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Study of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Subjects in Singapore

Sponsor
Sanofi Pasteur, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT00880893
Collaborator
(none)
1,198
Enrollment
5
Locations
2
Arms
66.2
Actual Duration (Months)
239.6
Patients Per Site
3.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objectives:

  • To evaluate safety after each CYD Dengue vaccination in terms of injection site and systemic reactogenicity.

  • To evaluate the occurrence of Serious Adverse Events (SAEs) throughout the trial period.

  • To evaluate the humoral immune response to each CYD Dengue serotype after each vaccination in a subset of participants.

Secondary Objectives:
  • To evaluate the persistence of the humoral immune response during 4 years after the last vaccination in a subset of participants.
Condition or Disease Intervention/Treatment Phase
  • Biological: CYD Dengue vaccine
  • Biological: NaCl + influenza virus or hepatitis A vaccine
 Phase 2

Detailed Description

This was a multicenter trial involving three vaccinations one each at 0, 6 and 12 months over a period of 1 year, and a 4-year follow-up following the last vaccination.

Study Design

Study Type:
Interventional
Actual Enrollment :
1198 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Masking Description:
An observer-design for the first vaccination and a single-blind design for the second and third vaccination were chosen to minimize the bias of the vaccine evaluation. The Investigator in charge of safety evaluation, the Sponsor, and the participants/parents did not know which vaccine was administrated at the first visit. For the second and third vaccinations, the participants/parents did not know which vaccine was administered.
Primary Purpose:
Prevention
Official Title:
Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore
Actual Study Start Date :
Apr 7, 2009
Actual Primary Completion Date :
Oct 1, 2014
Actual Study Completion Date :
Oct 14, 2014

Arms and Interventions

Arm Intervention/Treatment
Experimental: CYD Dengue Vaccine Group

Participant's received the CYD Dengue Vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

Biological: CYD Dengue vaccine
0.5 mL, Subcutaneous on Day 0, Months 6 and 12
Other Names:
  • Sanofi Pasteur's CYD Dengue Vaccine

    		•
    Sham Comparator: Placebo Group

    All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >= 12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

    Biological: NaCl + influenza virus or hepatitis A vaccine
    0.5 mL, Subcutaneous (Intramuscular - Hepatitis A)
    Other Names:
  • NaCl 0.9%
  • Vaxigrip®
  • Havrix® pediatric formulation

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo [Day 0 up to 14 days post-any and each injection]

      Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, incapacitating, unable to perform usual activities; Erythema and Swelling, >=5 cm. Grade 3 Solicited injection site reactions (adolescents and adults: >=12 years): Pain, significant; prevents daily activity; Erythema and Swelling: >10 cm. Grade 3 Solicited systemic reactions (all participants): Fever, >=39.0°C; Headache, Malaise, Myalgia, and Asthenia: significant; prevents daily activity.

    2. Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo [Day 0 up to 14 days post-each injection]

      Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.

    3. Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3]

      Seropositivity against each dengue virus serotype (parental strains) was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    4. Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1 and 28 days Post-Injection 3]

      Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    5. Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1 and 28 days Post-Injection 3]

      Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    6. Geometric Mean Titers (GMTs) of Antibodies in All Participants Against Each Serotype With the Parental Dengue Virus Strain Before and Following Each Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3]

      GMTs against each serotype with the parental dengue virus strains were assessed using a dengue PRNT assay.

    7. GMTs of Antibodies by Age Groups (2-11 Years, 12-17 Years, 18-45 Years) Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine [Pre-Injection 1 and 28 days Post-Injection 3]

      GMTs against each dengue virus serotype (parental strains) were assessed using a dengue PRNT assay.

    Secondary Outcome Measures

    1. Percentage of Participants Aged 2 to 11 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    2. Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each dengue virus serotypes (parental stains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with antibody titers >=10 (1/dilution).

    3. Percentage of Participants Aged 18 to 45 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each dengue virus serotypes (parental stains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    4. Percentage of Participants Aged 2 to 11 Years Old Who Achieved Seropositivity Against At Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    5. Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    6. Percentage of Participants Aged 18 to 45 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).

    7. GMTs of Antibodies in Participants 2 to 11 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      GMTs against each serotype with the dengue virus strain (parental strains) were assessed using a dengue PRNT assay.

    8. GMTs of Antibodies in Participants 12 to 17 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      GMTs against each serotype with the dengue virus strain (parental strains) were assessed using a dengue PRNT assay.

    9. GMTs of Antibodies in Participants 18 to 45 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo [Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      GMTs against each serotype with the dengue virus strain were assessed using a dengue PRNT assay.

    10. Percentage of Participants (Aged 2 to 11 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.

    11. Percentage of Participants (Aged 2 to 11 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.

    12. Percentage of Participants (Aged 12 to 17 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.

    13. Percentage of Participants (Aged 12 to 17 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each serotype with the dengue virus strain were assessed using a PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.

    14. Percentage of Participants (Aged 18 to 45 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.

    15. Percentage of Participants (Aged 18 to 45 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo [28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)]

      Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    2 Years to 45 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    Inclusion Criteria :

    • Aged from 2 to 45 years on the day of inclusion.

    • Participant in good health, based on medical history and physical examination.

    • Provision of informed consent form (and assent form for participants aged 6 to 12 years) signed by the participant and by the parent(s) or another legally acceptable representative for participants aged less than 21 years.

    • Participants and parent(s)/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures.

    • For a woman of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks before the first vaccination until 4 weeks after the last vaccination.

    Exclusion Criteria :

    • Febrile illness (temperature >= 37.5°C) or moderate or severe acute illness/infection on the day of the first vaccination, according to Investigator judgment.

    • For a woman of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of inclusion.

    • Breast-feeding woman.

    • Known systemic hypersensitivity to any of the components of the trial vaccines (especially egg proteins or neomycin) or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.

    • Personal or family history of thymic pathology or myasthenia.

    • Previous hepatitis A vaccination (for children only).

    • Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or long-term systemic corticosteroid therapy.

    • Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.

    • Receipt of blood or blood-derived products in the past 3 months that might interfere with the assessment of immune response.

    • Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.

    • Planned participation in another clinical trial during the 18 coming months.

    • Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.

    • Planned receipt of any vaccine in the 4 weeks following the first trial vaccination.

    • Participant deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.

    • Current or past alcohol abuse or drug addiction that may interfere with the participants ability to comply with trial procedures.

    • Participant who plans to move to another country within the 18 coming months.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Singapore Singapore 119074
    2 Singapore Singapore 169608
    3 Singapore Singapore 229899
    4 Singapore Singapore 308433
    5 Singapore Singapore 529889

    Sponsors and Collaborators

    • Sanofi Pasteur, a Sanofi Company

    Investigators

    • Study Director: Medical Director, Sanofi Pasteur Inc.

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Sanofi Pasteur, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT00880893
    Other Study ID Numbers:
    • CYD28
    • 2014-001713-26
    First Posted:
    Apr 14, 2009
    Last Update Posted:
    Mar 21, 2022
    Last Verified:
    Mar 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by Sanofi Pasteur, a Sanofi Company
    Dengue virus
    Dengue fever
    Dengue Hemorrhagic fever
    Dengue diseases
    Sanofi Pasteur's CYD Dengue Vaccine
    Additional relevant MeSH terms:
    Dengue
    Hemorrhagic Fevers, Viral
    Severe Dengue
    Fever
    Hyperthermia
    Vaccines

    Study Results

    Participant Flow

    Recruitment Details Study participants were enrolled from 07 April 2009 to 08 October 2009 at 5 clinical sites in Singapore.
    Pre-assignment Detail A total of 1198 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Period Title: Overall Study
    STARTED 898 300
    COMPLETED 791 255
    NOT COMPLETED 107 45

    Baseline Characteristics

    Arm/Group Title CYD Dengue Vaccine Group Placebo Group Total
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations. Total of all reporting groups
    Overall Participants 898 300 1198
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    22.1
    (12.0)
    21.7
    (11.8)
    22.0
    (11.9)
    Age, Customized (Count of Participants)
    2-11 years
    236
    26.3%
    80
    26.7%
    316
    26.4%
    12-17 years
    141
    15.7%
    46
    15.3%
    187
    15.6%
    18-45 years
    521
    58%
    174
    58%
    695
    58%
    Sex: Female, Male (Count of Participants)
    Female
    471
    52.4%
    139
    46.3%
    610
    50.9%
    Male
    427
    47.6%
    161
    53.7%
    588
    49.1%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo
    Description Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, incapacitating, unable to perform usual activities; Erythema and Swelling, >=5 cm. Grade 3 Solicited injection site reactions (adolescents and adults: >=12 years): Pain, significant; prevents daily activity; Erythema and Swelling: >10 cm. Grade 3 Solicited systemic reactions (all participants): Fever, >=39.0°C; Headache, Malaise, Myalgia, and Asthenia: significant; prevents daily activity.
    Time Frame Day 0 up to 14 days post-any and each injection

