Evaluating Intact Fish Skin Graft and Standard of Care Versus Standard of Care Alone in Nonhealing Venous Leg Ulcers

A Randomized Controlled Multicenter Clinical Trial Evaluating Intact Fish Skin Graft and Standard of Care Versus Standard of Care Alone in Nonhealing Venous Leg Ulcers

The purpose of this study is to determine the between-arm difference in the proportion of subjects achieving complete closure of hard-to-heal venous leg ulcers (VLU) between Intact Fish Skin Graft plus standard of care (IFSG/SOC) versus standard of care alone (SOC) over 12 weeks.

This is a randomized controlled multicenter clinical trial evaluating intact fish skin grand and standard of care vs. standard of care alone in nonhealing venous leg ulcers. The product classifies as a medical device and consists of a full thickness fish-skin that has been processed using Kerecis™ Limited's proprietary EnviroIntact™ method.

Inclusion Criteria:

1. Subjects must be at least 18 years of age or older.

2. Subjects must have a nonhealing venous leg ulcer present for a minimum of 4 weeks and cannot have received more than 52 weeks of high-level compression prior to the initial screening visit.

3. No visible signs of healing objectively, less than 40% reduction in wound size in the last 4 weeks.

4. At randomization, subjects must have a target ulcer with a minimum surface area of 1 cm2 and a maximum surface area of 25 cm2 measured post-debridement.

5. The affected limb must have adequate perfusion confirmed by vascular assessment. Any of the following methods performed within 3 months of the first screening visit are acceptable:

   1. ABI between 0.7 and ≤ 1.3;
   2. TBI ≥ 0.6;
   3. TCOM ≥ 40 mmHg;
   4. PVR: biphasic.

6. If the potential subject has two or more ulcers, and they are separated by at least 2 cm post-debridement, the largest ulcer satisfying the inclusion and exclusion criteria will be designated as the target ulcer. If the potential subject has two or more ulcers and they are separated by less than 2cm, the entire wound area is designated as the target ulcer.

7. Subjects must have a Functional Ambulatory Category Score (FACS) of 3 or greater.

8. Subjects must consent to using the prescribed compression method for the duration of the study.

9. Subjects must agree to attend the weekly study visits required by the protocol.

10. Subjects must be willing and able to participate in the informed consent process.

Exclusion Criteria:

1. The potential subject is known to have a life expectancy of < 6 months.
2. The index ulcer is determined to be due to a condition other than venous insufficiency.
3. The target ulcer exposes muscle, tendon, or bone.
4. The target ulcer exhibits overt clinical signs and symptoms of infection with cellulitis surrounding the wound margin.
5. The target ulcer has known or suspected skin malignancy.
6. The target ulcer has been previously exposed to radiation.
7. The target ulcer duration is greater than one year having received high level compression without closure for a year or more.
8. The potential subject has end stage renal disease requiring dialysis.
9. The potential subject is receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of prednisone per day or equivalent) or cytotoxic chemotherapy or is taking medications that the PI believes will interfere with wound healing (e.g., biologics).
10. A potential subject who, in the opinion of the investigator, has a medical or psychological condition that may interfere with study assessments.
11. The potential subject was treated with hyperbaric oxygen therapy (HBOT) or a cellular or tissue-based product (CTP) in the 30 days prior to the initial screening visit.
12. The potential subject has a malnutrition indicator score <17 as measured on the Mini Nutritional Assessment.
13. The potential subject has glycated hemoglobin (HbA1c) greater than or equal to 12% within 3 months of the initial screening visit.
14. The surface area of the target ulcer has reduced in size by more than 20% in the 2 weeks prior to the initial screening visit ("historical" run-in period). Digital planimetry is not required for measurements taken during the historical run-in period (e.g., calculating surface area using length X width is acceptable).
15. The surface area measurement of the target ulcer decreases by 20% or more during the active 2-week screening phase: the 2 weeks from the initial screening visit (SV-1) to the TV-1 visit during which time the potential subject received SOC.
16. The potential subject has a Functional Ambulatory Category Score (FACS) of less than 3.
17. The potential subject has a body mass index (BMI) greater than 42
18. In the last 8 weeks the patient has undergone revascularization (surgical or stenting) to the affected leg.
19. Venous intervention in the affected limb in the last 30 days.
20. Presence of any condition (including current drug or alcohol abuse, medical or psychiatric condition) that is likely to impair understanding of or compliance with the study protocol in the judgment of the Investigator.
21. Pregnancy at enrollment or women who are breastfeeding, or women of childbearing potential who are planning to become pregnant during the time of the study OR are unwilling/unable to use acceptable methods of contraception (birth control pills, barriers, or abstinence).
22. Know allergy to any of the components of fish skin or bovine collagen.
23. Participation in a clinical trial involving treatment with an investigational product within the previous 30 days.
24. A subject with a disorder that would create unacceptable risk of post-operative complications is excluded.