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Clinical Trial Results:
Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore

Summary
EudraCT number	2014-001713-26
Trial protocol	Outside EU/EEA
Global end of trial date	14 Oct 2014

Results information
Results version number	v1(current)
This version publication date	08 Feb 2016
First version publication date	17 Jul 2015
Other versions

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

CYD28

ISRCTN number

US NCT number

NCT00880893

WHO universal trial number (UTN)

Sponsor organisation name

Sanofi Pasteur SA

Sponsor organisation address

2, avenue Pont Pasteur, Lyon Cedex 07, France, 69367

Public contact

Director, Clinical Development, Sanofi Pasteur SA, 65 6431 2358, Anh.Wartel-Tram@sanofipasteur.com

Scientific contact

Director, Clinical Development, Sanofi Pasteur SA, 65 6431 2358, Anh.Wartel-Tram@sanofipasteur.com

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

Yes

EMA paediatric investigation plan number(s)

EMEA-001201-PIP01-11

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

30 Mar 2015

Is this the analysis of the primary completion data?

Global end of trial reached?

Yes

Global end of trial date

14 Oct 2014

Was the trial ended prematurely?

Main objective of the trial

Safety and reactogenicity Humoral immune response to dengue before and after each vaccination with CYD dengue vaccine

Protection of trial subjects

Only subjects that met all the study inclusion and none of the exclusion criteria were randomized and vaccinated in the study. Vaccinations were performed by qualified and trained study personnel. Subjects with allergy to any of the vaccine components were not vaccinated. After vaccination, subjects were also kept under clinical observation for 30 minutes to ensure their safety. Appropriate medical equipment was also available on site in case of any immediate allergic reactions.

Background therapy

Not applicable

Evidence for comparator

Not applicable

Actual start date of recruitment

07 Apr 2009

Long term follow-up planned

Independent data monitoring committee (IDMC) involvement?

Yes

Number of subjects enrolled per country

Country: Number of subjects enrolled

Singapore: 1198

Worldwide total number of subjects

1198

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)

316

Adolescents (12-17 years)

187

Adults (18-64 years)

695

From 65 to 84 years

85 years and over

Subject disposition

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Recruitment details

Study subjects were enrolled from 07 April 2009 to 08 October 2009 at 5 clinical sites in Singapore.

Screening details

A total of 1198 subjects who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized.

Period 1 title

Overall trial (overall period)

Is this the baseline period?

Yes

Allocation method

Randomised - controlled

Blinding used

Double blind

Roles blinded

Subject, Investigator, Monitor, Assessor

Blinding implementation details

An observer-design for the first vaccination and a single-blind design for the second and third vaccination were chosen to minimize the bias of the vaccine evaluation. The Investigator in charge of safety evaluation, the Sponsor, and the subjects/parents did not know which vaccine was administrated at the first visit. For the second and third vaccinations, the subjects/parents did not know which vaccine was administered.

Are arms mutually exclusive

Yes

CYD Dengue vaccine group

Arm description

Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

Arm type

Experimental

Investigational medicinal product name

CYD Dengue vaccine

Investigational medicinal product code

323

Other name

Pharmaceutical forms

Powder and solvent for suspension for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, 1 injection each at 0, 6, and 12 months.

Control group

Arm description

All subjects received a placebo at first vaccination (Month 0). Subjects <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Subjects ≥12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

Arm type

Placebo

Investigational medicinal product name

Placebo (NaCl)

Investigational medicinal product code

Other name

Pharmaceutical forms

Solution for injection

Routes of administration

Subcutaneous use

Dosage and administration details

0.5 mL, subcutaneous, 1 injection at Month 0.

Investigational medicinal product name

Hepatitis A vaccine (Havrix® pediatric formulation)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, subjects <12 years received hepatitis vaccine at second (Month 6) and third (Month 12) vaccinations.

Investigational medicinal product name

Influenza vaccine (split virion, inactivated) Northern and Southern hemispheres year 2009-2010 formulations (Vaxigrip®)

Investigational medicinal product code

Other name

Pharmaceutical forms

Suspension for injection in pre-filled syringe

Routes of administration

Intramuscular use

Dosage and administration details

0.5 mL, intramuscular, subjects ≥12 years received 1 injection of the influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

Number of subjects in period 1	CYD Dengue vaccine group	Control group
Started	898	300
Completed	791	255
Not completed	107	45
Consent withdrawn by subject	15	11
Serious adverse event	3	-
Lost to follow-up	76	33
Protocol deviation	13	1

Baseline characteristics

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Reporting group title

CYD Dengue vaccine group

Reporting group description

Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

Reporting group title

Control group

Reporting group description

Reporting group values	CYD Dengue vaccine group	Control group	Total
Number of subjects	898	300	1198
Age categorical
Units: Subjects
In utero	0	0	0
Preterm newborn infants (gestational age < 37 wks)	0	0	0
Newborns (0-27 days)	0	0	0
Infants and toddlers (28 days-23 months)	0	0	0
Children (2-11 years)	236	80	316
Adolescents (12-17 years)	141	46	187
Adults (18-64 years)	521	174	695
From 65-84 years	0	0	0
85 years and over	0	0	0
Age continuous
Units: years
arithmetic mean (standard deviation)	22.1 ( 11.97 )	21.7 ( 11.76 )	-
Gender categorical
Units: Subjects
Female	471	139	610
Male	427	161	588

End points

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Reporting group title

CYD Dengue vaccine group

Reporting group description

Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

Reporting group title

Control group

Reporting group description

Primary: Percentage of All Subjects Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

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End point title

Percentage of All Subjects Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine ^[1]

End point description

Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions (2-11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥5 cm. Grade 3 Solicited injection site reactions (adolescents and adults): Pain, Significant; prevents daily activity; Erythema and Swelling, >10 cm. Grade 3 Solicited systemic reactions: Fever, ≥39.0°C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity.

End point type

Primary

End point timeframe

Day 0 up to Day 14 post-any and each injection

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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	898	300
Units: Percentage of subjects
number (not applicable)
Injection site Pain; Post-Any Injection	53.9	66.7
Grade 3 Injection site Pain; Post-Any Injection	1	2
Injection site Erythema; Post-Any Injection	7.2	15.2
Grade 3 Inj. site Erythema; Post-Any Inj.	0	0
Injection site Swelling; Post-Any Injection	4.1	8.4
Grade 3 Inj. site Swelling; Post-Any Inj.	0	0
Injection site Pain; Post-Injection 1	31.3	21.9
Grade 3 Injection site Pain; Post-Injection 1	0.3	0.7
Injection site Erythema; Post-Injection 1	2	2
Grade 3 Injection site Erythema; Post-Injection 1	0	0
Injection site Swelling; Post-Injection 1	1.1	1.7
Grade 3 Injection site Swelling; Post-Injection 1	0	0
Injection site Pain; Post-Injection 2	36.9	54.4
Grade 3 Injection site Pain; Post-Injection 2	0.5	0.7
Injection site Erythema; Post-Injection 2	3.4	8.8
Grade 3 Injection site Erythema; Post-Injection 2	0	0
Injection site Swelling; Post-Injection 2	1.4	3.5
Grade 3 Injection site Swelling; Post-Injection 2	0	0
Injection site Pain; Post-Injection 3	34.9	50
Grade 3 Injection site Pain; Post-Injection 3	0.2	0.7
Injection site Erythema; Post-Injection 3	3.8	9.4
Grade 3 Injection site Erythema; Post-Injection 3	0	0
Injection site Swelling; Post-Injection 3	2.6	5.8
Grade 3 Injection site Swelling; Post-Injection 3	0	0
Fever; Post-Any Injection	11.3	7.4
Grade 3 Fever; Post-Any Injection	1.9	1
Headache; Post-Any Injection	45.1	38.4
Grade 3 Headache; Post-Any Injection	3.8	2.7
Malaise; Post-Any Injection	41.8	35.4
Grade 3 Malaise; Post-Any Injection	4.3	2.7
Myalgia; Post-Any Injection	44.2	43.8
Grade 3 Myalgia; Post-Any Injection	2.6	2
Asthenia; Post-Any Injection	20.5	17.5
Grade 3 Asthenia; Post-Any Injection	1.3	0.7
Fever; Post-Injection 1	4.6	2.7
Grade 3 Fever; Post-Injection 1	0.6	0.7
Headache; Post-Injection 1	30	27.3
Grade 3 Headache; Post-Injection 1	2.4	1.3
Malaise; Post-Injection 1	25	18.2
Grade 3 Malaise; Post-Injection 1	2	0.7
Myalgia; Post-Injection 1	29.4	19.2
Grade 3 Myalgia; Post-Injection 1	1.3	1
Asthenia; Post-Injection 1	12.8	6.1
Grade 3 Asthenia; Post-Injection 1	0.7	0.3
Fever; Post-Injection 2	3.3	2.8
Grade 3 Fever; Post-Injection 2	0.6	0
Headache; Post-Injection 2	22.8	21.8
Grade 3 Headache; Post-Injection 2	0.7	1.1
Malaise; Post-Injection 2	19.1	18.2
Grade 3 Malaise; Post-Injection 2	1.2	1.1
Myalgia; Post-Injection 2	24	29.5
Grade 3 Myalgia; Post-Injection 2	0.9	0.7
Asthenia; Post-Injection 2	9.3	10.2
Grade 3 Asthenia; Post-Injection 2	0.3	0
Fever; Post-Injection 3	4.8	2.9
Grade 3 Fever; Post-Injection 3	0.8	0.4
Headache; Post-Injection 3	20.1	19.8
Grade 3 Headache; Post-Injection 3	1	0.4
Malaise; Post-Injection 3	18.2	17.3
Grade 3 Malaise; Post-Injection 3	1.4	1.1
Myalgia; Post-Injection 3	21.8	26.3
Grade 3 Myalgia; Post-Injection 3	0.5	0.7
Asthenia; Post-Injection 3	8.5	9.4
Grade 3 Asthenia; Post-Injection 3	0.4	0.4

No statistical analyses for this end point

Primary: Percentage of Subjects By Age Group Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

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End point title

Percentage of Subjects By Age Group Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine ^[2]

End point description

Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia.

