Clinical Study to Evaluate the Safety and the Efficacy of EscharEx Drug Product (EX-03 Formulation) and Its Placebo Compared to Collagenase, Non-surgical Standard of Care, in Patients With Venous Leg Ulcers (VLU)

A Multicenter, Prospective, Randomized, Placebo and Collagenase (Non-surgical Standard-of-care) Controlled Study, Performed to Evaluate the Safety and the Efficacy of EscharEx Drug Product (EX-03 Formulation) and Its Placebo Compared to Collagenase in Patients With Venous Leg Ulcers

The main objective of this study is:

To assess the safety of EscharEx (EX-03 5% formulation) compared to placebo control and compared to Collagenase (NSSOC) in patients with VLU.

Study Overview

• Status: Not yet recruiting
• Conditions: Venus Leg Ulcers
• Intervention / Treatment: Drug: EscharEx (EX-03); Drug: Placebo (Gel vehicle)

Detailed Description

At least 45 eligible adult patients with VLU (with a surface area between 2 cm2 and 25 cm2, and wound age between 4 weeks and 12 months), will be randomized. The patients will be treated with IMP (either EX-03 5% or placebo) in a double blinded manner or with Collagenase in unblinded manner.

Total duration of the study is up to 15 weeks:

Screening period (2 visits, 7 days apart), Daily Visits Period - Debridement with IMP (up to 8 daily site visits within up to 2 weeks), Weekly Visits Period - wound management (up to 11 visits within up to 10 weeks) + optional wound closure confirmation (up to 2 weeks). Wound will be managed in a standardized manner.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Shelly Vander, MSc; Phone Number: +972 52 3527960; Email: shellyv@mediwound.com
• Study Contact Backup: Name: Keren David- Zarbiv, MSc; Phone Number: +972 54 2233052; Email: kerend@mediwound.com

Study Locations

• Poland
  • Warsaw, Poland
    • Wojskowy Instytut Medyczny
• United States
  • California
    • Carlsbad, California, United States, 92009
      • ILD Research Center

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. Patients 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 1 year,
4. The necrotic/slough/fibrin non-viable tissue area is at least 50% of the wound area (assessed by clinical evaluation),
5. Target wound surface area is in the range of 2-25 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 procedur

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 2 cm2, 3.Signs of clinical infection of the wound or peri-wound, including purulent discharge, deep-tissue abscess, erysipelas, cellulitis, 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 during 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, 6.Patients with skin disorders unrelated to the wound that are presented adjacent to the wound, 7.Patients suffering from chronic skin disorders (Idiopathic Pruritus, Psoriasis, 8. 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.Patients with primary lymphatic edema (Lymphedema), 11.A significant decrease in the arterial blood flow of the extremity , 12.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), 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.Patients with poor nutritional status: albumin < 2.5g/dl, poorly controlled diabetes Mellitus (HbA1c > 12%), anemia (hemoglobin<8 g/dL), a leukocyte counts < 3,000/μl or >15000/μl, neutrophil count ≤1000/ μl, platelets <100,000/μl, abnormal liver function (AST, ALT>2 x upper limit of normal range), renal failure (Cr > 2.5 mg/dl and eGFR < 30ml/ min /1.73m2), BMI>48, 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), 15.Patients undergoing renal or peritoneal dialysis, 16.Any condition that would preclude safe participation in the study, e.g. significant or unstable cardiovascular, pulmonary, liver, hematological, immunological, neoplastic disease, active COVID-19, or any immediate life threatening condition, 17.Recent history or concurrent acute injury or disease that might compromise the patient's welfare, according to investigator discretion, 18.Patient is currently receiving, or has received at any time 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 with topical skin changes (i.e. thin, fragile skin with multiple heamatomas or previous laceration history) immuno-suppressive drugs, immunomodulating medications, chemotherapy and radiation therapy, In case the subject is treated with Pentoxifylline, dosing is stable less than 4 weeks, 19.Mentally incompetent adults who are incapable of giving legal consent (e.g. dementia, psychiatric patients, etc.), 20.Concurrent use of non-approved drugs or alcohol abuse, 21.Pregnant women (positive pregnancy test) or nursing mothers, 22.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.

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Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

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: EscharEx (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 wound area.
Placebo Comparator: Placebo; Placebo (Gel Vehicle, hydrogel) contains the same excipients as in EX-03, without the API. A sterile powder containing excipients only (no proteolytic enzymes). The powder and sterile water are mixed to form a gel prior to application on the wound area Placebo powder, should be diluted with Water for Injection (WFI) prior usage	Drug: Placebo (Gel vehicle); A sterile powder containing excipients only (no proteolytic enzymes). The powder and sterile water are mixed to form a gel prior to application on the wound area
Other: Collagenase; Non-surgical standard of care treatment arm	Drug: EscharEx (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 wound area.; Drug: Placebo (Gel vehicle); A sterile powder containing excipients only (no proteolytic enzymes). The powder and sterile water are mixed to form a gel prior to application on the wound area

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence (number of patients) of target wound related AEs throughout the trial	The endpoint will assess number of patients, in each arm, with reported local (target wound related) AEs	Throughout the study (week 2- week 15)
Number of patients with Clinically significant changes in vital signs during the Daily Visits Period,	Number of patients with Clinically significant changes in vital signs	Weeks 2-3 (14 days)
Number of patients with Clinically significant changes in clinical laboratory parameters	Number of patients with Clinically significant changes in clinical laboratory parameters	Weeks 2-3 (14 days)
Time to complete wound closure	The outcome will assess time to reaching complete wound closure	Weeks 2-15
Incidence of complete wound closure	The outcome will assess number of patients reaching complete wound closure	2-15 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of complete debridement	the outcome will assess number of patients with complete debridement assessed clinically	Up to 8 applications (14 days)
Incidence of complete healthy viable granulation tissue	the outcome will assess number of patients with complete healthy viable granulation tissue on the treated wound, assessed clinically	Up to 8 applications (14 days)

Collaborators and Investigators

• Sponsor: MediWound Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): September 30, 2028

Study Registration Dates

• First Submitted: October 29, 2024
• First Submitted That Met QC Criteria: November 14, 2024
• First Posted (Actual): November 15, 2024

Study Record Updates

• Last Update Posted (Actual): November 15, 2024
• Last Update Submitted That Met QC Criteria: November 14, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Debridement; VLU; EscharEx
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Skin Diseases; Skin Ulcer; Varicose Veins; Ulcer; Varicose Ulcer; Leg Ulcer
• Other Study ID Numbers: MW2023-11-18

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