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Immunogenicity and Safety of Different Vaccination Schedules of Tetravalent Dengue Vaccine in Healthy Subjects 9 to 50 Years of Age

Sponsor
Sanofi Pasteur, a Sanofi Company (Industry)
Overall Status
Completed
CT.gov ID
NCT02628444
Collaborator
(none)
1,050
Enrollment
6
Locations
9
Arms
47.9
Actual Duration (Months)
175
Patients Per Site
3.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The aim of the study was to assess the immune response and the safety of different vaccination schedules of CYD dengue vaccine.

The primary objectives of the study were:

  • To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants 28 days after the last injection.

  • To demonstrate the non-inferiority of the immune response elicited against each dengue serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD vaccine given as a 3-dose schedule (Group 1) in previously dengue exposed participants, 1 year after the last injection.

  • To demonstrate the non-inferiority of the immune response elicited against each dengue serotype elicited by a booster dose of CYD dengue vaccine one year or two years after the last injection in the primary series in previously dengue exposed participants, compared to the immune response post dose 3 in Group 1.

The secondary objectives of the study were:

  • To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, 28 days after the last injection.

  • To demonstrate the superiority of the immune response elicited by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed participants, one year after the last injection.

  • To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 3 to the antibody levels immediately before receiving a booster dose, by baseline dengue serostatus.

  • To describe the neutralizing antibody levels of each dengue serotype at 28 days post-injection 2 and 28 days post-injection 3 from Group 1 in a primary series schedule by baseline dengue serostatus.

  • To demonstrate the superiority of the immune response elicited against each dengue serotype 28 days after administration of a booster dose of CYD dengue vaccine, in previously dengue exposed participants, at one year or two years after last injection in the primary series.

  • To describe the seroconversion rate 28 days post-booster injection in all 3 groups.

  • To describe all hospitalized virologically confirmed dengue (VCD) cases during the study.

  • To evaluate the safety profile of CYD after each and any injection during the trial. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.

Condition or Disease Intervention/Treatment Phase
  • Biological: CYD Dengue Vaccine
  • Biological: Placebo (Sodium chloride 0.9%)
 Phase 2

Detailed Description

Healthy participants aged between 9 and 50 year received CYD dengue vaccine in various schedules, in two sequential stages. In the first stage, participants received 1, 2 or 3 injections of CYD dengue vaccine over a 12-month period. In the second stage, participants were randomized to receive a booster dose of CYD dengue vaccine at either 12 months (Subgroup

  1. or 24 months (Subgroup b) after the third injection of study vaccine. During the conduction of this trial, the World Health Organization (WHO) indication about vaccinating only baseline seropositive participants was arisen; at this moment, STAGE I of the trial was completed. For STAGE II, only participants who were previously dengue exposed at baseline (dengue seropositive) were eligible to receive the booster dose.

Study Design

Study Type:
Interventional
Actual Enrollment :
1050 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Prevention
Official Title:
Immunogenicity and Safety of Tetravalent Dengue Vaccine Given in 1-, 2-, or 3- Dose Schedules (STAGE I) Followed by a Single Booster Injection of the Same Vaccine (STAGE II) 1 or 2 Years After the Last Primary Dose in Healthy Subjects 9 to 50 Years of Age in Colombia and the Philippines
Actual Study Start Date :
May 2, 2016
Actual Primary Completion Date :
Apr 29, 2020
Actual Study Completion Date :
Apr 29, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: STAGE-I Group 1: CYD Dengue Vaccine

Participants received 3 doses of CYD dengue vaccine 0.5 milliliters (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous
Experimental: STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)

Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous

Biological: Placebo (Sodium chloride 0.9%)
0.5 mL, Subcutaneous
Experimental: STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)

Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous

Biological: Placebo (Sodium chloride 0.9%)
0.5 mL, Subcutaneous
Experimental: STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)

Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous
Experimental: STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)

Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous

Biological: Placebo (Sodium chloride 0.9%)
0.5 mL, Subcutaneous
Experimental: STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)

Participants from Group 3 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous

Biological: Placebo (Sodium chloride 0.9%)
0.5 mL, Subcutaneous
Experimental: STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)

Participants from Group 1 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous
Experimental: STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)

Participants from Group 2 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous

Biological: Placebo (Sodium chloride 0.9%)
0.5 mL, Subcutaneous
Experimental: STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)

Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).

Biological: CYD Dengue Vaccine
0.5 mL, Subcutaneous

Biological: Placebo (Sodium chloride 0.9%)
0.5 mL, Subcutaneous

Outcome Measures

Primary Outcome Measures

  1. STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline [28 days after last CYD dengue vaccination]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using plaque reduction neutralization test (PRNT) assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline was defined as participants with titers >=10 (1/dilution) for at least 1 serotype with parental dengue virus strains. Per-protocol analysis set (PPAS) included all participants who had no protocol violations; and who met any of following study violations were excluded from PPAS (STAGE I/II): had not met all protocol-specified inclusion/exclusion criteria, had not received correct doses or injections, received vaccine other than randomized schedule, did not receive vaccination in proper time window, had not provided post-dose serology sample in proper time window, received protocol-restricted medication, therapy, or vaccine.

  2. STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline [1 year after last CYD dengue vaccination]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.

  3. STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline [Group 1: 28 days post-dose 3 in STAGE-I, Group 1a: 28 days post 12 months booster dose in STAGE-II]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1a (28 days 12 months Booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.

  4. STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline [Group 1: 28 days post-dose 3 in STAGE-I, Group 2a: 28 days post 12 months booster dose in STAGE-II]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2a (28 days post 12 months Booster dose) were reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.

  5. STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline [Group 1: 28 days post-dose 3 in STAGE-I, Group 1b: 28 days post 24 months booster dose in STAGE-II]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1b (28 days post 24 months booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.

  6. STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline [Group 1: 28 days post-dose 3 in STAGE-I, Group 2b: 28 days post 24 months Booster dose in STAGE-II]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2b (28 days post 24 months Booster dose) was reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.

Secondary Outcome Measures

  1. STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline-Comparison Between Group 1 and Group 2 [28 days and 1 year after last CYD dengue vaccination]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.

