Controlled Study, Performed to Evaluate the Safety and Efficacy of EscharEx and Its Placebo (Gel Vehicle) Compared to Non-surgical Standard of Care in Participants With Venous Leg Ulcers (VLU)

Inclusion Criteria: Criteria: Inclusion Criteria 1. Men or women, older than 18 years of age, 2. Participants with VLU (determined by medical history, physical examination, and a documented ultrasound scan demonstrating venous insufficiency), 3. Wound is present for at least 4 weeks but no longer than 18 months 4. The adherent necrotic/thick slough/fibrin non-viable tissue area, assessed following wound cleansing with wet gauze and sterile saline or water and mild soap, is at least 50% of the wound area (assessed by clinical evaluation), 5. Target wound surface area is in the range of 2-40 cm2 (assessed by eKare inSightTM), 6. Participant understands the nature of the procedure, is able to adhere to the Exclusion Criteria 1. Wound size decreased by \>20% after 7 (+3/-1) days of the screening period, 2. Participants with more than one leg ulcer8, on the leg of the target wound, with an area greater than or equal to 2 cm2, that are between 2 cm and 5 cm away from the edge of the target wound, 3. Signs of infection of the wound or peri-wound including purulent discharge, deep-tissue abscess, cellulitis, erysipelas, etc., 4. Severely damaged skin (e.g., abrasion, erosion, exfoliation) extending \>2 cm around the wound's edge, 5. Presence of gangrene, signs of systemic infection, sepsis, or osteomyelitis, 6. Clinical suspicion of skin cancer (e.g., basal cell carcinoma (BCC), squamous cell carcinoma (SCC), melanoma, or sarcoma), near the target wound, which was not ruled out by biopsy, 7. Participants with skin disorders unrelated to the wound that are present adjacent to the wound, 8. Participants 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, or penetrating into periosteum, fascia or bone, 10. Participants with primary lymphatic edema (Lymphedema), 11. A significant decrease in the arterial blood flow of the extremity, as demonstrated by either Toe-Brachial Index (TBI) ≤ 0.50, Ankle-Brachial Index (ABI) ≤ 0.70, Skin Perfusion Pressure (SPP) ≤ 40 mmHg, Transcutaneous oximetry (TCOM) ≤ 40 mmHg, or lack of bi-phasic or tri-phasic doppler wave forms, 12. Participants with pre-enrollment wounds which are covered by eschar heavily saturated with iodine or by silver sulfadiazine (SSD) pseudoeschar (i.e., pseudoeschar because of SSD treatment), 13. History of allergy or atopic disease or a known sensitivity to pineapples, bromelain, papaya or papain, as well as known sensitivity to latex proteins (known as latex-fruit syndrome), bee venom or olive tree pollen, 14. Participants with poor nutritional status: albumin \< 2.5g/dl; poorly controlled diabetes mellitus (HbA1c \> 12%); anemia (hemoglobin \<8 g/dL), leukocyte count \< 3,000/μl or \>15,000/μl; neutrophil count ≤1,000/μl; platelets \<100,000/μl, abnormal liver function (AST, ALT\>2 x upper limit of normal range), renal failure (Cr \> 2.5 mg/dl or eGFR \< 30ml/min /1.73m2), BMI\>48, 15. INR\>2 or PTT\> x2 ULN (unless the participant receives coumarin derivatives anticoagulants (e.g. warfarin), and the INR and PTT levels are in their required levels and are stable), 16. Participants undergoing renal or peritoneal dialysis, 17. Any known condition that would preclude safe participation in the study, e.g., significant or unstable cardiovascular, pulmonary, liver, hematological, immunological, neoplastic disease or any immediate life-threatening condition, 18. Recent history or concurrent acute injury or disease that might compromise the participant's welfare according to investigator discretion, The participant is currently receiving, has received within three months prior to enrollment, or is planned to receive during trial period, any medications or treatments at doses known to impair the wound healing 19. include chronic systemic steroid intake of more than 10 mg prednisone (or equivalent) per day for more than 2 weeks, immuno-suppressive drugs, immunomodulating medications, chemotherapy, and radiation therapy. Low and intermittent doses that the investigator determines as not clinically significant for wound healing may be permitted, provided that this determination is based on appropriate clinical judgment and is documented accordingly. 20. Participants treated with Pentoxifylline within 2 weeks prior to screening, 21. Venous ablation performed within one-month prior enrollment, in an area adjacent to the target wound, 22. Mentally incompetent adults who are incapable of giving legal consent (e.g., dementia, psychiatric participants, etc.), 23. Concurrent use of non-approved drugs or alcohol abuse, 24. Pregnant women (positive pregnancy test) or nursing mothers, 25. Exposure to investigational intervention within one month prior to enrollment, or anticipated participation in another investigational drug trial or other intervention trial, while enrolled in the study.