Clinical Trial Evaluating an Amnion Membrane Allograft for Use in the Management of Non- Healing Diabetic Foot Ulcers Versus Standard Of Care

A Randomized Controlled Clinical Trial Evaluating The Efficacy of an Amnion Membrane Allograft Intended for Use in the Management of Non- Healing Diabetic Foot Ulcers Versus Standard Of Care Alone

The main purpose of this research study is to compare the proportion of wound closure in subjects that receive E-GRAFT™ with Standard of Care (SOC) versus FIBRACOL™ with SOC. Other research purposes include the following:

• Rate of wound closure
• Change in ulcer size over 12 weeks
• Any adverse events or reactions (side effects)
• Changes in neuropathy (nerve damage)
• Change in pain levels
• Occurrence of infection

The purpose of this clinical evaluation is to collect patient outcome data on a commercially available E-GRAFT™ that is a dehydrated thick amniotic allograft processed and approved for use as a Human Cellular and Tissue- Based Product (HCT/P) under FDA 21 CFR 1271 and Section 361 of the Public Health Service (PHS) Act. In this trial, two groups of diabetic foot ulcers (DFUs) will receive standard of care (SOC) treatment for their condition. Half of the patients will receive a 510K FDA cleared Collagen alginate dressing FIBRACOL™ and the other half will have E-GRAFT™ dehydrated tissue allograft as the primary dressing. The primary endpoint is the percentage of patients that go on to complete closure of the target ulcer between the two groups: SOC with FIBRACOL™ or SOC with E-GRAFT™. Secondary endpoints include the proportion of subjects achieving complete wound closure of the target ulcer by the end of 12 weeks.

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 with manual measurement.

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.

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. Target ulcers located on the plantar aspect of the foot must be offloaded for at least 14 days prior to randomization.

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

11. The subject must agree to attend the weekly study visits required by the protocol.

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

Exclusion Criteria:

1. A subject known to have a life expectancy of < 6 months is excluded.
2. If the target ulcer is infected or if there is cellulitis in the surrounding skin, the subject is excluded.
3. Presence of osteomyelitis or exposed bone, probes to bone or joint capsule on investigator's exam or radiographic evidence.
4. Index ulcer and/or index ulcer limb may have had prior infection(s), but infection(s) must be adequately treated and controlled
5. A subject receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of Prednisone per day or equivalent) or cytotoxic chemotherapy is excluded.
6. The topical application of steroids to the ulcer surface within one month of initial screening is not permitted.
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. If a subject has a glycated hemoglobin (HbA1c) greater than or equal to 12% taken at or within 3 months of the initial screening visit he/she is excluded.
9. If a subject has a serum creatinine ≥ 3.0mg/dL within 6 months of randomization he/she is excluded.
10. The subject is excluded if the surface area measurement of the target ulcer has reduced in size by more than 30% in the 2 weeks prior to the initial screening during the 2-week screening phase: the 2 weeks from the initial screening visit (SV1) to the TV1/randomization visit during which time the subject received SOC.
11. A subject with an acute Charcot foot, or an inactive Charcot foot, that impedes proper offloading of the target ulcer is excluded.
12. Women who are pregnant or considering becoming pregnant within the next 6 months are excluded.
13. A potential subject with end stage renal disease requiring dialysis is excluded.
14. A subject who, in the opinion of the Investigator, has a medical or psychological condition that may interfere with study assessments is excluded.
15. Subject treated with hyperbaric oxygen therapy or a Cellular and/or Tissue Product (CTP) in the 30 days prior to the initial screening visit is excluded.