  2. STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants [Baseline, 28 days post vaccination 3, and 1 year post vaccination 3]

    GMTs of antibodies against each of the 4 dengue virus serotypes (parental strains) were assessed using the PRNT assay method.

  3. STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains (by Baseline Dengue Status) in Participants Who Were Seropositive and Seronegative at Baseline [Baseline, 28 days post vaccination 3, and 1 year post vaccination 3]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Dengue seronegative participants at Baseline were defined as the participants with valid titer <0 (1/dilution) for all serotypes with parental dengue virus strains.

  4. STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Participants Seropositive at Baseline [Baseline, 28 days post vaccination-3, and 28 days post booster dose]

    GMTs of antibodies against each of the 4 dengue virus serotype (1, 2, 3, or 4) were assessed using the PRNT assay. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Titers were measured in terms of 1/dilution.

  5. STAGE-I: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Participants [Baseline, 28 days post vaccination 3, and 1 year post vaccination 3]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay.

  6. STAGE-II: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Participants Seropositive at Baseline [Baseline, 28 days post vaccination 3, and 1 year post vaccination 3]

    GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.

  7. STAGE-I: Number of Participants With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination) [Within 30 minutes after any vaccination (1, 2, or 3)]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the electronic case report form (eCRF) in terms of diagnosis and/or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after any vaccination.

  8. STAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine [Within 30 minutes after CYD booster vaccination]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and / or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after vaccination.

  9. STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination) [Within 7 days after any vaccination (1, 2, or 3)]

    Adverse reaction (AR) was defined as all noxious and unintended responses to a medicinal product related to any dose. A Solicited Reaction (SR) was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.

  10. STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination) [Within 7 days after each vaccination (1, 2, and 3)]

    AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.

  11. STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination) [Within 14 days after any vaccination (1, 2, or 3)]

    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Systemic AEs were all AEs that were not injection site reactions. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.

  12. STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination) [Within 14 days after each vaccination (1, 2, and 3)]

    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.

  13. STAGE-II: Number of Participants With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine [Within 7 days after CYD booster vaccination]

    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.

  14. STAGE-II: Number of Participants With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine [Within 14 days after CYD booster vaccination]

    An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.

  15. STAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo [Within 28 days after any vaccination (1, 2, or 3)]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination.

  16. STAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine [Within 28 days after CYD booster Vaccination]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination.

  17. STAGE-I: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Event of Special Interests (AESI) Following Vaccination With CYD Dengue Vaccine or Placebo [From Day 0 (post vaccination) up to 12 months after last vaccination in STAGE-I (i.e., up to 24 months)]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.

  18. STAGE-II: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine [From Month 25 up to 6 months after CYD booster injection (either at 1 year or 2 year) (i.e., up to 30 months for Groups 1a, 2a, and 3a and up to 42 months for Groups 1b, 2b, and 3b)]

    An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.

Eligibility Criteria

Criteria

Ages Eligible for Study:
9 Years to 50 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
Inclusion Criteria:

  • Aged 9 to 50 years on the day of enrollment.

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

  • Assent form or informed consent form (ICF) had been signed and dated by the participant (based on local regulations), and ICF had been signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).

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

Exclusion Criteria:

  • Participant was pregnant, or lactating, or of childbearing potential (to be considered of non-childbearing potential, a female must be pre-menarche, surgically sterile, or using an effective method of contraception or abstinence from at least 4 weeks prior to the first vaccination until at least 4 weeks after the last vaccination).

  • Participation at the time of study enrollment (or in the 4 weeks preceding the first trial vaccination) or planned participation during the present trial period in another clinical trial investigating a vaccine, drug, medical device or medical procedure.

  • Self-reported or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

  • Self-reported systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine used in the trial or to a vaccine containing any of the same substances.

  • Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion.

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

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

  • Previous vaccination against dengue disease with either the trial vaccine or another vaccine.

  • Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily.

  • Current alcohol abuse or drug addiction that, based on investigator's judgment, might interfere with the participant's ability to comply with trial procedures.

  • Identified as a site employee of the Investigator, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center, as well as family members (i.e., immediate, husband, wife, and their children, adopted or natural) of the employees or the Investigator.

  • A prospective participant must not be included in the study until the following conditions and/or symptoms were resolved:

  • Febrile illness (temperature greater than or equal to [>=] 38.0 degree Celsius) or moderate or severe acute illness/infection (according to Investigator's judgment) on the day of vaccination.

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

Contacts and Locations

Locations

Site City State Country Postal Code
1 Investigational Site 102 Barranquilla Colombia
2 Investigational Site 101 Cali Colombia
3 Investigational Site 103 Medellin Colombia
4 Investigational Site 203 Manila Philippines
5 Investigational Site 204 Manila Philippines
6 Investigational Primary Site Muntinlupa 201_Satellite Site San Pablo 202 Muntinlupa Philippines

Sponsors and Collaborators

  • Sanofi Pasteur, a Sanofi Company

Investigators

  • Study Director: Clinical Sciences & Operations, Sanofi Pasteur, a Sanofi Company

Study Documents (Full-Text)

More Information

Publications

None provided.
Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT02628444
Other Study ID Numbers:
  • CYD65
  • U1111-1161-3242
  • 2020-002854-25
First Posted:
Dec 11, 2015
Last Update Posted:
Mar 24, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Sanofi Pasteur, a Sanofi Company
Dengue Fever
Dengue virus
Dengue Hemorrhagic Fever
CYD Dengue Vaccine
Additional relevant MeSH terms:
Dengue
Hemorrhagic Fevers, Viral
Severe Dengue
Fever
Hyperthermia