End point type

Primary

End point timeframe

Day 0 up to Day 14 post-each injection

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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	898	300
Units: Percentage of subjects
number (not applicable)
2-11 years; Injection site Pain, Post-Injection 1	33.9	30
2-11 years; Inj. site Erythema, Post-Inj. 1	6.4	7.5
2-11 years; Inj. site Swelling, Post-Inj. 1	3.8	6.3
12-17 years; Injection site Pain, Post-Injection 1	28.4	28.3
12-17 years; Inj. site Erythema, Post-Inj. 1	0	0
12-17 years; Inj. site Swelling, Post-Inj. 1	0	0
18-45 years; Injection site Pain, Post-Injection 1	30.9	16.4
18-45 years; Inj. site Erythema, Post-Inj. 1	0.6	0
18-45 years; Inj. site Swelling, Post-Inj. 1	0.2	0
2-11 years; Injection site Pain, Post-Injection 2	38.3	42.1
2-11 years; Inj. site Erythema, Post-Inj. 2	9.4	5.3
2-11 years; Inj. site Swelling, Post-Inj. 2	4.7	3.9
12-17 years; Injection site Pain, Post-Injection 2	29.4	44.4
12-17 years; Inj. site Erythema, Post-Inj. 2	0	0
12-17 years; Inj. site Swelling, Post-Inj. 2	0	0
18-45 years; Injection site Pain, Post-Injection 2	38.3	62.8
18-45 years; Inj. site Erythema, Post-Inj. 2	1.4	12.8
18-45 years; Inj. site Swelling, Post-Inj. 2	0.2	4.3
2-11 years; Injection site Pain, Post-Injection 3	32.6	34.2
2-11 years; Inj. site Erythema, Post-Inj. 3	8.2	6.6
2-11 years; Inj. site Swelling, Post-Inj. 3	6.4	2.6
12-17 years; Injection site Pain, Post-Injection 3	26.7	38.6
12-17 years; Inj. site Erythema, Post-Inj. 3	0	0
12-17 years; Inj. site Swelling, Post-Inj. 3	0	0
18-45 years; Injection site Pain, Post-Injection 3	38.5	60.8
18-45 years; Inj. site Erythema, Post-Inj. 3	2.8	13.3
18-45 years; Inj. site Swelling, Post-Inj. 3	1.5	8.9
2-11 years; Fever, Post-Injection 1	8.1	6.3
2-11 years; Headache, Post-Injection 1	25	16.3
2-11 years; Malaise, Post-Injection 1	19.9	13.8
2-11 years; Myalgia, Post-Injection 1	23.7	16.3
2-11 years; Asthenia, Post-Injection 1	7.2	3.8
12-17 years; Fever, Post-Injection 1	7.1	2.2
12-17 years; Headache, Post-Injection 1	39.3	39.1
12-17 years; Malaise, Post-Injection 1	29.3	17.4
12-17 years; Myalgia, Post-Injection 1	32.1	23.9
12-17 years; Asthenia, Post-Injection 1	13.6	6.5
18-45 years; Fever, Post-Injection 1	2.3	1.2
18-45 years; Headache, Post-Injection 1	29.7	29.2
18-45 years; Malaise, Post-Injection 1	26.2	20.5
18-45 years; Myalgia, Post-Injection 1	31.3	19.3
18-45 years; Asthenia, Post-Injection 1	15.1	7
2-11 years; Fever, Post-Injection 2	6.8	6.6
2-11 years; Headache, Post-Injection 2	21.7	15.8
2-11 years; Malaise, Post-Injection 2	21.7	13.2
2-11 years; Myalgia, Post-Injection 2	24.7	22.4
2-11 years; Asthenia, Post-Injection 2	7.7	7.9
12-17 years; Fever, Post-Injection 2	4.4	0
12-17 years; Headache, Post-Injection 2	19.9	22.2
12-17 years; Malaise, Post-Injection 2	16.2	20
12-17 years; Myalgia, Post-Injection 2	19.9	28.9
12-17 years; Asthenia, Post-Injection 2	8.8	6.7
18-45 years; Fever, Post-Injection 2	1.2	1.8
18-45 years; Headache, Post-Injection 2	24.2	24.4
18-45 years; Malaise, Post-Injection 2	18.6	20.1
18-45 years; Myalgia, Post-Injection 2	24.8	32.9
18-45 years; Asthenia, Post-Injection 2	10.2	12.2
2-11 years; Fever, Post-Injection 3	8.2	6.6
2-11 years; Headache, Post-Injection 3	17.6	11.8
2-11 years; Malaise, Post-Injection 3	18.5	14.5
2-11 years; Myalgia, Post-Injection 3	20.6	17.1
2-11 years; Asthenia, Post-Injection 3	7.7	3.9
12-17 years; Fever, Post-Injection 3	5.9	2.3
12-17 years; Headache, Post-Injection 3	20.7	20.5
12-17 years; Malaise, Post-Injection 3	18.5	18.2
12-17 years; Myalgia, Post-Injection 3	14.8	25
12-17 years; Asthenia, Post-Injection 3	5.9	11.4
18-45 years; Fever, Post-Injection 3	2.8	1.3
18-45 years; Headache, Post-Injection 3	21.2	23.4
18-45 years; Malaise, Post-Injection 3	17.9	18.4
18-45 years; Myalgia, Post-Injection 3	24.4	31
18-45 years; Asthenia, Post-Injection 3	9.6	11.4

No statistical analyses for this end point

Primary: Percentage of All Subjects Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine

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End point title

Percentage of All Subjects Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine ^[3]

End point description

Seropositivity against each dengue virus serotype was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).

End point type

Primary

End point timeframe

Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3

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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	424	140
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Pre-Injection 1	14.6	17.1
CYD dengue Serotype 1; Post-Injection 1	22.9	11.6
CYD dengue Serotype 1; Pre-Injection 2	30.1	16.7
CYD dengue Serotype 1; Post-Injection 2	54.9	18.3
CYD dengue Serotype 1; Pre-Injection 3	45.8	13.8
CYD dengue Serotype 1; Post-Injection 3	79.6	22
CYD dengue Serotype 2; Pre-Injection 1	16.1	15
CYD dengue Serotype 2; Post-Injection 1	39.5	10.1
CYD dengue Serotype 2; Pre-Injection 2	39.3	16.7
CYD dengue Serotype 2; Post-Injection 2	80.4	15
CYD dengue Serotype 2; Pre-Injection 3	58.3	13.8
CYD dengue Serotype 2; Post-Injection 3	88.1	20.2
CYD dengue Serotype 3; Pre-Injection 1	19.7	20.1
CYD dengue Serotype 3; Post-Injection 1	58.7	21.7
CYD dengue Serotype 3; Pre-Injection 2	63.9	31
CYD dengue Serotype 3; Post-Injection 2	87.4	26.7
CYD dengue Serotype 3; Pre-Injection 3	77.8	19
CYD dengue Serotype 3; Post-Injection 3	93.2	24.8
CYD dengue Serotype 4; Pre-Injection 1	12.8	12.9
CYD dengue Serotype 4; Post-Injection 1	67.3	11.6
CYD dengue Serotype 4; Pre-Injection 2	69.1	16.7
CYD dengue Serotype 4; Post-Injection 2	85.8	16.9
CYD dengue Serotype 4; Pre-Injection 3	79.3	8.6
CYD dengue Serotype 4; Post-Injection 3	93.7	19.3

No statistical analyses for this end point

Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects By Age Group Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine ^[4]

End point description

Seropositivity against each dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).

