Safety and Efficacy of realSKIN® to Provide Complete Wound Closure of Burn Wounds as an Alternative to Autografting

A Phase III Open-Label, Multicenter, Randomized, Controlled Clinical Trial to Evaluate the Safety and Efficacy of realSKIN® to Provide Complete Wound Closure of Mixed-Depth, Full-Thickness Burn Wounds as an Alternative to Autografting

To evaluate the safety and efficacy of realSKIN® to provide complete wound closure of mixed-depth, full-thickness burn wounds as an alternative treatment to autografting.

This study is a Phase 3 open-label, interventional, controlled, randomized, multicenter clinical trial. It is comprised of an estimated 50 men and women aged 18 years and older who experienced severe and extensive, mixed-depth and full-thickness thermal burn wounds up to 50% TBSA requiring surgical excision and skin grafting for which autografting is clinically indicated.

The comparator control for the study is autografting, the current standard of care procedure for the treatment of severe burns, which involves the removal of healthy skin from an uninjured site on the patient and using it to cover the original burn wound to achieve complete and durable wound closure.

After surgical preparation of the wound bed, subjects will receive approximately 100 square centimeters of realSKIN at a predesignated wound site and separately, autografting at an alternate site, per the standard of care, in accordance with the randomization schedule.

Thus, each patient represents both the experimental and control group, to be evaluated in isolated but comparable settings. The use of an intra-patient comparator allows for a matched control to eliminate significant underlying differences, including immunologic, physiologic, and scarring variable inherent in this patient population that may impact wound healing at the treatment sites.

After surgical excision to remove nonviable tissue or previously applied temporary wound dressings, two wound treatment sites of comparable area and depth will be identified.

Treatment assignment will be randomized to receive either realSKIN or a surgically harvested autograft. The pre-identified treatment sites must each be a wound area of comparable depth that is not contiguous (e.g., "sharing a common border or touching") to ensure the interpretability of the efficacy results.

Additionally, two unaffected areas of the patient's intact, healthy skin will be prospectively identified to provide sources of autografts for the control site and realSKIN treatment site (e.g., patient skin harvest sites.) These pre-identified regions may be in the same anatomic area or from two separate but comparable areas, depending on the amount of intact native patient skin available.

Inclusion Criteria:

1. The subject, or the subject's legally authorized representative (LAR), provides written informed consent to participate in this study

2. Males or females age greater than or equal to 18 years old

3. Total Burn Surface Area (TBSA) <50% to include mixed depth and full-thickness burn wounds as defined as "primarily full-thickness (FT) and deep-partial (DPT) thermal burns (e.g. >60% of the total burn area should be FT and DPT) before debridement", and full-thickness burns for which surgical intervention is clinically indicated

4. Having a mixed depth thermal burn wound including full thickness requiring skin grafting

5. Biological females must have a negative serum pregnancy test at Screening and must not be nursing

6. All subjects must agree to use a protocol-approved method of contraception for a minimum of 3 months following realSKIN placement, which includes a barrier method plus one or more of the following:

   • Hormonal contraceptives (e.g., birth control pills, skin patches, vaginal rings, and the Depo-Provera shot)
   • Intrauterine device (IUD)
   • Male or female condoms with spermicide
   • Diaphragm with spermicide
   • Permanent tubal occlusive birth control system

7. Sufficient area of burn wound for realSKIN and comparator autograft placement to not be located on face or hands or having a target graft site centered on high-impact areas such as joints, weight-bearing areas (e.g. soles of feet), or the inguinal region, per Investigator's judgment

Exclusion Criteria:

1. Pregnant or lactating women
2. Documented history of infection with human immunodeficiency virus (HIV) or other condition(s) that in the opinion of the Investigator may compromise patient safety or study objectives
3. Immunosuppressive medication regimens e.g. antineoplastics, high dose steroids (>10 mg prednisone/day), TNF alpha inhibitors, calcineurin inhibitors (cyclosporine, tacrolimus), anti- proliferative agents, and other immunomodulators
4. Active malignancy, including those requiring surgery, chemotherapy, and/or radiation in the past 5 years; non-metastatic basal or squamous cell carcinoma of the skin and cervical carcinoma in situ are allowed
5. Use of any experimental or investigational drugs within 30 days prior to placement of realSKIN
6. Previously received a porcine or other xenogeneic tissue product, including but not limited to: glutaraldehyde fixed porcine or bovine bioprosthetic heart valve replacements and glutaraldehyde fixed porcine dermal matrix (e.g., EZ Derm)
7. Patients with advanced or unstable/uncontrolled comorbid conditions, such as advanced renal disease, diabetes mellitus and liver disease
8. Patients with HbA1c ≥ 10.0%; specimen must be obtained for screening purposes if current (within past 3 months) value is not available
9. Patients with a history of chronic end stage renal disease defined as MDRD CrCL < 15mL/min or receiving chronic dialysis
10. Patients with a history of chronic liver disease or cirrhosis (Child-Pugh Score C); evidence of acute or chronic hepatitis B infection based on documented HBV serology testing
11. Known documented history of Hepatitis B, Hepatitis C, Treponema pallidum, Cytomegalovirus, herpes or varicella zoster; note: Successfully treated hepatitis C patients without evidence of end stage liver disease is allowed; if HCV antibody reactive, then HCV RNA must be undetectable
12. Recent (within 3 months prior to study enrollment) MI, unstable angina leading to hospitalization, uncontrolled, CABG, PCI, carotid surgery or stenting, cerebrovascular accident, transient ischemic attack, endovascular procedure, or surgical intervention for peripheral vascular disease or plans to undergo a major surgical or interventional procedure (e.g., PCI, CABG, carotid or peripheral revascularization)
13. Presence of venous or arterial vascular disorder directly affecting the area of burn wound
14. Pre-existing haemolytic anemia
15. Chronic malnourishment as determined by Investigator
16. Inhalation injury as determined by bronchoscopic exam if available, or diagnosis at the time of screening
17. Systemic anticoagulation at the time of treatment or INR > 2
18. Documented evidence of wound infection at Screening
19. Evidence of sepsis at Screening