Study of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Adacel® in Healthy Subjects

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02992418
• Collaborator: (none)
• Enrollment: 688
• Locations: 4
• Arms: 2
• Actual Duration (Months): 35.7
• Patients Per Site: 172
• Patients Per Site Per Month: 4.8

Study Details

Study Description

Brief Summary

The aim of the study was to investigate the immunogenicity and safety of CYD dengue vaccine and Tetanus Toxoid (T), Reduced Diphtheria Toxoid (D) and Acellular Pertussis Vaccine Adsorbed (ap) (Tdap) vaccine when both vaccines were administered concomitantly or sequentially.

Primary Objectives:

• To demonstrate the non-inferiority of the humoral immune response to the Tdap booster dose concomitantly administered with the first dose of CYD dengue vaccine as compared to sequential administration, measured 28 days after Tdap booster dose.

• To demonstrate the non-inferiority of the humoral immune response to the first dose of CYD dengue vaccine concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the first dose of CYD dengue vaccine.

Secondary Objectives:

• To demonstrate the non-inferiority of the humoral immune response of 3 doses of CYD dengue vaccine with the first dose concomitantly administered with Tdap as compared to sequential administration, measured 28 days after the third dose of CYD dengue vaccine.

• To describe the humoral immune response at baseline and 28 days after the first and third doses of CYD dengue vaccine, in each and any group.

• To describe the humoral immune response of Tdap vaccine at baseline and 28 days after concomitant administration with the first dose of CYD dengue vaccine as compared to the sequential administration, in each and any group.

• To describe the safety of the CYD dengue vaccine and of the Tdap booster dose after each and any injection in each group.

Condition or Disease	Intervention/Treatment	Phase
Dengue Fever; Dengue Hemorrhagic Fever	Biological: CYD Dengue Vaccine; Biological: Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbed; Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed	Phase 3

Detailed Description

Participants were to receive CYD dengue vaccine according to a 3-dose schedule administered 6 months apart, with the first dose of CYD dengue vaccine administered either concomitantly or sequentially with a booster dose of the Tdap vaccine, Adacel®.

During the conduct of the study, a safety signal was identified which led to the Independent Data Monitoring Committee (IDMC) recommendation not to vaccinate participants who had never been infected by dengue prior to the first injection, i.e., dengue non-immune participants. The protocol was amended accordingly but never implemented due to absence of response of Health Authorities (HA) from The Philippines.

After having waited for more than 1.5 years, and as the participants became out of window to complete their immunization schedule and the last safety follow-up call (6 months after the last dose), the Sponsor decided to stop the trial. Participants only attended a last safety follow-up visit to terminate the study and were informed about the end of the study. As a consequence, the study was prematurely terminated before injection of the last dose (3rd dose) of the CYD dengue vaccine.

As a consequence of the IDMC recommendations, the main immunogenicity analyses were done in dengue immune participants which is not what was planned in the protocol (and this is why the primary endpoints are not exactly the same as those defined in the protocol as they were finally assessed only in dengue immune participants whereas initially it was planned to be assessed regardless of baseline status).

All participants were assessed for immunogenicity and safety. Safety assessments included 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 688 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Prevention
• Official Title: Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Adacel® in Healthy Subjects Aged 9 to 60 Years in the Philippines
• Actual Study Start Date: Dec 19, 2016
• Actual Primary Completion Date: Dec 10, 2019
• Actual Study Completion Date: Dec 10, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Concomitant Administration Group Participants will be administered the first dose of CYD dengue vaccine concomitantly with a dose of Tdap vaccine.	Biological: CYD Dengue Vaccine; 0.5 milliliter (mL), Subcutaneous at Month 1, 7 and Month 13, respectively; Other Names: Dengvaxia® ; Biological: Tdap: Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine adsorbed; 0.5 mL, intramuscularly (IM) at Month 1.; Other Names: Adacel®
Experimental: Sequential Administration Group Participants will be administered the first dose of CYD dengue vaccine 28 days after a dose of Tdap vaccine.	Biological: CYD Dengue Vaccine; 0.5 milliliter (mL), Subcutaneous at Month 1, 7 and Month 13, respectively; Other Names: Dengvaxia® ; Biological: Tdap: Tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine adsorbed; 0.5 mL, intramuscularly at Day 0.; Other Names: Adacel®

Outcome Measures

Primary Outcome Measures

1. Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Participants [28 days after Tdap vaccination]

   GMCs against each pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM2+3]) were assessed using an enzyme-linked immunosorbent assay (ELISA) method and were measured in ELISA unit/milliliter (EU/mL). Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.

2. Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants [28 days after Tdap vaccination]

   Seroprotection against diphtheria (Anti-D) and tetanus (Anti-T) antigens was performed by Micrometabolic Inhibition Test - Toxin Neutralization assay (MIT-TNA) and ELISA, respectively. Seroprotection was defined as anti-D and anti-T Ab concentration greater than 0.1 international units (IU)/mL. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.

3. Geometric Mean Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants [28 days after first CYD dengue vaccination]

   The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.

Secondary Outcome Measures

1. Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants [Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination]

   The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.

2. Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD at Baseline and 28 Days After First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants [Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination]

   The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.

3. Percentage of Participants With Neutralizing Antibody Titers Above Predefined Thresholds Against at Least 1, 2, 3, or 4 Serotypes of CYD at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants [Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination]

   Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (1, 2, 3, and 4) were measured by PRNT50. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Percentage of participants with neutralizing antibody titers above pre-defined thresholds (>=10 and >=100 [1/dilution]) against at least 1, 2, 3, or 4 serotypes of CYD were reported. Here, 'dil'=dilution and "vac"=vaccination in the specified categories.

4. Geometric Mean Concentrations of Serum Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants [Baseline (Pre-Tdap vaccination) and 28 days after the Tdap vaccination]

   GMCs against each pertussis antigens (PT, FHA, PRN, FIM2+3) were assessed using ELISA assay method and were measured in EU/mL. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.

5. Percentage of Participants Achieving Serum Antibody (>=0.1 IU/mL) Against Diphtheria and Tetanus Antigens at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants [Baseline (Pre-Tdap vaccination) and 28 days after the dose of Tdap vaccination]

   The GMC against diphtheria and tetanus antigens was performed by MIT-TNA and ELISA, respectively. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.

6. Number of Participants With Immediate Unsolicited Adverse Events (AE) Following Vaccination With Tdap or CYD Dengue Vaccine [Within 30 minutes after any and each vaccination]

   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. Any unsolicited AE occurred during first 30 minutes post-vaccination was recorded on the CRF as immediate AE. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccination and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.

7. Number of Participants With Solicited Injection Site Reactions Following Vaccination With Tdap or CYD Dengue Vaccine [Within 7 days after any and each vaccination]

   A solicited reaction (SR) was an AE 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 reactions included pain, erythema, and swelling. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received only CYD vaccination.

8. Number of Participants With Solicited Systemic Reactions Following Vaccination With Tdap or CYD Dengue Vaccine [Within 14 days after any and each vaccination]

   A SR reaction was an AE observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination. Solicited injection site reactions included fever, headache, malaise, myalgia, and asthenia. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received only CYD vaccination.

9. Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Tdap or CYD Dengue Vaccine [Within 28 days after any and each vaccination]

   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. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.

10. Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Tdap or CYD Dengue Vaccine [Within 7 days post any and each vaccination]

    Non-serious AESIs were non-serious AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.

11. Number of Participants Reporting Serious Adverse Events (SAEs) and Serious AESIs Following Vaccination With Tdap or CYD Dengue Vaccine [From Day 0 up to 6 months after the last Tdap or CYD vaccination]

    SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; required hospitalization or prolonged existing hospitalization; persistent or significant disability/incapacity; congenital anomaly or a medically important event. Serious AESIs were SAEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine.

12. Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Tdap or CYD Dengue Vaccine [From Day 0 up to 6 months after the last Tdap or CYD vaccination]

    Hospitalized suspected dengue case was defined as an acute febrile illness with diagnosis of dengue requiring hospitalization (with bed attribution). In such cases, 1 unplanned acute blood sample (within the first 5 days after fever onset) was collected for virological confirmation of hospitalized suspected dengue case. A suspected case was considered VCD if there was a detection of wild type dengue virus by dengue non-structural protein 1 antigen ELISA and/or dengue reverse transcriptase-polymerase chain reactions.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 9 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Participant aged 9 to 60 years (i.e., from the day of the 9th birthday to the day prior to the 61th birthday) on the day of inclusion.

