Clinical Study Evaluating Symphony™ Versus Standard of Care in the Treatment of Non-Healing Diabetic Foot Ulcers

Inclusion Criteria:

• 1. At least 18 years old, inclusive.
• 2. Presence of a DFU, Wagner Grade 1 or 2 (see Appendix B for definitions),extending through the dermis provided it is below the medial aspect of themalleolus.
• 3. The index ulcer (ulcer to be evaluated in the study) will be the largest ulcer iftwo or more DFUs are present with the same Wagner grade and will be the only oneevaluated in the study. If other ulcerations are present on the same foot, they mustbe more than 2 cm distant from the index ulcer.
• 4. Index ulcer has been present for greater than 4 weeks prior to SV1 and less than 1 year, as of the date the subject consents for study.
• 5. Index ulcer is a minimum of 1.0 cm2 and a maximum of 25 cm2 at SV1 and TV1.
• 6. Within 3 months of SV1, adequate circulation to the affected foot as documentedby a dorsal transcutaneous oxygen measurement (TCOM) or a skin perfusion pressure (SPP) measurement of ≥ 30 mmHg, or an Ankle Branchial Index (ABI) between 0.7 and 1.3 using the affected study extremity. As an alternative, arterial Dopplerultrasound can be performed evaluating for biphasic dorsalis pedis and posteriortibial vessels at the level of the ankle or a TBI (Toe Brachial Index) of > 0.6 isacceptable.
• 7. The target ulcer has been offloaded for at least 14 days, prior to TV1.
• 8. Females of childbearing potential must be willing to use acceptable methods ofcontraception (birth control pills, barriers or abstinence) during the course of thestudy and undergo pregnancy tests.
• 9. Subject understands and is willing to participate in the clinical study and cancomply with weekly visits.
• 10. Subjects must have read and signed the IRB approved ICF before screeningprocedures are performed.

Exclusion Criteria:

• 1. Index ulcer(s) deemed by the investigator to be caused by a medical conditionother than diabetes
• 2. Index ulcer, in the opinion of the investigator, is suspicious for cancer andshould undergo an ulcer biopsy to rule out a carcinoma of the ulcer
• 3. Index ulcer is overtly infected (i.e., purulent drainage)
• 4. Subjects with a history of more than two weeks of treatment withimmune-suppressants (including systemic corticosteroids >10mg daily dose), cytotoxicchemotherapy, or application of topical steroids to the ulcer surface within 1-monthprior to first SV1, or who receive such medications during the screening period orwho 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 dayspreceding SV1
• 6. History of radiation at the ulcer site (regardless of time since last radiationtreatment)
• 7. Index ulcer has been previously treated or will need to be treated with anyprohibited therapies
• 8. Subjects with a previous diagnosis of HIV or Hepatitis C
• 9. Presence of any condition(s) which seriously compromises the subject's ability tocomplete this study or has a known history of poor adherence with medical treatment
• 10. Osteomyelitis or bone infection of the affected foot as verified by xray within 30 days prior to the first screening visit. (In the event of an ambiguous diagnosis,the Principal Investigator will make the final decision)
• 11. Subject is pregnant or breast-feeding
• 12. Presence of diabetes with poor metabolic control as documented with an HbA1c >12.0 within last 90 days
• 13. Subjects with end stage renal disease as evidenced by a serum creatinine ≥3.0mg/dL within 6 months of enrollment
• 14. Presence of acute Charcot Neuroarthropathy to the affected limb
• 15. Index ulcer that has reduced in area by 30% or more after 14 days of SOC fromSV1 to the TV1/Randomization visit