A Study to Evaluate the Safety and the Efficacy of EscharEx (EX-02 Formulation) in Debridement of Venous Leg Ulcers

NCT03588130 | Completed Phase 2 FDA Drug

• 1 other identifier: MW2017-06-28
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 22

Brief Summary

This study is a multicenter, prospective, randomized, placebo controlled, adaptive design study performed to assess the safety and the efficacy of 5% EscharEx (EX-02) compared to Gel Vehicle (placebo) and non-surgical standard of care (NSSOC), in debridement of Venous Leg Ulcers (VLU) (in a ratio of 2:2:1) in debridement of VLU. The main objective of this study is: To assess the safety and the efficacy of EscharEx (EX-02 formulation) compared to Gel Vehicle (placebo) and non-surgical standard of care (NSSOC), in debridement of Venous Leg Ulcers (VLU). 120 randomized adult patients with VLU that fail to heal for 4 weeks to 2 years, and with \>50% non-viable tissue (necrotic/slough/fibrin) on the VLU. The maximum number of patients to be enrolled is 160. The total duration of the study of each participating subject is up to 17 weeks: screening (1 week) + Daily visit period (up to 2 weeks) + Twice-weekly visits period (2 weeks) + Weekly visits period (10 weeks) + closure confirmation (up to 2 weeks, if applicable). Each patient will go through 4 periods during the trial:

1. 1.Screening period (2 visits, 7 \[+2\] days apart). Including: recording demographics, medical history and concomitant medications, vital signs, physical examination, clinical laboratory tests, wound photography and assessments and questionnaires (pain, wound status and QoL). During this period, wounds will be treated by standard treatment (e.g. appropriate dressing, compression bandage) per investigator discretion, with the exclusion of mechanical and surgical debridement.
2. 2.Daily visits period (up to 8 daily site visits within up to 14 days): During the Daily visit period, the patient will arrive daily to site visits. During each visit, adverse events, concomitant medication, vital signs and pain will be recorded, the wound will be washed, photographed and assessed for wound size (by eKare inSightTM), % of non viable tissue (by clinical assessment), and wound healing status (assessed clinically).
3. 3.Twice-weekly visits period (4 visits within 14 days): the patients will be followed twice weekly for two weeks, (4 visits within 14 days). During each visit, safety parameters will be recorded (AEs, concomitant medications, pain, vital signs), the wound will be washed, photographed and assessed for wound size (by eKare inSightTM), % of nonviable tissue (by clinical assessment), and wound healing status (assessed clinically).
4. 4.Weekly visits period (up to10 visits within up to 10 weeks): patients will be followed once weekly for 10 weeks or until complete wound closure was achieved, (up to10 visits within up to 10 weeks). During each weekly visit, safety parameters will be recorded (AEs, concomitant medications, pain, vital signs), the wound will be washed, photographed and assessed for wound size (by eKare inSightTM), % of nonviable tissue (by clinical assessment), and wound healing status (assessed clinically).

Conditions

Venous Leg Ulcer

Keywords

Debridement

Outcome Measures

Primary Outcomes (1)

• Incidence of complete debridement in EX-02 vs. Gel Vehicle arms, scored dichotomously (yes/no), clinically assessed

  The clinical assessor will define complete debridement, after each application during the daily visits period

  up to 8 applications, within 14 days

Study Arms (3)

EscharEx (5% EX-02 formulation)

ACTIVE COMPARATOR

Debridement will be performed with 5% EX-02 for 24±3 hours, up to 8 applications

Drug: EscharEx (5% EX-02 formulation)

Gel Vehicle

PLACEBO COMPARATOR

Debridement will be performed with Gel vehicle for 24±3 hours, up to 8 applications

Drug: Gel Vehicle

Non-surgical standard of care (NSSOC)

ACTIVE COMPARATOR

Debridement will be performed with NSSOC (Santyl or commercially approved Hydrogel) per routine procedures, until complete debridement is achieved

Drug: Non-surgical standard of care (NSSOC)

Interventions

EscharEx (5% EX-02 formulation) DRUG

Active arm

EscharEx (5% EX-02 formulation)

Gel Vehicle DRUG

Control arm

Gel Vehicle

Non-surgical standard of care (NSSOC) DRUG

Santyl (Enzymatic debridement) or commercially approved Hydrogel

Non-surgical standard of care (NSSOC)

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients, men or women, between 18 and 90 years of age,
• Patients with a VLU (determined by medical history, physical examination, and an ultrasound scan demonstrating venous insufficiency),
• Wound is present for at least 4 weeks but no longer than 2 years.
• The necrotic/slough/fibrin non-viable tissue area is at least 50% of wound area (assessed by clinical evaluation),
• Target wound surface area is in the range of 2-100 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 procedure.

You may not qualify if:

• Wound size decreased by \> 20% after 1 week of standard-of-care-only period (screening period),
• Patients with more than one leg ulcer, on the leg of the target wound, with an area greater than or equal to 2cm2,
• Signs of clinically significant infection including purulent discharge, deep-tissue abscess, erysipelas, cellulitis, etc.,
• Severely damaged skin (e.g. abrasion, exfoliation) extending \>2 cm around the wound's edge,
• Presence of gangrene, signs of systemic infection, sepsis, or osteomyelitis during screening phase,
• Clinical suspicion of skin cancer (e.g. BCC, SCC, melanoma, sarcoma), which was not ruled out by biopsy,
• Patients with skin disorders unrelated to the wound that are presented adjacent to the wound,
• Patients suffering from chronic skin disorders (Idiopathic Pruritus, Psoriasis, Panniculitis, Pyoderma Gangrenosum, etc.) that might deteriorate as a result of local trauma or debridement,
• Wound has sinus tracts or tunnels extending under healthy tissue (following debridement "un-roofing"- if relevant), or penetrating into joint capsule,
• Vascular operations in proximity to the wound in the last month,
• Patients with primary lymphatic edema,
• A significant decrease in the arterial blood flow of the extremity
• 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),
• History of allergy or atopic disease or a known sensitivity to pineapples, papaya, bromelain or papain, as well as known sensitivity to latex proteins (known as latex-fruit syndrome), bee venom or olive tree pollen,
• Patients with poor nutritional status: albumin \< 2.5g/dl, poorly controlled Diabetes Mellitus (for diabetic patients; HbA1c \> 12%), anemia (hemoglobin\<8 g/dL), a leukocyte counts \< 3,800// μl or \>15000/μl, platelets \<100,000/μl, abnormal liver function (AST, ALT\>2 x upper limit of normal range), renal failure (Cr \> 2.5 mg/dl), BMI\>48,

Sponsors & Collaborators

• MediWound Ltd: lead

Study Sites (22)

ILD Research Center

Carlsbad, California, 92009, United States

Location

Limb Preservation Platform, Inc.

Fresno, California, 93710, United States

Location

Felix Sigal. D.P.M, PC

Los Angeles, California, 90057, United States

Location

Stanford

Redwood City, California, 94063, United States

Location

Center for Clinical Research Inc.

San Francisco, California, 94115, United States

Location

Medstar Health Georgetown University

Washington D.C., District of Columbia, 20007, United States

Location

C & R Research Services USA, Inc

Coral Gables, Florida, 33134, United States

Location

INTEGRAL - Clinical Trials Solutions

Doral, Florida, 33126, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Barry University Clinical Research

Miami Beach, Florida, 33169, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114-2621, United States

Location

Boston Medical Center/Boston University Medical Center

Boston, Massachusetts, 02118, United States

Location

South Shore Health System, Center for Wound Healing

Weymouth, Massachusetts, 02189, United States

Location

Advanced Foot & Ankle Center

Las Vegas, Nevada, 89119, United States

Location

Atlantic Health System - Overlook Wound Care Center

Summit, New Jersey, 07901, United States

Location

Bey Lea Ambulatory Surgical Center

Toms River, New Jersey, 08753, United States

Location

NYU Winthrop Hospital

Mineola, New York, 11501, United States

Location

Mount Sinai St. Luke's Hospital

New York, New York, 10025, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

AZH Wound Center

Milwaukee, Wisconsin, 53221, United States

Location

Hopitaux Universitaires de Geneva

Geneva, Canton, 1211, Switzerland

Location

Related Publications (1)

• Shoham Y, Snyder RJ, Katz Levy Y, David Zarbiv K, Klinger E, Kramer M, Dove CR, Avrahami R, Reyzelman A, Sigal F, Tovmassian G, Shapira E, Harats M, Perez-Clavijo F, Lantis JC, Cazzell SM, Dhillon YS, Cuffy CA, Egozi D, Vayser D, Singer AJ, Galperin RC, Hanft JR, Martinez C, Shalom A, Toutous-Trellu L, Rosenberg L. Once daily Bromelain-based enzymatic debridement of venous leg ulcers versus gel vehicle (placebo) and non-surgical standard of care: a three-arm multicenter, double blinded, randomized controlled study. EClinicalMedicine. 2024 Jul 27;75:102750. doi: 10.1016/j.eclinm.2024.102750. eCollection 2024 Sep.

  PMID: 39763591 DERIVED

MeSH Terms

Conditions

Varicose Ulcer

Interventions

Gels

Condition Hierarchy (Ancestors)

Varicose Veins; Vascular Diseases; Cardiovascular Diseases; Leg Ulcer; Skin Ulcer; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinding of subjects, study team on sites (e.g. investigators, study nurses etc.) and sponsor team to the assigned treatment will be employed between EX-02 arm and Gel Vehicle arm. Since the NSSOC appearance and dosing regimen are different from that of IMP (EX-02 or Gel vehicle), treatment with NSSOC arm can not be masked to study team or sponsor.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2018
• First Posted: July 17, 2018
• Study Start: December 2, 2019
• Primary Completion: December 7, 2021
• Study Completion: March 23, 2022
• Last Updated: November 14, 2022

Record last verified: 2022-01

Locations

US (21); CH (1)