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Clinical Trial Results:
A Double-Blind, Randomized, Placebo-Controlled, Age Descending and Expansion Phase 2 Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years

Summary
EudraCT number	2022-003455-33
Trial protocol	Outside EU/EEA
Global end of trial date	15 Apr 2016

Results information
Results version number	v2(current)
This version publication date	26 May 2023
First version publication date	26 Jan 2023
Other versions	v1
Version creation reason
Summary report(s)	Additional Endpoints

Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information

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Trial information

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Sponsor protocol code

INV-DEN-203

ISRCTN number

US NCT number

NCT01511250

WHO universal trial number (UTN)

Sponsor organisation name

Takeda

Sponsor organisation address

95 Hayden Avenue, Lexington, United States, MA 02421

Public contact

Study Director, Takeda, TrialDisclosures@takeda.com

Scientific contact

Study Director, Takeda, TrialDisclosures@takeda.com

Is trial part of an agreed paediatric investigation plan (PIP)

Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?

Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?

Yes

Analysis stage

Final

Date of interim/final analysis

15 Apr 2016

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

15 Apr 2016

Was the trial ended prematurely?

Main objective of the trial

The purpose of this study is to assess the immunogenicity, safety and tolerability of Takeda's tetravalent dengue vaccine (TDV) (previously wild-type dengue virus vaccine [DENVax]) administered subcutaneously in healthy adults and children. In addition, the antibody response to the four dengue virus serotypes will be evaluated.

Protection of trial subjects

All study participants were required to read and sign an Informed Consent Form. Assent is also obtained from the study participant where required.

Background therapy

Evidence for comparator

Actual start date of recruitment

16 Nov 2011

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Colombia: 47

Country: Number of subjects enrolled

Puerto Rico: 136

Country: Number of subjects enrolled

Singapore: 53

Country: Number of subjects enrolled

Thailand: 124

Worldwide total number of subjects

360

EEA total number of subjects

Number of subjects enrolled per age group

In utero

Preterm newborn - gestational age < 37 wk

Newborns (0-27 days)

Infants and toddlers (28 days-23 months)

Children (2-11 years)

282

Adolescents (12-17 years)

Adults (18-64 years)

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Participants took part in the study at 8 investigative sites in Puerto Rico, Colombia, Singapore and Thailand from 16 November 2011 to 15 April 2016. Healthy participants were enrolled in this study in 2-parts.

Screening details

Participants received 0.5 mL TDV or placebo in 1 of 4 groups for Part1:21-45,12-20,6-11,1.5-5 years, and in 1 group for Part II:1.5-11 years. Part1 was in participants whose safety data for at least 28 days after first dose in each preceding age cohort, 12 and 24 participants in 1.5 to 5 years of age were evaluated and were safe to continue Part2.

Period 1 title

Overall Study (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Data analyst, Carer, Assessor

Are arms mutually exclusive

Yes

Part I: TDV 21 to 45 Years

Arm description

TDV 0.5 mL, injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 21 to 45 years. TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 plaque forming units (PFU), 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU.

Arm type

Experimental

Investigational medicinal product name

Dengue Tetravalent Vaccine (Live, Attenuated)

Investigational medicinal product code

TAK-003

Other name

TDV

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part I: Placebo 21 to 45 Years

Arm description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 21 to 45 years.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part I: TDV 12 to 20 Years

Arm description

TDV 0.5 mL, injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 12 to 20 years. TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU.

Arm type

Experimental

Investigational medicinal product name

Dengue Tetravalent Vaccine (Live, Attenuated)

Investigational medicinal product code

TAK-003

Other name

TDV

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part I: Placebo 12 to 20 Years

Arm description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 12 to 20 years.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part I: TDV 6 to 11 Years

Arm description

TDV 0.5 mL, injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 6 to 11 years. TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU.

Arm type

Experimental

Investigational medicinal product name

Dengue Tetravalent Vaccine (Live, Attenuated)

Investigational medicinal product code

TAK-003

Other name

TDV

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part I: Placebo 6 to 11 Years

Arm description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 6 to 11 years.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part I: TDV 1.5 to 5 Years

Arm description

TDV 0.5 mL, injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years. TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU.

Arm type

Experimental

Investigational medicinal product name

Dengue Tetravalent Vaccine (Live, Attenuated)

Investigational medicinal product code

TAK-003

Other name

TDV

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part I: Placebo 1.5 to 5 Years

Arm description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part II: TDV 1.5 to 11 Years

Arm description

TDV 0.5 mL, injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 11 years. TDV comprised of 4 recombinant, live attenuated dengue virus strains: TDV-1, TDV-2, TDV-3 and TDV-4 containing 2*10^4 PFU, 5*10^4 PFU, 1*10^5 PFU, and 3*10^5 PFU respectively, total virus per dose: 4.7*10^5 PFU.

Arm type

Experimental

Investigational medicinal product name

Dengue Tetravalent Vaccine (Live, Attenuated)

Investigational medicinal product code

TAK-003

Other name

TDV

Pharmaceutical forms

Powder and solvent for solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV 0.5 mL, injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Part II: Placebo 1.5 to 11 Years

Arm description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Arm type

Placebo

Investigational medicinal product name

Placebo

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose).

Number of subjects in period 1	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Started	24	14	22	14	21	17	23	13	159	53
Completed	15	9	18	11	21	17	21	9	145	48
Not completed	9	5	4	3	0	0	2	4	14	5
Withdrawal of Consent	1	-	-	-	-	-	-	1	1	-
Lost to follow-up	7	3	3	3	-	-	2	3	13	5
Sponsor/Investigator Decision	1	-	-	-	-	-	-	-	-	-
Protocol deviation	-	2	1	-	-	-	-	-	-	-

Baseline characteristics

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Reporting group title

Part I: TDV 21 to 45 Years

Reporting group description

Reporting group title

Part I: Placebo 21 to 45 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 21 to 45 years.

Reporting group title

Part I: TDV 12 to 20 Years

Reporting group description

Reporting group title

Part I: Placebo 12 to 20 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 12 to 20 years.

Reporting group title

Part I: TDV 6 to 11 Years

Reporting group description

Reporting group title

Part I: Placebo 6 to 11 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 6 to 11 years.

Reporting group title

Part I: TDV 1.5 to 5 Years

Reporting group description

Reporting group title

Part I: Placebo 1.5 to 5 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Reporting group title

Part II: TDV 1.5 to 11 Years

Reporting group description

Reporting group title

Part II: Placebo 1.5 to 11 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Reporting group values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years	Total
Number of subjects	24	14	22	14	21	17	23	13	159	53
Age Categorical
Units: Subjects
Age continuous
Units: years
arithmetic mean (full range (min-max))	29.2 (21.0 to 45.0)	30.1 (21.0 to 40.0)	15.5 (12.0 to 19.0)	16.8 (12.0 to 20.0)	8.4 (6.0 to 11.0)	7.8 (6.0 to 11.0)	3.3 (1.5 to 5.0)	3.5 (2.3 to 5.0)	6.6 (1.6 to 11.0)	6.8 (2.1 to 11.0)	-
Gender categorical
Units: Subjects
Male	14	6	10	7	15	9	16	6	71	34	188
Female	10	8	12	7	6	8	7	7	88	19	172
Race
Units: Subjects
Asian	3	3	16	8	16	12	12	6	77	24	177
Hispanic or Latino	20	10	6	6	4	5	11	7	79	27	175
White	1	1	0	0	1	0	0	0	0	0	3
Black or African American	0	0	0	0	0	0	0	0	3	2	5
Seropositive to any Serotype at Day 0
Seropositivity is defined as a reciprocal neutralising titer measured by a microneutralising test 50% (MNT50) greater or equal to (≥)10.
Units: Subjects
Seropositive to any Serotype=No	5	2	7	1	12	14	16	12	93	24	186
Seropositive to any Serotype=Yes	19	12	15	13	9	3	7	1	66	29	174
Height
Units: meters (m)
arithmetic mean (full range (min-max))	1.68 (1.57 to 1.82)	1.65 (1.53 to 1.87)	1.58 (1.38 to 1.72)	1.60 (1.41 to 1.73)	1.29 (1.08 to 1.52)	1.27 (1.13 to 1.42)	0.98 (0.83 to 1.13)	0.99 (0.90 to 1.06)	1.20 (0.77 to 1.62)	1.22 (0.83 to 1.63)	-
Weight
Units: kilograms (kg)
arithmetic mean (full range (min-max))	81.6 (41.4 to 115.1)	80.2 (56.3 to 120.4)	57.0 (28.6 to 93.4)	59.5 (48.6 to 89.9)	31.2 (18.5 to 51.2)	27.0 (20.3 to 37.5)	15.1 (10.3 to 22.2)	16.5 (13.3 to 20.8)	25.7 (10.4 to 61.0)	26.7 (10.6 to 53.2)	-
Body Mass Index (BMI)
Units: kg/m^2
arithmetic mean (full range (min-max))	28.81 (14.70 to 41.30)	29.05 (21.30 to 38.70)	22.60 (15.00 to 33.60)	23.09 (18.60 to 31.50)	18.38 (12.90 to 28.80)	16.56 (14.20 to 20.60)	15.63 (12.50 to 19.00)	16.95 (13.20 to 20.40)	17.02 (12.10 to 30.10)	17.08 (13.20 to 24.30)	-

End points

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Reporting group title

Part I: TDV 21 to 45 Years

Reporting group description

Reporting group title

Part I: Placebo 21 to 45 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 21 to 45 years.

Reporting group title

Part I: TDV 12 to 20 Years

Reporting group description

Reporting group title

Part I: Placebo 12 to 20 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 12 to 20 years.

Reporting group title

Part I: TDV 6 to 11 Years

Reporting group description

Reporting group title

Part I: Placebo 6 to 11 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 6 to 11 years.

Reporting group title

Part I: TDV 1.5 to 5 Years

Reporting group description

Reporting group title

Part I: Placebo 1.5 to 5 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Reporting group title

Part II: TDV 1.5 to 11 Years

Reporting group description

Reporting group title

Part II: Placebo 1.5 to 11 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Subject analysis set title

c vbxcv

Subject analysis set type

Full analysis

Subject analysis set description

xcvbxc

Primary: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity

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End point title

Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity ^[1]

End point description

Solicited local injection site reactions were collected by subject diary and graded based on the Common Terminology Criteria for Adverse Events (CTCAE), Version 4.03 for pain [Grade 0 (no pain), 1 (mild), 2 (moderate) and 3 (severe)] and itching (pruritus) [Grade 0 (no itching), 1 (mild), 2 (moderate) and 3 (Severe]. Severity grade for redness (erythema) and swelling (edema/induration) were derived from recorded length of the longest diameter measurement using the FDA Guidance for Industry: Toxicity Grading Scale of Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trial were Grade 0 (<2.5 cm), 1 (mild: 2.5-5 cm), 2 (moderate: 5.1-10 cm) and 3 (severe: >10 cm) and Grade 4 (Potentially Life-threatening: necrosis or exfoliative dermatitis). The safety set included all randomised participants who received at least one dose of study vaccine (or placebo). Only severity categories for which there was at least 1 participant are reported.