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

• Informed consent form (ICF) or assent form was signed and dated by the participant (based on local regulations), and/or ICF was signed and dated by the parent(s) or another legally acceptable representative (and by an independent witness if required by local regulations).

• For participant aged 9 to 11 years: known (documented) receipt of at least 4 previous doses of diphtheria toxoid, tetanus toxoid and acellular pertussis-containing (DTaP) vaccines, with the last dose not within the last 5 years prior to enrolment.

OR For participant aged at least 12 years: known (documented or self-reported) receipt of at least 3 previous doses of diphtheria toxoid, tetanus toxoid, and whole cell pertussis-containing (DTwP) vaccines, with the last dose not within the last 5 years prior to enrolment.

• Participant (or participant and parent[s]/legally acceptable representatives) was able to attend all scheduled visits and complied 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 or post-menopausal for at least 1 year, 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.

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

• Previous vaccination against dengue disease with the trial CYD dengue vaccine.

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

• Known or suspected congenital or acquired immunodeficiency (including human immunodeficiency virus (HIV) infection with impaired immune function); or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroids therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).

• A previous severe reaction to pertussis, diphtheria or tetanus vaccine including immediate anaphylaxis, encephalopathy within 7 days or seizure within 3 days of receiving the vaccine.

• Known 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.

• Thrombocytopenia, contraindicating IM vaccination.

• Bleeding disorder or receipt of anticoagulants within 3 weeks preceding inclusion, which might be a contraindication for IM vaccination, at the discretion of the Investigator.

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

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

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

• Identified as an Investigator or employee of the Investigator with direct involvement in the proposed study, or identified as an immediate family member (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with direct involvement in the proposed study.

• Self-reported HIV, Hepatitis B, or Hepatitis C infection.

• Personal history of Guillain-Barré syndrome.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Muntinlupa	Alabang	Philippines
2		Manila		Philippines	1000
3		Quezon City		Philippines
4		Quezon		Philippines

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur SA

Study Documents (Full-Text)

• Study Protocol - Jan 4, 2018
• Statistical Analysis Plan - Sep 19, 2019

More Information

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT02992418
• Other Study ID Numbers: CYD66; U1111-1161-3294; 2019-003136-23
• First Posted: Dec 14, 2016
• Last Update Posted: Mar 25, 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 Hemorrhagic Fever; CYD Dengue Vaccine; Dengavaxia®
• Additional relevant MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Fever; Hyperthermia; Vaccines

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled from 19 December 2016 to 17 April 2017 at 4 centers in the Philippines. A total of 688 participants were enrolled and randomized in this study.
Pre-assignment Detail	Safety signal was spotted in dengue non-immune participants, which led to IDMC suggestion to not vaccinate them anymore. As no Health Authority feedback was received on amendment, study was terminated before 3rd (last) injection of CYD dengue vaccine. Hence, no participants received 3rd CYD dengue dose (as planned) and all were followed for safety.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tetanus Toxoid (T), Reduced Diphtheria Toxoid (D) and Acellular Pertussis Vaccine Adsorbed (ap) (Tdap) vaccine 0.5 milliliter (mL) intramuscular (IM) injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL subcutaneous (SC) injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Period Title: Overall Study
STARTED	346	342
Safety Analysis Set (SafAS)	338	342
COMPLETED	0	0
NOT COMPLETED	346	342

Baseline Characteristics

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)	Total
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.	Total of all reporting groups
Overall Participants	346	342	688
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	26.2 (16.3)	27.1 (16.7)	26.6 (16.5)
Sex: Female, Male (Count of Participants)
Female	187 54%	193 56.4%	380 55.2%
Male	159 46%	149 43.6%	308 44.8%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Dengue Baseline Status (Count of Participants)
Dengue immune	314 90.8%	315 92.1%	629 91.4%
Dengue non-immune	32 9.2%	27 7.9%	59 8.6%

Outcome Measures

1. Primary Outcome

Title	Geometric Mean Concentrations (GMCs) of Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) 28 Days After Dose of Tdap Vaccine in Previously Dengue Immune Participants
Description	GMCs against each pertussis antigens (pertussis toxoid [PT], filamentous hemagglutinin [FHA], pertactin [PRN], fimbriae types 2 and 3 [FIM2+3]) were assessed using an enzyme-linked immunosorbent assay (ELISA) method and were measured in ELISA unit/milliliter (EU/mL). Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Time Frame	28 days after Tdap vaccination

