Evaluation of Safety and Efficacy of realSKIN® (Skin Xenotransplant) for Complete Closure of Severe Burn Wounds

NCT03695939 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2018P001839
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 2

Brief Summary

This is a Phase 1/2, Open-label, Multi-center, Clinical Trial to evaluate the safety, tolerability, and efficacy of realSKIN® to provide complete wound closure of severe and extensive deep-partial and full-thickness burn wounds. Approximately 25 total subjects will be enrolled. Subjects who meet eligibility criteria and provide written informed consent will receive realSKIN® placement at a single burn wound site. The designated realSKIN® product size will be placed on the burn wound following wound site preparation, including necessary debridement and tangential excision as determined by burn surgeon and secured in place via suturing or stapling. The remaining burn wound will be covered with human cadaver allograft and treated according to local standard of care with care to avoid any overlap or significant contact of the two temporary wound dressings. The Investigator will assess the wounds and identify the matched pair of burn sites then the treatments will be randomly assigned to the sites. realSKIN® will remain in place until intentional removal per Investigator's direction consistent with subject's overall clinical course, or if it is deemed to no longer provide effective wound closure and barrier function to the wound bed. The Investigator will follow local standard of care relevant to wound care and dressing changes while the realSKIN® is in place. Standard of care burn management will be provided by the Investigator. Routine vital sign assessments, photography, laboratory tests (hematology, chemistry, and urinalysis), physical exams, and adverse event monitoring will occur while realSKIN® is in place and for up to 1 year following initial placement. Subjects will be monitored via a passive and active screening program using blood samples collected at time points throughout the study period, as adapted from FDA Guidance for Industry. The risk of transmission of infectious disease is expected to be extremely low and while limited human trial data are available there have been no reports of transmission of porcine microorganisms to humans, and to date, there have been no adverse events (AEs) related to the use of realSKIN® observed or reported, and independent analysis of PERV data and medical records by the Safety Review Committee has indicated no evidence of zoonotic transmission in this trial.

Conditions

Deep Full-thickness Burn Injury (Disorder)

Keywords

xenotransplant; skin; burns; temporary; allograft; porcine; closure; dressing; live biotherapeutic; xenograft; pig; genetically engineered; alpha-Gal; GalT-KO

Outcome Measures

Primary Outcomes (2)

• Temporary Wound Closure

  To assess the capability of realSKIN® to improve wound healing by providing supportive care until definitive closure can be accomplished by functioning as a barrier, much like human skin, as compared to similar wound site(s) treated with human cadaver allograft (HCA).

  Prior to autograft placement (within 14 days)

• Long-term Safety and Tolerability

  To further demonstrate the long-term safety and tolerability of realSKIN®, to include evidence that Xeno-Skin® does not significantly impede wound healing.

  Prior to autograft placement (continued follow up through 6 months)

Secondary Outcomes (2)

• Definitive Wound Closure

  Post autograft placement (continued follow up through 1 year)

• Improved Wound Healing

  Post autograft placement (continued follow up through 1 year)

Study Arms (2)

Experimental Treatment: realSKIN (skin xenotransplant)

EXPERIMENTAL

In the experimental arm, patients are treated with the investigational drug, realSKIN®, in a side-by-side comparison to the active comparator, thus, each patient serves as their own control. The designated realSKIN® product size will be placed on the burn wound and secured in place via suturing or stapling. The Investigator will assess the wounds and identify the matched pair of burn sites then the treatments will be randomly assigned to the sites.

Biological: realSKIN (skin xenotransplant)

Active Comparator: Human Allograft Skin

ACTIVE COMPARATOR

In the active comparator arm, patients are treated with human cadaver allograft, in a side-by-side comparison to the investigational drug, thus, each patient serves as their own control. The allograft active comparator will be placed adjacently to the investigational drug, in the same anatomical location, on wound sites following debridement and secured via suture or staples. All other treatment aspects were consistent with the standard of care. The Investigator will assess the wounds and identify the matched pair of burn sites then the treatments will be randomly assigned to the sites.

Biological: Human Cadaver Allograft

Interventions

realSKIN (skin xenotransplant) BIOLOGICAL

3+3 Dose-escalation Study Design; 2 dosage strengths will be utilized during this Phase 1/2 Trial; an expansion cohort (9 patients) receive the highest dose.

Experimental Treatment: realSKIN (skin xenotransplant)

Human Cadaver Allograft BIOLOGICAL

HCA is used as a temporary wound dressing between debridement and definitive closure in many well-resourced contexts.

Also known as: Human Allograft Skin, HCA

Active Comparator: Human Allograft Skin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The subject provides written informed consent to participate in this study
• Males or females age greater than 18 years old
• Females must have a negative serum pregnancy test at Screening and at Baseline and must not be nursing
• Male and female subjects must agree to use a protocol-approved method of contraception for a minimum of 3 months following Xeno-Skin® 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
• Total Body Surface Area (TBSA) \<30%, to include deep-partial thickness or full-thickness burn wounds
• Burn injuries would otherwise require debridement and tangential excision
• Burn injury requiring temporary grafting with human cadaver allograft skin, based on clinical judgment prior to definitive wound closure via autologous grafting
• Sufficient area of burn wound for Xeno-Skin® placement and not located on face or hands or having an engraftment 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

You may not qualify if:

• Pregnant or lactating women
• 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
• 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
• Known allergy to penicillins (such as ampicillin), ceftazidime or aztreonam, glycopeptide antibiotics (such as vancomycin) or amphotericin B
• 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
• Use of any experimental or investigational drugs within 30 days prior to placement of Xeno-Skin®
• 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)
• BMI \> 40 kg/m2
• HbA1c ≥ 7.0%
• Treatment with systemic corticosteroids within 30 days before screening (not including inhaled steroids)
• Electrical, chemical, or radiation burns
• History of chronic end stage renal disease defined as an MDRD CrCl \< 15 mL/min, or receiving chronic dialysis
• 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
• 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.
• 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 (TIA), endovascular procedure or surgical intervention for peripheral vascular disease or plans to undergo a major surgical or interventional procedure (eg, PCI, CABG, carotid or peripheral revascularization)

Sponsors & Collaborators

• XenoTherapeutics, Inc.: lead
• Massachusetts General Hospital: collaborator
• Joseph M. Still Research Foundation, Inc.: collaborator

Study Sites (2)

JMS Burn Center at Doctors Hospital

Augusta, Georgia, 30909, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Related Publications (34)

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MeSH Terms

Conditions

Burns

Condition Hierarchy (Ancestors)

Wounds and Injuries

Study Officials

• Jeremy Goverman, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase 1/2, Open-label, Multi-center, Clinical Trial to evaluate the safety, tolerability, and efficacy of realSKIN® to provide complete wound closure of severe and extensive deep-partial or full-thickness burn wounds. Approximately 25 total subjects will be enrolled. The designated realSKIN® product size will be placed on the burn wound following wound site preparation, including necessary debridement and tangential excision as determined by burn surgeon and secured in place via suturing or stapling. The remaining burn wound will be covered with human cadaver allograft and treated according to local standard of care with care to avoid any overlap or significant contact of the two temporary wound dressings. The Investigator will assess the wounds and identify the matched pair of burn sites then the treatments will be randomly assigned to the sites.

Study Record Dates

• First Submitted: September 28, 2018
• First Posted: October 4, 2018
• Study Start: March 15, 2019
• Primary Completion: December 30, 2023
• Study Completion: December 30, 2023
• Last Updated: January 12, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)