Trial Outcomes & Findings for Lot-to-lot Consistency of 3 Lots of Tetravalent Dengue Vaccine (TDV) in Non-endemic Country(Ies) for Dengue (NCT NCT03423173)

Last Updated: 2020-10-20

Results Overview

GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% \[MNT50\]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

923 participants

Primary outcome timeframe

1 month post second dose (Day 120)

Results posted on

2020-10-20

Participant Flow

Participants took part in the study at 14 investigative sites in the United States from 12 February 2018 to 14 January 2019.

Healthy participants were enrolled in 2:2:2:1 ratio into one of the four trial groups and received either Tetravalent Dengue Vaccine (TDV) lot 1, TDV Lot 2, TDV Lot 3 or Placebo for the investigation of lot to lot consistency of three consecutive lots.

Participant milestones

Participant milestones
Measure	Placebo TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Overall Study STARTED	132	263	264	264
Overall Study Received at Least 1 Dose of the IP	131	263	262	263
Overall Study COMPLETED	113	228	237	234
Overall Study NOT COMPLETED	19	35	27	30

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Overall Study Randomized but not vaccinated	1	0	2	1
Overall Study Adverse Event	1	1	1	1
Overall Study Lost to Follow-up	10	19	17	22
Overall Study Withdrawal of consent	4	10	4	5
Overall Study Death	1	0	0	0
Overall Study Reason not Specified	2	5	3	1

Baseline Characteristics

Number analyzed is the number of participants with data available for height at Baseline.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo n=132 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=263 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=264 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=264 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.	Total n=923 Participants Total of all reporting groups
Age, Continuous	40.7 years STANDARD_DEVIATION 11.70 • n=132 Participants	40.8 years STANDARD_DEVIATION 12.54 • n=263 Participants	42.0 years STANDARD_DEVIATION 11.71 • n=264 Participants	40.9 years STANDARD_DEVIATION 12.77 • n=264 Participants	41.2 years STANDARD_DEVIATION 12.25 • n=923 Participants
Sex: Female, Male Female	69 Participants n=132 Participants	144 Participants n=263 Participants	150 Participants n=264 Participants	134 Participants n=264 Participants	497 Participants n=923 Participants
Sex: Female, Male Male	63 Participants n=132 Participants	119 Participants n=263 Participants	114 Participants n=264 Participants	130 Participants n=264 Participants	426 Participants n=923 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	9 Participants n=132 Participants	16 Participants n=263 Participants	25 Participants n=264 Participants	20 Participants n=264 Participants	70 Participants n=923 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	120 Participants n=132 Participants	247 Participants n=263 Participants	239 Participants n=264 Participants	244 Participants n=264 Participants	850 Participants n=923 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	3 Participants n=132 Participants	0 Participants n=263 Participants	0 Participants n=264 Participants	0 Participants n=264 Participants	3 Participants n=923 Participants
Race (NIH/OMB) American Indian or Alaska Native	2 Participants n=132 Participants	0 Participants n=263 Participants	0 Participants n=264 Participants	2 Participants n=264 Participants	4 Participants n=923 Participants
Race (NIH/OMB) Asian	3 Participants n=132 Participants	2 Participants n=263 Participants	4 Participants n=264 Participants	3 Participants n=264 Participants	12 Participants n=923 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=132 Participants	1 Participants n=263 Participants	0 Participants n=264 Participants	1 Participants n=264 Participants	2 Participants n=923 Participants
Race (NIH/OMB) Black or African American	23 Participants n=132 Participants	55 Participants n=263 Participants	56 Participants n=264 Participants	44 Participants n=264 Participants	178 Participants n=923 Participants
Race (NIH/OMB) White	104 Participants n=132 Participants	200 Participants n=263 Participants	202 Participants n=264 Participants	208 Participants n=264 Participants	714 Participants n=923 Participants
Race (NIH/OMB) More than one race	0 Participants n=132 Participants	5 Participants n=263 Participants	2 Participants n=264 Participants	6 Participants n=264 Participants	13 Participants n=923 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=132 Participants	0 Participants n=263 Participants	0 Participants n=264 Participants	0 Participants n=264 Participants	0 Participants n=923 Participants
Height	171.7 cm STANDARD_DEVIATION 10.67 • n=132 Participants • Number analyzed is the number of participants with data available for height at Baseline.	171.0 cm STANDARD_DEVIATION 9.68 • n=263 Participants • Number analyzed is the number of participants with data available for height at Baseline.	171.6 cm STANDARD_DEVIATION 10.11 • n=263 Participants • Number analyzed is the number of participants with data available for height at Baseline.	171.8 cm STANDARD_DEVIATION 9.86 • n=264 Participants • Number analyzed is the number of participants with data available for height at Baseline.	171.5 cm STANDARD_DEVIATION 9.99 • n=922 Participants • Number analyzed is the number of participants with data available for height at Baseline.
Weight	82.37 kg STANDARD_DEVIATION 15.275 • n=131 Participants • Number analyzed is the number of participants with data available for weight at Baseline.	79.63 kg STANDARD_DEVIATION 15.203 • n=263 Participants • Number analyzed is the number of participants with data available for weight at Baseline.	81.31 kg STANDARD_DEVIATION 16.543 • n=262 Participants • Number analyzed is the number of participants with data available for weight at Baseline.	82.35 kg STANDARD_DEVIATION 15.928 • n=263 Participants • Number analyzed is the number of participants with data available for weight at Baseline.	81.28 kg STANDARD_DEVIATION 15.827 • n=919 Participants • Number analyzed is the number of participants with data available for weight at Baseline.
Body Mass Index (BMI)	27.84 kg/m^2 STANDARD_DEVIATION 3.825 • n=131 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.	27.17 kg/m^2 STANDARD_DEVIATION 4.270 • n=263 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.	27.50 kg/m^2 STANDARD_DEVIATION 4.464 • n=262 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.	27.84 kg/m^2 STANDARD_DEVIATION 4.408 • n=263 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.	27.55 kg/m^2 STANDARD_DEVIATION 4.309 • n=919 Participants • Number analyzed is the number of participants with data available for BMI at Baseline.

