A Double Blind Study Performed to Evaluate the Efficacy and the Safety of EscharEx in Debridement of VLU (VALUE) (VALUE)

March 27, 2026 updated by: MediWound Ltd

A Multicenter, Prospective, Randomized, Double Blind, Placebo Controlled, Adaptive Design Study Performed to Evaluate the Efficacy and the Safety of EscharEx in Debridement of Venous Leg Ulcers (VALUE)

The main objective of this study is:

To assess the efficacy and safety of EscharEx (EX-03 5% formulation) compared to placebo control,in debridement and wound bed preparation of Venous Leg Ulcers (VLU).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

At least 216 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.

Total duration of the study is up to 29 weeks:

  1. Screening period (2 visits, 7 days apart),
  2. Daily Visits Period - Debridement with IMP (up to 8 daily site visits within up to 2 weeks),
  3. Weekly Visits Period - wound management (up to 13 visits within up to 12 weeks) + optional wound closure confirmation (up to 2 weeks). Wound will be managed in a standardized manner.
  4. Monthly Visits Period - Wound Closure Durability Period of 12 weeks starting after wound closure confirmation (3 visits within 12 weeks) performed for all wounds.

Study Type

Interventional

Enrollment (Estimated)

216

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Austria
      • Graz, Austria, 8036
      • Vienna, Austria, 1090
        • Recruiting
        • Medical University Wien
        • Contact:
        • Principal Investigator:
          • Christine Christine Radtke, MD
  • Germany
      • Bochum, Germany
        • Recruiting
        • Ruhr-University Bochum
        • Contact:
        • Principal Investigator:
          • Markus Stücker, MD
      • Dresden, Germany
      • Erlangen, Germany
        • Recruiting
        • Wundzentrum Dermatologie Erlangen
        • Contact:
        • Principal Investigator:
          • Cornelia Erfurt-Berge, MD
      • Kiel, Germany
        • Recruiting
        • DermaKiel - Allergie und Haut Centrum
        • Principal Investigator:
          • Harald Brüning, MD
        • Contact:
        • Contact:
  • Israel
      • Be’er Ya‘aqov, Israel
        • Recruiting
        • Asaf Harofeh (Shamir) Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Eyal Shapira, MD
      • Rehovot, Israel
        • Recruiting
        • Kaplan Medical Center
        • Contact:
        • Principal Investigator:
          • Dana Egozi, MD
  • Poland
      • Lodz, Poland
        • Recruiting
        • MIKOMED Sp. z o.o.
        • Contact:
        • Principal Investigator:
          • Jacek Mikosiński, MD
      • Nowy Targ, Poland
        • Recruiting
        • Allmedica Badania Kliniczne
        • Contact:
        • Principal Investigator:
          • Urszula Brudnik, MD
      • Poznan, Poland
        • Recruiting
        • Centrum Medyczne Solumed
        • Contact:
        • Principal Investigator:
          • Piotr Zelga, MD
  • United States
    • California
      • Fresno, California, United States, 93710
        • Not yet recruiting
        • Limb Preservation Platform, Inc
        • Principal Investigator:
          • Shawn Cazzell, DPM
        • Contact:
      • Los Angeles, California, United States, 90010
      • San Francisco, California, United States, 94115
        • Recruiting
        • Center for Clinical Research INC
        • Principal Investigator:
          • Alexander Reyzelman, DPM
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Mher Vartivarian, DPM
      • Vista, California, United States, 92081
        • Not yet recruiting
        • ILD Research Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Dean Dean Vayser, MD
    • Florida
      • Miami, Florida, United States, 33136
        • Recruiting
        • University of Miami
        • Principal Investigator:
          • Robert Kirsner, MD
        • Contact:
        • Contact:
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
        • Principal Investigator:
          • Jeremy Goverman, MD
        • Contact:
        • Contact:
      • Boston, Massachusetts, United States, 02118
        • Not yet recruiting
        • Boston Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Elizabeth Sanders, MD
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • Recruiting
        • Rutgers New Jersey Medical Center
        • Contact:
        • Contact:
        • Principal Investigator:
          • Alex Wong, MD
    • New York
      • Lake Success, New York, United States, 11042
        • Active, not recruiting
        • Northwell Health Comprehensive Wound Healing Center
      • Mineola, New York, United States, 11501
        • Recruiting
        • NYU Langone Health Long Island - Research & Academic Center
        • Principal Investigator:
          • Scott Gorenstein, MD
        • Contact:
        • Contact:
      • New York, New York, United States, 10019
        • Recruiting
        • Mount Sinai West
        • Contact:
        • Contact:
        • Principal Investigator:
          • Michael Michael Dudkiewicz, MD
        • Sub-Investigator:
          • John Lantis, MD
        • Sub-Investigator:
          • Mary Bridge, MD
    • Ohio
      • Circleville, Ohio, United States, 43113
        • Recruiting
        • Cutting Edge Research LLC.,
        • Contact:
        • Principal Investigator:
          • Brock Liden, MD
    • Texas
      • Houston, Texas, United States, 77074
        • Recruiting
        • Clinical Trial Network Houston
        • Contact:
        • Contact:
        • Principal Investigator:
          • Ullabritt Larka, MD
      • San Antonio, Texas, United States, 78251

