Clinical Trials Register

Summary
EudraCT Number:	2014-001119-38
Sponsor's Protocol Code Number:	116945
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2015-08-28
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Czechia - SUKL

A.2

EudraCT number

2014-001119-38

A.3

Full title of the trial

A Phase IV, observer-blind, randomised, cross-over, placebo-controlled, multicentre study to assess the immunogenicity and safety of a single dose of Boostrix™ in pregnant women.

Fáze IV, pro pozorovatele zaslepená, randomizovaná, zkřížená, placebem kontrolovaná, multicentrická studie hodnotící imunogenitu a bezpečnost vakcíny dTpa, BoostrixTM (263855) společnosti GSK Biologicals u těhotných žen

A.3.1

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

Immunogenicity and safety study of Boostrix in pregnant women.

Studie hodnotící imunogenitu a bezpečnost vakcíny dTpa, BoostrixTM (263855) společnosti GSK Biologicals u těhotných žen

A.3.2

Name or abbreviated title of the trial where available

DTPA (BOOSTRIX)-047

A.4.1

Sponsor's protocol code number

116945

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	GlaxoSmithKline Biologicals
B.1.3.4	Country	Belgium
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	GlaxoSmithKline Biologicals
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Biologicals
B.5.2	Functional name of contact point	Clinical Disclosure Advisor
B.5.3	Address:
B.5.3.1	Street Address	Rue De l'Institut, 89
B.5.3.2	Town/ city	Rixensart
B.5.3.3	Post code	1330
B.5.3.4	Country	Belgium
B.5.4	Telephone number	442089904466
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

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	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.3.4	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	NA
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	2
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	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	20
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	PT
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	8
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	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	8
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	2.5
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.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Suspension for injection in pre-filled syringe
D.8.4	Route of administration of the placebo	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Booster immunisation against diphtheria, tetanus and pertussis diseases. The study population for this study will include pregnant women.

E.1.1.1

Medical condition in easily understood language

Booster immunisation against diphtheria, lockjaw and whopping cough diseases. The study population for this study will include pregnant women.

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10047976
E.1.2	Term	Whooping cough due to bordetella pertussis (B. pertussis)
E.1.2	System Organ Class	100000004862

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10009663
E.1.2	Term	Clostridium tetani infection
E.1.2	System Organ Class	100000004862

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
E.1.2	Level	LLT
E.1.2	Classification code	10054237
E.1.2	Term	Corynebacterium diphtheriae infection
E.1.2	System Organ Class	100000004862

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 demonstrate that the maternally transferred antibodies against pertussis in the dTpa Group is superior to that in the Control Group in terms of geometric mean concentrations (GMCs) for the pertussis antibodies, in the cord blood sample.
Criterion:
The lower limit (LL) of the 95% confidence interval (CI) of the GMC ratio [dTpa Group divided by Control Group] for anti-pertussis toxoid (anti-PT), anti-filamentous haemagglutinin (anti-FHA) and anti-pertactin (anti-PRN) antibodies is ≥ 1.5.

E.2.2

Secondary objectives of the trial

To assess the safety of Boostrix in pregnant women, administered during 27-36 weeks of gestation, in terms of the outcomes of pregnancy, pregnancy-related adverse events of interest/neonate-related events up to two months post-delivery. To assess the immunogenicity of Boostrix administered during pregnancy in terms of seropositivity status for antibodies against pertussis, in the cord blood sample.To assess the immunogenicity of Boostrix in terms of seroprotection/seropositivity status, vaccine response and GMCs for antibodies against diphtheria, tetanus, pertussis, one month post-vaccination.To evaluate the reactogenicity of Boostrix administered during pregnancy and post-delivery in terms of solicited symptoms during the 8-day follow-up period after vaccination.To assess the safety of Boostrix during pregnancy and post-delivery in terms of unsolicited symptoms during the 31-day follow-up period and SAEs during the entire study period.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol (e.g. completion of the diary cards, return for follow-up visits).
• Written informed consent obtained from the subject prior to performing any study specific procedure, as per local regulations.
• A healthy pregnant woman between, and including, 18 and 45 years of age at the time of screening.
• Pregnant subjects at 270/7-366/7 weeks (completed 27 weeks but not 37 weeks) of gestation at the time of vac-cination (Visit 1), as established by ultrasound examination.
• Not at high risk for complications, as determined by the obstetrical algorithm for identification of eligible subjects and the Obstetrical Risk Assessment Form.
• No significant foetal abnormalities, as observed by the level II ultrasound testing conducted after 18 weeks of gestation.
• Nuchal translucency scan, serum testing and any other prenatal tests, if conducted, should suggest normal preg-nancy.
• Willing to have the infant born immunised with Infanrix hexa and Prevenar 13, as per national recommendations, in the follow-up clinical studies DTPA (BOOSTRIX)-048 PRI and DTPA (BOOSTRIX)-049 BST: 048.
• Subjects who do not plan to give their child for adoption or place the child in care.

