Clinical Trials Register

Summary
EudraCT Number:	2014-001538-28
Sponsor's Protocol Code Number:	P130930
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-12-03
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

2014-001538-28

A.3

Full title of the trial

Search for the measles vaccine virus excretion in breast milk of breastfeeding women after postpartum vaccination with a combined measles-mumps-rubella (MMR) vaccine

Recherche de l’excrétion du virus vaccinal de la rougeole dans le lait de femmes vaccinées en postpartum par un vaccin trivalent Rougeole-Oreillons-Rubéole (ROR)

A.3.1

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

To look for the measles vaccine in breast milk of breastfeading women, vaccinated after delivery by measles-mumps-rubella (MMR) vaccine

Recherche du vaccin de la rougeole dans le lait de femmes allaitantes, vaccinées après l'accouchement par un vaccin Rougeole-Oreillons-Rubéole (ROR)

A.3.2

Name or abbreviated title of the trial where available

BREMEAVAC

A.4.1

Sponsor's protocol code number

P130930

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	ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS (AP-HP)
B.1.3.4	Country	France
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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	PRIORIX
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline
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	PRIORIX
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	virus vivants atténués Rougeole-Oreillons-Rubéole
D.3.10	Strength
D.3.10.1	Concentration unit	ml millilitre(s)
D.3.10.2	Concentration type	equal
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	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
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

Pregnant women, rubella negatives and measles negatives

Femmes enceintes rubéole négative et rougeole négative

E.1.1.1

Medical condition in easily understood language

Pregnant women, rubella negatives and measles negatives

Femmes enceintes rubéole négative et rougeole négative

E.1.1.2

Therapeutic area

Body processes [G] - Biological Phenomena [G16]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
E.1.2	Level	LLT
E.1.2	Classification code	10070264
E.1.2	Term	Measles virus test positive
E.1.2	System Organ Class	100000004848

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Detection of measles vaccine strain excretion in breast milk of breastfeeding women, with negative rubella and measles serologies, after postpartum vaccination with a combined measles-mumps-rubella (MMR) vaccine

Détection de l'excrétion de la souche vaccinale du virus de la rougeole dans le lait de femmes allaitantes ayant des sérologies rougeole et rubéole négatives, après vaccination en postpartum par un vaccin trivalent Rougeole-Oreillons-Rubéole (ROR)

E.2.2

Secondary objectives of the trial

1/ Evaluate the clinical impact of MMR vaccination in breastfeeding infant.
2/ Evaluate the immunological impact of MMR vaccination in breastfeeding infant.
3/ Detection of measles vaccine strain excretion in urine of breastfeeding women

In case of detection of measles vaccine virus strain excretion in breast milk:
4/ Quantification of the measles vaccine virus strain in breast milk
5/ Evaluate the infectious activity of the measles vaccine virus in breast milk

1/ Evaluer l'impact clinique de la vaccination ROR sur l'enfant allaité.
2/ Evaluer l'impact immunologique de la vaccination ROR sur l'enfant allaité.
3/ Détecter l'excrétion de la souche vaccinale du virus de la rougeole dans les urines des femmes allaitantes
En cas de détection de l'excrétion de la souche vaccinale du virus de la rougeole dans le lait:
4/ Quantification de la souche vaccinale du virus de la rougeole dans le lait maternel
5/ Evaluation de l'infectiosité de la souche vaccinale du virus de la rougeole dans le lait maternel

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Women:
1. Pregnant woman
2. Age ≥ 18 years
3. Planning to breastfeed her infant (mixed feeding is allowed)
4. Having a negative serology for rubella during pregnancy
5. Negative serology for measles based on the result from local laboratory
6. Affiliated to a social security regimen (applicable only for France)

Infants:
1. Informed consent form signed by the person(s) holding parental authority.
2. Born after 36LPM (≥36LPM)

Mère:
1.Femme enceinte
2.Âgée de >ou = 18 ans
3.Planifiant d'allaiter son enfant (l'allaitement mixte est autorisé)
4.Ayant eu une sérologie rubéole négative durant sa grossesse
5.Sérologie rougeole négative basée sur le résultat d'une analyse réalisée dans le laboratoire de routine de l'hôpital
6.Affiliée à un régime de sécurité social (applicable seulement pour la France)

Enfant:
1.Formulaire de consentement éclairé signé par la ou les personnes détenant l'autorité parentale.
2.Nouveau-né né à terme (>ou =37SA)

E.4

Principal exclusion criteria

Women:
1. Woman having a multiple pregnancy
2. Woman planning to get pregnant in the month following the 2nd vaccination
3. Woman with known or suspected HIV infection
4. Woman with known or suspected immunodeficiency
5. Woman with family history of hereditary immune deficiency
6. Woman not mastering enough the reading / understanding of the French language to be able to consent to participate to the study
7. Woman incapable to follow the procedures of the study and to respect study visits for the whole period of the study.
8. Woman with contraindication for MMR vaccination:
o Scarce hereditary problems of fructose intolerance
o Woman with history of hypersensitivity to the active substances or to any of the excipients of the vaccine
o Administration of human gammaglobulins in the past 3 to 11 months depending on the dose of human globulins administered (except for Rhophylac®)
o Blood transfusion in the past 3 months
o Acute severe febrile illness within 7 days prior to injection
9. Woman under systemic corticosteroids (prednisone, or equivalent ≥10 mg/day) within the previous 15 days or planning to use corticosteroids (i.e. prednisone, or equivalent ≥10 mg/day) during the 15 days following vaccination
10. Woman under immunosuppressive therapy within the previous 3 months before vaccination or planning to use immunosuppressive therapy during the 15 days following vaccination
11. Woman participating in any clinical trial with another investigational product 28 days prior to visit V0 or intent to participate in another clinical study with another investigational product at any time during the conduct of this study
12. Any other reason which, according to the investigator, may interfere with the evaluation of the study objectives
13. Woman with documented history of measles vaccination (1 or 2 doses) and/or history of documented measles

