A Study of Granexin Gel to Treat Diabetic Foot Ulcer

DFU patients will undergo a one week screening period and those with changes in ulcer size of
less than 30% will be eligible for randomization providing all other criteria are met.
Participants enrolled in the study will receive treatment based on randomization into 1 of 2
treatment arms for up to 12 weeks. The participants will have an additional 12 week follow-up
period beyond the treatment period to assess durability of wound closure.

Inclusion Criteria:

1. Age 18 years or older

2. Established diagnosis of diabetes mellitus (type I or II)

3. Glycosylated hemoglobin (HbA1c) value < 10.0% at the screening visit

4. Diagnosis of neuropathic foot ulcer by 10g monofilament test, tuning fork (128 Hz),
cotton wisp, or quantitative sensory test

5. Designated foot ulcer meets the following criteria at both the screening and baseline
visits:a. Present for at least 4 weeks; b. Full-thickness cutaneous ulcer below the
ankle surface; c. University of Texas grade A1; d. Diameter (after debridement) 1 to
40.0 cm2; e. Viable, granulating wound (investigator discretion)

6. Ankle brachial index 0.7 to 1.3 at both the screening and baseline visits

7. Signed informed consent

8. Female patients of childbearing potential must have a negative pregnancy test at
screening and must agree to use hormonal contraceptive, intrauterine device, diaphragm
with spermicide, condom with spermicide, or abstinence throughout until 2 weeks after
the last administration of study drug

Exclusion Criteria:

1. Change (decrease or increase) in size of the designated target ulcer by ≥ 30% during
the 7-day screening period

2. Cannot tolerate the off-loading method or cannot comply with study-defined
standard-of-care treatment

3. Has an ulcer that meets any of the following criteria: a. Shows signs of severe
clinical infection, defined as pus oozing from the ulcer site; b. Requires operative
debridement; c. Is positive for β-hemolytic streptococci upon culture; d. Has > 50%
slough, significant necrotic tissue, bone, tendon, or capsule exposure; e. Is highly
exuding (i.e., requires daily change of dressing)

4. Requires total contact cast

5. Ankle brachial pressure index < 0.7 or > 1.3 or ankle systolic pressure < 70 mmHg

6. Has a local or systemic infection or local erythema ≥ 0.5 cm

7. Has any 1 of the following (only 1 of the 3 tests is required): a. On Doppler waveform
analysis of the dorsalis pedis and posterior tibial arteries, a monophasic or biphasic
flow (with loss of reverse flow) in either the artery of either foot; b. Toe:brachial
index < 0.75 or > 1.3

c. Transcutaneous oxygen pressure < 40 mmHg

8. Presence of active systemic or local cancer or tumor of any kind (exception:
nonmelanoma skin cancer allowable at investigator discretion)

9. Congestive heart failure (New York Heart Association class II-IV) or coronary heart
disease with ST segment elevation myocardial infarction or coronary artery bypass
graft or percutaneous transluminal coronary angioplasty within the last 6 months

10. Active osteomyelitis of the foot with the target ulcer detected by x-ray, CT scan, or
MRI

11. Active connective tissue disease

12. Acute Charcot's neuro-arthropathy as determined by clinical and/or radiographic
examination

13. Active treatment with systemic corticosteroids

14. Previous or current radiation therapy to the distal lower extremity or likelihood to
receive this therapy during study participation

15. Pregnant or nursing

16. Uncontrolled anemia (hemoglobin < 10 g/dL in females and < 12 g/dL in males)

17. Estimated glomerular filtration rate < 25 mL/min

18. Poor nutritional status, defined as an albumin < 25 g/L (< 2,500 mg/dl)

19. Significant peripheral edema as per investigator's discretion

20. Known inability or unavailability to complete required study visits during study
participation

21. A psychiatric condition (e.g., suicidal ideation) or chronic alcohol or drug abuse
problem, determined from the patient's medical history, which, in the opinion of the
investigator, may pose a threat to patient compliance

22. Use of a platelet-derived growth factor within 28 days before screening

23. Use of any investigational drug or therapy within 28 days before screening

24. Has any other factor which may, in the opinion of the investigator, compromise
participation and/or follow-up in the study