Dehydrated Human Amnion Membrane and Standard of Care Versus Standard of Care Alone in Nonhealing Diabetic Foot Ulcers

Inclusion Criteria:

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

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

• At randomization subjects must have a target ulcer with a minimum surface area of 1.0 cm2 and a maximum surface area of 5.0 cm2 measured post debridement.

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

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

• The target ulcer must be Wagner 1 or 2 grade, extending at least through the dermisor subcutaneous tissue and may involve the muscle provided it is below the medialaspect of the malleolus. The ulcer may not include exposed tendon or bone.

• The affected limb must have adequate perfusion confirmed by vascular assessment. Anyof the following methods performed within 3 months of the first screening visit areacceptable:

1. ABI ≥ 0.7 and ≤ 1.3;

2. TBI ≥ 0.6;

3. TCOM ≥ 40 mmHg;

4. PVR: biphasic.

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

• The subject must consent to using the prescribed offloading method for the durationof the study.

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

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

Exclusion Criteria:

• A subject known to have a life expectancy of < 6 months is excluded.

• The subject is excluded if the target ulcer is not secondary to diabetes.

• If the target ulcer is infected or if there is cellulitis in the surrounding skin,the subject is excluded.

• If there is evidence of osteomyelitis complicating the target ulcer, the subject isexcluded.

• A potential subject cannot have an infection in the target ulcer or in a remotelocation that requires systemic antibiotic therapy.

• A subject receiving immunosuppressants (including systemic corticosteroids at dosesgreater than 10 mg of Prednisone per day or equivalent) or cytotoxic chemotherapy isexcluded.

• The topical application of steroids to the ulcer surface within one month of initialscreening is not permitted.

• A subject with a previous partial amputation on the affected foot is excluded if theresulting deformity impedes proper offloading of the target ulcer.

• The subject is excluded if the surface area of the target ulcer has reduced in sizeby more than 20% in the 2 weeks prior to the initial screening visit ("historical"run-in period). Photographic planimetry is not required for measurements takenduring the historical run-in period (e.g. calculating surface area using length xwidth is acceptable).

• The subject is excluded if the surface area measurement of the Target ulcerdecreases by 20% or more during the 2-week screening phase: the 2 weeks from theinitial screening visit (S1) to the TV-1/randomization visit, during which time thesubject received SOC.

• A subject is excluded if they are malnourished: a score of less than 17 on the MiniNutritional Assessment (MNA).

• A Subject with an acute Charcot foot, or an inactive Charcot foot, that impedesproper offloading of the target ulcer is excluded.

• Women who are pregnant or considering becoming pregnant within the next 6 months areexcluded.

• A potential subject with end stage renal disease requiring dialysis is excluded.

• A subject who, in the opinion of the investigator, has a medical or psychologicalcondition that may interfere with study assessments is excluded.

• A Subject treated with hyperbaric oxygen therapy or a Cellular Acellular, orMatrix-like Product (CAMP) in the 30 days prior to the initial screening visit isexcluded.