An Open Label, Single Treatment, Single Arm, Multiple Dose Phase-2 Study to Evaluate the Pharmacokinetics, Safety, and Clinical Performance of EscharEx (EX-03) in Participants With Venous Leg Ulcers

This is a pharmacokinetics (PK) study - the main objective of this study is to assess the PK, safety and clinical performance of 5% EscharEx (EX-03 formulation) in debridement of Venous Leg Ulcers

Study Overview

• Status: Not yet recruiting
• Conditions: Venous Leg Ulcer (VLU)
• Intervention / Treatment: Drug: EX-03

Detailed Description

Approximately 20 eligible adult participants with VLU (with a surface area between 10 cm2 and 80 cm2, and wound age between 4 weeks and 2 Years), will be enrolled. The participants will be treated with EX-03 5%.

Each participant will go through 3 periods during the trial:

• Screening period (2 visits, 7 (+3/-1) days apart),
• Daily visits period (up to 8 daily site visits within up to 14 days), During the Daily visits period, Blood will be drawn for PK analysis before and after EscharEx application (i.e. during debridement treatment).

PK sampling will be obtained during and following applications of treatment at time points relative to the first application.

• Weekly visits period (2 visits within 14 days), The overall duration of the study for a patient will be up to 5 weeks.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shelly Vander; Phone Number: +972-523527960; Email: shellyv@mediwound.com
• Study Contact Backup: Name: Vered Sasson; Phone Number: +972-546145559; Email: vereds@mediwound.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Men or women, older than 18 years of age,
2. Participants with a 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 2 years,
4. The adherent necrotic/thick slough/fibrin non-viable tissue area, assessed following wound cleansing with wet gauze and either 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 10-80 cm2 (assessed by eKare inSightTM),
6. Participants understand the nature of the procedure, is able to adhere to the protocol regimen, and provides written informed consent prior to any study procedure.

Exclusion Criteria:

1. Wound size that has decreased by > 20% after 7 (+3/-1) days of the screening period,
2. Participants with more than one leg ulcer , 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. Severely damaged skin (e.g., abrasion, erosion, exfoliation) extending >2 cm around the wound's edge,
4. Signs of clinical infection of the wound or peri-wound, including purulent discharge, deep-tissue abscess, erysipelas, cellulitis, etc.,
5. Presence of gangrene, signs of systemic infection, sepsis, or osteomyelitis during the screening phase,
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-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),
13. 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,
14. Participants with poor nutritional status: albumin < 2.5g/dl, poorly controlled Diabetes Mellitus (for diabetic participants; HbA1c > 12%), anemia (hemoglobin<8 g/dL), a leukocyte counts < 3,000/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/d or eGFR < 30ml/min /1.73m2l ), BMI>48,
15. INR>2 or PTT > x 2 ULN (unless the patient 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 cardiac, vascular, pulmonary, liver, hematological, infectious, immunological, neoplastic disease, or any immediate life-threatening condition,
18. Recent history or concurrent acute injury or disease that might compromise the patient's welfare, according to investigator discretion,
19. The Patient is currently receiving, or has received within three months prior to enrollment, or is planned to receive during trial period, any medications or treatments known to affect the wound healing processes; these include chronic systemic steroid intake or chronic systemic steroid intake with topical skin changes (i.e. thin, fragile skin with multiple hematomas or previous laceration history), 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 the past month in an area adjacent to the target wound,
22. Mentally incapacitated 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Active Comparator: EscharEx (EX-03); EX-03 is the code name of the third generation of EscharEx investigational medicinal product (IMP) formulation. A sterile lyophilized powder containing a concentrate of proteolytic enzymes enriched in bromelain (anacaulase-bcdb ), the active pharmaceutical ingredient (API), that is blended with excipients. EX-03 5% powder, should be diluted with Water for Injection (WFI) prior usage.

Drug: EX-03; a sterile lyophilized powder containing a concentrate of proteolytic enzymes enriched in bromelain (anacaulase-bcdb). The powder and sterile water are mixed to form a gel prior to application on the w; Other Names: Gel vehicle; 5% EscharEx; EX-03 formulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Evaluation	Cmax (maximal observed serum concentration),	Up to 2 weeks
Safety and Tolerability Endpoints	Incidence and severity of systemic and local adverse events (AEs),	up to 5 weeks
PK Evaluation	AUC (area under the concentration -time curve)	Up to 2 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of complete debridement, clinically (visually) assessed after each application during the Daily Visits Period (up to 8 applications)	counting events of complete debridement	up to 2 weeks
Incidence of complete healthy viable granulation tissue, at the end of the Daily Visits Period, as assessed clinically	counting events of complete granulation	up to 2 weeks

Collaborators and Investigators

• Sponsor: MediWound Ltd
• Collaborators: TFS HealthScience

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): August 1, 2028
• Study Completion (Estimated): August 1, 2028

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 9, 2026

Study Record Updates

• Last Update Posted (Actual): July 9, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Debridement; VLU; Wound bed preparation; EscharEx
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Skin Diseases; Skin Ulcer; Varicose Veins; Leg Ulcer; Skin and Connective Tissue Diseases; Varicose Ulcer; Pharmaceutical Preparations; Dosage Forms; Complex Mixtures; Colloids; Gels
• Other Study ID Numbers: MW2022-04-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No