Randomized Clinical Study Assessing NuShield Versus Standard of Care in Diabetic Foot Ulcers

One hundred and twenty five (125) subjects with a chronic DFU ranging in size from 0.5cm2 and
25 cm2 will be randomized 1:1 to either NuShield® and SOC or SOC alone following the 14 day
screening period. Following screening and randomization, subjects shall be seen weekly for up
to 24 weeks. For subjects that heal prior to week 24, a healing confirmation visit shall
occur two weeks later to confirm maintenance of complete wound closure.

Subjects that are randomized into the SOC group whose DFU has not healed by week 12 may be
crossed over to receive NuShield® and followed for an additional 12-14 weeks.

Inclusion Criteria:

1. Subject must be at least 18 years old and a maximum of 85 years old.

2. Subjects with diabetic foot ulcers which extend into the papillary (shallow) dermis,
or into the reticular (deep) dermis, or into subcutaneous fat, but not extending into
muscle, tendon, capsule, or bone.

3. Subject must have a Glycosylated hemoglobin (HbA1c) ≤ 10% within 4 weeks prior to the
initial screening visit.

4. Index ulcer (i.e. current episode of ulceration) has been present for greater than 4
weeks prior to the initial screening visit and less than 1 year.

5. Subject has adequate circulation to the foot as documented by either:

1. Skin perfusion pressure (SPP) measurement of ≥ 45 mmHg.

2. Toe-brachial index (TBI) ≥ 0.6/ Toe pressure greater than 40 mmHg.

3. Ankle-brachial index (ABI) between 0.60 and ≤ 1.3

6. Index ulcer is a minimum of 0.5 cm2 and a maximum of 25cm2 at first treatment visit.

7. The index ulcer has been offloaded for at least 14 days prior to randomization.

8. Subject must have a serum albumin level more than 3g/ DL total lymphocyte count of
more than 1500/mm3

9. Subject understands and is willing to participate in the clinical study and can comply
with weekly visits and the follow-up regimen.

10. Subject has read, understood, and signed the IRB/IEC approved Informed Consent Form
before screening procedures are undertaken.

Exclusion Criteria:

1. Index ulcer(s) deemed by the investigator to be caused by a medical condition other
than diabetes.

2. Treatment with wound dressings that include growth factors, bioengineered tissues, or
skin substitutes within 30 days of the Screening visit and throughout the study (with
the exception of skin substitutes containing antimicrobials which are excluded from
the Screening visit and throughout the study).

3. History of bone cancer or metastatic disease of the affected limb or chemotherapy
within the 12 months prior to randomization.

4. Subjects with a history of more than two weeks treatment with immunosuppressant's
(including systemic corticosteroids > 10mg daily), cytotoxic chemotherapy, or
application of topical steroids to the ulcer surface within one month prior to first
Screening Visit, or who receive such medications during the screening period, or who
are anticipated to require such medications during the course of the study.

5. Subjects on any investigational drug(s) or therapeutic device(s) within 30 days
preceding the first Screening Visit.

6. History of radiation at the ulcer site.

7. Index ulcer has been previously treated or will need to be treated with any prohibited
therapies within 30 days prior to randomization.

8. Presence of any condition(s) which seriously compromises the subject's ability to
complete this study or has a known history of poor adherence with medical treatment.

9. Active infection at the index ulcer at the time of Randomization.

10. Acute osteomyelitis or bone infection of the affected foot, where subject has received
less than 4 weeks of systemic antibiotics at the time of Screening and less than 6
weeks prior to Randomization (systemic antibiotic regimen must be completed at the
time of Randomization).

11. Subjects with suspected infection who have received less than 2 weeks of systemic
antibiotics or have not had surgical resection of clinically diagnosed osteomyelitis

12. Subjects with suspected osteomyelitis who have not had an X-ray, CT scan or MRI within
14 days prior to Randomization.

13. Subject unwilling or unable to comply with the study requirement for offloading the
index ulcer

14. Index ulcer has reduced in area by >20% within 2 weeks prior to randomization.

15. Subjects on dialysis, with serum creatinine level ≥3.0 mg/dL and/ or a history of
kidney transplant