End point type

Primary

End point timeframe

Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)

Notes
[1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Number of participants is the analysis defined in the description.

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: participants
Pain, Any Severity	7	0	14	3	9	0	7	2	56	6
Pain, Grade 1	7	0	11	2	4	0	7	2	41	3
Pain, Grade 2	0	0	3	1	4	0	0	0	11	3
Pain, Grade 3	0	0	0	0	1	0	0	0	4	0
Itching, Any Severity	3	1	7	1	2	1	2	0	26	4
Itching, Grade 1	3	1	7	1	1	1	2	0	19	3
Itching, Grade 2	0	0	0	0	1	0	0	0	6	1
Itching, Grade 3	0	0	0	0	0	0	0	0	1	0
Erythema, Any Severity	6	0	4	0	2	0	3	0	24	1
Erythema, Grade 1	5	0	4	0	1	0	3	0	21	0
Erythema, Grade 2	1	0	0	0	0	0	0	0	2	0
Erythema, Grade 3	0	0	0	0	1	0	0	0	1	1
Edema, Any Severity	0	0	1	0	3	0	1	0	13	0
Edema, Grade 1	0	0	1	0	3	0	1	0	9	0
Edema, Grade 2	0	0	0	0	0	0	0	0	3	0
Edema, Grade 3	0	0	0	0	0	0	0	0	1	0

No statistical analyses for this end point

Primary: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (In Clinic Assessment) Following Either Vaccination Dose by Severity

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End point title

Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (In Clinic Assessment) Following Either Vaccination Dose by Severity ^[2]

End point description

End point type

Primary

End point timeframe

Within 28 days after either of the vaccination given on Day 0 or 90 (Day 28 for first vaccination, Day 118 for second vaccination)

Notes
[2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Number of participants is the analysis defined in the description.

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: participants
Pain, Any Severity	2	0	4	2	9	5	5	1	33	14
Pain, Grade 1	2	0	3	2	9	5	5	1	28	13
Pain, Grade 2	0	0	1	0	0	0	0	0	3	1
Itching, Any Severity	2	2	2	1	1	1	1	0	4	5
Itching, Grade 1	2	2	2	1	1	1	1	0	4	5
Erythema, Any Severity	0	0	0	0	0	0	0	0	0	0
Edema, Any Severity	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Primary: Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity

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End point title

Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity ^[3]

End point description

Solicited systemic AEs (headache, muscle pain [myalgia], joint pain [arthralgia], eye pain, sensitivity to light [photophobia], tiredness [fatigue], body rash, nausea:recorded in participant's-diary with vomiting [number of times]), body temperature). Diary-recorded severity grades:based on Common Terminology Criteria for Adverse Events (CTCAE). Severity grades:Mild(Grade 1):transient symptoms, discomfort noticed but was easily tolerated by participant with no interference to normal daily activities. Moderate(Grade 2):marked symptoms, moderate interference with participant's daily activities. Severe(Grade 3):Considerable interference with participant's daily activities.CTCAE severity grades for fever and vomiting:derived from diary-recorded measurements of temperature level, number of episodes, respectively.Safety set:all randomised participants who received at least one dose of study vaccine(or placebo).Only severity categories for which there was at least 1 participant are reported.

End point type

Primary

End point timeframe

Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)

Notes
[3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Number of participants is the analysis defined in the description.

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: participants
Fever, Any Severity	1	3	4	1	1	1	4	4	33	9
Fever, Grade 1	0	1	4	1	1	1	4	2	27	6
Fever, Grade 2	1	2	0	0	0	0	0	1	5	2
Fever, Grade 3	0	0	0	0	0	0	0	1	1	1
Headache, Any Grade	6	4	9	8	4	5	3	4	46	12
Headache, Grade 1	3	1	4	5	3	3	3	3	30	6
Headache, Grade 2	2	2	5	3	1	2	0	1	12	4
Headache, Grade 3	1	1	0	0	0	0	0	0	4	2
Myalgia, Any Severity	4	3	4	5	1	3	5	2	30	6
Myalgia, Grade 1	3	1	2	2	1	3	3	0	21	4
Myalgia, Grade 2	0	1	2	2	0	0	2	1	6	1
Myalgia, Grade 3	1	1	0	1	0	0	0	1	3	1
Arthralgia, Any Severity	1	3	2	2	0	0	1	1	10	2
Arthralgia, Grade 1	1	1	1	0	0	0	1	0	7	1
Arthralgia, Grade 2	0	1	1	2	0	0	0	0	3	1
Arthralgia, Grade 3	0	1	0	0	0	0	0	1	0	0
Eye Pain, Any Severity	3	3	1	3	0	0	2	1	14	3
Eye Pain, Grade 1	1	2	0	2	0	0	2	1	11	3
Eye Pain, Grade 2	1	0	1	1	0	0	0	0	3	0
Eye Pain, Grade 3	1	1	0	0	0	0	0	0	0	0
Photophobia, Any Severity	3	1	0	4	1	0	0	0	11	3
Photophobia, Grade 1	1	1	0	4	0	0	0	0	9	3
Photophobia, Grade 2	1	0	0	0	1	0	0	0	2	0
Photophobia, Grade 3	1	0	0	0	0	0	0	0	0	0
Fatigue, Any Severity	4	4	9	6	2	5	3	3	29	10
Fatigue, Grade 1	2	2	7	2	1	2	1	2	19	6
Fatigue, Grade 2	0	0	2	4	0	3	2	0	7	3
Fatigue, Grade 3	2	2	0	0	1	0	0	1	3	1
Body rash, Any Severity	1	0	2	2	2	1	2	2	14	2
Body rash, Grade 1	1	0	1	1	2	1	2	2	12	2
Body rash, Grade 2	0	0	1	0	0	0	0	0	1	0
Body rash, Grade 3	0	0	0	1	0	0	0	0	1	0
Nausea, Any Severity	4	1	3	4	1	0	3	3	22	4
Nausea, Grade 1	2	1	3	2	0	0	2	3	14	4
Nausea, Grade 2	1	0	0	2	1	0	1	0	4	0
Nausea, Grade 3	1	0	0	0	0	0	0	0	4	0
Vomiting, Any Severity	2	1	0	2	1	1	4	5	18	3
Vomiting, Grade 1	0	1	0	2	0	1	1	2	5	2
Vomiting, Grade 2	1	0	0	0	1	0	3	3	11	1
Vomiting, Grade 3	1	0	0	0	0	0	0	0	2	0

No statistical analyses for this end point

Primary: Number of Participants With Any Solicited AE Following Either Vaccination Dose

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End point title

Number of Participants With Any Solicited AE Following Either Vaccination Dose ^[4]

End point description

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. Solicited local injection site reactions included pain, itching, erythema, edema and solicited systemic AEs include myalgia, arthralgia, eye pain, photophobia, fatigue, body rash, nausea, vomiting, and fever. The safety set included all randomised participants who received at least one dose of study vaccine (or placebo).

End point type

Primary

End point timeframe

Within 14 days after either of the vaccination given on Day 0 or 90 (Day 14 for first vaccination, Day 104 for second vaccination)

Notes
[4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Number of participants is the analysis defined in the description.

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: participants	13	9	17	12	12	8	17	10	110	28

No statistical analyses for this end point

Primary: Number of Participants With at Least One Unsolicited AE Following Either Vaccination Dose by Severity

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End point title

Number of Participants With at Least One Unsolicited AE Following Either Vaccination Dose by Severity ^[5]

End point description

An Adverse Event (AE) is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. The severity of all unsolicited AEs was evaluated by the Investigator (using the Common Terminology Criteria for Adverse Events [CTCAE] v4.03) as follows. Mild (Grade 1): Transient symptoms, discomfort noticed but was easily tolerated by the participant with no interference to normal daily activities. Moderate (Grade 2): Marked symptoms, moderate interference with participant's daily activities. Severe (Grade 3): Considerable interference with participant's daily activities. The safety set included all randomised participants who received at least one dose of study vaccine (or placebo).

End point type

Primary

End point timeframe

Unsolicited AEs were collected within 28 days of all vaccinations. Serious AEs were collected throughout the study up to Day 1080

Notes
[5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Number of participants is the analysis defined in the description.

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: participants
At least one unsolicited AE	13	7	14	8	12	11	17	12	101	37
Unsolicited AEs by severity: Mild	6	2	7	2	10	8	13	10	72	31
Unsolicited AEs by severity: Moderate	5	5	6	5	1	3	4	2	25	6
Unsolicited AEs by severity: Severe	2	0	1	1	1	0	0	0	4	0

No statistical analyses for this end point

Primary: Seropositivity Rate to Each of the Four Dengue Serotypes at Day 120

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End point title

Seropositivity Rate to Each of the Four Dengue Serotypes at Day 120 ^[6]

End point description

Seropositivity rate, defined as the percentage of participants seropositive, was derived from titers of dengue-neutralising antibodies. Participants were classified by titer after Day 0 as seropositive or seronegative. Seropositive was defined as a MNT50 titre value of ≥10 for any serotype and seronegative was defined as titre value of less than (<) 10 for all 4 serotypes. Seropositivity was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, TDV-4. FAS included all randomised participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample has been received.

End point type

Primary

End point timeframe

30 days after second vaccination (Day 120)

Notes
[6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
Justification: Percentage of participants is defined in the description of this endpoint.

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	22	13	22	14	21	17	22	11	156	53
Units: percentage of participants
number (confidence interval 95%)
TDV-1	100.0 (84.6 to 100.0)	92.3 (64 to 99.8)	100.0 (84.6 to 100.0)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	100.0 (97.7 to 100.0)	43.4 (29.8 to 57.7)
TDV-2	100.0 (84.6 to 100.0)	84.6 (54.6 to 98.1)	95.5 (77.2 to 99.9)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	100.0 (97.7 to 100.0)	35.8 (23.1 to 50.2)
TDV-3	100.0 (84.6 to 100.0)	100.0 (75.3 to 100.0)	100.0 (84.6 to 100.0)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	29.4 (10.3 to 56.0)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	99.4 (96.5 to 100.0)	35.8 (23.1 to 50.2)
TDV-4	90.9 (70.8 to 98.9)	61.5 (31.6 to 86.1)	72.7 (49.8 to 89.3)	71.4 (41.9 to 91.6)	85.7 (63.7 to 97.0)	29.4 (10.3 to 56.0)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	94.9 (90.1 to 97.8)	35.8 (23.1 to 50.2)

No statistical analyses for this end point

Secondary: Part I: Number of Participants Positive for Vaccine Viremia for Each of Four Vaccine Strain Serotypes After the Each Vaccination

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End point title

Part I: Number of Participants Positive for Vaccine Viremia for Each of Four Vaccine Strain Serotypes After the Each Vaccination

End point description

Vaccine viremia was assessed for each of the four vaccine strain serotypes: TDV-1, TDV-2, TDV-3 and TDV-4 for Part-1. Vaccine viral ribonucleic acid (RNA) was detected by a quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assay. The FAS included all randomised participants who received at least one dose of study vaccine and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received.

