PEP on a Skin Graft Donor Site Wound

• ClinicalTrials.gov Identifier: NCT04664738
• Recruitment Status: Enrolling by invitation
• First Posted: December 11, 2020
• Last Update Posted: February 15, 2022
• Sponsor: Steven L. Moran
• Collaborator: Rion LLC
• Information provided by (Responsible Party): Steven L. Moran, Mayo Clinic

Study Description

Brief Summary:

The purpose of this study is to determine the safety of a biological agent called PEP in people who have a skin graft donor site wound.

Condition or disease	Intervention/treatment	Phase
Skin Graft	Biological: 10% PEP; Drug: TISSEEL; Biological: 20% PEP	Phase 1

Detailed Description:

This is an open label phase 1 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I Open-Label Trial to Determine the Safety of PEP on Skin Graft Wounds
• Actual Study Start Date: March 16, 2021
• Estimated Primary Completion Date: July 2022
• Estimated Study Completion Date: December 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: 10 % PEP only; Cohort 1: Subjects will receive 10% PEP to the skin graft donor wound.	Biological: 10% PEP; PEP is comprised of platelet derived extracellular vesicles enriched in anti-inflammatory and angiogenic growth factors.
Experimental: 20% PEP only; Cohort 2: Subjects will receive 20% PEP to the skin graft donor wound	Biological: 20% PEP; PEP is comprised of platelet derived extracellular vesicles enriched in anti-inflammatory and angiogenic growth factors.
Experimental: 10% PEP and TISSEEL; Cohort 3: Subjects will receive 10% PEP and TISSEEL to the skin graft donor wound.	Biological: 10% PEP; PEP is comprised of platelet derived extracellular vesicles enriched in anti-inflammatory and angiogenic growth factors.; Drug: TISSEEL; Fibrin sealant made from pooled human plasma; Other Name: fibrin sealant
Experimental: 20% PEP and TISSEEL; Cohort 4: Subjects will receive 20% PEP and TISSEEL to the skin graft donor wound.	Drug: TISSEEL; Fibrin sealant made from pooled human plasma; Other Name: fibrin sealant; Biological: 20% PEP; PEP is comprised of platelet derived extracellular vesicles enriched in anti-inflammatory and angiogenic growth factors.

Outcome Measures

Primary Outcome Measures :

1. Acute dose limiting toxicities (DLTs) [ Time Frame: Up to 2 weeks (within the first 14 days) for each dosing cohort ]
   Number of participants who experience DLTs of grade 3 or higher adverse reaction identified within the first 2 weeks of study intervention.
2. Maximum Tolerated Dose (MTD) of PEP [ Time Frame: Up to 2 weeks (within the first 14 days) for each dosing cohort ]
   Determined by testing increasing doses of PEP from 10% to 20% on dose escalation cohorts 1 to 2. The first cohort of three patients will be treated at the starting dose of 10% PEP and observed for at least two weeks from start of treatment to assess toxicity. If dose-limiting toxicity (DLT) is not seen in any of the first 3 patients, up to 3 new patients will be accrued and treated at the next higher dose level of 20% PEP.

Secondary Outcome Measures :

1. Adverse events [ Time Frame: 6 months ]
   Number of treatment-related adverse events

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Males and females 18 years of age or older.
• Requiring at least two 40 cm^2 or larger split-thickness skin grafts by a Mayo Clinic plastic surgeon or dermatologist.
• Skin graft that meets all of the following criteria:
• Each graft site has a size of 40 cm^2 (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.
• 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.
• Patient is able and willing to return to study site for all follow-up visits.

Exclusion Criteria:

• Actively undergoing cancer treatment.
• 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 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.
• Patients on systemic immunosuppression, or have systemic autoimmune or chronic inflammatory disease.
• Subjects with hepatic impairment.
• Participation in another clinical study in the past 30 days or concurrent participation in another clinical trial.
• Patients with poorly controlled diabetes mellitus (HbA1C ≥ 8%).
• Patients with known peripheral neuropathy, or known concomitant vascular problems (such as peripheral artery disease, arterial insufficiency, or venous hypertension) or calciphylaxis.
• Currently on or planned to receive hyperbaric wound therapy.
• Pregnant or lactating female patients.
• Sexually active woman of child bearing potential who is unwilling to use approved contraception method for three months after receiving dose of investigational drug
• Prisoners.

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Steven L. Moran

Rion LLC

Investigators

• Principal Investigator: Steven Moran, MD; Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Steven L. Moran, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT04664738
• Other Study ID Numbers: 18-004995
• First Posted: December 11, 2020
• Last Update Posted: February 15, 2022
• Last Verified: February 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: ALL IPD that underlie the results in a publication.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Prior to study initiation, the study protocol and informed consent form will be provided to Rion, LLC. During the study, all safety reports (as they happen or quarterly), and all SAEs as they happen will be reported to Rion, LLC. At the end of the study after database is locked, a formal clinical study report will be provided to Rion, LLC.
• Access Criteria: IPD will only be shared with the collaborator Rion LLC

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Fibrin Tissue Adhesive; Hemostatics; Coagulants