CONCENTRATE OF PROTEOLYTIC ENZYMES ENRICHED IN BROMELAIN for Venous leg ulcer | Venous stasis ulcer

Inclusion criteria

• {"criterion_text":"- Men or women, older than 18 years of age"}
• {"criterion_text":"- Patients with a VLU (determined by medical history, physical examination, and a documented ultrasound scan demonstrating venous insufficiency)"}
• {"criterion_text":"- Wound is present for at least 4 weeks but no longer than 1 year"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Target wound surface area is in the range of 2-25 cm2 (assessed by eKare inSightTM)"}
• {"criterion_text":"- 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

• {"criterion_text":"- Wound size that has decreased by > 20% after 7 (+3/-1) days of the screening period"}
• {"criterion_text":"- Patients with primary lymphatic edema (Lymphedema)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Patients undergoing renal or peritoneal dialysis"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Recent history or concurrent acute injury or disease that might compromise the patient’s welfare, according to investigator discretion"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Patients treated with Pentoxifylline within 2 weeks prior to screening"}
• {"criterion_text":"- Mentally incompetent adults who are incapable of giving legal consent (e.g. dementia, psychiatric patients, etc.)"}
• {"criterion_text":"- Concurrent use of non-approved drugs or alcohol abuse"}
• {"criterion_text":"- Pregnant women (positive pregnancy test) or nursing mothers"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Signs of clinical infection of the wound or peri-wound, including purulent discharge, deep-tissue abscess, erysipelas, cellulitis, etc"}
• {"criterion_text":"- Severely damaged skin (e.g. abrasion, erosion, exfoliation) extending >2 cm around the wound's edge"}
• {"criterion_text":"- 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)"}
• {"criterion_text":"- Presence of gangrene, signs of systemic infection, sepsis, or osteomyelitis during screening phase"}
• {"criterion_text":"- 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"}
• {"criterion_text":"- Patients with skin disorders unrelated to the wound that are presented adjacent to the wound"}
• {"criterion_text":"- Patients suffering from chronic skin disorders (Idiopathic Pruritus, Psoriasis, Panniculitis, Pyoderma gangrenosum, etc.) that might deteriorate as a result of local trauma or debridement"}
• {"criterion_text":"- Wound has sinus tracts or tunnels extending under healthy tissue or penetrating into periosteum, fascia or bone"}
• {"criterion_text":"- Venous ablation performed within the past month in an area adjacent to the target wound"}

Primary endpoints

• {"endpoint_text":"- Incidence of complete debridement, clinically (visually) assessed after each application during the Daily Visits Period (up to 8 applications),","definition_or_measurement_approach":"Clinically (visually) assessed after each application during the Daily Visits Period (up to 8 applications)."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time to complete wound closure, clinically assessed from initiation of study treatment until the end of the Weekly Visits Period."}

Secondary endpoints

• {"endpoint_text":"- Incidence of complete healthy viable granulation tissue, at the end of the Daily Visits Period, as assessed clinically","definition_or_measurement_approach":"Clinically assessed incidence of complete healthy viable granulation tissue at end of the Daily Visits Period."}
• {"endpoint_text":"- Time to the first declaration of complete debridement, clinically assessed, from the initiation of study treatment until the end of the Weekly Visits Period","definition_or_measurement_approach":"Time from initiation of study treatment to first clinical declaration of complete debridement, assessed until end of Weekly Visits Period."}
• {"endpoint_text":"- Time to Wound Bed Prepared, clinically assessed, from the initiation of study treatment until the end of the Weekly Visits Period","definition_or_measurement_approach":"Time from initiation of study treatment to clinical assessment of wound bed preparation, assessed until end of Weekly Visits Period."}
• {"endpoint_text":"- Incidence of complete wound closure, clinically assessed, from the initiation of study treatment, until the end of the Weekly Visits Period.","definition_or_measurement_approach":"Clinically assessed incidence of complete wound closure from initiation of study treatment until end of Weekly Visits Period."}

Austria

Earliest CTIS Part Ii Submission Date

14-05-2025

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

364

Number Of Sites

2

Number Of Participants

12

Italy

Earliest CTIS Part Ii Submission Date

13-05-2025

Latest Decision Or Authorization Date

20-04-2026

Processing Time Days

342

Number Of Sites

6

Number Of Participants

30

Germany

Earliest CTIS Part Ii Submission Date

19-05-2025

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

359

Number Of Sites

6

Number Of Participants

30

Poland

Earliest CTIS Part Ii Submission Date

19-05-2025

Latest Decision Or Authorization Date

13-05-2026

Processing Time Days

359

Number Of Sites

9

Number Of Participants

27

Primary sponsor

Full Name

Mediwound Ltd.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Israel

Contract research organisations

Name

Bioforum C.D.M.C Ltd.

Responsibilities

6

Name

Almac Clinical Services Limited

Responsibilities

14

Name

Trialog Clinical Trials Ltd.

Responsibilities

IMP Labeling

Third parties

• {"country":"United States","full_name":"Mimedx Group Inc.","duties_or_roles":"Provider of allograft tissue product (AxMP)","organisation_type":"Pharmaceutical company"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services SARL","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Healthlink Europe B.V.","duties_or_roles":"14; AxMP importer","organisation_type":"Pharmaceutical company"}
• {"country":"Israel","full_name":"Bioforum C.D.M.C Ltd.","duties_or_roles":"6","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"14","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Biologics Development Services LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
• {"country":"Czechia","full_name":"PrimeVigilance s.r.o.","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Israel","full_name":"Trialog Clinical Trials Ltd.","duties_or_roles":"IMP Labeling","organisation_type":"Pharmaceutical company"}