Clinical Trials Register

Summary
EudraCT Number:	2012-005644-26
Sponsor's Protocol Code Number:	1.2012
National Competent Authority:	Belgium - FPS Health-DGM
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-12-21
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Belgium - FPS Health-DGM

A.2

EudraCT number

2012-005644-26

A.3

Full title of the trial

Prospective Open Label study of Parenteral vs Enteral iron in Young IBD patients and Effect on physical fitness

Prospectief onderzoek bij kinderen naar effectiviteit van oraal versus parenteraal ijzer op fysieke gezondheid.

A.3.1

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

Administration of iron given intravenously versus orally in children with anemia and chronic inflammatory bowel disease.

Studie naar de effectiviteit van toediening van ijzer via de mond bij kinderen met een chronische darmziekte en bloedarmoede.

A.3.2

Name or abbreviated title of the trial where available

POPEYE study

POPEYE onderzoek

A.4.1

Sponsor's protocol code number

1.2012

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN44870000

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	Atrium Medical Centre
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	Atrium Medical Centre
B.4.2	Country	Netherlands
B.4.1	Name of organisation providing support	Vifor Pharma
B.4.2	Country	Switzerland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Antwerp University Hospital
B.5.2	Functional name of contact point	Dr. Els Van de Vijver
B.5.3	Address:
B.5.3.1	Street Address	Wilrijkstraat 10
B.5.3.2	Town/ city	Edegem
B.5.3.3	Post code	2650
B.5.3.4	Country	Belgium
B.5.4	Telephone number	003238215524
B.5.5	Fax number	003238291194
B.5.6	E-mail	els.vandevijver@uza.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	Injectafer /ferinject.
D.2.1.1.2	Name of the Marketing Authorisation holder	Vifor France SA
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	Concentrate and solvent for solution for injection/infusion
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous drip use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	FERRIC CARBOXYMALTOSE
D.3.9.1	CAS number	9007-72-1
D.3.9.2	Current sponsor code	Injectafer 50 mg/ml ijzer/ml oplossing voor injectie/infusie
D.3.9.4	EV Substance Code	SUB66620
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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	Comparator
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	Ferrofumaraat Apotex
D.2.1.1.2	Name of the Marketing Authorisation holder	Apotex Europe BV
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.3.1	Product name	ferrofumaraat
D.3.4	Pharmaceutical form	Film-coated tablet
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Ferrous Fumarate
D.3.9.1	CAS number	141-01-5
D.3.9.2	Current sponsor code	ferrofumaraat
D.3.9.3	Other descriptive name	FERROUS FUMARATE
D.3.9.4	EV Substance Code	SUB13865MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	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

Anemia and fatigue in children with Inflammatory Bowel disease (IBD)

anemie en vermoeidheid bij kinderen met inflammatoire darmziekten

E.1.1.1

Medical condition in easily understood language

Anemia and fatigue in children with chronic inflamed intestines

Bloedarmoede en vermoeidheid bij kinderen met chronisch ontstoken darmen.

E.1.1.2

Therapeutic area

Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

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 current application is to compare the effect
of intravenous iron supplementation to oral supplementation on
recovery of physical activity, anemia, subclinical inflammation, quality of
life and fatigue.

Onderzoeken of intraveneus danwel oraal ijzer meer effectief is in het
verbeteren van fysieke conditie, ijzerstatus en vermindering van
vermoeidheidsklachten.

E.2.2

Secondary objectives of the trial

To examine the effectiveness of intravenous administration of iron
therapy, on improving hemoglobin (improvement of Hb with 1.25
mmol/L (2g/dl) in comparison to the Hb at the start of the study).
To examine the effect of intravenous iron on physical fitness compared
with usual care.
To examine the effect of intravenous iron on quality of life and fatigue
compared with usual care.
To identify predictors for fatigue in children with IBD.
To assess baseline physical activity levels and quality of life in children
with IBD.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Children attending a pediatrician/ pediatric gastroenterologist/
gastro-enterologist.
2. Children aged 8 – 18 years
3. Suffering from CD/CU/IBDU diagnosed according to the Porto criteria
(1)
4. Written informed consent of both parents with authority or from
custodial parent and if age> 12y: also from the child itself.
5. Ability to understand and speak Dutch language.