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Safety analysis set. Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 898 300
    Injection site Pain; Post-Any Injection
    53.9
    6%
    66.7
    22.2%
    Grade 3 Injection site Pain; Post-Any Injection
    1.0
    0.1%
    2.0
    0.7%
    Injection site Erythema; Post-Any Injection
    7.2
    0.8%
    15.2
    5.1%
    Grade 3 Inj. site Erythema; Post-Any Inj.
    0.0
    0%
    0.0
    0%
    Injection site Swelling; Post-Any Injection
    4.1
    0.5%
    8.4
    2.8%
    Grade 3 Inj. site Swelling; Post-Any Inj.
    0.0
    0%
    0.0
    0%
    Injection site Pain; Post-Injection 1
    31.3
    3.5%
    21.9
    7.3%
    Grade 3 Injection site Pain; Post- Injection 1
    0.3
    0%
    0.7
    0.2%
    Injection site Erythema; Post-Injection 1
    2.0
    0.2%
    2.0
    0.7%
    Grade 3 Injection site Erythema; Post- Injection 1
    0.0
    0%
    0.0
    0%
    Injection site Swelling; Post-Injection 1
    1.1
    0.1%
    1.7
    0.6%
    Grade 3 Injection site Swelling; Post- Injection 1
    0.0
    0%
    0.0
    0%
    Injection site Pain; Post-Injection 2
    36.9
    4.1%
    54.4
    18.1%
    Grade 3 Injection site Pain; Post- Injection 2
    0.5
    0.1%
    0.7
    0.2%
    Injection site Erythema; Post-Injection 2
    3.4
    0.4%
    8.8
    2.9%
    Grade 3 Injection site Erythema; Post- Injection 2
    0.0
    0%
    0.0
    0%
    Injection site Swelling; Post-Injection 2
    1.4
    0.2%
    3.5
    1.2%
    Grade 3 Injection site Swelling; Post- Injection 2
    0.0
    0%
    0.0
    0%
    Injection site Pain; Post-Injection 3
    34.9
    3.9%
    50.0
    16.7%
    Grade 3 Injection site Pain; Post- Injection 3
    0.2
    0%
    0.7
    0.2%
    Injection site Erythema; Post-Injection 3
    3.8
    0.4%
    9.4
    3.1%
    Grade 3 Injection site Erythema; Post- Injection 3
    0.0
    0%
    0.0
    0%
    Injection site Swelling; Post-Injection 3
    2.6
    0.3%
    5.8
    1.9%
    Grade 3 Injection site Swelling; Post- Injection 3
    0.0
    0%
    0.0
    0%
    Fever; Post-Any Injection
    11.3
    1.3%
    7.4
    2.5%
    Grade 3 Fever; Post-Any Injection
    1.9
    0.2%
    1.0
    0.3%
    Headache; Post-Any Injection
    45.1
    5%
    38.4
    12.8%
    Grade 3 Headache; Post-Any Injection
    3.8
    0.4%
    2.7
    0.9%
    Malaise; Post-Any Injection
    41.8
    4.7%
    35.4
    11.8%
    Grade 3 Malaise; Post-Any Injection
    4.3
    0.5%
    2.7
    0.9%
    Myalgia; Post-Any Injection
    44.2
    4.9%
    43.8
    14.6%
    Grade 3 Myalgia; Post-Any Injection
    2.6
    0.3%
    2.0
    0.7%
    Asthenia; Post-Any Injection
    20.5
    2.3%
    17.5
    5.8%
    Grade 3 Asthenia; Post-Any Injection
    1.3
    0.1%
    0.7
    0.2%
    Fever; Post-Injection 1
    4.6
    0.5%
    2.7
    0.9%
    Grade 3 Fever; Post-Injection 1
    0.6
    0.1%
    0.7
    0.2%
    Headache; Post-Injection 1
    30.0
    3.3%
    27.3
    9.1%
    Grade 3 Headache; Post-Injection 1
    2.4
    0.3%
    1.3
    0.4%
    Malaise; Post-Injection 1
    25.0
    2.8%
    18.2
    6.1%
    Grade 3 Malaise; Post-Injection 1
    2.0
    0.2%
    0.7
    0.2%
    Myalgia; Post-Injection 1
    29.4
    3.3%
    19.2
    6.4%
    Grade 3 Myalgia; Post-Injection 1
    1.3
    0.1%
    1.0
    0.3%
    Asthenia; Post-Injection 1
    12.8
    1.4%
    6.1
    2%
    Grade 3 Asthenia; Post-Injection 1
    0.7
    0.1%
    0.3
    0.1%
    Fever; Post-Injection 2
    3.3
    0.4%
    2.8
    0.9%
    Grade 3 Fever; Post-Injection 2
    0.6
    0.1%
    0.0
    0%
    Headache; Post-Injection 2
    22.8
    2.5%
    21.8
    7.3%
    Grade 3 Headache; Post-Injection 2
    0.7
    0.1%
    1.1
    0.4%
    Malaise; Post-Injection 2
    19.1
    2.1%
    18.2
    6.1%
    Grade 3 Malaise; Post-Injection 2
    1.2
    0.1%
    1.1
    0.4%
    Myalgia; Post-Injection 2
    24.0
    2.7%
    29.5
    9.8%
    Grade 3 Myalgia; Post-Injection 2
    0.9
    0.1%
    0.7
    0.2%
    Asthenia; Post-Injection 2
    9.3
    1%
    10.2
    3.4%
    Grade 3 Asthenia; Post-Injection 2
    0.3
    0%
    0.0
    0%
    Fever; Post-Injection 3
    4.8
    0.5%
    2.9
    1%
    Grade 3 Fever; Post-Injection 3
    0.8
    0.1%
    0.4
    0.1%
    Headache; Post-Injection 3
    20.1
    2.2%
    19.8
    6.6%
    Grade 3 Headache; Post-Injection 3
    1.0
    0.1%
    0.4
    0.1%
    Malaise; Post-Injection 3
    18.2
    2%
    17.3
    5.8%
    Grade 3 Malaise; Post-Injection 3
    1.4
    0.2%
    1.1
    0.4%
    Myalgia; Post-Injection 3
    21.8
    2.4%
    26.3
    8.8%
    Grade 3 Myalgia; Post-Injection 3
    0.5
    0.1%
    0.7
    0.2%
    Asthenia; Post-Injection 3
    8.5
    0.9%
    9.4
    3.1%
    Grade 3 Asthenia; Post-Injection 3
    0.4
    0%
    0.4
    0.1%
    2. Primary Outcome
    Title Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo
    Description Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.
    Time Frame Day 0 up to 14 days post-each injection