Outcome Measure Data

Analysis Population Description

Per protocol analysis set of Tdap (PPT) included dengue immune participants who received at least one dose of Tdap and had no relevant protocol deviations. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	312	314
Anti-PT	65.2	76.0
Anti-FHA	273	267
Anti-PRN	50.6	44.9
Anti-FIM2+3	705	643

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Anti-PT
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% confidence interval (CI) of the ratio of GMCs between groups (Group 1/ Group 2) was greater than (>) 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	0.848
	Confidence Interval	(2-Sided) 95%; 0.721 to 0.997
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Anti-FHA
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMCs between groups (Group 1/ Group 2) was > 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.02
	Confidence Interval	(2-Sided) 95%; 0.892 to 1.18
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Anti-PRN
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMCs between groups (Group 1/ Group 2) was > 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.836 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Anti-FIM2+3
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMCs between groups (Group 1/ Group 2) was > 1/1.5 for each antigen. Overall non-inferiority was demonstrated if the 4 antigens achieved non-inferiority.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	GMC ratio
	Estimated Value	1.05
	Confidence Interval	(2-Sided) 95%; 0.827 to 1.33
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants With Seroprotection Against Diphtheria and Tetanus Antigens 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
Description	Seroprotection against diphtheria (Anti-D) and tetanus (Anti-T) antigens was performed by Micrometabolic Inhibition Test - Toxin Neutralization assay (MIT-TNA) and ELISA, respectively. Seroprotection was defined as anti-D and anti-T Ab concentration greater than 0.1 international units (IU)/mL. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Time Frame	28 days after Tdap vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on PPT population. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	312	314
Anti-D	90.1 26%	89.8 26.3%
Anti-T	98.4 28.4%	99.0 28.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Anti-D
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the percentage difference was > -10% for all antigens.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	0.26
	Confidence Interval	(2-Sided) 95%; -4.53 to 5.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Anti-T
	Type of Statistical Test	Non-Inferiority
	Comments	The non-inferiority was demonstrated if the lower limit of all the 95% CI of the percentage difference was > -10% for all antigens.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Percentage difference
	Estimated Value	-0.66
	Confidence Interval	(2-Sided) 95%; -2.87 to 1.37
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	Geometric Mean Titers (GMTs) of Antibodies Against Each Dengue Virus Serotype 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Description	The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using the 50% plaque reduction neutralization test (PRNT50) assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.
Time Frame	28 days after first CYD dengue vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on per-protocol analysis set for CYD dengue vaccine (PPC) population which included dengue immune participants who received 1st dose of CYD dengue vaccine and had no relevant protocol deviations.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	312	308
Serotype 1	513	461
Serotype 2	677	568
Serotype 3	653	706
Serotype 4	378	472

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Serotype 1
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. 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	1.11
	Confidence Interval	(2-Sided) 95%; 0.862 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Serotype 2
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. 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) 95%; 0.97 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Serotype 3
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. 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	0.925
	Confidence Interval	(2-Sided) 95%; 0.739 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration), CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Comments	Serotype 4
	Type of Statistical Test	Non-Inferiority
	Comments	Non-inferiority was demonstrated if the lower limit of the two-sided 95% CI of the ratio of GMTs between groups (Group 1/Group 2) was > 1/2 for each serotype. 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	0.802
	Confidence Interval	(2-Sided) 95%; 0.644 to 0.999
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Description	The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Titers were measured in terms of 1/dilution.
Time Frame	Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the subset of participants who received at least one dose of study vaccines (CYD dengue or Tdap) and were immune to dengue at baseline. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	314	315
Serotype 1: Pre-vaccination 1	265	250
Serotype 1: 28 days post-vaccination 1	513	468
Serotype 2: Pre-vaccination 1	404	343
Serotype 2: 28 days post-vaccination 1	679	577
Serotype 3: Pre-vaccination 1	327	327
Serotype 3: 28 days post-vaccination 1	655	709
Serotype 4: Pre-vaccination 1	136	172
Serotype 4: 28 days post-vaccination 1	379	478

5. Secondary Outcome

Title	Percentage of Participants With Neutralizing Antibody Titers Against Each of the 4 Dengue Virus Serotypes of CYD at Baseline and 28 Days After First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Description	The GMTs against each of the four parenteral dengue virus serotypes (1, 2, 3 and 4) of CYD dengue vaccine were assessed using PRNT50 assay method. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Time Frame	Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the subset of participants who received at least one dose of study vaccines (CYD dengue or Tdap) and were immune to dengue at baseline. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	314	315
Serotype 1: Pre-vaccination 1	92.7 26.8%	93.3 27.3%
Serotype 1: 28 days post-vaccination 1	97.8 28.3%	98.4 28.8%
Serotype 2: Pre-vaccination 1	98.1 28.4%	96.5 28.2%
Serotype 2: 28 days post-vaccination 1	100.0 28.9%	99.0 28.9%
Serotype 3: Pre-vaccination 1	95.5 27.6%	97.1 28.4%
Serotype 3: 28 days post-vaccination 1	100.0 28.9%	99.7 29.2%
Serotype 4: Pre-vaccination 1	93.0 26.9%	97.5 28.5%
Serotype 4: 28 days post-vaccination 1	99.4 28.7%	100.0 29.2%

6. Secondary Outcome

Title	Percentage of Participants With Neutralizing Antibody Titers Above Predefined Thresholds Against at Least 1, 2, 3, or 4 Serotypes of CYD at Baseline and 28 Days After the First Dose of CYD Dengue Vaccination in the Previously Dengue Immune Participants
Description	Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (1, 2, 3, and 4) were measured by PRNT50. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain. Percentage of participants with neutralizing antibody titers above pre-defined thresholds (>=10 and >=100 [1/dilution]) against at least 1, 2, 3, or 4 serotypes of CYD were reported. Here, 'dil'=dilution and "vac"=vaccination in the specified categories.
Time Frame	Baseline (Pre-CYD vaccination 1) and 28 days after the first CYD dengue vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on subset of participants who received at least one dose of study vaccines (CYD dengue or Tdap) and were immune to dengue at baseline. Here, 'Number analyzed' = participants with available data for each specified categories.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	314	315
At least 1 Serotype: pre-vac 1: >=10 (1/dil)	100.0 28.9%	100.0 29.2%
At least 1 Serotype: pre-vac1: >=100 (1/dil)	97.8 28.3%	97.1 28.4%
At least 1 Serotype: post-vac 1: >=10 (1/dil)	100.0 28.9%	100.0 29.2%
At least 1 Serotype: post-vac 1: >=100 (1/dil)	99.7 28.8%	99.7 29.2%
At least 2 Serotype: pre-vac 1: >=10 (1/dil)	96.5 27.9%	98.1 28.7%
At least 2 Serotype: pre-vac 1: >=100 (1/dil)	84.4 24.4%	87.0 25.4%
At least 2 Serotype: post-vac 1: >=10 (1/dil)	100.0 28.9%	99.7 29.2%
At least 2 Serotype: post-vac 1: >=100 (1/dil)	95.8 27.7%	96.5 28.2%
At least 3 Serotype: pre-vac 1: >=10 (1/dil)	93.6 27.1%	95.2 27.8%
At least 3 Serotype: pre-vac 1: >=100 (1/dil)	76.1 22%	76.8 22.5%
At least 3 Serotype: post-vac 1: >=10 (1/dil)	99.7 28.8%	99.4 29.1%
At least 3 Serotype: post-vac 1: >=100 (1/dil)	90.4 26.1%	92.1 26.9%
At least 4 Serotype: pre-vac 1: >=10 (1/dil)	89.2 25.8%	91.1 26.6%
At least 4 Serotype: pre-vac 1: >=100 (1/dil)	52.9 15.3%	54.3 15.9%
At least 4 Serotype: post-vac 1: >=10 (1/dil)	97.4 28.2%	98.1 28.7%
At least 4 Serotype: post-vac 1: >=100 (1/dil)	73.8 21.3%	75.6 22.1%

