Clinical Trials Register

Summary
EudraCT Number:	2020-003466-39
Sponsor's Protocol Code Number:	Protocol_MAMA_studie_22/05/2018
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:	2021-07-29
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

2020-003466-39

A.3

Full title of the trial

Pertussis immunization during pregnancy: assessment of the role of maternal antibodies on immune responses in term and preterm infants (the MAMA study)

A.3.1

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

TDaP (Tetanus, Diphtheria, acellular Pertussis) immunization during pregnancy results in an augmentation of maternal antibodies, which are in turn transferred from the mother to fetus and offer additional protection to the newborn infant during the first months of life. The role of these high maternal antibodies levels on the infant’s immune responses after vaccination will be assessed in term and preterm infants (the MAMA study).

A.3.2

Name or abbreviated title of the trial where available

the MAMA study

A.4.1

Sponsor's protocol code number

Protocol_MAMA_studie_22/05/2018

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	University of Antwerp
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	Sanofi Pasteur
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	University of Antwerp
B.5.2	Functional name of contact point	Kirsten Maertens
B.5.3	Address:
B.5.3.1	Street Address	Universiteitsplein 1
B.5.3.2	Town/ city	Wilrijk
B.5.3.3	Post code	2610
B.5.3.4	Country	Belgium
B.5.6	E-mail	Kirsten.maertens@uantwerpen.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	Tetravac
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur
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	Tetravac
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	Yes
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)	No
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	Hexyon
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur
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	Hexyon
D.3.4	Pharmaceutical form	Suspension for injection
D.3.4.1	Specific paediatric formulation	Yes
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)	No
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: 3
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	Boostrix
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline Biologicals
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	Boostrix
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)	No
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

The effect of pertussis vaccination during pregnancy on the immune response after infant and childhood vaccinations in term and preterm infants.

E.1.1.1

Medical condition in easily understood language

Investigating the effect of in-pregnancy vaccination against pertussis (a highly contagious respiratory disease) on the infants immune response after vaccination.

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

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 effect of vaccination during pregnancy on the amount of pertussis specific antibodies (Pertussis Toxin (anti-PT), Filamentous Haemagglutinin (anti-FHA) and pertactin (anti-PRN)) in both women and offspring will be measured in 4 different cohorts: vaccinated and non-vaccinated women with either term and preterm born infants.

E.2.2

Secondary objectives of the trial

What is the functionality of the IgG against Pertussis Toxin (anti-PT), Filamentous Haemagglutinin (anti-FHA) and pertactin (anti-PRN), in women at delivery, in children at birth and before and after vaccination.

What are the concentrations of SIgA and IgG (both specific against pertussis toxin antigen as well as total IgA and IgG) in breast milk.

What type of T cell response, Th1, Th2 and Th17 directed, is present before and after pertussis vaccination.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

If yes give the full title, date and version of each sub-study and their related objectives:
Pertussis immunization during pregnancy: assessment of the role of maternal antibodies on immune responses in term and preterm infants (the MAMA study): long-term effects on children’s immunity.

Start: 06/2019

Objectives:

What are the concentrations of IgG against Pertussis Toxin (anti-PT), Filamentous Haemagglutinin (anti-FHA) and pertactin (anti-PRN) between the fourth and fifth booster vaccine (at 3 years of age), before the fifth pertussis vaccine booster (at 5 years of age) and one month after the fifth pertussis vaccine booster (around the age of 6 year) in a term and preterm born infant population.

What is the functionality of the IgG antibodies between the fourth and fifth booster vaccine (at 3 years of age), before the fifth pertussis vaccine booster (at 5 years of age) and one month after the fifth pertussis vaccine booster (around the age of 6 year) in a term and preterm born infant population.

What type of T cell response, Th1, Th2 and Th17 directed, is present before the fifth pertussis vaccine booster (at 5 years of age) and one month after the fifth pertussis vaccine booster (around the age of 6 year) in a term and preterm born infant population.

E.3

Principal inclusion criteria

I. Female population older than 18 Years
II. Women in the vaccinated cohort: received a pertussis containing vaccine (paper-proven) during pregnancy within the present Belgian recommendation. They will not receive the vaccine within the study.
III. Women in the unvaccinated cohorts: received no pertussis containing vaccine at least 5 year before study entrance, but can receive a vaccine in postpartal period. The cocoon strategy has to be taken into account in the analysis of breast milk samples.
IV. Intend to be available for follow-up visits and phone call access through 16 months following delivery.
V. Willing to have infant immunized with hexavalent vaccine according to the general Belgian schedule.
VI. Influenza vaccination during pregnancy is allowed.

