Clinical Trials Register

Summary
EudraCT Number:	2022-002697-80
Sponsor's Protocol Code Number:	MADI-02
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:
Date on which this record was first entered in the EudraCT database:	2022-09-12
Trial 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
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2022-002697-80

A.3

Full title of the trial

Maternal determinants of infant immunity to pertussis

A.3.1

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

Immunization during pregnancy is an efficient and safe approach to provide protection against infectious pathogens affecting the young infant. The objective is to identify the determinants of antibody-mediated immunity in infants born to mothers immunized during pregnancy. A systems biology approaches will be used to delineate pre-vaccination and post-vaccination cellular and molecular correlates of the immune response to pertussis immunization in peripheral blood and in breastmilk.

A.3.2

Name or abbreviated title of the trial where available

MADI-02

A.4.1

Sponsor's protocol code number

MADI-02

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	Université Libre de Bruxelles
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	National Institute of Health
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	CHU Saint Pierre
B.5.2	Functional name of contact point	Dr Tessa Goetghebuer
B.5.3	Address:
B.5.3.1	Street Address	Rue Haute, 322
B.5.3.2	Town/ city	Bruxelles
B.5.3.3	Post code	1000
B.5.3.4	Country	Belgium
B.5.4	Telephone number	+3225354369
B.5.5	Fax number	+3225354171
B.5.6	E-mail	tessa.goetghebuer@stpierre-bru.be

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	Yes
D.2.1.1.1	Trade name	TRIAXIS ®
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Belgium
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	Triaxis®
D.3.2	Product code	J07AJ52
D.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PURIFIED DIPHTHERIA TOXOID
D.3.9.2	Current sponsor code	D
D.3.9.3	Other descriptive name	DIPHTHERIA TOXOID
D.3.9.4	EV Substance Code	SUB12489MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PURIFIED TETANUS TOXOID
D.3.9.2	Current sponsor code	T
D.3.9.3	Other descriptive name	TETANUS TOXOID
D.3.9.4	EV Substance Code	SUB12608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	up to
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PERTUSSIS TOXOID
D.3.9.2	Current sponsor code	P
D.3.9.3	Other descriptive name	PERTUSSIS TOXOID
D.3.9.4	EV Substance Code	SUB14817MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	2.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PERTUSSIS FILAMENTOUS HAEMAGGLUTININ
D.3.9.2	Current sponsor code	FHA
D.3.9.3	Other descriptive name	FILAMENTOUS HAEMAGGLUTININ
D.3.9.4	EV Substance Code	SUB38509
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	PRN
D.3.9.3	Other descriptive name	PERTUSSIS PERTACTIN
D.3.9.4	EV Substance Code	SUB20527
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	3
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	FIM 2
D.3.9.3	Other descriptive name	BORDETELLA PERTUSSIS FIMBRIAE TYPE 2 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB181465
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	NA
D.3.9.2	Current sponsor code	FIM 3
D.3.9.3	Other descriptive name	BORDETELLA PERTUSSIS FIMBRIAE TYPE 3 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB181466
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	5
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.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	Vaxelis ®
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur Europe
D.2.1.2	Country which granted the Marketing Authorisation	Belgium
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	Vaxelis ®
D.3.2	Product code	J07CA09
D.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PURIFIED DIPHTERIA TOXOID
D.3.9.2	Current sponsor code	D
D.3.9.3	Other descriptive name	DIPHTHERIA TOXOID
D.3.9.4	EV Substance Code	SUB12489MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	20
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PURIFIED TETANUS TOXOID
D.3.9.2	Current sponsor code	T
D.3.9.3	Other descriptive name	TETANUS TOXOID
D.3.9.4	EV Substance Code	SUB12608MIG
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PERTUSSIS TOXOID
D.3.9.2	Current sponsor code	P
D.3.9.3	Other descriptive name	PERTUSSIS TOXOID
D.3.9.4	EV Substance Code	SUB14817MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PERTUSSIS FILAMENTOUS HAEMAGGLUTININ
D.3.9.2	Current sponsor code	FHA
D.3.9.3	Other descriptive name	FILAMENTOUS HAEMAGGLUTININ
D.3.9.4	EV Substance Code	SUB38509
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POLIOVIRUS (INACTIVATED) TYPE 1
D.3.9.2	Current sponsor code	ipv
D.3.9.3	Other descriptive name	POLIOVIRUS (INACTIVATED) TYPE 1 (MAHONEY STRAIN) PRODUCED ON VERO CELLS
D.3.9.4	EV Substance Code	SUB25669
D.3.10	Strength
D.3.10.1	Concentration unit	DAgU D antigen unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	40
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POLIOVIRUS (INACTIVATED) TYPE 2
D.3.9.2	Current sponsor code	IPV
D.3.9.3	Other descriptive name	POLIOVIRUS (INACTIVATED) TYPE 2 (MEF-1 STRAIN) PRODUCED ON VERO CELLS
D.3.9.4	EV Substance Code	SUB25670
D.3.10	Strength
D.3.10.1	Concentration unit	DAgU D antigen unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	8
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	POLIOVIRUS (INACTIVATED) TYPE 3
D.3.9.2	Current sponsor code	IPV
D.3.9.3	Other descriptive name	POLIOVIRUS (INACTIVATED) TYPE 3 (SAUKETT STRAIN) PRODUCED ON VERO CELLS
D.3.9.4	EV Substance Code	SUB25671
D.3.10	Strength
D.3.10.1	Concentration unit	DAgU D antigen unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	32
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HEPATITIS B (rDNA)
D.3.9.2	Current sponsor code	Hep B
D.3.9.3	Other descriptive name	HEPATITIS B SURFACE ANTIGEN
D.3.9.4	EV Substance Code	SUB14083MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HAEMOPHILUS TYPE B CONJUGATE
D.3.9.2	Current sponsor code	Hib
D.3.9.3	Other descriptive name	HAEMOPHILUS TYPE B CONJUGATE VACCINE (TETANUS TOXOID CONJUGATE)
D.3.9.4	EV Substance Code	SUB14050MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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	Yes
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