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Safety analysis set. Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 898 300
    2-11 years; Injection site Pain, Post-Inj. 1
    33.9
    3.8%
    30.0
    10%
    2-11 years; Inj. site Erythema, Post-Inj. 1
    6.4
    0.7%
    7.5
    2.5%
    2-11 years; Inj. site Swelling, Post-Inj. 1
    3.8
    0.4%
    6.3
    2.1%
    12-17 years; Injection site Pain, Post- Inj. 1
    28.4
    3.2%
    28.3
    9.4%
    12-17 years; Inj. site Erythema, Post- Inj. 1
    0.0
    0%
    0.0
    0%
    12-17 years; Inj. site Swelling, Post-Inj. 1
    0.0
    0%
    0.0
    0%
    18-45 years; Injection site Pain, Post- Inj. 1
    30.9
    3.4%
    16.4
    5.5%
    18-45 years; Inj. site Erythema, Post- Inj. 1
    0.6
    0.1%
    0.0
    0%
    18-45 years; Inj. site Swelling, Post-Inj. 1
    0.2
    0%
    0.0
    0%
    2-11 years; Injection site Pain, Post- Inj. 2
    38.3
    4.3%
    42.1
    14%
    2-11 years; Inj. site Erythema, Post-Inj. 2
    9.4
    1%
    5.3
    1.8%
    2-11 years; Inj. site Swelling, Post-Inj. 2
    4.7
    0.5%
    3.9
    1.3%
    12-17 years; Injection site Pain, Post- Inj. 2
    29.4
    3.3%
    44.4
    14.8%
    12-17 years; Inj. site Erythema, Post- Inj. 2
    0.0
    0%
    0.0
    0%
    12-17 years; Inj. site Swelling, Post-Inj. 2
    0.0
    0%
    0.0
    0%
    18-45 years; Injection site Pain, Post- Inj. 2
    38.3
    4.3%
    62.8
    20.9%
    18-45 years; Inj. site Erythema, Post- Inj. 2
    1.4
    0.2%
    12.8
    4.3%
    18-45 years; Inj. site Swelling, Post-Inj. 2
    0.2
    0%
    4.3
    1.4%
    2-11 years; Injection site Pain, Post- Inj. 3
    32.6
    3.6%
    34.2
    11.4%
    2-11 years; Inj. site Erythema, Post-Inj. 3
    8.2
    0.9%
    6.6
    2.2%
    2-11 years; Inj. site Swelling, Post-Inj. 3
    6.4
    0.7%
    2.6
    0.9%
    12-17 years; Injection site Pain, Post- Inj. 3
    26.7
    3%
    38.6
    12.9%
    12-17 years; Inj. site Erythema, Post- Inj. 3
    0.0
    0%
    0.0
    0%
    12-17 years; Inj. site Swelling, Post-Inj. 3
    0.0
    0%
    0.0
    0%
    18-45 years; Injection site Pain, Post- Inj. 3
    38.5
    4.3%
    60.8
    20.3%
    18-45 years; Inj. site Erythema, Post- Inj. 3
    2.8
    0.3%
    13.3
    4.4%
    18-45 years; Inj. site Swelling, Post-Inj. 3
    1.5
    0.2%
    8.9
    3%
    2-11 years; Fever, Post-Inj. 1
    8.1
    0.9%
    6.3
    2.1%
    2-11 years; Headache, Post-Inj. 1
    25.0
    2.8%
    16.3
    5.4%
    2-11 years; Malaise, Post-Inj. 1
    19.9
    2.2%
    13.8
    4.6%
    2-11 years; Myalgia, Post-Inj. 1
    23.7
    2.6%
    16.3
    5.4%
    2-11 years; Asthenia, Post-Inj. 1
    7.2
    0.8%
    3.8
    1.3%
    12-17 years; Fever, Post-Inj. 1
    7.1
    0.8%
    2.2
    0.7%
    12-17 years; Headache, Post-Inj. 1
    39.3
    4.4%
    39.1
    13%
    12-17 years; Malaise, Post-Inj. 1
    29.3
    3.3%
    17.4
    5.8%
    12-17 years; Myalgia, Post-Inj. 1
    32.1
    3.6%
    23.9
    8%
    12-17 years; Asthenia, Post-Inj. 1
    13.6
    1.5%
    6.5
    2.2%
    18-45 years; Fever, Post-Inj. 1
    2.3
    0.3%
    1.2
    0.4%
    18-45 years; Headache, Post-Inj. 1
    29.7
    3.3%
    29.2
    9.7%
    18-45 years; Malaise, Post-Inj. 1
    26.2
    2.9%
    20.5
    6.8%
    18-45 years; Myalgia, Post-Inj. 1
    31.3
    3.5%
    19.3
    6.4%
    18-45 years; Asthenia, Post-Inj. 1
    15.1
    1.7%
    7.0
    2.3%
    2-11 years; Fever, Post-Inj. 2
    6.8
    0.8%
    6.6
    2.2%
    2-11 years; Headache, Post-Inj. 2
    21.7
    2.4%
    15.8
    5.3%
    2-11 years; Malaise, Post-Inj. 2
    21.7
    2.4%
    13.2
    4.4%
    2-11 years; Myalgia, Post-Inj. 2
    24.7
    2.8%
    22.4
    7.5%
    2-11 years; Asthenia, Post-Inj. 2
    7.7
    0.9%
    7.9
    2.6%
    12-17 years; Fever, Post-Inj. 2
    4.4
    0.5%
    0.0
    0%
    12-17 years; Headache, Post-Inj. 2
    19.9
    2.2%
    22.2
    7.4%
    12-17 years; Malaise, Post-Inj. 2
    16.2
    1.8%
    20.0
    6.7%
    12-17 years; Myalgia, Post-Inj. 2
    19.9
    2.2%
    28.9
    9.6%
    12-17 years; Asthenia, Post-Inj. 2
    8.8
    1%
    6.7
    2.2%
    18-45 years; Fever, Post-Inj. 2
    1.2
    0.1%
    1.8
    0.6%
    18-45 years; Headache, Post-Inj. 2
    24.2
    2.7%
    24.4
    8.1%
    18-45 years; Malaise, Post-Inj. 2
    18.6
    2.1%
    20.1
    6.7%
    18-45 years; Myalgia, Post-Inj. 2
    24.8
    2.8%
    32.9
    11%
    18-45 years; Asthenia, Post-Inj. 2
    10.2
    1.1%
    12.2
    4.1%
    2-11 years; Fever, Post-Inj. 3
    8.2
    0.9%
    6.6
    2.2%
    2-11 years; Headache, Post-Inj. 3
    17.6
    2%
    11.8
    3.9%
    2-11 years; Malaise, Post-Inj. 3
    18.5
    2.1%
    14.5
    4.8%
    2-11 years; Myalgia, Post-Inj. 3
    20.6
    2.3%
    17.1
    5.7%
    2-11 years; Asthenia, Post-Inj. 3
    7.7
    0.9%
    3.9
    1.3%
    12-17 years; Fever, Post-Inj. 3
    5.9
    0.7%
    2.3
    0.8%
    12-17 years; Headache, Post-Inj. 3
    20.7
    2.3%
    20.5
    6.8%
    12-17 years; Malaise, Post-Inj. 3
    18.5
    2.1%
    18.2
    6.1%
    12-17 years; Myalgia, Post-Inj. 3
    14.8
    1.6%
    25.0
    8.3%
    12-17 years; Asthenia, Post-Inj. 3
    5.9
    0.7%
    11.4
    3.8%
    18-45 years; Fever, Post-Inj. 3
    2.8
    0.3%
    1.3
    0.4%
    18-45 years; Headache, Post-Inj. 3
    21.2
    2.4%
    23.4
    7.8%
    18-45 years; Malaise, Post-Inj. 3
    17.9
    2%
    18.4
    6.1%
    18-45 years; Myalgia, Post-Inj. 3
    24.4
    2.7%
    31.0
    10.3%
    18-45 years; Asthenia, Post-Inj. 3
    9.6
    1.1%
    11.4
    3.8%
    3. Primary Outcome
    Title Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each dengue virus serotype (parental strains) was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Per-Protocol (PP) analysis set which included all participants who were vaccinated and had no protocol deviations. Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 424 140
    CYD dengue Serotype 1; Pre-Injection 1
    14.6
    1.6%
    17.1
    5.7%
    CYD dengue Serotype 1; Post-Injection 1
    22.9
    2.6%
    11.6
    3.9%
    CYD dengue Serotype 1; Pre-Injection 2
    30.1
    3.4%
    16.7
    5.6%
    CYD dengue Serotype 1; Post-Injection 2
    54.9
    6.1%
    18.3
    6.1%
    CYD dengue Serotype 1; Pre-Injection 3
    45.8
    5.1%
    13.8
    4.6%
    CYD dengue Serotype 1; Post-Injection 3
    79.6
    8.9%
    22.0
    7.3%
    CYD dengue Serotype 2; Pre-Injection 1
    16.1
    1.8%
    15.0
    5%
    CYD dengue Serotype 2; Post-Injection 1
    39.5
    4.4%
    10.1
    3.4%
    CYD dengue Serotype 2; Pre-Injection 2
    39.3
    4.4%
    16.7
    5.6%
    CYD dengue Serotype 2; Post-Injection 2
    80.4
    9%
    15.0
    5%
    CYD dengue Serotype 2; Pre-Injection 3
    58.3
    6.5%
    13.8
    4.6%
    CYD dengue Serotype 2; Post-Injection 3
    88.1
    9.8%
    20.2
    6.7%
    CYD dengue Serotype 3; Pre-Injection 1
    19.7
    2.2%
    20.1
    6.7%
    CYD dengue Serotype 3; Post-Injection 1
    58.7
    6.5%
    21.7
    7.2%
    CYD dengue Serotype 3; Pre-Injection 2
    63.9
    7.1%
    31.0
    10.3%
    CYD dengue Serotype 3; Post-Injection 2
    87.4
    9.7%
    26.7
    8.9%
    CYD dengue Serotype 3; Pre-Injection 3
    77.8
    8.7%
    19.0
    6.3%
    CYD dengue Serotype 3; Post-Injection 3
    93.2
    10.4%
    24.8
    8.3%
    CYD dengue Serotype 4; Pre-Injection 1
    12.8
    1.4%
    12.9
    4.3%
    CYD dengue Serotype 4; Post-Injection 1
    67.3
    7.5%
    11.6
    3.9%
    CYD dengue Serotype 4; Pre-Injection 2
    69.1
    7.7%
    16.7
    5.6%
    CYD dengue Serotype 4; Post-Injection 2
    85.8
    9.6%
    16.9
    5.6%
    CYD dengue Serotype 4; Pre-Injection 3
    79.3
    8.8%
    8.6
    2.9%
    CYD dengue Serotype 4; Post-Injection 3
    93.7
    10.4%
    19.3
    6.4%
    4. Primary Outcome
    Title Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1 and 28 days Post-Injection 3

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Per-Protocol analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 148 47
    2-11 years, CYD dengue Serotype 1; Pre-Inj. 1
    4.7
    0.5%
    8.5
    2.8%
    2-11 years, CYD dengue Serotype 1; Post-Inj. 3
    92.4
    10.3%
    10.8
    3.6%
    2-11 years, CYD dengue Serotype 2; Pre-Inj. 1
    5.4
    0.6%
    2.1
    0.7%
    2-11 years, CYD dengue Serotype 2; Post-Inj. 3
    93.9
    10.5%
    16.2
    5.4%
    2-11 years, CYD dengue Serotype 3; Pre-Inj. 1
    11.6
    1.3%
    10.6
    3.5%
    2-11 years, CYD dengue Serotype 3; Post-Inj. 3
    98.5
    11%
    13.5
    4.5%
    2-11 years, CYD dengue Serotype 4; Pre-Inj. 1
    6.8
    0.8%
    6.4
    2.1%
    2-11 years, CYD dengue Serotype 4; Post-Inj. 3
    96.9
    10.8%
    18.9
    6.3%
    12-17 years, CYD dengue Serotype 1; Pre-Inj. 1
    5.7
    0.6%
    4.3
    1.4%
    12-17 years, CYD dengue Serotype 1; Post-Inj. 3
    68.3
    7.6%
    13.2
    4.4%
    12-17 years, CYD dengue Serotype 2; Pre-Inj. 1
    10.0
    1.1%
    4.3
    1.4%
    12-17 years, CYD dengue Serotype 2; Post-Inj. 3
    87.0
    9.7%
    10.5
    3.5%
    12-17 years, CYD dengue Serotype 3; Pre-Inj. 1
    11.5
    1.3%
    10.9
    3.6%
    12-17 years, CYD dengue Serotype 3; Post-Inj. 3
    88.5
    9.9%
    21.1
    7%
    12-17 years, CYD dengue Serotype 4; Pre-Inj. 1
    6.5
    0.7%
    2.2
    0.7%
    12-17 years, CYD dengue Serotype 4; Post-Inj. 3
    91.1
    10.1%
    10.5
    3.5%
    18-45 years, CYD dengue Serotype 1; Pre-Inj. 1
    34.6
    3.9%
    38.3
    12.8%
    18-45 years, CYD dengue Serotype 1; Post-Inj. 3
    76.5
    8.5%
    44.1
    14.7%
    18-45 years, CYD dengue Serotype 2; Pre-Inj. 1
    34.1
    3.8%
    38.3
    12.8%
    18-45 years, CYD dengue Serotype 2; Post-Inj. 3
    81.6
    9.1%
    35.3
    11.8%
    18-45 years, CYD dengue Serotype 3; Pre-Inj. 1
    37.0
    4.1%
    39.1
    13%
    18-45 years, CYD dengue Serotype 3; Post-Inj. 3
    91.8
    10.2%
    41.2
    13.7%
    18-45 years, CYD dengue Serotype 4; Pre-Inj. 1
    26.1
    2.9%
    30.4
    10.1%
    18-45 years, CYD dengue Serotype 4; Post-Inj. 3
    92.8
    10.3%
    29.4
    9.8%
    5. Primary Outcome
    Title Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1 and 28 days Post-Injection 3

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Per-Protocol analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 148 47
    2-11 yrs, CYD dengue >=1 serotype; Pre- Inj. 1
    19.6
    2.2%
    27.7
    9.2%
    2-11 yrs, CYD dengue >=1 serotype; Post-Inj. 3
    100
    11.1%
    56.8
    18.9%
    2-11 yrs, CYD dengue >=2 serotypes; Pre-Inj. 1
    6.1
    0.7%
    0.0
    0%
    2-11 yrs, CYD dengue >=2 serotypes; Post-Inj. 3
    99.2
    11%
    2.7
    0.9%
    2-11 yrs, CYD dengue >=3 serotypes; Pre-Inj. 1
    2.0
    0.2%
    0.0
    0%
    2-11 yrs, CYD dengue >=3 serotypes; Post-Inj. 3
    97.0
    10.8%
    0.0
    0%
    2-11 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1
    0.7
    0.1%
    0.0
    0%
    2-11 yrs, CYD dengue All 4 serotypes; Post-Inj. 3
    84.8
    9.4%
    0.0
    0%
    12-17 yrs, CYD dengue >=1 serotype; Pre-Inj. 1
    13.6
    1.5%
    15.2
    5.1%
    12-17 yrs, CYD dengue >=1 serotype; Post-Inj. 3
    98.4
    11%
    26.3
    8.8%
    12-17 yrs, CYD dengue >=2 serotypes; Pre-Inj. 1
    7.9
    0.9%
    4.3
    1.4%
    12-17 yrs, CYD dengue >=2 serotypes; Post-Inj. 3
    95.1
    10.6%
    10.5
    3.5%
    12-17 yrs, CYD dengue >=3 serotypes; Pre-Inj. 1
    7.1
    0.8%
    2.2
    0.7%
    12-17 yrs, CYD dengue >=3 serotypes; Post-Inj. 3
    81.3
    9.1%
    10.5
    3.5%
    12-17 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1
    5.0
    0.6%
    0.0
    0%
    12-17 yrs, CYD dengue All 4 serotypes; Post-Inj. 3
    59.3
    6.6%
    7.9
    2.6%
    18-45 yrs, CYD dengue >=1 serotype; Pre-Inj. 1
    47.1
    5.2%
    53.2
    17.7%
    18-45 yrs, CYD dengue >=1 serotype; Post-Inj. 3
    100
    11.1%
    55.9
    18.6%
    18-45 yrs, CYD dengue >=2 serotypes; Pre-Inj. 1
    33.8
    3.8%
    38.3
    12.8%
    18-45 yrs, CYD dengue >=2 serotypes; Post-Inj. 3
    96.9
    10.8%
    35.3
    11.8%
    18-45 yrs, CYD dengue >=3 serotypes; Pre-Inj. 1
    27.9
    3.1%
    31.9
    10.6%
    18-45 yrs, CYD dengue >=3 serotypes; Post-Inj. 3
    83.7
    9.3%
    32.4
    10.8%
    18-45 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1
    22.1
    2.5%
    21.3
    7.1%
    18-45 yrs, CYD dengue All 4 serotypes; Post-Inj. 3
    61.2
    6.8%
    26.5
    8.8%
    6. Primary Outcome
    Title Geometric Mean Titers (GMTs) of Antibodies in All Participants Against Each Serotype With the Parental Dengue Virus Strain Before and Following Each Vaccination With CYD Dengue Vaccine or Placebo
    Description GMTs against each serotype with the parental dengue virus strains were assessed using a dengue PRNT assay.
    Time Frame Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Per-Protocol analysis set. Here, 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 424 140
    CYD dengue Serotype 1; Pre-Injection 1
    8.20
    8.23
    CYD dengue Serotype 1; Post-Injection 1
    10.0
    7.09
    CYD dengue Serotype 1; Pre-Injection 2
    12.9
    7.85
    CYD dengue Serotype 1; Post-Injection 2
    22.4
    7.91
    CYD dengue Serotype 1; Pre-Injection 3
    18.0
    7.40
    CYD dengue Serotype 1; Post-Injection 3
    46.6
    8.93
    CYD dengue Serotype 2; Pre-Injection 1
    9.06
    8.48
    CYD dengue Serotype 2; Post-Injection 1
    17.2
    7.39
    CYD dengue Serotype 2; Pre-Injection 2
    19.1
    9.79
    CYD dengue Serotype 2; Post-Injection 2
    50.3
    9.48
    CYD dengue Serotype 2; Pre-Injection 3
    24.4
    6.98
    CYD dengue Serotype 2; Post-Injection 3
    72.7
    8.88
    CYD dengue Serotype 3; Pre-Injection 1
    8.45
    8.93
    CYD dengue Serotype 3; Post-Injection 1
    28.2
    9.56
    CYD dengue Serotype 3; Pre-Injection 2
    29.7
    11.1
    CYD dengue Serotype 3; Post-Injection 2
    70.8
    10.5
    CYD dengue Serotype 3; Pre-Injection 3
    39.1
    8.23
    CYD dengue Serotype 3; Post-Injection 3
    100
    9.52
    CYD dengue Serotype 4; Pre-Injection 1
    6.93
    6.84
    CYD dengue Serotype 4; Post-Injection 1
    65.9
    6.31
    CYD dengue Serotype 4; Pre-Injection 2
    47.5
    7.91
    CYD dengue Serotype 4; Post-Injection 2
    90.2
    8.00
    CYD dengue Serotype 4; Pre-Injection 3
    47.1
    6.04
    CYD dengue Serotype 4; Post-Injection 3
    99.4
    7.66
    7. Primary Outcome
    Title GMTs of Antibodies by Age Groups (2-11 Years, 12-17 Years, 18-45 Years) Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
    Description GMTs against each dengue virus serotype (parental strains) were assessed using a dengue PRNT assay.
    Time Frame Pre-Injection 1 and 28 days Post-Injection 3

