Rising Tide - Amniotic Tissue(s) Treatments for Chronic Diabetic Foot Ulcers

A Multi-Center, Randomized Controlled Clinical Investigation Evaluating an Amnion/Chorion/Amnion Allograft, Amnion/Chorion Allograft, And/or an Amnion/Amnion Allograft Versus Standard of Care in the Treatment of Non-Healing Diabetic Foot Ulcers

The purpose of this clinical investigation is to evaluate the safety and efficacy of Amnion/Chorion/Amnion allograft , Amnion/Chorion allograft, and/or Amnion/Amnion allograft, plus Standard of Care (SOC) each versus SOC alone in the treatment of chronic non-healing diabetic foot ulcers (DFU) after 12 weeks of treatment.

Inclusion Criteria:

Potential subjects are required to meet all of the following criteria for enrollment into the study.

1. At least 18 years old, inclusive.
2. Presence of a DFU, Wagner Grade 1, extending through the dermis provided it is below the medial aspect of the malleolus.
3. The index ulcer (ulcer to be evaluated in the study) will be the largest ulcer if two or more DFUs are present with the same Wagner grade and will be the only one evaluated in the study. If other ulcerations are present on the same foot, they must be 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 documented by 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 Doppler ultrasound can be performed evaluating for biphasic dorsalis pedis and posterior tibial vessels at the level of the ankle or a TBI (Toe Brachial Index) of > 0.6 is acceptable.
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 of contraception (birth control pills, barriers or abstinence) during the course of the study and undergo pregnancy tests.
9. Subject understands and is willing to participate in the clinical study and can comply with weekly visits.
10. Subjects must have read and signed the IRB approved ICF before screening procedures are performed.

Exclusion Criteria:

Potential subjects meeting any of the following criteria will be excluded from enrollment and subsequent treatment.

1. Index ulcer(s) deemed by the investigator to be caused by a medical condition other than diabetes
2. Index ulcer, in the opinion of the investigator, is suspicious for cancer and should undergo an ulcer biopsy to rule out a carcinoma of the ulcer
3. Index ulcer is infected
4. Subjects with a history of more than two weeks of treatment with immune-suppressants (including systemic corticosteroids >10mg daily dose), cytotoxic chemotherapy, or application of topical steroids to the ulcer surface within 1-month prior to first SV1, or who receive such medications during the screening period or who are anticipated to require such medications during the course of the study
5. Subjects on any investigational drug(s), Investigational products, or therapeutic device(s) within 30 days preceding SV1
6. History of radiation at the ulcer site (regardless of time since last radiation treatment)
7. Index ulcer has been previously treated or will need to be treated with any prohibited 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 to complete 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 x-ray 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 ≥3.0 mg/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 from SV1 to the TV1/Randomization visit