Long-Term Study of Hospitalized Dengue & Safety in Thai Children Included in a Tetravalent Dengue Vaccine Efficacy Study

• Sponsor: Sanofi Pasteur, a Sanofi Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01983553
• Collaborator: (none)
• Enrollment: 3,203
• Location: 1
• Actual Duration (Months): 34.7
• Patients Per Site Per Month: 92.3

Study Details

Study Description

Brief Summary

The purpose of this study was to conduct a passive surveillance of hospitalized dengue cases in participants who participated in study CYD23 (NCT00842530).

The Objectives:

• To describe the incidence of virologically-confirmed hospitalized dengue cases.

• To characterize hospitalized dengue cases.

• To evaluate the occurrence of related and fatal serious adverse events (SAEs).

Condition or Disease	Intervention/Treatment	Phase
Dengue; Dengue Fever; Dengue Hemorrhagic Fever

Detailed Description

This study was a passive surveillance of hospitalized dengue cases in participants who participated in study CYD23 (NCT00842530) where participants were initially randomized to receive 3 injections of either CYD dengue vaccine or control at 6 month intervals. Any SAE related to a study procedure or related to a previous injection from study CYD23, or any fatal SAEs (even if unrelated) were reported to the Sponsor.

An Independent Data Monitoring Committee (IDMC) was also involved in the regular review of virologically-confirmed hospitalized dengue cases. Any fatal outcome or related SAE were be promptly reviewed by the IDMC.

No study vaccinations were administered.

Study Design

• Study Type: Observational
• Actual Enrollment: 3203 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• Official Title: Long-Term Follow-Up of Hospitalized Dengue and Safety in Thai Children Who Were Included in an Efficacy Study of a Tetravalent Dengue Vaccine
• Actual Study Start Date: Sep 10, 2013
• Actual Primary Completion Date: Jun 15, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
CYD Dengue Vaccine Group Participants who received 3 injections of 0.5 milliliter (mL) CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Control Group Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively in the study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.

Outcome Measures

Primary Outcome Measures

1. Event Rate Per 100 Participant-years for Hospitalized Virologically-Confirmed Dengue (VCD) Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in the Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported.

2. Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Cases were defined as the number of participants with at least one hospitalized VCD episode.

3. Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Episodes were defined as the number of hospitalized VCD episodes.

4. Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1.

5. Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Cases were defined as the number of participants with at least one hospitalized VCD episode.

6. Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Episodes were defined as the number of hospitalized VCD episodes.

7. Event Rate Per 100 Participant-years for Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Event rate per 100 participant-years for Clinically Severe hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1.

8. Number of Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Cases were defined as the number of participants with at least one hospitalized VCD episode.

9. Number of Episodes of Clinically Severe Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

   Episodes were defined as the number of hospitalized VCD episodes.

10. Number of Cases of Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23) [During Year 1 to Year 4 post 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sera sample collection time interval of 14 days]

    Cases were defined as the number of participants with at least one non-serotype specific dengue viremia among hospitalized VCD cases.

11. Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23) [Year 1 to Year 4 post-vaccination after 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sample collection time interval of 14 days]

    Quantified viremia was defined as greater than or equal to (>=) lower limit of quantitation (log10 plaque forming unit [pfu]/mL).

12. Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype and Meeting World Health Organization (WHO) 1997 Criteria Collected Following Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

    Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1. The WHO criteria were fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.

13. Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

    Cases were defined as the number of participants with at least one hospitalized VCD episode meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue hemorrhagic fever was graded as - Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation was a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.

14. Number of Episodes of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23) [Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23]

    Episodes were defined as the number of hospitalized virologically confirmed dengue episodes meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 7 Years to 16 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ongoing participation in study CYD23 at the time of enrolment.

• Assent form was signed and dated by the participant (for participants >= 7 years old), and informed consent form was signed and dated by the parent(s) or another legally accepted representative and by 2 independent witnesses.

• Participant and parent/legally accepted representative were able to attend all scheduled visits to comply with all study procedures.

Exclusion Criteria:

• Planned participation in another dengue clinical trial during the present study

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Ratchaburi	Muang District	Thailand

Sponsors and Collaborators

• Sanofi Pasteur, a Sanofi Company

Investigators

• Study Director: Medical Director, Sanofi Pasteur SA

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Related Info
• Related Info

Publications

None provided.

