Clinical Trials Register

Summary
EudraCT Number:	2014-001714-26
Sponsor's Protocol Code Number:	CYD29
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2014-05-26
Trial results	View results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2014-001714-26

A.3

Full title of the trial

Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril®) Administered Concomitantly with Tetravalent Dengue Vaccine in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Study of Yellow Fever Vaccine Administered With Sanofi Pasteur's Dengue Vaccine in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru

A.4.1

Sponsor's protocol code number

CYD29

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT01436396

A.5.3

WHO Universal Trial Reference Number (UTRN)

U1111-1116-4913

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/113/2014

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Sanofi Pasteur SA
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Sanofi Pasteur SA
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Sanofi Pasteur SA
B.5.2	Functional name of contact point	R&D, Clinical Development dpt
B.5.3	Address:
B.5.3.1	Street Address	1541 Avenue Marcel Mérieux
B.5.3.2	Town/ city	MARCY L'ETOILE
B.5.3.3	Post code	69280
B.5.3.4	Country	France
B.5.4	Telephone number	3304 37 65 60 60

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	No
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CYD Dengue Vaccine
D.3.2	Product code	323
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Live, attenuated, chimeric dengue virus serotype 1
D.3.9.3	Other descriptive name	LIVE, ATTENUATED, CHIMERIC DENGUE VIRUS
D.3.9.4	EV Substance Code	SUB165738
D.3.10	Strength
D.3.10.1	Concentration unit	log10 CCID50/dose log10 cell culture infective dose 50/dose
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	4.5 to 6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Live, attenuated, chimeric dengue virus serotype 2
D.3.9.3	Other descriptive name	LIVE, ATTENUATED, CHIMERIC DENGUE VIRUS
D.3.9.4	EV Substance Code	SUB165738
D.3.10	Strength
D.3.10.1	Concentration unit	log10 CCID50/dose log10 cell culture infective dose 50/dose
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	4.5 to 6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Live, attenuated, chimeric dengue virus serotype 3
D.3.9.3	Other descriptive name	LIVE, ATTENUATED, CHIMERIC DENGUE VIRUS
D.3.9.4	EV Substance Code	SUB165738
D.3.10	Strength
D.3.10.1	Concentration unit	log10 CCID50/dose log10 cell culture infective dose 50/dose
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	4.5 to 6
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Live, attenuated, chimeric dengue virus serotype 4
D.3.9.3	Other descriptive name	LIVE, ATTENUATED, CHIMERIC DENGUE VIRUS
D.3.9.4	EV Substance Code	SUB165738
D.3.10	Strength
D.3.10.1	Concentration unit	log10 CCID50/dose log10 cell culture infective dose 50/dose
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	4.5 to 6
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	Yes
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	Stamaril®
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI PASTEUR
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Yellow Fever Vaccine (Stamaril®)
D.3.2	Product code	105
D.3.4	Pharmaceutical form	Powder and solvent for suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Yellow fever virus1 17 D-204 strain (live, attenuated)
D.3.9.3	Other descriptive name	YELLOW FEVER VIRUS STRAIN 17D-204 (LIVE, ATTENUATED)
D.3.9.4	EV Substance Code	SUB26732
D.3.10	Strength
D.3.10.1	Concentration unit	PFU e.1000 mouse LD50 plaque forming unit equiv 1000 mouse LD50
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	1000
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Prevention of symptomatic dengue disease

E.1.1.1

Medical condition in easily understood language

Prevention of dengue disease with clinical symptoms

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To demonstrate the non-inferiority of the immune response against Yellow Fever (YF) in Flavivirus (FV)-naïve subjects at baseline receiving one dose of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine compared to subjects receiving one dose of Stamaril vaccine concomitantly with placebo.