E.4

Principal exclusion criteria

• Subjects diagnosed with multiple pregnancies (twins, triplets etc.).
• Previous vaccination containing diphtheria, tetanus or pertussis antigens or diphtheria and tetanus toxoids at any time during the current pregnancy.
• Women with co-morbid medical or obstetric conditions that in the opinion of the investigator have the potential to complicate the pregnancy course and outcomes [for eg., such as hypertension (requiring medications), uterine anomalies and bleeding disorders etc.].
• Gestational diabetes as determined by glucose tolerance test conducted after 20 weeks of gestation, as per local recommendations of the country [Canadian Diabetes As-sociation 2013 Clinical Practice Guidelines for the Pre-vention and Management of diabetes in Canada, 2013; International Association of Diabetes and Pregnancy Study groups Consensus Panel, 2010; GEDE, 2006].
• History of early onset (<34 weeks of gestation) of eclampsia/pre-eclampsia in previous pregnancy.
• History of major congenital anomalies in previous preg-nancies.
• Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine anytime during the current pregnancy or planned use during the study period.
• Any medical condition that in the judgment of the investi-gator would make intramuscular injection unsafe.
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting six months prior to the first vaccine. For corticosteroids, this will mean prednisone >= 20 mg/day, or equivalent. Inhaled and topical steroids are allowed.
• Administration of long-acting immune-modifying drugs at any time during the study period (e.g. infliximab).
• Planned administration/administration of a vaccine not foreseen by the study protocol in the period within the pe-riod starting 30 days before and 30 days after the dose of vaccine with the exception of seasonal influenza vaccine that can be administered anytime during the study period.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
• Serious underlying medical condition [e.g., immunosup-pressive disease or therapy, human immunodeficiency virus infection, collagen vascular disease, epilepsy, dia-betes mellitus, chronic hypertension, moderate to severe asthma, lung/heart disease, liver/kidney disease, infections including TORCHES (toxoplasmosis, rubella, cy-tomegalovirus, herpes simplex, syphilis) infections].
• History of an encephalopathy of unknown aetiology, oc-curring within 7 days following previous vaccination with pertussis-containing vaccine.
• History of transient thrombocytopenia or neurological complications (for convulsions or hypotonic-hyporesponsive episodes) following an earlier immunisa-tion against diphtheria and/or tetanus
• Significant mental illness (e.g. schizophrenia, psychosis and major depression).
• Family history (first degree relatives only) of congenital anomalies, recurrent pregnancy losses (two or more consecutive losses) and unexplained neonatal death(s) in the subject.
• Any confirmed or suspected immunosuppressive or im-munodeficient condition, based on medical history and physical examination (no laboratory testing required).
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
• History of febrile illness within the past 72 hours.
• History of physician-diagnosed or laboratory-confirmed pertussis within the past five years.
• Anything that would prevent subject from completing the study or put the subject at risk, as determined by the in-vestigator.
• Acute disease and/or fever at the time of enrolment.
- Fever is defined as temperature>= 37.5°C /99.5°F for oral, axillary or tympanic route, or >= 38.0°C /100.4°F on rectal route.
- Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may be enrolled at the discretion of the investigator.
• Administration of immunoglobulins and/or any blood products within the 3 months preceding the dose of study vaccine, or planned administration during the study period, with the exception of anti-D (Rh)-immunoglobulin.
• History of chronic excessive alcohol consumption and/or drug abuse.

E.5 End points

E.5.1

Primary end point(s)

Immunogenicity with respect to components of the study vaccine, in cord blood sample:
Anti-PT, anti-FHA and anti-PRN antibody concentrations

E.5.1.1

Timepoint(s) of evaluation of this end point

At delivery (28 weeks to 40 weeks of gestation)

E.5.2

Secondary end point(s)

Pregnancy outcomes will include live birth with no con-genital anomalies, live birth with congenital anomalies, still birth with no congenital anomalies, still birth with congenital anomalies, elective termination with no congenital anomalies and elective termination with congenital anomalies.
Pregnancy-related adverse events of interest/ neonate-related events will include gestational diabetes, pregnancy-related hypertension, premature rupture of membranes, preterm premature rupture of membranes, premature labour, premature uterine contractions, intrauterine growth restriction/poor foetal growth, pre-eclampsia, eclampsia, vaginal or intrauterine haemorrhage, maternal death, preterm birth, neonatal death, small for gestational age, neonatal hypoxic ischaemic encephalopathy and failure to thrive/growth deficiency.
Anti-D, anti-T, anti-PT, anti-FHA and anti-PRN seroprotection/seropositivity status and antibody concentrations.
Vaccine response to PT, FHA and PRN
Vaccine response to anti-D and anti-T
Anti-PT, anti-FHA and anti-PRN seropositivity status.
Occurrence of each solicited local/general symptoms (at Visit 1 and Visit 3)
Occurrence of unsolicited AEs, according to the Medical Dictionary for Regulatory Activities (MedDRA) classification (at Visit 1 and Visit 3).
Occurrence of serious adverse events.

E.5.2.1

Timepoint(s) of evaluation of this end point

outcome of pregnancy in terms of pregnancy outcomes and pregnancy-related adverse events of interest/ neonate-related events: Up to two months post-delivery.
Seroprotection/seropositivity and vaccine response: One month post vaccination
Anti-PT, anti-FHA and anti-PRN seropositivity: At delivery (28 weeks to 40 weeks of gestation)
Solicited local and general symptoms: During the 8-day (Day 0-Day 7) follow-up period after the vac-cination.
unsolicited AEs: Within 31 days (Day 0 – Day 30) after vaccination
SAEs: From Day 0 up to two months post-delivery.

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

Yes

E.6.13.1

Other scope of the trial description

immunogenicity

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

Yes

E.8.1.2

Open

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

Yes

E.8.1.7.1

Other trial design description

Observer-blind

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

Australia

Canada

Czech Republic

Spain

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

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

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

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)

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:

680

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

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

100

F.4.2

For a multinational trial

F.4.2.1

In the EEA

330

F.4.2.2

In the whole clinical trial

680

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)

A plan for treatment or care after the subject has ended the participation in this trial is not provided for prophylactic vaccine studies as the subjects are healthy and do not need any treatment or care after end of the study.

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

2015-10-08

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-09-03

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-10-24

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials