A Study to Evaluate the Safety and the Efficacy of EscharEx (EX-02 Formulation) in Debridement of Venous Leg Ulcers
Condition: Venous Leg Ulcer
MeSH terms: Varicose Ulcer; Leg Ulcer; Ulcer
Study type: Interventional
Phase: Phase 2

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. 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.

           During the one week screening period, patients whose wound size (surface area, as
           measured by eKare inSightTM) decreases by more than 20 percent will be excluded.

        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).

           Eligible patients will be randomized into one of the study arms: EX-02, or Gel Vehicle
           (Placebo), or NSSOC in a 2:2:1 ratio. Patients will be treated with up to 8 daily 24±3
           hours applications or until complete debridement is achieved, whichever occurs first.

           On the weekends between treatments of EX-02 or Gel material, the wound will be dressed
           with a compatible dressing, and by compression therapy. Patients treated with NSSOC
           continue using NSSOC during the weekend according to label or instructions for use, and
           compression therapy.

        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).

           The investigator will clinically assess complete debridement, upon achieving a viable
           wound bed after removal of all non-viable tissue, suitable for initiation of the wound
           healing stage.

        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).

      The investigator will clinically assess complete debridement, upon achieving a viable wound
      bed after removal of all non-viable tissue, suitable for initiation of the wound healing
      stage.

      Complete wound closure defined as skin re-epithelialization without drainage or dressing
      requirements confirmed at two consecutive study visits, 2 weeks apart will be assessed
      clinically. Thus, if closure occurs close to the end of weekly visit period, i.e. on 9th or
      10th visit of the weekly period, an additional confirmation visit will be performed 2 weeks
      later.
    


Intervention name(s): EscharEx (5% EX-02 formulation); Gel Vehicle; Non-surgical standard of care (NSSOC)
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Active arm; Control arm; Santyl (Enzymatic debridement) or commercially approved Hydrogel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Debridement