End point type

Primary

End point timeframe

Pre-Injection 1 and Post-Injection 3

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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	148	47
Units: Percentage of subjects
number (not applicable)
2-11 years, CYD dengue Serotype 1; Pre-Injection 1	4.7	8.5
2-11 years, CYD dengue Serotype 1; Post-Inj. 3	92.4	10.8
2-11 years, CYD dengue Serotype 2; Pre-Injection 1	5.4	2.1
2-11 years, CYD dengue Serotype 2; Post-Inj. 3	93.9	16.2
2-11 years, CYD dengue Serotype 3; Pre-Injection 1	11.6	10.6
2-11 years, CYD dengue Serotype 3; Post-Inj. 3	98.5	13.5
2-11 years, CYD dengue Serotype 4; Pre-Injection 1	6.8	6.4
2-11 years, CYD dengue Serotype 4; Post-Inj. 3	96.9	18.9
12-17 years, CYD dengue Serotype 1; Pre-Inj. 1	5.7	4.3
12-17 years, CYD dengue Serotype 1; Post-Inj. 3	68.3	13.2
12-17 years, CYD dengue Serotype 2; Pre-Inj. 1	10	4.3
12-17 years, CYD dengue Serotype 2; Post-Inj. 3	87	10.5
12-17 years, CYD dengue Serotype 3; Pre-Inj. 1	11.5	10.9
12-17 years, CYD dengue Serotype 3; Post-Inj. 3	88.5	21.1
12-17 years, CYD dengue Serotype 4; Pre-Inj. 1	6.5	2.2
12-17 years, CYD dengue Serotype 4; Post-Inj. 3	91.1	10.5
18-45 years, CYD dengue Serotype 1; Pre-Inj. 1	34.6	38.3
18-45 years, CYD dengue Serotype 1; Post-Inj. 3	76.5	44.1
18-45 years, CYD dengue Serotype 2; Pre-Inj. 1	34.1	38.3
18-45 years, CYD dengue Serotype 2; Post-Inj. 3	81.6	35.3
18-45 years, CYD dengue Serotype 3; Pre-Inj. 1	37	39.1
18-45 years, CYD dengue Serotype 3; Post-Inj. 3	91.8	41.2
18-45 years, CYD dengue Serotype 4; Pre-Inj. 1	26.1	30.4
18-45 years, CYD dengue Serotype 4; Post-Inj. 3	92.8	29.4

No statistical analyses for this end point

Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects By Age Group Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine ^[5]

End point description

Seropositivity against at least 1, 2, 3, or 4 dengue virus serotypes was assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil).

End point type

Primary

End point timeframe

Pre-Injection 1 and Post-Injection 3

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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	148	47
Units: Percentage of subjects
number (not applicable)
2-11 yrs, CYD dengue ≥1 serotype; Pre-Inj. 1	19.6	27.7
2-11 yrs, CYD dengue ≥1 serotype; Post-Inj. 3	100	56.8
2-11 yrs, CYD dengue ≥2 serotypes; Pre-Inj. 1	6.1	0
2-11 yrs, CYD dengue ≥2 serotypes; Post-Inj. 3	99.2	2.7
2-11 yrs, CYD dengue ≥3 serotypes; Pre-Inj. 1	2	0
2-11 yrs, CYD dengue ≥3 serotypes; Post-Inj. 3	97	0
2-11 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1	0.7	0
2-11 yrs, CYD dengue All 4 serotypes; Post-Inj. 3	84.8	0
12-17 yrs, CYD dengue ≥1 serotype; Pre-Inj. 1	13.6	15.2
12-17 yrs, CYD dengue ≥1 serotype; Post-Inj. 3	98.4	26.3
12-17 yrs, CYD dengue ≥2 serotypes; Pre-Inj. 1	7.9	4.3
12-17 yrs, CYD dengue ≥2 serotypes; Post-Inj. 3	95.1	10.5
12-17 yrs, CYD dengue ≥3 serotypes; Pre-Inj. 1	7.1	2.2
12-17 yrs, CYD dengue ≥3 serotypes; Post-Inj. 3	81.3	10.5
12-17 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1	5	0
12-17 yrs, CYD dengue All 4 serotypes; Post-Inj. 3	59.3	7.9
18-45 yrs, CYD dengue ≥1 serotype; Pre-Inj. 1	47.1	53.2
18-45 yrs, CYD dengue ≥1 serotype; Post-Inj. 3	100	55.9
18-45 yrs, CYD dengue ≥2 serotypes; Pre-Inj. 1	33.8	38.3
18-45 yrs, CYD dengue ≥2 serotypes; Post-Inj. 3	96.9	35.3
18-45 yrs, CYD dengue ≥3 serotypes; Pre-Inj. 1	27.9	31.9
18-45 yrs, CYD dengue ≥3 serotypes; Post-Inj. 3	83.7	32.4
18-45 yrs, CYD dengue All 4 serotypes; Pre-Inj. 1	22.1	21.3
18-45 yrs, CYD dengue All 4 serotypes; Post-Inj. 3	61.2	26.5

No statistical analyses for this end point

Primary: Geometric Mean Titers (GMTs) of Antibodies In All Subjects Against Each Serotype with the Parental Dengue Virus Strain Before and Following Each Injection with CYD Dengue Vaccine

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End point title

Geometric Mean Titers (GMTs) of Antibodies In All Subjects Against Each Serotype with the Parental Dengue Virus Strain Before and Following Each Injection with CYD Dengue Vaccine ^[6]

End point description

Geometric mean titers against each serotype with the parental dengue virus strains were assessed using a dengue plaque reduction neutralization test (PRNT) assay.

End point type

Primary

End point timeframe

Pre-Injections 1, 2, and 3 and Post-Injections 1, 2, and 3

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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	424	140
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
CYD dengue Serotype 1; Pre-Injection 1	8.2 (7.2 to 9.33)	8.23 (6.62 to 10.2)
CYD dengue Serotype 1; Post-Injection 1	10 (8.06 to 12.4)	7.09 (5.48 to 9.18)
CYD dengue Serotype 1; Pre-Injection 2	12.9 (9.89 to 16.7)	7.85 (5.79 to 10.6)
CYD dengue Serotype 1; Post-Injection 2	22.4 (17.1 to 29.3)	7.91 (5.85 to 10.7)
CYD dengue Serotype 1; Pre-Injection 3	18 (14 to 23.2)	7.4 (5.54 to 9.88)
CYD dengue Serotype 1; Post-Injection 3	46.6 (39 to 55.6)	8.93 (7.08 to 11.3)
CYD dengue Serotype 2; Pre-Injection 1	9.06 (7.86 to 10.4)	8.48 (6.69 to 10.8)
CYD dengue Serotype 2; Post-Injection 1	17.2 (13.3 to 22.2)	7.39 (5.49 to 9.94)
CYD dengue Serotype 2; Pre-Injection 2	19.1 (14.3 to 25.5)	9.79 (6.45 to 14.9)
CYD dengue Serotype 2; Post-Injection 2	50.3 (39 to 65)	9.48 (6.22 to 14.4)
CYD dengue Serotype 2; Pre-Injection 3	24.4 (19.2 to 31.1)	6.98 (5.38 to 9.07)
CYD dengue Serotype 2; Post-Injection 3	72.7 (61.6 to 85.8)	8.88 (6.9 to 11.4)
CYD dengue Serotype 3; Pre-Injection 1	8.45 (7.54 to 9.47)	8.93 (7.11 to 11.2)
CYD dengue Serotype 3; Post-Injection 1	28.2 (22 to 36.3)	9.56 (6.72 to 13.6)
CYD dengue Serotype 3; Pre-Injection 2	29.7 (23.2 to 38)	11.1 (7.6 to 16.3)
CYD dengue Serotype 3; Post-Injection 2	70.8 (56.8 to 88.2)	10.5 (7.36 to 14.9)
CYD dengue Serotype 3; Pre-Injection 3	39.1 (31.2 to 48.9)	8.23 (5.88 to 11.5)
CYD dengue Serotype 3; Post-Injection 3	100 (86.9 to 116)	9.52 (7.41 to 12.2)
CYD dengue Serotype 4; Pre-Injection 1	6.93 (6.31 to 7.6)	6.84 (5.86 to 7.99)
CYD dengue Serotype 4; Post-Injection 1	65.9 (49.1 to 88.3)	6.31 (5.3 to 7.5)
CYD dengue Serotype 4; Pre-Injection 2	47.5 (36.5 to 61.8)	7.91 (5.91 to 10.6)
CYD dengue Serotype 4; Post-Injection 2	90.2 (71.7 to 114)	8 (5.89 to 10.9)
CYD dengue Serotype 4; Pre-Injection 3	47.1 (37.9 to 58.5)	6.04 (5.09 to 7.17)
CYD dengue Serotype 4; Post-Injection 3	99.4 (87.4 to 113)	7.66 (6.35 to 9.24)

No statistical analyses for this end point

Primary: Geometric Mean Titers (GMTs) of Antibodies By Age Groups Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

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End point title

Geometric Mean Titers (GMTs) of Antibodies By Age Groups Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine ^[7]

End point description

Geometric mean titers against each dengue virus serotype were assessed using a dengue plaque reduction neutralization test (PRNT) assay.