Study Results

Participant Flow

Recruitment Details The study was conducted at 6 active centers in 2 countries. A total of 1050 participants were enrolled from 02 May 2016 to 16 September 2016.
Pre-assignment Detail Participants were enrolled and randomized in 1:1:1 ratio to 1 of 3 treatment arms in STAGE-I. After STAGE-I, participants identified as seropositive at Baseline were randomized in ratio 1:1 to 1 of 2 subgroups (a [1a, 2a, 3a] or b [1b, 2b, 3b]) and received one CYD booster vaccine in STAGE-II at either 12 months (Subgroup a) or 24 months (Subgroup b) post last vaccination in STAGE-I. Here, 'M' in the period titles signifies months.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 milliliters (mL) subcutaneously (SC) at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at Baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Period Title: Stage-I(24M:12M Treatment+12M Follow-up)
STARTED 350 348 352 0 0 0 0 0 0
Vaccinated 348 348 352 0 0 0 0 0 0
Full Analysis Set (FAS) 333 328 332 0 0 0 0 0 0
COMPLETED 314 309 310 0 0 0 0 0 0
NOT COMPLETED 36 39 42 0 0 0 0 0 0
Period Title: Stage-I(24M:12M Treatment+12M Follow-up)
STARTED 0 0 0 145 152 157 149 152 151
Vaccinated 0 0 0 55 59 62 53 56 53
COMPLETED 0 0 0 55 59 62 53 54 52
NOT COMPLETED 0 0 0 90 93 95 96 98 99

Baseline Characteristics

Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) Total
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3). Total of all reporting groups
Overall Participants 350 348 352 1050
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
30.8
(14.42)
31.3
(14.47)
31.1
(14.62)
31.1
(14.49)
Sex: Female, Male (Count of Participants)
Female
190
54.3%
197
56.6%
185
52.6%
572
54.5%
Male
160
45.7%
151
43.4%
167
47.4%
478
45.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
171
48.9%
172
49.4%
169
48%
512
48.8%
Asian
174
49.7%
172
49.4%
177
50.3%
523
49.8%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
0
0%
Black or African American
5
1.4%
3
0.9%
6
1.7%
14
1.3%
White
0
0%
1
0.3%
0
0%
1
0.1%
More than one race
0
0%
0
0%
0
0%
0
0%
Unknown or Not Reported
0
0%
0
0%
0
0%
0
0%
Dengue Baseline Status (Count of Participants)
Seropositive participants
281
80.3%
288
82.8%
291
82.7%
860
81.9%
Seronegative participants
52
14.9%
40
11.5%
41
11.6%
133
12.7%
Undetermined
17
4.9%
20
5.7%
20
5.7%
57
5.4%

Outcome Measures

1. Primary Outcome
Title STAGE-I: Geometric Mean Titers (GMTs) Against Each Dengue Virus Serotype 28 Days After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using plaque reduction neutralization test (PRNT) assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline was defined as participants with titers >=10 (1/dilution) for at least 1 serotype with parental dengue virus strains. Per-protocol analysis set (PPAS) included all participants who had no protocol violations; and who met any of following study violations were excluded from PPAS (STAGE I/II): had not met all protocol-specified inclusion/exclusion criteria, had not received correct doses or injections, received vaccine other than randomized schedule, did not receive vaccination in proper time window, had not provided post-dose serology sample in proper time window, received protocol-restricted medication, therapy, or vaccine.
Time Frame 28 days after last CYD dengue vaccination

Outcome Measure Data

Analysis Population Description
Analysis performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Group 3, as pre-specified in protocol.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).
Measure Participants 265 272
Serotype 1
822
899
Serotype 2
875
869
Serotype 3
610
599
Serotype 4
531
510
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 1
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% confidence interval (CI) of the ratio of GMTs between groups (Group 2/Group 1) was greater than (>) 1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.09
Confidence Interval (2-Sided) 95%
0.862 to 1.39
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 2
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.993
Confidence Interval (2-Sided) 95%
0.820 to 1.20
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 3
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.983
Confidence Interval (2-Sided) 95%
0.816 to 1.18
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 4
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.960
Confidence Interval (2-Sided) 95%
0.809 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments
2. Primary Outcome
Title STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
Time Frame 1 year after last CYD dengue vaccination

Outcome Measure Data

Analysis Population Description
Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure. Data for this outcome measure was not planned to be collected and analyzed for Group 3, as pre-specified in protocol.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).
Measure Participants 185 190
Serotype 1
490
504
Serotype 2
821
737
Serotype 3
477
437
Serotype 4
270
238
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 1
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.757 to 1.40
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 2
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.897
Confidence Interval (2-Sided) 95%
0.705 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 3
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.917
Confidence Interval (2-Sided) 95%
0.724 to 1.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2/Group 1: Serotype 4
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.884
Confidence Interval (2-Sided) 95%
0.720 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments
3. Primary Outcome
Title STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1a (28 days 12 months Booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.
Time Frame Group 1: 28 days post-dose 3 in STAGE-I, Group 1a: 28 days post 12 months booster dose in STAGE-II

Outcome Measure Data

Analysis Population Description
Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure.
Arm/Group Title Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose
Arm/Group Description Participants who received 3 doses of CYD dengue vaccine in STAGE-I, and were seropositive at Baseline were assessed 28 days after third CYD vaccine in STAGE-I. Participants from Group 1 (STAGE-I) who were seropositive at Baseline and received a booster dose at 1 year (or 12 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.
Measure Participants 53 53
Serotype 1
853
483
Serotype 2
1186
884
Serotype 3
696
722
Serotype 4
592
383
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1a Booster/Group 1 Post-dose 3: Serotype 1
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 0.567
Confidence Interval (2-Sided) 98.75%
0.399 to 0.805
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1a Booster/Group 1 Post-dose 3: Serotype 2
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 0.746
Confidence Interval (2-Sided) 98.75%
0.550 to 1.01
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1a Booster/Group 1 Post-dose 3: Serotype 3
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 1.04
Confidence Interval (2-Sided) 98.75%
0.686 to 1.57
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1a Booster/Group 1 Post-dose 3: Serotype 4
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 0.647
Confidence Interval (2-Sided) 98.75%
0.434 to 0.963
Parameter Dispersion Type:
Value:
Estimation Comments
4. Primary Outcome
Title STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2a and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2a (28 days post 12 months Booster dose) were reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2a: 28 days post 12 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
Time Frame Group 1: 28 days post-dose 3 in STAGE-I, Group 2a: 28 days post 12 months booster dose in STAGE-II

