Clinical Study to Compare Two Skin Substitute Categories for Their Effectiveness to Treat Diabetic Foot Ulcers

A Randomized Controlled Clinical Trial Evaluating the Efficacy of a Unique Advanced Bioengineered Skin Substitute With Standard of Care Versus an Active Comparator With Standard of Care in the Treatment of Non-Healing Diabetic Foot Ulcers

The purpose of this clinical evaluation is to collect patient outcome data on a commercially available 510K FDA cleared advanced skin substitute. The commercially available product is Helicoll® Advanced Skin Substitute.

In this trial two groups of subjects with Wagner 1 diabetic foot ulcers (DFUs), will receive standard of care (SOC) treatment for their condition. Half of the patients will have their SOC treatment with Epifix® or Grafix® and the other half will receive a 510K FDA cleared Helicoll® Advanced Skin Substitute as the primary treatment. The primary endpoint is the percentage wound area reduction of the target ulcer. Secondary endpoints include the proportion of subjects that obtain complete closure over the 5-week treatment period, the time to achieve complete wound closure of the target ulcer by the end of 5 weeks, and mean number of IP applications.

Inclusion Criteria:

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

2. Subjects must have a diagnosis of type 1 or 2 Diabetes mellitus.

3. At randomization, subjects must have a target diabetic foot ulcer with a minimum surface area of 1.0 cm2 and a maximum surface area of 10.0 cm2 measured post debridement using a ruler to measure wound area.

4. The target ulcer must have been present for a minimum of 4 weeks and a maximum of 52 weeks of standard of care prior to the initial screening visit.

5. The target ulcer must be located on the foot with at least 50% of the ulcer below the malleolus.

6. The target ulcer must be full thickness on the foot or ankle that does not probe to bone.

7. Adequate circulation to the affected foot as documented by any of the following methods performed within 3 months of the first screening visit:

   1. TCOM ≥30 mmHg
   2. ABI between 0.7 and 1.3
   3. PVR: Biphasic
   4. TBI ˃0.6
   5. As an alternative, arterial Doppler ultrasound can be performed evaluating for biphasic dorsalis pedis and posterior tibial vessels at the level of the ankle of the target extremity.

8. If the subject has two or more ulcers, they must be separated by at least 2 cm. The largest ulcer satisfying the inclusion and exclusion criteria will be designated as the target ulcer.

9. The subject must consent to using the prescribed off-loading method for the duration of the study.

10. The subject must agree to attend the twice-weekly/weekly study visits required by the protocol.

11. The subject must be willing and able to participate in the informed consent process.

12. Patients must have read and signed the IRB approved ICF before screening procedures are undertaken.

Exclusion Criteria:

1. A subject known to have a life expectancy of < 6 months.
2. If the target ulcer is infected or if there is cellulitis in the surrounding skin.
3. Presence of osteomyelitis or exposed bone, probes to bone or joint capsule on investigator's exam or radiographic evidence.
4. A subject has an infection in the target ulcer or in a remote location that requires systemic antibiotic therapy.
5. A subject receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of Prednisone per day or equivalent) or cytotoxic chemotherapy.
6. Topical application of steroids to the ulcer surface within one month of initial screening.
7. A subject with a previous partial amputation on the affected foot is excluded if the resulting deformity impedes proper offloading of the target ulcer.
8. A subject with a glycated hemoglobin (HbA1c) greater than or equal to 13% taken at or within 3 months of the initial screening visit.
9. A subject with a serum creatinine ≥ 3.0mg/dL within 6 months of the initial screening visit.
10. A subject with an acute Charcot foot, or an inactive Charcot foot, that impedes proper offloading of the target ulcer.
11. Women who are pregnant or considering becoming pregnant within the next 6 months.
12. A subject with end stage renal disease requiring dialysis.
13. A subject who participated in a clinical trial involving treatment with an investigational product within the previous 30 days.
14. A subject who, in the opinion of the Investigator, has a medical or psychological condition that may interfere with study assessments.
15. A subject treated with hyperbaric oxygen therapy or a Cellular and/or Tissue Product (CTP) in the 30 days prior to the initial screening visit.
16. A subject who has a sensitivity to bovine (cattle) or ovine (sheep) material.
17. A subject that is allergic to aminoglycoside antibiotics (gentamycin, tobramycin, etc.)