PriMatrix for the Management of Diabetic Foot Ulcers

The study will evaluate the efficacy of PriMatrix Dermal Repair Scaffold in the management of diabetic foot ulcers in subjects with diabetes mellitus versus the Standard of Care treatment. Half of patients will be treated using PriMatrix while the other half will receive Standard of Care treatment.

A diabetic foot ulcer (DFU) is a major health complication that affects up to 15% of individuals with diabetes mellitus over their lifetime. The treatment of DFUs is extremely challenging as these ulcers may not respond to standard of care (SC) treatment and frequently become infected.

Advanced wound therapies like PriMatrix have become an important strategy in the treatment of hard-to-heal chronic DFUs by trapping and binding the patients' own cells to rebuild the dermis layer of the skin to aid in healing.

The study will evaluate the efficacy of PriMatrix Dermal Repair Scaffold in the closure of DFUs in subjects with diabetes mellitus in comparison to Standard of Care treatment.

Eligibility Criteria:
Inclusion Criteria

Subjects are required to meet all of the following criteria for enrollment into the study and subsequent randomization:

1. The subject has signed and dated an informed consent form.
2. In the opinion of the investigator, subject is able and willing to comply with study procedures, including study visits, study dressing regimens and compliance with study required off-loading device.
3. The subject is ≥ 18 years of age.
4. The subject, if female of child-bearing potential, must not be pregnant. To document pregnancy status, subject statement is acceptable.
5. The subject has Type I or Type II diabetes mellitus with investigator-confirmed glycosylated hemoglobin (HbA1c) of ≤ 12% within 3 months prior to screening visit.
6. The subject has at least one diabetic foot ulcer that meets ALL of the following criteria:

   * Ulcer which has been in existence for a minimum of two weeks, prior to signing the Informed Consent Form for trial participation.
   * Ulcer is a partial or full thickness diabetic foot ulcer without capsule/tendon/bone exposure.
   * Ulcer does not have tunneling, undermining, or sinus tracts that necessitates surgical OR debridement and/or penetrates to capsule/tendon/bone.
   * Ulcer is located on the foot or ankle (with no portion above the top of the malleolus).
   * Ulcer size (area) is \> 1 cm2 and \< 12 cm2 post-debridement.
7. There is a minimum 1 cm margin between the qualifying study ulcer and any other ulcer on that same foot, post-debridement.

   • If the subject has more than one ulcer that meets the eligibility criteria, the ulcer designated as the study ulcer will be at the discretion of the investigator.
8. The subject has adequate vascular perfusion of the affected limb as defined by at least one of the following:

   * Ankle-Brachial Index (ABI) ≥ 0.65 or ≤1.2, performed within 3 months of screening,
   * Toe pressure (plethysmography) \> 50 mmHg at time of screening,
   * TcPO2 \> 40 mmHg at time of screening
9. The subject or responsible caregiver is willing and able to maintain required applicable dressing changes as well as study required off-loading/protective device for the duration of the study.

Exclusion Criteria

Subjects will not be enrolled in the study if any of the following criteria are met:

1. The subject was previously randomized and treated under this clinical study protocol.
2. The subject has suspected or confirmed gangrene or ulcer infection of the study ulcer or receiving systemic antibiotics for the treatment of such.
3. The subject has suspected or confirmed osteomyelitis of the foot with the study ulcer.
4. The subject has a history of hypersensitivity to bovine collagen, as determined by prior medical history.

   Protocol Number: T-PMXDFU-01 Confidential Page 23 of 64 Version 5.0 06 Nov 2018
5. The subject has participated in another clinical trial involving a device or a systemically administered investigational study drug/treatment within 28 days of randomization.
6. The subject has received, within 28 of signing Informed Consent Form, or is scheduled to receive during study participation, a medication or treatment which is known to interfere with or affect the rate and quality of ulcer healing (e.g., systemic steroids, immunosuppressive therapy, autoimmune disease therapy, dialysis, radiation therapy to the foot, vascular surgery, angioplasty, or thrombolysis).
7. The subject has a history of bone cancer or metastatic disease of the affected limb, radiation therapy to the foot, or has had chemotherapy within the 12 months prior to signing Informed Consent Form for trial participation.
8. In the opinion of the investigator, the subject has a history of, or is currently diagnosed with, any illness or condition, other than diabetes, that could interfere with ulcer healing (e.g., end-stage renal disease, severe malnutrition, liver disease, aplastic anemia, connective tissue disorder, acquired immune deficiency syndrome, HIV positive, or sickle cell anemia).
9. In the opinion of the investigator, the subject has unstable Charcot foot or Charcot with bony prominence that could inhibit ulcer healing.
10. The subject has ulcers secondary to a disease other than diabetes (e.g., vasculitis, neoplasms, or hematological disorders).
11. In the opinion of the investigator, the subject has excessive lymphedema that could interfere with off-loading and/or ulcer healing.
12. The study ulcer has received ulcer dressings that included growth factors, engineered tissues, or skin substitutes within 28 days of randomization or is scheduled to receive treatment during the study (e.g., Regranex, Dermagraft, Apligraf, EpiFix, GraftJacket, OASIS, Omnigraft, or Integra BMWD).
13. At the end of the screening phase and based on planimetric assessment, the area of the study ulcer after sharp debridement has decreased by more than 30% over the two-week screening period.