Trial Outcomes & Findings for Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America (NCT NCT01374516)

Last Updated: 2022-03-21

Results Overview

Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue reverse transcriptase polymerase chain reaction (RT-PCR) and/or dengue non-structural (NS) protein 1 antigen enzyme-linked immunosorbent assay (ELISA). Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

20869 participants

Primary outcome timeframe

28 days and up to 13 months post-injection 3

Results posted on

2022-03-21

Participant Flow

Study participants were enrolled from 08 June 2011 to 16 March 2012 at 5 clinical centers in Brazil, 9 in Colombia, 1 in Honduras, 5 in Mexico, and 2 in Puerto Rico.

A total of 20869 participants were enrolled and randomized in the study.

Participant milestones

Participant milestones
Measure	CYD Dengue Vaccine Group Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Placebo Group Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Vaccination Phase (Up to 25 Months) STARTED	13920	6949
Vaccination Phase (Up to 25 Months) COMPLETED	13281	6640
Vaccination Phase (Up to 25 Months) NOT COMPLETED	639	309
Surveillance Expansion Period STARTED	13281	6640
Surveillance Expansion Period COMPLETED	10932	5387
Surveillance Expansion Period NOT COMPLETED	2349	1253

Reasons for withdrawal

Reasons for withdrawal
Measure	CYD Dengue Vaccine Group Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Placebo Group Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).
Vaccination Phase (Up to 25 Months) Protocol Violation	43	14
Vaccination Phase (Up to 25 Months) Adverse Event	3	0
Vaccination Phase (Up to 25 Months) Withdrawal by Subject	480	240
Vaccination Phase (Up to 25 Months) Lost to Follow-up	106	46
Vaccination Phase (Up to 25 Months) Serious adverse event	7	9
Surveillance Expansion Period Protocol Violation	386	217
Surveillance Expansion Period Withdrawal by Subject	1870	986
Surveillance Expansion Period Lost to Follow-up	73	45
Surveillance Expansion Period Serious adverse event	20	5

Baseline Characteristics

Study of a Novel Tetravalent Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	CYD Dengue Vaccine Group n=13920 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Placebo Group n=6949 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months and were followed up to 60 months after last vaccination (or a total duration of up to 72 months).	Total n=20869 Participants Total of all reporting groups
Age, Categorical <=18 years	13920 Participants n=5 Participants	6949 Participants n=7 Participants	20869 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous Age Continuous	12.5 Years STANDARD_DEVIATION 2.14 • n=5 Participants	12.5 Years STANDARD_DEVIATION 2.13 • n=7 Participants	12.5 Years STANDARD_DEVIATION 2.14 • n=5 Participants
Sex: Female, Male Female	7048 Participants n=5 Participants	3532 Participants n=7 Participants	10580 Participants n=5 Participants
Sex: Female, Male Male	6872 Participants n=5 Participants	3417 Participants n=7 Participants	10289 Participants n=5 Participants
Region of Enrollment Colombia	6497 Participants n=5 Participants	3246 Participants n=7 Participants	9743 Participants n=5 Participants
Region of Enrollment Brazil	2370 Participants n=5 Participants	1178 Participants n=7 Participants	3548 Participants n=5 Participants
Region of Enrollment Mexico	2312 Participants n=5 Participants	1152 Participants n=7 Participants	3464 Participants n=5 Participants
Region of Enrollment Honduras	1866 Participants n=5 Participants	933 Participants n=7 Participants	2799 Participants n=5 Participants
Region of Enrollment Puerto Rico	875 Participants n=5 Participants	440 Participants n=7 Participants	1315 Participants n=5 Participants

PRIMARY outcome

Timeframe: 28 days and up to 13 months post-injection 3

Population: Number of symptomatic VCD cases were assessed in the Per-Protocol Analysis Set for Efficacy, defined as participants who had no protocol deviations.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=12574 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6261 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Symptomatic Virologically Confirmed Dengue (VCD) Cases Due to Any Serotype During the Active Phase Post-dose 3 Following Injection With Either CYD Dengue Vaccine or a Placebo	176 Cases	221 Cases

SECONDARY outcome

Timeframe: Day 0 up to 13 months post-injection 3

Population: Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included all participants who received at least 1 injection.

Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>=38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=13914 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6940 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Symptomatic VCD Cases Due to Any Serotype During the Active Phase Following Injection With Either CYD Dengue Vaccine or a Placebo	277 Cases	385 Cases

SECONDARY outcome

Timeframe: 28 days post-injection 1 and up to 13 months post-injection 3

Population: Number of symptomatic VCD cases were assessed in the Full Analysis Set for Efficacy, which included participants who received at least 1 dose of study vaccine.

Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=13914 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6940 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Symptomatic VCD Cases Due to Any Serotype Occurring 28 Days Post-dose 1 Following Injection With Either CYD Dengue Vaccine or a Placebo	273 Cases	380 Cases

SECONDARY outcome

Timeframe: 28 days post-injection 2 and up to 13 months post-injection 3

Population: Number of symptomatic VCD cases were assessed in the Other Efficacy Analysis Set, which included participants who received at least 2 doses of study vaccine.

Symptomatic VCD cases were defined as occurrence of acute febrile illness (temperature \>= 38°C on at least 2 consecutive days) and confirmation of dengue virus infection by dengue RT-PCR and/or dengue NS 1 ELISA. Vaccine efficacy was defined as 1 minus the ratio of density incidence due to any serotype after at least 1 dose in the CYD Dengue Vaccine Group over the density incidence of the Placebo Group.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=13506 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6765 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Symptomatic VCD Cases Due to Any Serotype Post-dose 2 Following Injection With Either CYD Dengue Vaccine or a Placebo	236 Cases	306 Cases

SECONDARY outcome

Timeframe: Day 0 to the end of study (up to 72 months)

Population: Number of WHO dengue hemorrhagic fever cases were assessed in the Safety Analysis Set, which included all participants who received at least one dose of study vaccine. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Dengue hemorrhagic fever (DHF) cases were defined as number of participants with at least one symptomatic VCD episode meeting the 1997 WHO criteria. (a) Fever: acute onset, high (\>= 38°C) and continuous, lasting 2 to 7 days and (b) any of the pre-listed hemorrhagic manifestations and laboratory findings of thrombocytopenia (platelet \<=100 x 109/L) and plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion (seen on CXR) and/or ascites and/ or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish a clinical diagnosis of DHF. DHF was graded as follows: 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 hemorrhage.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=12809 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6380 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Any Grade	7 Cases	15 Cases
Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade I	0 Cases	2 Cases
Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade II	7 Cases	13 Cases
Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade III	0 Cases	0 Cases
Number of Symptomatic VCD Cases Meeting World Health Organization (WHO) Criteria Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade IV	0 Cases	0 Cases

SECONDARY outcome

Timeframe: From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)

Population: Number of WHO dengue hemorrhagic fever cases were assessed in the Full Analysis Set for Surveillance Expansion Period, which included all participants who received at least 1 injection and accepted to be included in the Surveillance Expansion Period.

The 1997 WHO criteria are: a) Fever: acute onset, high (\>= 38°C) and continuous, for 2 to 7 days and (b) any of the following: thrombocytopenia (platelet \<=100 x 109/L) and plasma leakage as shown by hematocrit increased by 20% or more or pleural effusion and/or ascites and/or hypoalbuminemia. The first two clinical criteria plus thrombocytopenia and signs of plasma leakage are enough to establish diagnosis of DHF. DHF was graded as follows: 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 participant, 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; and Grade IV: Profound shock with undetectable blood pressure and pulse.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=11063 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=5430 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade I	0 Cases	0 Cases
Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Any Grade	2 Cases	0 Cases
Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade II	2 Cases	0 Cases
Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade III	0 Cases	0 Cases
Number of Symptomatic VCD Cases Meeting WHO Criteria During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo Due to Any of the 4 Serotypes: Grade IV	0 Cases	0 Cases

SECONDARY outcome

Timeframe: Day 0 up to the end of study (up to 72 months)