End point type

Secondary

End point timeframe

Days 0, 7, 14, 90, 97, and 104

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	4	5
Units: participants
Day 0, TDV-1	0	0	0	0	0	0	0	0	0	0
Day 0, TDV-2	0	0	0	0	0	0	0	0	0	0
Day 0, TDV-3	0	0	0	0	0	0	0	0	0	0
Day 0, TDV-4	0	0	0	0	0	0	0	0	0	0
Day 7, TDV-1	0	0	0	0	0	0	0	0	0	0
Day 7, TDV-2	2	0	4	0	4	0	9	0	0	0
Day 7, TDV-3	0	0	0	0	0	0	0	0	0	0
Day 7, TDV-4	0	0	0	0	0	0	0	0	0	0
Day 14, TDV-1	0	0	0	0	0	0	0	0	0	0
Day 14, TDV-2	0	0	3	0	6	0	4	0	0	0
Day 14, TDV-3	0	0	0	0	0	0	0	0	0	0
Day 14, TDV-4	0	0	0	0	0	0	0	0	0	0
Day 90, TDV-1	0	0	0	0	0	0	0	0	0	0
Day 90, TDV-2	0	0	0	0	0	0	0	0	0	0
Day 90, TDV-3	0	0	0	0	0	0	0	0	0	0
Day 90, TDV-4	0	0	0	0	0	0	0	0	0	0
Day 97, TDV-1	0	0	0	0	0	0	0	0	0	0
Day 97, TDV-2	0	0	0	0	1	0	0	0	0	0
Day 97, TDV-3	0	0	0	0	0	0	0	0	0	0
Day 97, TDV-4	0	0	0	0	0	0	0	0	0	0
Day 104, TDV-1	0	0	0	0	0	0	0	0	0	0
Day 104, TDV-2	1	0	0	0	0	0	1	0	0	0
Day 104, TDV-3	0	0	0	0	0	0	0	0	0	0
Day 104, TDV-4	0	0	0	0	0	0	0	0	0	0

No statistical analyses for this end point

Secondary: Seropositivity Rate to Each of the Four Dengue Serotypes

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End point title

Seropositivity Rate to Each of the Four Dengue Serotypes

End point description

Seropositivity rate, defined as the percentage of participants seropositive, was derived from titers of dengue-neutralising antibodies. Participants were classified by titer after Day 0 as seropositive or seronegative. Seropositive was defined as a MNT50 titre value of ≥10 and seronegative was defined as titre value of less than (<) 10. Seropositivity was assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, TDV-4. FAS included all randomised participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received. n=number of subjects available for analysis at a specific timepoint. 9999=Data were not collected at this timepoint.

End point type

Secondary

End point timeframe

Day 28 and Day 90 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: percentage of participants
number (confidence interval 95%)
Day28, TDV-1(n=24,13,22,14,21,17,23,13,158,53)	100.0 (85.8 to 100.0)	92.3 (64.0 to 99.8)	86.4 (65.1 to 97.1)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	100.0 (85.2 to 100.0)	7.7 (0.2 to 36.0)	100.0 (97.7 to 100.0)	41.5 (28.1 to 55.9)
Day 28, TDV-2(n=24,13,22,14,21,17,23,13,158,53)	100.0 (85.8 to 100.0)	92.3 (64.0 to 99.8)	86.4 (65.1 to 97.1)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	95.7 (78.1 to 99.9)	0.0 (0.0 to 24.7)	96.8 (92.8 to 99.0)	34.0 (21.5 to 48.3)
Day 28, TDV-3(n=24,13,22,14,21,17,23,13,158,53)	95.8 (78.9 to 99.9)	84.6 (54.6 to 98.1)	90.9 (70.8 to 98.9)	92.9 (66.1 to 99.8)	100.0 (83.9 to 100.0)	17.6 (3.8 to 43.4)	91.3 (72.0 to 98.9)	0.0 (0.0 to 24.7)	95.6 (91.1 to 98.2)	39.6 (26.5 to 54.0)
Day 28, TDV-4(n=24,13,22,14,21,17,23,13,158,53)	79.2 (57.8 to 92.9)	76.9 (46.2 to 95.0)	59.1 (36.4 to 79.2)	78.6 (49.2 to 95.3)	85.7 (63.7 to 97.0)	11.8 (1.5 to 36.4)	69.6 (47.1 to 86.8)	0.0 (0.0 to 24.7)	74.1 (66.5 to 80.7)	35.8 (23.1 to 50.2)
Day 90, TDV-1(n=23,13,22,14,21,17,22,11,159,53)	100.0 (85.2 to 100.0)	92.3 (64.0 to 99.8)	90.9 (70.8 to 98.9)	85.7 (57.2 to 98.2)	95.2 (76.2 to 99.9)	17.6 (3.8 to 43.4)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	99.4 (96.5 to 100.0)	41.5 (28.1 to 55.9)
Day 90, TDV-2(n=23,13,22,14,21,17,22,11,159,53)	100.0 (85.2 to 100.0)	84.6 (54.6 to 98.1)	90.9 (70.8 to 98.9)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	17.6 (3.8 to 43.4)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	98.7 (95.5 to 99.8)	34.0 (21.5 to 48.3)
Day 90, TDV-3(n=23,13,22,14,21,17,22,11,159,53)	95.7 (78.1 to 99.9)	100.0 (75.3 to 100.0)	90.9 (70.8 to 98.9)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	17.6 (3.8 to 43.4)	81.8 (59.7 to 94.8)	9.1 (0.2 to 41.3)	89.9 (84.2 to 94.1)	34.0 (21.5 to 48.3)
Day 90, TDV-4(n=23,13,22,14,21,17,22,11,159,53)	82.6 (61.2 to 95.0)	69.2 (38.6 to 90.9)	77.3 (54.6 to 92.2)	78.6 (49.2 to 95.3)	66.7 (43.0 to 85.4)	11.8 (1.5 to 36.4)	63.6 (40.7 to 82.8)	9.1 (0.2 to 41.3)	69.8 (62.0 to 76.8)	35.8 (23.1 to 50.2)
Day 180, TDV-1(n=20,12,21,14,21,17,22,11,0,0)	100.0 (83.2 to 100.0)	91.7 (61.5 to 99.8)	95.2 (76.2 to 99.9)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-2(n=20,12,21,14,21,17,22,11,0,0)	100.0 (83.2 to 100.0)	83.3 (51.6 to 97.9)	95.2 (76.2 to 99.9)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-3(n=20,12,21,14,21,17,22,11,0,0)	100.0 (83.2 to 100.0)	91.7 (61.5 to 99.8)	95.2 (76.2 to 99.9)	85.7 (57.2 to 98.2)	100.0 (83.9 to 100.0)	35.3 (14.2 to 61.7)	95.5 (77.2 to 99.9)	9.1 (0.2 to 41.3)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-4(n=20,12,21,14,21,17,22,11,0,0)	90.0 (68.3 to 98.8)	66.7 (34.9 to 90.1)	76.2 (52.8 to 91.8)	78.6 (49.2 to 95.3)	81.0 (58.1 to 94.6)	17.6 (3.8 to 43.4)	77.3 (54.6 to 92.2)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-1(n=19,12,21,13,21,17,22,11,0,0)	100.0 (82.4 to 100.0)	91.7 (61.5 to 99.8)	90.5 (69.6 to 98.8)	84.6 (54.6 to 98.1)	95.2 (76.2 to 99.9)	29.4 (10.3 to 56.0)	100.0 (84.6 to 100.0)	9.1 (0.2 to 41.3)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-2(n=19,12,21,13,21,17,22,11,0,0)	100.0 (82.4 to 100.0)	83.3 (51.6 to 97.9)	95.2 (76.2 to 99.9)	84.6 (54.6 to 98.1)	95.2 (76.2 to 99.9)	29.4 (10.3 to 56.0)	100.0 (84.6 to 100.0)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-3(n=19,12,21,13,21,17,22,11,0,0)	89.5 (66.9 to 98.7)	83.3 (51.6 to 97.9)	81.0 (58.1 to 94.6)	84.6 (54.6 to 98.1)	95.2 (76.2 to 99.9)	29.4 (10.3 to 56.0)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-4(n=19,12,21,13,21,17,22,11,0,0)	84.2 (60.4 to 96.6)	75.0 (42.8 to 94.5)	66.7 (43.0 to 85.4)	84.6 (54.6 to 98.1)	61.9 (38.4 to 81.9)	17.6 (3.8 to 43.4)	63.6 (40.7 to 82.8)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-1(n=16,9,19,13,21,17,22,10,0,0)	100.0 (79.4 to 100.0)	100.0 (66.4 to 100.0)	89.5 (66.9 to 98.7)	84.6 (54.6 to 98.1)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	100.0 (84.6 to 100.0)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-2(n=16,9,19,13,21,17,22,10,0,0)	100.0 (79.4 to 100.0)	88.9 (51.8 to 99.7)	94.7 (74.0 to 99.9)	84.6 (54.6 to 98.1)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	100.0 (84.6 to 100.0)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-3(n=16,9,19,13,21,17,22,10,0,0)	87.5 (61.7 to 98.4)	88.9 (51.8 to 99.7)	68.4 (43.4 to 87.4)	84.6 (54.6 to 98.1)	71.4 (47.8 to 88.7)	17.6 (3.8 to 43.4)	90.9 (70.8 to 98.9)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-4(n=16,9,19,13,21,17,22,10,0,0)	81.3 (54.4 to 96.0)	77.8 (40.0 to 97.2)	63.2 (38.4 to 83.7)	84.6 (54.6 to 98.1)	57.1 (34.0 to 78.2)	23.5 (6.8 to 49.9)	72.7 (49.8 to 89.3)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-1(n=15,8,18,11,21,17,21,9,0,0)	100.0 (78.2 to 100.0)	100.0 (63.1 to 100.0)	94.4 (72.7 to 99.9)	81.8 (48.2 to 97.7)	95.2 (76.2 to 99.9)	23.5 (6.8 to 49.9)	100.0 (83.9 to 100.0)	11.1 (0.3 to 48.2)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-2(n=15,8,18,11,21,17,21,9,0,0)	100.0 (78.2 to 100.0)	87.5 (47.3 to 99.7)	100.0 (81.5 to 100.0)	81.8 (48.2 to 97.7)	100.0 (83.9 to 100.0)	23.5 (6.8 to 49.9)	95.2 (76.2 to 99.9)	0.0 (0.0 to 33.6)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-3(n=15,8,18,11,21,17,21,9,0,0)	93.3 (68.1 to 99.8)	87.5 (47.3 to 99.7)	77.8 (52.4 to 93.6)	81.8 (48.2 to 97.7)	85.7 (63.7 to 97.0)	23.5 (6.8 to 49.9)	95.2 (76.2 to 99.9)	11.1 (0.3 to 48.2)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-4(n=15,8,18,11,21,17,21,9,0,0)	80.0 (51.9 to 95.7)	87.5 (47.3 to 99.7)	61.1 (35.7 to 82.7)	72.7 (39.0 to 94.0)	42.9 (21.8 to 66.0)	17.6 (3.8 to 43.4)	47.6 (25.7 to 70.2)	11.1 (0.3 to 48.2)	9999 (9999 to 9999)	9999 (9999 to 9999)

No statistical analyses for this end point

Secondary: Seroconversion Rate to Each of the Four Dengue Serotypes

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End point title

Seroconversion Rate to Each of the Four Dengue Serotypes

End point description

Seroconversion rate was defined as the percentage of participants with microneutralisation test 50% (MNT50) titer ≥10 or, if the titer on Day 0 was ≥10, a 4-fold rise in antibody titer. FAS included all randomised participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received. n=number of subjects available for analysis at a specific timepoint. 9999=Data were not collected at this timepoint.