End point type

Primary

End point timeframe

Pre-Injection 1 and Post-Injection 3

Notes
[7] - 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: Descriptive analyses were performed based on the study groups and the study vaccine administered for this outcome.

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	148	47
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
2-11 years, CYD dengue Serotype 1; Pre-Injection 1	5.33 (5.08 to 5.6)	5.44 (5.01 to 5.92)
2-11 years, CYD dengue Serotype 1; Post-Inj. 3	60.7 (49.5 to 74.3)	6.32 (4.92 to 8.13)
2-11 years, CYD dengue Serotype 2; Pre-Injection 1	5.85 (5.18 to 6.6)	5.18 (4.82 to 5.57)
2-11 years, CYD dengue Serotype 2; Post-Inj. 3	95.9 (76.7 to 120)	6.09 (5.18 to 7.16)
2-11 years, CYD dengue Serotype 3; Pre-Injection 1	6.24 (5.57 to 6.99)	6.02 (5.04 to 7.17)
2-11 years, CYD dengue Serotype 3; Post-Inj. 3	138 (115 to 165)	6.67 (5.11 to 8.71)
2-11 years, CYD dengue Serotype 4; Pre-Injection 1	5.64 (5.2 to 6.11)	5.42 (4.92 to 5.97)
2-11 years, CYD dengue Serotype 4; Post-Inj. 3	101 (84.6 to 122)	6.92 (5.47 to 8.76)
12-17 years, CYD dengue Serotype 1; Pre-Inj. 1	6.49 (5.31 to 7.92)	5.47 (4.8 to 6.24)
12-17 years, CYD dengue Serotype 1; Post-Inj. 3	28.9 (21.5 to 38.7)	6.56 (5.14 to 8.37)
12-17 years, CYD dengue Serotype 2; Pre-Inj. 1	7.47 (5.96 to 9.37)	5.54 (4.69 to 6.56)
12-17 years, CYD dengue Serotype 2; Post-Inj. 3	54 (41.1 to 70.9)	6.35 (5.03 to 8)
12-17 years, CYD dengue Serotype 3; Pre-Inj. 1	6.86 (5.82 to 8.09)	6.83 (4.84 to 9.65)
12-17 years, CYD dengue Serotype 3; Post-Inj. 3	74.1 (57.5 to 95.5)	8.32 (5.57 to 12.4)
12-17 years, CYD dengue Serotype 4; Pre-Inj. 1	5.83 (5.18 to 6.57)	5.08 (4.92 to 5.23)
12-17 years, CYD dengue Serotype 4; Post-Inj. 3	80.4 (64.2 to 101)	6.68 (4.87 to 9.15)
18-45 years, CYD dengue Serotype 1; Pre-Inj. 1	16.7 (12.2 to 22.8)	18.5 (10.4 to 32.9)
18-45 years, CYD dengue Serotype 1; Post-Inj. 3	59.5 (38.7 to 91.6)	18.3 (10.2 to 33)
18-45 years, CYD dengue Serotype 2; Pre-Inj. 1	17.8 (12.8 to 24.7)	21.1 (11.3 to 39.2)
18-45 years, CYD dengue Serotype 2; Post-Inj. 3	72.7 (49.4 to 107)	19.5 (9.69 to 39.1)
18-45 years, CYD dengue Serotype 3; Pre-Inj. 1	14.6 (11.2 to 19)	17.5 (10.2 to 30)
18-45 years, CYD dengue Serotype 3; Post-Inj. 3	94.9 (69.4 to 130)	16.3 (9.06 to 29.4)
18-45 years, CYD dengue Serotype 4; Pre-Inj. 1	10.4 (8.22 to 13.2)	11.7 (7.65 to 17.9)
18-45 years, CYD dengue Serotype 4; Post-Inj. 3	127 (96 to 167)	9.96 (6.47 to 15.3)

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Pre-Injection 1	4.7	8
CYD dengue Serotype 1; Post-Injection 3	91	8.9
CYD dengue Serotype 1; 1st year follow up	41.8	6.8
CYD dengue Serotype 1; 2nd year follow up	27.1	0
CYD dengue Serotype 1; 3rd year follow up	16.5	0
CYD dengue Serotype 1; 4th year follow up	9.6	0
CYD dengue Serotype 2; Pre-Injection 1	5.4	2
CYD dengue Serotype 2; Post-Injection 3	94.4	13.3
CYD dengue Serotype 2; 1st year follow up	59.6	8.9
CYD dengue Serotype 2; 2nd year follow up	52.1	11.6
CYD dengue Serotype 2; 3rd year follow up	34.3	7
CYD dengue Serotype 2; 4th year follow up	36.9	2.4
CYD dengue Serotype 3; Pre-Injection 1	11.6	10
CYD dengue Serotype 3; Post-Injection 3	97.9	13.6
CYD dengue Serotype 3; 1st year follow up	66	9.1
CYD dengue Serotype 3; 2nd year follow up	74.4	29.3
CYD dengue Serotype 3; 3rd year follow up	50	4.7
CYD dengue Serotype 3; 4th year follow up	37.7	2.4
CYD dengue Serotype 4; Pre-Injection 1	6.8	6
CYD dengue Serotype 4; Post-Injection 3	97.2	20.5
CYD dengue Serotype 4; 1st year follow up	75.2	4.7
CYD dengue Serotype 4; 2nd year follow up	72.9	4.7
CYD dengue Serotype 4; 3rd year follow up	60.6	7
CYD dengue Serotype 4; 4th year follow up	49.3	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Pre-Injection 1	5.7	4.3
CYD dengue Serotype 1; Post-Injection 3	67.4	11.6
CYD dengue Serotype 1; 1st year follow up	25.8	7.3
CYD dengue Serotype 1; 2nd year follow up	19.5	7.5
CYD dengue Serotype 1; 3rd year follow up	16.1	5
CYD dengue Serotype 1; 4th year follow up	11.9	5.4
CYD dengue Serotype 2; Pre-Injection 1	9.9	4.3
CYD dengue Serotype 2; Post-Injection 3	83.7	9.3
CYD dengue Serotype 2; 1st year follow up	44.3	4.9
CYD dengue Serotype 2; 2nd year follow up	52.3	10
CYD dengue Serotype 2; 3rd year follow up	35.5	5
CYD dengue Serotype 2; 4th year follow up	36.2	5.4
CYD dengue Serotype 3; Pre-Injection 1	11.4	10.9
CYD dengue Serotype 3; Post-Injection 3	88.8	20.9
CYD dengue Serotype 3; 1st year follow up	61.7	5
CYD dengue Serotype 3; 2nd year follow up	56.3	12.5
CYD dengue Serotype 3; 3rd year follow up	48.8	5
CYD dengue Serotype 3; 4th year follow up	47.5	5.4
CYD dengue Serotype 4; Pre-Injection 1	6.4	2.2
CYD dengue Serotype 4; Post-Injection 3	91.1	9.3
CYD dengue Serotype 4; 1st year follow up	73.5	2.4
CYD dengue Serotype 4; 2nd year follow up	71.1	10
CYD dengue Serotype 4; 3rd year follow up	66.7	5
CYD dengue Serotype 4; 4th year follow up	61	8.1

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Top of page

End point title

Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Pre-Injection 1	33.1	38.8
CYD dengue Serotype 1; Post-Injection 3	71.7	39.5
CYD dengue Serotype 1; 1st year follow up	45.9	31.8
CYD dengue Serotype 1; 2nd year follow up	43.6	34.1
CYD dengue Serotype 1; 3rd year follow up	40.4	30.8
CYD dengue Serotype 1; 4th year follow up	39.6	31.6
CYD dengue Serotype 2; Pre-Injection 1	32.6	38.8
CYD dengue Serotype 2; Post-Injection 3	80.3	30.2
CYD dengue Serotype 2; 1st year follow up	66.4	40.9
CYD dengue Serotype 2; 2nd year follow up	68.4	34.1
CYD dengue Serotype 2; 3rd year follow up	55.3	35.9
CYD dengue Serotype 2; 4th year follow up	55.2	31.6
CYD dengue Serotype 3; Pre-Injection 1	36.9	41.7
CYD dengue Serotype 3; Post-Injection 3	92.9	34.9
CYD dengue Serotype 3; 1st year follow up	68.6	38.6
CYD dengue Serotype 3; 2nd year follow up	77.8	46.3
CYD dengue Serotype 3; 3rd year follow up	67.9	35.9
CYD dengue Serotype 3; 4th year follow up	56.6	29.7
CYD dengue Serotype 4; Pre-Injection 1	25	31.3
CYD dengue Serotype 4; Post-Injection 3	93.7	32.6
CYD dengue Serotype 4; 1st year follow up	86.9	29.5
CYD dengue Serotype 4; 2nd year follow up	81.2	24.4
CYD dengue Serotype 4; 3rd year follow up	79.8	20.5
CYD dengue Serotype 4; 4th year follow up	77.6	21.1

