Clinical Trials Register

Summary
EudraCT Number:	2006-002758-31
Sponsor's Protocol Code Number:	ECD01
National Competent Authority:	Bulgarian Drug Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-08-05
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

Bulgarian Drug Agency

A.2

EudraCT number

2006-002758-31

A.3

Full title of the trial

A randomized, double-blind, multi-centre, placebo-controlled, parallel-group study to examine the efficacy and safety of low dose Epoetin beta on wound healing in diabetes patients with foot ulcer

A.4.1

Sponsor's protocol code number

ECD01

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	EPOPLUS GmbH & Co.KG
B.1.3.4	Country	Germany
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
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	NeoRecormon Multidose 50.000 I.E. Lyophilisat und Lösungsmittel zur Herstellung einer Injektionslösung (5.000 I.E./ml)
D.2.1.1.2	Name of the Marketing Authorisation holder	Roche Registration Limited
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 solvent for solution for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Epoetin beta
D.3.9.3	Other descriptive name	recombinant human erythropoietin
D.3.10	Strength
D.3.10.1	Concentration unit	IU international unit(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	50.000
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)	Information not present in EudraCT
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	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	Information not present in EudraCT
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	Information not present in EudraCT
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	Yes
D.3.11.13.1	Other medicinal product type	recombinant medicinal product

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	Solution for injection
D.8.4	Route of administration of the placebo	Subcutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

wound healing in diabetes patients with foot ulcer

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	8.1
E.1.2	Level	LLT
E.1.2	Classification code	10048037
E.1.2	Term	Wound healing disturbance of

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 the effects of a systemic treatment with erythropoietin on wound closure in
patients with diabetes and diabetic foot syndrome

E.2.2

Secondary objectives of the trial

The secondary objectives of the study are:
a) To evaluate the wound healing, i.e. area of the target (biggest) ulcer, from baseline to
week 13 (percentage and absolute change).
b) To evaluate the microcirculation (only at selected study sites).
c) To describe the one-year survival status/amputation rate/recurrence of target ulcer.
d) To evaluate the wound healing, i.e. depth of the target ulcer from baseline to week 13.
e) To evaluate the time to wound closure.
f) To evaluate the reduction of pain.
g) Safety and tolerability.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Diabetic patients with foot ulcer below the ankle will be randomised into 2 treatment
arms:
a. diagnosis of diabetes and neuropathic ulcer Wagner I or II (as indicated by a
neuropathy deficit score 6-10, palpaple foot pulses and an ABI-index ≥1.0)
or
b. diagnosis of diabetes and ulcer Wagner I/II or wounds after amputations in
patients with peripheral arterial occlusive disease (as indicated by the
presence of one of the following: missing foot pulses and an ABI-index ≤0.8,
or a history of insufficient vascularisation on the target leg*).
*Angiographically documented peripheral arterial occlusive disease and no
surgical or endovascular treatment option.
2. Ulcer size over 0.5 cm2.
3. Male or female aged ≥ 18 years.
4. Signed written informed consent to participate in this trial.
5. Female of childbearing potential with a negative pregnancy test, and agrees to use
an acceptable contraceptive method (hormonal or IUD) throughout the study.
6. HbA1c ≤ 10% or, if > 10% then stable blood glucose level within the last 4 weeks,
i.e. fasting blood glucose value < 160 mg/dl.
7. At least one foot ulcer, the size of which can be documented using a transparent
foil.
8. Weight between 50 kg and 160 kg.
9. Patients without significant healing after a 4 week Run-In period can be randomized
into a treatment arm.

E.4

Principal exclusion criteria

1. Pregnant or nursing women.
2. Myeloplastic or proliferative disease.
3. Known infection with hepatitis B or hepatitis C or HIV.
4. Therapy with rHuEPO or analogic medicine within the last 6 months.
5. Bleeding episodes which affect the Hb value or known gastro-intestinale bleedings
within the last 3 months.
6. Known or suspected intolerance to erythropoetic factors, e.g. NeoRecormon®,
Aranesp®, Erypo®.
7. Treatment with systemic chemotherapy or radiotherapy or immunosuppressives or
systemic corticosteroids within the last 6 months prior to treatment start.
8. Previous therapy with growth factors, e.g. GM-CSF, VEGF in the last 6 months.
9. Intake of any medication which interacts with epoetin beta (e.g. Cyclosporin).
10. Uncontrolled systolic blood pressure > 160 mmHg (supine) and/or diastolic blood
pressure > 100 mmHg.
11. Deep vein thrombosis or pulmonary embolism within the previous 6 months
12. Stroke, instable angina pectoris, STEMI or NSTEMI within the last 3 months.
13. Psychiatric disease or chronic cerebellar fits.
14. Scheduled for vascular surgery or any other intervention surgery within 4 weeks to trial
start or during the trial or patients, who could benefit from vascular surgery or other
invasive intervention.
15. Hereditary or acquired thrombophilia, recurrent thrombotic events (> 2) or thrombosis
of uncertain aetiology.
16. Atrial septum defect.
17. Transient ischaemic attack (TIA) within the last 3 months.
18. Prolonged reversible ischemic neurological deficit (PRIND) within the last 3 months.
19. Artificial heart valves (mechanical or biological)
20. Alcohol or drug abuse.
21. Non-compliance and/or participation in a clinical trial within the last 3 months prior to
screening.
22. Patients in dialysis program or chronical renal failure Grad IV.
23. Patients with known bleedings, MCV below normal ranges, and iron deficiency anemia
24. Hemoglobin, hematocrit and platelet count above the upper limit of normal according
to the local laboratory
25. Antibiotic treatment of the target wound at time of randomization.

E.5 End points

E.5.1

Primary end point(s)

Primary endpoint is complete wound closure of the target ulcer.

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.5

Parallel group

Yes

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

Yes

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

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

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

The duration of double-blind treatment will be 12 weeks. This will be followed by further 12 weeks follow-up period with standard-of-care treatment. This will be followed by long-term follow-up telephone contact after 12 months to inguire on the survival and amputation status of the patients.

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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	50
F.4.2	For a multinational trial
F.4.2.1	In the EEA	90
F.4.2.2	In the whole clinical trial	90

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

2010-08-09

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2010-11-10

P. End of Trial
P.	End of Trial Status	Prematurely Ended

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