Outcome Measure Data

Analysis Population Description
Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure.
Arm/Group Title Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose
Arm/Group Description Participants who received 3 doses of CYD dengue vaccine in STAGE-I, and were seropositive at Baseline were assessed 28 days after third CYD vaccine in STAGE-I. Participants from Group 2 (STAGE-I) who were seropositive at Baseline and received a booster dose at 1 year (or 12 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.
Measure Participants 112 58
Serotype 1
875
549
Serotype 2
1023
828
Serotype 3
568
676
Serotype 4
540
270
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2a Booster dose/Group 1 Post-dose 3: Serotype 1
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.627
Confidence Interval (2-Sided) 98.75%
0.342 to 1.15
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2a Booster/Group 1 Post-dose 3: Serotype 2
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.809
Confidence Interval (2-Sided) 98.75%
0.505 to 1.30
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2a Booster/Group 1 Post-dose 3: Serotype 3
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.19
Confidence Interval (2-Sided) 98.75%
0.732 to 1.94
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2a Booster/Group 1 Post-dose 3: Serotype 4
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided Bonferroni corrected 95% CI for the ratio of GMTs between groups (Group 2a Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.499
Confidence Interval (2-Sided) 98.75%
0.331 to 0.754
Parameter Dispersion Type:
Value:
Estimation Comments
5. Primary Outcome
Title STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Within Group 1b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 1b (28 days post 24 months booster dose) were reported and compared in this outcome measure. GMT paired ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 1b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days Post-dose 3 in STAGE-I.
Time Frame Group 1: 28 days post-dose 3 in STAGE-I, Group 1b: 28 days post 24 months booster dose in STAGE-II

Outcome Measure Data

Analysis Population Description
Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure.
Arm/Group Title Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose
Arm/Group Description Participants who received 3 doses of CYD dengue vaccine in STAGE-I, and were seropositive at Baseline were assessed 28 days after third CYD vaccine in STAGE-I. Participants from Group 1 (STAGE-I) who were seropositive at Baseline and received a booster dose at 2 years (or 24 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.
Measure Participants 48 48
Serotype 1
1017
700
Serotype 2
838
730
Serotype 3
486
559
Serotype 4
556
364
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1b Booster/Group 1 Post-dose 3: Serotype 1
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 0.688
Confidence Interval (2-Sided) 98.75%
0.479 to 0.989
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1b Booster/Group 1 Post-dose 3: Serotype 2
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 0.871
Confidence Interval (2-Sided) 98.75%
0.673 to 1.13
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1b Booster/Group 1 Post-dose 3: Serotype 3
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 1.15
Confidence Interval (2-Sided) 98.75%
0.887 to 1.49
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 1b Booster/Group 1 Post-dose 3: Serotype 4
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs within groups (Group 1b booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT paired ratio
Estimated Value 0.655
Confidence Interval (2-Sided) 98.75%
0.471 to 0.911
Parameter Dispersion Type:
Value:
Estimation Comments
6. Primary Outcome
Title STAGE-II: Geometric Mean Titers Against Each Dengue Virus Serotype Comparison Between Group 2b and Group 1 After the Third Dose of CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Data of Group 1 (28 days post-dose 3 in STAGE-I) and Group 2b (28 days post 24 months Booster dose) was reported and compared in this outcome measure. GMT ratio (given in statistical analysis section) was calculated by dividing geometric mean values of Group 2b: 28 days post 24 months booster dose in STAGE-II by Group 1: 28 days post-dose 3 in STAGE-I.
Time Frame Group 1: 28 days post-dose 3 in STAGE-I, Group 2b: 28 days post 24 months Booster dose in STAGE-II

Outcome Measure Data

Analysis Population Description
Analysis was performed on PPAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure.
Arm/Group Title Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose
Arm/Group Description Participants who received 3 doses of CYD dengue vaccine in STAGE-I, and were seropositive at Baseline were assessed 28 days after third CYD vaccine in STAGE-I. Participants from Group 1 (STAGE-I) who were seropositive at Baseline and received a booster dose at 2 years (or 24 months) post last dose in STAGE-I, were assessed 28 days after CYD dengue booster dose vaccination.
Measure Participants 112 50
Serotype 1
875
778
Serotype 2
1023
692
Serotype 3
568
517
Serotype 4
540
379
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2b Booster/Group 1 Post-dose 3: Serotype 1
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.889
Confidence Interval (2-Sided) 98.75%
0.462 to 1.71
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2b Booster/Group 1 Post-dose 3: Serotype 2
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.677
Confidence Interval (2-Sided) 98.75%
0.402 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2b Booster/Group 1 Post-dose 3: Serotype 3
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.911
Confidence Interval (2-Sided) 98.75%
0.573 to 1.45
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group 2b Booster/Group 1 Post-dose 3: Serotype 4
Type of Statistical Test Non-Inferiority
Comments The non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 2b Booster/Group 1) was >1/2. Overall non-inferiority was demonstrated if all 4 serotypes achieved non-inferiority.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT ratio
Estimated Value 0.702
Confidence Interval (2-Sided) 98.75%
0.447 to 1.10
Parameter Dispersion Type:
Value:
Estimation Comments
7. Secondary Outcome
Title STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline-Comparison Between Group 1 and Group 2
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
Time Frame 28 days and 1 year after last CYD dengue vaccination

Outcome Measure Data

Analysis Population Description
Analysis was performed on FAS population included participants who had received either at least 1 injection of CYD dengue vaccine or placebo; and had at least 1 blood sample drawn and valid post-injection serology results. Here,'Overall number of participant analyzed'=participants with available data for this outcome measure and 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3).
Measure Participants 281 288
28 days after last vaccination: Serotype 1
834
877
28 days after last vaccination: Serotype 2
879
870
28 days after last vaccination: Serotype 3
620
602
28 days after last vaccination: Serotype 4
527
507
1 year after last vaccination: Serotype 1
498
512
1 year after last vaccination: Serotype 2
815
747
1 year after last vaccination: Serotype 3
477
444
1 year after last vaccination: Serotype 4
263
241
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 1 (28 days after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.05
Confidence Interval (2-Sided) 95%
0.833 to 1.33
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 2 (28 days after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.99
Confidence Interval (2-Sided) 95%
0.821 to 1.19
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 3 (28 days after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.972
Confidence Interval (2-Sided) 95%
0.810 to 1.17
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 4 (28 days after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.963
Confidence Interval (2-Sided) 95%
0.814 to 1.14
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 1 (1 year after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.762 to 1.39
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 2 (1 year after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.917
Confidence Interval (2-Sided) 95%
0.724 to 1.16
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 3 (1 year after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.933
Confidence Interval (2-Sided) 95%
0.742 to 1.17
Parameter Dispersion Type:
Value:
Estimation Comments
Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection STAGE-I Group 1: CYD Dengue Vaccine, STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Comments Group2/Group1: Serotype 4 (1 year after last vaccination)
Type of Statistical Test Superiority
Comments The superiority was demonstrated if the lower limit of the two-sided 95% CI was greater than 1 between groups (Group 2/Group 1). Overall superiority of Group 2 to Group 1 was demonstrated if individual serotype null hypotheses were rejected.
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter GMT Ratio
Estimated Value 0.916
Confidence Interval (2-Sided) 95%
0.750 to 1.12
Parameter Dispersion Type:
Value:
Estimation Comments
8. Secondary Outcome
Title STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants
Description GMTs of antibodies against each of the 4 dengue virus serotypes (parental strains) were assessed using the PRNT assay method.
Time Frame Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

