Étude pour évaluer l'efficacité et l'innocuité d'EscharEx (formulation EX-02) dans le débridement des ulcères veineux de jambe

Drug: EscharEx (5% EX-02 formulation);Drug: Gel Vehicle;Drug: Non-surgical standard of care (NSSOC)

Inclusion Criteria

1. Patients, men or women, between 18 and 90 years of age,

2. Patients with a VLU (determined by medical history, physical examination, and an
ultrasound scan demonstrating venous insufficiency),

3. Wound is present for at least 4 weeks but no longer than 2 years.

4. The necrotic/slough/fibrin non-viable tissue area is at least 50% of wound area
(assessed by clinical evaluation),

5. Target wound surface area is in the range of 2-100 cm2 (assessed by eKare inSightTM),

6. Patient understands the nature of the procedure, is able to adhere to the protocol
regimen, and provides a written informed consent prior to any study procedure.

Exclusion Criteria

1. Wound size decreased by > 20% after 1 week of standard-of-care-only period (screening
period),

2. Patients with more than one leg ulcer, on the leg of the target wound, with an area
greater than or equal to 2cm2,

3. Signs of clinically significant infection including purulent discharge, deep-tissue
abscess, erysipelas, cellulitis, etc.,

4. Severely damaged skin (e.g. abrasion, exfoliation) extending >2 cm around the wound's
edge,

5. Presence of gangrene, signs of systemic infection, sepsis, or osteomyelitis during
screening phase,

6. Clinical suspicion of skin cancer (e.g. BCC, SCC, melanoma, sarcoma), which was not
ruled out by biopsy,

7. Patients with skin disorders unrelated to the wound that are presented adjacent to the
wound,

8. Patients suffering from chronic skin disorders (Idiopathic Pruritus, Psoriasis,
Panniculitis, Pyoderma Gangrenosum, etc.) that might deteriorate as a result of local
trauma or debridement,

9. Wound has sinus tracts or tunnels extending under healthy tissue (following
debridement un-roofing- if relevant), or penetrating into joint capsule,

10. Vascular operations in proximity to the wound in the last month,

11. Patients with primary lymphatic edema,

12. A significant decrease in the arterial blood flow of the extremity

13. Patients with pre-enrolment wounds which are covered by eschar heavily saturated with
iodine or by silver sulfadiazine (SSD) pseudoeschar (i.e. pseudoeschar as a result of
SSD treatment),

14. 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), bee venom or olive tree pollen,

15. Patients with poor nutritional status: albumin < 2.5g/dl, poorly controlled Diabetes
Mellitus (for diabetic patients; HbA1c > 12%), anemia (hemoglobin<8 g/dL), a leukocyte
counts < 3,800// µl or >15000/µl, platelets <100,000/µl, abnormal liver function (AST,
ALT>2 x upper limit of normal range), renal failure (Cr > 2.5 mg/dl), BMI>48,

16. Patients undergoing renal or peritoneal dialysis,

17. Any condition that would preclude safe participation in the study, e.g. evidence of
significant or unstable cardiovascular, pulmonary, liver, hematological,
immunological, or neoplastic disease, or any immediate life threatening condition,

18. Recent history (less than 6 months) of myocardial infarction (MI) or concurrent acute
injury or disease that might compromise the patient's welfare,

19. Patient is currently receiving, or has received at any time within three months prior
to enrollment, any medications or treatments known to affect the wound healing
processes; these include, chronic systemic steroid intake with topical skin changes
(i.e. thin, fragile skin with multiple heamatomas or previous laceration history)
immuno-suppressive drugs, radiation therapy, immunomodulating medications and
chemotherapy,

20. Mentally incapacitated adults who are incapable of giving legal consent (e.g.
dementia, psychiatric patients, etc.),

21. Concurrent use of non-approved drugs or alcohol abuse,

22. Pregnant women (positive pregnancy test) or nursing mothers,

23. Exposure to investigational intervention within three months prior to enrollment, or
anticipated participation in another investigational drug trial or other intervention
trial, while enrolled in the study.