End point type

Secondary

End point timeframe

Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: percentage of participants
number (confidence interval 95%)
Day28, TDV-1(n=24,13,22,14,21,17,23,13,158,53)	45.8 (25.6 to 67.2)	7.7 (0.2 to 36.0)	63.6 (40.7 to 82.8)	0.0 (0.0 to 23.2)	90.5 (69.6 to 98.8)	5.9 (0.1 to 28.7)	87.0 (66.4 to 97.2)	7.7 (0.2 to 36.0)	86.1 (79.7 to 91.1)	1.9 (0.0 to 10.1)
Day28, TDV-2(n=24,13,22,14,21,17,23,13,158,53)	33.3 (15.6 to 55.3)	15.4 (1.9 to 45.4)	59.1 (36.4 to 79.3)	0.0 (0.0 to 23.2)	85.7 (63.7 to 97.0)	11.8 (1.5 to 36.4)	87.0 (66.4 to 97.2)	0.0 (0.0 to 24.7)	86.7 (80.4 to 91.6)	0.0 (0.0 to 6.7)
Day28, TDV-3(n=24,13,22,14,21,17,23,13,158,53)	33.3 (15.6 to 55.3)	0.0 (0.0 to 24.7)	63.6 (40.7 to 82.8)	7.1 (0.2 to 33.9)	90.5 (69.6 to 98.8)	0.0 (0.0 to 19.5)	78.3 (56.3 to 92.5)	0.0 (0.0 to 24.7)	82.3 (75.4 to 87.9)	1.9 (0.0 to 10.1)
Day28, TDV-4(n=24,13,22,14,21,17,23,13,158,53)	20.8 (7.1 to 42.2)	15.4 (1.9 to 45.4)	31.8 (13.9 to 54.9)	0.0 (0.0 to 23.2)	71.4 (47.8 to 88.7)	5.9 (0.1 to 28.7)	60.9 (38.5 to 80.3)	0.0 (0.0 to 24.7)	62.7 (54.6 to 70.2)	5.7 (1.2 to 15.7)
Day 90, TDV-1(n=23,13,22,14,21,17,22,11,159,53)	39.1 (19.7 to 61.5)	15.4 (1.9 to 45.4)	54.5 (32.2 to 75.6)	7.1 (0.2 to 33.9)	81.0 (58.1 to 94.6)	0.0 (0.0 to 19.5)	81.8 (59.7 to 94.8)	0.0 (0.0 to 28.5)	82.4 (75.6 to 88.0)	3.8 (0.5 to 13.0)
Day 90, TDV-2(n=23,13,22,14,21,17,22,11,159,53)	30.4 (13.2 to 52.9)	15.4 (1.9 to 45.4)	59.1 (36.4 to 79.3)	7.1 (0.2 to 33.9)	85.7 (63.7 to 97.0)	0.0 (0.0 to 19.5)	90.9 (70.8 to 98.9)	0.0 (0.0 to 28.5)	86.2 (79.8 to 91.1)	1.9 (0.0 to 10.1)
Day 90, TDV-3(n=23,13,22,14,21,17,22,11,159,53)	30.4 (13.2 to 52.9)	23.1 (5.0 to 53.8)	59.1 (36.4 to 79.3)	14.3 (1.8 to 42.8)	81.0 (58.1 to 94.6)	0.0 (0.0 to 19.5)	63.6 (40.7 to 82.8)	9.1 (0.2 to 41.3)	76.1 (68.7 to 82.5)	0.0 (0.0 to 6.7)
Day 90, TDV-4(n=23,13,22,14,21,17,22,11,159,53)	21.7 (7.5 to 43.7)	0.0 (0.0 to 24.7)	50.0 (28.2 to 71.8)	21.4 (4.7 to 50.8)	61.9 (38.4 to 81.9)	5.9 (0.1 to 28.7)	54.5 (32.2 to 75.6)	9.1 (0.2 to 41.3)	57.9 (49.8 to 65.6)	5.7 (1.2 to 15.7)
Day 120, TDV-1(n=22,13,22,14,21,17,22,11,156,53)	45.5 (24.4 to 67.8)	0.0 (0.0 to 24.7)	68.2 (45.1 to 86.1)	14.3 (1.8 to 42.8)	90.5 (69.6 to 98.8)	5.9 (0.1 to 28.7)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	88.5 (82.4 to 93.0)	3.8 (0.5 to 13.0)
Day 120, TDV-2(n=22,13,22,14,21,17,22,11,156,53)	45.5 (24.4 to 67.8)	0.0 (0.0 to 24.7)	63.6 (40.7 to 82.8)	0.0 (0.0 to 23.2)	95.2 (76.2 to 99.9)	5.9 (0.1 to 28.7)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	90.4 (84.6 to 94.5)	3.8 (0.5 to 13.0)
Day 120, TDV-3(n=22,13,22,14,21,17,22,11,156,53)	45.5 (24.4 to 67.8)	30.8 (9.1 to 61.4)	68.2 (45.1 to 86.1)	14.3 (1.8 to 42.8)	90.5 (69.6 to 98.8)	17.6 (3.8 to 43.4)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	86.5 (80.2 to 91.5)	1.9 (0.0 to 10.1)
Day 120, TDV-4(n=22,13,22,14,21,17,22,11,156,53)	40.9 (20.7 to 63.6)	7.7 (0.2 to 36.0)	45.5 (24.4 to 67.8)	14.3 (1.8 to 42.8)	85.7 (63.7 to 97.0)	23.5 (6.8 to 49.9)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	84.0 (77.3 to 89.4)	3.8 (0.5 to 13.0)
Day 180, TDV-1(n=20,12,21,14,21,17,22,11,0,0)	50.0 (27.2 to 72.8)	8.3 (0.2 to 38.5)	61.9 (38.4 to 81.9)	0.0 (0.0 to 23.2)	95.2 (76.2 to 99.9)	5.9 (0.1 to 28.7)	90.9 (70.8 to 99.9)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-2(n=20,12,21,14,21,17,22,11,0,0)	60.0 (36.1 to 80.9)	8.3 (0.2 to 38.5)	61.9 (38.4 to 81.9)	7.1 (0.2 to 33.9)	95.2 (76.2 to 99.9)	5.9 (0.1 to 28.7)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-3(n=20,12,21,14,21,17,22,11,0,0)	40.0 (19.1 to 63.9)	8.3 (0.2 to 38.5)	61.9 (38.4 to 81.9)	7.1 (0.2 to 33.9)	90.5 (69.5 to 98.8)	17.6 (3.8 to 43.4)	86.4 (65.1 to 97.1)	9.1 (0.2 to 41.3)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-4(n=20,12,21,14,21,17,22,11,0,0)	45.0 (23.1 to 68.5)	8.3 (0.2 to 38.5)	47.6 (25.7 to 70.2)	7.1 (0.2 to 33.9)	81.0 (58.1 to 94.6)	11.8 (1.5 to 36.4)	72.7 (49.8 to 98.3)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-1(n=19,12,21,13,21,17,22,11,0,0)	52.6 (28.9 to 75.6)	0.0 (0.0 to 26.5)	57.1 (34.0 to 78.2)	15.4 (1.9 to 45.4)	85.7 (63.7 to 97.0)	11.8 (1.5 to 36.4)	90.9 (70.8 to 98.9)	9.1 (0.2 to 41.3)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-2(n=19,12,21,13,21,17,22,11,0,0)	47.4 (24.4 to 71.1)	0.0 (0.0 to 26.5)	61.9 (38.4 to 81.9)	15.4 (1.9 to 45.4)	76.2 (52.8 to 91.8)	17.6 (3.8 to 43.4)	95.5 (77.2 to 99.9)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-3(n=19,12,21,13,21,17,22,11,0,0)	36.8 (16.3 to 61.6)	0.0 (0.0 to 26.5)	57.1 (34.0 to 78.2)	15.4 (1.9 to 45.4)	76.2 (52.8 to 91.8)	11.8 (1.5 to 36.4)	81.8 (59.7 to 94.8)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-4(n=19,12,21,13,21,17,22,11,0,0)	42.1 (20.3 to 66.5)	0.0 (0.0 to 26.5)	38.1 (18.1 to 61.6)	7.7 (0.2 to 36.0)	57.1 (34.0 to 78.2)	11.8 (1.5 to 36.4)	59.1 (36.4 to 79.3)	0.0 (0.0 to 28.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-1(n=16,9,19,13,21,17,22,10,0,0)	50.0 (24.7 to 75.3)	0.0 (0.0 to 33.6)	47.4 (24.4 to 71.1)	15.4 (1.9 to 45.4)	95.2 (76.2 to 99.9)	5.9 (0.1 to 28.7)	86.4 (65.1 to 97.1)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-2(n=16,9,19,13,21,17,22,10,0,0)	50.0 (24.7 to 75.3)	0.0 (0.0 to 33.6)	57.9 (33.5 to 79.7)	7.7 (0.2 to 36.0)	85.7 (63.7 to 97.0)	5.9 (0.1 to 28.7)	95.5 (77.2 to 99.9)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-3(n=16,9,19,13,21,17,22,10,0,0)	43.8 (19.8 to 70.1)	0.0 (0.0 to 33.6)	31.6 (12.6 to 56.6)	15.4 (1.9 to 45.4)	66.7 (43.0 to 85.4)	5.9 (0.1 to 28.7)	86.4 (65.1 to 97.1)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-4(n=16,9,19,13,21,17,22,10,0,0)	18.8 (4.0 to 45.6)	0.0 (0.0 to 36.9)	36.8 (16.3 to 61.6)	15.4 (1.9 to 45.4)	47.6 (25.7 to 70.2)	17.6 (3.8 to 43.4)	63.6 (40.7 to 82.8)	10.0 (0.3 to 44.5)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-1(n=15,8,18,11,21,17,21,9,0,0)	46.7 (21.3 to 73.4)	0.0 (0.0 to 36.9)	55.6 (30.8 to 78.5)	18.2 (2.3 to 51.8)	90.5 (69.6 to 98.8)	5.9 (0.1 to 28.7)	85.7 (63.7 to 97.0)	11.1 (0.3 to 48.2)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-2(n=15,8,18,11,21,17,21,9,0,0)	46.7 (21.3 to 73.4)	0.0 (0.0 to 36.9)	61.1 (35.7 to 82.7)	9.1 (0.2 to 41.3)	81.0 (58.1 to 94.6)	5.9 (0.1 to 28.7)	85.7 (63.7 to 97.0)	0.0 (0.0 to 33.6)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-3(n=15,8,18,11,21,17,21,9,0,0)	33.3 (11.8 to 61.6)	0.0 (0.0 to 36.9)	44.4 (21.5 to 69.2)	18.2 (2.3 to 51.8)	81.0 (58.1 to 94.6)	5.9 (0.1 to 28.7)	90.5 (69.6 to 98.8)	11.1 (0.3 to 48.2)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-4(n=15,8,18,11,21,17,21,9,0,0)	13.3 (1.7 to 40.5)	12.5 (0.3 to 52.7)	27.8 (9.7 to 53.5)	18.2 (2.3 to 51.8)	33.3 (14.6 to 57.0)	11.8 (1.5 to 36.4)	38.1 (18.1 to 61.6)	11.1 (0.3 to 48.2)	9999 (9999 to 9999)	9999 (9999 to 9999)