• Responsible Party: Sanofi Pasteur, a Sanofi Company
• ClinicalTrials.gov Identifier: NCT01983553
• Other Study ID Numbers: CYD57; U1111-1127-7380
• First Posted: Nov 14, 2013
• Last Update Posted: Mar 29, 2022
• Last Verified: Mar 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sanofi Pasteur, a Sanofi Company: Dengue Virus; Dengue Fever; Dengue Hemorrhagic Fever; CYD Dengue Vaccine
• Additional relevant MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Fever; Hyperthermia

Study Results

Participant Flow

Recruitment Details	Study participants were enrolled in the original study CYD23 (NCT00842530) from 10 September 2013 to 29 November 2013 at 1 clinic center in Thailand.
Pre-assignment Detail	Of the 3997 participants who were treated in the original study CYD23, a total of 3203 participants were included in this CYD57 study to continue the 4-year safety follow-up.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Period Title: Overall Study
STARTED	2131	1072
COMPLETED	2131	1072
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	CYD Dengue Vaccine Group	Control Group	Total
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Total of all reporting groups
Overall Participants	2131	1072	3203
Age (Count of Participants)
<=18 years	2131 100%	1072 100%	3203 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.11 (2.02)	8.15 (2.06)	8.13 (2.03)
Sex: Female, Male (Count of Participants)
Female	1118 52.5%	579 54%	1697 53%
Male	1013 47.5%	493 46%	1506 47%

Outcome Measures

1. Primary Outcome

Title	Event Rate Per 100 Participant-years for Hospitalized Virologically-Confirmed Dengue (VCD) Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in the Previous Study (CYD23)
Description	Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Any of the 4 Serotypes	1.0	1.1
Serotype 1	0.2	0.3
Serotype 2	0.3	0.3
Serotype 3	0.2	0.2
Serotype 4	0.2	0.3
Unserotyped	0.0	0.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative risk; Any of the 4 Serotypes
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Any of the 4 Serotypes between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.930
	Confidence Interval	(2-Sided) 95%; 0.64 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative risk; Serotype 1
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 1 between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.960
	Confidence Interval	(2-Sided) 95%; 0.44 to 2.21
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative risk; Serotype 2
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 2 between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.326
	Confidence Interval	(2-Sided) 95%; 0.64 to 2.94
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative risk; Serotype 3
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 3 between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.056
	Confidence Interval	(2-Sided) 95%; 0.48 to 2.51
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative risk; Serotype 4
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 4 between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.629
	Confidence Interval	(2-Sided) 95%; 0.27 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative risk; Unserotyped
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Unserotyped between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.000
	Confidence Interval	(2-Sided) 95%; 0.00 to 1.22
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

2. Primary Outcome

Title	Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23)
Description	Cases were defined as the number of participants with at least one hospitalized VCD episode.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Cases: Any of the 4 Serotypes	85	46
Cases: Serotype 1	21	11
Cases: Serotype 2	29	11
Cases: Serotype 3	21	10
Cases: Serotype 4	15	12
Cases: Unserotyped	0	3

3. Primary Outcome

Title	Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With Either CYD Dengue Vaccine or a Placebo in a Previous Study (CYD23)
Description	Episodes were defined as the number of hospitalized VCD episodes.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Episodes: Any of the 4 Serotypes	85	46
Episodes: Serotype 1	21	11
Episodes: Serotype 2	29	11
Episodes: Serotype 3	21	10
Episodes: Serotype 4	15	12
Episodes: Unserotyped	0	3

