Study to Assess the Safety of DERMASEAL for Diabetic Foot Ulcers

A double-blind, randomized, placebo-controlled, multi-center, phase 1 study to evaluate the safety of the DERMASEAL advanced wound care dressing in the treatment of non-healing diabetic foot ulcers located distal to the malleolus in subjects with controlled diabetes mellitus and without significantly compromised arterial circulation. Subjects will be randomized in a 1:1:2 ratio to one of 3 treatment groups:

• SOC alone (n=6)
• SOC + plasma film (n=6)
• SOC + DERMASEAL (n=12)

A subject's study duration will be up to a total of 18 weeks from screening to end of study. This includes a two-week active run-in followed by up to 4 weeks of treatment, plus a final follow-up visit 12 weeks after the last treatment.

The primary endpoint is safety of topically applying a plasma film containing metallic silver microparticles plus fibrin in patients with chronic, non-healing neuropathic diabetic foot ulcers. Secondary endpoints to be assessed in each group include:

• Percent of study wounds healed during the post-treatment weeks 1 through 4,
• Time to complete wound closure,
• Percent area reduction during the post-treatment weeks 2, 4, 6 and 16, and
• Cost of treatment

Inclusion criteria

• Men or women ≥ 21 years of age.
• The subject is able and willing to adhere to study procedures and informed consent is obtained.
• A non-healing ulcer that is diabetic and neuropathic in origin, located on the foot as defined by beginning >50% below the malleoli of the ankle.
• Target ulcer surface area between 1 - 10 cm2 after debridement with no active infection.
• Patients with Type 1 or Type 2 diabetes (criteria for the diagnosis of diabetes mellitus per American Diabetes Association.)
• Additional wounds may be present but not within 2 cm of the target ulcer.
• Patient has adequate arterial perfusion of the affected extremity as demonstrated by any one of the following within the past 90 days from the time of screening:

i. Toe pressure (plethysmography) >50 mm/Hg OR ii. Ankle Brachial Index (ABI) with results ≥ 0.70 and ≤ 1.2 OR iii. TcpO2 ≥30 mm Hg from the foot OR iv. Doppler arterial waveforms consistent with adequate flow in the foot (biphasic or triphasic waveforms at the ankle of affected leg)

• Target ulcer involves a full thickness skin loss, WITHOUT exposure of tendon, muscle, or bone (University of Texas Grade 1-A or Wagner Grade 1) that has been present ≥ 4 weeks. at the time of screening.
• HbA1c <10% taken within 30 days prior to Visit 3.
• Serum creatinine <3.0 mg/dl within the last 6 months.
• Willing and able (subject or responsible caregiver) to maintain required off-loading (as applicable for the location of the ulcer).
• Negative urine pregnancy test at Visit 3 for women of childbearing potential. i) Women participants are considered of non-childbearing potential if they are pre-menopausal with a documented hysterectomy or bilateral oophorectomy; or post-menopausal defined as the cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; or have a serum Follicle Stimulating Hormone level confirming the post-menopausal state.

Exclusion criteria

• Suspected or confirmed signs/symptoms of wound infection (subjects may be rescreened if the infection has been treated.) Infection is defined as, for example:

i. purulence, erythema, cellulitis, excessively high temperatures in/around the ulcer, atypical smell, and/or excessive pain in/around the ulcer (infection may be treated and subject reconsidered for study participation).

ii. osteomyelitis, with necrotic soft bone. (x-ray to be obtained if in the opinion of the investigator additional confirmation of diagnosis required)

• Patients presenting with an ulcer probing to tendon, capsule or bone (University of Texas Grade 2 or 3 or deep Wagner 2 or 3).
• Hypersensitivity to silver or fresh frozen plasma.
• The subject was previously entered into this study or had participated in any study drug or medical device study within 30 days of screening.
• Currently on a treatment regimen or medications which in the opinion of the investigator are known to interfere with wound healing (for example: cancer chemotherapy or equivalent immunosuppressants, systemic steroids > 10 days of treatment, cytostatic drugs, cyclooxygenase-2 inhibitors, or radiation therapy).
• Excessive lymphedema that in the opinion of the investigator will interfere with wound healing.
• A cognitive, physical, or psychological condition interfering with subject's ability to comply with the treatment regimen.
• Active Charcot foot or unstable Charcot that in the opinion of the investigator will inhibit wound healing.
• Wounds secondary to vasculitis, neoplasms, or hematological disorders. Patients on anticoagulation medication will as in any surgical procedure, be monitored according to the protocols employed at the enrolling center.
• An ulcer that in the opinion of the investigator is not associated with the subject's diabetic neuropathic condition.
• Subjects is on dialysis.
• History of radiation to the target foot.
• Patients with uncontrolled autoimmune connective tissue diseases.
• Patients who are pregnant, breast feeding, or unwilling to practice contraceptive methods during participation in the study, if applicable. Effective methods of contraception include:

i. oral, injectable, or implanted hormonal contraceptives ii. intrauterine device or system, iii. barrier method with spermicide, or iv. bilateral tubal occlusion.

• Patients with uncontrolled anemia (Hgb<10 g/dL in women; <12 g/dL in men) at Screening.
• Severe malnutrition (serum albumin ≤2.0 with a normal C-reactive protein).
• Wounds healed by >30% in area following the 2-week, active run-in period as measured during Visit 3.
• Use of hyperbaric oxygen, and active dressings that include growth factors, engineered tissues, or skin substitutes (e.g., Regranex, Dermagraft, Apligraf, etc.) within 30 days of study screening.
• Wounds >5 mm deep after sharp debridement.
• Clinical suspicion of skin cancer at or near the ulcer location which has not been ruled out by biopsy.