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CompletedNCT02628444Updated Mar 24, 2022Results posted

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

A Phase 2 interventional study of CYD Dengue Vaccine and Placebo (Sodium chloride 0.9%) in Dengue Fever and Dengue Hemorrhagic Fever, sponsored by Sanofi Pasteur, a Sanofi Company. Completed at 6 sites in 2 countries. Open to participants aged 9 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2022-03-24.

Sponsored by Sanofi Pasteur, a Sanofi Company · Phase 2, Interventional, and Prevention

Phase
Phase 2
Study type
Interventional
Enrollment
1,050
Allocation
Randomized
Ages
9 Years to 50 Years
Sex
All
01

Study 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.
Read the 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 a) 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.

02

Conditions studied

  • Dengue Fever
  • Dengue Hemorrhagic Fever

Keywords

  • Dengue Fever
  • Dengue virus
  • Dengue Hemorrhagic Fever
  • CYD Dengue Vaccine
03

In context

Dengue

279 studies on the registry are indexed under Dengue; 45 are open to participants now.

This study's enrollment of 1,050 is above the median of 123 across 195 interventional studies indexed under Dengue.

Browse Dengue studies →

Lead sponsor

Sanofi Pasteur, a Sanofi Company is the lead sponsor of 366 studies on the registry; 4 are open to participants now.

Of its 94 completed or terminated interventional studies of FDA-regulated products, 73 (78%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
9 Years to 50 Years
Sexes eligible
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

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.
05

Study design

Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
1,050 participants (actual)

Study arms

  • 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

  • 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 · Biological: Placebo (Sodium chloride 0.9%)

  • 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 · Biological: Placebo (Sodium chloride 0.9%)

  • 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

  • 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 · Biological: Placebo (Sodium chloride 0.9%)

  • 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 · Biological: Placebo (Sodium chloride 0.9%)

  • 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

  • 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 · Biological: Placebo (Sodium chloride 0.9%)

  • 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 · Biological: Placebo (Sodium chloride 0.9%)

Interventions

  • BiologicalCYD Dengue Vaccine

    0.5 mL, Subcutaneous

  • BiologicalPlacebo (Sodium chloride 0.9%)

    0.5 mL, Subcutaneous

06

What researchers measure

Primary outcomes

  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

    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

  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

    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

  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

    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

  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

    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

  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

    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

  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

    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

Secondary outcomes

  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

    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

  2. STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants

    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

  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

    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

  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

    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

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

    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

  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

    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

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

  8. STAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine

    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

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

    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)

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

    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)

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

    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)

  12. STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each 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.

    Time frame: Within 14 days after each vaccination (1, 2, and 3)

  13. STAGE-II: Number of Participants With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine

    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

  14. STAGE-II: Number of Participants With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine

    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

  15. STAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo

    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)

  16. STAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine

    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

  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

    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)

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

    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)

07

Results

Posted Feb 23, 2021

Participant flow

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.

Stage-I(24M:12M Treatment+12M Follow-up)
Participant flow — Stage-I(24M:12M Treatment+12M Follow-up)
MilestoneSTAGE-I Group 1: CYD Dengue VaccineSTAGE-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)
Started350348352000000
Vaccinated348348352000000
Full analysis set (fas)333328332000000
Completed314309310000000
Not completed363942000000
Withdrew: Adverse event (ae) intensity less than (<) grade 1100000000
Withdrew: Serious ae (sae)043000000
Withdrew: Voluntary withdrawal not due to ae211625000000
Withdrew: Non-compliance with protocol9169000000
Withdrew: Lost to follow-up535000000
STAGE-II(18M:12M Treatment+6M Follow-up)
Participant flow — STAGE-II(18M:12M Treatment+6M Follow-up)
MilestoneSTAGE-I Group 1: CYD Dengue VaccineSTAGE-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)
Started000145152157149152151
Vaccinated000555962535653
Completed000555962535452
Not completed000909395969899
Withdrew: Other ae000100000
Withdrew: Non-compliance with protocol000838383818485
Withdrew: Voluntary withdrawal not due to ae000561012119
Withdrew: Sae000030023
Withdrew: Lost to follow-up000112312