Infants:
1. Blood draw is contraindicated or cannot be performed
2. Infant with family history of hereditary immune deficiency and/or suspected or confirmed immunodeficiency
3. Any other reason which, according to the investigator, may interfere with the evaluation of the study objectives

Mère:
1.Femme ayant une grossesse multiple
2.Femme planifiant de tomber enceinte dans le mois suivant la 2ième vaccination
3.Femme ayant une infection VIH connue ou suspectée
4.Femme ayant une immunodéficience connue ou suspectée
5.Femme ayant des antécédents familiaux de déficit immunitaire héréditaire
6.Femme ne maîtrisant pas assez la lecture et la compréhension de la langue française pour être capable de consentir de participer à l'étude.
7.Femme incapable de suivre les procédures de l'étude et de respecter les visites durant toute la période de l'étude.
8.Femme ayant une contre-indication pour la vaccination ROR :
o Problème héréditaire rare d'intolérance au fructose
o Femme ayant des antécédents d'hypersensibilité aux substances actives ou à un des excipients composant le vaccin.
o Administration de gammaglobulines humaines dans les 3 à 11 derniers mois selon la dose de globulines humaines administrée (excepté pour Rhophylac)
o Transfusion sanguine dans les trois derniers mois
o Maladie fébrile sévère aiguë dans les 7 jours précédant l'injection.
9.Femme sous corticostéroïde systémique (prednisone ou équivalent ?10 mg/jour) dans les 15 jours précédant ou planifiant de prendre des corticostéroïdes (i.e. prednisone ou équivalent ?10 mg/jour) pendant les 15 jours suivant la vaccination.
10.Femme sous traitement immunosuppresseur durant les trois mois précédant la vaccination ou planifiant de suivre un traitement immunosuppresseur dans les 15 jours suivant la vaccination.
11.Femme participant à un essai clinique avec un autre produit expérimental dans les 28 jours précédant la visite V0, ou ayant l'intention de participer à un autre essai clinique avec un autre produit expérimental à tout moment au cours de la réalisation de cette étude.
12.Tout autre raison qui, selon l'investigateur, pourrait interférer avec l'évaluation des objectifs de l'étude.
13. Femmes ayant des antécédents documentés de vaccination rougeole (1 ou 2 doses) et/ou antécédent de rougeole documenté

Enfant:
1.Prélèvement sanguin contre-indiqué ou ne pouvant être réalisé
2.Enfant ayant des antécédents familiaux de déficit immunitaire héréditaire et/ou une immunodéficience connue ou suspectée
3.Tout autre raison qui, selon l'investigateur, pourrait interférer avec l'évaluation des objectifs de l'étude.

E.5 End points

E.5.1

Primary end point(s)

Number of subject with positive RT-PCR for measles vaccine virus strain in breast milk for at least one sample from day 7, 11 and 14. RT PCR will be considered positive if the measurements exceed the limit of detection of 10 copies of genome per reaction

Nombre de sujets ayant une RT-PCR positive pour la souche vaccinale du virus de la rougeole dans au moins un échantillon de lait maternel. recueilli à J7, J11 et J14. La RT-PCR sera considérée positive, si la mesure dépasse la limite de détection de 10 copies de génome de la souche vaccinale du virus de la rougeole par réaction.

E.5.1.1

Timepoint(s) of evaluation of this end point

V0 (first day of vaccine administration), V0 + 7 days, V0 + 11 days, V0 + 14 days

E.5.2

Secondary end point(s)

1/
a) Number of infant with reported clinical symptoms of measles:
- at week 8 (V1)
- from data reported in the infant diary card between visit V0 and visit V1.
b) Number of woman with reported clinical symptoms of measles.
2/ Number of infant with positive measles serology (IgM) at week 8 (V1).
3/ Number of woman with positive RT-PCR for measles vaccine virus strain in urine, in at least one of the following samples: day 7, 11 and 14.

In case of detection of measles vaccine virus strain excretion in breast milk :
4/ Measles vaccine strain will be quantitatively measured in breast milk by RT PCR.
5/ Measles vaccine virus strain multiplication will be measured in cell culture : all samples in which a RT-PCR signal is detected will be submitted to an in vitro infectivity assay. A result is considered as positive when at least one positive fluorescent cell is detected.

E.5.2.1

Timepoint(s) of evaluation of this end point

V0 (first day of vaccine administration), V0 + 7 days, V0 + 11 days, V0 + 14 days, V0 + 8 weeks

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

E.6.5

Efficacy

E.6.6

Pharmacokinetic

Yes

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

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

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in 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

Information not present in EudraCT

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:

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)

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:

F.1.3

Elderly (>=65 years)

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

250

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

2015-12-24

Ethics Committee Opinion of the trial application

Withdrawn

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2016-04-07

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-05-03

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