Outcome Measure Data

Analysis Population Description
Analysis was performed on FAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 333 328 332
Serotype 1: Baseline
131
187
198
Serotype 1: 28 days post vaccination 3
497
586
735
Serotype 1: 1 year post vaccination 3
259
279
331
Serotype 2: Baseline
172
202
181
Serotype 2: 28 days post vaccination 3
567
628
734
Serotype 2: 1 year post vaccination 3
470
457
500
Serotype 3: Baseline
163
180
169
Serotype 3: 28 days post vaccination 3
432
446
505
Serotype 3: 1 year post vaccination 3
294
288
258
Serotype 4: Baseline
86.7
83.8
81.2
Serotype 4: 28 days post vaccination 3
429
441
546
Serotype 4: 1 year post vaccination 3
203
192
177
9. Secondary Outcome
Title STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains (by Baseline Dengue Status) in Participants Who Were Seropositive and Seronegative at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3, or 4) were assessed using the PRNT assay method. Titers were measured in terms of 1/dilution. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Dengue seronegative participants at Baseline were defined as the participants with valid titer <0 (1/dilution) for all serotypes with parental dengue virus strains.
Time Frame Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

Outcome Measure Data

Analysis Population Description
Analysis was performed on FAS. 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 STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 281 288 291
Seropositive- Serotype 1: Baseline
239
304
328
Seropositive- Serotype 1: 28 days post vaccination 3
834
877
1201
Seropositive- Serotype 1: 1 year post vaccination 3
498
512
618
Seropositive- Serotype 2: Baseline
331
326
293
Seropositive- Serotype 2: 28 days post vaccination 3
879
870
1046
Seropositive- Serotype 2: 1 year post vaccination 3
815
747
798
Seropositive- Serotype 3: Baseline
310
290
269
Seropositive- Serotype 3: 28 days post vaccination 3
620
602
694
Seropositive- Serotype 3: 1 year post vaccination 3
477
444
390
Seropositive- Serotype 4: Baseline
147
123
118
Seropositive- Serotype 4: 28 days post vaccination 3
527
507
581
Seropositive- Serotype 4: 1 year post vaccination 3
263
241
227
Seronegative- Serotype 1: Baseline
5.00
5.57
5.49
Seronegative- Serotype 1: 28 days post vaccination 3
32.4
34.3
20.2
Seronegative- Serotype 1: 1 year post vaccination 3
10.4
9.01
8.04
Seronegative- Serotype 2: Baseline
5.00
6.47
5.86
Seronegative- Serotype 2: 28 days post vaccination 3
56.2
63.0
55.2
Seronegative- Serotype 2: 1 year post vaccination 3
31.3
28.7
30.9
Seronegative- Serotype 3: Baseline
5.00
5.69
6.09
Seronegative- Serotype 3: 28 days post vaccination 3
64.2
53.7
49.5
Seronegative- Serotype 3: 1 year post injection 3
27.5
25.3
21.8
Seronegative- Serotype 4: Baseline
5.00
5.41
5.64
Seronegative- Serotype 4: 28 days post vaccination 3
145
164
349
Seronegative- Serotype 4: 1 year post vaccination 3
57.1
53.8
40.8
10. Secondary Outcome
Title STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Participants Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotype (1, 2, 3, or 4) were assessed using the PRNT assay. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains. Titers were measured in terms of 1/dilution.
Time Frame Baseline, 28 days post vaccination-3, and 28 days post booster dose

Outcome Measure Data

Analysis Population Description
Analysis was performed on FAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure and 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Measure Participants 141 144 147 140 144 144
Serotype 1: Baseline
246
283
309
231
327
350
Serotype 1: 28 days post vaccination 3
828
933
1111
840
824
1301
Serotype 1 : 28 days post booster dose
505
552
861
707
749
1199
Serotype 2 : Baseline
370
335
283
296
318
303
Serotype 2 : 28 days post vaccination 3
986
897
1018
783
844
1077
Serotype 2 : 28 days post booster dose
856
858
867
813
655
967
Serotype 3 : Baseline
363
399
287
266
210
253
Serotype 3: 28 days post vaccination 3
733
659
725
524
551
663
Serotype 3:28 days post booster dose
721
667
743
586
477
506
Serotype 4: Baseline
147
142
115
147
106
122
Serotype 4:28 day post vaccination 3
512
536
570
543
480
593
Serotype 4 : 28 days post booster dose
380
265
300
368
360
413
11. Secondary Outcome
Title STAGE-I: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Participants
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay.
Time Frame Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

Outcome Measure Data

Analysis Population Description
Analysis was performed on FAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 333 328 332
Serotype 1: Baseline
77.8
22.2%
80.5
23.1%
83.4
23.7%
Serotype 1: 28 days post vaccination 3
96.3
27.5%
97.2
27.9%
94.1
26.7%
Serotype 1: 1 year post vaccination 3
88.3
25.2%
87.5
25.1%
88.3
25.1%
Serotype 2: Baseline
82.6
23.6%
83.8
24.1%
85.2
24.2%
Serotype 2: 28 days post vaccination 3
98.2
28.1%
96.6
27.8%
96.0
27.3%
Serotype 2: 1 year post vaccination 3
95.7
27.3%
94.4
27.1%
94.8
26.9%
Serotype 3: Baseline
82.6
23.6%
84.1
24.2%
87.0
24.7%
Serotype 3: 28 days post vaccination 3
98.5
28.1%
98.1
28.2%
97.5
27.7%
Serotype 3: 1 year post vaccination 3
95.7
27.3%
95.7
27.5%
94.3
26.8%
Serotype 4: Baseline
79.6
22.7%
81.4
23.4%
81.6
23.2%
Serotype 4: 28 days post vaccination 3
99.7
28.5%
99.4
28.6%
98.8
28.1%
Serotype 4: 1 year post vaccination 3
99.1
28.3%
96.6
27.8%
95.7
27.2%
12. Secondary Outcome
Title STAGE-II: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Participants Seropositive at Baseline
Description GMTs of antibodies against each of the 4 dengue virus serotypes (1, 2, 3 or 4) were assessed using the PRNT assay method. Dengue seropositive participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strains.
Time Frame Baseline, 28 days post vaccination 3, and 1 year post vaccination 3