4. Primary Outcome

Title	Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS. Here, "number analyzed" signifies participants with available data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
4 to 5 Years: Any of the 4 Serotypes	1.7	1.2
6 to 11 Years: Any of the 4 Serotypes	0.8	1.1
4 to 5 Years: Serotype 1	0.6	0.1
6 to 11 Years: Serotype 1	0.2	0.3
4 to 5 Years: Serotype 2	0.4	0.1
6 to 11 Years: Serotype 2	0.3	0.3
4 to 5 Years: Serotype 3	0.3	0.3
6 to 11 Years: Serotype 3	0.2	0.2
4 to 5 Years: Serotype 4	0.4	0.4
6 to 11 Years: Serotype 4	0.1	0.3
4 to 5 Years: Unserotyped	0.0	0.3
6 to 11 Years: Unserotyped	0.0	0.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 4 to 5 years; Any Serotype
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Any of the 4 Serotypes (4 to 5 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 585 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.411
	Confidence Interval	(2-Sided) 95%; 0.64 to 3.42
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 6 to 11 years; Any Serotype
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Any of the 4 Serotypes (6 to 11 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 2618 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.807
	Confidence Interval	(2-Sided) 95%; 0.53 to 1.25
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 4 to 5 years; Serotype 1
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 1 (4 to 5 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 585 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	4.885
	Confidence Interval	(2-Sided) 95%; 0.70 to 212.02
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 6 to 11 years; Serotype 1
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 1 (6 to 11 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 2618 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.557
	Confidence Interval	(2-Sided) 95%; 0.21 to 1.46
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 4 to 5 years; Serotype 2
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 2 (4 to 5 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 585 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	2.931
	Confidence Interval	(2-Sided) 95%; 0.36 to 134.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 6 to 11 years; Serotype 2
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 2 (6 to 11 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 2618 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.165
	Confidence Interval	(2-Sided) 95%; 0.53 to 2.74
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 4 to 5 years; Serotype 3
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants at Year 1 for Serotype 3 (4 to 5 year) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 585 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.221
	Confidence Interval	(2-Sided) 95%; 0.20 to 12.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 6 to 11 years; Serotype 3
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 3 (6 to 11 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 2618 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.013
	Confidence Interval	(2-Sided) 95%; 0.41 to 2.73
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 9

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 4 to 5 years; Serotype 4
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 4 (4 to 5 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 585 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.977
	Confidence Interval	(2-Sided) 95%; 0.21 to 6.04
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 10

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 6 to 11 years; Serotype 4
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 4 (6 to 11 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 2618 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.506
	Confidence Interval	(2-Sided) 95%; 0.18 to 1.44
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 11

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 4 to 5 years; Unserotyped
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Unserotyped (4 to 5 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 585 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.000
	Confidence Interval	(2-Sided) 95%; 0.00 to 2.60
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 12

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; 6 to 11 years; Unserotyped
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Unserotyped (6 to 11 years) between the CYD Dengue vaccine group and the Control group. Total number of participants analyzed were 2618 instead of 3203.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.000
	Confidence Interval	(2-Sided) 95%; 0.00 to 19.75
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

5. Primary Outcome

Title	Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Cases were defined as the number of participants with at least one hospitalized VCD episode.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS. Here, "number analyzed" signifies participants with evaluable data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
4 to 5 years cases: Any of the 4 serotype	26	9
6 to 11 years cases: Any of the 4 Serotypes	59	37
4 to 5 years cases: Serotype 1	10	1
6 to 11 years cases: Serotype 1	11	10
4 to 5 years cases: Serotype 2	6	1
6 to 11 years cases: Serotype 2	23	10
4 to 5 years cases: Serotype 3	5	2
6 to 11 years cases: Serotype 3	16	8
4 to 5 years cases: Serotype 4	6	3
6 to 11 years cases: Serotype 4	9	9
4 to 5 years cases: Unserotyped	0	2
6 to 11 years cases: Unserotyped	0	1

6. Primary Outcome

Title	Number of Episodes of Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Collected By Age Group (Aged: 4-5; 6-11 Years) Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Episodes were defined as the number of hospitalized VCD episodes.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS. Here, "number analyzed" signifies participants with evaluable data for each specified category.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
4 to 5 years episodes: Any of 4 serotype	26	9
6 to11 years episodes: Any of 4 Serotypes	59	37
4 to 5 years episodes: Serotype 1	10	1
6 to 11 years episodes: Serotype 1	11	10
4 to 5 years episodes: Serotype 2	6	1
6 to 11 years episodes: Serotype 2	23	10
4 to 5 years episodes: Serotype 3	5	2
6 to 11 years episodes: Serotype 3	16	8
4 to 5 years episodes: Serotype 4	6	3
6 to 11 years episodes: Serotype 4	9	9
4 to 5 years episodes: Unserotyped	0	2
6 to 11 years episodes: Unserotyped	0	1