Vaccination against whooping cough in non-pregnant women and in pregnant women.
Vaccination against whooping cough in the Belgian vaccination program in children from 2 months of age

E.1.1.1

Medical condition in easily understood language

Vaccination against whooping cough in non-pregnant women and in pregnant women.
Vaccination against whooping cough in the Belgian vaccination program in children from 2 months of age

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

The overall objective of the project is to identify the determinants of antibody-mediated immunity to pertussis in infants born to mothers immunised during pregnancy

E.2.2

Secondary objectives of the trial

1. Determine the impact of pregnancy on the quality of antibody response to pertussis immunization and identify immune predictors of vaccine responses in pregnant and non-pregnant women;
2. Identify immune predictors of the transfer of maternal antibodies to the newborn and the presence of antibody in breastmilk following pertussis immunization during pregnancy
3. Determine the impact of maternal antibodies on the quality of antibody response to pertussis immunization in infants born to mothers immunised compared to infants born to mothers not immunized during pregnancy and identify immune predictors of vaccine responses in the first months of life.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Eligibility of pregnant and non-pregnant women
- Age between 18 and 45 years
- Eligible for Tdap vaccination
- Last Pertussis vaccination < 12 months ago
- Consent form signed

2. Eligibility of infants:
- Infants of 2 months (+- 1 week) of age (boys and girls)
- Born after 35 weeks of gestation
- Birthweight above 2.5 kg
- Consent form signed by the parents

E.4

Principal exclusion criteria

1. Exclusion criteria (non-pregnant women and pregnant women):
- Inability to understand the nature and extent of the study and the procedures required
- Grade III/IV anemia,
- Acute infection at the time of immunization
- Chronic infections such as HBV, HCV or HIV infection, acute toxoplasmosis
- Current or recent use of immunosuppressive drugs
- Active neoplasia
- Other vaccination at the same time as pertussis vaccination
Specific to pregnant women:
- Risk of premature delivery or intrauterine growth retardation
- Twin or triplet pregnancies

2. Exclusion criteria (infants):

- Severe neonatal distress
- Serious congenital abnormalities or congenital infection.

E.5 End points

E.5.1

Primary end point(s)

Magnitude and quality of the adaptive immune responses to Tdap immunization.
The magnitude and quality of antibody responses to pertussis vaccine will be analysed using an innovative approach pioneered by Galit Alter and Margaret Ackerman, partners on the project, named systems serology including:
- Biophysical antibody profiling
- Functional antibody profiling
- Antibody and B cell repertoire analysis
- T lymphocyte response to Tdap immunization

Determinants of antibody responses to pertussis immunization:
Identification of determinants of vaccine responses in pregnant women and infants will be based on a systems biology approach involving the analysis of peripheral blood cell frequencies, phenotype and transcriptome and of plasma proteome

E.5.1.1

Timepoint(s) of evaluation of this end point

In non-pregnant women:
- The day of vaccination - Day 1 after vaccination - Day 7 after vaccination - Day 28 after vaccination - 5 months after vaccination
In pregnant women:
- The day of vaccination - Day 1 after vaccination - Day 7 after vaccination - Day 28 after vaccination - At delivery - 6 weeks and 12 weeks after delivery
In newborns: - cord blood
In infants:
- The day of first vaccination (2 months) - Day 1 after the first vaccine dose - the day of the third vaccination and Day 28 after the third vaccine dose

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

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

E.6.5

Efficacy

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity
Molecular profile

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

Yes

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

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

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

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:

120

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)

Yes

F.1.1.3.1

Number of subjects for this age range:

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

120

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

120

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

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2022-09-12.

Yes

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

80 infants of mothers vaccinated with Tdap (enrolled in the study or not)
40 infants born to mothers who were not vaccinated during pregnancy will be recruited after birth

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

240

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

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2022-10-12

Ethics Committee Opinion of the trial application

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

P. End of Trial
P.	End of Trial Status

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