Clinical Trials Register

Summary
EudraCT Number:	2016-004109-15
Sponsor's Protocol Code Number:	1ABC
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-05-10
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2016-004109-15

A.3

Full title of the trial

Evaluation of the safety and efficacy of the treatment of chronic wounds in diabetic foot syndrome with the use of autologous stem cells isolated from adipose tissue - within the project: "Therapeutic potential of adipose-derived stem cells, proven in clinical trials and examined in vitro - rationale for banking of well characterized cells”

Ocena bezpieczeństwa i skuteczności leczenia ran przewlekłych w zespole stopy cukrzycowej z użyciem autologicznych komórek macierzystych, izolowanych z tkanki tłuszczowej – w ramach projektu pt.: „Potencjał terapeutyczny mezenchymalnych komórek macierzystych, testowany w próbach klinicznych oraz in vitro - uzasadnienie dla bankowania scharakteryzowanych komórek”

A.3.1

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

A.4.1

Sponsor's protocol code number

1ABC

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	Medical University of Warsaw
B.1.3.4	Country	Poland
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	The National Centre for Research and Development
B.4.2	Country	Poland
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Medical University of Warsaw
B.5.2	Functional name of contact point	Dep.ofGen.,Vasc.&TransplantSurgery
B.5.3	Address:
B.5.3.1	Street Address	Banacha 1a
B.5.3.2	Town/ city	Warsaw
B.5.3.3	Post code	02-097
B.5.3.4	Country	Poland
B.5.4	Telephone number	004822599 24 67
B.5.5	Fax number	004822599 14 68
B.5.6	E-mail	slawomir.nazarewski@wum.edu.pl

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	No
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	Autologous stromal vascular fraction for diabetic foot ulcers treatment
D.3.4	Pharmaceutical form	Cutaneous suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous 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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
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	Yes
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	Yes
D.3.11.3.5.1	CAT classification and reference number	Ref.EMA/CAT/771738/2015
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	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	No
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	Autologous adipose derived mesenchymal stem cells for diabetic foot ulcers treatment
D.3.4	Pharmaceutical form	Cutaneous suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Cutaneous 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)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	Yes
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	Yes
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	Yes
D.3.11.3.5.1	CAT classification and reference number	Ref.EMA/CAT/771738/2015
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
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Cutaneous solution
D.8.4	Route of administration of the placebo	Cutaneous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Diabetic foot ulcer

Owrzodzenie w przebiegu zespołu stopy cukrzycowej

E.1.1.1

Medical condition in easily understood language

Hard to heal wounds.

Trudno gojące się rany.

E.1.1.2

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	20.0
E.1.2	Level	LLT
E.1.2	Classification code	10012664
E.1.2	Term	Diabetic foot ulcer
E.1.2	System Organ Class	100000004858

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluation of the safety and efficacy of the therapy with autologous stem cells isolated from adipose tissue of the patient in the treatment of chronic wounds in the diabetic foot syndrome.

Ocena bezpieczeństwa i skuteczności terapii autologicznymi komórkami macierzystymi izolowanymi z tkanki tłuszczowej pacjenta w leczeniu przewlekłych ran w zespole stopy cukrzycowej.

E.2.2

Secondary objectives of the trial

Assessment of wound’s morphology: effusion, redness and / or swelling of the skin around the wound, presence of granular or fibrous.
Analysis of the expression of selected pro-angiogenic factors in the wound treated with the studied method compared to the wound treated in standard manner.

Ocena zmian morfologii rany: wysięk, zaczerwienienie i/lub obrzęk skóry wokół rany, obecność ziarniny lub włóknika
Analiza ekspresji wybranych czynników pro-angiogennych w ranie leczonej badaną metodą, w stosunku do rany leczonej w sposób standardowy.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Signing informed consent form.
2. Above the age of 18
3. Voluntary participation in the research, following the requirements of the protocol and acceptance for procedures related with its implementation
4. Chronic wound in the course of diabetic foot syndrome, with duration of at least 12 weeks and the wound surface not less than 2 sq. cm and not greater than 25 sq. cm, without evidence of active infection of the wound at the time of qualification to participate in the study
5. Blood glucose control - fasting not more than 180 mg% OR HbA1c not more than 10%.
6. Good tolerance of the current standard of treatment lasting at least one week before including the patient into the study
7. Satisfactory blood supply to the wound verified by the measurement of the oxygen level of the foot tissue (> 20mmHg) in patients with neuropathic etiology of diabetic foot syndrome
8. In the case of the patients with the wounds of ischemic component, the condition for qualification is a clinical improvement of the limb’s blood supply as a result of the revascularization procedure documented by X-ray or ultrasound.
9. Ankle-brachial index (ABI) ≥ 0.8
10. No active infection of the wound and surrounding tissue verified by quantitative microbiological testing (105 bacteria per 1 g of tissue taken for testing from a wound)
11. For women of childbearing potential - a negative pregnancy test result during the screening visit and using of effective contraceptive methods during participation in the research.

1. Podpisanie dokumentu świadomej zgody
2. Wiek powyżej 18 lat
3. Chęć dobrowolnego udziału w badaniu, postępowania zgodnie z wymogami protokołu i akceptacji procedur związanych z jego realizacją
4. Rana przewlekła w przebiegu zespołu stopy cukrzycowej, o czasie trwania co najmniej 12 tyg. i powierzchni rany nie mniejszej niż 2 cm2 i nie większej niż 25 cm2, bez cech czynnej infekcji rany w chwili kwalifikacji do udziału w badaniu
5. Kontrola glikemii – na czczo nie więcej niż 180 mg% LUB poziom HbA1c nie wyższy niż 10%.
6. Dobra tolerancja dotychczasowego leczenia standardowego, z co najmniej tygodniowym okresem jego stosowania, poprzedzającym włączenie pacjenta do badania
7. Zadowalające ukrwienie rany, weryfikowane pomiarem poziomu wysycenia tlenem tkanek stopy (>20mmHg) u chorych z neuropatyczną etiologią zespołu stopy cukrzycowej
8. W przypadku pacjentów z ranami z komponentą niedokrwienną warunkiem kwalifikacji jest kliniczna poprawa ukrwienia kończyny w wyniku zabiegu rewaskularyzacyjnego udokumentowana radiologicznie lub ultrasonograficznie.
9. Wskaźnik kostka-ramię ≥0,8
10. Brak aktywnego zakażenia rany i tkanek otaczających, weryfikowany ilościowym badaniem mikrobiologicznym (105 bakterii na 1 g tkanki pobranej do badania z rany)
11. W przypadku kobiet w wieku rozrodczym – ujemny wynik testu ciążowego w czasie wizyty przesiewowej i stosowanie skutecznej metody antykoncepcyjnej w czasie udziału w badaniu

E.4

Principal exclusion criteria

1. Lack of patient’s cooperation
2. Ischemia of lower limbs; ankle-brachial index <0.8; significant vein component in medical patient’s history shown in the Duplex-Doppler tests made within 6 months before joining the research.
3. Active cancer during chemotherapy or radiotherapy, or recent cancer, if the remission had place less than 5 years before joining the study
4. No clinical improvement after revascularization procedures performed on the vascular system of the treated limb during the last 2 weeks
5. Venous thromboembolism in the past 3 months preceding participation in the research
6. Sings of severe osteolysis and / or bone and marrow infection around wounds on the basis of the result of X-ray, CT or MRI of the feet made within 6 months before participation in the study.
7. The active inflammation phase in the course of Charcot's neuroartropathy.
8. Treatment with antibiotics, immunosuppressive therapy, including systemic steroid therapy (excluding inhaled medicines) at the time of joining the study.
9. Chronic diseases in the stage of exacerbation, not stabilized, that in the opinion of the investigator may hinder or make impossible a patient’s participation in the study and reviewed on the basis of subjective and objective examination and laboratory tests carried out during the screening visit (blood type, morphology, electrolytes, coagulation system, blood glucose, urea, creatinine, and viral tests). Test results behind laboratory standards for a specific parameter are considered as incorrect. In the case of treatment with vitamin K antagonists, normal ranges suitable for this treatment will apply.
10. Known allergic reactions to ingredients of dressing (thrombin, penicillin).
11. The diagnosis of AIDS, HBV or HCV
12. Reactive result of serological and viral tests:
HIV-1 and 2 (HIV Ag / Ab);
Hepatitis B Virus Infection, Anti-HBc;
Hepatitis C Virus Infection, Anti-HCV;
Syphilis specific tests

1. Brak współpracy chorego
2. Niedokrwienie kończyn dolnych; wskaźnik kostka-ramię <0.8; w wywiadach istotna komponenta żylna wykazana w badaniu Duplex-Doppler wykonanym w ciągu 6 miesięcy przed włączeniem do badania.
3. Czynna choroba nowotworowa, w trakcie chemio- lub radioterapii, lub przebyta choroba nowotworowa, jeżeli od uzyskania remisji nie upłynęło co najmniej 5 lat
4. Brak klinicznej poprawy po zabiegach rewaskularyzacyjnych wykonywanych na układzie naczyniowym leczonej kończyny w okresie ostatnich 2 tygodni
5. Choroba zakrzepowo-zatorowa w ciągu ostatnich 3 miesięcy, poprzedzających włączenie do udziału w badaniu
6. Cechy nasilonej osteolizy i/lub zakażenia kości i szpiku w okolicy rany w oparciu o wynik badania RTG, TK lub MRI stopy wykonanych w ciągu 6 miesięcy przed włączeniem do badania.
7. Faza aktywnego zapalenia w przebiegu neuroartropatii Charcota.
8. Leczenie antybiotykami, leczenie immunosupresyjne, w tym steroidoterapia systemowa (z wyłączeniem leków stosowanych wziewnie) w chwili włączenia do badania.
9. Choroby przewlekłe w stadium zaostrzenia, niewyrównane, które w opinii badacza mogą utrudnić lub uniemożliwić pacjentowi udział w badaniu, weryfikowane na podstawie badania podmiotowego i przedmiotowego oraz badań laboratoryjnych wykonanych w ramach wizyty screeningowej ( grupa krwi, morfologia, jonogram, układ krzepnięcia, poziom glikemii, mocznik, kreatynina, układ krzepnięcia oraz badania wirusologiczne). Wyniki badań nie mieszczące się w normach laboratoryjnych dla danego parametru uznawane będą za nieprawidłowe. W przypadku leczenia antagonistami witaminy K stosowane będą normy odpowiednie dla tego leczenia.
10. Znane reakcje alergiczne na składniki opatrunku (trombina, penicylina).
11. Rozpoznanie AIDS, HBV lub HCV
12. Reaktywny wynik badań serologicznych i wirusologicznych:
• HIV-1 i 2 (HIV Ag/Ab);
• wirusowe zapalenie wątroby typu B-HbsAg i Anty HBc;
• wirusowe zapalenie wątroby typu C-Anty-HCV;
• kiła testy swoiste

E.5 End points

E.5.1

Primary end point(s)

Time needed for a 50% reduction in wound size in comparison to the original volume

Czas potrzebny na zmniejszenie o 50% wielkości rany w stosunku do wielkości początkowej

E.5.1.1

Timepoint(s) of evaluation of this end point

Time to first occurence.

Czas jaki upłynie do pierwszego wystąpienia

E.5.2

Secondary end point(s)

Evaluation of changes in the morphology of the wound, and expression analysis of selected proangiogenic factors in the wound treated with the tested method (AKM), relative to the wound being treated in a standard way.

Ocena zmian morfologii rany oraz analiza ekspresji wybranych czynników pro-angiogennych w ranie leczonej badaną metodą (AKM), w stosunku do rany leczonej w sposób standardowy

E.5.2.1

Timepoint(s) of evaluation of this end point

Time to first occurence.

Czas jaki upłynie do pierwszego wystąpienia.

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

Yes

E.8.2.3.1

Comparator description

Materiał hydrowłóknisty lub piankowy -z nanosrebrem w okresie przesiewowym, bez nanosrebra w badaniu

Hydro-fibrous or foam material (with nanosilver at screening,without nanosilver during the study).

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the 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

When the complete healing of wound is achieved or 6 weeks after the first application (whatever occurs first).
In case of an adverse event or in any other situation in which (in the investigator’s opinion) the patient continued participation in the study may jeopardize his health.
In case of relevant violation of the study protocol by the patient and the withdrawal of his consent to participate in the study.

W chwili uzyskania całkowitego wygojenia rany, lub po 6 tyg. od pierwszej aplikacji (w zależności od tego, co nastąpi pierwsze).
W przypadku wystąpienia zdarzenia niepożądanego, lub w innej sytuacji, w której, w opinii badacza, dalszy udział pacjenta w badaniu może stanowić istotne zagrożenie dla jego zdrowia.
Podstawą do wcześniejszego zakończenia badania może być istotne naruszenia protokołu badania przez pacjenta oraz wycofanie jego zgody na udział w badaniu.

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

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:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

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

Yes

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

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

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)

If after 6 weeks since the first application the complete healing of the wound is not achieved then the patient will be further treated in accordance with standard of care for the healing diabetic foot ulcer.

Jeśli po 6 tygodniach od pierwszej aplikacji nie dojdzie do całkowitego zagojenia rany, chory będzie dalej leczony zgodnie z zasadami leczenia ran w przebiegu stopy cukrzycowej.

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

2017-12-13

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-04-11

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

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