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Top of page

End point title

Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Percentage of subjects
number (not applicable)
CYD dengue ≥1 serotype; Pre-Injection 1	19.6	26
CYD dengue ≥1 serotype; Post-Injection 3	100	51.1
CYD dengue ≥1 serotype; 1st year follow up	92.3	20
CYD dengue ≥1 serotype; 2nd year follow up	95	34.9
CYD dengue ≥1 serotype; 3rd year follow up	76.9	7
CYD dengue ≥1 serotype; 4th year follow up	72.1	4.8
CYD dengue ≥2 serotypes; Pre-Injection 1	6.1	0
CYD dengue ≥2 serotypes; Post-Injection 3	99.3	4.4
CYD dengue ≥2 serotypes; 1st year follow up	66.2	6.7
CYD dengue ≥2 serotypes; 2nd year follow up	70.7	9.3
CYD dengue ≥2 serotypes; 3rd year follow up	48.5	7
CYD dengue ≥2 serotypes; 4th year follow up	35.3	0
CYD dengue ≥3 serotypes; Pre-Injection 1	2	0
CYD dengue ≥3 serotypes; Post-Injection 3	96.5	0
CYD dengue ≥3 serotypes; 1st year follow up	52.8	2.2
CYD dengue ≥3 serotypes; 2nd year follow up	42.1	0
CYD dengue ≥3 serotypes; 3rd year follow up	23.9	4.7
CYD dengue ≥3 serotypes; 4th year follow up	16.2	0
CYD dengue All 4 serotypes; Pre-Injection 1	0.7	0
CYD dengue All 4 serotypes; Post-Injection 3	84	0
CYD dengue All 4 serotypes; 1st year follow up	29.6	0
CYD dengue All 4 serotypes; 2nd year follow up	15	0
CYD dengue All 4 serotypes; 3rd year follow up	11.2	0
CYD dengue All 4 serotypes; 4th year follow up	6.6	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Top of page

End point title

Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Percentage of subjects
number (not applicable)
CYD dengue ≥1 Serotype; Pre-Injection 1	13.5	15.2
CYD dengue ≥1 Serotype; Post-Injection 3	97.8	25.6
CYD dengue ≥1 Serotype; 1st year follow up	94.7	7.3
CYD dengue ≥1 Serotype; 2nd year follow up	93	15
CYD dengue ≥1 Serotype; 3rd year follow up	89.5	5
CYD dengue ≥1 serotype; 4th year follow up	81.4	8.1
CYD dengue ≥2 Serotypes; Pre-Injection 1	7.8	4.3
CYD dengue ≥2 Serotypes; Post-Injection 3	94.8	9.3
CYD dengue ≥2 Serotypes; 1st year follow up	60.2	4.9
CYD dengue ≥2 Serotypes; 2nd year follow up	62.5	10
CYD dengue ≥2 Serotypes; 3rd year follow up	45.2	5
CYD dengue ≥2 serotypes; 4th year follow up	44.9	5.4
CYD dengue ≥3 Serotypes; Pre-Injection 1	7.1	2.2
CYD dengue ≥3 Serotypes; Post-Injection 3	80.7	9.3
CYD dengue ≥3 Serotypes; 1st year follow up	33.1	4.9
CYD dengue ≥3 Serotypes; 2nd year follow up	31.3	7.5
CYD dengue ≥3 Serotypes; 3rd year follow up	22.6	5
CYD dengue ≥3 serotypes; 4th year follow up	20.3	5.4
CYD dengue All 4 Serotypes; Pre-Injection 1	5	0
CYD dengue All 4 Serotypes; Post-Injection 3	57	7
CYD dengue All 4 Serotypes; 1st year follow up	15.8	2.4
CYD dengue All 4 Serotypes; 2nd year follow up	11.7	7.5
CYD dengue All 4 Serotypes; 3rd year follow up	8.9	5
CYD dengue All 4 serotypes; 4th year follow up	9.3	5.4

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Top of page

End point title

Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Percentage of subjects
number (not applicable)
CYD dengue ≥1 Serotype; Pre-Injection 1	46.5	55.1
CYD dengue ≥1 Serotype; Post-Injection 3	100	53.5
CYD dengue ≥1 Serotype; 1st year follow up	96.7	50
CYD dengue ≥1 Serotype; 2nd year follow up	96.6	56.1
CYD dengue ≥1 Serotype; 3rd year follow up	93	41
CYD dengue ≥1 serotype; 4th year follow up	92.5	36.8
CYD dengue ≥2 Serotypes; Pre-Injection 1	32.4	38.8
CYD dengue ≥2 Serotypes; Post-Injection 3	97.6	32.6
CYD dengue ≥2 Serotypes; 1st year follow up	73.8	38.6
CYD dengue ≥2 Serotypes; 2nd year follow up	76.9	34.1
CYD dengue ≥2 Serotypes; 3rd year follow up	63.2	33.3
CYD dengue ≥2 serotypes; 4th year follow up	54.2	28.9
CYD dengue ≥3 Serotypes; Pre-Injection 1	26.8	32.7
CYD dengue ≥3 Serotypes; Post-Injection 3	83.5	27.9
CYD dengue ≥3 Serotypes; 1st year follow up	55.7	34.1
CYD dengue ≥3 Serotypes; 2nd year follow up	56.4	29.3
CYD dengue ≥3 Serotypes; 3rd year follow up	46.5	30.8
CYD dengue ≥3 serotypes; 4th year follow up	43	26.3
CYD dengue All 4 Serotypes; Pre-Injection 1	21.1	22.4
CYD dengue All 4 Serotypes; Post-Injection 3	56.7	23.3
CYD dengue All 4 Serotypes; 1st year follow up	41	18.2
CYD dengue All 4 Serotypes; 2nd year follow up	41	19.5
CYD dengue All 4 Serotypes; 3rd year follow up	39.5	17.9
CYD dengue All 4 serotypes; 4th year follow up	37.4	21.1

No statistical analyses for this end point

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 2 to 11 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Top of page

End point title

Geometric Mean Titers (GMTs) of Antibodies In Subjects 2 to 11 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

End point description

Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay.

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
CYD dengue Serotype 1; Pre-Injection 1	5.33 (5.08 to 5.6)	5.42 (5 to 5.86)
CYD dengue Serotype 1; Post-Injection 3	56.6 (46.5 to 68.9)	6.06 (4.93 to 7.46)
CYD dengue Serotype 1; 1st year follow up	12.1 (9.92 to 14.7)	5.52 (4.92 to 6.19)
CYD dengue Serotype 1; 2nd year follow up	8.89 (7.5 to 10.5)	5 (5 to 5)
CYD dengue Serotype 1; 3rd year follow up	7.35 (6.22 to 8.67)	5 (5 to 5)
CYD dengue Serotype 1; 4th year follow up	6.21 (5.51 to 7)	5 (5 to 5)
CYD dengue Serotype 2; Pre-Injection 1	5.85 (5.18 to 6.6)	5.17 (4.83 to 5.53)
CYD dengue Serotype 2; Post-Injection 3	101 (81.7 to 125)	5.88 (5.15 to 6.72)
CYD dengue Serotype 2; 1st year follow up	21.1 (16.6 to 26.9)	5.86 (4.79 to 7.16)
CYD dengue Serotype 2; 2nd year follow up	16.4 (12.9 to 20.9)	6.11 (5.1 to 7.32)
CYD dengue Serotype 2; 3rd year follow up	11.7 (9.1 to 15.1)	5.58 (4.86 to 6.41)
CYD dengue Serotype 2; 4th year follow up	14.2 (10.7 to 19)	5.11 (4.89 to 5.32)
CYD dengue Serotype 3; Pre-Injection 1	6.24 (5.57 to 6.99)	5.95 (5.04 to 7.02)
CYD dengue Serotype 3; Post-Injection 3	136 (114 to 162)	6.54 (5.2 to 8.22)
CYD dengue Serotype 3; 1st year follow up	25.4 (20.1 to 32.1)	5.87 (5 to 6.89)
CYD dengue Serotype 3; 2nd year follow up	29.9 (23.4 to 38.1)	10.1 (6.68 to 15.2)
CYD dengue Serotype 3; 3rd year follow up	14.6 (11.7 to 18.3)	5.43 (4.83 to 6.1)
CYD dengue Serotype 3; 4th year follow up	11.4 (9.22 to 14.1)	5.09 (4.91 to 5.29)
CYD dengue Serotype 4; Pre-Injection 1	5.64 (5.2 to 6.11)	5.39 (4.92 to 5.91)
CYD dengue Serotype 4; Post-Injection 3	104 (87.2 to 125)	7.2 (5.74 to 9.05)
CYD dengue Serotype 4; 1st year follow up	31.8 (25.6 to 39.6)	5.69 (4.7 to 6.89)
CYD dengue Serotype 4; 2nd year follow up	30.6 (24.2 to 38.6)	5.68 (4.74 to 6.82)
CYD dengue Serotype 4; 3rd year follow up	22.3 (17.5 to 28.5)	6.31 (4.84 to 8.24)
CYD dengue Serotype 4; 4th year follow up	16.5 (13.1 to 20.7)	5 (5 to 5)

No statistical analyses for this end point

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 12 to 17 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

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End point title

Geometric Mean Titers (GMTs) of Antibodies In Subjects 12 to 17 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

End point description

Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay.