7. Secondary Outcome

Title	Geometric Mean Concentrations of Serum Antibodies Against Pertussis Antigens (Pertussis Toxoid, Filamentous Hemagglutinin, Pertactin, and Fimbriae 2+3) at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
Description	GMCs against each pertussis antigens (PT, FHA, PRN, FIM2+3) were assessed using ELISA assay method and were measured in EU/mL. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Time Frame	Baseline (Pre-Tdap vaccination) and 28 days after the Tdap vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the subset of participants who received at least one dose of study vaccines (CYD dengue or Tdap) and were immune to dengue at baseline. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	314	315
Anti-PT: Pre-vaccination	8.46	9.56
Anti-PT: 28 days post-vaccination	65.0	76.1
Anti-FHA: Pre-vaccination	19.9	19.4
Anti-FHA: 28 days post-vaccination	272	266
Anti-PRN: Pre-vaccination	3.79	3.65
Anti-PRN: 28 days post-vaccination	50.6	45.0
Anti-FIM2+3: Pre-vaccination	15.1	14.9
Anti-FIM2+3: 28 days post-vaccination	700	642

8. Secondary Outcome

Title	Percentage of Participants Achieving Serum Antibody (>=0.1 IU/mL) Against Diphtheria and Tetanus Antigens at Baseline and 28 Days After the Dose of Tdap Vaccine in the Previously Dengue Immune Participants
Description	The GMC against diphtheria and tetanus antigens was performed by MIT-TNA and ELISA, respectively. Dengue immune participants at Baseline were defined as participants with titers >=10 (1/dilution) for at least one serotype with the parental dengue virus strain.
Time Frame	Baseline (Pre-Tdap vaccination) and 28 days after the dose of Tdap vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on the subset of participants who received at least one dose of study vaccines (CYD dengue or Tdap) and were immune to dengue at baseline. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	314	315
Anti-D: Pre-vaccination	31.8 9.2%	32.8 9.6%
Anti-T: Pre-vaccination	63.7 18.4%	69.6 20.4%
Anti-D: 28 days post-vaccination	90.1 26%	89.8 26.3%
Anti-T: 28 days post-vaccination	98.1 28.4%	99.0 28.9%

9. Secondary Outcome

Title	Number of Participants With Immediate Unsolicited Adverse Events (AE) Following Vaccination With Tdap or CYD Dengue Vaccine
Description	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. Any unsolicited AE occurred during first 30 minutes post-vaccination was recorded on the CRF as immediate AE. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccination and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.
Time Frame	Within 30 minutes after any and each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population, which included participants who received at least one dose of the study vaccines (CYD dengue or Tdap). Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	338	342
Post any vaccination	0 0%	0 0%
Post Tdap vaccination 1 (Visit 1)	0 0%
Post CYD/Tdap vaccination (Visit 2)	0 0%	0 0%
Post CYD vaccination 2 (Visit 4)	0 0%	0 0%

10. Secondary Outcome

Title	Number of Participants With Solicited Injection Site Reactions Following Vaccination With Tdap or CYD Dengue Vaccine
Description	A solicited reaction (SR) was an AE 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 reactions included pain, erythema, and swelling. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received only CYD vaccination.
Time Frame	Within 7 days after any and each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	338	342
Pain: Post any vaccination	229 66.2%	237 69.3%
Pain: Post Tdap vaccination (Visit 1)	212 61.3%
Pain: Post CYD/Tdap vaccination (Visit 2)	218 63%	53 15.5%
Pain: Post CYD vaccination 2 (Visit 4)	61 17.6%	55 16.1%
Erythema: Post any vaccination	14 4%	17 5%
Erythema: Post Tdap vaccination (Visit 1)	14 4%
Erythema: Post CYD/Tdap vaccination (Visit 2)	13 3.8%	5 1.5%
Erythema: Post CYD vaccination 2 (Visit 4)	2 0.6%	2 0.6%
Swelling: Post any vaccination	25 7.2%	32 9.4%
Swelling: Post Tdap vaccination (Visit 1)	30 8.7%
Swelling: Post CYD/Tdap vaccination (Visit 2)	25 7.2%	3 0.9%
Swelling: Post CYD vaccination 2 (Visit 4)	2 0.6%	2 0.6%

