A Study of Granexin Gel to Treat Diabetic Foot Ulcer

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 baselinevisits:a. Present for at least 4 weeks; b. Full-thickness cutaneous ulcer below theankle 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 atscreening and must agree to use hormonal contraceptive, intrauterine device, diaphragmwith spermicide, condom with spermicide, or abstinence throughout until 2 weeks afterthe last administration of study drug

Exclusion Criteria:

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

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

3. Has an ulcer that meets any of the following criteria: a. Shows signs of severeclinical infection, defined as pus oozing from the ulcer site; b. Requires operativedebridement; c. Is positive for β-hemolytic streptococci upon culture; d. Has > 50%slough, significant necrotic tissue, bone, tendon, or capsule exposure; e. Is highlyexuding (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 waveformanalysis of the dorsalis pedis and posterior tibial arteries, a monophasic or biphasicflow (with loss of reverse flow) in either the artery of either foot; b. Toe:brachialindex < 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 heartdisease with ST segment elevation myocardial infarction or coronary artery bypassgraft 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, orMRI

11. Active connective tissue disease

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

13. Active treatment with systemic corticosteroids

14. Previous or current radiation therapy to the distal lower extremity or likelihood toreceive 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 studyparticipation

21. A psychiatric condition (e.g., suicidal ideation) or chronic alcohol or drug abuseproblem, determined from the patient's medical history, which, in the opinion of theinvestigator, 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, compromiseparticipation and/or follow-up in the study