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Per-Protocol analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 148 47
    2-11 years, CYD dengue Serotype 1; Pre-Inj. 1
    5.33
    5.44
    2-11 years, CYD dengue Serotype 1; Post-Inj. 3
    60.7
    6.32
    2-11 years, CYD dengue Serotype 2; Pre-Inj. 1
    5.85
    5.18
    2-11 years, CYD dengue Serotype 2; Post-Inj. 3
    95.9
    6.09
    2-11 years, CYD dengue Serotype 3; Pre-Inj. 1
    6.24
    6.02
    2-11 years, CYD dengue Serotype 3; Post-Inj. 3
    138
    6.67
    2-11 years, CYD dengue Serotype 4; Pre-Inj. 1
    5.64
    5.42
    2-11 years, CYD dengue Serotype 4; Post-Inj. 3
    101
    6.92
    12-17 years, CYD dengue Serotype 1; Pre-Inj. 1
    6.49
    5.47
    12-17 years, CYD dengue Serotype 1; Post-Inj. 3
    28.9
    6.56
    12-17 years, CYD dengue Serotype 2; Pre-Inj. 1
    7.47
    5.54
    12-17 years, CYD dengue Serotype 2; Post-Inj. 3
    54.0
    6.35
    12-17 years, CYD dengue Serotype 3; Pre-Inj. 1
    6.86
    6.83
    12-17 years, CYD dengue Serotype 3; Post-Inj. 3
    74.1
    8.32
    12-17 years, CYD dengue Serotype 4; Pre-Inj. 1
    5.83
    5.08
    12-17 years, CYD dengue Serotype 4; Post-Inj. 3
    80.4
    6.68
    18-45 years, CYD dengue Serotype 1; Pre-Inj. 1
    16.7
    18.5
    18-45 years, CYD dengue Serotype 1; Post-Inj. 3
    59.5
    18.3
    18-45 years, CYD dengue Serotype 2; Pre-Inj. 1
    17.8
    21.1
    18-45 years, CYD dengue Serotype 2; Post-Inj. 3
    72.7
    19.5
    18-45 years, CYD dengue Serotype 3; Pre-Inj. 1
    14.6
    17.5
    18-45 years, CYD dengue Serotype 3; Post-Inj. 3
    94.9
    16.3
    18-45 years, CYD dengue Serotype 4; Pre-Inj. 1
    10.4
    11.7
    18-45 years, CYD dengue Serotype 4; Post-Inj. 3
    127
    9.96
    8. Secondary Outcome
    Title Percentage of Participants Aged 2 to 11 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each dengue virus serotypes (parental strains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Full analysis set included participants who received at least 1 dose of CYD dengue vaccine or Placebo, had at least 1 blood sample drawn and valid post-vaccination serology result. Here, 'overall number of participants analyzed'=participants evaluable for outcome measure and 'number analyzed'=participants with available data for specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 236 80
    CYD dengue Serotype 1; Pre-Injection 1
    4.7
    0.5%
    8.0
    2.7%
    CYD dengue Serotype 1; Post-Injection 3
    91.0
    10.1%
    8.9
    3%
    CYD dengue Serotype 1; 1st year follow up
    41.8
    4.7%
    6.8
    2.3%
    CYD dengue Serotype 1; 2nd year follow up
    27.1
    3%
    0.0
    0%
    CYD dengue Serotype 1; 3rd year follow up
    16.5
    1.8%
    0.0
    0%
    CYD dengue Serotype 1; 4th year follow up
    9.6
    1.1%
    0.0
    0%
    CYD dengue Serotype 2; Pre-Injection 1
    5.4
    0.6%
    2.0
    0.7%
    CYD dengue Serotype 2; Post-Injection 3
    94.4
    10.5%
    13.3
    4.4%
    CYD dengue Serotype 2; 1st year follow up
    59.6
    6.6%
    8.9
    3%
    CYD dengue Serotype 2; 2nd year follow up
    52.1
    5.8%
    11.6
    3.9%
    CYD dengue Serotype 2; 3rd year follow up
    34.3
    3.8%
    7.0
    2.3%
    CYD dengue Serotype 2; 4th year follow up
    36.9
    4.1%
    2.4
    0.8%
    CYD dengue Serotype 3; Pre-Injection 1
    11.6
    1.3%
    10.0
    3.3%
    CYD dengue Serotype 3; Post-Injection 3
    97.9
    10.9%
    13.6
    4.5%
    CYD dengue Serotype 3; 1st year follow up
    66.0
    7.3%
    9.1
    3%
    CYD dengue Serotype 3; 2nd year follow up
    74.4
    8.3%
    29.3
    9.8%
    CYD dengue Serotype 3; 3rd year follow up
    50.0
    5.6%
    4.7
    1.6%
    CYD dengue Serotype 3; 4th year follow up
    37.7
    4.2%
    2.4
    0.8%
    CYD dengue Serotype 4; Pre-Injection 1
    6.8
    0.8%
    6.0
    2%
    CYD dengue Serotype 4; Post-Injection 3
    97.2
    10.8%
    20.5
    6.8%
    CYD dengue Serotype 4; 1st year follow up
    75.2
    8.4%
    4.7
    1.6%
    CYD dengue Serotype 4; 2nd year follow up
    72.9
    8.1%
    4.7
    1.6%
    CYD dengue Serotype 4; 3rd year follow up
    60.6
    6.7%
    7.0
    2.3%
    CYD dengue Serotype 4; 4th year follow up
    49.3
    5.5%
    0.0
    0%
    9. Secondary Outcome
    Title Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each dengue virus serotypes (parental stains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 141 46
    CYD dengue Serotype 1; Pre-Injection 1
    5.7
    0.6%
    4.3
    1.4%
    CYD dengue Serotype 1; Post-Injection 3
    67.4
    7.5%
    11.6
    3.9%
    CYD dengue Serotype 1; 1st year follow up
    25.8
    2.9%
    7.3
    2.4%
    CYD dengue Serotype 1; 2nd year follow up
    19.5
    2.2%
    7.5
    2.5%
    CYD dengue Serotype 1; 3rd year follow up
    16.1
    1.8%
    5.0
    1.7%
    CYD dengue Serotype 1; 4th year follow up
    11.9
    1.3%
    5.4
    1.8%
    CYD dengue Serotype 2; Pre-Injection 1
    9.9
    1.1%
    4.3
    1.4%
    CYD dengue Serotype 2; Post-Injection 3
    83.7
    9.3%
    9.3
    3.1%
    CYD dengue Serotype 2; 1st year follow up
    44.3
    4.9%
    4.9
    1.6%
    CYD dengue Serotype 2; 2nd year follow up
    52.3
    5.8%
    10.0
    3.3%
    CYD dengue Serotype 2; 3rd year follow up
    35.5
    4%
    5.0
    1.7%
    CYD dengue Serotype 2; 4th year follow up
    36.2
    4%
    5.4
    1.8%
    CYD dengue Serotype 3; Pre-Injection 1
    11.4
    1.3%
    10.9
    3.6%
    CYD dengue Serotype 3; Post-Injection 3
    88.8
    9.9%
    20.9
    7%
    CYD dengue Serotype 3; 1st year follow up
    61.7
    6.9%
    5.0
    1.7%
    CYD dengue Serotype 3; 2nd year follow up
    56.3
    6.3%
    12.5
    4.2%
    CYD dengue Serotype 3; 3rd year follow up
    48.8
    5.4%
    5.0
    1.7%
    CYD dengue Serotype 3; 4th year follow up
    47.5
    5.3%
    5.4
    1.8%
    CYD dengue Serotype 4; Pre-Injection 1
    6.4
    0.7%
    2.2
    0.7%
    CYD dengue Serotype 4; Post-Injection 3
    91.1
    10.1%
    9.3
    3.1%
    CYD dengue Serotype 4; 1st year follow up
    73.5
    8.2%
    2.4
    0.8%
    CYD dengue Serotype 4; 2nd year follow up
    71.1
    7.9%
    10.0
    3.3%
    CYD dengue Serotype 4; 3rd year follow up
    66.7
    7.4%
    5.0
    1.7%
    CYD dengue Serotype 4; 4th year follow up
    61.0
    6.8%
    8.1
    2.7%
    10. Secondary Outcome
    Title Percentage of Participants Aged 18 to 45 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each dengue virus serotypes (parental stains) was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 521 174
    CYD dengue Serotype 1; Pre-Injection 1
    33.1
    3.7%
    38.8
    12.9%
    CYD dengue Serotype 1; Post-Injection 3
    71.7
    8%
    39.5
    13.2%
    CYD dengue Serotype 1; 1st year follow up
    45.9
    5.1%
    31.8
    10.6%
    CYD dengue Serotype 1; 2nd year follow up
    43.6
    4.9%
    34.1
    11.4%
    CYD dengue Serotype 1; 3rd year follow up
    40.4
    4.5%
    30.8
    10.3%
    CYD dengue Serotype 1; 4th year follow up
    39.6
    4.4%
    31.6
    10.5%
    CYD dengue Serotype 2; Pre-Injection 1
    32.6
    3.6%
    38.8
    12.9%
    CYD dengue Serotype 2; Post-Injection 3
    80.3
    8.9%
    30.2
    10.1%
    CYD dengue Serotype 2; 1st year follow up
    66.4
    7.4%
    40.9
    13.6%
    CYD dengue Serotype 2; 2nd year follow up
    68.4
    7.6%
    34.1
    11.4%
    CYD dengue Serotype 2; 3rd year follow up
    55.3
    6.2%
    35.9
    12%
    CYD dengue Serotype 2; 4th year follow up
    55.2
    6.1%
    31.6
    10.5%
    CYD dengue Serotype 3; Pre-Injection 1
    36.9
    4.1%
    41.7
    13.9%
    CYD dengue Serotype 3; Post-Injection 3
    92.9
    10.3%
    34.9
    11.6%
    CYD dengue Serotype 3; 1st year follow up
    68.6
    7.6%
    38.6
    12.9%
    CYD dengue Serotype 3; 2nd year follow up
    77.8
    8.7%
    46.3
    15.4%
    CYD dengue Serotype 3; 3rd year follow up
    67.9
    7.6%
    35.9
    12%
    CYD dengue Serotype 3; 4th year follow up
    56.6
    6.3%
    29.7
    9.9%
    CYD dengue Serotype 4; Pre-Injection 1
    25.0
    2.8%
    31.3
    10.4%
    CYD dengue Serotype 4; Post-Injection 3
    93.7
    10.4%
    32.6
    10.9%
    CYD dengue Serotype 4; 1st year follow up
    86.9
    9.7%
    29.5
    9.8%
    CYD dengue Serotype 4; 2nd year follow up
    81.2
    9%
    24.4
    8.1%
    CYD dengue Serotype 4; 3rd year follow up
    79.8
    8.9%
    20.5
    6.8%
    CYD dengue Serotype 4; 4th year follow up
    77.6
    8.6%
    21.1
    7%
    11. Secondary Outcome
    Title Percentage of Participants Aged 2 to 11 Years Old Who Achieved Seropositivity Against At Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 236 80
    CYD dengue >=1 serotype; Pre-Injection 1
    19.6
    2.2%
    26.0
    8.7%
    CYD dengue >=1 serotype; Post-Injection 3
    100.0
    11.1%
    51.1
    17%
    CYD dengue >=1 serotype; 1st year follow up
    92.3
    10.3%
    20.0
    6.7%
    CYD dengue >=1 serotype; 2nd year follow up
    95.0
    10.6%
    34.9
    11.6%
    CYD dengue >=1 serotype; 3rd year follow up
    76.9
    8.6%
    7.0
    2.3%
    CYD dengue >=1 serotype; 4th year follow up
    72.1
    8%
    4.8
    1.6%
    CYD dengue >=2 serotypes; Pre-Injection 1
    6.1
    0.7%
    0.0
    0%
    CYD dengue >=2 serotypes; Post- Injection 3
    99.3
    11.1%
    4.4
    1.5%
    CYD dengue >=2 serotypes; 1st year follow up
    66.2
    7.4%
    6.7
    2.2%
    CYD dengue >=2 serotypes; 2nd year follow up
    70.7
    7.9%
    9.3
    3.1%
    CYD dengue >=2 serotypes; 3rd year follow up
    48.5
    5.4%
    7.0
    2.3%
    CYD dengue >=2 serotypes; 4th year follow up
    35.3
    3.9%
    0.0
    0%
    CYD dengue >=3 serotypes; Pre-Injection 1
    2.0
    0.2%
    0.0
    0%
    CYD dengue >=3 serotypes; Post- Injection 3
    96.5
    10.7%
    0.0
    0%
    CYD dengue >=3 serotypes; 1st year follow up
    52.8
    5.9%
    2.2
    0.7%
    CYD dengue >=3 serotypes; 2nd year follow up
    42.1
    4.7%
    0.0
    0%
    CYD dengue >=3 serotypes; 3rd year follow up
    23.9
    2.7%
