Clinical Trials Register

Summary
EudraCT Number:	2015-003500-23
Sponsor's Protocol Code Number:	Td517
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2016-01-13
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

2015-003500-23

A.3

Full title of the trial

Safety and Immunogenicity of Tdap Vaccine Compared to DTaP vaccine
as Fifth Dose Booster in Children 4 to 6 Years of Age

A.3.1

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

Safety and Immunogenicity of Tdap Vaccine Compared to DTaP vaccine
as Fifth Dose Booster in Children 4 to 6 Years of Age

A.4.1

Sponsor's protocol code number

Td517

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00467519

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	SANOFI PASTEUR INC.
B.1.3.4	Country	United States
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
B.4.2	Country	United States
B.4.1	Name of organisation providing support	SANOFI PASTEUR
B.4.2	Country	Canada
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	SANOFI PASTEUR
B.5.2	Functional name of contact point	Oladayo OYELOLA
B.5.3	Address:
B.5.3.1	Street Address	1 Discovery Drive
B.5.3.2	Town/ city	SWIFTWATER, PA
B.5.3.3	Post code	18370
B.5.3.4	Country	United States
B.5.6	E-mail	oladayo.oyelola@sanofipasteur.com

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Comparator
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	Adacel, Covaxis, Triaxis
D.2.1.1.2	Name of the Marketing Authorisation holder	SANOFI PASTEUR, SANOFI
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccine Adsorbed (Adacel®)
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Active immunization against tetanus, diphtheria and pertussis

E.1.1.1

Medical condition in easily understood language

Protection against tetanus, diphtheria and pertussis

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10054129
E.1.2	Term	Diphtheria immunisation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10069577
E.1.2	Term	Pertussis immunisation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	PT
E.1.2	Classification code	10054131
E.1.2	Term	Tetanus immunisation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

1) To compare the immune responses of Tdap to DTaP vaccine when
each is administered as a 5th dose to DAPTACEL- or Pentacel-primed
subjects and given concurrently, but in a separate arm from
poliomyelitis, measles, mumps, rubella (MMR) and varicella vaccines to
children aged 4 to 6 years, as measured by seroprotection rates (³ 0.1
IU/mL), serothreshold rates (³ 1.0 IU/mL) and booster response rates
for diphtheria and tetanus.

2) To compare immune responses of Tdap to DTaP vaccine when
administered as a 5th dose to DAPTACEL- or Pentacel-primed subjects
and given concurrently, but in a separate arm from poliomyelitis,
measles, mumps, rubella (MMR) and varicella vaccines to children aged
4 to 6 years, as measured by booster response rates and GMTs for
pertussis antigens (PT, FHA, PRN and FIM).

E.2.2

Secondary objectives of the trial

Immunogenicity
To compare immune responses of Tdap to DTaP vaccine when administered as a 5th dose and given concurrently; but in a separate arm from poliomyelitis, MMR, and varicella vaccines to children aged 4 to 6 years, as measured by 4-fold
rise rates (post-/pre-vaccination ≥ 4) for pertussis antigens (PT, FHA, PRN, and FIM).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1) Healthy, as determined by medical history and physical examination.
2) Aged 4 to 6 (< 7) years at the time of study vaccination on Day 0.
3) Signed and dated informed consent form that has been approved by the Institutional Review Board (IRB) by the parent or legally authorized representative.
4) Signed and dated informed assent form from the subject if required by the IRB.
5) Able to attend scheduled visits at Visit 1 and Visit 2 and able to comply with all trial procedures. Subjects will be invited to participate in the long-term immunogenicity follow-up study but a commitment to participate in the long-term is not required as an inclusion criterion.
6) Documented vaccination history of 4 previous doses of DAPTACEL (consisting of 3 infant doses in the first year of life and a 4th dose in the 2nd year of life) or 4 previous doses of Pentacel and Prevnar®.