Outcome Measure Data

Analysis Population Description
Analysis was performed on FAS. Here, 'Overall number of participant analyzed'=participants with available data for this outcome measure and 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Measure Participants 141 144 147 140 144 144
Serotype 1: Baseline
92.2
26.3%
90.3
25.9%
91.8
26.1%
92.1
8.8%
91.7
NaN
97.2
NaN
Serotype 1: 28 days post vaccination 3
100.0
28.6%
99.3
28.5%
100.0
28.4%
99.3
9.5%
99.3
NaN
100.0
NaN
Serotype 1 : 1 year post vaccination 3
100.0
28.6%
99.3
28.5%
99.3
28.2%
100.0
9.5%
96.9
NaN
98.5
NaN
Serotype 2: Baseline
99.3
28.4%
94.4
27.1%
94.6
26.9%
96.4
9.2%
94.4
NaN
97.2
NaN
Serotype 2 : 28 days post vaccination 3
100.0
28.6%
99.3
28.5%
100.0
28.4%
100.0
9.5%
99.3
NaN
100.0
NaN
Serotype 2 : 1 year post vaccination 3
100.0
28.6%
99.3
28.5%
100.0
28.4%
100.0
9.5%
98.5
NaN
100.0
NaN
Serotype 3: Baseline
98.6
28.2%
96.5
27.7%
95.2
27%
97.1
9.2%
93.1
NaN
100.0
NaN
Serotype 3: 28 days post vaccination
100.0
28.6%
100.0
28.7%
100.0
28.4%
99.3
9.5%
100.0
NaN
100.0
NaN
Serotype 3 : 1 year post vaccination 3
100.0
28.6%
99.3
28.5%
99.3
28.2%
100.0
9.5%
100.0
NaN
100.0
NaN
Serotype 4: Baseline
93.6
26.7%
93.1
26.8%
89.8
25.5%
95.0
9%
91.7
NaN
94.4
NaN
Serotype 4: 28 days post vaccination 3
100.0
28.6%
100.0
28.7%
100.0
28.4%
100.0
9.5%
100.0
NaN
100.0
NaN
Serotype 4: 1 year post vaccination 3
100.0
28.6%
99.3
28.5%
98.6
28%
100.0
9.5%
98.5
NaN
100.0
NaN
13. Secondary Outcome
Title STAGE-I: Number of Participants With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
Description An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the electronic case report form (eCRF) in terms of diagnosis and/or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after any vaccination.
Time Frame Within 30 minutes after any vaccination (1, 2, or 3)

Outcome Measure Data

Analysis Population Description
Analysis was performed on safety analysis set (SafAS) that included participants who had received at least one injection of either CYD dengue vaccine or placebo.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 348 348 352
Count of Participants [Participants]
0
0%
3
0.9%
0
0%
14. Secondary Outcome
Title STAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
Description An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and / or onset post-vaccination. Immediate unsolicited AE were AEs that occurred within 30 minutes after vaccination.
Time Frame Within 30 minutes after CYD booster vaccination

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS.
Arm/Group Title STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Measure Participants 55 59 62 53 56 53
Count of Participants [Participants]
0
0%
0
0%
0
0%
0
0%
0
NaN
0
NaN
15. Secondary Outcome
Title STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
Description Adverse reaction (AR) was defined as all noxious and unintended responses to a medicinal product related to any dose. A Solicited Reaction (SR) was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.
Time Frame Within 7 days after any vaccination (1, 2, or 3)

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 347 347 352
Pain
109
31.1%
114
32.8%
97
27.6%
Erythema
4
1.1%
3
0.9%
3
0.9%
Swelling
2
0.6%
5
1.4%
5
1.4%
16. Secondary Outcome
Title STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
Description AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.
Time Frame Within 7 days after each vaccination (1, 2, and 3)

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 347 347 352
Post-vaccination 1: Pain
61
17.4%
61
17.5%
61
17.3%
Post-vaccination 1: Erythema
3
0.9%
3
0.9%
2
0.6%
Post vaccination 1: Swelling
0
0%
2
0.6%
2
0.6%
Post-vaccination 2: Pain
50
14.3%
53
15.2%
50
14.2%
Post-vaccination 2: Erythema
1
0.3%
0
0%
1
0.3%
Post-vaccination 2: Swelling
1
0.3%
1
0.3%
2
0.6%
Post-vaccination 3: Pain
43
12.3%
49
14.1%
35
9.9%
Post-vaccination 3: Erythema
0
0%
0
0%
1
0.3%
Post-vaccination 3: Swelling
1
0.3%
2
0.6%
2
0.6%
17. Secondary Outcome
Title STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
Description An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. An SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Systemic AEs were all AEs that were not injection site reactions. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.
Time Frame Within 14 days after any vaccination (1, 2, or 3)

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 347 347 352
Fever
29
8.3%
21
6%
31
8.8%
Headache
129
36.9%
122
35.1%
124
35.2%
Malaise
114
32.6%
98
28.2%
102
29%
Myalgia
110
31.4%
92
26.4%
86
24.4%
Asthenia
98
28%
80
23%
71
20.2%
18. Secondary Outcome
Title STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
Description An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.
Time Frame Within 14 days after each vaccination (1, 2, and 3)