PRIMARY outcome

Timeframe: 1 month post second dose (Day 120)

Population: Per protocol Set (PPS) included all DENV-naïve participants in immunogenicity subset who received at least 1 dose of trial vaccine, with data available for Baseline (Day 1) and at least 1 post-Baseline immunogenicity measurement and had no major protocol violations.Number of participants analyzed:participants with data available at given timepoint.

GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% \[MNT50\]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

Outcome measures

Outcome measures
Measure	Placebo n=60 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=120 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=129 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=118 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 in the Immunogenicity Subset DENV-1	5.3 titer Interval 4.7 to 6.1	202.9 titer Interval 155.9 to 264.1	293.8 titer Interval 214.9 to 401.6	322.1 titer Interval 238.1 to 435.9
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 in the Immunogenicity Subset DENV-2	6.3 titer Interval 4.8 to 8.2	3090.3 titer Interval 2494.8 to 3828.0	2386.0 titer Interval 1913.0 to 2976.1	3574.1 titer Interval 3087.8 to 4137.0
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 in the Immunogenicity Subset DENV-3	5.4 titer Interval 4.6 to 6.3	149.5 titer Interval 116.6 to 191.6	117.3 titer Interval 92.7 to 148.4	122.8 titer Interval 97.4 to 155.0
Geometric Mean Titers (GMTs) of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 120 in the Immunogenicity Subset DENV-4	5.4 titer Interval 4.7 to 6.2	116.3 titer Interval 93.8 to 144.2	187.9 titer Interval 154.4 to 228.6	115.8 titer Interval 94.0 to 142.5

SECONDARY outcome

Timeframe: 1 month post second dose (Day 120) and 6 months post second dose (Day 270)

Population: PPS included all DENV-naïve participants in the immunogenicity subset who received at least 1 dose of trial vaccine, with data available for Baseline (Day 1) and at least 1 post-Baseline immunogenicity measurement, and who had no major protocol violations. Number analyzed are participants with data available at the given timepoint.