Outcome measures

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

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
Reported as:
Geometric mean · titers
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
titersSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Serotype 1822 (700 to 964)899 (752 to 1075)
Serotype 2875 (770 to 995)869 (754 to 1002)
Serotype 3610 (535 to 694)599 (524 to 685)
Serotype 4531 (470 to 601)510 (453 to 575)
Statistical analysis
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 1.09 · 95% CI 0.862 to 1.39
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.993 · 95% CI 0.820 to 1.20
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.983 · 95% CI 0.816 to 1.18
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.960 · 95% CI 0.809 to 1.14
PrimarySTAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline

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
Reported as:
Geometric mean · titers
STAGE-I: Geometric Mean Titers Against Each Dengue Virus Serotype 1 Year After Last CYD Dengue Vaccination in Participants Who Were Seropositive at Baseline
titersSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
Serotype 1490 (398 to 604)504 (403 to 630)
Serotype 2821 (704 to 957)737 (611 to 888)
Serotype 3477 (405 to 561)437 (368 to 519)
Serotype 4270 (235 to 310)238 (205 to 277)
Statistical analysis
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 1.03 · 95% CI 0.757 to 1.40
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.897 · 95% CI 0.705 to 1.14
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.917 · 95% CI 0.724 to 1.16
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.884 · 95% CI 0.720 to 1.09
PrimarySTAGE-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

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
Reported as:
Geometric mean · titers
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
titersGroup 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-IGroup 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose
Serotype 1853 (526 to 1384)483 (281 to 832)
Serotype 21186 (809 to 1738)884 (602 to 1300)
Serotype 3696 (483 to 1002)722 (458 to 1140)
Serotype 4592 (400 to 876)383 (269 to 545)
Statistical analysis
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose · Gmt paired ratio: 0.567 · 98.75% CI 0.399 to 0.805
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose · Gmt paired ratio: 0.746 · 98.75% CI 0.550 to 1.01
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose · Gmt paired ratio: 1.04 · 98.75% CI 0.686 to 1.57
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1a: CYD Dengue Vaccine-28 Days Post 12 Month Booster Dose · Gmt paired ratio: 0.647 · 98.75% CI 0.434 to 0.963
PrimarySTAGE-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

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
Reported as:
Geometric mean · titers
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
titersGroup 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-IGroup 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose
Serotype 1875 (614 to 1248)549 (331 to 911)
Serotype 21023 (771 to 1356)828 (569 to 1203)
Serotype 3568 (433 to 745)676 (436 to 1049)
Serotype 4540 (418 to 697)270 (200 to 364)
Statistical analysis
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose · Gmt ratio: 0.627 · 98.75% CI 0.342 to 1.15
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose · Gmt ratio: 0.809 · 98.75% CI 0.505 to 1.30
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose · Gmt ratio: 1.19 · 98.75% CI 0.732 to 1.94
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2a: CYD Dengue Vaccine-28 Days Post 12 Months Booster Dose · Gmt ratio: 0.499 · 98.75% CI 0.331 to 0.754
PrimarySTAGE-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

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
Reported as:
Geometric mean · titers
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
titersGroup 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-IGroup 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose
Serotype 11017 (592 to 1746)700 (401 to 1220)
Serotype 2838 (554 to 1269)730 (497 to 1071)
Serotype 3486 (333 to 708)559 (395 to 792)
Serotype 4556 (400 to 774)364 (260 to 510)
Statistical analysis
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt paired ratio: 0.688 · 98.75% CI 0.479 to 0.989
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt paired ratio: 0.871 · 98.75% CI 0.673 to 1.13
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt paired ratio: 1.15 · 98.75% CI 0.887 to 1.49
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 1b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt paired ratio: 0.655 · 98.75% CI 0.471 to 0.911
PrimarySTAGE-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

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
Reported as:
Geometric mean · titers
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
titersGroup 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-IGroup 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose
Serotype 1875 (614 to 1248)778 (429 to 1414)
Serotype 21023 (771 to 1356)692 (430 to 1116)
Serotype 3568 (433 to 745)517 (365 to 733)
Serotype 4540 (418 to 697)379 (261 to 551)
Statistical analysis
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt ratio: 0.889 · 98.75% CI 0.462 to 1.71
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt ratio: 0.677 · 98.75% CI 0.402 to 1.14
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt ratio: 0.911 · 98.75% CI 0.573 to 1.45
  • Group 1: CYD Dengue Vaccine-28 Days Post-dose 3 in STAGE-I vs Group 2b: CYD Dengue Vaccine-28 Days Post 24 Month Booster Dose · Gmt ratio: 0.702 · 98.75% CI 0.447 to 1.10
SecondarySTAGE-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

