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)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Mediwound Ltd.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Skin and Connective Tissue Diseases [C17]

Trial duration

20 Oct 2025 → ongoing

Decision date (initial)

2025-06-11

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-519623-23-00

ClinicalTrials.gov

NCT06568627

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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

Conditions and MedDRA coding

Venous leg ulcer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency, Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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. Patients understand 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 25

1. Wound size that has decreased by > 20% after 7 (+3/-1) days of the screening period
2. Patients with primary lymphatic edema (Lymphedema)
3. 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
4. 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)
5. 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
6. 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 or eGFR < 30ml/ min /1.73m2), BMI>48
7. 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)
8. Patients undergoing renal or peritoneal dialysis
9. 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
10. Recent history or concurrent acute injury or disease that might compromise the patient’s welfare, according to investigator discretion
11. The 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 at doses known to affectimpair the wound healing processes; these. These include chronic systemic steroid intake associated with topical skin changes (i.e. thin, fragile skin with multiple hematomas or previous history of laceration), immunosuppressive 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
12. 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
13. Patients treated with Pentoxifylline within 2 weeks prior to screening
14. Mentally incompetent adults who are incapable of giving legal consent (e.g. dementia, psychiatric patients, etc.)
15. Concurrent use of non-approved drugs or alcohol abuse
16. Pregnant women (positive pregnancy test) or nursing mothers
17. 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
18. Signs of clinical infection of the wound or peri-wound, including purulent discharge, deep-tissue abscess, erysipelas, cellulitis, etc
19. Severely damaged skin (e.g. abrasion, erosion, exfoliation) extending >2 cm around the wound's edge
20. Presence of gangrene, signs of systemic infection, sepsis, or osteomyelitis during screening phase
21. 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
22. Patients with skin disorders unrelated to the wound that are presented adjacent to the wound
23. Patients suffering from chronic skin disorders (Idiopathic Pruritus, Psoriasis, Panniculitis, Pyoderma gangrenosum, etc.) that might deteriorate as a result of local trauma or debridement
24. Wound has sinus tracts or tunnels extending under healthy tissue or penetrating into periosteum, fascia or bone
25. Venous ablation performed within the past month in an area adjacent to the target wound

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Incidence of complete debridement, clinically (visually) assessed after each application during the Daily Visits Period (up to 8 applications),
2. Facilitation of wound closure, as measured by time to complete wound closure, clinically assessed from the initiation of study treatment until the end of the Weekly Visits Period.

Secondary endpoints 4

1. Incidence of complete healthy viable granulation tissue, at the end of the Daily Visits Period, as assessed clinically
2. Time to the first declaration of complete debridement, clinically assessed, from the initiation of study treatment until the end of the Weekly Visits Period
3. Time to Wound Bed Prepared, clinically assessed, from the initiation of study treatment until the end of the Weekly Visits Period
4. Incidence of complete wound closure, clinically assessed, from the initiation of study treatment, until the end of the Weekly Visits Period.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Mediwound Ltd.

Sponsor organisation

Mediwound Ltd.

Address

42, Ha-Yarkon

City

Yavne

Postcode

8122745

Country

Israel

Scientific contact point

Organisation

Mediwound Ltd.

Contact name

Director, EscharEx Clinical Development Program

Public contact point

Organisation

Mediwound Ltd.

Contact name

Director, EscharEx Clinical Development Program

Third parties 9

Locations

4 EU/EEA countries · 23 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 48 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications