Evaluation of the Efficacy and Safety of 5% EscharEx (Concentrate of Proteolytic Enzymes Enriched in Bromelain) in Debridement of Venous Leg Ulcers

The primary objective of this study is to assess the **efficacy** and **safety** of 5% EscharEx (EX-03 formulation) compared to placebo in the debridement and wound bed preparation of **Venous Leg Ulcers** (VLU). This evaluation is clinically relevant as effective debridement is crucial for promoting wound healing and preventing complications in patients with VLU. The study aims to provide evidence on whether EscharEx can enhance the debridement process, potentially leading to improved patient outcomes and reduced healthcare burden associated with chronic wound management.

The clinical trial involves a total of **120 participants** diagnosed with **venous leg ulcers**. The study population includes both male and female subjects, all of whom are over the age of 18. Participants were selected based on specific criteria, including the presence of a venous leg ulcer confirmed by medical history, physical examination, and ultrasound scan demonstrating venous insufficiency. The ulcers must have been present for a minimum of four weeks and no longer than one year, with at least 50% of the wound area consisting of necrotic, slough, or fibrin non-viable tissue. The target wound surface area is required to be between 2 and 25 cm². Participants are expected to understand the nature of the procedure, adhere to the protocol regimen, and provide written informed consent prior to any study procedure. The trial does not include a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted in the selection process.

The clinical trial is designed as a **randomized**, **double-blind**, **placebo-controlled** study to evaluate the efficacy and safety of EscharEx in the debridement of **venous leg ulcers**. The trial will involve a multicenter approach and will employ an adaptive design to assess the primary and secondary endpoints effectively. The study is expected to commence recruitment in July 2025 and conclude by December 2027, with the trial phase categorized as Phase III.

Participants will be randomly assigned to receive either the investigational product, EscharEx, or a placebo (gel vehicle). The investigational product is a **powder for gel** containing a concentrate of proteolytic enzymes enriched in bromelain, applied topically on the wound. The placebo will serve as a control to ensure the reliability of the results. The trial will include a screening visit to confirm eligibility based on specific inclusion criteria, such as age, presence of a venous leg ulcer, and the extent of non-viable tissue.

The study will consist of several visits, including daily visits for up to eight applications during the initial treatment period, followed by weekly visits to monitor wound closure and granulation tissue formation. The primary endpoints include the incidence of complete debridement and wound closure, while secondary endpoints focus on the time to achieve these outcomes. The expected duration of participant involvement is approximately two months, with conditions for early termination including adverse events or non-compliance with the study protocol.

Participants will be monitored closely throughout the trial, with the end-of-study visit marking the completion of their involvement. This visit will include a final assessment of the wound and overall health status. The trial aims to provide valuable insights into the treatment of venous leg ulcers, potentially improving patient outcomes through effective wound management strategies.

The clinical trial involves the evaluation of three treatments, including an experimental medication and two non-experimental treatments. The **experimental medication**, EscharEx, is a **powder for gel** formulation containing a **concentrate of proteolytic enzymes enriched in bromelain**. This botanical product is applied topically on wounds, specifically for the debridement of **venous leg ulcers**. The maximum daily dose is 3500 gm/m², with a total maximum dose of 28000 gm/m² over a treatment period of up to 2 weeks. The application is performed once daily, and participant compliance is monitored through regular assessments.

The first non-experimental treatment is a **placebo**, formulated as a gel vehicle. The placebo is used to maintain the double-blind nature of the study and is applied topically on the wound in a manner identical to the experimental medication. The placebo does not contain any active substances and serves as a control to evaluate the efficacy of EscharEx.

The second non-experimental treatment is the **Amnion/Chorion Membrane Allograft**, provided as a **cutaneous patch**. This tissue-based product is applied topically on the wound and serves as an auxiliary treatment in the study. The maximum daily dose is 1 cm², with a total maximum dose of 1 cm² over a treatment period of up to 1 week. The application is performed once daily, and adherence to the treatment protocol is ensured through participant monitoring.

The efficacy of the clinical trial evaluating EscharEx for the debridement of **Venous Leg Ulcers** (VLU) will be assessed using both primary and secondary endpoints. The primary endpoints include the incidence of complete debridement, which will be clinically and visually assessed after each application during the Daily Visits Period, allowing for up to eight applications. Additionally, the incidence of complete wound closure will be clinically assessed from the initiation of the study treatment until the end of the Weekly Visits Period.

Secondary endpoints will further evaluate efficacy by measuring the incidence of complete healthy viable granulation tissue at the end of the Daily Visits Period, as assessed clinically. The time to the first declaration of complete debridement and the time to complete wound closure will also be clinically assessed from the initiation of the study treatment until the end of the Weekly Visits Period. These assessments will provide comprehensive data on the efficacy of EscharEx in wound debridement and wound bed preparation for patients with VLU.