Population: Number of hospitalized dengue hemorrhagic fever cases were assessed in the Safety Analysis Set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Hospitalized VCD cases were defined as VCD confirmed by dengue RT-PCR and/or dengue NS 1 ELISA in participants with acute febrile illness (temperature \>=38°C on at least 2 consecutive days) requiring hospitalization.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=12809 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6380 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Hospitalized VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	46 Cases	71 Cases

SECONDARY outcome

Timeframe: From consent to participate in the Surveillance Expansion Period to end of the study (up to 72 months)

Population: Analysis was performed in the Safety Analysis Set.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=13915 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6939 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Hospitalized VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	5 Cases	2 Cases

SECONDARY outcome

Timeframe: Day 0 to the end of study (up to 72 months)

Population: Number of clinically severe VCD cases were assessed in the Safety Analysis Set. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The severity of VCD cases was assessed by an Independent Data monitoring Committee (IDMC) based on a medical review of cases and any of the following criteria:1) Platelet count \<=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20 mmHg in a child, or hypotension \[\<= 90 mmHg\] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by Glasgow Coma Scale (GCS) score 5) Liver impairment (AST \>1000 IU/L or prothrombin time \[PT\] International normalized ratio \[INR\] \>1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine \>= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=12809 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=6380 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Clinically Severe VCD Cases Throughout the Trial Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	9 Cases	16 Cases

SECONDARY outcome

Timeframe: From consent to participate in the Surveillance Expansion Period to the end of study (up to 72 months)

Population: Number of clinically severe VCD cases were assessed in the Full Analysis Set for Surveillance Expansion Period. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

The severity of VCD cases was assessed by an IDMC based on a medical review of cases and any of the following criteria:-1) Platelet count \<=100000 /μl and bleeding (tourniquet, petechiae or any bleeding) plus plasma leakage 2) Shock (pulse pressure \<= 20 mmHg in a child, or hypotension \[\<= 90 mmHg\] with tachycardia, weak pulse and poor perfusion) 3) Bleeding requiring blood transfusion 4) Encephalopathy i.e. Unconsciousness or poor conscious state or fitting not attributable to simple febrile convulsion or focal neurological signs. Poor conscious state or unconsciousness must be supported by GCS score 5) Liver impairment (AST \>1000 IU/L or PT INR \>1.5) excluding other causes of viral hepatitis 6) Impaired kidney function (serum creatinine \>= 1.5 mg/dL) 7) Myocarditis, pericarditis or clinical heart failure supported by CXR, echocardiography, ECG or cardiac enzymes.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=11061 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=5431 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Clinically Severe VCD Cases During the Surveillance Expansion Period Due to Any Serotype Following Injection With Either CYD Dengue Vaccine or a Placebo	42 Cases	34 Cases

SECONDARY outcome

Timeframe: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (Visit [V] 07) and 60 months (Visit [V] 12) post-injection 3

Population: Antibody titers against each dengue virus serotype strain were assessed in Full Analysis Set for Immunogenicity(FASI),which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose.Here, 'number analyzed'=participants with available data for each specified category.

Dengue neutralizing antibody levels against each of the 4 dengue virus serotypes (parental strains) were measured by the plaque reduction neutralization test in a pre-defined subset of participants.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=1301 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=643 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 3; Pre-Inj. 1	76.5 Percentage of participants	73.6 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 3; Post-Inj. 2	98.5 Percentage of participants	75.7 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 1: Pre-Inj.1	72.8 Percentage of participants	70.5 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 1: Post-Inj. 2	92.7 Percentage of participants	71.8 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 1: Post-Inj. 3	94.9 Percentage of participants	74.2 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 1; 1 year Post-Inj. 3 (V 07)	85.6 Percentage of participants	73.6 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 1; 5 year Post-Inj. 3 (V 12)	90.0 Percentage of participants	81.1 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 2; Pre-Inj. 1	76.1 Percentage of participants	73.8 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 2; Post-Inj. 2	97.5 Percentage of participants	75.1 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 2; Post-Inj. 3	98.5 Percentage of participants	77.2 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 2; 1 year Post-Inj. 3 (V 07)	94.1 Percentage of participants	78.9 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 2; 5 year Post-Inj. 3 (V 12)	93.5 Percentage of participants	83.1 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 3; Post-Inj. 3	98.4 Percentage of participants	78.0 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 3; 1 year Post-Inj. 3 (V 07)	92.7 Percentage of participants	76.2 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 3; 5 year Post-Inj. 3 (V 12)	95.4 Percentage of participants	82.7 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 4; Pre-Inj. 1	68.2 Percentage of participants	65.0 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 4; Post-Inj. 2	96.9 Percentage of participants	67.0 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 4; Post-Inj. 3	98.1 Percentage of participants	68.9 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 4; 1 year Post-Inj. 3 (V 07)	94.9 Percentage of participants	69.0 Percentage of participants
Percentage of Participants With Antibody Titers >=10 1/Dil Against Each Dengue Virus Serotype Before and Following Injection (Inj.) With CYD Dengue Vaccine or Placebo Dengue virus Serotype 4; 5 year Post-Inj. 3 (V 12)	96.3 Percentage of participants	78.9 Percentage of participants