No statistical analyses for this end point

Secondary: Geometric Mean Neutralising Antibody Titers (GMTs) of All Four Dengue Serotypes

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End point title

Geometric Mean Neutralising Antibody Titers (GMTs) of All Four Dengue Serotypes

End point description

GMTs were assessed for the four dengue serotypes: TDV-1, TDV-2, TDV-3, and TDV-4. The FAS included all randomised participants who received at least one dose of study vaccine and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received. Here "n" is the number of participants with microneutralising (MN) assay samples. 9999=Data were not collected at this timepoint. 0.99999 and 99999=Lower and upper limits of CI could not be evaluated as titers were below the lower limit of detection (LLOD).

End point type

Secondary

End point timeframe

Day 28, 90 and 120 (Parts 1 and 2) and Days 180, 360, 720 and 1080 in Part 1

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: titer
geometric mean (confidence interval 95%)
Day 28, TDV-1(n=24,13,22,14,21,17,23,13,158,53)	1156.9 (582.0 to 2299.9)	396.1 (120.6 to 1301.2)	919.5 (273.1 to 3096.1)	204.9 (59.8 to 702.6)	383.7 (178.1 to 826.5)	11.3 (4.4 to 29.3)	395.2 (190.0 to 822.0)	5.3 (4.7 to 5.9)	522.2 (396.5 to 687.7)	28.7 (14.8 to 55.5)
Day 28, TDV-2(n=24,13,22,14,21,17,23,13,158,53)	2313.9 (1328.1 to 4031.2)	178.0 (44.4 to 712.9)	1726.6 (539.2 to 5528.8)	420.2 (116.5 to 1515.6)	2357.2 (1218.6 to 4559.7)	13.9 (5.0 to 38.6)	1134.6 (479.9 to 2682.6)	5.0 (0.99999 to 99999)	1496.5 (1129.1 to 1983.4)	16.4 (9.7 to 27.9)
Day 28, TDV-3(n=24,13,22,14,21,17,23,13,158,53)	538.2 (218.3 to 1326.5)	226.3 (70.1 to 730.7)	330.2 (94.4 to 1155.9)	304.5 (83.9 to 1105.6)	314.8 (135.3 to 732.3)	8.5 (4.1 to 17.4)	129.6 (52.9 to 317.6)	5.0 (0.99999 to 99999)	206.9 (149.9 to 285.7)	19.4 (11.5 to 32.6)
Day 28, TDV-4(n=24,13,22,14,21,17,23,13,158,53)	130.7 (54.3 to 314.5)	55.1 (15.6 to 194.9)	56.6 (19.1 to 167.3)	46.4 (17.6 to 122.4)	61.4 (27.1 to 139.4)	7.2 (3.9 to 13.4)	27.0 (12.5 to 58.5)	5.0 (0.99999 to 99999)	45.4 (33.2 to 62.0)	11.0 (7.8 to 15.6)
Day 90, TDV-1(n=23,13,22,14,21,17,22,11,159,53)	961.3 (413.5 to 2235.2)	751.0 (227.1 to 2483.1)	555.4 (156.9 to 1966.2)	215.3 (55.4 to 836.4)	245.7 (82.2 to 734.7)	10.8 (4.2 to 28.3)	165.1 (69.4 to 392.8)	5.0 (0.99999 to 99999)	324.2 (239.1 to 439.6)	27.9 (14.6 to 53.4)
Day 90, TDV-2(n=23,13,22,14,21,17,22,11,159,53)	2073.1 (1267.0 to 3392.1)	320.0 (74.2 to 1379.3)	1146.4 (416.7 to 3153.6)	463.9 (120.1 to 1792.0)	966.9 (451.8 to 2069.2)	10.0 (4.3 to 23.1)	467.0 (205.7 to 1060.3)	5.0 (0.99999 to 99999)	463.5 (364.0 to 590.2)	15.2 (8.9 to 25.9)
Day 90, TDV-3(n=23,13,22,14,21,17,22,11,159,53)	510.5 (218.3 to 1194.1)	272.7 (86.4 to 860.4)	193.3 (54.9 to 680.7)	336.2 (95.3 to 1185.8)	195.0 (73.3 to 518.8)	8.5 (4.4 to 16.5)	66.2 (28.3 to 154.8)	5.3 (4.6 to 6.1)	139.5 (99.7 to 195.1)	17.1 (10.2 to 28.5)
Day 90, TDV-4(n=23,13,22,14,21,17,22,11,159,53)	125.7 (57.7 to 274.1)	36.0 (13.3 to 97.2)	76.3 (29.3 to 198.9)	69.0 (23.7 to 200.4)	31.2 (12.3 to 79.3)	7.5 (4.0 to 14.3)	16.8 (9.3 to 30.5)	5.3 (4.6 to 6.1)	33.7 (25.4 to 44.7)	11.8 (8.2 to 16.9)
Day 120, TDV-1(n=22,13,22,14,21,17,22,11,156,53)	1240.3 (585.2 to 2628.8)	356.0 (117.8 to 1076.1)	1300.3 (528.5 to 3199.4)	164.0 (52.8 to 509.4)	551.7 (231.6 to 1313.8)	13.9 (4.9 to 39.2)	582.3 (275.9 to 1229.1)	5.0 (0.99999 to 99999)	710.4 (547.5 to 921.9)	29.6 (15.6 to 56.1)
Day 120, TDV-2(n=22,13,22,14,21,17,22,11,156,53)	2403.7 (1443.5 to 4002.6)	272.7 (60.9 to 1221.6)	1754.0 (744.2 to 4134.4)	399.9 (109.7 to 1457.7)	983.0 (423.5 to 2281.6)	17.3 (4.6 to 65.9)	459.7 (232.6 to 908.7)	5.0 (0.99999 to 99999)	605.4 (490.6 to 747.1)	16.2 (9.5 to 27.8)
Day 120, TDV-3(n=22,13,22,14,21,17,22,11,156,53)	650.2 (288.1 to 1467.0)	287.6 (116.7 to 709.1)	340.8 (121.3 to 957.6)	289.8 (82.7 to 1016.1)	377.4 (170.3 to 836.6)	14.4 (5.0 to 41.8)	196.4 (115.2 to 334.8)	5.0 (0.99999 to 99999)	332.3 (263.1 to 419.7)	19.0 (11.3 to 32.0)
Day 120, TDV-4(n=22,13,22,14,21,17,22,11,156,53)	193.3 (84.7 to 441.1)	36.0 (10.5 to 123.2)	82.6 (31.8 to 214.1)	69.0 (23.5 to 202.7)	64.6 (27.6 to 151.1)	13.9 (5.4 to 35.3)	41.3 (24.9 to 68.3)	5.0 (0.99999 to 99999)	76.5 (60.5 to 96.8)	11.2 (8.0 to 15.9)
Day 180, TDV-1(n=20,12,21,14,21,17,22,11,0,0)	831.7 (332.7 to 2078.8)	320.0 (86.0 to 1191.4)	954.7 (280.8 to 3245.7)	141.6 (38.8 to 516.4)	230.5 (107.2 to 495.4)	12.8 (4.7 to 34.4)	249.2 (113.5 to 546.8)	5.0 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-2(n=20,12,21,14,21,17,22,11,0,0)	2521.2 (1444.5 to 4400.4)	226.3 (48.9 to 1046.4)	1515.6 (593.7 to 3869.0)	412.3 (104.9 to 1620.6)	642.5 (325.9 to 1266.8)	14.4 (4.9 to 42.4)	399.3 (194.7 to 819.1)	5.0 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-3(n=20,12,21,14,21,17,22,11,0,0)	422.2 (179.1 to 995.5)	285.1 (74.7 to 1087.6)	321.2 (101.3 to 1018.4)	206.1 (65.9 to 645.0)	189.1 (84.2 to 424.6)	12.5 (5.5 to 28.4)	93.6 (41.4 to 211.7)	6.0 (4.0 to 9.2)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-4(n=20,12,21,14,21,17,22,11,0,0)	146.7 (62.8 to 342.7)	44.9 (13.0 to 155.7)	71.5 (27.6 to 185.0)	51.2 (19.8 to 132.4)	47.2 (20.4 to 109.3)	9.2 (4.4 to 19.4)	28.3 (14.3 to 56.0)	5.0 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-1(n=19,12,21,13,21,17,22,11,0,0)	1417.4 (474.5 to 4233.5)	320.0 (78.5 to 1304.5)	642.5 (179.5 to 2299.8)	221.0 (48.9 to 999.6)	132.0 (51.6 to 338.0)	15.7 (5.5 to 45.2)	220.9 (90.3 to 540.2)	5.3 (4.6 to 6.1)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-2(n=19,12,21,13,21,17,22,11,0,0)	2410.7 (1120.9 to 5185.0)	271.8 (60.9 to 1212.7)	852.2 (369.9 to 1963.3)	523.6 (113.4 to 2416.7)	329.5 (161.7 to 671.1)	17.1 (6.0 to 48.7)	298.8 (141.1 to 632.8)	5.0 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-3(n=19,12,21,13,21,17,22,11,0,0)	537.9 (158.5 to 1825.3)	256.2 (70.2 to 935.3)	171.3 (51.1 to 574.0)	209.5 (55.4 to 792.9)	103.1 (40.0 to 265.6)	11.8 (5.3 to 26.0)	89.9 (43.9 to 184.1)	5.0 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-4(n=19,12,21,13,21,17,22,11,0,0)	163.6 (56.2 to 476.4)	44.9 (13.5 to 149.1)	73.8 (26.9 to 202.8)	59.9 (19.4 to 184.4)	27.0 (11.9 to 61.0)	7.5 (4.0 to 14.0)	20.0 (10.8 to 37.0)	5.0 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-1(n=16,9,19,13,21,17,22,10,0,0)	924.9 (289.1 to 2959.4)	691.2 (175.7 to 2720.1)	452.5 (124.5 to 1644.5)	258.5 (67.0 to 997.9)	115.0 (45.4 to 291.1)	12.8 (4.8 to 34.2)	248.7 (103.4 to 597.9)	5.7 (4.2 to 7.9)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-2(n=16,9,19,13,21,17,22,10,0,0)	1399.4 (704.8 to 2778.8)	244.9 (50.1 to 1197.1)	714.0 (247.9 to 2056.8)	396.1 (98.3 to 1595.4)	280.4 (135.1 to 582.2)	13.0 (5.0 to 33.9)	219.3 (106.7 to 450.7)	5.4 (4.6 to 6.3)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-3(n=16,9,19,13,21,17,22,10,0,0)	515.4 (140.6 to 1888.5)	403.2 (96.0 to 1692.5)	154.3 (36.7 to 649.1)	303.4 (70.9 to 1297.4)	65.6 (21.2 to 203.0)	8.8 (4.5 to 17.5)	104.6 (37.7 to 289.8)	8.1 (2.7 to 24.3)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-4(n=16,9,19,13,21,17,22,10,0,0)	106.0 (40.5 to 277.3)	48.5 (13.1 to 180.2)	66.7 (22.5 to 197.2)	93.9 (29.0 to 303.8)	24.4 (10.8 to 55.2)	8.5 (4.7 to 15.2)	26.6 (12.3 to 57.3)	5.7 (4.2 to 7.9)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-1(n=15,8,18,11,21,17,21,9,0,0)	718.4 (239.3 to 2156.7)	905.1 (243.2 to 3368.4)	508.0 (137.6 to 1874.9)	219.3 (41.2 to 1165.6)	92.8 (36.5 to 236.2)	12.8 (4.8 to 34.2)	149.8 (63.9 to 351.1)	6.3 (3.7 to 10.7)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-2(n=15,8,18,11,21,17,21,9,0,0)	702.0 (403.1 to 1222.4)	146.7 (27.3 to 787.7)	615.8 (277.5 to 1366.8)	256.7 (61.0 to 1079.3)	160.0 (76.5 to 334.8)	12.8 (5.2 to 31.7)	118.9 (57.0 to 248.0)	5.0 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-3(n=15,8,18,11,21,17,21,9,0,0)	291.8 (82.5 to 1032.3)	472.6 (84.6 to 2641.0)	201.6 (54.6 to 744.0)	264.9 (53.4 to 1313.1)	70.1 (27.6 to 178.4)	9.6 (4.6 to 20.1)	80.0 (31.9 to 200.7)	9.3 (2.2 to 38.3)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-4(n=15,8,18,11,21,17,21,9,0,0)	81.9 (30.9 to 216.9)	80.0 (17.5 to 364.8)	61.1 (21.7 to 172.3)	80.0 (18.9 to 338.6)	17.5 (8.4 to 36.6)	7.2 (4.2 to 12.3)	17.0 (8.6 to 33.3)	5.4 (4.5 to 6.4)	9999 (9999 to 9999)	9999 (9999 to 9999)