E.4

Principal exclusion criteria

Exclusion criteria for women (limited since premature delivery is usually the result of serious events):
Pregnant women who meet any exclusion criteria at baseline will be excluded from the study.
I. Significant mental illness (e.g. schizophrenia, psychosis, major depression)
II. Serious underlying immunological condition (e.g. immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection)
III. Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk.
IV. Receipt of a blood product or experimental medicine within 4 weeks prior to delivery or prior to blood sampling. Exclusion for 1 time point is possible after blood transfusion, with reboot of the study 1 month after transfusion.
Exclusion criteria for children:
I. No signed informed consent from both parents.
II. Severe reactions to any vaccine.
III. Serious underlying medical condition (e.g., genetic disorder (eg Down syndrome), immunosuppressive disease or therapy, human immunodeficiency virus (HIV) infection, lung/heart disease, liver/kidney disease, chronic or recurrent infections).
IV. Children suffering from primary humoral immune disorders (B cell related): severe X linked agammaglobulinaemia, CVID (Common variable immunodeficiency, late onset agammaglobulnaemia) and SAD (specific antibody deficiency); suffering from primary cellular immune deficiencies (T cell related): SCID (Severe combined immune deficiency syndrome), CID, hyper IGM syndrome, di George's syndrome and others;
suffering from disorders in phagocytosis and chemotaxis (CGD, Schwach Diamond syndrome) and disorders from the complement cascade.
V. In addition, children on immunodepressive medication and with hemato-oncologic disorders will be excluded. All these children can receive the inactivated pertussis vaccines, but will respond different from the normal population to vaccination.
VI. Anything in the opinion of the investigator that would prevent volunteers from completing the study or put the volunteer at risk.
VII. Receipt of a blood product 1 month prior to blood sampling. Exclusion for 1 time point is possible after blood transfusion, with reboot of the study 1 month after transfusion.

E.5 End points

E.5.1

Primary end point(s)

To assess whether there is a difference in humoral immune response in the presence of vaccine-induced maternal antibodies in term and preterm infants before and after vaccination.

E.5.1.1

Timepoint(s) of evaluation of this end point

01/2015: Start practical organization, ethical approval of the study and recruiting willing participants. After informed consent is obtained both the mother and her newborn infant are followed-up.
7/2017: End of recruitment. Conduct of mother and infant follow-up. 01/2019: Finalizing mother-infant follow-up, humoral immunity testing.
09/2020: Statistical analysis of the results. Deliver papers for peer review and formulate possible updated recommendations.

E.5.2

Secondary end point(s)

To assess whether there is a difference in the functionality of the humoral and cellular immune response in the presence of vaccine- induced maternal antibodies in term and preterm infants before and after vaccination. Differences in breastmilk composition after term and preterm delivery in the presence of maternal antibodies will be determined.

E.5.2.1

Timepoint(s) of evaluation of this end point

01/2015: Start practical organization, ethical approval of the study and recruiting willing participants. After informed consent is obtained both the mother and her newborn infant are followed-up. Cellular immunity testing performed on fresh blood samples.
7/2017: End of recruitment. Conduct of mother and infant follow-up and cellular immunity testing.
01/2019: Finalizing mother-infant follow-up and cellular immunity testing. Start breastmilk antibody testing.
10/2020: Statistical analysis of the results. Deliver papers for peer review and formulate possible updated recommendations.
05/2021 Humoral functionality testing
12/2021: Statistical analysis of the humoral functionality results. Deliver papers for peer review and formulate possible updated recommendations.

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

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

Yes

E.8.2.3.1

Comparator description

Mothers who did not receive a pertussis containing vaccine during pregnancy or in the last 10 years

E.8.2.4

Number of treatment arms in the trial

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 01/2020. The LVLS is dependent on the last vaccination visit of the last recruited mother-infant pair, which is performed by local E.8.9 healthcare providers as part of the governments recommendations

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

E.8.9.2

In all countries concerned by the trial years

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:

300

F.1.1.1

In Utero

Yes

F.1.1.1.1

Number of subjects for this age range:

300

F.1.1.2

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

Yes

F.1.1.2.1

Number of subjects for this age range:

150

F.1.1.3

Newborns (0-27 days)

Yes

F.1.1.3.1

Number of subjects for this age range:

300

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

300

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

300

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:

300

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

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

Yes

F.3.3.4

Nursing women

Yes

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

This study includes newborn infants and their mothers. Mother-infant pairs were included after both term and preterm delivery and are followed-up till the infant receives its first booster vaccination at +/-15 months of age.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

300

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

2021-09-06

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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