E.2.2

Secondary objectives of the trial

YF Immunogenicity (All Subjects)
1) To assess the non-inferiority of YF immune response 28 days post-Stamaril vaccination based on seroconversion rates regardless of the FV status of subjects at baseline.
2) To describe the YF immune response 28 days post-Stamaril vaccination

Dengue Immunogenicity (in a subset)
To describe the antibody response to each dengue virus serotype 28 days post CYD dengue vaccination

Safety and reactogenicity (All Subjects)
1) To describe the safety of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine, or Stamaril administered concomitantly with placebo
2) To describe the safety of CYD dengue vaccine after the first dose of CYD dengue vaccine administered concomitantly with Stamaril vaccine or CYD vaccine administered alone
3) To describe the safety of the CYD dengue vaccine in all subjects after each dose

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Aged 12 to 13 months on the day of inclusion.
2) Born at full term of pregnancy (≥37 weeks) and with a birth weight ≥2.5 kg as reported by the parent/legally acceptable representative.
3) Subject in good health, based on medical history and physical examination.
4) Subject has completed his/her vaccination schedule according to the official immunization calendar of Colombia and/or Peru, respectively.
5) Informed consent form has been signed and dated by the parent(s) or other legally acceptable representative (and by 2 independent witnesses if required by local regulations).
6) Subject and parent/legally acceptable representative/tutor able to attend all scheduled visits and to comply with all trial procedures.

E.4

Principal exclusion criteria

1) Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination.
2) Planned participation in another clinical trial during the present trial period.
3) Planned receipt of any vaccine in the 4 weeks following first trial vaccination.
4) Previous vaccination against YF, hepatitis A or measles, mumps and rubella.
5) Receipt of blood or blood-derived products in the past 3 months which might interfere with assessment of the immune response.
6) Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 weeks or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
7) Personal known seropositivity for human immunodeficiency virus (HIV) as reported by the parent/legally acceptable representative.
8) History of previous maternal vaccination against YF as reported by the parent/legally acceptable representative.
9) Personal history of YF or dengue infection/disease as reported by the
parent/legally acceptable representative.
10) Known systemic hypersensitivity to any of the vaccine components of the vaccines that will be used in the trial, or history of a life-threatening reaction to the vaccines used in the trial or to vaccines containing any of the same substances.
11) History of contraindication to receipt of vaccines containing components of Stamaril (yellow fever vaccine), measles, mumps and rubella vaccine, hepatitis A vaccine, pneumococcal conjugated vaccine or of diphtheria (D) toxoid, tetanus (T) toxoid, pertussis toxoid (PT), filamentous hemagglutinin (FHA), polyribosylribitol phosphate (PRP) and polio or other DTP vaccine (e.g., DTwP).
12) Thrombocytopenia, as reported by the parent/legally acceptable representative.
13) Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating IM vaccination.
14) History of central nervous system disorder or disease, including seizures.
15) Personal history of thymic pathology (e.g., thymoma), and/or thymectomy.
16) Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.
17) Identified as a child (adopted or natural) of the Investigator or of employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center.
Temporary Contraindications:
A prospective subject must not be included in the study until the following conditions and/or symptoms are resolved:
18) Febrile illness (temperature ≥38.0°C) or moderate or severe acute
illness/infection (according to Investigator judgment) on the day of vaccination.
19) Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.

E.5 End points

E.5.1

Primary end point(s)

YF Immunogenicity: YF seroconversion rate (antibody titers)

E.5.1.1

Timepoint(s) of evaluation of this end point

YF Immunogenicity: 28 days after YF vaccine injection

E.5.2

Secondary end point(s)

YF Immunogenicity: YF seroconversion rate (antibody titers)
Dengue immunogenicity: dengue immune response (serotype specific neutralizing antibodies)
Safety and reactogenicity: Adverse events including non-serious adverse events of special interest (AESIs), and serious adverse events, including serious AESIs

E.5.2.1

Timepoint(s) of evaluation of this end point

YF immunogenicity: 28 days (D28) after YF vaccine injection
Dengue immunogenicity: on D28 after each injection in the immunogenicity subset
Safety and reactogenicity:
- AEs up to day 28 (D28) after each injection.
- Non-serious AESIs up to 7 days after each injection.
- SAEs, including serious AESIs, throughout the study

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

Yes

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Observer-blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

At 0 Mo: YF Vaccine (Stamaril) + Placebo (NaCl 0.9%) (co-ad); 6 and 12 Mo: CYD Dengue Vaccine

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Colombia

Peru

E.8.7

Trial has a data monitoring committee

Yes

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

792

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

792

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

F.3.2

Patients

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

792

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Colombia

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