Safety Evaluation of Intracoronary Infusion of Extracellular Vesicles in Patients Following Coronary Stent Implantation

Safety Evaluation of Intracoronary Infusion of Extracellular Vesicles in Patients Following Coronary Stent Implantation (EV-CSI)

The purpose of this study is to determine the safety of using a biological drug called PEP in people who have had a coronary stent placed. A biological drug is a substance that is made from a living organism or its products (parts). In this case, PEP is made of certain parts of blood from living blood donors obtained from a certified blood bank. PEP comes in a powder form and is mixed with heparinized saline (a solution used to prevent clots in catheters) to create a solution that can be injected. The investigators want to see if PEP can be used to stop or slow heart damage.

Study Overview

• Status: Enrolling by invitation
• Conditions: Percutaneous Coronary Intervention
• Intervention / Treatment: Drug: PEP

Detailed Description

Patients who undergo Percutaneous Coronary Intervention (PCI) will be treated with a single dose of PEP within 20 minutes after stent placement or post-dilation (whichever is last). Subjects will be screened at the time of emergency room presentation. Subjects will be treated in the cardiac catheterization laboratory where the PCI will be completed and PEP will be administered. Subjects will be followed for one year after PEP administration through clinic visits.

• Study Type: Interventional
• Enrollment (Estimated): 12
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Dereen Ernst, RN; Phone Number: 507-266-1994; Email: ernst.dereen@mayo.edu
• Study Contact Backup: Name: Rebecca Sweeney; Phone Number: 507-422-2816; Email: sweeney.rebecca@mayo.edu

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Undergoing ≥1 elective, urgent, or emergent coronary stent implantation
• Angiographic evidence of TIMI 3 flow through the stented vessel after stent placement
• Angiographic evidence of residual stenosis visually <30% after stent placement
• Willing and able to provide signed informed consent
• Lives within 90 mile radius of study site
• Willing and able to return to study site for all follow-up visits

Exclusion Criteria:

• Prior solid organ transplantation at any time
• Pregnant or lactating at screening
• Known presence of chronic systemic inflammatory disorder that requires ongoing therapy with immunosuppressive agents
• Known immune system compromise including but not limited to human immunodeficiency virus (HIV), hepatitis A, hepatitis B (HBV) or hepatitis C (HCV) infection
• Known history of malignancy of any type except non-melanoma skin cancer
• Known serum creatinine >2 mg/dL or GFR ≤30 mL/min within the last twelve months
• Known AST, ALT, and/or bilirubin (total) elevated twice the upper limit of normal for age & gender within the last twelve months
• Known Hemoglobin lower than 8.0 g/dL within the last twelve months
• Known current illicit drug use at screening
• Other major surgical procedure or major trauma within the previous 14 days prior to enrollment
• Female of child bearing potential who is unwilling to agree to use acceptable contraception methods for 3 months after receiving the investigational drug
• Pacemaker/ICD implant in place
• Adult lacking decision-making capacity
• Prisoner
• Non-English speaking
• English-speaking but illiterate
• Legally blind
• Known allergy to heparin or heparin-induced thrombocytopenia
• Known history of positive SARS-CoV2 testing within the last 30 days
• DNR/DNI status prior to PCI procedure or planned DNR/DNI status after PCI procedure
• Homeless or no permanent address at the time of enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: PEP in Coronary Stent Implantation; Patients undergoing a percutaneous coronary intervention (PCI) and possible stent placement procedure will receive a one-time intracoronary infusion of PEP within 20 minutes after stent placement or post-dilation (whichever comes last).	Drug: PEP; A biological drug made of certain parts of blood from living blood donors obtained from a certified blood bank. At the time of cardiac catheterization patients will undergo one-time intracoronary infusion of 10 milliliters of PEP dosage consisting of approximately 5%, 10%, or 20% PEP. PEP dose will be infused immediately distal to the newly placed stent over approximately 5 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicities (DLTs) and maximum tolerated dose (MTD) of a single dose (10 mL) of PEP at escalating concentrations of extracellular vesicles delivered at a single time point (after PCI).	DLTs are defined as: signs of infection present in the judgement of a reviewing MD, CTCAE Grade 2 or higher bronchial stricture (rhonchi/wheezing), or CTCAE Grade 3 or higher defined as new or reoccurring angina or anginal equivalent after infusion with PEP; elevated ALT, AST, total or direct bilirubin, unless due to procedural complications or complications of ischemic cardiomyopathy (ICM); decreased hemoglobin or platelet level, unless due to procedural complications or complications of ICM; sustained ventricular arrhythmia during PEP infusion; hypersensitivity or anaphylaxis during PEP infusion; any other grade 3 or higher adverse event.	Days 1-14 of the study period for each study participant.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Infarction scar size	Cardiac MRI will be used to assess myocardial infarction scar size.	Day 7 and Day 40 of the study period for each study participant.
Ejection fraction	Cardiac MRI will be used to assess ejection fraction.	Day 7 and Day 40 of the study period for each study participant.
Alloimmune Response	Class I & II Antibody Single Antigen Bead testing will be completed. Changes will be documented and evaluated.	Day 1 (Baseline/Screening) visit, Day 40 and Day 365

Collaborators and Investigators

• Sponsor: Christopher J. McLeod
• Collaborators: Rion LLC
• Investigators: Principal Investigator: Guy S Reeder, MD, Mayo Clinic

Publications and helpful links

General Publications

• Kisby CK, Shadrin IY, Peng LT, Stalboerger PG, Trabuco EC, Behfar A, Occhino JA. Impact of Repeat Dosing and Mesh Exposure Chronicity on Exosome-Induced Vaginal Tissue Regeneration in a Porcine Mesh Exposure Model. Female Pelvic Med Reconstr Surg. 2021 Mar 1;27(3):195-201. doi: 10.1097/SPV.0000000000001017.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): November 2, 2021
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 1, 2025

Study Registration Dates

• First Submitted: March 25, 2020
• First Submitted That Met QC Criteria: March 30, 2020
• First Posted (Actual): March 31, 2020

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 15, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Coronary Stent Placement
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Myocardial Infarction
• Other Study ID Numbers: 18-011636

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: There is a plan to make IPD, related data dictionaries, and all IPD that underlie results in a publication available.
• 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