Secondary
    End point timeframe
    Within 28 days after CYD booster Vaccination
    End point values
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Number of subjects analysed
    55
    59
    62
    53
    56
    53
    Units: subjects
    1
    3
    5
    3
    2
    4
    No statistical analyses for this end point

    Secondary: STAGE-I: Number of Subjects Reporting Serious Adverse Events Including Serious Adverse Event of Special Interests Following Vaccination With CYD Dengue Vaccine or Placebo

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    End point title
    STAGE-I: Number of Subjects Reporting Serious Adverse Events Including Serious Adverse Event of Special Interests Following Vaccination With CYD Dengue Vaccine or Placebo
    End point description
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. Analysis was performed on SafAS.
    End point type
    Secondary
    End point timeframe
    From Day 0 (post vaccination) up to 12 months after last vaccination in STAGE-I (i.e., up to 24 months)
    End point values
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Number of subjects analysed
    348
    348
    352
    Units: subjects
        SAE
    14
    26
    18
        Serious AESI
    0
    0
    0
    No statistical analyses for this end point

    Secondary: STAGE-II: Number of Subjects Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine

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    End point title
    STAGE-II: Number of Subjects Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine
    End point description
    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalisation or prolongation of existing hospitalisation, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. Analysis was performed on SafAS.
    End point type
    Secondary
    End point timeframe
    From Month 25 up to 6 months after CYD booster injection (either at 1 year or 2 year) (i.e., up to 30 months for Groups 1a, 2a, and 3a and up to 42 months for Groups 1b, 2b, and 3b)
    End point values
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Number of subjects analysed
    55
    59
    62
    53
    56
    53
    Units: subjects
        SAE
    3
    0
    2
    2
    0
    1
        Serious AESI
    0
    0
    0
    0
    0
    0
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Unsolicited non-serious AEs: Day 0 to Day 28 post any vacc. SR: within 7 & 14 days post any vacc. SAE: throughout trial (up to 24 months [STAGE-I]; up to 30 months [Groups 1a,2a,&3a]; & up to 42 months [Groups 1b,2b,&3b], i.e. 6 months after last vacc.)
    Adverse event reporting additional description
    Analysis was performed on SafAS. SR was AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    STAGE-I Group 1: CYD Dengue Vaccine
    Reporting group description
    Subjects received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3).

    Reporting group title
    STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
    Reporting group description
    Subjects received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).

    Reporting group title
    STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
    Reporting group description
    Subjects received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).

    Reporting group title
    STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)
    Reporting group description
    Subjects from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e. at Month 24).

    Reporting group title
    STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)
    Reporting group description
    Subjects from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e. at Month 36).

    Reporting group title
    STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)
    Reporting group description
    Subjects from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e. at Month 24).

    Reporting group title
    STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)
    Reporting group description
    Subjects from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e. at Month 36).

    Reporting group title
    STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)
    Reporting group description
    Subjects from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e. at Month 24).

    Reporting group title
    STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Reporting group description
    Subjects from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e. at Month 36).