SECONDARY outcome

Timeframe: Pre-injection 1, 28 days post Injections 2 and 3, 13 months (V 07) and 60 months (V 12) post-injection 3

Population: Antibody titers against each dengue virus serotype strain were assessed in FASI, which included a subset of participants who received at least one dose of vaccine and had a blood sample drawn and result available after the dose. Here,'number analyzed' = participants with available data for each specified category.

Geometric mean titers for each of the 4 dengue virus serotypes (parental strains) were assessed using the plaque reduction neutralization test in a pre-defined subset of participants.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=1301 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=643 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 4; Post Inj. 2	261 Titers (1/dilution) Interval 242.0 to 281.0	40.9 Titers (1/dilution) Interval 35.5 to 47.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 4; Post Inj. 3	241 Titers (1/dilution) Interval 226.0 to 258.0	44.3 Titers (1/dilution) Interval 38.6 to 50.8
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 2; Post Inj. 3	574 Titers (1/dilution) Interval 528.0 to 624.0	129 Titers (1/dilution) Interval 109.0 to 152.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 3; Year 1 Post Inj. 3 (V 07)	292 Titers (1/dilution) Interval 263.0 to 325.0	137 Titers (1/dilution) Interval 114.0 to 165.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 3; Year 5 Post Inj. 3 (V 12)	346 Titers (1/dilution) Interval 313.0 to 383.0	224 Titers (1/dilution) Interval 185.0 to 271.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 4; Pre Inj. 1	43.6 Titers (1/dilution) Interval 39.6 to 48.0	39.0 Titers (1/dilution) Interval 33.9 to 44.7
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 2; Year 1 Post-Inj. 3 (V 07)	371 Titers (1/dilution) Interval 336.0 to 409.0	145 Titers (1/dilution) Interval 122.0 to 173.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 2; Year 5 Post-Inj. 3 (V 12)	297 Titers (1/dilution) Interval 269.0 to 328.0	201 Titers (1/dilution) Interval 168.0 to 242.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 3; Pre-Inj. 1	121 Titers (1/dilution) Interval 108.0 to 136.0	114 Titers (1/dilution) Interval 95.9 to 136.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 3; Post Inj. 2	556 Titers (1/dilution) Interval 506.0 to 610.0	117 Titers (1/dilution) Interval 98.3 to 139.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 3; Post Inj. 3	508 Titers (1/dilution) Interval 465.0 to 555.0	124 Titers (1/dilution) Interval 105.0 to 147.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 1; Pre-Inj. 1	128 Titers (1/dilution) Interval 112.0 to 145.0	119 Titers (1/dilution) Interval 98.7 to 142.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 1; Post Inj. 2	458 Titers (1/dilution) Interval 406.0 to 517.0	128 Titers (1/dilution) Interval 106.0 to 154.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 1; Post Inj. 3	395 Titers (1/dilution) Interval 353.0 to 441.0	121 Titers (1/dilution) Interval 101.0 to 145.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 1; Year 1 Post Inj. 3 (V 07)	266 Titers (1/dilution) Interval 234.0 to 302.0	146 Titers (1/dilution) Interval 121.0 to 176.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 1; Year 5 Post Inj. 3 (V 12)	284 Titers (1/dilution) Interval 252.0 to 321.0	210 Titers (1/dilution) Interval 172.0 to 255.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 2; Pre-Inj. 1	138 Titers (1/dilution) Interval 123.0 to 156.0	115 Titers (1/dilution) Interval 97.2 to 136.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 2; Post Inj. 2	622 Titers (1/dilution) Interval 566.0 to 684.0	124 Titers (1/dilution) Interval 104.0 to 148.0
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 4; Year 1 Post Inj. 3 (V 07)	174 Titers (1/dilution) Interval 161.0 to 188.0	51.5 Titers (1/dilution) Interval 44.3 to 59.8
Geometric Mean Titers of Antibodies Against Each Dengue Virus Serotype Before and Following Injection With Either CYD Dengue Tetravalent Vaccine or a Placebo Dengue virus Serotype 4; Year 5 Post Inj. 3 (V 12)	144 Titers (1/dilution) Interval 134.0 to 156.0	73.6 Titers (1/dilution) Interval 63.4 to 85.5