Seropositivity was defined as a reciprocal neutralizing titer ≥ 10. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=124 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=131 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=124 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-1, Day 120	1.7 percentage of participants Interval 0.0 to 8.9	97.5 percentage of participants Interval 92.9 to 99.5	96.9 percentage of participants Interval 92.3 to 99.1	99.2 percentage of participants Interval 95.4 to 100.0
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-2, Day 120	6.7 percentage of participants Interval 1.8 to 16.2	99.2 percentage of participants Interval 95.4 to 100.0	98.4 percentage of participants Interval 94.5 to 99.8	100.0 percentage of participants Interval 96.9 to 100.0
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-3, Day 120	1.7 percentage of participants Interval 0.0 to 8.9	97.5 percentage of participants Interval 92.9 to 99.5	94.6 percentage of participants Interval 89.1 to 97.8	98.3 percentage of participants Interval 94.0 to 99.8
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-4, Day 120	1.7 percentage of participants Interval 0.0 to 8.9	97.5 percentage of participants Interval 92.9 to 99.5	100.0 percentage of participants Interval 97.2 to 100.0	97.5 percentage of participants Interval 92.7 to 99.5
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-1, Day 270	3.4 percentage of participants Interval 0.4 to 11.7	97.3 percentage of participants Interval 92.3 to 99.4	89.4 percentage of participants Interval 82.6 to 94.3	95.8 percentage of participants Interval 90.5 to 98.6
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-2, Day 270	6.8 percentage of participants Interval 1.9 to 16.5	100.0 percentage of participants Interval 96.7 to 100.0	97.6 percentage of participants Interval 93.1 to 99.5	99.2 percentage of participants Interval 95.4 to 100.0
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-3, Day 270	0 percentage of participants Interval 0.0 to 6.1	95.5 percentage of participants Interval 89.8 to 98.5	88.7 percentage of participants Interval 81.8 to 93.7	92.5 percentage of participants Interval 86.2 to 96.5
Percentage of Participants Who Are Seropositive for Each of the 4 Dengue Serotypes at Days 120 and 270 in the Immunogenicity Subset DENV-4, Day 270	0 percentage of participants Interval 0.0 to 6.1	92.8 percentage of participants Interval 86.3 to 96.8	94.3 percentage of participants Interval 88.6 to 97.7	91.7 percentage of participants Interval 85.2 to 95.9

SECONDARY outcome

Timeframe: 6 months post second dose (Day 270)

GMTs of neutralizing antibodies for each of the 4 Dengue Serotypes was measured by microneutralization test 50% \[MNT50\]. The 4 dengue virus serotypes were DENV-1, DENV-2, DENV-3 and DENV-4.

Outcome measures

Outcome measures
Measure	Placebo n=63 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=124 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=131 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=124 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset DENV-1	5.4 titer Interval 4.9 to 5.9	122.5 titer Interval 93.0 to 161.3	136.7 titer Interval 95.2 to 196.3	168.4 titer Interval 120.8 to 234.8
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset DENV-2	5.8 titer Interval 5.0 to 6.8	1507.2 titer Interval 1242.3 to 1828.4	1097.5 titer Interval 856.9 to 1405.5	1693.3 titer Interval 1399.9 to 2048.3
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset DENV-3	NA titer Neutralizing antibodies were below the lower limit of detection (LLOD) and therefore geometric mean and 95% confidence interval couldn't be calculated.	88.0 titer Interval 69.2 to 111.9	63.1 titer Interval 49.9 to 79.7	71.6 titer Interval 57.3 to 89.5
GMTs of Neutralizing Antibodies for Each of the 4 Dengue Serotypes at Day 270 in the Immunogenicity Subset DENV-4	NA titer Neutralizing antibodies were below the LLOD and therefore geometric mean and 95% confidence interval couldn't be calculated.	64.1 titer Interval 49.5 to 83.1	77.5 titer Interval 60.8 to 98.8	51.2 titer Interval 40.0 to 65.5

SECONDARY outcome

Timeframe: Within 7 Days of each Vaccination (day of vaccination + 6 days)

Population: Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated. Number analyzed are participants with data available for the specific category. Only categories with at least one participant are reported.

Solicited local AEs (at injection site) were collected by participants using diary cards within 7 days after vaccination and included pain (none, mild: no interference with daily activity, moderate: interference with daily activity with or without treatment and severe: prevents daily activity with or without treatment), redness (erythema) (\<25 mm, mild: \>25 - ≤50 mm, moderate: \>50 - ≤100 mm, severe: \>100 mm) and swelling (edema/induration) (\<25 mm, mild: \>25 - ≤50 mm, moderate: \>50 - ≤100 mm, severe: \>100 mm ). The percentages were rounded off to the first decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=131 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=264 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=261 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=263 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Any Local AE	17.5 percentage of participants	51.0 percentage of participants	48.4 percentage of participants	50.0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Pain-Any Severity	16.7 percentage of participants	45.5 percentage of participants	40.6 percentage of participants	41.7 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Pain-Mild	15.0 percentage of participants	39.9 percentage of participants	34.8 percentage of participants	37.7 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Pain-Moderate	1.7 percentage of participants	5.5 percentage of participants	5.1 percentage of participants	4.0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Pain-Severe	0 percentage of participants	0 percentage of participants	0.8 percentage of participants	0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Erythema-Any Severity	0.8 percentage of participants	25.7 percentage of participants	20.3 percentage of participants	23.0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Erythema-Mild: 2.5-5(cm)	0 percentage of participants	23.7 percentage of participants	18.4 percentage of participants	21.8 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1,Erythema-Moderate: >5-<=10(cm)	0 percentage of participants	1.2 percentage of participants	2.0 percentage of participants	0.8 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Erythema-Missing Severity	0.8 percentage of participants	0.8 percentage of participants	0 percentage of participants	0.4 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Swelling-Any Severity	0.8 percentage of participants	7.9 percentage of participants	5.5 percentage of participants	6.3 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Swelling-Mild: 2.5-5(cm)	0 percentage of participants	7.1 percentage of participants	5.1 percentage of participants	5.6 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1,Swelling-Moderate: >5-<=10(cm)	0 percentage of participants	0.4 percentage of participants	0.4 percentage of participants	0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Swelling-Missing Severity	0.8 percentage of participants	0.4 percentage of participants	0 percentage of participants	0.8 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Local AE-Any	13.0 percentage of participants	37.9 percentage of participants	42.1 percentage of participants	37.1 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Pain-Any Severity	13.0 percentage of participants	32.8 percentage of participants	34.6 percentage of participants	30.9 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Pain-Mild	13.0 percentage of participants	27.6 percentage of participants	30.0 percentage of participants	28.4 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Pain-Moderate	0 percentage of participants	3.9 percentage of participants	3.8 percentage of participants	2.5 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Pain-Severe	0 percentage of participants	1.3 percentage of participants	0.8 percentage of participants	0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Erythema-Any Severity	0 percentage of participants	19.0 percentage of participants	18.8 percentage of participants	14.3 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2,Erythema-Mild: 2.5-5(cm)	0 percentage of participants	18.1 percentage of participants	17.1 percentage of participants	13.1 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2,Erythema-Moderate: >5-<=10(cm)	0 percentage of participants	0.4 percentage of participants	1.7 percentage of participants	1.3 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2,Erythema-Missing Severity	0 percentage of participants	0.4 percentage of participants	0 percentage of participants	0 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Swelling-Any Severity	0 percentage of participants	6.9 percentage of participants	4.2 percentage of participants	4.7 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2,Swelling-Mild: 2.5-5(cm)	0 percentage of participants	6.5 percentage of participants	4.2 percentage of participants	4.2 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2,Swelling-Moderate: >5-<=10(cm)	0 percentage of participants	0 percentage of participants	0 percentage of participants	0.4 percentage of participants
Percentage of Participants With Solicited Local (Injection Site) Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2,Swelling-Missing Severity	0 percentage of participants	0.4 percentage of participants	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Within 14 Days of each Vaccination (day of vaccination + 13 days)