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
Reported as:
Geometric mean · titers
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
titersSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)
28 days after last vaccination: Serotype 1834 (713 to 975)877 (737 to 1043)
28 days after last vaccination: Serotype 2879 (775 to 997)870 (758 to 1000)
28 days after last vaccination: Serotype 3620 (545 to 704)602 (529 to 686)
28 days after last vaccination: Serotype 4527 (467 to 595)507 (451 to 570)
1 year after last vaccination: Serotype 1498 (406 to 611)512 (411 to 638)
1 year after last vaccination: Serotype 2815 (702 to 947)747 (622 to 897)
1 year after last vaccination: Serotype 3477 (407 to 558)444 (376 to 525)
1 year after last vaccination: Serotype 4263 (230 to 302)241 (208 to 279)
Statistical analysis
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 1.05 · 95% CI 0.833 to 1.33
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.99 · 95% CI 0.821 to 1.19
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.972 · 95% CI 0.810 to 1.17
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.963 · 95% CI 0.814 to 1.14
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 1.03 · 95% CI 0.762 to 1.39
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.917 · 95% CI 0.724 to 1.16
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.933 · 95% CI 0.742 to 1.17
  • STAGE-I Group 1: CYD Dengue Vaccine vs STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12) · Gmt ratio: 0.916 · 95% CI 0.750 to 1.12
SecondarySTAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants

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
Reported as:
Geometric mean · titers
STAGE-I: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains in All Participants
titersSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Serotype 1: Baseline131 (103 to 165)187 (147 to 237)198 (157 to 250)
Serotype 1: 28 days post vaccination 3497 (410 to 602)586 (482 to 714)735 (589 to 916)
Serotype 1: 1 year post vaccination 3259 (200 to 336)279 (213 to 365)331 (252 to 435)
Serotype 2: Baseline172 (138 to 214)202 (163 to 252)181 (147 to 222)
Serotype 2: 28 days post vaccination 3567 (482 to 666)628 (532 to 741)734 (614 to 878)
Serotype 2: 1 year post vaccination 3470 (380 to 582)457 (364 to 574)500 (402 to 623)
Serotype 3: Baseline163 (131 to 202)180 (145 to 222)169 (138 to 207)
Serotype 3: 28 days post vaccination 3432 (373 to 500)446 (383 to 519)505 (428 to 595)
Serotype 3: 1 year post vaccination 3294 (240 to 361)288 (235 to 354)258 (213 to 312)
Serotype 4: Baseline86.7 (71.4 to 105)83.8 (69.9 to 100)81.2 (67.7 to 97.4)
Serotype 4: 28 days post vaccination 3429 (380 to 484)441 (392 to 496)546 (475 to 629)
Serotype 4: 1 year post vaccination 3203 (176 to 235)192 (164 to 226)177 (150 to 210)
SecondarySTAGE-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