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 347 347 352
Post-vaccination 1: Fever
10
2.9%
8
2.3%
13
3.7%
Post-vaccination 1: Headache
90
25.7%
83
23.9%
84
23.9%
Post-vaccination 1: Malaise
74
21.1%
60
17.2%
61
17.3%
Post-vaccination 1: Myalgia
67
19.1%
55
15.8%
48
13.6%
Post-vaccination 1: Asthenia
63
18%
52
14.9%
45
12.8%
Post-vaccination 2: Fever
12
3.4%
7
2%
12
3.4%
Post-vaccination 2: Headache
54
15.4%
55
15.8%
53
15.1%
Post-vaccination 2: Malaise
50
14.3%
44
12.6%
47
13.4%
Post-vaccination 2: Myalgia
49
14%
33
9.5%
35
9.9%
Post-vaccination 2: Asthenia
40
11.4%
30
8.6%
33
9.4%
Post-vaccination 3: Fever
9
2.6%
8
2.3%
9
2.6%
Post-vaccination 3: Headache
55
15.7%
47
13.5%
47
13.4%
Post-vaccination 3: Malaise
46
13.1%
41
11.8%
39
11.1%
Post-vaccination 3: Myalgia
26
7.4%
37
10.6%
28
8%
Post-vaccination 3: Asthenia
29
8.3%
32
9.2%
21
6%
19. Secondary Outcome
Title STAGE-II: Number of Participants With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine
Description An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited injection site reaction was an AR at and around the injection site that included pain, erythema, and swelling.
Time Frame Within 7 days after CYD booster vaccination

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Measure Participants 55 59 62 53 54 52
Pain
6
1.7%
7
2%
11
3.1%
7
0.7%
12
NaN
10
NaN
Erythema
0
0%
0
0%
0
0%
0
0%
1
NaN
0
NaN
Swelling
0
0%
0
0%
0
0%
0
0%
1
NaN
1
NaN
20. Secondary Outcome
Title STAGE-II: Number of Participants With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine
Description An AR was defined as all noxious and unintended responses to a medicinal product related to any dose. A SR was defined as an AR observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the eCRF and considered as related to vaccination. Solicited systemic reactions included fever, headache, malaise, myalgia, and asthenia.
Time Frame Within 14 days after CYD booster vaccination

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS. Here, 'Number analyzed'=participants with available data for each specified category.
Arm/Group Title STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Measure Participants 55 59 62 53 54 52
Fever
1
0.3%
0
0%
1
0.3%
2
0.2%
2
NaN
0
NaN
Headache
5
1.4%
11
3.2%
6
1.7%
7
0.7%
11
NaN
7
NaN
Malaise
5
1.4%
9
2.6%
7
2%
7
0.7%
9
NaN
5
NaN
Myalgia
5
1.4%
8
2.3%
9
2.6%
9
0.9%
12
NaN
6
NaN
Asthenia
4
1.1%
6
1.7%
6
1.7%
7
0.7%
9
NaN
3
NaN
21. Secondary Outcome
Title STAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo
Description An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that did not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination.
Time Frame Within 28 days after any vaccination (1, 2, or 3)

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 348 348 352
Count of Participants [Participants]
73
20.9%
94
27%
75
21.3%
22. Secondary Outcome
Title STAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
Description An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An unsolicited AE was an observed AE that does not fulfill the conditions prelisted in the eCRF in terms of diagnosis and/or onset post-vaccination.
Time Frame Within 28 days after CYD booster Vaccination

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS.
Arm/Group Title STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Measure Participants 55 59 62 53 56 53
Count of Participants [Participants]
1
0.3%
3
0.9%
5
1.4%
3
0.3%
2
NaN
4
NaN
23. Secondary Outcome
Title STAGE-I: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Event of Special Interests (AESI) Following Vaccination With CYD Dengue Vaccine or Placebo
Description An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.
Time Frame From Day 0 (post vaccination) up to 12 months after last vaccination in STAGE-I (i.e., up to 24 months)

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3).
Measure Participants 348 348 352
SAE
14
4%
26
7.5%
18
5.1%
Serious AESI
0
0%
0
0%
0
0%
24. Secondary Outcome
Title STAGE-II: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine
Description An AE was defined as any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An SAE was any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was congenital anomaly/birth defect, or was an important medical event. AESI were AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.
Time Frame From Month 25 up to 6 months after CYD booster injection (either at 1 year or 2 year) (i.e., up to 30 months for Groups 1a, 2a, and 3a and up to 42 months for Groups 1b, 2b, and 3b)

Outcome Measure Data

Analysis Population Description
Analysis was performed on SafAS.
Arm/Group Title STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants from Group 1 who received vaccination in STAGE-I; and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e., at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e., at Month 36).
Measure Participants 55 59 62 53 56 53
SAE
3
0.9%
0
0%
2
0.6%
2
0.2%
0
NaN
1
NaN
Serious AESI
0
0%
0
0%
0
0%
0
0%
0
NaN
0
NaN

Adverse Events

Time Frame Unsolicited non-serious AEs: Day 0 to Day 28 post any vaccination SR: within 7 & 14 days post any vaccination; SAE: up to 24 months for STAGE-I); up to 6 months after last vaccination for Stage-2 (i.e., up to 30 months [for Groups 1a, 2a, and 3a]; & up to 42 months [for Groups 1b, 2b, and 3b])
Adverse Event Reporting Description Analysis was performed on SafAS. SR was AE that was prelisted (i.e., solicited) in the eCRF and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination. Reported AEs were presented as pre-specified in the study protocol.
Arm/Group Title STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Arm/Group Description Participants received 3 doses of CYD dengue vaccine 0.5 mL SC at Day 0 (Vaccination 1), Month 6 (Vaccination 2), and Month 12 (Vaccination 3). Participants received a dose of placebo at Day 0 (Vaccination 1) along with 2 doses of CYD dengue vaccine 0.5 mL SC at Month 6 (Vaccination 2) and Month 12 (Vaccination 3). Participants received 2 doses of placebo at Day 0 (Vaccination 1) and Month 6 (Vaccination 2) along with a dose of CYD dengue vaccine 0.5 mL SC at Month 12 (Vaccination 3). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at Baseline received a booster dose of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e. at Month 24). Participants from Group 1 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e. at Month 36). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e. at Month 24). Participants from Group 2 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e. at Month 36). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 1 year post last dose in STAGE-I (i.e. at Month 24). Participants from Group 3 who received vaccination in STAGE-I and were seropositive at baseline received a booster injection of CYD dengue vaccine in STAGE-II at 2 years post last dose in STAGE-I (i.e. at Month 36).
All Cause Mortality
STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/348 (0%) 1/348 (0.3%) 1/352 (0.3%) 0/55 (0%) 0/53 (0%) 0/59 (0%) 0/56 (0%) 0/62 (0%) 0/53 (0%)
Serious Adverse Events
STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 14/348 (4%) 26/348 (7.5%) 18/352 (5.1%) 3/55 (5.5%) 2/53 (3.8%) 0/59 (0%) 0/56 (0%) 2/62 (3.2%) 1/53 (1.9%)
Cardiac disorders
Myocardial Infarction 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Congenital, familial and genetic disorders
Branchial Cyst 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Endocrine disorders
Thyroid Cyst 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Gastrointestinal disorders
Food Poisoning 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Immune system disorders
Food Allergy 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Infections and infestations
Appendicitis 1/348 (0.3%) 1 4/348 (1.1%) 4 3/352 (0.9%) 3 1/55 (1.8%) 1 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 1/53 (1.9%) 1
Cellulitis 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Diarrhoea Infectious 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Gastroenteritis 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Groin Abscess 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Hepatitis A 0/348 (0%) 0 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 1/62 (1.6%) 1 0/53 (0%) 0
Orchitis 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Pneumonia 0/348 (0%) 0 1/348 (0.3%) 1 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Pneumonia Staphylococcal 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Urinary Tract Infection 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 1/53 (1.9%) 1 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Viral Infection 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Injury, poisoning and procedural complications
Animal Bite 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Forearm Fracture 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 1/62 (1.6%) 1 0/53 (0%) 0
Gun Shot Wound 1/348 (0.3%) 1 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Head Injury 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Jaw Fracture 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Radius Fracture 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Road Traffic Accident 0/348 (0%) 0 1/348 (0.3%) 1 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Thermal Burn 0/348 (0%) 0 0/348 (0%) 0 0/352 (0%) 0 1/55 (1.8%) 1 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Metabolism and nutrition disorders
Hypokalaemia 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Musculoskeletal and connective tissue disorders
Back Pain 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Intervertebral Disc Degeneration 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Pathological Fracture 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Rheumatoid Arthritis 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Papillary Thyroid Cancer 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Nervous system disorders
Headache 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Migraine 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Seizure 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Subarachnoid Haemorrhage 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Syncope 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 1/53 (1.9%) 1 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Pregnancy, puerperium and perinatal conditions
Abortion Spontaneous 2/348 (0.6%) 2 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Abortion Spontaneous Incomplete 0/348 (0%) 0 1/348 (0.3%) 1 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Threatened Labour 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Psychiatric disorders
Confusional State 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Renal and urinary disorders
Calculus Urinary 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Nephrolithiasis 0/348 (0%) 0 0/348 (0%) 0 1/352 (0.3%) 1 1/55 (1.8%) 1 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Renal Colic 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Reproductive system and breast disorders
Adenomyosis 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Bartholin's Cyst 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Dysfunctional Uterine Bleeding 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Uterine Polyp 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Pleural Effusion 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Skin and subcutaneous tissue disorders
Toxic Skin Eruption 1/348 (0.3%) 1 0/348 (0%) 0 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Vascular disorders
Arteriosclerosis 0/348 (0%) 0 1/348 (0.3%) 1 0/352 (0%) 0 0/55 (0%) 0 0/53 (0%) 0 0/59 (0%) 0 0/56 (0%) 0 0/62 (0%) 0 0/53 (0%) 0
Other (Not Including Serious) Adverse Events
STAGE-I Group 1: CYD Dengue Vaccine STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12) STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year) STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years) STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years) STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year) STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 203/348 (58.3%) 189/348 (54.3%) 182/352 (51.7%) 10/55 (18.2%) 13/53 (24.5%) 15/59 (25.4%) 20/56 (35.7%) 18/62 (29%) 15/53 (28.3%)
General disorders
Asthenia 98/348 (28.2%) 133 80/348 (23%) 114 71/352 (20.2%) 100 4/55 (7.3%) 4 7/53 (13.2%) 7 6/59 (10.2%) 6 9/56 (16.1%) 9 6/62 (9.7%) 6 3/53 (5.7%) 3
Fever 29/348 (8.3%) 31 21/348 (6%) 23 31/352 (8.8%) 34 1/55 (1.8%) 1 2/53 (3.8%) 2 0/59 (0%) 0 2/56 (3.6%) 2 1/62 (1.6%) 1 0/53 (0%) 0
Injection Site Pain 109/348 (31.3%) 154 114/348 (32.8%) 164 97/352 (27.6%) 146 6/55 (10.9%) 6 7/53 (13.2%) 7 7/59 (11.9%) 7 12/56 (21.4%) 12 11/62 (17.7%) 11 10/53 (18.9%) 10
Malaise 114/348 (32.8%) 170 98/348 (28.2%) 146 103/352 (29.3%) 148 5/55 (9.1%) 5 7/53 (13.2%) 7 9/59 (15.3%) 9 9/56 (16.1%) 9 7/62 (11.3%) 7 5/53 (9.4%) 5
Musculoskeletal and connective tissue disorders
Myalgia 110/348 (31.6%) 143 92/348 (26.4%) 126 87/352 (24.7%) 112 5/55 (9.1%) 5 9/53 (17%) 9 8/59 (13.6%) 8 12/56 (21.4%) 12 9/62 (14.5%) 9 6/53 (11.3%) 6
Nervous system disorders
Headache 129/348 (37.1%) 201 123/348 (35.3%) 190 124/352 (35.2%) 184 5/55 (9.1%) 5 7/53 (13.2%) 7 11/59 (18.6%) 11 12/56 (21.4%) 12 7/62 (11.3%) 7 7/53 (13.2%) 7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

The 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 Trial Transparency Team
Organization Sanofi Pasteur
Phone 800-633-1610 ext 1#
Email Contact-US@sanofi.com
Responsible Party:
Sanofi Pasteur, a Sanofi Company
ClinicalTrials.gov Identifier:
NCT02628444
Other Study ID Numbers:
  • CYD65
  • U1111-1161-3242
  • 2020-002854-25
First Posted:
Dec 11, 2015
Last Update Posted:
Mar 24, 2022
Last Verified:
Mar 1, 2022