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

NCT06690177 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MW2023-11-18
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 2

Brief Summary

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.

Conditions

Venus Leg Ulcers

Keywords

VLU; EscharEx; Debridement

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (2)

• Incidence of complete debridement

  Up to 8 applications (14 days)

• Incidence of complete healthy viable granulation tissue

  Up to 8 applications (14 days)

Study Arms (3)

EscharEx (EX-03)

ACTIVE COMPARATOR

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)

Placebo

PLACEBO COMPARATOR

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)

Collagenase

OTHER

Non-surgical standard of care treatment arm

Drug: EscharEx (EX-03); Drug: Placebo (Gel vehicle)

Interventions

EscharEx (EX-03) DRUG

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.

Collagenase; EscharEx (EX-03)

Placebo (Gel vehicle) DRUG

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

Collagenase; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women, older than 18 years of age,
• Patients with a VLU (determined by medical history, physical examination, and a documented ultrasound scan demonstrating venous insufficiency),
• Wound is present for at least 4 weeks but no longer than 1 year,
• The necrotic/slough/fibrin non-viable tissue area is at least 50% of the wound area (assessed by clinical evaluation),
• Target wound surface area is in the range of 2-25 cm2 (assessed by eKare inSightTM),
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• MediWound Ltd: lead

Study Sites (2)

ILD Research Center

Carlsbad, California, 92009, United States

Location

Wojskowy Instytut Medyczny

Warsaw, Poland

Location

MeSH Terms

Interventions

Gels

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Central Study Contacts

Shelly Vander, MSc

CONTACT

+972 52 3527960; shellyv@mediwound.com

Keren David- Zarbiv, MSc

CONTACT

+972 54 2233052; kerend@mediwound.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2024
• First Posted: November 15, 2024
• Study Start: April 30, 2025
• Primary Completion (Estimated): December 30, 2027
• Study Completion (Estimated): September 30, 2028
• Last Updated: November 15, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

PL (1); US (1)