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
Reported as:
Geometric mean · titers
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
titersSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Seropositive- Serotype 1: Baseline239 (194 to 295)304 (244 to 379)328 (267 to 404)
Seropositive- Serotype 1: 28 days post vaccination 3834 (713 to 975)877 (737 to 1043)1201 (1007 to 1431)
Seropositive- Serotype 1: 1 year post vaccination 3498 (406 to 611)512 (411 to 638)618 (500 to 764)
Seropositive- Serotype 2: Baseline331 (279 to 394)326 (271 to 393)293 (247 to 347)
Seropositive- Serotype 2: 28 days post vaccination 3879 (775 to 997)870 (758 to 1000)1046 (912 to 1201)
Seropositive- Serotype 2: 1 year post vaccination 3815 (702 to 947)747 (622 to 897)798 (676 to 942)
Seropositive- Serotype 3: Baseline310 (263 to 367)290 (241 to 349)269 (227 to 319)
Seropositive- Serotype 3: 28 days post vaccination 3620 (545 to 704)602 (529 to 686)694 (604 to 797)
Seropositive- Serotype 3: 1 year post vaccination 3477 (407 to 558)444 (376 to 525)390 (338 to 450)
Seropositive- Serotype 4: Baseline147 (124 to 174)123 (104 to 144)118 (100 to 140)
Seropositive- Serotype 4: 28 days post vaccination 3527 (467 to 595)507 (451 to 570)581 (507 to 666)
Seropositive- Serotype 4: 1 year post vaccination 3263 (230 to 302)241 (208 to 279)227 (194 to 265)
Seronegative- Serotype 1: Baseline5.00 (NA to NA)5.57 (4.65 to 6.67)5.49 (4.75 to 6.34)
Seronegative- Serotype 1: 28 days post vaccination 332.4 (23.1 to 45.6)34.3 (23.8 to 49.4)20.2 (12.0 to 34.1)
Seronegative- Serotype 1: 1 year post vaccination 310.4 (7.12 to 15.1)9.01 (6.30 to 12.9)8.04 (5.86 to 11.0)
Seronegative- Serotype 2: Baseline5.00 (NA to NA)6.47 (4.43 to 9.45)5.86 (4.99 to 6.89)
Seronegative- Serotype 2: 28 days post vaccination 356.2 (40.1 to 78.7)63.0 (37.5 to 106)55.2 (27.8 to 110)
Seronegative- Serotype 2: 1 year post vaccination 331.3 (20.2 to 48.6)28.7 (17.3 to 47.7)30.9 (17.5 to 54.5)
Seronegative- Serotype 3: Baseline5.00 (NA to NA)5.69 (4.86 to 6.66)6.09 (5.05 to 7.34)
Seronegative- Serotype 3: 28 days post vaccination 364.2 (48.6 to 84.9)53.7 (36.1 to 80.0)49.5 (30.1 to 81.5)
Seronegative- Serotype 3: 1 year post injection 327.5 (17.4 to 43.5)25.3 (15.8 to 40.3)21.8 (13.6 to 35.0)
Seronegative- Serotype 4: Baseline5.00 (NA to NA)5.41 (4.61 to 6.35)5.64 (4.90 to 6.50)
Seronegative- Serotype 4: 28 days post vaccination 3145 (112 to 187)164 (114 to 237)349 (189 to 646)
Seronegative- Serotype 4: 1 year post vaccination 357.1 (42.5 to 76.8)53.8 (32.0 to 90.5)40.8 (24.9 to 66.8)
SecondarySTAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Participants Seropositive at Baseline

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
Reported as:
Geometric mean · titers
STAGE-II: Geometric Mean Titers Against Each Serotype With the Parental Dengue Virus Strains After Booster CYD Dengue Vaccination in Participants Seropositive at Baseline
titersSTAGE-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)
Serotype 1: Baseline246 (183 to 331)283 (207 to 385)309 (227 to 421)231 (171 to 313)327 (239 to 447)350 (265 to 462)
Serotype 1: 28 days post vaccination 3828 (671 to 1022)933 (730 to 1192)1111 (868 to 1423)840 (664 to 1061)824 (644 to 1056)1301 (1011 to 1675)
Serotype 1 : 28 days post booster dose505 (335 to 763)552 (375 to 812)861 (572 to 1297)707 (472 to 1057)749 (465 to 1207)1199 (755 to 1902)
Serotype 2 : Baseline370 (295 to 466)335 (258 to 437)283 (221 to 363)296 (228 to 385)318 (244 to 413)303 (241 to 382)
Serotype 2 : 28 days post vaccination 3986 (834 to 1166)897 (735 to 1096)1018 (850 to 1218)783 (648 to 947)844 (695 to 1025)1077 (871 to 1331)
Serotype 2 : 28 days post booster dose856 (638 to 1147)858 (639 to 1152)867 (640 to 1174)813 (600 to 1100)655 (461 to 931)967 (697 to 1343)
Serotype 3 : Baseline363 (285 to 462)399 (308 to 519)287 (222 to 371)266 (211 to 335)210 (164 to 271)253 (201 to 317)
Serotype 3: 28 days post vaccination 3733 (617 to 871)659 (547 to 794)725 (607 to 865)524 (434 to 631)551 (459 to 661)663 (534 to 823)
Serotype 3:28 days post booster dose721 (511 to 1018)667 (477 to 933)743 (557 to 992)586 (455 to 754)477 (364 to 626)506 (370 to 691)
Serotype 4: Baseline147 (114 to 190)142 (113 to 178)115 (89.6 to 146)147 (117 to 183)106 (84.5 to 133)122 (97.3 to 153)
Serotype 4:28 day post vaccination 3512 (433 to 605)536 (456 to 631)570 (463 to 701)543 (456 to 647)480 (406 to 568)593 (495 to 711)
Serotype 4 : 28 days post booster dose380 (292 to 495)265 (210 to 334)300 (223 to 405)368 (290 to 466)360 (273 to 474)413 (297 to 574)
SecondarySTAGE-I: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Participants

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
Reported as:
Number · percentage of participants
STAGE-I: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strains in All Participants
percentage of participantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Serotype 1: Baseline77.8 (72.9 to 82.1)80.5 (75.8 to 84.6)83.4 (79.0 to 87.3)
Serotype 1: 28 days post vaccination 396.3 (93.7 to 98.1)97.2 (94.8 to 98.7)94.1 (91.0 to 96.4)
Serotype 1: 1 year post vaccination 388.3 (83.5 to 92.2)87.5 (82.5 to 91.5)88.3 (83.4 to 92.1)
Serotype 2: Baseline82.6 (78.1 to 86.5)83.8 (79.4 to 87.7)85.2 (81.0 to 88.9)
Serotype 2: 28 days post vaccination 398.2 (96.0 to 99.3)96.6 (94.0 to 98.3)96.0 (93.2 to 97.8)
Serotype 2: 1 year post vaccination 395.7 (92.2 to 97.9)94.4 (90.6 to 97.0)94.8 (91.1 to 97.3)
Serotype 3: Baseline82.6 (78.1 to 86.5)84.1 (79.7 to 87.9)87.0 (83.0 to 90.5)
Serotype 3: 28 days post vaccination 398.5 (96.5 to 99.5)98.1 (96.0 to 99.3)97.5 (95.2 to 98.9)
Serotype 3: 1 year post vaccination 395.7 (92.2 to 97.9)95.7 (92.2 to 97.9)94.3 (90.5 to 97.0)
Serotype 4: Baseline79.6 (74.8 to 83.8)81.4 (76.8 to 85.5)81.6 (77.0 to 85.6)
Serotype 4: 28 days post vaccination 399.7 (98.3 to 100.0)99.4 (97.8 to 99.9)98.8 (96.9 to 99.7)
Serotype 4: 1 year post vaccination 399.1 (96.9 to 99.9)96.6 (93.3 to 98.5)95.7 (92.1 to 97.9)
SecondarySTAGE-II: Percentage of Participants With Antibodies Titer >=10 (1/Dilution) Against Each Serotype With the Parental Dengue Virus Strain in Participants Seropositive at Baseline

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
Reported as:
Number · percentage of participants
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
percentage of participantsSTAGE-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)
Serotype 1: Baseline92.2 (86.5 to 96.0)90.3 (84.2 to 94.6)91.8 (86.2 to 95.7)92.1 (86.4 to 96.0)91.7 (85.9 to 95.6)97.2 (93.0 to 99.2)
Serotype 1: 28 days post vaccination 3100.0 (97.3 to 100.0)99.3 (96.1 to 100.0)100.0 (97.5 to 100.0)99.3 (96.0 to 100.0)99.3 (96.1 to 100.0)100.0 (97.4 to 100.0)
Serotype 1 : 1 year post vaccination 3100.0 (97.3 to 100.0)99.3 (96.0 to 100.0)99.3 (96.2 to 100.0)100.0 (97.2 to 100.0)96.9 (92.3 to 99.2)98.5 (94.6 to 99.8)
Serotype 2: Baseline99.3 (96.1 to 100.0)94.4 (89.3 to 97.6)94.6 (89.6 to 97.6)96.4 (91.9 to 98.8)94.4 (89.3 to 97.6)97.2 (93.0 to 99.2)
Serotype 2 : 28 days post vaccination 3100.0 (97.3 to 100.0)99.3 (96.1 to 100.0)100.0 (97.5 to 100.0)100.0 (97.3 to 100.0)99.3 (96.1 to 100.0)100.0 (97.4 to 100.0)
Serotype 2 : 1 year post vaccination 3100.0 (97.3 to 100.0)99.3 (96.0 to 100.0)100.0 (97.5 to 100.0)100.0 (97.2 to 100.0)98.5 (94.6 to 99.8)100.0 (97.2 to 100.0)
Serotype 3: Baseline98.6 (95.0 to 99.8)96.5 (92.1 to 98.9)95.2 (90.4 to 98.1)97.1 (92.8 to 99.2)93.1 (87.6 to 96.6)100.0 (97.5 to 100.0)
Serotype 3: 28 days post vaccination100.0 (97.3 to 100.0)100.0 (97.4 to 100.0)100.0 (97.5 to 100.0)99.3 (96.0 to 100.0)100.0 (97.4 to 100.0)100.0 (97.4 to 100.0)
Serotype 3 : 1 year post vaccination 3100.0 (97.3 to 100.0)99.3 (96.0 to 100.0)99.3 (96.2 to 100.0)100.0 (97.2 to 100.0)100.0 (97.2 to 100.0)100.0 (97.2 to 100.0)
Serotype 4: Baseline93.6 (88.2 to 97.0)93.1 (87.6 to 96.6)89.8 (83.7 to 94.2)95.0 (90.0 to 98.0)91.7 (85.9 to 95.6)94.4 (89.3 to 97.6)
Serotype 4: 28 days post vaccination 3100.0 (97.3 to 100.0)100.0 (97.4 to 100.0)100.0 (97.5 to 100.0)100.0 (97.3 to 100.0)100.0 (97.4 to 100.0)100.0 (97.4 to 100.0)
Serotype 4: 1 year post vaccination 3100.0 (97.3 to 100.0)99.3 (96.0 to 100.0)98.6 (95.0 to 99.8)100.0 (97.2 to 100.0)98.5 (94.6 to 99.8)100.0 (97.2 to 100.0)
SecondarySTAGE-I: Number of Participants With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any 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 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)
Reported as:
Count of participants · Participants
STAGE-I: Number of Participants With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
ParticipantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
STAGE-I: Number of Participants With Immediate Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)030
SecondarySTAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine

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
Reported as:
Count of participants · Participants
STAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
ParticipantsSTAGE-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)
STAGE-II: Number of Participants With Immediate Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine000000
SecondarySTAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)

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)
Reported as:
Count of participants · Participants
STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
ParticipantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Pain10911497
Erythema433
Swelling255
SecondarySTAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)

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)
Reported as:
Count of participants · Participants
STAGE-I: Number of Participants With Solicited Injection Site Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
ParticipantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Post-vaccination 1: Pain616161
Post-vaccination 1: Erythema332
Post vaccination 1: Swelling022
Post-vaccination 2: Pain505350
Post-vaccination 2: Erythema101
Post-vaccination 2: Swelling112
Post-vaccination 3: Pain434935
Post-vaccination 3: Erythema001
Post-vaccination 3: Swelling122
SecondarySTAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)

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)
Reported as:
Count of participants · Participants
STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Any Vaccination)
ParticipantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Fever292131
Headache129122124
Malaise11498102
Myalgia1109286
Asthenia988071
SecondarySTAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each 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.

Time frame:
Within 14 days after each vaccination (1, 2, and 3)
Reported as:
Count of participants · Participants
STAGE-I: Number of Participants With Solicited Systemic Reactions Following Vaccination With CYD Dengue Vaccine or Placebo (Post Each Vaccination)
ParticipantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
Post-vaccination 1: Fever10813
Post-vaccination 1: Headache908384
Post-vaccination 1: Malaise746061
Post-vaccination 1: Myalgia675548
Post-vaccination 1: Asthenia635245
Post-vaccination 2: Fever12712
Post-vaccination 2: Headache545553
Post-vaccination 2: Malaise504447
Post-vaccination 2: Myalgia493335
Post-vaccination 2: Asthenia403033
Post-vaccination 3: Fever989
Post-vaccination 3: Headache554747
Post-vaccination 3: Malaise464139
Post-vaccination 3: Myalgia263728
Post-vaccination 3: Asthenia293221
SecondarySTAGE-II: Number of Participants With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine

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
Reported as:
Count of participants · Participants
STAGE-II: Number of Participants With Solicited Injection Site Reactions Following Booster Vaccination With CYD Dengue Vaccine
ParticipantsSTAGE-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)
Pain671171210
Erythema000010
Swelling000011
SecondarySTAGE-II: Number of Participants With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine

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
Reported as:
Count of participants · Participants
STAGE-II: Number of Participants With Solicited Systemic Reactions Following Booster Vaccination With CYD Dengue Vaccine
ParticipantsSTAGE-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)
Fever101220
Headache51167117
Malaise597795
Myalgia5899126
Asthenia466793
SecondarySTAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo

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)
Reported as:
Count of participants · Participants
STAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo
ParticipantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
STAGE-I: Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With CYD Dengue Vaccine or Placebo739475
SecondarySTAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine

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
Reported as:
Count of participants · Participants
STAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine
ParticipantsSTAGE-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)
STAGE-II: Number of Participants Reporting Unsolicited Adverse Events Following Booster Vaccination With CYD Dengue Vaccine135324
SecondarySTAGE-I: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Event of Special Interests (AESI) Following Vaccination With CYD Dengue Vaccine or Placebo

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)
Reported as:
Count of participants · Participants
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
ParticipantsSTAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)
SAE142618
Serious AESI000
SecondarySTAGE-II: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine

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)
Reported as:
Count of participants · Participants
STAGE-II: Number of Participants Reporting Serious Adverse Events Including Serious Adverse Events Special Interest Following Booster Vaccination With CYD Dengue Vaccine
ParticipantsSTAGE-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)
SAE302201
Serious AESI000000

Adverse events

Collected over 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]). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
STAGE-I Group 1: CYD Dengue Vaccine0/348 (0%)14/348 (4%)203/348 (58.3%)
STAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)1/348 (0.3%)26/348 (7.5%)189/348 (54.3%)
STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)1/352 (0.3%)18/352 (5.1%)182/352 (51.7%)
STAGE-II Group 1a: CYD Vaccine + CYD Booster Vaccine (1 Year)0/55 (0%)3/55 (5.5%)10/55 (18.2%)
STAGE-II Group 1b: CYD Vaccine + CYD Booster Vaccine (2 Years)0/53 (0%)2/53 (3.8%)13/53 (24.5%)
STAGE-II Group 2a: Placebo + CYD + CYD Booster (1 Year)0/59 (0%)0/59 (0%)15/59 (25.4%)
STAGE-II Group 2b: Placebo + CYD + CYD Booster (2 Years)0/56 (0%)0/56 (0%)20/56 (35.7%)
STAGE-II Group 3a: Placebo + CYD + CYD Booster (1 Year)0/62 (0%)2/62 (3.2%)18/62 (29%)
STAGE-II Group 3b: Placebo + CYD + CYD Booster (2 Years)0/53 (0%)1/53 (1.9%)15/53 (28.3%)
Most frequent serious events
Showing 10 of 51
Most frequent serious events
EventSTAGE-I Group 1: CYD Dengue VaccineSTAGE-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)
AppendicitisInfections and infestations1/3484/3483/3521/550/530/590/560/621/53
Urinary Tract InfectionInfections and infestations1/3480/3480/3520/551/530/590/560/620/53
SyncopeNervous system disorders0/3480/3481/3520/551/530/590/560/620/53
Thermal BurnInjury, poisoning and procedural complications0/3480/3480/3521/550/530/590/560/620/53
NephrolithiasisRenal and urinary disorders0/3480/3481/3521/550/530/590/560/620/53
Hepatitis AInfections and infestations0/3480/3480/3520/550/530/590/561/620/53
Forearm FractureInjury, poisoning and procedural complications0/3481/3480/3520/550/530/590/561/620/53
Abortion SpontaneousPregnancy, puerperium and perinatal conditions2/3480/3480/3520/550/530/590/560/620/53
Myocardial InfarctionCardiac disorders0/3481/3480/3520/550/530/590/560/620/53
Branchial CystCongenital, familial and genetic disorders1/3480/3480/3520/550/530/590/560/620/53
Most frequent other events
Most frequent other events
EventSTAGE-I Group 1: CYD Dengue VaccineSTAGE-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)
HeadacheNervous system disorders129/348123/348124/3525/557/5311/5912/567/627/53
Injection Site PainGeneral disorders109/348114/34897/3526/557/537/5912/5611/6210/53
MalaiseGeneral disorders114/34898/348103/3525/557/539/599/567/625/53
MyalgiaMusculoskeletal and connective tissue disorders110/34892/34887/3525/559/538/5912/569/626/53
AstheniaGeneral disorders98/34880/34871/3524/557/536/599/566/623/53
FeverGeneral disorders29/34821/34831/3521/552/530/592/561/620/53