SECONDARY outcome

Timeframe: Within 7 days after each and any injection

Population: Solicited injection site reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, 'number analyzed' = participants with available data for specified category.

Solicited injection site reactions: Pain, Erythema, and Swelling. Grade 3 reactions (9-11 years): Pain: incapacitating, unable to perform usual activities; Erythema and Swelling, \>= 50 mm. Grade 3 Solicited injection site reactions (12-16 years): Pain: significant, prevents daily activity; Erythema and Swelling, \>100 mm.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=1333 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=664 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Pain (Post any injection)	650 Participants	270 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Erythema (Post-any injection)	83 Participants	44 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Swelling (Post-any injection)	77 Participants	27 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Pain (Post-injection 1)	430 Participants	173 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Pain (Post-injection 1)	11 Participants	6 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Erythema (Post-injection 1)	55 Participants	31 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Erythema (Post-injection 1)	0 Participants	1 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Swelling (Post-injection 1)	47 Participants	18 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Swelling (Post-injection 1)	0 Participants	1 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Pain (Post-injection 2)	332 Participants	105 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Pain (Post-injection 2)	7 Participants	0 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Erythema (Post-injection 2)	25 Participants	11 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Erythema (Post-injection 2)	1 Participants	0 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Swelling (Post-injection 2)	25 Participants	6 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Swelling (Post-injection 2)	0 Participants	0 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Pain (Post-injection 3)	288 Participants	104 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Pain (Post-injection 3)	11 Participants	2 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Erythema (Post-injection 3)	19 Participants	10 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Erythema (Post-injection 3)	0 Participants	0 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Injection-site Swelling (Post-injection 3)	20 Participants	8 Participants
Number of Participants With Solicited Injection Site Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Injection-site Swelling (Post-injection 3)	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Within 14 days after each and any injection

Population: Solicited systemic reactions were assessed in a subset of the Safety Analysis Set, which included all participants who received at least one dose of study vaccine and who were evaluated for reactogenicity. Here, 'number analyzed' = participants with available data for specified category.

Solicited systemic reactions: Fever (Temperature), Headache, Malaise, Myalgia, and Asthenia. Grade 3 reactions: Fever: \>= 39°C; Headache, Malaise, Myalgia, and Asthenia: significant, prevents daily activity.

Outcome measures

Outcome measures
Measure	CYD Dengue Vaccine Group n=1333 Participants Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=664 Participants Participants received 3 doses of placebo matched to vaccine; one each at 0, 6, and 12 months.
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Fever (Post any injection)	220 Participants	123 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Fever (Post-injection 1)	86 Participants	42 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Myalgia (Post-injection 1)	29 Participants	10 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Asthenia (Post-injection 2)	24 Participants	7 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Headache (Post any injection)	727 Participants	379 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Malaise (Post any injection)	536 Participants	261 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Myalgia (Post any injection)	576 Participants	267 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Asthenia (Post any injection)	496 Participants	251 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Fever (Post-injection 1)	21 Participants	7 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Headache (Post-injection 1)	528 Participants	273 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Headache (Post-injection 1)	67 Participants	27 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Malaise (Post-injection 1)	324 Participants	170 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Malaise (Post-injection 1)	32 Participants	15 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Myalgia (Post-injection 1)	386 Participants	180 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Asthenia (Post-injection 1)	326 Participants	148 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Asthenia (Post-injection 1)	36 Participants	17 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Fever (Post-injection 2)	72 Participants	42 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Fever (Post-injection 2)	10 Participants	7 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Headache (Post-injection 2)	386 Participants	182 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Headache (Post-injection 2)	27 Participants	15 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Malaise (Post-injection 2)	270 Participants	106 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Malaise (Post-injection 2)	17 Participants	8 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Myalgia (Post-injection 2)	273 Participants	101 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Myalgia (Post-injection 2)	21 Participants	5 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Asthenia (Post-injection 2)	231 Participants	105 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Fever (Post-injection 3)	89 Participants	52 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Fever (Post-injection 3)	13 Participants	5 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Headache (Post-injection 3)	378 Participants	158 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Headache (Post-injection 3)	33 Participants	12 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Malaise (Post-injection 3)	246 Participants	96 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Malaise (Post-injection 3)	18 Participants	7 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Myalgia (Post-injection 3)	255 Participants	116 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Myalgia (Post-injection 3)	19 Participants	5 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Asthenia (Post-injection 3)	208 Participants	110 Participants
Number of Participants With Solicited Systemic Reactions Following Any and Each Injection With Either CYD Dengue Vaccine or a Placebo Grade 3 Asthenia (Post-injection 3)	17 Participants	8 Participants

Adverse Events

CYD Dengue Vaccine Group

Serious events: 1765 serious events

Other events: 1038 other events

Deaths: 42 deaths

Placebo Group

Serious events: 911 serious events

Other events: 515 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	CYD Dengue Vaccine Group n=1333 participants at risk；n=13915 participants at risk Participants received 3 doses of CYD dengue vaccine; one each at 0, 6, and 12 months.	Placebo Group n=664 participants at risk；n=6939 participants at risk Participants received 3 doses of placebo vaccine; one each at 0, 6, and 12 months.
General disorders Asthenia	37.5% 500/1333 • Number of events 771 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	38.1% 253/664 • Number of events 366 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
General disorders Injection Site Erythema	6.2% 83/1333 • Number of events 99 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	6.6% 44/664 • Number of events 52 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
General disorders Injection Site Pain	48.8% 650/1333 • Number of events 1056 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	40.7% 270/664 • Number of events 384 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
General disorders Injection Site Swelling	5.8% 77/1333 • Number of events 92 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	4.1% 27/664 • Number of events 32 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
General disorders Malaise	40.4% 539/1333 • Number of events 853 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	39.8% 264/664 • Number of events 383 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
General disorders Pyrexia	17.9% 238/1333 • Number of events 270 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	19.1% 127/664 • Number of events 142 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
Infections and infestations Influenza	5.7% 76/1333 • Number of events 80 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	5.6% 37/664 • Number of events 40 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
Infections and infestations Nasopharyngitis	11.3% 150/1333 • Number of events 163 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	9.0% 60/664 • Number of events 70 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
Musculoskeletal and connective tissue disorders Myalgia	43.4% 578/1333 • Number of events 921 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	40.2% 267/664 • Number of events 400 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.
Nervous system disorders Headache	56.5% 753/1333 • Number of events 1385 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.	58.4% 388/664 • Number of events 652 • Unsolicited adverse event (AE) data were collected from Day 0 (post-vaccination) up to 28 days after each vaccination. Solicited Reaction (SR) data were collected within 7 and 14 days after vaccination. Serious adverse event (SAE) data were collected throughout the study (up to 72 months). Analysis were performed on Safety Analysis Set. A SR was an AE that was prelisted (i.e., solicited) in the electronic case report form (eCRF) and considered to be related to vaccination (adverse drug reaction). An unsolicited AE was an observed AE that did not fulfill the conditions prelisted (i.e., solicited) in the eCRF in terms of symptom and/or onset post-vaccination.

Additional Information

Medical Director

Sanofi Pasteur Inc.

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER