Clinical Trials Register

Summary
EudraCT Number:	2015-001466-25
Sponsor's Protocol Code Number:	MW2013-07-10
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2015-04-27
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2015-001466-25

A.3

Full title of the trial

A multicenter, prospective, randomized, vehicle controlled, assessor blinded study performed in subjects with hard to heal wounds, to evaluate the efficacy and safety of enzymatic debridement with EscharEx

Multicentrikus, prospektív, randomizált, vivőanyag kontrollált, a sebet értékelő vizsgáló orvos felé vakosított klinikai vizsgálat az EscharEx-vel történő enzimatikus debridement hatékonyságának és biztonságosságának értékelésére nehezen gyógyuló sebbel rendelkező betegeknél

A.3.1

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

Examining the effect of a new treatment for removing the dead tissue from a chronic wound

Elhalt szövet krónikus sebből történő eltávolítására szolgáló új kezelés hatékonyságának vizsgálata

A.4.1

Sponsor's protocol code number

MW2013-07-10

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT02020746

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	MediWound, Ltd.
B.1.3.4	Country	Israel
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	MediWound, Ltd.
B.4.2	Country	Israel
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	MediWound, Ltd.
B.5.2	Functional name of contact point	Yael Katz-Levy
B.5.3	Address:
B.5.3.1	Street Address	42 Hayarkon Street, North Industrial Area
B.5.3.2	Town/ city	Yavne
B.5.3.3	Post code	8122745
B.5.3.4	Country	Israel
B.5.4	Telephone number	+97254 6774149
B.5.5	Fax number	+97277 971 4187
B.5.6	E-mail	yaelkl@mediwound.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	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	EscharEx
D.3.2	Product code	EscharEx
D.3.4	Pharmaceutical form	Powder and gel for gel
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Topical use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	-
D.3.9.2	Current sponsor code	NexoBrid Drug Substance
D.3.9.3	Other descriptive name	CONCENTRATE OF PROTEOLYTIC ENZYMES ENRICHED IN BROMELAIN
D.3.9.4	EV Substance Code	SUB91744
D.3.10	Strength
D.3.10.1	Concentration unit	mg/g milligram(s)/gram
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	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)	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	Yes
D.3.11.13.1	Other medicinal product type	Concentrate of proteolytic enzymes enriched in Bromelain, a complex mixture of enzymes extracted from the stem of the Ananas comosus as the active component.

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	Gel
D.8.4	Route of administration of the placebo	Topical use (Noncurrent)

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Hard to heal venous leg ulcers, diabetic lower extremity ulcers and traumatic/post operative wounds.

E.1.1.1

Medical condition in easily understood language

Hard to heal venous leg ulcers, diabetic lower extremity ulcers and traumatic/post operative wounds.

E.1.1.2

Therapeutic area

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

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 assess the safety and the efficacy of EscharEx in preparing the wound’s bed in patients with hard to heal venous leg ulcers, diabetic lower extremity ulcers and traumatic/post operative wounds.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Patients, men or women, between 18 and 90 years of age.
2. Patient with venous leg ulcer or diabetic (lower extremity) ulcer or traumatic/post operative wound (determined by medical history and physical examination)
3. Wound is not healing for at least 4 weeks
4. The necrotic/slough/Fibrin non-viable tissue area is at least 50% of wound area (by clinical evaluation, i.e., inspection).
5. Wound surface area (length X width) is in the range of 5 – 200 cm2
6. Patient understands the nature of the procedure, able to adhere to the protocol regimen, and provides written informed consent prior to any study procedure
7. The wound is classified as a wound involving full skin thickness but not penetrating to cavities, or open joint spaces (joint surfaces following disarticulation could be included)

E.4

Principal exclusion criteria

1. Evidence of active osteomyelitis of target organ,
2. Patients with more than one hard to heal wounds which require debridement and with an area greater than or equal to 2cm2,
3. Presence of purulent discharge, deep-tissue abscess, cellulitis or tissue damage extending >2 cm around the wound's edge, gangrene or signs of systemic infection.
4. Wound surface area decreased by > 20% after 1 week of standard-of-care-only period (screening period);
5. Patients with wounds which are covered by eschar heavily saturated with iodine or by Silver sulfadiazine (SSD) pseudoeschar (e.g. pseudoeschar as a result of SSD treatment),
6. Ankle-Brachial Index (ABI) ≤ 0.7 or a significant decrease in the blood flow of the extremity as demonstrated by US Doppler.
7. Wound has sinus tracts or tunnels extending under healthy tissue or into body cavities,
8. Patients undergoing renal or peritoneal dialysis,
9. Recent history (less than 4 weeks) of myocardial infarction (MI) or concurrent acute injury or disease that might compromise the patient’s welfare,
10. Any condition that would preclude safe participation in the study: evidence of significant hematological (pre-existing coagulation disorder), cardiovascular, liver or neoplastic disease, active gastric ulcer, or any other immediate life threatening condition
11. Patient is currently receiving, or has received at any time within one month prior to enrollment, any medications or treatments known to affect the wound healing processes; these include, chronic systemic steroid intake with topical skin changes (thin, fragile with multiple heamatomas and previous laceration history, immuno-suppressive drugs, radiation therapy and chemotherapy.
12. History of allergy or atopic disease or a known sensitivity to pineapples, papaya, bromelain or papain, as well as known sensitivity to latex proteins (known as latex-fruit syndrome) or olive tree pollen,
13. Pregnant women (positive pregnancy test) or nursing mothers,
14. Participation in another investigational drug trial within 30 days prior to enrollment or anticipated participation while enrolled in the study,
15. Concurrent use of non-approved drugs or alcohol abuse.
16. Patients with poor nutritional status (albumin < 2.5g/dl), poor diabetic control (HbA1c > 12%), anemia (hemoglobin< 8 g/dL), a leukocyte counts < 4,000// μl or >15000/μl, abnormal liver function (AST, ALT>2 x upper limit of normal range), renal failure (Cr > 3 mg/dl);
17. Mentally incapacitated adults who are incapable of giving legal consent (e.g. dementia, psychiatric patients, etc),
18. Patients with general skin disorders (Psoriasis, Panniculitis, etc.) that might deteriorate as a result of local trauma.
19. Patients with skin disorders unrelated to the wound that are presented adjacent to the wound
20. Clinical suspicion of skin cancer associated with the wound (e.g, BCC, SCC), which was not ruled out by biopsy,
21. Patients with diagnosed Sepsis during screening phase,
22. Patients suffering from Idiopathic Pruritus,
23. Patients treated with anticoagulant medication.

E.5 End points

E.5.1

Primary end point(s)

Incidence of complete debridement (non-viable tissue removal) at the end of the debridement period (up to 10 treatment days).
Primary analysis will be conducted for all wounds. Secondary sub group analysis will be conducted per etiology, for venous leg ulcers for diabetic lower extremity ulcers and for traumatic/ post operative wounds.

E.5.1.1

Timepoint(s) of evaluation of this end point

at the end of the debridement period (up to 10 treatment days)

E.5.2

Secondary end point(s)

Primary analysis will be conducted for all wounds. Secondary sub group analysis will be conducted per etiology, for venous leg ulcers for diabetic lower extremity ulcers and for traumatic/ post operative wounds.

Secondary Endpoints:
1. Time to achieve complete debridement (up to10 treatment days) (survival analysis)
2. Number of applications/treatment days to achieve complete debridement
3. Time to achieve >75% debridement (up to 10 treatment days)
4. Incidence of >75% debridement (up to 10 treatment days)
5. Assessment of changes in wound debridement status during treatment period : percentage reduction in non viable tissue ( daily, during 10 treatment days)
6. Time to achieve wound bed prepared for healing and closure: a wound bed that can be successfully autografted1 (facilitation of surgical WC by partial healing ) (level >7 in the granulometer scale)
7. Time to achieve complete granulation and time to achieve > 75% granulation (up to 12 weeks from end of treatment)
8. Incidence of complete granulation and incidence of >75% granulation (on week 12 from end of treatment)
9. Percent of change in granulation tissue over time (weekly, during baseline-12 weeks from end of treatment)
10. Incidence of complete wound closure (up to 12 weeks from end of treatment)
11. Time to complete wound closure (up to 12 weeks from end of treatment)
12. Wound area reduction: percentage reduction in wound size over time (weekly, from baseline up to 12 weeks)
13. Changes in the condition of the wound (wound healing status) as assessed by The Leg Ulcer Measurement Tool (LUMT)3 (end of debridement and weekly up to 12 weeks/wound closure)
14. Change in Quality of Life as assessed by the SF-36 (on week 12 and 3 months after wound closure follow-up period)
15. Recurrence rate of wounds (3 months after wound closure)
16. Time to recurrence of wounds (during 3 months after closure)

Exploratory Endpoints:
1. Incidence of complete debridement (non-viable tissue removal) at the end of the debridement period, by subgroups: Eschar/ Slough / Fibrin.
2. In cases of debridement failure: Incidence of surgical debridement and % of non-viable area removed as part of sharp debridement - reported during the weekly FU visits
3. In cases of surgical closure (e.g. auto graft): time to surgical closure
4. Incidence of recurrence of non-viable tissue - as measured during the weekly FU visits
5. Immunogenicity evaluation (for some of the patients).

Safety Outcome Measures:
Severity and incidence of systemic and local adverse events, vital signs, pain assessment (using VAS), evidence of infection, clinical laboratory parameters (blood chemistry, hematology, coagulation), physical examination and blood loss.

E.5.2.1

Timepoint(s) of evaluation of this end point

Secondary Endpoints:
1. on treatment days
2. at the end of treatment period
3. on treatment days
4. on treatment days
5. on treatment days
6. on treatment days
7. on treatment days and weekly in the 12 week FU period from EOTreatment
8. on week 12 from EOTreatment
9. at baseline, on treatment days and weekly in the 12 week FU period from EOTreatment
10. at the end of the wound closure FU
11. on treatment days and weekly in the 12 week wound closure FU
12. at baseline and weekly in the 12 week wound closure FU period
13. at baseline, at end of treatment period and weekly in the 12 week wound closure FU period
14. at baseline, at the end of wound closure FU period and 3 months after wound closure
15. during 3 months after wound closure
16. during 3 months after wound closure

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

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

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

assessor and subject blinded

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

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

Hungary

Israel

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

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:

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 For clinical trials recorded in the database before the 10th March 2011 this question read: "Women of childbearing potential" and did not include the words "not using contraception". An answer of yes could have included women of child bearing potential whether or not they would be using contraception. The answer should therefore be understood in that context. This trial was recorded in the database on 2015-04-27.

Yes

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.4.2.2

In the whole clinical trial

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)

expected normal treatment of that condition

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

2015-06-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2015-06-10

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