Solicited systemic AEs include fever, headache, asthenia, malaise and myalgia that occurred within 14 days after each vaccination. Solicited systemic AEs (headache, asthenia, malaise and myalgia) was graded from 0 to 3 by severity; where 0=None, 1=Mild: No interference with daily activity, 2=Moderate: Interference with daily activity, 3=Severe: Prevents daily activity; A systemic AE of fever (defined as ≥38°C or ≥100.4°F) was derived from a daily temperature reading recorded within 14 days after vaccination. Fever was excluded from the overall count as no severity grading was applied for it. The percentages were rounded off to the first decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=131 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=264 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=261 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=263 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Malaise-Any Severity	7.8 percentage of participants	11.6 percentage of participants	11.3 percentage of participants	7.7 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Malaise-Mild	5.2 percentage of participants	7.3 percentage of participants	7.5 percentage of participants	4.7 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Malaise-Moderate	2.6 percentage of participants	4.3 percentage of participants	3.3 percentage of participants	2.1 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Malaise-Severe	0 percentage of participants	0 percentage of participants	0.4 percentage of participants	0.9 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Systemic AEs-Any	34.7 percentage of participants	43.3 percentage of participants	39.5 percentage of participants	42.9 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Headache-Any Severity	22.5 percentage of participants	28.9 percentage of participants	27.0 percentage of participants	28.6 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Headache-Mild	17.5 percentage of participants	21.3 percentage of participants	19.9 percentage of participants	21.4 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Headache-Moderate	4.2 percentage of participants	5.9 percentage of participants	5.5 percentage of participants	6.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Headache-Severe	0.8 percentage of participants	1.6 percentage of participants	1.6 percentage of participants	1.2 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Asthenia-Any Severity	9.2 percentage of participants	13.1 percentage of participants	15.2 percentage of participants	11.9 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Asthenia-Mild	7.5 percentage of participants	7.9 percentage of participants	9.4 percentage of participants	6.3 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Asthenia-Moderate	0.8 percentage of participants	3.6 percentage of participants	4.3 percentage of participants	4.8 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Asthenia-Severe	0.8 percentage of participants	1.6 percentage of participants	1.6 percentage of participants	0.8 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Malaise-Any Severity	12.4 percentage of participants	15.5 percentage of participants	14.5 percentage of participants	15.5 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Malaise-Mild	9.1 percentage of participants	7.1 percentage of participants	7.8 percentage of participants	8.3 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Malaise-Moderate	2.5 percentage of participants	6.3 percentage of participants	4.7 percentage of participants	5.6 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Malaise-Severe	0.8 percentage of participants	2.0 percentage of participants	2.0 percentage of participants	1.6 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Myalgia-Any Severity	15.8 percentage of participants	26.5 percentage of participants	25.4 percentage of participants	22.2 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Myalgia-Mild	13.3 percentage of participants	19.0 percentage of participants	16.0 percentage of participants	14.3 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Myalgia-Moderate	2.5 percentage of participants	7.1 percentage of participants	7.8 percentage of participants	7.5 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Myalgia-Severe	0 percentage of participants	0.4 percentage of participants	1.6 percentage of participants	0.4 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Fever-Any Severity	1.7 percentage of participants	0.8 percentage of participants	2.4 percentage of participants	2.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Fever-38.0-<38.5	0.8 percentage of participants	0.4 percentage of participants	0.8 percentage of participants	1.2 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Fever-38.5-<39.0	0 percentage of participants	0.4 percentage of participants	0.8 percentage of participants	0.8 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Fever-39.0-<39.5	0.8 percentage of participants	0 percentage of participants	0.4 percentage of participants	0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 1, Fever-≥41.0	0 percentage of participants	0 percentage of participants	0.4 percentage of participants	0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Systemic AEs-Any	23.5 percentage of participants	26.7 percentage of participants	29.2 percentage of participants	28.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Headache-Any Severity	19.1 percentage of participants	18.1 percentage of participants	22.5 percentage of participants	18.6 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Headache-Mild	15.7 percentage of participants	15.1 percentage of participants	15.8 percentage of participants	13.6 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Headache-Moderate	3.5 percentage of participants	3.0 percentage of participants	5.4 percentage of participants	4.2 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Headache-Severe	0 percentage of participants	0 percentage of participants	1.3 percentage of participants	0.8 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Asthenia-Any Severity	8.7 percentage of participants	9.1 percentage of participants	8.8 percentage of participants	6.0 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Asthenia-Mild	7.0 percentage of participants	6.0 percentage of participants	6.3 percentage of participants	3.4 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Asthenia-Moderate	1.7 percentage of participants	3.0 percentage of participants	2.1 percentage of participants	2.1 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Asthenia-Severe	0 percentage of participants	0 percentage of participants	0.4 percentage of participants	0.4 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Myalgia-Any Severity	7.8 percentage of participants	16.8 percentage of participants	14.6 percentage of participants	14.9 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Myalgia-Mild	5.2 percentage of participants	12.1 percentage of participants	10.4 percentage of participants	11.9 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Myalgia-Moderate	2.6 percentage of participants	3.9 percentage of participants	3.3 percentage of participants	2.6 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Myalgia-Severe	0 percentage of participants	0.9 percentage of participants	0.8 percentage of participants	0.4 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Fever-Any Severity	1.7 percentage of participants	0.9 percentage of participants	0.8 percentage of participants	2.1 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Fever-38.0-<38.5	1.7 percentage of participants	0.9 percentage of participants	0.4 percentage of participants	0.9 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Fever-38.5-<39.0	0 percentage of participants	0 percentage of participants	0.4 percentage of participants	0.4 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Fever-39.0-<39.5	0 percentage of participants	0 percentage of participants	0 percentage of participants	0.4 percentage of participants
Percentage of Participants With Solicited Systemic Adverse Events (AEs) by Severity After Each Vaccination After Vaccination 2, Fever-39.5-<40.0	0 percentage of participants	0 percentage of participants	0 percentage of participants	0.4 percentage of participants

SECONDARY outcome

Timeframe: Within 28 days (day of vaccination + 27 days) after each vaccination

Population: Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated. Number analyzed is the number of participants with data available for the specific category.

An AE was defined as any untoward medical occurrence in a clinical investigation participant administered a trial vaccine; it does not necessarily have to have a causal relationship with trial vaccine administration.

Outcome measures

Outcome measures
Measure	Placebo n=131 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=264 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=261 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=263 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination After First Vaccination	13.7 percentage of participants	18.6 percentage of participants	18.0 percentage of participants	16.7 percentage of participants
Percentage of Participants With Any Unsolicited Adverse Events (AEs) After Each Vaccination After Second Vaccination	7.8 percentage of participants	10.5 percentage of participants	7.7 percentage of participants	6.6 percentage of participants

SECONDARY outcome

Timeframe: From the first vaccination on Day 1 until the end of the trial (Day 270)

Population: Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.

An SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, is an important medical event that may require intervention to prevent any of the above mentioned criteria and/or may expose the participant to danger, even though the event is not immediately life threatening or fatal or does not result in hospitalization. The percentages were rounded off to the first decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=131 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=264 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=261 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=263 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Percentage of Participants With Serious Adverse Events (SAEs)	3.1 percentage of participants	3.8 percentage of participants	1.1 percentage of participants	1.1 percentage of participants

SECONDARY outcome

Timeframe: From the first vaccination on Day 1 until the end of the trial (Day 270)

Population: Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.

MAAEs are defined as AEs leading to an unscheduled visit to or by a healthcare professional, including visits to an emergency department, but not fulfilling seriousness criteria. The percentages were rounded off to the first decimal place.

Outcome measures

Outcome measures
Measure	Placebo n=131 Participants TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=264 Participants Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=261 Participants Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=263 Participants Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
Percentage of Participants With Medically Attended Adverse Events (MAAEs)	13.7 percentage of participants	17.8 percentage of participants	12.3 percentage of participants	11.8 percentage of participants

Adverse Events

Placebo

Serious events: 4 serious events

Other events: 4 other events

Deaths: 1 deaths

TDV Lot 1

Serious events: 10 serious events

Other events: 16 other events

Deaths: 0 deaths

TDV Lot 2

Serious events: 3 serious events

Other events: 26 other events

Deaths: 0 deaths

TDV Lot 3

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo n=131 participants at risk TDV placebo matching injection, subcutaneously (SC) once on Day 1, and Day 90.	TDV Lot 1 n=264 participants at risk Participants were administered TDV lot 1, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 2 n=261 participants at risk Participants were administered TDV lot 2, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection, once on Day 1, and Day 90.	TDV Lot 3 n=263 participants at risk Participants were administered TDV lot 3, 0.5 ml (each TDV 0.5 mL dose contained TDV-1, TDV-2, TDV-3, and TDV-4), SC injection once on Day 1, and Day 90.
General disorders Injection site bruising	0.76% 1/131 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	1.9% 5/264 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	3.8% 10/261 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	4.6% 12/263 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.
General disorders Injection site pruritus	0.00% 0/131 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	3.0% 8/264 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	5.7% 15/261 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	1.1% 3/263 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.
Infections and infestations Upper respiratory tract infection	3.1% 4/131 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	1.5% 4/264 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	2.3% 6/261 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.	3.4% 9/263 • All-cause mortality and Serious adverse events: From the first vaccination on Day 1 until the end of the trial (Day 270); Other adverse events: Up to 28 days (Day of vaccination+27 subsequent days) after each vaccination. At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Set included all participants who received at least 1 dose of trial vaccine (TDV or placebo). Participants were analyzed as treated.

Additional Information

Medical Director

Takeda

Phone: +1-877-825-3327

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The first study related publication will be a multi-center publication submitted within 24 months after conclusion or termination of a study at all sites. After such multi site publication, all proposed site publications and presentations will be submitted to sponsor for review 60 days in advance of publication. Site will remove Sponsor confidential information unrelated to study results. Sponsor can delay a proposed publication for another 60 days to preserve intellectual property.
Publication restrictions are in place

Restriction type: OTHER