7. Primary Outcome

Title	Event Rate Per 100 Participant-years for Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype Following Vaccination With Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Event rate per 100 participant-years for Clinically Severe hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Any of the 4 Serotypes	0.1	0.1
Serotype 1	0.1	0.0
Serotype 2	0.1	0.1
Serotype 3	0.1	0.0
Serotype 4	0.1	0.1
Unserotyped	0.0	0.0

8. Primary Outcome

Title	Number of Clinically Severe Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Cases were defined as the number of participants with at least one hospitalized VCD episode.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Cases: Any of the 4 Serotypes	8	3
Cases: Serotype 1	6	0
Cases: Serotype 2	1	1
Cases: Serotype 3	1	0
Cases: Serotype 4	1	2
Cases: Unserotyped	0	0

9. Primary Outcome

Title	Number of Episodes of Clinically Severe Hospitalized VCD Due to Any and Each Serotype (1, 2, 3 and 4) Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Episodes were defined as the number of hospitalized VCD episodes.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Episodes: Any of the 4 Serotypes	8	3
Episodes: Serotype 1	6	0
Episodes: Serotype 2	1	1
Episodes: Serotype 3	1	0
Episodes: Serotype 4	1	2
Episodes: Unserotyped	0	0

10. Primary Outcome

Title	Number of Cases of Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23)
Description	Cases were defined as the number of participants with at least one non-serotype specific dengue viremia among hospitalized VCD cases.
Time Frame	During Year 1 to Year 4 post 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sera sample collection time interval of 14 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS. Here, 'number analyzed' = number of hospitalized VCD episodes in the specified time period.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Cases - Anytime	78 3.7%	42 3.9%
Cases - 0-3 days	25 1.2%	12 1.1%
Cases - 4-7 days	53 2.5%	27 2.5%
Cases - 0-7 days	78 3.7%	39 3.6%
Cases - After 7 days	NA NaN	3 0.3%

11. Primary Outcome

Title	Non-Serotype Specific Dengue Viremia Among Hospitalized VCD Cases Following Vaccination With CYD Dengue Vaccine or Placebo in Previous Study (CYD23)
Description	Quantified viremia was defined as greater than or equal to (>=) lower limit of quantitation (log10 plaque forming unit [pfu]/mL).
Time Frame	Year 1 to Year 4 post-vaccination after 3rd vaccination at Month 12 in CYD23 at each of the following time points: Anytime, 0-3 days, 4-7 days, 0-7 days, After 7 days during the sample collection time interval of 14 days

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS. Here, 'number analyzed' = number of hospitalized VCD episodes in the specified time period.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Mean Viremia - Anytime	3.64 (1.17)	3.38 (1.21)
Mean Viremia - 0-3 days	4.35 (1.11)	3.83 (1.53)
Mean Viremia - 4-7 days	3.31 (1.06)	3.12 (0.957)
Mean Viremia - 0-7 days	3.64 (1.17)	3.34 (1.19)
Mean Viremia - After 7 days	NA (NA)	3.88 (1.63)