    Serious adverse events
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    14 / 348 (4.02%)
    26 / 348 (7.47%)
    18 / 352 (5.11%)
    3 / 55 (5.45%)
    2 / 53 (3.77%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    2 / 62 (3.23%)
    1 / 53 (1.89%)
         number of deaths (all causes)
    0
    1
    1
    0
    0
    0
    0
    0
    0
         number of deaths resulting from adverse events
    0
    Vascular disorders
    Arteriosclerosis
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast Cancer
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Papillary Thyroid Cancer
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Food Allergy
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pregnancy, puerperium and perinatal conditions
    Abortion Spontaneous
         subjects affected / exposed
    2 / 348 (0.57%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Abortion Spontaneous Incomplete
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Threatened Labour
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Confusional State
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Adenomyosis
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bartholin's Cyst
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysfunctional Uterine Bleeding
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Uterine Polyp
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Animal Bite
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Forearm Fracture
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    1 / 62 (1.61%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gun Shot Wound
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Head Injury
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Jaw Fracture
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Radius Fracture
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Road Traffic Accident
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Thermal Burn
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    1 / 55 (1.82%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Myocardial Infarction
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Branchial Cyst
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Acute Respiratory Distress Syndrome
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural Effusion
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Headache
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Migraine
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Seizure
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Subarachnoid Haemorrhage
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    1 / 53 (1.89%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Food Poisoning
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Calculus Urinary
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nephrolithiasis
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    1 / 55 (1.82%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal Colic
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Toxic Skin Eruption
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back Pain
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertebral Disc Degeneration
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pathological Fracture
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Rheumatoid Arthritis
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Endocrine disorders
    Thyroid Cyst
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hypokalaemia
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    1 / 348 (0.29%)
    4 / 348 (1.15%)
    3 / 352 (0.85%)
    1 / 55 (1.82%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    1 / 53 (1.89%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 4
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cellulitis
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea Infectious
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Groin Abscess
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatitis A
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    1 / 62 (1.61%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Orchitis
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia Staphylococcal
         subjects affected / exposed
    0 / 348 (0.00%)
    1 / 348 (0.29%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary Tract Infection
         subjects affected / exposed
    1 / 348 (0.29%)
    0 / 348 (0.00%)
    0 / 352 (0.00%)
    0 / 55 (0.00%)
    1 / 53 (1.89%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Viral Infection
         subjects affected / exposed
    0 / 348 (0.00%)
    0 / 348 (0.00%)
    1 / 352 (0.28%)
    0 / 55 (0.00%)
    0 / 53 (0.00%)
    0 / 59 (0.00%)
    0 / 56 (0.00%)
    0 / 62 (0.00%)
    0 / 53 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    203 / 348 (58.33%)
    189 / 348 (54.31%)
    182 / 352 (51.70%)
    10 / 55 (18.18%)
    13 / 53 (24.53%)
    15 / 59 (25.42%)
    20 / 56 (35.71%)
    18 / 62 (29.03%)
    15 / 53 (28.30%)
    Nervous system disorders
    Headache
    Additional description: Events of headache that occurred after 14 days post-vaccination were considered as unsolicited AE.
         subjects affected / exposed
    129 / 348 (37.07%)
    123 / 348 (35.34%)
    124 / 352 (35.23%)
    5 / 55 (9.09%)
    7 / 53 (13.21%)
    11 / 59 (18.64%)
    12 / 56 (21.43%)
    7 / 62 (11.29%)
    7 / 53 (13.21%)
         occurrences all number
    201
    190
    184
    5
    7
    11
    12
    7
    7
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    98 / 348 (28.16%)
    80 / 348 (22.99%)
    71 / 352 (20.17%)
    4 / 55 (7.27%)
    7 / 53 (13.21%)
    6 / 59 (10.17%)
    9 / 56 (16.07%)
    6 / 62 (9.68%)
    3 / 53 (5.66%)
         occurrences all number
    133
    114
    100
    4
    7
    6
    9
    6
    3
    Fever
         subjects affected / exposed
    29 / 348 (8.33%)
    21 / 348 (6.03%)
    31 / 352 (8.81%)
    1 / 55 (1.82%)
    2 / 53 (3.77%)
    0 / 59 (0.00%)
    2 / 56 (3.57%)
    1 / 62 (1.61%)
    0 / 53 (0.00%)
         occurrences all number
    31
    23
    34
    1
    2
    0
    2
    1
    0
    Injection Site Pain
         subjects affected / exposed
    109 / 348 (31.32%)
    114 / 348 (32.76%)
    97 / 352 (27.56%)
    6 / 55 (10.91%)
    7 / 53 (13.21%)
    7 / 59 (11.86%)
    12 / 56 (21.43%)
    11 / 62 (17.74%)
    10 / 53 (18.87%)
         occurrences all number
    154
    164
    146
    6
    7
    7
    12
    11
    10
    Malaise
    Additional description: Events of malaise that occurred after 14 days post-vaccination were considered as unsolicited AE.
         subjects affected / exposed
    114 / 348 (32.76%)
    98 / 348 (28.16%)
    103 / 352 (29.26%)
    5 / 55 (9.09%)
    7 / 53 (13.21%)
    9 / 59 (15.25%)
    9 / 56 (16.07%)
    7 / 62 (11.29%)
    5 / 53 (9.43%)
         occurrences all number
    170
    146
    148
    5
    7
    9
    9
    7
    5
    Musculoskeletal and connective tissue disorders
    Myalgia
    Additional description: Events of myalgia that occurred after 14 days post-vaccination were considered as unsolicited AE.
         subjects affected / exposed
    110 / 348 (31.61%)
    92 / 348 (26.44%)
    87 / 352 (24.72%)
    5 / 55 (9.09%)
    9 / 53 (16.98%)
    8 / 59 (13.56%)
    12 / 56 (21.43%)
    9 / 62 (14.52%)
    6 / 53 (11.32%)
         occurrences all number
    143
    126
    112
    5
    9
    8
    12
    9
    6

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    12 Dec 2017
    As per Independent Data Monitoring Committee recommendation not to further vaccinate subjects not previously infected by dengue, Sanofi Pasteur amended the study protocol so that only subjects assessed as previously infected by dengue before receiving the first CYD dengue vaccine injection were eligible to receive any further dose of the CYD dengue vaccine in the study. All subjects were informed about their serostatus at Baseline. Moreover, all subjects were asked about their willingness to continue participating in this study by signing an updated informed consent form and/or assent form, as applicable. Subjects assessed as dengue seropositive confirmed their participation in the study and continued to be eligible to receive the booster injection at Year 1 or Year 2. Subjects classified as seronegative at Baseline were only able to continue in the study for safety follow-up and for the evaluation of Ab persistence at Year 1. It consisted in the addition of a co-primary objective, to determine the non-inferiority of the immune response at both 28 days and 1 year after the last dose (3 doses versus 2 doses schedule). Non-inferiority tests between Group 3 and Group 1 became no longer applicable. Rather, the immunogenicity of the 1-dose regimen was described as part of the additional objectives. Addition of a visit to the study centers for subjects from Subgroup b who did not have such a visit planned in the original protocol. It required subjects and/or their parents/legally accepted representatives to provide their written consent. Subjects assigned to Subgroup b were asked to provide a blood sample at 1 year post last primary series injection, regardless of whether or not they were eligible to receive a booster vaccination.

    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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