Baseline characteristics

Analysis was performed on all randomized population.

Age, Continuous
Age, Continuous(years)STAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)Total
Mean30.8 ± 14.4231.3 ± 14.4731.1 ± 14.6231.1 ± 14.49
Sex: Female, Male
Sex: Female, Male(Participants)STAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)Total
Female190197185572
Male160151167478
Race (NIH/OMB)
Race (NIH/OMB)(Participants)STAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)Total
American Indian or Alaska Native171172169512
Asian174172177523
Native Hawaiian or Other Pacific Islander0000
Black or African American53614
White0101
More than one race0000
Unknown or Not Reported0000
Dengue Baseline Status
Dengue Baseline Status(Participants)STAGE-I Group 1: CYD Dengue VaccineSTAGE-I Group 2: Placebo + CYD Dengue Vaccine (Months 6,12)STAGE-I Group 3: Placebo + CYD Dengue Vaccine (Month 12)Total
Seropositive participants281288291860
Seronegative participants524041133
Undetermined17202057
08

Study locations

6 sites
  • Investigational Site 102
    Barranquilla, Colombia
  • Investigational Site 101
    Cali, Colombia
  • Investigational Site 103
    Medellin, Colombia
  • Investigational Site 203
    Manila, Philippines
  • Investigational Site 204
    Manila, Philippines
  • Investigational Primary Site Muntinlupa 201_Satellite Site San Pablo 202
    Muntinlupa, Philippines
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References and documents

Publications

  • Coronel-Martinez DL, Park J, Lopez-Medina E, Capeding MR, Bonfanti AAC, Montalban MC, Ramirez I, Gonzales MLA, Zambrano B, Dayan G, Chen Z, Wang H, Bonaparte M, Rojas A, Ramirez JC, Verdan MA, Noriega F. Immunogenicity and safety of booster CYD-TDV dengue vaccine after alternative primary vaccination schedules in healthy individuals aged 9-50 years: a randomised, controlled, phase 2, non-inferiority study. Lancet Infect Dis. 2022 Jun;22(6):901-911. doi: 10.1016/S1473-3099(21)00706-4. Epub 2022 Mar 29. PubMed 35364022 ↗
  • Coronel-MartInez DL, Park J, Lopez-Medina E, Capeding MR, Cadena Bonfanti AA, Montalban MC, Ramirez I, Gonzales MLA, DiazGranados CA, Zambrano B, Dayan G, Savarino S, Chen Z, Wang H, Sun S, Bonaparte M, Rojas A, Ramirez JC, Verdan MA, Noriega F. Immunogenicity and safety of simplified vaccination schedules for the CYD-TDV dengue vaccine in healthy individuals aged 9-50 years (CYD65): a randomised, controlled, phase 2, non-inferiority study. Lancet Infect Dis. 2021 Apr;21(4):517-528. doi: 10.1016/S1473-3099(20)30767-2. Epub 2020 Nov 16. PubMed 33212067 ↗

Study documents

  • Study protocol · Dec 12, 2017
  • Statistical analysis plan · Mar 19, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Mar 24, 2022, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT02628444
Lead sponsor
Sanofi Pasteur, a Sanofi Company
Responsible party
Sponsor
First posted
Dec 11, 2015
Start date
May 2, 2016
Primary completion
Apr 29, 2020
Completion
Apr 29, 2020
Results posted
Feb 23, 2021
Last update
Mar 24, 2022

Study contacts

Clinical Sciences & Operations
study director · Sanofi Pasteur, a Sanofi Company

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Mar 2022. You cannot join it, but the record below documents what was studied.

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