PEP on a Skin Graft Donor Site Wound

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety of a biological therapeutic PEP in participants who have skin graft donor site wounds.

Detailed Description
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This is an open label phase 1b study of PEP (a leukocyte depleted blood preparation derived from human U.S. sourced pooled apheresed platelets) in patients with at least two donor split-thickness skin graft wounds. One donor site will be treated with the standard post-operative dressing, while the other site will be treated with PEP or PEP+TISSEEL and covered with a standard dressing. TISSEEL is a commercially available fibrin sealant.

Official Title
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A Phase I Open-Label Trial to Determine the Safety of PEP on a Skin Graft Donor Site Wound

Conditions
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Skin Graft

Intervention / Treatment
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* Biological: 10% PEP
* Drug: TISSEEL
* Biological: 20% PEP


Participation Criteria
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Eligibility Criteria
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Main Criteria for Inclusion: Males and females 18-75 years of age. Requiring at least two 20-40 cm2 split-thickness skin grafts by a licensed surgeon or dermatologist Skin graft that meets all the following criteria: Each graft site has a size of 20-40 cm2 (but can be up to 90 cm2 if found to be clinically indicated during the graft procedure) Located anywhere on the body (with exception of oral mucosal membranes) Split-thickness skin graft wound depth of between 8/1000-14/1000 inch Study donor sites are ≥ 1 cm apart Ability to safely undergo skin graft harvest procedure Capacity to provide informed consent Ability to comply with protocol Subject is judged, by the clinical investigator, to be healthy as evidenced by lack of clinically significant abnormal findings on medical history, physical examination, vital signs, and clinical laboratory tests Subject is able and willing to return to study site for all follow-up visits Main Criteria for Exclusion: Actively undergoing chemotherapy treatment (localized radiation treatment is allowed if it is not on the skin graft donor site and no active cancer is present) Known history of MRSA (methicillin-resistant Staphylococcus aureus) Known hypersensitivity to aprotinin (Trasylol®) Subjects who are positive for hepatitis B surface antigen (HbsAg), hepatitis C antibody or human immunodeficiency virus (HIV) Any known allergy or sensitivity to adhesive dressings (e.g., Tegaderm) Clinically significant cardiovascular, pulmonary, renal, endocrine, hepatic, neurological, psychiatric, immunological, gastrointestinal, hematological, or metabolic disease that is, in the opinion of the investigator, not stabilized or may otherwise impact the results of the study Participation in another interventional clinical study or trial in the past 30 days or concurrent participation in another interventional clinical study or trial Subjects with poorly controlled diabetes mellitus (Hemoglobin A1c [HbA1c] ≥ 8%) Subjects with known peripheral neuropathy, or known concomitant vascular problems (such as peripheral artery disease, arterial insufficiency, or venous hypertension) or calciphylaxis Subjects with burns covering ≥ 30% of Total Body Surface Area Currently on or planned to receive hyperbaric wound therapy Pregnant or lactating female subjects Sexually active woman of childbearing potential who is unwilling to use approved contraception method for 3 months after receiving dose of investigational drug Prisoners

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 10 % PEP only<br>Cohort 1: Subjects will receive 10% PEP to the skin graft donor wound. | Biological: 10% PEP<br>* PEP is comprised of platelet derived extracellular vesicles enriched in anti-inflammatory and angiogenic growth factors.<br>|
| Experimental: 20% PEP only<br>Cohort 2: Subjects will receive 20% PEP to the skin graft donor wound | Biological: 20% PEP<br>* PEP is comprised of platelet derived extracellular vesicles enriched in anti-inflammatory and angiogenic growth factors.<br>|
| Experimental: 20% PEP and TISSEEL<br>Cohort 3: Subjects will receive 20% PEP and TISSEEL to the skin graft donor wound. | Drug: TISSEEL<br>* Fibrin sealant made from pooled human plasma<br>* Other names: fibrin sealant;Biological: 20% PEP<br>* PEP is comprised of platelet derived extracellular vesicles enriched in anti-inflammatory and angiogenic growth factors.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute dose limiting toxicities (DLTs) of PEP / PEP-Tisseel | The primary endpoint is to determine the acute (within first 14 days) safety and tolerability of PEP or PEP-TISSEEL, as assessed by the occurrence of DLTs on a 20-40 cm2 (but can be up to 90 cm2 if found to be clinically indicated during the graft procedure) skin graft donor site wound at escalating concentrations of PEP delivered at one time point through the 14-day DLT period. | Up to 2 weeks (within the first 14 days) for each dosing cohort | 
| Maximum Tolerated Dose (MTD) of PEP / PEP-Tisseel | The endpoint is to determine the acute (within first 14 days) safety and tolerability of PEP or PEP-TISSEEL, as assessed by the occurrence of MTDs on a 20-40 cm2 (but can be up to 90 cm2 if found to be clinically indicated during the graft procedure) skin graft donor site wound at escalating concentrations of PEP delivered at one time point through the 14-day MTD period. | Up to 2 weeks (within the first 14 days) for each dosing cohort | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long Term safety of PEP / PEP-Tisseel | The secondary endpoint is to determine the safety and tolerability of a single dose of PEP or PEP-Tisseel delivered at a single time point, as assessed by the occurrence of DLTs through the Day 15-182 DLT period | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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skin graft, exosome, PEP, wound, healing