Clinical Trials Register

Summary
EudraCT Number:	2013-003090-98
Sponsor's Protocol Code Number:	IIV-266
National Competent Authority:	Netherlands - Competent Authority
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-09-09
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
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

Netherlands - Competent Authority

A.2

EudraCT number

2013-003090-98

A.3

Full title of the trial

Maternal pertussis (Tdap) vaccination and its effects on the immune response of the newborn up to 12 months of age.

Maternale Kinkhoest vaccinatie en de effecten hiervan op de immuunrespons van baby's t/m 12 maanden

A.3.1

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

The effects of Pertussis vaccination of pregnant woman on the production of antibody's in the blood of newborns up to 12 months of age

De effecten van vaccinatie van de moeder tegen kinkhoest tijdens de zwangerschap op de bescherming van de baby t/m 12 maanden

A.3.2

Name or abbreviated title of the trial where available

MIKI

Maternale Immunisatie Kinkhoest= MIKI

A.4.1

Sponsor's protocol code number

IIV-266

A.5.4

Other Identifiers

Name:	ABR	Number:	NL-45652.000.13
Name:	NTR	Number:	16010

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	RIVM
B.1.3.4	Country	Netherlands
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	Ministry of Health, Welfare and Sport (VWS).
B.4.2	Country	Netherlands
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	RIVM
B.5.2	Functional name of contact point	Information MIKI study
B.5.3	Address:
B.5.3.1	Street Address	Antonie van Leeuwenhoeklaan 9
B.5.3.2	Town/ city	Bilthoven
B.5.3.3	Post code	3720 MA
B.5.3.4	Country	Netherlands
B.5.6	E-mail	MIKI@rivm.nl

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	Boostrix
D.2.1.1.2	Name of the Marketing Authorisation holder	RVG 35121
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.4	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.3.11 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	Synflorix
D.2.1.1.2	Name of the Marketing Authorisation holder	EU/1/09/508/001
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	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)	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: 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	Infanrix hexa
D.2.1.1.2	Name of the Marketing Authorisation holder	EU/1/00/152/001
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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.3.4	Pharmaceutical form	Powder and suspension for 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)	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

Healthy pregnant woman < 20 months pregnant

Gezonde zwangere vrouwen < 20 maanden zwanger

E.1.1.1

Medical condition in easily understood language

Healthy pregnant woman < 20 months pregnant

Gezonde zwangere vrouwen < 20 maanden zwanger

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

To evaluate superiority of IgG antibody levels against pertussis toxin (Ptx), present in the acellular vaccines, in infants at the age of 3 months of mothers having received a pertussis vaccine during pregnancy versus infants of mothers who have been vaccinated postpartum.

Het verschil bepalen van het de IgG antistof levels tegen Pertussis toxine tussen baby's van 3 maanden waarvan de moeders wel respectievelijk niet gevaccineerd zijn tijdens de zwangerschap

E.2.2

Secondary objectives of the trial

Determine effect of maternal antibodies on infant's immune response to active immunization with pertussis (PT) vaccine and on routine DTaP-IPV-Hib-Hep and PCV10 vaccination
Compare serum IgA levels against PT antigens of infants of both groups
Determine rate of maternal antibody decline in infants between birth and at 2 and 3 months of age before first PT vaccination
Determine levels of PT IgG antibodies transferred from mother to neonate
Assess cellular immune response (Pl B cells and Mem B cells) before and 7-9 days after the booster at 11-months of age
Safety evaluation after Boostrix vaccination during pregnancy
Assess PT IgG antibody levels in mothers of both groups, pre-vaccination, at delivery and 6, and 12 months post-delivery;
Compare infants’ pain response and maternal attitude to infant blood collection by heel stick and venipuncture.
Compare IgA levels against PT antigens in breast milk of mothers of both groups at 7-10 days, 3 months and 6 months after delivery

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Pregnant women 18-40 years of age
• Women with a low risk of pregnancy complications as assessed by a midwife/obstetrician/gynaecologist with a normal 20 weeks ultrasound of the fetus
• Women who are willing to adhere to the protocol and perform all planned visits and sample collections for themselves and their newborn child
• Parents have to be willing to have their infant vaccinated with the hexavalent (DaKTP-Hib-Hep) vaccine at 3, 5 and 11 months of age according to the described procedures
• Presence of a signed informed consent

E.4

Principal exclusion criteria

Pregnant Woman:
History of having received a pertussis vaccination in the past 5 years
- History of having received a TD containing vaccine in the past 2 years
- Known or suspected serious underlying condition that can interfere with the results of the study such as but not limited to cancer, autoimmune disease, immunodeficiency, seizure disorder or significant psychiatric illness
- Receipt of any high-dose (≥ 20 mg of prednisone daily or equivalent) daily corticosteroids (inhaled steroids are acceptable) within 2 weeks of study entry
- Receipt of other immune modulating medication, for instance biologicals
- Receipt of blood products or immunoglobulin, within three months of study entry (Rhesus negative women who receive antirhesus (D)- immunoglobuline will not be excluded from the trial)
- Presence of bleeding disorder
- Having experienced a previous severe adverse reaction to any vaccine
- Receipt of any vaccine(s) within 2 weeks of study vaccine (except influenza vaccine which may be given concomitantly)
- History of febrile illness (>38.0°C orally) within the past 72 hours (immunization may be deferred)

Exclusion criteria for newborns of participating mothers:
• Serious underlying medical condition that can interfere with the results of the study
• Premature infants born before 37 weeks gestational age

E.5 End points

E.5.1

Primary end point(s)

Difference in infant serum IgG antibody levels against pertussis vaccine antigen Ptx at 3 months of age, before start of infant vaccination, between both groups

E.5.1.1

Timepoint(s) of evaluation of this end point

Infants 2 and 3 months of age, before start of primary vaccination series

E.5.2

Secondary end point(s)

1 Difference between both groups in serum IgG antibody levels against pertussis vaccine antigens Ptx, FHA and Prn of the newborns
2 Difference between both groups in serum IgA antibody levels against pertussis vaccine antigens Ptx, FHA and Prn of the new-borns
3 Difference between both groups in serum IgG antibody levels against tetanus and diphtheria to assess influence of maternal antibodies on the response to D and T vaccination of the new-borns.
4 Difference between both groups in serum IgG antibody levels against other concomitantly administered vaccine components Hib, HepB and pneumococcal serotypes(PCV10) of the new-borns
5 Difference between both groups in serum IgG antibody levels against pertussis vaccine antigens Ptx, FHA and Prn of the mothers,
6 Frequency of local and systemic reactions after Tdap vaccination during pregnancy
7 Frequency of pertussis specific memory B-cells and plasma cells

E.5.2.1

Timepoint(s) of evaluation of this end point

1: infants at birth and at 2,3,6,11 and 12 months of age
2: infants at birth and at 2,3,6,11 and 12 months of age
3: infants at birth and at 2,3,6,11 and 12 months of age
4: infants at birth and at 2,3,6,11 and 12 months of age
5: mothers pre vaccination (group 1), at birth, and at 6 and 12 months after birth
6: mothers up to 5 days after vaccination (Group 1)
7: infants immediately before and 7-9 days after the booster dose at 11 months.

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

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

Effect of maternal Pertussis vaccination on the Immuunrespons of Infants up to 12 months of age

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

Yes

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

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

LSLV

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:

112

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:

112

F.1.1.4

Infants and toddlers (28 days-23 months)

Yes

F.1.1.4.1

Number of subjects for this age range:

112

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:

112

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

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

224

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)

Not Applicable

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

2013-09-05

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-10-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2020-07-22

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