12. Primary Outcome

Title	Event Rate Per 100 Participant-years for Hospitalized VCD Cases Due to Any and Each Serotype and Meeting World Health Organization (WHO) 1997 Criteria Collected Following Either CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Event rate per 100 participant-years for hospitalized VCD cases, due to any and each serotype (1, 2, 3 and 4) following vaccination with either CYD Dengue vaccine or Placebo in the previous study (CYD23) were reported. Endpoint values <0.1 were rounded to 0.1. The WHO criteria were fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Any of the 4 Serotypes: Any Grade	0.1	0.1
Any of the 4 Serotypes: Grade I	0.1	0.1
Any of the 4 Serotypes: Grade II	0.1	0.1
Any of the 4 Serotypes: Grade III	0.1	0.0
Any of the 4 Serotypes: Grade IV	0.0	0.0
Serotype 1: Any Grade	0.1	0.0
Serotype 1: Grade I	0.1	0.0
Serotype 1: Grade II	0.1	0.0
Serotype 1: Grade III	0.1	0.0
Serotype 1: Grade IV	0.0	0.0
Serotype 2: Any Grade	0.1	0.1
Serotype 2: Grade I	0.1	0.1
Serotype 2: Grade II	0.0	0.0
Serotype 2: Grade III	0.0	0.0
Serotype 2: Grade IV	0.0	0.0
Serotype 3: Any Grade	0.1	0.0
Serotype 3: Grade I	0.0	0.0
Serotype 3: Grade II	0.1	0.0
Serotype 3 Grade III	0.0	0.0
Serotype 3: Grade IV	0.0	0.0
Serotype 4: Any Grade	0.1	0.1
Serotype 4: Grade I	0.0	0.1
Serotype 4: Grade II	0.1	0.1
Serotype 4: Grade III	0.0	0.0
Serotype 4: Grade IV	0.0	0.0
Unserotyped: Any Grade	0.0	0.0
Unserotyped: Grade I	0.0	0.0
Unserotyped: Grade II	0.0	0.0
Unserotyped: Grade III	0.0	0.0
Unserotyped: Grade IV	0.0	0.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Any serotype; Any grade
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Any of the 4 Serotypes; Any grade between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	1.174
	Confidence Interval	(2-Sided) 95%; 0.27 to 7.03
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Any serotype; Grade I
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Any of the 4 Serotypes; Grade I between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.252
	Confidence Interval	(2-Sided) 95%; 0.00 to 4.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Any serotype; Grade II
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Any of the 4 Serotypes Grade II between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	2.012
	Confidence Interval	(2-Sided) 95%; 0.20 to 99.10
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Serotype 2; Any grade
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 2 Any grade between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.503
	Confidence Interval	(2-Sided) 95%; 0.01 to 39.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Serotype 2; Grade I
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 2 Grade I between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.503
	Confidence Interval	(2-Sided) 95%; 0.01 to 39.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Serotype 4; Any grade
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 4 Any grade between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.252
	Confidence Interval	(2-Sided) 95%; 0.00 to 4.83
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 7

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Serotype 4; Grade I
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 4 Grade I between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.000
	Confidence Interval	(2-Sided) 95%; 0.00 to 19.62
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

Statistical Analysis 8

Statistical Analysis Overview	Comparison Group Selection	CYD Dengue Vaccine Group, Control Group
	Comments	Relative Risk; Serotype 4; Grade II
	Type of Statistical Test	Other
	Comments	Relative risk analysis of the event rate per 100 participants during Year 1 to Year 4 for Serotype 4 Grade II between the CYD Dengue vaccine group and the Control group.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Relative Risk
	Estimated Value	0.503
	Confidence Interval	(2-Sided) 95%; 0.01 to 39.49
	Parameter Dispersion	Type: Value:
	Estimation Comments	The 95% confidence interval of the relative risk was calculated using the Exact method described by Breslow and Day.

13. Primary Outcome

Title	Number of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Cases were defined as the number of participants with at least one hospitalized VCD episode meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue hemorrhagic fever was graded as - Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation was a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Cases: Any of the 4 Serotypes: Any Grade	7	3
Cases: Any of the 4 Serotypes: Grade I	1	2
Cases: Any of the 4 Serotypes: Grade II	4	1
Cases: Any of the 4 Serotypes: Grade III	2	0
Cases: Any of the 4 Serotypes: Grade IV	0	0
Cases: Serotype 1: Any Grade	5	0
Cases: Serotype 1: Grade I	1	0
Cases: Serotype 1: Grade II	2	0
Cases: Serotype 1: Grade III	2	0
Cases: Serotype 1: Grade IV	0	0
Cases: Serotype 2: Any Grade	1	1
Cases: Serotype 2: Grade I	1	1
Cases: Serotype 2: Grade II	0	0
Cases: Serotype 2: Grade III	0	0
Cases: Serotype 2: Grade IV	0	0
Cases: Serotype 3: Any Grade	1	0
Cases: Serotype 3: Grade I	0	0
Cases: Serotype 3: Grade II	1	0
Cases: Serotype 3: Grade III	0	0
Cases: Serotype 3: Grade IV	0	0
Cases: Serotype 4: Any Grade	1	2
Cases: Serotype 4: Grade I	0	1
Cases: Serotype 4: Grade II	1	1
Cases: Serotype 4: Grade III	0	0
Cases: Serotype 4: Grade IV	0	0
Cases: Unserotyped: Any Grade	0	0
Cases: Unserotyped: Grade I	0	0
Cases: Unserotyped: Grade II	0	0
Cases: Unserotyped: Grade III	0	0
Cases: Unserotyped: Grade IV	0	0

