PEP on a Skin Graft Donor Site Wound

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Skin Graft
• Intervention / Treatment: Biological: 10% PEP; Biological: 20% PEP; Drug: TISSEEL

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Doral, Florida, United States, 33122
      • International Research Partners
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

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

Description

Main Criteria for Inclusion:

1. Males and females 18-75 years of age.
2. Requiring at least two 20-40 cm2 split-thickness skin grafts by a licensed surgeon or dermatologist

3. Skin graft that meets all the following criteria:

   1. 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)
   2. Located anywhere on the body (with exception of oral mucosal membranes)
   3. Split-thickness skin graft wound depth of between 8/1000-14/1000 inch
   4. Study donor sites are ≥ 1 cm apart
4. Ability to safely undergo skin graft harvest procedure
5. Capacity to provide informed consent
6. Ability to comply with protocol
7. 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
8. Subject is able and willing to return to study site for all follow-up visits

Main Criteria for Exclusion:

1. 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)
2. Known history of MRSA (methicillin-resistant Staphylococcus aureus)
3. Known hypersensitivity to aprotinin (Trasylol®)
4. Subjects who are positive for hepatitis B surface antigen (HbsAg), hepatitis C antibody or human immunodeficiency virus (HIV)
5. Any known allergy or sensitivity to adhesive dressings (e.g., Tegaderm)
6. 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
7. Participation in another interventional clinical study or trial in the past 30 days or concurrent participation in another interventional clinical study or trial
8. Subjects with poorly controlled diabetes mellitus (Hemoglobin A1c [HbA1c] ≥ 8%)
9. Subjects with known peripheral neuropathy, or known concomitant vascular problems (such as peripheral artery disease, arterial insufficiency, or venous hypertension) or calciphylaxis
10. Subjects with burns covering ≥ 30% of Total Body Surface Area
11. Currently on or planned to receive hyperbaric wound therapy
12. Pregnant or lactating female subjects
13. Sexually active woman of childbearing potential who is unwilling to use approved contraception method for 3 months after receiving dose of investigational drug
14. Prisoners

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / 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: 20% PEP and TISSEEL; Cohort 3: Subjects will receive 20% PEP and TISSEEL 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.; Drug: TISSEEL; Fibrin sealant made from pooled human plasma; Other Names: fibrin sealant

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory Endpoint	The exploratory endpoint is to assess wound closure as defined as 100% re-epithelialization after treatment with PEP and PEP-TISSEEL.	6 months

Collaborators and Investigators

• Sponsor: Rion Inc.
• Collaborators: ProPharma
• Investigators: Study Director: Michael Sabbah, MD, Rion Inc.

Publications and helpful links

Helpful Links

• Rion company website

Study record dates

Study Major Dates

• Study Start (Actual): March 16, 2021
• Primary Completion (Actual): August 9, 2023
• Study Completion (Estimated): February 2, 2024

Study Registration Dates

• First Submitted: December 7, 2020
• First Submitted That Met QC Criteria: December 7, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2023
• Last Update Submitted That Met QC Criteria: September 6, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: wound; healing; PEP; exosome; skin graft
• Additional Relevant MeSH Terms: Hemostatics; Coagulants; Fibrin Tissue Adhesive
• Other Study ID Numbers: PRO-00068; 18-004995 (Other Identifier: Mayo Clinic)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: ALL IPD that underlie the results in a publication.
• IPD Sharing 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.
• IPD Sharing Access Criteria: IPD will only be shared with the collaborator Rion LLC
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No