A Prospective Clinical Study to Evaluate the Effectiveness and Safety of Xcell Amnio MatrixTM (XAM) in the Management of Chronic Non-healing DFUs

Inclusion Criteria:

Subjects will be eligible for enrollment in the study only if they meet ALL the following criteria at time of Screening:

1. Subject is 18 years of age or older.

2. Subject has diabetes mellitus (Type 1 or Type 2), requiring insulin ororal/injectable medications to control blood glucose levels

3. Glycosylated hemoglobin (HbA1c) level is <12% Note: Prior documented HbA1c within 12 weeks of Screening is acceptable.

4. Duration of ulcer is ≥ 4 weeks but ≤ 1 year, unresponsive to SOC

5. Ulcer area is ≥ 1.5cm2 and ≤ 20cm2 and with a clean, granulating base with minimaladherent slough at the Baseline Visit

6. Ulcer location is at or below the ankle (malleolus)

7. Subject is amenable to use of off-loading, as needed for plantar ulcer

8. Ulcer extends through the full thickness of the skin but not down to muscle, tendon,or bone

9. Subject is at least 12 weeks post lower extremity revascularization procedure, ifone has been performed.

10. Subject is in general good health, with no clinically significant medical conditionsor abnormalities that, in the opinion of the Investigator, would interfere withstudy participation, the assessment of study endpoints, or pose additional risk tothe subject.

11. Adequate circulation to the affected lower extremities as demonstrated by one of thefollowing within 12 weeks of screening:

12. Dorsum transcutaneous oxygen measurement (TCOM) ≥ 30 mmHg,

13. Skin perfusion pressure (SPP) measurement ≥ 30 mmHg,

14. Ankle-Brachial Index (ABI) ≥0.7 and ≤1.2, OR

15. Toe-Brachial Index (TBI) ≥ 0.6

16. Subject is willing to use an acceptable method of contraception throughout theduration of the trial, if of childbearing potential. Acceptable methods of contraception include abstinence, female subject/partner's useof hormonal contraceptive (oral, patch, injectable, depot or vaginal) in conjunctionwith a barrier method (e.g., diaphragm, cervical cap, condom, spermicide or sponge),or female subject/partner's use of an implantable device (implantable rod orintrauterine device). Female subject/partners of non-childbearing potential are defined as surgicallysterile (e.g., bilateral tubal ligation, hysterectomy) or two years postmenopausalat time of screening. All male subjects (excluding men who have been sterilized) with female partners ofchild-bearing potential must agree to consistently and correctly use a condom forthe duration of the study. In addition, subjects may not donate sperm for the sametime period.

17. Subject is able to read, understand and sign the informed consent form (ICF).

18. Subject is available and willing to complete all study assessments and can complywith standard of care (debridement, dressing changes etc.) as applicable.

Exclusion Criteria:

Subjects meeting ANY of the following criteria at time of Screening will be excluded from enrollment:

1. Clinical evidence of ongoing infection and/or receipt of IV, oral, or topicalantimicrobials.

2. Wheelchair bound or bed-ridden (ambulatory with assistance is acceptable).

3. Ulceration at the site of amputation.

4. Undergoing renal dialysis.

5. Known or suspected malignancy in the target ulcer, or a history of cancer in thepreceding 5 years (other than carcinoma in situ of the cervix or adequately treatednon-melanoma skin cancer).

6. Documented history of osteomyelitis at the target ulcer location within 6 months ofscreening.

7. History of radiation at the ulcer site.

8. New York Heart Association Class III or IV congestive heart failure or uncontrolledcardiac dysrhythmia.

9. Diagnosis of autoimmune disease(s) (rheumatoid arthritis, lupus, psoriasis,Sjogren's syndrome) or arthritis requiring corticosteroid treatment.

10. Subject has received in the past 4 weeks or is scheduled to receive any of followingmedication or therapies during the course of the study:

11. Immunosuppressants (including chronic systemic corticosteroids or applicationof topical steroids to the ulcer surface)

12. Cytotoxic chemotherapy

13. Growth hormone

14. Oral or systemic antifungal or antituberculosis treatment

15. Use of any investigational drug(s) or therapeutic device(s)

16. Target ulcer(s) previously treated with negative pressure, hyperbaric oxygen, ortissue engineered materials (e.g., Apligraf®, EpiFix® or Dermagraft®) or otherscaffold materials (e.g., Oasis, Matristem) within 4 weeks prior to screening.

17. Target ulcer(s) anticipated to require negative pressure wound therapy or hyperbaricoxygen at any time during the study.

18. Healing of target ulcer is observed to be ≥35% at the end of the Run-in Period (between Screening and Baseline Visits)

19. Subject is pregnant or breastfeeding.

20. Presence of any other condition(s) which seriously compromises the subject's abilityto complete this study or has a known history of poor adherence with medicaltreatment.

21. Active Charcot foot (stable chronic Charcot foot is not exclusionary).

22. Ulcers on toes 2, 3, 4, and/or 5 only (ulcer on plantar surface of the great toeonly is not exclusionary).