14. Primary Outcome

Title	Number of Episodes of Hospitalized VCD Cases Due to Any and Each Serotype (1, 2, 3 and 4) and Meeting WHO 1997 Criteria Following Vaccination With CYD Dengue Vaccine or Placebo in a Previous Study (CYD23)
Description	Episodes were defined as the number of hospitalized virologically confirmed dengue episodes meeting WHO criteria. The WHO criteria was fever, any haemorrhagic manifestations, thrombocytopenia, plasma leakage or pleural effusion and/or ascites and/or hypoalbuminemia. Dengue haemorrhagic fever was graded as Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.
Time Frame	Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23

Outcome Measure Data

Analysis Population Description

Analysis was performed on FupAS.

Arm/Group Title	CYD Dengue Vaccine Group	Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.	Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
Measure Participants	2131	1072
Episodes: Any of the 4 Serotypes: Any Grade	7	3
Episodes: Any of the 4 Serotypes: Grade I	1	2
Episodes: Any of the 4 Serotypes: Grade II	4	1
Episodes: Any of the 4 Serotypes: Grade III	2	0
Episodes: Any of the 4 Serotypes: Grade IV	0	0
Episodes: Serotype 1: Any Grade	5	0
Episodes: Serotype 1: Grade I	1	0
Episodes: Serotype 1: Grade II	2	0
Episodes: Serotype 1: Grade III	2	0
Episodes: Serotype 1: Grade IV	0	0
Episodes: Serotype 2: Any Grade	1	1
Episodes: Serotype 2: Grade I	1	1
Episodes: Serotype 2: Grade II	0	0
Episodes: Serotype 2: Grade III	0	0
Episodes: Serotype 2 Grade IV	0	0
Episodes: Serotype 3: Any Grade	1	0
Episodes: Serotype 3: Grade I	0	0
Episodes: Serotype 3: Grade II	1	0
Episodes: Serotype 3: Grade III	0	0
Episodes: Serotype 3: Grade IV	0	0
Episodes: Serotype 4: Any Grade	1	2
Episodes: Serotype 4: Grade I	0	1
Episodes: Serotype 4: Grade II	1	1
Episodes: Serotype 4: Grade III	0	0
Episodes: Serotype: 4 Grade IV	0	0
Episodes: Unserotyped: Any Grade	0	0
Episodes: Unserotyped: Grade I	0	0
Episodes: Unserotyped: Grade II	0	0
Episodes: Unserotyped: Grade III	0	0
Episodes: Unserotyped: Grade IV	0	0

Adverse Events

Time Frame	Adverse event data was collected throughout the study period (Year 1 to Year 4 post- 3rd vaccination at Month 12 in CYD23)
Adverse Event Reporting Description	This study involved a passive surveillance of hospitalized dengue cases and related and fatal serious adverse events in participants that participated in a previous study (CYD23). Non-serious adverse event data was not collected since no vaccine was administered in the present study. Analysis was performed on FupAS.
Arm/Group Title	CYD Dengue Vaccine Group		Control Group
Arm/Group Description	Participants who received 3 injections of 0.5 mL CYD dengue vaccine, 1 injection each at 0, 6, and 12 months, subcutaneously in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.		Participants who received either 0.5 mL Rabies vaccine (Verorab®) or placebo control, subcutaneously as a first injection on Day 0, placebo for second and third injections at 6 and 12 months, respectively, in the previous study CYD23, were followed up for safety in this study for 4 years after the 3rd vaccination at Month 12 in CYD23.
All Cause Mortality
	CYD Dengue Vaccine Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/2131 (0.1%)		2/1072 (0.2%)
Serious Adverse Events
	CYD Dengue Vaccine Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/2131 (0.1%)		2/1072 (0.2%)
General disorders
Drowning	0/2131 (0%)	0	1/1072 (0.1%)	1
Injury, poisoning and procedural complications
Gun-shot wound	2/2131 (0.1%)	2	0/1072 (0%)	0
Road traffic accident	1/2131 (0%)	1	1/1072 (0.1%)	1
Other (Not Including Serious) Adverse Events
	CYD Dengue Vaccine Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

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