Grafix® DFU: Open-Label Extension Option to Evaluate Safety & Efficacy of Grafix® for Chronic Diabetic Foot Ulcers

The treatment indication is for chronic, diabetic foot ulcers (DFUs) between 1cm2 and 15cm2
located below the malleoli on the plantar or dorsal surface of the foot. Patients must have
confirmed Type I or Type II Diabetes.

Patients will receive treatment every week for 12 weeks duration in the Single-Blind
Treatment phase of the trial.

Patients who receive Grafix® or control will be evaluated for primary efficacy up to 84
days, and for safety and wound re-occurrence for 84 days after wound closure. Patients in
the control group whose wounds are not closed at the end of treatment may be offered Grafix®
in an Open-Label Treatment phase. The Open-Label Treatment phase can last up to an
additional 84 days.

Inclusion Criteria:

1. Between 18 years and 80 years of age inclusive, as of the date of screening

2. Confirmed diagnosis of Type I or Type II Diabetes

3. An Index Ulcer defined as chronic (presence of wound for > 4 weeks) but not present
for more than 52 weeks at the Screening Visit

4. Index Ulcer is located below the malleoli on the plantar or dorsal surface of the
foot

5. The Index Ulcer is between 1cm2 and 15 cm2 at the Screening Visit

6. The Index Ulcer extends into the dermis or subcutaneous tissue without evidence of
exposed muscle, tendon, bone, or joint capsule

7. Wound is free of necrotic debris

8. Patient has adequate circulation to the foot as documented by either:

- Ankle Brachial Index (ABI) > 0.70 and < 1.30, or

- In patients with non-compressible ankle vessels defined as an ABI ≥ 1.30, a Toe
Brachial Index (TBI) ≥ 0.50

- In patients with non-compressible ankle vessels defined as an ABI ≥ 1.30 and TBI
cannot be performed (e.g., toe is absent, wounds are present, or site cannot
perform a TBI), a Doppler waveform in the posterior tibial or dorsalis pedis
arteries at the ankle consistent with adequate flow in the foot (biphasic or
triphasic) and other diagnostic confirmation of adequate flow (e.g., duplex
imaging, normal pulse volume recording [PVR] testing).

Exclusion Criteria:

1. Index Ulcer is of non-diabetic pathophysiology

2. Gangrene is present on any part of the affected foot

3. Index Ulcer is over an active Charcot deformity

4. The longest dimension of the Index Ulcer exceeds 5 cm at the Baseline Visit

5. Patient is currently receiving dialysis

6. Patient has a glycated hemoglobin A1c (HbA1c) level of > 12%

7. Chronic oral steroid use > 7.5 mg daily

8. Requiring intravenous (IV) antibiotics to treat the index wound infection

9. Patient has an ulcer within 15cm of the Index Ulcer identified for study
consideration

10. Patient is receiving oral or parenteral corticosteroids, immunosuppressive or
cytotoxic agents

11. Patient is Human Immunodeficiency Virus (HIV) positive or has Acquired Immune
Deficiency Syndrome (AIDS)

12. Current evidence of osteomyelitis, cellulitis, or other evidence of infection
including fever or pus drainage from the wound site

13. Patient has active malignancy other than non-melanoma skin cancer

14. Patient's Index Ulcer has decreased by ≥ 30% during 1-week screening period as
determined by criteria provided by the Wound Core Lab

15. Patient's random blood sugar is > 450 mg/dl at screening

16. Patient has untreated alcohol or substance abuse at the time of screening

17. Pregnant women

18. Patient is currently enrolled or participated in another investigational device,
drug, or biological trial within 60 days of screening

19. Patient has allergy to primary or secondary dressing materials used in this trial

20. Patient has had within the last 30 days, or is currently undergoing, or is planning
for wound treatments with enzymes, growth factors, living skin, dermal substitutes or
other advanced biological therapies