Nonhealing Venous Leg Ulcers Treated With a Standard of Care (SoC) Alone or Standard of Care and Dehydrated Human Placenta Tissue (dHPT) With Crossover

A Multicenter, Randomized Trial Evaluating Dehydrated Human Placenta Tissue (dHPT) and Standard of Care Versus Standard of Care Alone in Nonhealing Venous Leg Ulcers With Crossover for Subjects Randomized to Standard of Care

The purpose of this study is to determine how well our dHPT (Dehydrated Human Placental Tissue) Product and Standard of Care work when compared to Standard of Care alone in achieving complete closure of venous leg ulcers.

In 2020, more than 4.5 billion people around the world were estimated to have chronic venous disease stages C1-C6, and approximately 3 in every 1000 people globally develop a VLU annually. While the pathophysiology of VLUs is complex, risk factors are thought to include noncompliance with compression therapy, incorrect ulcer diagnosis, obesity, and a history of deep vein thrombosis. It is estimated that 7% of VLUs do not heal within a 12-month period. As with DFUs, treatment of VLUs focuses on prevention. Low-income individuals, especially those from minority communities, often face difficulties in accessing advanced wound care centers. The estimated annual cost of treating VLUs in the United States in 2022 was over $4.9 billion, which includes expenses for practitioners, wound care products, hospital stays, medications, and compression therapy.

Despite the well-established standard of care for chronic wounds, which includes sharp debridement, offloading, compression therapy, and maintaining proper moisture balance, a notable gap remains between clinical outcomes and desired results in chronic wound care. The reported recurrence rate for venous leg ulcers (VLUs) also ranges from 24% - 57%, illustrating the long-term burden this pathology places on patients.

One approach to treating chronic wounds involves the use of cellular, acellular, and matrix-like products (CAMPs), which are defined as 'A broad category of biomaterials, synthetic materials, or biosynthetic matrices that support repair or regeneration of injured tissues through various mechanisms of action. The application of CAMPs in chronic wound treatment provides several benefits, including creating a protective environment for healing, covering deep structures, aiding surgical closure, enhancing functional outcomes, and improving appearance. The cellular category of CAMPS includes allografts, which are human donor tissue samples intended for use in other human patients. Utilizing dehydrated human placental tissue (dHPT) as an allograft displays considerable promise for chronic wound treatment.

Inclusion Criteria:

Participants are required to meet all the following criteria for enrollment into the study:

1. 18 years of age or older.

2. Hemoglobin A1c (HbA1c) level is <12% (108 mmol/mol).

3. Target ulcer with a surface area of between 1.0 cm 2 and 25.0 cm 2 measured post debridement at randomization.

4. Target ulcer must have been present for a minimum of 4 weeks with standard of care prior to the initial screening visit.

5. Affected limb must have adequate perfusion confirmed by vascular assessment performed within 90 days of screening visit. Any of the following methods are acceptable:

   1. ABI ≥ 0.7 and ≤ 1.3;
   2. TBI ≥ 0.6;
   3. TCOM ≥ 40 mmHg;
   4. PVR: biphasic or triphasic.

6. If the participant has two or more ulcers, they must be separated by at least 2 cm post debridement. The largest ulcer satisfying the inclusion and exclusion criteria will be designated as the target ulcer.

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

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

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from enrollment:

1. Known life expectancy of <6 months.
2. Target ulcer is infected or there is cellulitis in the surrounding skin.
3. Evidence of osteomyelitis complicating the target ulcer.
4. Participant requires systemic antibiotic therapy or has used within the last 7 days.
5. Receiving immunosuppressants (including systemic corticosteroids at doses greater than 10 mg of Prednisone per day or equivalent), receiving cytotoxic chemotherapy, or taking medications that the investigator believes will interfere with wound healing (e.g., biologics).
6. Topical application of steroids to the ulcer surface within 30 days of screening.
7. Target ulcer exposes tendon or bone.
8. Surface area of the target ulcer decreases by more than 20% during the 2-week screening phase.
9. Mini Nutritional Assessment (MNA) score of less than 17.
10. Participants of child bearing potential who are pregnant, considering becoming pregnant within the next 6 months, and/or are unwilling to utilize an appropriate form of contraception.
11. Currently requiring dialysis or planning to start within 6 months.
12. Medical or psychological condition that, in the opinion of the investigator, may interfere with study assessments.
13. Treated with hyperbaric oxygen therapy or a skin substitute within the 30 days prior to screening visit.
14. Sensitivity to ofloxacin, vancomycin, or amphotericin antibiotics.
15. Participation in a clinical trial involving treatment with an investigational product within the previous 30 days.