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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 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, 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 procedure.

Exclusion Criteria:

  1. Wound size that has decreased by > 20% after 7 (+3/-1) days of the 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, that are between 2cm and 5cm away from the edge of the target wound,
  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,
  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 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, 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. Patients with pre-enrollment 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 < 2.5 g/dl; poorly controlled diabetes mellitus (HbA1c > 12%); anemia (hemoglobin<8 g/dL), leukocyte count < 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 or eGFR < 30ml/min /1.73m2), 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. Patients undergoing renal or peritoneal dialysis,
  17. Any condition that would preclude safe participation in the study, e.g., significant or unstable cardiac, vascular, pulmonary, liver, hematological, immunological, neoplastic disease, active COVID-19 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, 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 processes. These include chronic systemic steroid intake5 associated with topical skin changes (i.e. thin, fragile skin with multiple hematomas or a history of laceration), 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. Patients 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 incompetent adults who are incapable of giving legal consent (e.g., dementia, psychiatric patients, 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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

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.
Other Names:
  • EX-03
Placebo Comparator: Placebo

Placebo (Gel Vehicle, hydrogel) contains the same excipients as in EX-03, without the API.

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 Names:
  • Gel vehicle

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of complete debridement, clinically (visually) assessed after each application
Time Frame: up to 2 weeks
counting events of complete debridement
up to 2 weeks
Facilitation of wound closure, clinically assessed, as measured by time to complete wound closure
Time Frame: up to 12 weeks
counting events of complete wound closure until completion of weekly visits
up to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of complete healthy viable granulation tissue, as assessed clinically
Time Frame: up to 2 weeks
counting events of complete granulation
up to 2 weeks
Time to the first declaration of complete debridement, clinically assessed
Time Frame: up to 12 weeks
count in days
up to 12 weeks
Time to Wound Bed Prepared, clinically assessed
Time Frame: up to 12 weeks
Number of events counted in days
up to 12 weeks
Incidence of complete wound closure, clinically assessed,
Time Frame: up to 12 weeks
count of number of events
up to 12 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of systemic and local adverse events
Time Frame: up to 27 weeks
up to 27 weeks
Incidence of target wound infections
Time Frame: up to 27 weeks
counting events
up to 27 weeks
Incidence of discontinuation due to adverse events
Time Frame: up to 27 weeks
counting events of discontinuation
up to 27 weeks
Change in pain, as assessed by Numeric Pain Rating Scale (NPRS)
Time Frame: up to 12 weeks
up to 12 weeks
Immunogenicity evaluation
Time Frame: baseline, post last daily visit, 4 and 10 weeks following last daily visit, and on last monthly visit
measurement of Anti-Drug-Antibodies levels
baseline, post last daily visit, 4 and 10 weeks following last daily visit, and on last monthly visit

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

MediWound Ltd

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

June 1, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

August 4, 2024

First Submitted That Met QC Criteria

August 22, 2024

First Posted (Actual)

August 23, 2024

Study Record Updates

Last Update Posted (Actual)

April 2, 2026

Last Update Submitted That Met QC Criteria

March 27, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MW2022-06-22

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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