No statistical analyses for this end point

Secondary: Geometric Mean Fold Rise (GMFR) of Dengue Neutralising Antibody Titers for Each of the 4 Dengue Serotypes

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End point title

Geometric Mean Fold Rise (GMFR) of Dengue Neutralising Antibody Titers for Each of the 4 Dengue Serotypes

End point description

FAS included all randomised participants who received at least one dose of study vaccine or placebo and for whom valid pre-dosing and at least one valid post-dosing blood sample have been received. n=number of subjects available for analysis at a specific timepoint. 9999=Data were not evaluated at this timepoint. 0.99999 and 99999=Lower and upper limits of CI could not be evaluated as titers were below the LLOD.

End point type

Secondary

End point timeframe

Day 28 and Day 90 (Parts 1 and 2) and Days 120, 180, 360, 720 and 1080 in Part 1

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: fold rise
geometric mean (confidence interval 95%)
Day 28, TDV-1(n=24,13,22,14,21,17,23,13,158,53)	3.41 (1.61 to 7.24)	0.90 (0.57 to 1.41)	8.93 (3.61 to 22.09)	1.03 (0.67 to 1.56)	29.47 (11.70 to 74.22)	1.00 (0.88 to 1.13)	27.94 (13.64 to 57.23)	1.05 (0.94 to 1.18)	27.58 (20.91 to 36.38)	0.97 (0.82 to 1.16)
Day 28, TDV-2(n=24,13,22,14,21,17,23,13,158,53)	7.89 (2.01 to 31.00)	0.71 (0.45 to 1.11)	20.26 (5.34 to 76.93)	1.05 (0.69 to 1.59)	181.02 (47.86 to 684.60)	1.39 (0.81 to 2.37)	128.00 (44.62 to 367.22)	1.00 (0.99999 to 99999)	113.02 (0.1 to 8192.0)	0.94 (0.0 to 2.0)
Day 28, TDV-3(n=24,13,22,14,21,17,23,13,158,53)	2.34 (1.22 to 4.52)	0.97 (0.74 to 1.28)	4.40 (1.85 to 10.48)	1.08 (0.71 to 1.63)	24.17 (10.16 to 57.49)	1.02 (0.98 to 1.07)	13.76 (6.01 to 31.50)	1.00 (0.99999 to 99999)	12.47 (9.18 to 16.92)	0.82 (0.71 to 0.94)
Day 28, TDV-4(n=24,13,22,14,21,17,23,13,158,53)	1.71 (0.88 to 3.31)	1.11 (0.65 to 1.90)	2.74 (1.11 to 6.80)	0.82 (0.53 to 1.26)	7.49 (3.60 to 15.58)	1.13 (0.94 to 1.36)	4.00 (1.85 to 8.66)	0.95 (0.84 to 1.06)	74.1 (66.5 to 80.7)	35.8 (23.1 to 50.2)
Day 90, TDV-1(n=23,13,22,14,21,17,22,11,159,53)	3.10 (1.26 to 7.59)	1.70 (0.75 to 3.90)	5.40 (2.50 to 11.63)	1.08 (0.71 to 1.63)	18.87 (7.61 to 46.81)	0.96 (0.88 to 1.05)	11.14 (5.37 to 23.09)	1.00 (0.99999 to 99999)	324.2 (239.1 to 439.6)	27.9 (14.6 to 53.4)
Day 90, TDV-2(n=23,13,22,14,21,17,22,11,159,53)	7.09 (2.20 to 22.83)	1.27 (0.78 to 2.08)	13.45 (4.52 to 40.08)	1.16 (0.74 to 1.83)	74.25 (30.35 to 181.64)	1.00 (0.88 to 1.13)	51.33 (20.33 to 129.62)	1.00 (0.99999 to 99999)	463.5 (364.0 to 590.2)	15.2 (8.9 to 25.9)
Day 90, TDV-3(n=23,13,22,14,21,17,22,11,159,53)	2.29 (1.29 to 4.05)	1.17 (0.74 to 1.85)	2.57 (1.14 to 5.80)	1.19 (0.67 to 2.13)	14.98 (6.11 to 36.75)	1.02 (0.92 to 1.13)	6.83 (3.13 to 14.93)	1.07 (0.93 to 1.23)	139.5 (99.7 to 195.1)	17.1 (10.2 to 28.5)
Day 90, TDV-4(n=23,13,22,14,21,17,22,11,159,53)	1.64 (1.02 to 2.66)	0.73 (0.52 to 1.01)	3.70 (1.78 to 7.66)	1.22 (0.72 to 2.07)	3.81 (1.73 to 8.36)	1.18 (0.90 to 1.54)	2.45 (1.39 to 4.32)	1.00 (0.81 to 1.23)	33.7 (25.4 to 44.7)	11.8 (8.2 to 16.9)
Day 120, TDV-1(n=22,13,22,14,21,17,22,11,156,53)	3.64 (1.09 to 12.10)	0.81 (0.56 to 1.16)	12.63 (5.56 to 28.70)	0.82 (0.34 to 2.01)	42.36 (19.57 to 91.70)	1.23 (0.72 to 2.09)	39.27 (24.12 to 63.94)	1.00 (0.99999 to 99999)	35.44 (26.46 to 47.48)	1.01 (0.79 to 1.28)
Day 120, TDV-2(n=22,13,22,14,21,17,22,11,156,53)	8.79 (2.81 to 27.47)	1.08 (0.79 to 1.49)	20.59 (6.45 to 65.66)	1.00 (0.67 to 1.50)	75.48 (29.82 to 191.08)	1.73 (0.56 to 5.38)	50.53 (24.11 to 105.89)	1.00 (0.99999 to 99999)	44.16 (33.51 to 58.20)	0.92 (0.67 to 1.28)
Day 120, TDV-3(n=22,13,22,14,21,17,22,11,156,53)	2.78 (1.44 to 5.37)	1.24 (0.70 to 2.20)	4.54 (2.02 to 10.17)	1.03 (0.60 to 1.75)	28.98 (14.52 to 57.87)	1.73 (0.73 to 4.14)	20.26 (12.02 to 34.17)	1.00 (0.99999 to 99999)	19.20 (14.75 to 24.98)	0.80 (0.64 to 1.01)
Day 120, TDV-4(n=22,13,22,14,21,17,22,11,156,53)	2.45 (1.44 to 4.19)	0.73 (0.43 to 1.23)	4.00 (2.00 to 8.00)	1.22 (0.72 to 2.07)	7.87 (4.25 to 14.57)	2.17 (0.99 to 4.76)	6.02 (3.81 to 9.53)	0.94 (0.82 to 1.08)	7.43 (5.96 to 9.27)	1.03 (0.91 to 1.16)
Day 180, TDV-1(n=20,12,21,14,21,17,22,11,0,0)	3.94 (1.35 to 11.54)	0.89 (0.59 to 1.35)	9.16 (2.89 to 29.05)	0.71 (0.45 to 1.10)	17.70 (10.04 to 31.22)	1.13 (0.77 to 1.66)	16.81 (9.56 to 29.53)	1.00 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-2(n=20,12,21,14,21,17,22,11,0,0)	11.53 (3.61 to 36.83)	0.94 (0.55 to 1.63)	17.16 (5.15 to 57.17)	1.03 (0.58 to 1.84)	49.34 (22.02 to 110.57)	1.44 (0.66 to 3.17)	43.89 (21.22 to 90.80)	1.00 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-3(n=20,12,21,14,21,17,22,11,0,0)	2.42 (1.23 to 4.76)	1.26 (0.95 to 1.68)	4.58 (1.72 to 12.21)	0.73 (0.44 to 1.20)	14.52 (7.70 to 27.38)	1.50 (0.86 to 2.64)	9.66 (4.84 to 19.30)	1.21 (0.79 to 1.84)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 180, TDV-4(n=20,12,21,14,21,17,22,11,0,0)	2.38 (1.43 to 3.95)	1.00 (0.63 to 1.58)	3.35 (1.60 to 7.01)	0.91 (0.60 to 1.37)	5.76 (3.14 to 10.55)	1.44 (0.88 to 2.36)	4.13 (2.29 to 7.43)	0.94 (0.82 to 1.08)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-1(n=19,12,21,13,21,17,22,11,0,0)	5.51 (2.13 to 14.26)	0.67 (0.47 to 0.95)	6.17 (2.36 to 16.14)	1.09 (0.50 to 2.37)	10.14 (4.81 to 21.39)	1.39 (0.91 to 2.12)	14.90 (7.48 to 29.66)	1.07 (0.93 to 1.23)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-2(n=19,12,21,13,21,17,22,11,0,0)	9.04 (2.76 to 29.60)	0.93 (0.64 to 1.34)	9.65 (3.34 to 27.83)	1.16 (0.54 to 2.46)	25.30 (10.10 to 63.38)	1.71 (0.81 to 3.59)	32.84 (15.76 to 68.42)	1.00 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-3(n=19,12,21,13,21,17,22,11,0,0)	2.56 (1.21 to 5.39)	0.95 (0.71 to 1.27)	2.44 (1.00 to 5.96)	0.83 (0.44 to 1.57)	7.92 (3.28 to 19.10)	1.41 (0.88 to 2.29)	9.28 (4.55 to 18.92)	1.00 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 360, TDV-4(n=19,12,21,13,21,17,22,11,0,0)	2.32 (1.15 to 4.70)	0.75 (0.53 to 1.06)	3.45 (1.66 to 7.17)	1.03 (0.45 to 2.38)	3.29 (1.83 to 5.89)	1.18 (0.96 to 1.44)	2.92 (1.71 to 4.98)	0.94 (0.82 to 1.08)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-1(n=16,9,19,13,21,17,22,10,0,0)	4.65 (1.45 to 14.97)	0.63 (0.43 to 0.92)	3.65 (1.68 to 7.96)	1.27 (0.64 to 2.54)	8.83 (4.69 to 16.64)	1.13 (0.87 to 1.46)	16.77 (7.12 to 39.51)	1.15 (0.84 to 1.57)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-2(n=16,9,19,13,21,17,22,10,0,0)	9.13 (2.52 to 33.07)	0.80 (0.51 to 1.24)	8.61 (3.28 to 22.56)	0.88 (0.52 to 1.48)	21.53 (9.91 to 46.81)	1.30 (0.73 to 2.32)	24.10 (11.73 to 49.52)	1.07 (0.92 to 1.25)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-3(n=16,9,19,13,21,17,22,10,0,0)	3.15 (1.38 to 7.21)	0.93 (0.67 to 1.28)	2.00 (0.76 to 5.28)	1.21 (0.72 to 2.02)	5.04 (2.21 to 11.50)	1.06 (0.80 to 1.41)	10.79 (4.16 to 28.00)	1.62 (0.54 to 4.87)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 720, TDV-4(n=16,9,19,13,21,17,22,10,0,0)	1.54 (0.77 to 3.10)	0.56 (0.39 to 0.82)	2.88 (1.41 to 5.90)	1.62 (0.76 to 3.43)	2.97 (1.56 to 5.66)	1.33 (0.95 to 1.86)	3.88 (1.89 to 7.96)	1.07 (0.74 to 1.55)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-1(n=15,8,18,11,21,17,21,9,0,0)	3.91 (1.40 to 10.94)	0.77 (0.45 to 1.31)	3.43 (1.66 to 7.08)	1.33 (0.73 to 2.41)	7.13 (3.86 to 13.17)	1.13 (0.79 to 1.62)	9.59 (4.72 to 19.48)	1.26 (0.74 to 2.15)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-2(n=15,8,18,11,21,17,21,9,0,0)	4.59 (1.45 to 14.59)	0.68 (0.51 to 0.90)	6.35 (2.54 to 15.87)	0.83 (0.51 to 1.34)	12.29 (5.76 to 26.22)	1.28 (0.73 to 2.24)	12.70 (5.92 to 27.25)	1.00 (0.99999 to 99999)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-3(n=15,8,18,11,21,17,21,9,0,0)	1.87 (0.98 to 3.54)	1.04 (0.75 to 1.45)	2.33 (0.97 to 5.59)	1.17 (0.65 to 2.10)	5.38 (2.71 to 10.71)	1.15 (0.89 to 1.50)	8.55 (3.97 to 18.38)	1.85 (0.45 to 7.67)	9999 (9999 to 9999)	9999 (9999 to 9999)
Day 1080, TDV-4(n=15,8,18,11,21,17,21,9,0,0)	1.15 (0.71 to 1.87)	1.00 (0.58 to 1.71)	2.42 (1.18 to 4.98)	1.46 (0.66 to 3.21)	2.14 (1.23 to 3.72)	1.13 (0.94 to 1.36)	2.44 (1.40 to 4.25)	1.00 (0.77 to 1.31)	9999 (9999 to 9999)	9999 (9999 to 9999)

No statistical analyses for this end point

Secondary: Number of Participants With Confirmed Dengue Fever

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End point title

Number of Participants With Confirmed Dengue Fever

End point description

Dengue fever was assessed in participants who had 3 consecutive days of fever >38°C and tested positive for dengue virus by polymerase chain reaction (PCR) analysis. The safety set included all randomised participants who received at least one dose of study vaccine (or placebo).

End point type

Secondary

End point timeframe

Day 1 to Day 1080

End point values	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Number of subjects analysed	24	14	22	14	21	17	23	13	159	53
Units: participants	0	0	1	0	1	0	0	1	2	1

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Serious AEs were collected throughout the study Day 0 up to Day 1080. Other (non-serious) AEs were collected within 28 days of all vaccinations (up to Day 28 and Day 118).

Adverse event reporting additional description

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.

Assessment type

Systematic

Dictionary name

MedDRA

Dictionary version

14.0

Reporting group title

Part I: TDV 21 to 45 Years

Reporting group description

Reporting group title

Part I: Placebo 21 to 45 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 21 to 45 years.

Reporting group title

Part I: TDV 12 to 20 Years

Reporting group description

Reporting group title

Part I: Placebo 12 to 20 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 12 to 20 years.

Reporting group title

Part I: TDV 6 to 11 Years

Reporting group description

Reporting group title

Part I: Placebo 6 to 11 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 6 to 11 years.

Reporting group title

Part I: TDV 1.5 to 5 Years

Reporting group description

Reporting group title

Part I: Placebo 1.5 to 5 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, subcutaneously, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Reporting group title

Part II: TDV 1.5 to 11 Years

Reporting group description

Reporting group title

Part II: Placebo 1.5 to 11 Years

Reporting group description

TDV placebo-matching 0.5 mL injection, SC, once on Day 0 (first dose) and Day 90 (second dose) in participants aged 1.5 to 5 years.

Serious adverse events	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Total subjects affected by serious adverse events
subjects affected / exposed	4 / 24 (16.67%)	0 / 14 (0.00%)	1 / 22 (4.55%)	0 / 14 (0.00%)	4 / 21 (19.05%)	1 / 17 (5.88%)	1 / 23 (4.35%)	2 / 13 (15.38%)	14 / 159 (8.81%)	2 / 53 (3.77%)
number of deaths (all causes)	0	0	0	0	0	0	0	0	0	0
number of deaths resulting from adverse events	0	0	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Incision site haemorrhage
subjects affected / exposed	1 / 24 (4.17%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Incision site haematoma
subjects affected / exposed	1 / 24 (4.17%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Child maltreatment syndrome
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Forearm fracture
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Skull fractured base
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Brain contusion
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 24 (4.17%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hepatobiliary disorders
Cholecystitis
subjects affected / exposed	1 / 24 (4.17%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cholecystitis acute
subjects affected / exposed	1 / 24 (4.17%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Tonsillar hypertrophy
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Infections and infestations
Abscess limb
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Cellulitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Appendicitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	3 / 159 (1.89%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	2 / 159 (1.26%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 1	0 / 2	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastritis viral
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	5 / 159 (3.14%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 5	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Gastroenteritis rotavirus
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 23 (4.35%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Hand-foot-and-mouth disease
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	1 / 22 (4.55%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Influenza
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	2 / 159 (1.26%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Viral infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Urinary tract infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0
Metabolism and nutrition disorders
Dehydration
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	1 / 53 (1.89%)
occurrences causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0	0 / 0

Frequency threshold for reporting non-serious adverse events: 5%

Non-serious adverse events	Part I: TDV 21 to 45 Years	Part I: Placebo 21 to 45 Years	Part I: TDV 12 to 20 Years	Part I: Placebo 12 to 20 Years	Part I: TDV 6 to 11 Years	Part I: Placebo 6 to 11 Years	Part I: TDV 1.5 to 5 Years	Part I: Placebo 1.5 to 5 Years	Part II: TDV 1.5 to 11 Years	Part II: Placebo 1.5 to 11 Years
Total subjects affected by non serious adverse events
subjects affected / exposed	11 / 24 (45.83%)	7 / 14 (50.00%)	13 / 22 (59.09%)	8 / 14 (57.14%)	9 / 21 (42.86%)	11 / 17 (64.71%)	14 / 23 (60.87%)	12 / 13 (92.31%)	87 / 159 (54.72%)	30 / 53 (56.60%)
General disorders and administration site conditions
Injection site pain
subjects affected / exposed	2 / 24 (8.33%)	0 / 14 (0.00%)	2 / 22 (9.09%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	2 / 159 (1.26%)	0 / 53 (0.00%)
occurrences all number	2	0	3	0	0	0	0	0	2	0
Influenza like illness
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	1	0	0
Fatigue
subjects affected / exposed	0 / 24 (0.00%)	2 / 14 (14.29%)	2 / 22 (9.09%)	2 / 14 (14.29%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	6 / 159 (3.77%)	1 / 53 (1.89%)
occurrences all number	0	3	2	4	0	4	0	0	7	1
Injection site erythema
subjects affected / exposed	1 / 24 (4.17%)	0 / 14 (0.00%)	2 / 22 (9.09%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	0	3	0	0	0	0	0	0	0
Pyrexia
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	2 / 22 (9.09%)	1 / 14 (7.14%)	1 / 21 (4.76%)	0 / 17 (0.00%)	2 / 23 (8.70%)	1 / 13 (7.69%)	11 / 159 (6.92%)	6 / 53 (11.32%)
occurrences all number	0	2	3	1	1	0	2	1	12	6
Reproductive system and breast disorders
Endometriosis
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Dysmenorrhoea
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Respiratory, thoracic and mediastinal disorders
Nasal congestion
subjects affected / exposed	1 / 24 (4.17%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	2 / 17 (11.76%)	0 / 23 (0.00%)	0 / 13 (0.00%)	2 / 159 (1.26%)	0 / 53 (0.00%)
occurrences all number	1	1	0	0	0	2	0	0	2	0
Cough
subjects affected / exposed	1 / 24 (4.17%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	2 / 159 (1.26%)	3 / 53 (5.66%)
occurrences all number	1	1	0	0	0	0	0	0	2	3
Rhinitis allergic
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	1 / 22 (4.55%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	5 / 159 (3.14%)	1 / 53 (1.89%)
occurrences all number	0	0	1	0	0	0	0	1	5	2
Oropharyngeal pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	1 / 22 (4.55%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences all number	0	2	2	1	0	0	0	0	1	0
Asthma
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	1 / 23 (4.35%)	1 / 13 (7.69%)	4 / 159 (2.52%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	1	0	1	1	4	0
Rhinorrhoea
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	2 / 14 (14.29%)	0 / 21 (0.00%)	0 / 17 (0.00%)	2 / 23 (8.70%)	1 / 13 (7.69%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences all number	0	1	0	2	0	0	2	1	1	0
Psychiatric disorders
Depression
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
Anxiety
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	2	0	0	0	0	0	0	0	0
Investigations
Blood pressure increased
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Injury, poisoning and procedural complications
Procedural pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0
Laceration
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	1 / 53 (1.89%)
occurrences all number	0	1	0	0	0	0	0	0	0	1
Joint sprain
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Nervous system disorders
Headache
subjects affected / exposed	4 / 24 (16.67%)	3 / 14 (21.43%)	7 / 22 (31.82%)	1 / 14 (7.14%)	4 / 21 (19.05%)	3 / 17 (17.65%)	1 / 23 (4.35%)	0 / 13 (0.00%)	13 / 159 (8.18%)	3 / 53 (5.66%)
occurrences all number	6	4	9	2	4	6	1	0	16	3
Blood and lymphatic system disorders
Anaemia
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	1	0	0	0	0	0	0
Lymphadenitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Eye disorders
Conjunctival haemorrhage
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Photophobia
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	1 / 53 (1.89%)
occurrences all number	0	0	0	1	0	0	0	0	1	1
Eye pain
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 23 (4.35%)	0 / 13 (0.00%)	1 / 159 (0.63%)	1 / 53 (1.89%)
occurrences all number	0	1	0	1	0	0	1	0	1	1
Conjunctivitis allergic
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Conjunctivitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	1 / 159 (0.63%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	0	0	1	1	1
Gastrointestinal disorders
Diarrhoea
subjects affected / exposed	1 / 24 (4.17%)	0 / 14 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	1 / 21 (4.76%)	0 / 17 (0.00%)	3 / 23 (13.04%)	1 / 13 (7.69%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences all number	1	0	0	1	1	0	3	1	1	0
Vomiting
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	3 / 13 (23.08%)	4 / 159 (2.52%)	1 / 53 (1.89%)
occurrences all number	0	1	0	0	0	0	0	3	4	1
Food poisoning
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Mouth ulceration
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	0	0
Nausea
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	1 / 22 (4.55%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	1 / 53 (1.89%)
occurrences all number	0	0	1	1	0	0	0	0	1	1
Aphthous stomatitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	2 / 159 (1.26%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	2	0
Skin and subcutaneous tissue disorders
Rash
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	1 / 22 (4.55%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	1 / 23 (4.35%)	1 / 13 (7.69%)	2 / 159 (1.26%)	2 / 53 (3.77%)
occurrences all number	0	0	1	0	0	1	1	1	2	2
Urticaria papular
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Dermatitis contact
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	0 / 53 (0.00%)
occurrences all number	0	0	0	1	0	0	0	0	1	0
Skin ulcer
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Pruritus
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	1 / 21 (4.76%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	2 / 159 (1.26%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	1	1	0	0	2	0
Musculoskeletal and connective tissue disorders
Joint stiffness
subjects affected / exposed	1 / 24 (4.17%)	1 / 14 (7.14%)	1 / 22 (4.55%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	1	1	1	0	0	0	0	0	0	0
Back pain
subjects affected / exposed	2 / 24 (8.33%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0
Arthralgia
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	2 / 22 (9.09%)	1 / 14 (7.14%)	1 / 21 (4.76%)	0 / 17 (0.00%)	1 / 23 (4.35%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	2	2	1	0	1	0	0	0
Myalgia
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	2 / 22 (9.09%)	4 / 14 (28.57%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 23 (4.35%)	0 / 13 (0.00%)	2 / 159 (1.26%)	0 / 53 (0.00%)
occurrences all number	0	1	3	4	0	0	1	0	2	0
Infections and infestations
Laryngitis
subjects affected / exposed	2 / 24 (8.33%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	2	0	0	0	0	0	0	0	0	0
Hordeolum
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	0	0
Nasopharyngitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	3 / 22 (13.64%)	0 / 14 (0.00%)	1 / 21 (4.76%)	0 / 17 (0.00%)	2 / 23 (8.70%)	1 / 13 (7.69%)	16 / 159 (10.06%)	3 / 53 (5.66%)
occurrences all number	0	0	3	0	1	0	2	1	19	3
Bronchitis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	1 / 13 (7.69%)	8 / 159 (5.03%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	0	0	1	8	0
Viral infection
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	1 / 159 (0.63%)	1 / 53 (1.89%)
occurrences all number	0	0	0	0	0	1	0	0	1	2
Upper respiratory tract infection
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	1 / 14 (7.14%)	3 / 21 (14.29%)	2 / 17 (11.76%)	8 / 23 (34.78%)	7 / 13 (53.85%)	32 / 159 (20.13%)	14 / 53 (26.42%)
occurrences all number	0	1	0	1	3	3	11	10	34	18
Gastroenteritis
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	1 / 14 (7.14%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	6 / 159 (3.77%)	2 / 53 (3.77%)
occurrences all number	0	0	0	1	0	1	0	0	6	2
Pharyngitis
subjects affected / exposed	2 / 24 (8.33%)	1 / 14 (7.14%)	1 / 22 (4.55%)	1 / 14 (7.14%)	0 / 21 (0.00%)	0 / 17 (0.00%)	1 / 23 (4.35%)	0 / 13 (0.00%)	3 / 159 (1.89%)	2 / 53 (3.77%)
occurrences all number	2	1	1	1	0	0	1	0	3	2
Viral rash
subjects affected / exposed	0 / 24 (0.00%)	0 / 14 (0.00%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	1 / 17 (5.88%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	0	0	0	0	1	0	0	0	0
Metabolism and nutrition disorders
Dyslipidaemia
subjects affected / exposed	0 / 24 (0.00%)	1 / 14 (7.14%)	0 / 22 (0.00%)	0 / 14 (0.00%)	0 / 21 (0.00%)	0 / 17 (0.00%)	0 / 23 (0.00%)	0 / 13 (0.00%)	0 / 159 (0.00%)	0 / 53 (0.00%)
occurrences all number	0	1	0	0	0	0	0	0	0	0

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Were there any global substantial amendments to the protocol? Yes

14 Oct 2011

The following changes were implemented with Protocol Amendment 1: -Most references regarding the Day 14 safety review were changed to Day 28 throughout the protocol. Additional clarification was added with regard to the review of group data in Part 1 as the basis for when Part 2 would be initiated. In addition, vaccine viremia testing was to be performed up to Day 120 if subjects developed systemic AEs consistent with dengue fever including fever (>38.0°C for 3 consecutive days) and generalized rash. Other changes included: -Updated inclusion criteria number 4 that defined the upper limit of normal for BMI. -Updated exclusion criteria number 2 that provided the lower age limit for exclusion from having an ECG performed. -Updated exclusion criteria number 4 that clarified measurement of body temperature. -The differentiation between solicited and unsolicited treatment emergent adverse events (TEAE) was removed from the protocol. -The word ‘approximately’ was added to each enrollment number.

11 May 2012

The following changes were implemented with Protocol Amendment 2: -Added clarification on how the study was to transition from Part 1 to Part 2 in terms of age cohort succession in conjunction with safety data review by the DSMB and in conjunction with the Sponsor during Part 1 and subsequent initiation of Part 2. Other changes included: -Changes to the required storage conditions for TDV (below 60°C at all times). -Updated inclusion criteria 4, 6, and 12. -Changes regarding how clinical laboratory data were to be reviewed and updated regarding total blood volumes to be drawn from study subjects. -Because it was known that a number of subjects living in a region endemic for dengue virus would be seropositive prior to study participation, instead of measuring seroconversion to one or more of the 4 dengue strains, an overall measure of seropositivity was to be performed instead.

Were there any global interruptions to the trial? No

Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.

None reported

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Clinical trials

Clinical Trial Results: A Double-Blind, Randomized, Placebo-Controlled, Age Descending and Expansion Phase 2 Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity

Primary: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity

Primary: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (In Clinic Assessment) Following Either Vaccination Dose by Severity

Primary: Number of Participants With Solicited Local (Injection Site) Adverse Events (AEs) (In Clinic Assessment) Following Either Vaccination Dose by Severity

Primary: Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity

Primary: Number of Participants With Solicited Systemic Adverse Events (AEs) (Diary-Recorded) Following Either Vaccination Dose by Severity

Primary: Number of Participants With Any Solicited AE Following Either Vaccination Dose

Primary: Number of Participants With Any Solicited AE Following Either Vaccination Dose

Primary: Number of Participants With at Least One Unsolicited AE Following Either Vaccination Dose by Severity

Primary: Number of Participants With at Least One Unsolicited AE Following Either Vaccination Dose by Severity

Primary: Seropositivity Rate to Each of the Four Dengue Serotypes at Day 120

Primary: Seropositivity Rate to Each of the Four Dengue Serotypes at Day 120

Secondary: Part I: Number of Participants Positive for Vaccine Viremia for Each of Four Vaccine Strain Serotypes After the Each Vaccination

Secondary: Part I: Number of Participants Positive for Vaccine Viremia for Each of Four Vaccine Strain Serotypes After the Each Vaccination

Secondary: Seropositivity Rate to Each of the Four Dengue Serotypes

Secondary: Seropositivity Rate to Each of the Four Dengue Serotypes

Secondary: Seroconversion Rate to Each of the Four Dengue Serotypes

Secondary: Seroconversion Rate to Each of the Four Dengue Serotypes

Secondary: Geometric Mean Neutralising Antibody Titers (GMTs) of All Four Dengue Serotypes

Secondary: Geometric Mean Neutralising Antibody Titers (GMTs) of All Four Dengue Serotypes

Secondary: Geometric Mean Fold Rise (GMFR) of Dengue Neutralising Antibody Titers for Each of the 4 Dengue Serotypes

Secondary: Geometric Mean Fold Rise (GMFR) of Dengue Neutralising Antibody Titers for Each of the 4 Dengue Serotypes

Secondary: Number of Participants With Confirmed Dengue Fever

Secondary: Number of Participants With Confirmed Dengue Fever

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
A Double-Blind, Randomized, Placebo-Controlled, Age Descending and Expansion Phase 2 Study to Investigate the Safety and Immunogenicity of a Tetravalent Chimeric Dengue Vaccine in Healthy Volunteers Between the Ages of 1.5 - 45 Years