E.4

Principal exclusion criteria

1) Participation in another clinical trial in the 4 weeks preceding the trial vaccination.
2) Planned participation in another clinical trial during the original trial period.
3) Congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy.
4) Systemic hypersensitivity to any of the vaccine components or history of life-threatening reaction to the trial vaccine or a vaccine containing the same substances.
5) Chronic illness at a stage that could interfere with trial conduct or completion.
6) Blood or blood-derived products received in the past 3 months.
7) Receipt of any other vaccine within 30 days prior to study vaccination, or planning to receive another vaccine within 30 days before the Visit 2 blood draw (with the exception of the annual influenza vaccine).
8) History of diphtheria, tetanus or pertussis infection (confirmed either serologically or microbiologically).
9)Thrombocytopenia or bleeding disorder contraindicating IM vaccination.

E.5 End points

E.5.1

Primary end point(s)

1) For diphtheria and tetanus antibodies, seroprotection rates, serothreshold rates and booster response rates will be assessed as follows:
- Percent of subjects with anti-diphtheria and anti-tetanus antibody concentrations pre- (Day 0), post-vaccination (Day 30) ³ 0.1 IU/mL (for seroprotection) and ³ 1.0 IU/mL (for serothreshold)
- Percent of subjects demonstrating a booster response postvaccination (Day 30) for anti-diphtheria and anti-tetanus antibody concentrations. The criterion for demonstrating a booster response is as follows:
- Subjects whose pre-vaccination antibody concentrations are < 0.1 IU/mL will demonstrate the booster response if they have postvaccination levels ≥ 0.4 IU/mL
- Subjects whose pre-vaccination antibody concentrations are ≥ 0.1 to < 2 IU/mL will demonstrate the booster response if they have a 4-fold rise rate (i.e., post-/pre-vaccination ≥ 4)
- Subjects whose pre-vaccination antibody concentrations are ≥ 2.0 IU/mL will demonstrate the booster response if they have a 2-fold response (i.e., post-/pre-vaccination ≥ 2)
2) For each anti-pertussis antibody (PT, FHA, PRN and FIM) the percent of subjects demonstrating the booster response and the GMTs will be assessed as follows:
- The booster response rate partially adjusts for individual and population differences in pre-vaccination antibody concentrations. The criterion for demonstrating a booster response is as follows:
- Subjects whose pre-vaccination antibody concentrations are less than the Lower Limit of Quantitation (< LLOQ) for each anti-pertussis (PT, FHA, PRN and FIM) antibody, will demonstrate the booster response if they have post-vaccination levels ≥ 4xLLOQ
- Subjects whose pre-vaccination antibody concentrations are ≥ LLOQ but < 4xLLOQ, will demonstrate the booster response if they have a 4-fold rise rate (i.e., post-/pre-vaccination ≥ 4)
- Subjects whose pre-vaccination antibody concentrations are ≥ 4xLLOQ, will demonstrate the booster response if they have a 2-fold response (i.e., post-/pre-vaccination ≥ 2) Pre- and post-vaccination GMTs will be assesed.

E.5.1.1

Timepoint(s) of evaluation of this end point

1 vaccination visit. Each subject received 3/4* injections
Day 0 Visit 1 Group A:Tdap (left arm)+polio, MMR, & varicella vaccines (right arm) Day 0; Visit 1 Group B:DTaP (left arm; +polio, MMR, & varicella vaccines (right arm) Day 0; Visit 1 MMR & varicella vaccines were given either as 1 dose MMRV or as 2 separate doses 2 blood samples (BL1&BL2) totaling approx. 10 mL were collected from each subject: BL1 (5mL) collected prior to Visit 1 vaccination (Day 0). BL2 (5mL) collected on Visit 2 (Day 30). Each subject was followed for safety up to 180 days after vaccination initiated at 3, 8, 30, & 180 days after vaccination. Study duration was approx. 6 months. Subjects in the LTI follow-up, up to 2 blood samples (BL3 & BL4) collected from each subject up to 5 yrs after Visit 1 vaccination.

E.5.2

Secondary end point(s)

Immunogenicity
Antibody concentrations against pertussis antigens (PT, FHA, PRN and FIM) as measured by 4-fold rise rates (i.e., post-/pre-vaccination ≥ 4) were assessed

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable.

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

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

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

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

Canada

United States

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 years

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:

1045

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)

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

1045

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

Yes

F.3.3.1

Women of childbearing potential not using contraception