    4.7
    1.6%
    CYD dengue >=3 serotypes; 4th year follow up
    16.2
    1.8%
    0.0
    0%
    CYD dengue All 4 serotypes; Pre- Injection 1
    0.7
    0.1%
    0.0
    0%
    CYD dengue All 4 serotypes; Post- Injection 3
    84.0
    9.4%
    0.0
    0%
    CYD dengue All 4 serotypes; 1st year follow up
    29.6
    3.3%
    0.0
    0%
    CYD dengue All 4 serotypes; 2nd year follow up
    15.0
    1.7%
    0.0
    0%
    CYD dengue All 4 serotypes; 3rd year follow up
    11.2
    1.2%
    0.0
    0%
    CYD dengue All 4 serotypes; 4th year follow up
    6.6
    0.7%
    0.0
    0%
    12. Secondary Outcome
    Title Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 141 46
    CYD dengue >=1 Serotype; Pre-Injection 1
    13.5
    1.5%
    15.2
    5.1%
    CYD dengue >=1 Serotype; Post- Injection 3
    97.8
    10.9%
    25.6
    8.5%
    CYD dengue >=1 Serotype; 1st year follow up
    94.7
    10.5%
    7.3
    2.4%
    CYD dengue >=1 Serotype; 2nd year follow up
    93.0
    10.4%
    15.0
    5%
    CYD dengue >=1 Serotype; 3rd year follow up
    89.5
    10%
    5.0
    1.7%
    CYD dengue >=1 serotype; 4th year follow up
    81.4
    9.1%
    8.1
    2.7%
    CYD dengue >=2 Serotypes; Pre- Injection 1
    7.8
    0.9%
    4.3
    1.4%
    CYD dengue >=2 Serotypes; Post- Injection 3
    94.8
    10.6%
    9.3
    3.1%
    CYD dengue >=2 Serotypes; 1st year follow up
    60.2
    6.7%
    4.9
    1.6%
    CYD dengue >=2 Serotypes; 2nd year follow up
    62.5
    7%
    10.0
    3.3%
    CYD dengue >=2 Serotypes; 3rd year follow up
    45.2
    5%
    5.0
    1.7%
    CYD dengue >=2 serotypes; 4th year follow up
    44.9
    5%
    5.4
    1.8%
    CYD dengue >=3 Serotypes; Pre- Injection 1
    7.1
    0.8%
    2.2
    0.7%
    CYD dengue >=3 Serotypes; Post- Injection 3
    80.7
    9%
    9.3
    3.1%
    CYD dengue >=3 Serotypes; 1st year follow up
    33.1
    3.7%
    4.9
    1.6%
    CYD dengue >=3 Serotypes; 2nd year follow up
    31.3
    3.5%
    7.5
    2.5%
    CYD dengue >=3 Serotypes; 3rd year follow up
    22.6
    2.5%
    5.0
    1.7%
    CYD dengue >=3 serotypes; 4th year follow up
    20.3
    2.3%
    5.4
    1.8%
    CYD dengue All 4 Serotypes; Pre- Injection 1
    5.0
    0.6%
    0.0
    0%
    CYD dengue All 4 Serotypes; Post- Injection 3
    57.0
    6.3%
    7.0
    2.3%
    CYD dengue All 4 Serotypes; 1st year follow up
    15.8
    1.8%
    2.4
    0.8%
    CYD dengue All 4 Serotypes; 2nd year follow up
    11.7
    1.3%
    7.5
    2.5%
    CYD dengue All 4 Serotypes; 3rd year follow up
    8.9
    1%
    5.0
    1.7%
    CYD dengue All 4 serotypes; 4th year follow up
    9.3
    1%
    5.4
    1.8%
    13. Secondary Outcome
    Title Percentage of Participants Aged 18 to 45 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution).
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 521 174
    CYD dengue >=1 Serotype; Pre-Injection 1
    46.5
    5.2%
    55.1
    18.4%
    CYD dengue >=1 Serotype; Post- Injection 3
    100.0
    11.1%
    53.5
    17.8%
    CYD dengue >=1 Serotype; 1st year follow up
    96.7
    10.8%
    50.0
    16.7%
    CYD dengue >=1 Serotype; 2nd year follow up
    96.6
    10.8%
    56.1
    18.7%
    CYD dengue >=1 Serotype; 3rd year follow up
    93.0
    10.4%
    41.0
    13.7%
    CYD dengue >=1 serotype; 4th year follow up
    92.5
    10.3%
    36.8
    12.3%
    CYD dengue >=2 Serotypes; Pre- Injection 1
    32.4
    3.6%
    38.8
    12.9%
    CYD dengue >=2 Serotypes; Post- Injection 3
    97.6
    10.9%
    32.6
    10.9%
    CYD dengue >=2 Serotypes; 1st year follow up
    73.8
    8.2%
    38.6
    12.9%
    CYD dengue >=2 Serotypes; 2nd year follow up
    76.9
    8.6%
    34.1
    11.4%
    CYD dengue >=2 Serotypes; 3rd year follow up
    63.2
    7%
    33.3
    11.1%
    CYD dengue >=2 serotypes; 4th year follow up
    54.2
    6%
    28.9
    9.6%
    CYD dengue >=3 Serotypes; Pre- Injection 1
    26.8
    3%
    32.7
    10.9%
    CYD dengue >=3 Serotypes; Post- Injection 3
    83.5
    9.3%
    27.9
    9.3%
    CYD dengue >=3 Serotypes; 1st year follow up
    55.7
    6.2%
    34.1
    11.4%
    CYD dengue >=3 Serotypes; 2nd year follow up
    56.4
    6.3%
    29.3
    9.8%
    CYD dengue >=3 Serotypes; 3rd year follow up
    46.5
    5.2%
    30.8
    10.3%
    CYD dengue >=3 serotypes; 4th year follow up
    43.0
    4.8%
    26.3
    8.8%
    CYD dengue All 4 Serotypes; Pre- Injection 1
    21.1
    2.3%
    22.4
    7.5%
    CYD dengue All 4 Serotypes; Post- Injection 3
    56.7
    6.3%
    23.3
    7.8%
    CYD dengue All 4 Serotypes; 1st year follow up
    41.0
    4.6%
    18.2
    6.1%
    CYD dengue All 4 Serotypes; 2nd year follow up
    41.0
    4.6%
    19.5
    6.5%
    CYD dengue All 4 Serotypes; 3rd year follow up
    39.5
    4.4%
    17.9
    6%
    CYD dengue All 4 serotypes; 4th year follow up
    37.4
    4.2%
    21.1
    7%
    14. Secondary Outcome
    Title GMTs of Antibodies in Participants 2 to 11 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
    Description GMTs against each serotype with the dengue virus strain (parental strains) were assessed using a dengue PRNT assay.
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 236 80
    CYD dengue Serotype 1; Pre-Injection 1
    5.33
    5.42
    CYD dengue Serotype 1; Post-Injection 3
    56.6
    6.06
    CYD dengue Serotype 1; 1st year follow up
    12.1
    5.52
    CYD dengue Serotype 1; 2nd year follow up
    8.89
    5.00
    CYD dengue Serotype 1; 3rd year follow up
    7.35
    5.00
    CYD dengue Serotype 1; 4th year follow up
    6.21
    5.00
    CYD dengue Serotype 2; Pre-Injection 1
    5.85
    5.17
    CYD dengue Serotype 2; Post-Injection 3
    101
    5.88
    CYD dengue Serotype 2; 1st year follow up
    21.1
    5.86
    CYD dengue Serotype 2; 2nd year follow up
    16.4
    6.11
    CYD dengue Serotype 2; 3rd year follow up
    11.7
    5.58
    CYD dengue Serotype 2; 4th year follow up
    14.2
    5.11
    CYD dengue Serotype 3; Pre-Injection 1
    6.24
    5.95
    CYD dengue Serotype 3; Post-Injection 3
    136
    6.54
    CYD dengue Serotype 3; 1st year follow up
    25.4
    5.87
    CYD dengue Serotype 3; 2nd year follow up
    29.9
    10.1
    CYD dengue Serotype 3; 3rd year follow up
    14.6
    5.43
    CYD dengue Serotype 3; 4th year follow up
    11.4
    5.09
    CYD dengue Serotype 4; Pre-Injection 1
    5.64
    5.39
    CYD dengue Serotype 4; Post-Injection 3
    104
    7.20
    CYD dengue Serotype 4; 1st year follow up
    31.8
    5.69
    CYD dengue Serotype 4; 2nd year follow up
    30.6
    5.68
    CYD dengue Serotype 4; 3rd year follow up
    22.3
    6.31
    CYD dengue Serotype 4; 4th year follow up
    16.5
    5.00
    15. Secondary Outcome
    Title GMTs of Antibodies in Participants 12 to 17 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description GMTs against each serotype with the dengue virus strain (parental strains) were assessed using a dengue PRNT assay.
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 141 46
    CYD dengue Serotype 1; Pre-Injection 1
    6.47
    5.47
    CYD dengue Serotype 1; Post-Injection 3
    28.5
    6.36
    CYD dengue Serotype 1; 1st year follow up
    9.69
    5.69
    CYD dengue Serotype 1; 2nd year follow up
    8.31
    5.91
    CYD dengue Serotype 1; 3rd year follow up
    8.02
    5.54
    CYD dengue Serotype 1; 4th year follow up
    7.41
    5.51
    CYD dengue Serotype 2; Pre-Injection 1
    7.45
    5.54
    CYD dengue Serotype 2; Post-Injection 3
    48.7
    6.17
    CYD dengue Serotype 2; 1st year follow up
    16.6
    5.58
    CYD dengue Serotype 2; 2nd year follow up
    18.7
    6.38
    CYD dengue Serotype 2; 3rd year follow up
    13.3
    5.77
    CYD dengue Serotype 2; 4th year follow up
    14.0
    5.80
    CYD dengue Serotype 3; Pre-Injection 1
    6.84
    6.83
    CYD dengue Serotype 3; Post-Injection 3
    71.4
    8.10
    CYD dengue Serotype 3; 1st year follow up
    19.7
    6.27
    CYD dengue Serotype 3; 2nd year follow up
    20.5
    7.54
    CYD dengue Serotype 3; 3rd year follow up
    15.3
    6.17
    CYD dengue Serotype 3; 4th year follow up
    13.7
    6.47
    CYD dengue Serotype 4; Pre-Injection 1
    5.83
    5.08
    CYD dengue Serotype 4; Post-Injection 3
    79.2
    6.45
    CYD dengue Serotype 4; 1st year follow up
    30.8
    5.17
    CYD dengue Serotype 4; 2nd year follow up
    33.4
    6.18
    CYD dengue Serotype 4; 3rd year follow up
    23.1
    5.55
    CYD dengue Serotype 4; 4th year follow up
    20.8
    5.43
    16. Secondary Outcome
    Title GMTs of Antibodies in Participants 18 to 45 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description GMTs against each serotype with the dengue virus strain were assessed using a dengue PRNT assay.
    Time Frame Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 521 174
    CYD dengue Serotype 1; Pre-Injection 1
    15.8
    19.2
    CYD dengue Serotype 1; Post-Injection 3
    48.7
    16.2
    CYD dengue Serotype 1; 1st year follow up
    26.3
    15.2
    CYD dengue Serotype 1; 2nd year follow up
    26.3
    16.3
    CYD dengue Serotype 1; 3rd year follow up
    24.1
    13.9
    CYD dengue Serotype 1; 4th year follow up
    23.5
    14.4
    CYD dengue Serotype 2; Pre-Injection 1
    16.9
    21.0
    CYD dengue Serotype 2; Post-Injection 3
    66.9
    15.2
    CYD dengue Serotype 2; 1st year follow up
    50.4
    19.3
    CYD dengue Serotype 2; 2nd year follow up
    66.5
    20.0
    CYD dengue Serotype 2; 3rd year follow up
    38.4
    17.0
    CYD dengue Serotype 2; 4th year follow up
    32.9
    15.5
    CYD dengue Serotype 3; Pre-Injection 1
    14.5
    19.4
    CYD dengue Serotype 3; Post-Injection 3
    88.4
    13.3
    CYD dengue Serotype 3; 1st year follow up
    45.2
    14.8
    CYD dengue Serotype 3; 2nd year follow up
    64.8
    19.9
    CYD dengue Serotype 3; 3rd year follow up
    48.3
    14.7
    CYD dengue Serotype 3; 4th year follow up
    28.6
    11.8
    CYD dengue Serotype 4; Pre-Injection 1
    10.1
    11.7
    CYD dengue Serotype 4; Post-Injection 3
    122
    10.0
    CYD dengue Serotype 4; 1st year follow up
    70.3
    9.87
    CYD dengue Serotype 4; 2nd year follow up
    52.6
    8.50
    CYD dengue Serotype 4; 3rd year follow up
    46.4
    8.39
    CYD dengue Serotype 4; 4th year follow up
    32.6
    7.54
    17. Secondary Outcome
    Title Percentage of Participants (Aged 2 to 11 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.
    Time Frame 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 29 13
    CYD dengue Serotype 1; Post-Injection 3
    96.3
    10.7%
    0.0
    0%
    CYD dengue Serotype 1; 1st year follow up
    74.1
    8.3%
    7.7
    2.6%
    CYD dengue Serotype 1; 2nd year follow up
    55.6
    6.2%
    0.0
    0%
    CYD dengue Serotype 1; 3rd year follow up
    33.3
    3.7%
    0.0
    0%
    CYD dengue Serotype 1; 4th year follow up
    22.2
    2.5%
    0.0
    0%
    CYD dengue Serotype 2; Post-Injection 3
    100.0
    11.1%
    15.4
    5.1%
    CYD dengue Serotype 2; 1st year follow up
    85.2
    9.5%
    15.4
    5.1%
    CYD dengue Serotype 2; 2nd year follow up
    66.7
    7.4%
    16.7
    5.6%
    CYD dengue Serotype 2; 3rd year follow up
    48.1
    5.4%
    16.7
    5.6%
    CYD dengue Serotype 2; 4th year follow up
    48.1
    5.4%
    0.0
    0%
    CYD dengue Serotype 3; Post-Injection 3
    100.0
    11.1%
    23.1
    7.7%
    CYD dengue Serotype 3; 1st year follow up
    88.9
    9.9%
    7.7
    2.6%
    CYD dengue Serotype 3; 2nd year follow up
    81.5
    9.1%
    16.7
    5.6%
    CYD dengue Serotype 3; 3rd year follow up
    59.3
    6.6%
    8.3
    2.8%
    CYD dengue Serotype 3; 4th year follow up
    50.0
    5.6%
    0.0
    0%
    CYD dengue Serotype 4; Post-Injection 3
    100.0
    11.1%
    23.1
    7.7%
    CYD dengue Serotype 4; 1st year follow up
    88.9
    9.9%
    15.4
    5.1%
    CYD dengue Serotype 4; 2nd year follow up
    74.1
    8.3%
    0.0
    0%
    CYD dengue Serotype 4; 3rd year follow up
    70.4
    7.8%
    16.7
    5.6%
    CYD dengue Serotype 4; 4th year follow up
    70.4
    7.8%
    0.0
    0%
    18. Secondary Outcome
    Title Percentage of Participants (Aged 2 to 11 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.
    Time Frame 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 118 37
    CYD dengue Serotype 1; Post-Injection 3
    89.6
    10%
    12.5
    4.2%
    CYD dengue Serotype 1; 1st year follow up
    33.6
    3.7%
    6.5
    2.2%
    CYD dengue Serotype 1; 2nd year follow up
    20.5
    2.3%
    0.0
    0%
    CYD dengue Serotype 1; 3rd year follow up
    12.4
    1.4%
    0.0
    0%
    CYD dengue Serotype 1; 4th year follow up
    6.5
    0.7%
    0.0
    0%
    CYD dengue Serotype 2; Post-Injection 3
    93.0
    10.4%
    12.5
    4.2%
    CYD dengue Serotype 2; 1st year follow up
    54.0
    6%
    6.3
    2.1%
    CYD dengue Serotype 2; 2nd year follow up
    49.1
    5.5%
    9.7
    3.2%
    CYD dengue Serotype 2; 3rd year follow up
    31.1
    3.5%
    3.2
    1.1%
    CYD dengue Serotype 2; 4th year follow up
    34.3
    3.8%
    3.3
    1.1%
    CYD dengue Serotype 3; Post-Injection 3
    97.4
    10.8%
    9.7
    3.2%
    CYD dengue Serotype 3; 1st year follow up
    60.2
    6.7%
    9.7
    3.2%
    CYD dengue Serotype 3; 2nd year follow up
    72.4
    8.1%
    34.5
    11.5%
    CYD dengue Serotype 3; 3rd year follow up
    47.2
    5.3%
    3.2
    1.1%
    CYD dengue Serotype 3; 4th year follow up
    34.3
    3.8%
    3.3
    1.1%
    CYD dengue Serotype 4; Post-Injection 3
    96.5
    10.7%
    19.4
    6.5%
    CYD dengue Serotype 4; 1st year follow
    71.7
    8%
    0.0
    0%
    CYD dengue Serotype 4; 2nd year follow up
    73.2
    8.2%
    6.5
    2.2%
    CYD dengue Serotype 4; 3rd year follow up
    58.7
    6.5%
    3.2
    1.1%
    CYD dengue Serotype 4; 4th year follow up
    44.4
    4.9%
    0.0
    0%
    19. Secondary Outcome
    Title Percentage of Participants (Aged 12 to 17 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.
    Time Frame 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 19 7
    CYD dengue Serotype 1; Post-Injection 3
    94.4
    10.5%
    33.3
    11.1%
    CYD dengue Serotype 1; 1st year follow up
    58.8
    6.5%
    20.0
    6.7%
    CYD dengue Serotype 1; 2nd year follow up
    46.7
    5.2%
    16.7
    5.6%
    CYD dengue Serotype 1; 3rd year follow up
    43.8
    4.9%
    16.7
    5.6%
    CYD dengue Serotype 1; 4th year follow up
    42.9
    4.8%
    20.0
    6.7%
    CYD dengue Serotype 2; Post-Injection 3
    94.4
    10.5%
    16.7
    5.6%
    CYD dengue Serotype 2; 1st year follow up
    82.4
    9.2%
    20.0
    6.7%
    CYD dengue Serotype 2; 2nd year follow up
    73.3
    8.2%
    33.3
    11.1%
    CYD dengue Serotype 2; 3rd year follow up
    68.8
    7.7%
    16.7
    5.6%
    CYD dengue Serotype 2; 4th year follow up
    71.4
    8%
    20.0
    6.7%
    CYD dengue Serotype 3; Post-Injection 3
    100.0
    11.1%
    50.0
    16.7%
    CYD dengue Serotype 3; 1st year follow up
    76.5
    8.5%
    20.0
    6.7%
    CYD dengue Serotype 3; 2nd year follow up
    80.0
    8.9%
    50.0
    16.7%
    CYD dengue Serotype 3; 3rd year follow up
    68.8
    7.7%
    16.7
    5.6%
    CYD dengue Serotype 3; 4th year follow up
    71.4
    8%
    20.0
    6.7%
    CYD dengue Serotype 4; Post-Injection 3
    100.0
    11.1%
    33.3
    11.1%
    CYD dengue Serotype 4; 1st year follow up
    100.0
    11.1%
    20.0
    6.7%
    CYD dengue Serotype 4; 2nd year follow up
    100.0
    11.1%
    16.7
    5.6%
    CYD dengue Serotype 4; 3rd year follow up
    93.8
    10.4%
    16.7
    5.6%
    CYD dengue Serotype 4; 4th year follow up
    100.0
    11.1%
    20.0
    6.7%
    20. Secondary Outcome
    Title Percentage of Participants (Aged 12 to 17 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each serotype with the dengue virus strain were assessed using a PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.
    Time Frame 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 121 39
    CYD dengue Serotype 1; Post-Injection 3
    62.9
    7%
    8.1
    2.7%
    CYD dengue Serotype 1; 1st year follow up
    20.9
    2.3%
    5.6
    1.9%
    CYD dengue Serotype 1; 2nd year follow up
    16.1
    1.8%
    5.9
    2%
    CYD dengue Serotype 1; 3rd year follow up
    12.0
    1.3%
    2.9
    1%
    CYD dengue Serotype 1; 4th year follow up
    7.7
    0.9%
    3.1
    1%
    CYD dengue Serotype 2; Post-Injection 3
    81.9
    9.1%
    8.1
    2.7%
    CYD dengue Serotype 2; 1st year follow up
    38.6
    4.3%
    2.8
    0.9%
    CYD dengue Serotype 2; 2nd year follow up
    49.1
    5.5%
    5.9
    2%
    CYD dengue Serotype 2; 3rd year follow up
    30.6
    3.4%
    2.9
    1%
    CYD dengue Serotype 2; 4th year follow up
    31.4
    3.5%
    3.1
    1%
    CYD dengue Serotype 3; Post-Injection 3
    87.0
    9.7%
    16.2
    5.4%
    CYD dengue Serotype 3; 1st year follow up
    59.5
    6.6%
    2.9
    1%
    CYD dengue Serotype 3; 2nd year follow up
    53.6
    6%
    5.9
    2%
    CYD dengue Serotype 3; 3rd year follow up
    45.8
    5.1%
    2.9
    1%
    CYD dengue Serotype 3; 4th year follow up
    44.2
    4.9%
    3.1
    1%
    CYD dengue Serotype 4; Post-Injection 3
    89.7
    10%
    5.4
    1.8%
    CYD dengue Serotype 4; 1st year follow up
    69.6
    7.8%
    0.0
    0%
    CYD dengue Serotype 4; 2nd year follow up
    67.0
    7.5%
    8.8
    2.9%
    CYD dengue Serotype 4; 3rd year follow up
    62.6
    7%
    2.9
    1%
    CYD dengue Serotype 4; 4th year follow up
    55.8
    6.2%
    6.3
    2.1%
    21. Secondary Outcome
    Title Percentage of Participants (Aged 18 to 45 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants immune at baseline was defined as those participants with titers >=10 (1/dilution) against at least one dengue serotype at baseline.
    Time Frame 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 66 27
    CYD dengue Serotype 1; Post-Injection 3
    89.3
    9.9%
    70.0
    23.3%
    CYD dengue Serotype 1; 1st year follow up
    77.8
    8.7%
    57.1
    19%
    CYD dengue Serotype 1; 2nd year follow up
    86.3
    9.6%
    65.0
    21.7%
    CYD dengue Serotype 1; 3rd year follow up
    80.8
    9%
    63.2
    21.1%
    CYD dengue Serotype 1; 4th year follow up
    84.8
    9.4%
    66.7
    22.2%
    CYD dengue Serotype 2; Post-Injection 3
    91.1
    10.1%
    65.0
    21.7%
    CYD dengue Serotype 2; 1st year follow up
    88.9
    9.9%
    71.4
    23.8%
    CYD dengue Serotype 2; 2nd year follow up
    92.2
    10.3%
    70.0
    23.3%
    CYD dengue Serotype 2; 3rd year follow up
    88.5
    9.9%
    68.4
    22.8%
    CYD dengue Serotype 2; 4th year follow up
    91.5
    10.2%
    66.7
    22.2%
    CYD dengue Serotype 3; Post-Injection 3
    98.2
    10.9%
    60.0
    20%
    CYD dengue Serotype 3; 1st year follow up
    90.7
    10.1%
    66.7
    22.2%
    CYD dengue Serotype 3; 2nd year follow up
    98.0
    10.9%
    70.0
    23.3%
    CYD dengue Serotype 3; 3rd year follow up
    94.2
    10.5%
    73.7
    24.6%
    CYD dengue Serotype 3; 4th year follow up
    91.5
    10.2%
    61.1
    20.4%
    CYD dengue Serotype 4; Post-Injection 3
    100.0
    11.1%
    65.0
    21.7%
    CYD dengue Serotype 4; 1st year follow up
    98.1
    10.9%
    47.6
    15.9%
    CYD dengue Serotype 4; 2nd year follow up
    96.1
    10.7%
    45.0
    15%
    CYD dengue Serotype 4; 3rd year follow up
    100.0
    11.1%
    42.1
    14%
    CYD dengue Serotype 4; 4th year follow up
    97.9
    10.9%
    44.4
    14.8%
    22. Secondary Outcome
    Title Percentage of Participants (Aged 18 to 45 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
    Description Seropositivity against each serotype with the dengue virus strain were assessed using a dengue PRNT assay. Seropositive participants were defined as participants with neutralizing antibody titers >=10 (1/dilution). Dengue participants naïve at baseline was defined as those participants with titers <10 (1/dilution) against all dengue serotypes at baseline.
    Time Frame 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)

    Outcome Measure Data

    Analysis Population Description
    Analysis was performed on Full analysis set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure and 'number analyzed' = participants with available data for each specified category.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    Measure Participants 74 22
    CYD dengue Serotype 1; Post-Injection 3
    59.4
    6.6%
    14.3
    4.8%
    CYD dengue Serotype 1; 1st year follow up
    21.3
    2.4%
    9.5
    3.2%
    CYD dengue Serotype 1; 2nd year follow up
    10.2
    1.1%
    5.3
    1.8%
    CYD dengue Serotype 1; 3rd year follow up
    7.1
    0.8%
    0
    0%
    CYD dengue Serotype 1; 4th year follow up
    5.6
    0.6%
    0
    0%
    CYD dengue Serotype 2; Post-Injection 3
    73.4
    8.2%
    0
    0%
    CYD dengue Serotype 2; 1st year follow up
    49.2
    5.5%
    14.3
    4.8%
    CYD dengue Serotype 2; 2nd year follow up
    50.8
    5.7%
    0
    0%
    CYD dengue Serotype 2; 3rd year follow up
    28.6
    3.2%
    5.6
    1.9%
    CYD dengue Serotype 2; 4th year follow up
    26.4
    2.9%
    0
    0%
    CYD dengue Serotype 3; Post-Injection 3
    87.5
    9.7%
    14.3
    4.8%
    CYD dengue Serotype 3; 1st year follow up
    48.3
    5.4%
    14.3
    4.8%
    CYD dengue Serotype 3; 2nd year follow up
    61.0
    6.8%
    21.1
    7%
    CYD dengue Serotype 3; 3rd year follow up
    46.3
    5.2%
    0
    0%
    CYD dengue Serotype 3; 4th year follow up
    28.3
    3.2%
    0
    0%
    CYD dengue Serotype 4; Post-Injection 3
    87.5
    9.7%
    4.8
    1.6%
    CYD dengue Serotype 4; 1st year follow up
    78.7
    8.8%
    14.3
    4.8%
    CYD dengue Serotype 4; 2nd year follow up
    71.2
    7.9%
    5.3
    1.8%
    CYD dengue Serotype 4; 3rd year follow up
    66.1
    7.4%
    0
    0%
    CYD dengue Serotype 4; 4th year follow up
    63.0
    7%
    0
    0%

    Adverse Events

    Time Frame Adverse events (AE) were collected from Day 0 (post-vaccination) up to the end of 4th year of follow up (up to 60 months).
    Adverse Event Reporting Description Solicited reaction (SR) was an adverse reaction observed and reported under conditions (nature and onset) prelisted (i.e., solicited) in the electronic case report form (eCRF). An unsolicited AE was an observed AE that did not fulfill conditions prelisted in eCRF in terms of symptom and/or onset post-vaccination. Safety analysis set.
    Arm/Group Title CYD Dengue Vaccine Group Placebo Group
    Arm/Group Description Participants received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively. All participants received a placebo at first vaccination (Month 0). Participants <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Participants >=12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.
    All Cause Mortality
    CYD Dengue Vaccine Group Placebo Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 3/898 (0.3%) 0/300 (0%)
    Serious Adverse Events
    CYD Dengue Vaccine Group Placebo Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 43/898 (4.8%) 13/300 (4.3%)
    Cardiac disorders
    Acute coronary syndrome 1/898 (0.1%) 1 0/300 (0%) 0
    Endocrine disorders
    Hyperthyroidism 1/898 (0.1%) 1 0/300 (0%) 0
    Thyroid disorder 1/898 (0.1%) 1 0/300 (0%) 0
    Gastrointestinal disorders
    Abdominal pain 1/898 (0.1%) 1 1/300 (0.3%) 1
    Colitis 1/898 (0.1%) 1 0/300 (0%) 0
    Diarrhoea 1/898 (0.1%) 1 0/300 (0%) 0
    Gingivitis 1/898 (0.1%) 1 0/300 (0%) 0
    General disorders
    Adverse drug reaction 1/898 (0.1%) 1 0/300 (0%) 0
    Chest pain 1/898 (0.1%) 1 0/300 (0%) 0
    Infections and infestations
    Appendicitis 2/898 (0.2%) 2 0/300 (0%) 0
    Bronchitis 1/898 (0.1%) 1 0/300 (0%) 0
    Conjunctivitis viral 2/898 (0.2%) 2 0/300 (0%) 0
    Corneal infection 1/898 (0.1%) 1 0/300 (0%) 0
    Dengue fever 3/898 (0.3%) 3 0/300 (0%) 0
    Gastroenteritis 2/898 (0.2%) 3 1/300 (0.3%) 1
    Gastroenteritis viral 1/898 (0.1%) 1 2/300 (0.7%) 2
    Groin abscess 1/898 (0.1%) 1 0/300 (0%) 0
    Hand-foot-and-mouth disease 2/898 (0.2%) 2 0/300 (0%) 0
    Herpangina 1/898 (0.1%) 1 0/300 (0%) 0
    Lymph node tuberculosis 1/898 (0.1%) 1 0/300 (0%) 0
    Meningitis viral 0/898 (0%) 0 1/300 (0.3%) 1
    Pharyngitis 1/898 (0.1%) 1 1/300 (0.3%) 1
    Pharyngitis bacterial 1/898 (0.1%) 1 0/300 (0%) 0
    Subcutaneous abscess 1/898 (0.1%) 1 1/300 (0.3%) 1
    Upper respiratory tract infection 2/898 (0.2%) 2 0/300 (0%) 0
    Viral infection 1/898 (0.1%) 1 0/300 (0%) 0
    Injury, poisoning and procedural complications
    Foot fracture 0/898 (0%) 0 1/300 (0.3%) 1
    Hand fracture 0/898 (0%) 0 1/300 (0.3%) 1
    Intentional overdose 1/898 (0.1%) 1 0/300 (0%) 0
    Traumatic haematoma 0/898 (0%) 0 1/300 (0.3%) 1
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/898 (0.1%) 1 0/300 (0%) 0
    Back pain 0/898 (0%) 0 1/300 (0.3%) 2
    Intervertebral disc protrusion 0/898 (0%) 0 1/300 (0.3%) 1
    Musculoskeletal pain 1/898 (0.1%) 1 0/300 (0%) 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Acute leukaemia 1/898 (0.1%) 1 0/300 (0%) 0
    Acute lymphocytic leukaemia 1/898 (0.1%) 1 0/300 (0%) 0
    Ovarian cancer metastatic 1/898 (0.1%) 1 0/300 (0%) 0
    Ovarian germ cell teratoma benign 0/898 (0%) 0 1/300 (0.3%) 1
    Papillary thyroid cancer 0/898 (0%) 0 1/300 (0.3%) 1
    Nervous system disorders
    Migraine 2/898 (0.2%) 2 0/300 (0%) 0
    Radial nerve palsy 1/898 (0.1%) 1 0/300 (0%) 0
    Syncope vasovagal 1/898 (0.1%) 1 0/300 (0%) 0
    Tension headache 1/898 (0.1%) 1 0/300 (0%) 0
    Pregnancy, puerperium and perinatal conditions
    Abortion spontaneous 1/898 (0.1%) 1 0/300 (0%) 0
    Ruptured ectopic pregnancy 1/898 (0.1%) 1 0/300 (0%) 0
    Psychiatric disorders
    Depression 1/898 (0.1%) 1 0/300 (0%) 0
    Reproductive system and breast disorders
    Ovarian cyst 0/898 (0%) 0 1/300 (0.3%) 1
    Respiratory, thoracic and mediastinal disorders
    Asthma 2/898 (0.2%) 2 1/300 (0.3%) 2
    Bronchial hyperreactivity 1/898 (0.1%) 1 0/300 (0%) 0
    Rhinitis allergic 1/898 (0.1%) 1 0/300 (0%) 0
    Surgical and medical procedures
    Osteotomy 1/898 (0.1%) 1 0/300 (0%) 0
    Other (Not Including Serious) Adverse Events
    CYD Dengue Vaccine Group Placebo Group
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 481/898 (53.6%) 198/300 (66%)
    General disorders
    Injection site Pain; Post-Any Injection 481/892 (53.9%) 481 198/297 (66.7%) 198
    Injection site Erythema; Post-Any Injection 64/891 (7.2%) 64 45/297 (15.2%) 45
    Injection site Swelling; Post-Any Injection 37/892 (4.1%) 37 25/297 (8.4%) 25
    Fever; Post-Any Injection 101/892 (11.3%) 101 22/297 (7.4%) 22
    Malaise; Post-Any Injection 372/891 (41.8%) 372 105/297 (35.4%) 105
    Asthenia; Post-Any Injection 183/891 (20.5%) 183 52/297 (17.5%) 52
    Infections and infestations
    Upper respiratory tract infection 72/898 (8%) 77 27/300 (9%) 30
    Musculoskeletal and connective tissue disorders
    Myalgia; Post-Any Injection 394/891 (44.2%) 394 130/297 (43.8%) 130
    Nervous system disorders
    Headache; Post-Any Injection 402/891 (45.1%) 402 114/297 (38.4%) 114
    Respiratory, thoracic and mediastinal disorders
    Cough 42/898 (4.7%) 48 15/300 (5%) 17
    Rhinorrhoea 42/898 (4.7%) 47 15/300 (5%) 15

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Sponsor must have the opportunity to review at least 60 days prior to submission for publication or presentation. If review indicates that potentially patentable subject matter would be disclosed, publication or public disclosure may be delayed for a maximum of an additional 60 days to allow for filing the necessary patent applications.

    Results Point of Contact

    Name/Title Director
    Organization Sanofi Pasteur
    Phone
    Email Contact-US@sanofi.com
    Responsible Party:
    Sanofi Pasteur, a Sanofi Company
    ClinicalTrials.gov Identifier:
    NCT00880893
    Other Study ID Numbers:
    • CYD28
    • 2014-001713-26
    First Posted:
    Apr 14, 2009
    Last Update Posted:
    Mar 21, 2022
    Last Verified:
    Mar 1, 2022