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

January 11, 2024 updated by: XenoTherapeutics, Inc.

An Open-label Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of realSKIN® (Skin Xenotransplant) for Complete Closure of Severe and Extensive Deep-Partial and Full-Thickness Burn Wounds

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Product Name: realSKIN®

Chemical Name: alpha-1,3-galactosyltransferase knock-out (GalT-KO) porcine (Sus scrofa) epidermal and dermal layers.

Chemical Structure: realSKIN® a biologically active, split-thickness, xenotransplantation skin product. realSKIN® is derived from specialized, genetically engineered (alpha 1,3 galactosyltransferase knockout [GalT-KO]), Designated Pathogen Free (DPF), porcine donors, containing vital, metabolically active (i.e., non-terminally sterilized) porcine cells within the dermal and epidermal tissue layers.

Proposed Indication: realSKIN is indicated for the treatment of mixed-depth, full-thickness burn wounds requiring hospitalization, surgical excision, and skin grafting.

Drug Type: realSKIN® is classified as a Live Biotherapeutic Product (LBP). (Guidance to Industry, Early Clinical Trials with Live Biotherapeutic Products, Section 1.b.)

Active Ingredient: Live (i.e. non-terminally sterilized) porcine cells, including endothelial cells of intact vasculature and those comprising the dermal and epidermal tissue layers

Product Structure: realSKIN® has an approximate thickness of 0.022 inches (0.55mm) and is currently provided in one investigational size: approximately 5x15 cm2 (22.5g/75 cm2).

Formulation: Each lot or releasable batch of realSKIN® is derived from a single source animal and each batch is independently processed and tested for various adventitious agents, histology, morphology, sterility, and purity.

Route of Administration: Surgical engraftment, via sutures or staples

Dosing Regimen: A single topical application of realSKIN has an approximate size of 150 cm2, with dimensions of 5 cm x 15 cm, meshed in a 2:1 ratio, and has an approximate thickness of 0.022 inches (0.55 mm).

realSKIN is intended for a one-time, topical application to a surgically prepared wound bed via sutures or staples and may be trimmed to fit the shape and size of the actual wound area. realSKIN can be used in the treatment of an overall injury size of up to 30% TBSA burn injury.

Drug's Mechanism of Action: realSKIN is intended for topical use directly on debrided, severe and extensive, mixed-depth and full-thickness burn wounds to provide complete and durable wound closure.

As a living skin transplant, realSKIN forms microvascular connections with host vessels in the burn wound bed which leads to wound closure. realSKIN replaces elements of whole, living skin that are analogous and functionally equivalent to those found in healthy human skin. realSKIN does not remain permanently engrafted but is replaced by the patient's own cells over time.

This mechanism of action distinguishes realSKIN from traditional xenograft products which are terminally sterilized, rendering the cells inactive, limiting their therapeutic capability to effect complete and durable wound closure.

Drug Packaging: Each realSKIN® product is individually packaged in a clear plastic, externally threaded, 10-ml polypropylene vial with threaded seal-cap, stored on a rolled, sterile nylon mesh backing on the dermal-side of the realSKIN® product that serves to support and protect the graft during processing and transport. Within this container, each realSKIN® product is individually immersed in 7-ml of sterile cryoprotective medium with 5% dimethyl sulfoxide (DMSO) (CryoStor CS5, BioLifeSolutions). Source animal serum is NOT included or used in this process. The contents are cryopreserved via controlled rate, phase freezer and stored at -80o C until use. All packaging materials are removed prior to the surgical procedure and dressing placement.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Augusta, Georgia, United States, 30909
        • JMS Burn Center at Doctors Hospital
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. The subject provides written informed consent to participate in this study
  2. Males or females age greater than 18 years old
  3. Females must have a negative serum pregnancy test at Screening and at Baseline and must not be nursing

  4. 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:

    1. Hormonal contraceptives (e.g., birth control pills, skin patches, vaginal rings, and the Depo- Provera shot)
    2. Intrauterine device (IUD)
    3. Male or female condoms with spermicide
    4. Diaphragm with spermicide
    5. Permanent tubal occlusive birth control system
  5. Total Body Surface Area (TBSA) <30%, to include deep-partial thickness or full-thickness burn wounds
  6. Burn injuries would otherwise require debridement and tangential excision
  7. Burn injury requiring temporary grafting with human cadaver allograft skin, based on clinical judgment prior to definitive wound closure via autologous grafting
  8. 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

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. Known allergy to penicillins (such as ampicillin), ceftazidime or aztreonam, glycopeptide antibiotics (such as vancomycin) or amphotericin B
  5. 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
  6. Use of any experimental or investigational drugs within 30 days prior to placement of Xeno-Skin®
  7. 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)
  8. BMI > 40 kg/m2
  9. HbA1c ≥ 7.0%
  10. Treatment with systemic corticosteroids within 30 days before screening (not including inhaled steroids)
  11. Electrical, chemical, or radiation burns
  12. History of chronic end stage renal disease defined as an MDRD CrCl < 15 mL/min, or receiving chronic dialysis
  13. 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
  14. 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.
  15. 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)
  16. Presence of venous or arterial vascular disorder directly affecting the area of burn wound
  17. Pre-existing haemolytic anemia
  18. Chronic malnourishment as determined by Investigator
  19. Significant pulmonary compromise
  20. Systemic anticoagulation at the time of treatment or INR > 2
  21. Documented evidence of wound infection at Screening or Baseline
  22. Evidence of sepsis and/or end organ damage
  23. Acute lung injury
  24. Life expectancy of less than 180 days
  25. Subject who is unable to self-consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Active Comparator: Human Allograft Skin

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
HCA is used as a temporary wound dressing between debridement and definitive closure in many well-resourced contexts.
Other Names:
  • Human Allograft Skin
  • HCA
Experimental: Experimental Treatment: realSKIN (skin xenotransplant)
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)
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Temporary Wound Closure
Time Frame: Prior to autograft placement (within 14 days)
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
Time Frame: Prior to autograft placement (continued follow up through 6 months)
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Definitive Wound Closure
Time Frame: Post autograft placement (continued follow up through 1 year)
To assess the quality of healing, to include scarring, contour and feel of healed skin, or normalization of skin markings or pigmentation, at wound treatment sites that received temporary closure with realSKIN®, as compared to that of wound treatment site(s) that received temporary closure with human cadaver allograft (HCA).
Post autograft placement (continued follow up through 1 year)
Improved Wound Healing
Time Frame: Post autograft placement (continued follow up through 1 year)
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).
Post autograft placement (continued follow up through 1 year)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

XenoTherapeutics, Inc.

Collaborators

Massachusetts General Hospital
Joseph M. Still Research Foundation, Inc.

Investigators

  • Principal Investigator: Jeremy Goverman, MD, Massachusetts General Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2019

Primary Completion (Actual)

December 30, 2023

Study Completion (Actual)

December 30, 2023

Study Registration Dates

First Submitted

September 28, 2018

First Submitted That Met QC Criteria

October 3, 2018

First Posted (Actual)

October 4, 2018

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 11, 2024

Last Verified

December 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2018P001839

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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