BIOxHEAL plus standard care for nonhealing diabetic foot ulcers

Inclusion Criteria:

Participants must be at least 18 years of age or older. Participants must have a diagnosis of type 1 or 2 diabetes mellitus. At randomization (or enrollment for the sentinel cohort), participants must have a target ulcer with a minimum surface area of 1.0 cm2 and a maximum surface area of 25.0 cm2 measured post debridement.

The target ulcer must have been present for a minimum of 4 weeks and a maximum of 52 weeks of standard of care prior to the initial screening visit.

The target ulcer must be located on the foot with at least 50% of the ulcer below the malleolus.

The target ulcer must be Wagner Grade 1 extending at least through the dermis or subcutaneous tissue.

The affected limb must have adequate perfusion confirmed by vascular assessment. Any of the following methods performed within 3 months of the first screening visit are acceptable:

ABI greater than or equal to 0.7 and less than or equal to 1.3 TBI greater than or equal to 0.6 TCOM greater than or equal to 40 mmHg Arterial Doppler ultrasound with biphasic dorsalis pedis and posterior tibial vessels at the level of the ankle on the extremity where the index ulcer is located If the participant has two or more ulcers, they must be separated by at least 2 cm. The largest ulcer satisfying the inclusion and exclusion criteria will be designated as the target ulcer.

The participant must consent to using the prescribed offloading method for the duration of the study.

The participant must agree to attend the weekly study visits required by the protocol.

The participant must be willing and able to participate in the informed consent process.

The participant must have a suitable living environment to manage prescribed offloading and wound care management.

Exclusion Criteria:

Known life expectancy of less than 6 months. Target ulcer is not secondary to diabetes. Wagner Grade 2 to 5 ulcers. Target ulcer is infected, or there is cellulitis in the surrounding skin.

Evidence of osteomyelitis complicating the target ulcer, based on clinical assessment supported by at least one of the following:

Imaging (for example, plain radiography, MRI, or nuclear medicine study) consistent with osteomyelitis Positive bone culture Abnormal inflammatory markers (for example, ESR, CRP) in conjunction with clinical signs highly suggestive of osteomyelitis per Investigator judgment - Documentation of the basis for diagnosing or excluding osteomyelitis must be available in the participant's source documents Infection in the target ulcer or in a remote location that requires systemic antibiotic therapy.

Receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of prednisone per day or equivalent) or cytotoxic chemotherapy.

Topical application of steroids to the ulcer surface within one month of initial screening.

Previous partial amputation on the affected foot, if the resulting deformity impedes proper offloading of the target ulcer.

Glycated hemoglobin (HbA1c) greater than or equal to 12% within 3 months of the initial screening visit.

The surface area of the target ulcer has reduced in size by more than 40% between Screening Visit 1 and Treatment Visit 1 during the protocol-defined screening period.

Acute Charcot foot, or an inactive Charcot foot, that impedes proper offloading of the target ulcer.

Women who are pregnant or considering becoming pregnant within the next 6 months.

Male or female participants who are unwilling or unable to comply with the required contraceptive measures for the duration of study participation.

End stage renal disease requiring dialysis. Serum creatinine level greater than 3.0 mg/dL. Aspartate aminotransferase (AST, GOT) and/or alanine aminotransferase (ALT, GPT) greater than 3 times the upper limit of normal.

A medical or psychological condition that, in the opinion of the investigator, may interfere with study assessments.

Treated with hyperbaric oxygen therapy or a Cellular and/or Tissue Product (CTP) in the 30 days prior to the initial screening visit.

Mini Nutritional Assessment (MNA) screening score below 12.