1. Kinderen zijn in behandeling bij kinderarts/ kinderMDL arts/MDL arts
2. Kinderen van 8 -18 jaar oud
3. Kinderen hebben diagnose Morbus Crohn/ colitis ulcerosa/IBDU
volgens Porto criteria
4. Er is geschreven informed consent van beide ouders en indien het kind
ouder is dan 12 jaar ook van het kind zelf
5. Kinderen en ouders begrijpen en spreken de Nederlandse taal

E.4

Principal exclusion criteria

1. Allergic reactions to intravenous iron therapy
2. Suffering from hemochromatosis
3. Patients who received oral or IV iron therapy three months prior to
the study
4. PUCAI > 65 - PCDAI > 30 (severe disease activity)

1. Allergische reacties tegen eerder toegediende intraveneuze
ijzertherapie
2. Kinderen die lijden aan hemochromatose
3. patienten die nog oraal of intraveneus ijzer hebben gekregen drie
maanden voorafgaand aan inclusie in de studie'
4. PUCAI> 65 - PCDAI > 30 (ernstige ziekte activiteit)

E.5 End points

E.5.1

Primary end point(s)

Primary outcome is the proportion of patients per group that show a
15% increase in 6 minute walking distance after four weeks from study
baseline.
The six minute walk test (6MWT) is an established method to assess
exercise capacity. It is expressed as the distance a person can walk at a
constant, uninterrupted pace in 6 minutes The patients are asked to walk
up and down the measured lap at their best pace but not to run or race
(47). With patients tested by the same technician, short-term
reproducibility of the 6MWT is excellent. 6MWT is expressed as absolute
distance in meters and is age and height dependent (31,32).
Healthy children below 12 years show the steepest increase in 6MWD
per year. After 12 years 6MWD further increases with age in boys,
whereas it essentially levels off in girls (31). When several 6MWTs are
done within a short time frame, 6 MWD usually reaches a plateau after
two tests done within a week (33). This training effect may be due to
improved coordination, finding optimal stride length, and overcoming
anxiety. The possibility of a training effect from tests repeated after
more than a month (like in our study) has not been studied or reported;
however, it is likely that the effect of training does not persist after a
few weeks.

E.5.1.1

Timepoint(s) of evaluation of this end point

After 4 weeks, after 3 and after 6 months

Na 4 weken en na 3 en 6 maanden

E.5.2

Secondary end point(s)

I. Secondary outcome variable in the study is an increase of Hb with 1.25 mmol/L (2 g/dl) one month after administration of IV ferric carboxymaltose therapy compared to the Hb level at time of inclusion.
II Other secondary endpoints include the IMPACT-III score and the PEDSQL fatigue scale.
The IMPACT-III score is a disease-specific quality of life score, composed of 35 items on 6 domains: IBD-related symptoms (7 items), systemic symptoms (3), emotional functioning (7), social functioning (12), body image (3) and treatment/intervention-related concerns (3). Each item can be scored on a 5 point Likert scale, coded from 0 to 4 points. Higher scores indicate better quality of life. The IMPACT questionnaire is validated for use in children 8 years and older and is recommended for the evaluation of new therapies because of its high sensitivity to change. The IMPACT-III (NL) is a translated and modified version of the original Canadian questionnaire that used a visual
analogue scale. The Likert scale was introduced as it has been shown that children consider it easier to complete than a visual analogue
scale. The PEDSQL fatigue scale: The 18-item PedsQL Multidimensional Fatigue Scale was designed to measure fatigue in pediatric patients and
comprises the General Fatigue Scale (6 items), Sleep/Rest Fatigue Scale (6 items), and Cognitive Fatigue Scale (6 items). The questionnaire is available in Dutch for children (8-12y) and adolescents (12-18y). The questionnaire comprises parallel child self-reports and parent proxyreports. The participants rate how often a particular problem occurred in the past month, using a 5-point Likert scale. Each item is reverse-scored
and rescaled to 0-100 scale, so that higher scores indicate fewer symptoms of fatigue.
III Other monitored parameters are the clinical disease activity according to PCDAI and PUCAI, laboratory markers for effectiveness of IV iron therapy in replenishment of iron stores (Ht, cell indices, thrombocytes, ferritin, transferrin, serum iron level, transferrin saturation, reticulocytes/retHb , sTfR, soluble transferrin receptors to log ferritin (sTfR-F ratio), transferrin/log ferritin ratio, hepcidin), side effects of IV iron therapy on liver functioning (AST, ALT, AF, total protein, albumin) and side effects on electrolyte homeostasis (phosphate).
IV Accelerometers will be used to measure the daily activity versus time spent in bed, giving a more objective idea about daily activities, sleeping
time and relationship with fatigue.

E.5.2.1

Timepoint(s) of evaluation of this end point

After 4 weeks, after 3 and 6 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

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

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

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)

Yes

E.8.2.2

Placebo

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

E.8.6.2

Trial being conducted completely outside of the EEA

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

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

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:

150

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

115

F.1.2

Adults (18-64 years)

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

Yes

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

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

Inclusion criteria are children (8-18 years): both parents with custody must give informed consent and, if the subject is 12 years or older, also the child itself gives written informed consent.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

F.4.2

For a multinational trial

F.4.2.1

In the EEA

150

F.4.2.2

In the whole clinical trial

150

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

2018-02-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2018-02-26

P. End of Trial
P.	End of Trial Status	Ongoing

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