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
CYD dengue Serotype 1; Pre-Injection 1	6.47 (5.31 to 7.89)	5.47 (4.8 to 6.24)
CYD dengue Serotype 1; Post-Injection 3	28.5 (21.4 to 37.9)	6.36 (5.12 to 7.89)
CYD dengue Serotype 1; 1st year follow up	9.69 (7.53 to 12.5)	5.69 (4.88 to 6.63)
CYD dengue Serotype 1; 2nd year follow up	8.31 (6.58 to 10.5)	5.91 (4.8 to 7.27)
CYD dengue Serotype 1; 3rd year follow up	8.02 (6.3 to 10.2)	5.54 (4.79 to 6.39)
CYD dengue Serotype 1; 4th year follow up	7.41 (5.85 to 9.38)	5.51 (4.8 to 6.34)
CYD dengue Serotype 2; Pre-Injection 1	7.45 (5.95 to 9.33)	5.54 (4.69 to 6.56)
CYD dengue Serotype 2; Post-Injection 3	48.7 (37.4 to 63.5)	6.17 (5.03 to 7.58)
CYD dengue Serotype 2; 1st year follow up	16.6 (12.4 to 22.1)	5.58 (4.78 to 6.52)
CYD dengue Serotype 2; 2nd year follow up	18.7 (14.1 to 24.7)	6.38 (4.92 to 8.27)
CYD dengue Serotype 2; 3rd year follow up	13.3 (10.1 to 17.6)	5.77 (4.71 to 7.07)
CYD dengue Serotype 2; 4th year follow up	14 (10.4 to 18.8)	5.8 (4.68 to 7.17)
CYD dengue Serotype 3; Pre-Injection 1	6.84 (5.81 to 8.06)	6.83 (4.84 to 9.65)
CYD dengue Serotype 3; Post-Injection 3	71.4 (56.3 to 90.7)	8.1 (5.66 to 11.6)
CYD dengue Serotype 3; 1st year follow up	19.7 (15.1 to 25.6)	6.27 (4.55 to 8.64)
CYD dengue Serotype 3; 2nd year follow up	20.5 (15.6 to 27.1)	7.54 (5.16 to 11)
CYD dengue Serotype 3; 3rd year follow up	15.3 (11.8 to 19.9)	6.17 (4.58 to 8.31)
CYD dengue Serotype 3; 4th year follow up	13.7 (10.7 to 17.6)	6.47 (4.49 to 9.3)
CYD dengue Serotype 4; Pre-Injection 1	5.83 (5.17 to 6.56)	5.08 (4.92 to 5.23)
CYD dengue Serotype 4; Post-Injection 3	79.2 (64.2 to 97.8)	6.45 (4.89 to 8.53)
CYD dengue Serotype 4; 1st year follow up	30.8 (24.3 to 39)	5.17 (4.84 to 5.52)
CYD dengue Serotype 4; 2nd year follow up	33.4 (25.6 to 43.6)	6.18 (4.99 to 7.65)
CYD dengue Serotype 4; 3rd year follow up	23.1 (18.3 to 29.2)	5.55 (4.79 to 6.42)
CYD dengue Serotype 4; 4th year follow up	20.8 (16.2 to 26.6)	5.43 (4.92 to 6)

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 2 to 11 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 2 to 11 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects immune at baseline are defined as those subjects with titers ≥10 (1/dil) against at least one dengue serotype at baseline.

End point type

Secondary

End point timeframe

Post-Injection 3 and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	114	47
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Post-Injection 3	96.3	0
CYD dengue Serotype 1; 1st year follow up	74.1	7.7
CYD dengue Serotype 1; 2nd year follow up	55.6	0
CYD dengue Serotype 1; 3rd year follow up	33.3	0
CYD dengue Serotype 1; 4th year follow up	22.2	0
CYD dengue Serotype 2; Post-Injection 3	100	15.4
CYD dengue Serotype 2; 1st year follow up	85.2	15.4
CYD dengue Serotype 2; 2nd year follow up	66.7	16.7
CYD dengue Serotype 2; 3rd year follow up	48.1	16.7
CYD dengue Serotype 2; 4th year follow up	48.1	0
CYD dengue Serotype 3; Post-Injection 3	100	23.1
CYD dengue Serotype 3; 1st year follow up	88.9	7.7
CYD dengue Serotype 3; 2nd year follow up	81.5	16.7
CYD dengue Serotype 3; 3rd year follow up	59.3	8.3
CYD dengue Serotype 3; 4th year follow up	50	0
CYD dengue Serotype 4; Post-Injection 3	100	23.1
CYD dengue Serotype 4; 1st year follow up	88.9	15.4
CYD dengue Serotype 4; 2nd year follow up	74.1	0
CYD dengue Serotype 4; 3rd year follow up	70.4	16.7
CYD dengue Serotype 4; 4th year follow up	70.4	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 2 to 11 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 2 to 11 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects naïve at baseline are defined as those subjects with titers <10 (1/dil) against all dengue serotypes at baseline.

End point type

Secondary

End point timeframe

Post-Injection 3 and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	313	98
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Post-Injection 3	89.6	12.5
CYD dengue Serotype 1; 1st year follow up	33.6	6.5
CYD dengue Serotype 1; 2nd year follow up	20.5	0
CYD dengue Serotype 1; 3rd year follow up	12.4	0
CYD dengue Serotype 1; 4th year follow up	6.5	0
CYD dengue Serotype 2; Post-Injection 3	93	12.5
CYD dengue Serotype 2; 1st year follow up	54	6.3
CYD dengue Serotype 2; 2nd year follow up	49.1	9.7
CYD dengue Serotype 2; 3rd year follow up	31.1	3.2
CYD dengue Serotype 2; 4th year follow up	34.3	3.3
CYD dengue Serotype 3; Post-Injection 3	97.4	9.7
CYD dengue Serotype 3; 1st year follow up	60.2	9.7
CYD dengue Serotype 3; 2nd year follow up	72.4	34.5
CYD dengue Serotype 3; 3rd year follow up	47.2	3.2
CYD dengue Serotype 3; 4th year follow up	34.3	3.3
CYD dengue Serotype 4; Post-Injection 3	96.5	19.4
CYD dengue Serotype 4; 1st year follow up	71.7	0
CYD dengue Serotype 4; 2nd year follow up	73.2	6.5
CYD dengue Serotype 4; 3rd year follow up	58.7	3.2
CYD dengue Serotype 4; 4th year follow up	44.4	0

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 12 to 17 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 12 to 17 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Post-Injection 3 and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	114	47
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Post-Injection 3	94.4	33.3
CYD dengue Serotype 1; 1st year follow up	58.8	20
CYD dengue Serotype 1; 2nd year follow up	46.7	16.7
CYD dengue Serotype 1; 3rd year follow up	43.8	16.7
CYD dengue Serotype 1; 4th year follow up	42.9	20
CYD dengue Serotype 2; Post-Injection 3	94.4	16.7
CYD dengue Serotype 2; 1st year follow up	82.4	20
CYD dengue Serotype 2; 2nd year follow up	73.3	33.3
CYD dengue Serotype 2; 3rd year follow up	68.8	16.7
CYD dengue Serotype 2; 4th year follow up	71.4	20
CYD dengue Serotype 3; Post-Injection 3	100	50
CYD dengue Serotype 3; 1st year follow up	76.5	20
CYD dengue Serotype 3; 2nd year follow up	80	50
CYD dengue Serotype 3; 3rd year follow up	68.8	16.7
CYD dengue Serotype 3; 4th year follow up	71.4	20
CYD dengue Serotype 4; Post-Injection 3	100	33.3
CYD dengue Serotype 4; 1st year follow up	100	20
CYD dengue Serotype 4; 2nd year follow up	100	16.7
CYD dengue Serotype 4; 3rd year follow up	93.8	16.7
CYD dengue Serotype 4; 4th year follow up	100	20

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 12 to 17 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 12 to 17 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects naïve at baseline are defined as those subjects with titers <10 (1/dil) against all dengue serotypes at baseline.

End point type

Secondary

End point timeframe

Post-Injection 3 and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	313	98
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Post-Injection 3	62.9	8.1
CYD dengue Serotype 1; 1st year follow up	20.9	5.6
CYD dengue Serotype 1; 2nd year follow up	16.1	5.9
CYD dengue Serotype 1; 3rd year follow up	12	2.9
CYD dengue Serotype 1; 4th year follow up	7.7	3.1
CYD dengue Serotype 2; Post-Injection 3	81.9	8.1
CYD dengue Serotype 2; 1st year follow up	38.6	2.8
CYD dengue Serotype 2; 2nd year follow up	49.1	5.9
CYD dengue Serotype 2; 3rd year follow up	30.6	2.9
CYD dengue Serotype 2; 4th year follow up	31.4	3.1
CYD dengue Serotype 3; Post-Injection 3	87	16.2
CYD dengue Serotype 3; 1st year follow up	59.5	2.9
CYD dengue Serotype 3; 2nd year follow up	53.6	5.9
CYD dengue Serotype 3; 3rd year follow up	45.8	2.9
CYD dengue Serotype 3; 4th year follow up	44.2	3.1
CYD dengue Serotype 4; Post-Injection 3	89.7	5.4
CYD dengue Serotype 4; 1st year follow up	69.6	0
CYD dengue Serotype 4; 2nd year follow up	67	8.8
CYD dengue Serotype 4; 3rd year follow up	62.6	2.9
CYD dengue Serotype 4; 4th year follow up	55.8	6.3

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 18 to 45 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 18 to 45 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

End point type

Secondary

End point timeframe

Post-Injection 3 and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	114	47
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Post-Injection 3	89.3	70
CYD dengue Serotype 1; 1st year follow up	77.8	57.1
CYD dengue Serotype 1; 2nd year follow up	86.3	65
CYD dengue Serotype 1; 3rd year follow up	80.8	63.2
CYD dengue Serotype 1; 4th year follow up	84.8	66.7
CYD dengue Serotype 2; Post-Injection 3	91.1	65
CYD dengue Serotype 2; 1st year follow up	88.9	71.4
CYD dengue Serotype 2; 2nd year follow up	92.2	70
CYD dengue Serotype 2; 3rd year follow up	88.5	68.4
CYD dengue Serotype 2; 4th year follow up	91.5	66.7
CYD dengue Serotype 3; Post-Injection 3	98.2	60
CYD dengue Serotype 3; 1st year follow up	90.7	66.7
CYD dengue Serotype 3; 2nd year follow up	98	70
CYD dengue Serotype 3; 3rd year follow up	94.2	73.7
CYD dengue Serotype 3; 4th year follow up	91.5	61.1
CYD dengue Serotype 4; Post-Injection 3	100	65
CYD dengue Serotype 4; 1st year follow up	98.1	47.6
CYD dengue Serotype 4; 2nd year follow up	96.1	45
CYD dengue Serotype 4; 3rd year follow up	100	42.1
CYD dengue Serotype 4; 4th year follow up	97.9	44.4

No statistical analyses for this end point

Secondary: Percentage of Subjects Aged 18 to 45 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

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End point title

Percentage of Subjects Aged 18 to 45 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

End point description

Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay. Seropositive was defined as subjects with antibody titers ≥10 (1/dil). Dengue subjects naïve at baseline are defined as those subjects with titers <10 (1/dil) against all dengue serotypes at baseline.

End point type

Secondary

End point timeframe

Post-Injection 3 and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	313	98
Units: Percentage of subjects
number (not applicable)
CYD dengue Serotype 1; Post-Injection 3	59.4	14.3
CYD dengue Serotype 1; 1st year follow up	21.3	9.5
CYD dengue Serotype 1; 2nd year follow up	10.2	5.3
CYD dengue Serotype 1; 3rd year follow up	7.1	0
CYD dengue Serotype 1; 4th year follow up	5.6	0
CYD dengue Serotype 2; Post-Injection 3	73.4	0
CYD dengue Serotype 2; 1st year follow up	49.2	14.3
CYD dengue Serotype 2; 2nd year follow up	50.8	0
CYD dengue Serotype 2; 3rd year follow up	28.6	5.6
CYD dengue Serotype 2; 4th year follow up	26.4	0
CYD dengue Serotype 3; Post-Injection 3	87.5	14.3
CYD dengue Serotype 3; 1st year follow up	48.3	14.3
CYD dengue Serotype 3; 2nd year follow up	61	21.1
CYD dengue Serotype 3; 3rd year follow up	46.3	0
CYD dengue Serotype 3; 4th year follow up	28.3	0
CYD dengue Serotype 4; Post-Injection 3	87.5	4.8
CYD dengue Serotype 4; 1st year follow up	78.7	14.3
CYD dengue Serotype 4; 2nd year follow up	71.2	5.3
CYD dengue Serotype 4; 3rd year follow up	66.1	0
CYD dengue Serotype 4; 4th year follow up	63	0

No statistical analyses for this end point

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 18 to 45 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

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End point title

Geometric Mean Titers (GMTs) of Antibodies In Subjects 18 to 45 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

End point description

Geometric mean titers against each serotype with the dengue virus strain were assessed using a dengue plaque reduction neutralization test (PRNT) assay.

End point type

Secondary

End point timeframe

Pre-Injection 1, Post-Injection 3, and up to 4 years of follow up

End point values	CYD Dengue vaccine group	Control group
Number of subjects analysed	438	147
Units: Titers (1/dil)
geometric mean (confidence interval 95%)
CYD dengue Serotype 1; Pre-Injection 1	15.8 (11.7 to 21.5)	19.2 (10.9 to 33.9)
CYD dengue Serotype 1; Post-Injection 3	48.7 (33.6 to 70.4)	16.2 (9.77 to 27)
CYD dengue Serotype 1; 1st year follow up	26.3 (17.9 to 38.6)	15.2 (8.76 to 26.3)
CYD dengue Serotype 1; 2nd year follow up	26.3 (17.7 to 38.9)	16.3 (9.09 to 29.3)
CYD dengue Serotype 1; 3rd year follow up	24.1 (15.9 to 36.5)	13.9 (7.89 to 24.6)
CYD dengue Serotype 1; 4th year follow up	23.5 (15.5 to 35.5)	14.4 (8.03 to 25.6)
CYD dengue Serotype 2; Pre-Injection 1	16.9 (12.3 to 23.1)	21 (11.5 to 38.2)
CYD dengue Serotype 2; Post-Injection 3	66.9 (47.9 to 93.5)	15.2 (8.61 to 27)
CYD dengue Serotype 2; 1st year follow up	50.4 (34.5 to 73.7)	19.3 (10.7 to 34.7)
CYD dengue Serotype 2; 2nd year follow up	66.5 (43.7 to 101)	20 (10.2 to 39)
CYD dengue Serotype 2; 3rd year follow up	38.4 (25.8 to 57.2)	17 (9.38 to 30.8)
CYD dengue Serotype 2; 4th year follow up	32.9 (22.4 to 48.2)	15.5 (8.51 to 28.2)
CYD dengue Serotype 3; Pre-Injection 1	14.5 (11.2 to 18.7)	19.4 (11.4 to 33.1)
CYD dengue Serotype 3; Post-Injection 3	88.4 (68.6 to 114)	13.3 (8.22 to 21.7)
CYD dengue Serotype 3; 1st year follow up	45.2 (32.1 to 63.6)	14.8 (8.96 to 24.3)
CYD dengue Serotype 3; 2nd year follow up	64.8 (46.8 to 89.7)	19.9 (11.5 to 34.5)
CYD dengue Serotype 3; 3rd year follow up	48.3 (33 to 70.8)	14.7 (8.46 to 25.7)
CYD dengue Serotype 3; 4th year follow up	28.6 (20.2 to 40.6)	11.8 (7.18 to 19.3)
CYD dengue Serotype 4; Pre-Injection 1	10.1 (8.03 to 12.7)	11.7 (7.74 to 17.6)
CYD dengue Serotype 4; Post-Injection 3	122 (96.5 to 155)	10 (6.96 to 14.4)
CYD dengue Serotype 4; 1st year follow up	70.3 (53.6 to 92.2)	9.87 (6.88 to 14.2)
CYD dengue Serotype 4; 2nd year follow up	52.6 (39.9 to 69.3)	8.5 (6.07 to 11.9)
CYD dengue Serotype 4; 3rd year follow up	46.4 (35.5 to 60.6)	8.39 (5.83 to 12.1)
CYD dengue Serotype 4; 4th year follow up	32.6 (25.2 to 42.3)	7.54 (5.69 to 10)

No statistical analyses for this end point

Adverse events

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Timeframe for reporting adverse events

Adverse events were collected from Day 0 (post-vaccination) up to the 4th year of follow up.

Assessment type

Non-systematic

Dictionary name

MedDRA

Dictionary version

11.0

Reporting group title

CYD Dengue vaccine group

Reporting group description

Subjects received the CYD dengue vaccine at 0, 6, and 12 months as first, second, and third vaccinations, respectively.

Reporting group title

Control group

Reporting group description

Subjects received a placebo at first vaccination (Month 0). Subjects <12 years received hepatitis A at second (Month 6) and third (Month 12) vaccinations. Subjects ≥12 years received influenza vaccine of Northern and Southern hemisphere formulations at second (Month 6) and third (Month 12) vaccinations.

Serious adverse events	CYD Dengue vaccine group	Control group
Total subjects affected by serious adverse events
subjects affected / exposed	43 / 898 (4.79%)	13 / 300 (4.33%)
number of deaths (all causes)	3	0
number of deaths resulting from adverse events	0	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute leukaemia
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Acute lymphocytic leukaemia
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Ovarian cancer metastatic
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Ovarian germ cell teratoma benign
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Papillary thyroid cancer
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Surgical and medical procedures
Osteotomy
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Ruptured ectopic pregnancy
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
General disorders and administration site conditions
Adverse drug reaction
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Chest pain
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Reproductive system and breast disorders
Ovarian cyst
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Respiratory, thoracic and mediastinal disorders
Asthma
subjects affected / exposed	2 / 898 (0.22%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 2	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchial hyperreactivity
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Rhinitis allergic
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Psychiatric disorders
Depression
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Injury, poisoning and procedural complications
Foot fracture
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Hand fracture
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Intentional overdose
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Traumatic haematoma
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Cardiac disorders
Acute coronary syndrome
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 1	0 / 0
Nervous system disorders
Migraine
subjects affected / exposed	2 / 898 (0.22%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Radial nerve palsy
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Syncope vasovagal
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Tension headache
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	1 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastrointestinal disorders
Abdominal pain
subjects affected / exposed	1 / 898 (0.11%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Colitis
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Diarrhoea
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gingivitis
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Endocrine disorders
Hyperthyroidism
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Thyroid disorder
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal and connective tissue disorders
Arthralgia
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Back pain
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Intervertebral disc protrusion
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Musculoskeletal pain
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Infections and infestations
Appendicitis
subjects affected / exposed	2 / 898 (0.22%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Bronchitis
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Conjunctivitis viral
subjects affected / exposed	2 / 898 (0.22%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Corneal infection
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Dengue fever
subjects affected / exposed	3 / 898 (0.33%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 3	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis
subjects affected / exposed	2 / 898 (0.22%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 3	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Gastroenteritis viral
subjects affected / exposed	1 / 898 (0.11%)	2 / 300 (0.67%)
occurrences causally related to treatment / all	0 / 1	0 / 2
deaths causally related to treatment / all	0 / 0	0 / 0
Groin abscess
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Hand-foot-and-mouth disease
subjects affected / exposed	2 / 898 (0.22%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Herpangina
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Lymph node tuberculosis
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Meningitis viral
subjects affected / exposed	0 / 898 (0.00%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 0	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis
subjects affected / exposed	1 / 898 (0.11%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Pharyngitis bacterial
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Subcutaneous abscess
subjects affected / exposed	1 / 898 (0.11%)	1 / 300 (0.33%)
occurrences causally related to treatment / all	0 / 1	0 / 1
deaths causally related to treatment / all	0 / 0	0 / 0
Upper respiratory tract infection
subjects affected / exposed	2 / 898 (0.22%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 2	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0
Viral infection
subjects affected / exposed	1 / 898 (0.11%)	0 / 300 (0.00%)
occurrences causally related to treatment / all	0 / 1	0 / 0
deaths causally related to treatment / all	0 / 0	0 / 0

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

Non-serious adverse events	CYD Dengue vaccine group	Control group
Total subjects affected by non serious adverse events
subjects affected / exposed	481 / 898 (53.56%)	198 / 300 (66.00%)
Nervous system disorders
Headache; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[1]	402 / 891 (45.12%)	114 / 297 (38.38%)
occurrences all number	402	114
General disorders and administration site conditions
Injection site Pain; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[2]	481 / 892 (53.92%)	198 / 297 (66.67%)
occurrences all number	481	198
Injection site Erythema; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[3]	64 / 891 (7.18%)	45 / 297 (15.15%)
occurrences all number	64	45
Injection site Swelling; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[4]	37 / 892 (4.15%)	25 / 297 (8.42%)
occurrences all number	37	25
Fever; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[5]	101 / 892 (11.32%)	22 / 297 (7.41%)
occurrences all number	101	22
Malaise; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[6]	372 / 891 (41.75%)	105 / 297 (35.35%)
occurrences all number	372	105
Asthenia; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[7]	183 / 891 (20.54%)	52 / 297 (17.51%)
occurrences all number	183	52
Respiratory, thoracic and mediastinal disorders
Cough
subjects affected / exposed	42 / 898 (4.68%)	15 / 300 (5.00%)
occurrences all number	48	17
Rhinorrhoea
subjects affected / exposed	42 / 898 (4.68%)	15 / 300 (5.00%)
occurrences all number	47	15
Musculoskeletal and connective tissue disorders
Myalgia; Post-Any Injection
alternative assessment type: Systematic
subjects affected / exposed ^[8]	394 / 891 (44.22%)	130 / 297 (43.77%)
occurrences all number	394	130
Infections and infestations
Upper respiratory tract infection
subjects affected / exposed	72 / 898 (8.02%)	27 / 300 (9.00%)
occurrences all number	77	30

Notes
[1] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[2] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 7 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[3] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 7 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[4] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 7 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[5] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[6] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[7] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.
[8] - The number of subjects exposed to this adverse event is less than the total number of subjects exposed for the reporting group. These numbers are expected to be equal.
Justification: This was a solicited event recorded in a diary within 14 days after any injection; the total number (N) reflects those subjects for which the diary cards were returned and for which data were available for the event during the period.

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Were there any global substantial amendments to the protocol? Yes

05 Dec 2008

Integrated comments from the Institutional Review Boards in the Protocol and Appendices.

20 May 2009

Modified the observer-blind design for the second vaccination into a single-blind design and modified the interim statistical analysis schedule to include an analysis at 24 and 36 months post-last vaccination to get supportive data regarding persistence of neutralizing antibodies.

06 Dec 2010

Changed from Pan Flavivirus reverse transcriptase-polymerase chain reaction (RT-PCR) to dengue screen RT-PCR to improve assay sensitivity, replaced the microneutralization assay by the plaque reduction neutralization test (PRNT) assay to determine dengue neutralizing antibodies to serotypes 1, 2, 3, and 4 in subjects, replaced the method of the assessment of the cross-reactivity (microneutralization assay) by a seroneutralization assay, added an observational objective regarding the cell mediated immunity and additional blood sample volumes were added at each visit during the 4-year follow up, and due to limited time between post-Injection 2 and 3 results the post-Injection 2 analysis of safety and immunogenicity was cancelled in order to analyze the results of post-Injection 2 and 3 samples obtained by PRNT at the same time; as a result, the blind was broken and subjects were informed about the vaccines after the database lock for statistical analyses.

28 Mar 2012

The Sponsor's Responsible Medical Officer for the study was replaced by T. Anh Wartel during the conduct of the long-term follow up and a new Principal Investigator (Low Chian Yong) was assigned to Center 004 from July 2011 following the resignation of the existing Principal Investigator.

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: Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore

Trial information

Trial information

Subject disposition

Subject disposition

Baseline characteristics

Baseline characteristics

End points

End points

Primary: Percentage of All Subjects Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

Primary: Percentage of All Subjects Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

Primary: Percentage of Subjects By Age Group Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

Primary: Percentage of Subjects By Age Group Reporting Solicited Injection-site and Systemic Reactions Following Each Injection with CYD Dengue Tetravalent Vaccine

Primary: Percentage of All Subjects Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine

Primary: Percentage of All Subjects Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine

Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Primary: Percentage of Subjects By Age Group Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Primary: Geometric Mean Titers (GMTs) of Antibodies In All Subjects Against Each Serotype with the Parental Dengue Virus Strain Before and Following Each Injection with CYD Dengue Vaccine

Primary: Geometric Mean Titers (GMTs) of Antibodies In All Subjects Against Each Serotype with the Parental Dengue Virus Strain Before and Following Each Injection with CYD Dengue Vaccine

Primary: Geometric Mean Titers (GMTs) of Antibodies By Age Groups Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Primary: Geometric Mean Titers (GMTs) of Antibodies By Age Groups Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Old Who Achieved Seropositivity Against At least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After The Third Vaccination With CYD Dengue Vaccine

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 2 to 11 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 2 to 11 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 12 to 17 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 12 to 17 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 2 to 11 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 12 to 17 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Immune at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Percentage of Subjects Aged 18 to 45 Years Naïve at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes Up to 4 Years After The Third Vaccination With CYD Dengue Vaccine

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 18 to 45 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Secondary: Geometric Mean Titers (GMTs) of Antibodies In Subjects 18 to 45 Years Old Against Each Serotype with the Parental Dengue Virus Strain Before and Following The Third Injection with CYD Dengue Vaccine

Adverse events

Adverse events

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Substantial protocol amendments (globally)

Interruptions (globally)

Limitations and caveats

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Clinical Trial Results:
Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore