Evaluating the Efficacy of FoundationDRS Solo in Addition to Standard of Care for the Treatment of Non-healing Diabetic Foot Ulcers

Patients with diabetes often develop ulcers on their lower extremities. While some ulcers can be managed using standard of care wound management techniques including debridement, moist dressings, infection control and off-loading, many develop into chronic, non-healing wounds. Chronic non-healing wounds can lead to higher risk of infection, amputation and decreased quality of life.

Advanced wound therapies aim to promote rapid and complete healing of chronic wounds. Examples of an advanced wound therapies include scaffolds that contain and / or mimic the structure and function of the natural extracellular matrix of tissue. Several biomimetic scaffolds have been cleared for the management of a variety of wounds (including DFU's) by the US FDA.

The focus of this clinical trial is to determine the clinical utility of treating diabetic foot ulcers with weekly applications of FoundationDRS Solo in addition to standard of care wound management techniques compared to applying standard of care wound management only.

It is hypothesized that the addition of FoundationDRS Solo to standard of care treatment will result in a higher percentage of ulcers achieving complete closure (i.e. healing) compared to ulcer being treated with standard of care alone after 12 weeks of treatment.

To test this hypothesis the study will consist of patients who will undergo standard of care for 4-weeks prior to entering a 12-week treatment phase. During the 4-week standard of care phase, patients meeting inclusion criteria (including confirmation that ulcer does not reduce in area by more than 50%) will be randomized into the treatment groups. During the 12-week treatment phase, index wounds will be treated weekly with FoundationDRS Solo and standard of care or standard of care alone.

Evaluation of data (outcome measures) associated with the trial will include intent to treat and per protocol analyses which will be performed by at least one blinded statistician and investigator.

Inclusion criteria

• 1. Subjects must be at least 18 years of age or older.
• Subjects must have a diagnosis of type 1 or 2 Diabetes mellitus requiring treatment with oral medications and/or insulin replacement therapy.
• At randomization subjects must have a target ulcer with a minimum surface area of 1.0 cm2 and a maximum surface area of 20.0 cm2 measured post debridement prior to randomization at treatment visit 1 (TV1).
• The target ulcer must have been present for a minimum of 4 weeks and is unresponsive (defined by less than 50% wound area reduction) to standard wound care.
• 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 1 or 2 grade, extending at least through the dermis or subcutaneous tissue and may involve the muscle provided it is below either malleoli.
• 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 between 0.7 and ≤ 1.3;
• TBI ≥ 0.6;
• TCOM ≥ 40 mmHg;
• PVR: biphasic;
• skin perfusion pressure (SPP) ≥ 30 mmHg.
• If the subject 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 index ulcer has been offloaded with protocol defined offloading device for at least 14 days prior to randomization (i.e. Screening through TV1/Randomization).
• The potential subject must consent to using the prescribed offloading method for the duration of the study.
• The potential subject must agree to attend the weekly study visits required by the protocol.
• The potential subject must be willing and able to participate in the informed consent process.
• Index ulcer and/or index ulcer limb may have had prior infection(s), but must be adequately treated and controlled as defined by IDSA Guidelines Grade level 1 (Appendix L).
• The index ulcer has a clean base and is free from necrotic debris at time of placement of product / treatment.
• Negative pregnancy test for females of childbearing potential (e.g., not post-menopausal for at least one yar or surgically sterile). Females of childbearing potential must be willing to use acceptable methods of contraception (birth control pills, barriers, or abstinence) starting at Screening and continuing through the duration of their study participation.

Exclusion criteria

• The target ulcer has been present for more than 52 weeks.
• The ulcer includes exposed tendon or bone.
• The potential subject is known to have a life expectancy of < 6 months.
• The potential subject's target ulcer is not secondary to diabetes.
• The target ulcer is infected or has cellulitis in the surrounding skin.
• There is evidence of osteomyelitis complicating the target ulcer.
• The potential subject has an infection in the target ulcer or in a remote location that requires systemic antibiotic therapy.
• The potential subject is receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of Prednisone per day or equivalent) or cytotoxic chemotherapy.
• The potential subject has applied topical steroids to the ulcer surface within one month of initial screening.
• The potential subject has a previous partial amputation on the affected foot that resulted in a deformity impeding proper offloading of the target ulcer.
• A potential subject must be excluded if either of the following conditions are met:

Condition A (Overall 4-week reduction)

The surface are of the target ulcer has decreased by more than 50% over the 4 weeks prior to Treatment Visit 1, which includes:

The historical run-in period, and

The 2-week Screening Phase.

OR

Condition B (Sequential reductions across both phases)

Both of the following are true:

• During the historical run-in period (the 2-weeks prior to the Screening Visit):

The target ulcer surface area decreases by more than 25%.

• During the active 2-week Screening Phase (from Screening Visit 1 [SV1] to Treatment Visit 1 [TV1]):

The target ulcer surface area decreases by an additional 25% or more.

• The surface area of the potential subject's target ulcer has reduced in size by more than 50% in the 4 weeks prior to Treatment Visit 1 (i.e. 2-week historical run-in and 2-week screening phase).

• The potential subject has glycated hemoglobin (HbA1c) greater than or equal to 12% within 3 months of the initial screening visit.

• The potential subject has an acute Charcot foot, or an inactive Charcot foot, that impedes proper offloading of the target ulcer.

• The potential subject is pregnant or considering becoming pregnant within the next 6 months.

• The potential subject has major uncontrolled medical disorders such as serious cardiovascular, renal, liver or pulmonary disease, lupus, palliative care or sickle cell anemia.

• Participation in a clinical trial involving treatment with an investigational product within the previous 30 days.

• The potential subject has, in the opinion of the investigator, a medical or psychological condition that may interfere with study assessments.

• The potential subject is treated with hyperbaric oxygen therapy or cellular, acellular and matrix-like products (CAMPS) in the 30 days prior to the initial screening visit .

• The potential subject has a score of less than 17 and is considered malnourished according to the Mini Nutritional Assessment (MNA).

• Presence of any condition(s) which seriously compromises the subject's ability to complete this study or has a known history of poor adherence to medical treatment.

• Subject has ulcers that are completely necrotic or fibrotic tissue. 23. Subject currently being treated for an active malignant disease or subjects with history of malignancy within the ulcer.

• Known contraindications to or known allergies to any of the Foundation DRS Solo components.

• Presence of diabetes with poor metabolic control as documented with an HbA1c ≥12.0 within 30 days of randomization (TV1).

• Index ulcer and/or index limb with presence of gangrene or unstable ischemia at the initial screening visit (SV1).

• Index ulcer in the opinion of the Principal Investigator, is suspicious for cancer and should undergo an ulcer biopsy to rule out a neoplasm of the ulcer.

• Any clinically significant finding, in the judgment of the Principal Investigator, that would place the subject at health risk, impact the study, or affect the completion of the study.