11. Secondary Outcome

Title	Number of Participants With Solicited Systemic Reactions Following Vaccination With Tdap or CYD Dengue Vaccine
Description	A SR reaction was an AE observed and reported under the conditions (symptom and onset) prelisted (i.e., solicited) in the CRF and considered as related to vaccination. Solicited injection site reactions included fever, headache, malaise, myalgia, and asthenia. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received only CYD vaccination.
Time Frame	Within 14 days after any and each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	338	342
Fever: Post any vaccination	21 6.1%	30 8.8%
Fever: Post Tdap vaccination (Visit 1)	15 4.3%
Fever: Post CYD/Tdap vaccination (Visit 2)	11 3.2%	6 1.8%
Fever: Post CYD vaccination 2 (Visit 4)	10 2.9%	9 2.6%
Headache: Post any vaccination	89 25.7%	115 33.6%
Headache: Post Tdap vaccination (Visit 1)	83 24%
Headache: Post CYD/Tdap vaccination (Visit 2)	70 20.2%	33 9.6%
Headache: Post CYD vaccination 2 (Visit 4)	36 10.4%	35 10.2%
Malaise: Post any vaccination	91 26.3%	111 32.5%
Malaise: Post Tdap vaccination (Visit 1)	81 23.4%
Malaise: Post CYD/Tdap vaccination (Visit 2)	74 21.4%	28 8.2%
Malaise: Post CYD vaccination 2 (Visit 4)	32 9.2%	33 9.6%
Myalgia: Post any vaccination	74 21.4%	100 29.2%
Myalgia: Post Tdap vaccination (Visit 1)	78 22.5%
Myalgia: Post CYD/Tdap vaccination (Visit 2)	67 19.4%	30 8.8%
Myalgia: Post CYD vaccination 2 (Visit 4)	26 7.5%	22 6.4%
Asthenia: Post any vaccination	67 19.4%	94 27.5%
Asthenia: Post Tdap vaccination (Visit 1)	69 19.9%
Asthenia: Post CYD/Tdap vaccination (Visit 2)	59 17.1%	24 7%
Asthenia: Post CYD vaccination 2 (Visit 4)	19 5.5%	22 6.4%

12. Secondary Outcome

Title	Number of Participants Reporting Unsolicited Adverse Events Following Vaccination With Tdap or CYD Dengue Vaccine
Description	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. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.
Time Frame	Within 28 days after any and each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	338	342
Post any vaccination	56 16.2%	70 20.5%
Post Tdap vaccination (Visit 1)	40 11.6%
Post CYD/Tdap vaccination (Visit 2)	37 10.7%	20 5.8%
Post CYD vaccination 2 (Visit 4)	28 8.1%	26 7.6%

13. Secondary Outcome

Title	Number of Participants Reporting Non-serious Adverse Event of Special Interests (AESIs) Following Vaccination With Tdap or CYD Dengue Vaccine
Description	Non-serious AESIs were non-serious AEs that were considered by the Sponsor to be relevant for the monitoring of the safety profile of the investigational vaccine. At Visit 1, participants of Group 1 received no vaccination and participants of Group 2 received only Tdap vaccination. At Visit 2, participants of Group 1 received both CYD and Tdap vaccinations and participants of Group 2 received only CYD vaccination. At Visit 4, participants of Groups 1 and 2 received CYD vaccination.
Time Frame	Within 7 days post any and each vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	338	342
Post any vaccination	0 0%	0 0%
Post Tdap vaccination (Visit 1)	0 0%
Post CYD/Tdap vaccination (Visit 2)	0 0%	0 0%
Post CYD vaccination 2 (Visit 4)	0 0%	0 0%

14. Secondary Outcome

Title	Number of Participants Reporting Serious Adverse Events (SAEs) and Serious AESIs Following Vaccination With Tdap or CYD Dengue Vaccine
Description	SAEs were AEs resulting in any of the following outcomes or deemed significant for any other reason: death; life-threatening; required hospitalization or prolonged existing hospitalization; persistent or significant disability/incapacity; congenital anomaly or a medically important event. Serious AESIs were SAEs 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 up to 6 months after the last Tdap or CYD vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	338	342
SAE	8 2.3%	11 3.2%
Serious AESI	1 0.3%	3 0.9%

15. Secondary Outcome

Title	Number of Participants Reporting Cases of Virologically Confirmed Dengue (VCD) Hospitalization Following Vaccination With Tdap or CYD Dengue Vaccine
Description	Hospitalized suspected dengue case was defined as an acute febrile illness with diagnosis of dengue requiring hospitalization (with bed attribution). In such cases, 1 unplanned acute blood sample (within the first 5 days after fever onset) was collected for virological confirmation of hospitalized suspected dengue case. A suspected case was considered VCD if there was a detection of wild type dengue virus by dengue non-structural protein 1 antigen ELISA and/or dengue reverse transcriptase-polymerase chain reactions.
Time Frame	From Day 0 up to 6 months after the last Tdap or CYD vaccination

Outcome Measure Data

Analysis Population Description

Analysis was performed on SafAS population.

Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)	CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
Measure Participants	338	342
Count of Participants [Participants]	0 0%	3 0.9%

Adverse Events

Time Frame	AE data were collected from Day 0 up to Day 28 post any vaccination. SR data were collected from Day 0 up to Day 14 post-vaccination. The SAEs were collected throughout the trial, i.e. up to 6 months after last Tdap or CYD vaccination.
Adverse Event Reporting Description	SR was an 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 in the CRF (i.e., solicited) in terms of symptom and/or onset post-vaccination. Analysis was performed on SafAS population.
Arm/Group Title	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)		CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
Arm/Group Description	Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Month 1, and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (concomitantly with Tdap booster dose) and at Month 7.		Participants received 1 booster dose of Tdap vaccine 0.5 mL IM injection at Day 0 and 2 doses of CYD dengue vaccine 0.5 mL SC injection at Month 1 (sequentially, one month after the Tdap booster dose) and at Month 7.
All Cause Mortality
	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)		CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/338 (0%)		0/342 (0%)
Serious Adverse Events
	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)		CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/338 (2.4%)		11/342 (3.2%)
Cardiac disorders
Hypertensive Heart Disease	0/338 (0%)	0	1/342 (0.3%)	1
Gastrointestinal disorders
Dyspepsia	0/338 (0%)	0	1/342 (0.3%)	1
Gastritis	1/338 (0.3%)	1	0/342 (0%)	0
Hepatobiliary disorders
Jaundice Cholestatic	0/338 (0%)	0	1/342 (0.3%)	1
Infections and infestations
Appendicitis	1/338 (0.3%)	1	0/342 (0%)	0
Atypical Pneumonia	0/338 (0%)	0	1/342 (0.3%)	1
Dengue Fever	1/338 (0.3%)	1	3/342 (0.9%)	3
Gastroenteritis	1/338 (0.3%)	1	1/342 (0.3%)	1
Injury, poisoning and procedural complications
Incisional Hernia	0/338 (0%)	0	1/342 (0.3%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast Cancer	0/338 (0%)	0	1/342 (0.3%)	1
Nervous system disorders
Cerebral Infarction	1/338 (0.3%)	1	0/342 (0%)	0
Seizure	0/338 (0%)	0	1/342 (0.3%)	1
Pregnancy, puerperium and perinatal conditions
Abortion Complete	1/338 (0.3%)	1	0/342 (0%)	0
Renal and urinary disorders
Nephrolithiasis	1/338 (0.3%)	1	0/342 (0%)	0
Skin and subcutaneous tissue disorders
Rash Generalised	1/338 (0.3%)	1	0/342 (0%)	0
Other (Not Including Serious) Adverse Events
	CYD Dengue Vaccine + Tdap Vaccine (Concomitant Administration)		CYD Dengue Vaccine + Tdap Vaccine (Sequential Administration)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	248/338 (73.4%)		263/342 (76.9%)
General disorders
Asthenia	67/338 (19.8%)	78	94/342 (27.5%)	115
Injection Site Pain	229/338 (67.8%)	376	237/342 (69.3%)	320
Injection Site Swelling	25/338 (7.4%)	29	32/342 (9.4%)	35
Malaise	91/338 (26.9%)	106	111/342 (32.5%)	142
Pyrexia	22/338 (6.5%)	22	32/342 (9.4%)	33
Infections and infestations
Upper Respiratory Tract Infection	17/338 (5%)	17	17/342 (5%)	21
Musculoskeletal and connective tissue disorders
Myalgia	74/338 (21.9%)	93	100/342 (29.2%)	130
Nervous system disorders
Headache	89/338 (26.3%)	106	116/342 (33.9%)	152

Limitations/Caveats

Due to absence of response of competent authorities from The Philippines on protocol amendment, the study was prematurely terminated before injection of last dose (3rd dose) of the CYD dengue vaccine. Objectives related to 3rd dose were not assessed.

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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 participant 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.