A RCT Evaluating Efficacy of Type-I Collagen Skin Substitute vs. Human Amnion Membrane in Treatment of Venous Leg Ulcers

Inclusion Criteria:

1. Subjects must be at least 18 years of age or older.

2. Subjects must have a diagnosis of a venous leg ulcer (confirmed by clinical andduplex ultrasound evaluation).

3. At enrolment subjects must have a target VLU with a minimum surface area of 2.0 cm2and a maximum surface area of 25.0 cm2 measured post debridement using a ruler tomeasure wound area.

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

5. The target ulcer must be located on the foot, ankle and lower leg region.

6. The target ulcer must be full thickness on the foot or ankle that does not probe tobone.

7. Adequate circulation to the affected foot as documented by any of the followingmethods performed within 3 months of the first screening visit:

i. TCOM ≥30 mmHg ii. ABI between 0.7 and 1.3 iii. PVR: Biphasic iv. TBI ˃0.6 v. As an alternative arterial, Doppler ultrasound can be performed evaluating for biphasic dorsalis pedis and posterior tibial vessels at the level of the ankle of the target extremity.

h. 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.

i. The subject must consent to using the prescribed off-loading method for the duration of the study.

j. The subject must agree to attend the twice-weekly/weekly study visits required by the protocol.

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

l. Patients must have read and signed the IRB approved ICF before screening procedures are undertaken.

Exclusion Criteria:

1. A subject known to have a life expectancy of <6 months

2. If the target ulcer is infected or if there is cellulitis in the surrounding skin.

3. Presence of osteomyelitis or exposed bone, probes to bone or joint capsule oninvestigator's exam or radiographic evidence.

4. A subject that has an infection in the target ulcer that requires systemicantibiotic therapy.

5. A subject receiving immunosuppressants (including systemic corticosteroids at dosesgreater than 10 mg of Prednisone per day or equivalent) or cytotoxic chemotherapy.

6. Topical application of steroids to the ulcer surface within one month of initialscreening.

7. A subject with a previous partial amputation on the affected foot is excluded if theresulting deformity impedes proper offloading of the target ulcer.

8. A subject with autoimmune or connective tissue disorders.

9. A subject with malignant wounds or non-venous ulcers.

10. A subject with a serum creatinine ≥ 3.0mg/dL within 6 months of the initialscreening visit.

11. Women who are pregnant or considering becoming pregnant within the next 6 months andthose who are breast feeding.

12. A subject with end stage renal disease requiring dialysis.

13. A subject who participated in a clinical trial involving treatment with aninvestigational product within the previous 30 days.

14. A subject who, in the opinion of the Investigator, has a medical or psychologicalcondition that may interfere with study assessments.

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

16. History of autoimmune disease, malignancy, or uncontrolled diabetes (HbA1c >10%).

17. Allergy to components of High Purity Type-I Collagen-based Skin Substitute orDehydrated Human Amnion/Chorion Membrane.