Safety Evaluation of Intracoronary Infusion of Extracellular Vesicles in Patients With AMI
Study Details
Study Description
Brief Summary
Determine the safety of up to 3 dose levels of a study drug called PEP in patients who have had a recent (within the last 12 hours) heart attack.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Patients with Acute Myocardial Infarction (AMI) who undergo percutaneous coronary intervention (PCI) at least 4 hours (but no more than 12 hours) after onset of heart attack symptoms 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. From the emergency room, subjects will proceed to 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.
In the event there are patients enrolled with unknown COVID-19 status or previously negative COVID-19 status and subsequently found to be positive by SARS-Cov-2 PCR testing at visit 1, visit 4, visit 6, or any unscheduled visit within the first 14 days after receiving the study drug, then those patients will be excluded from the primary endpoint analysis.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PEP in Acute Myocardial Infarction Patients with an acute myocardial infarction who undergo cardiac catheterization at least four hours after onset of symptoms will receive a one-time intracoronary infusion of PEP within 20 minutes after stent placement or post-dilation. |
Drug: PEP in Acute Myocardial Infarction
PEP dosage will consist of 5%, 10%, or 20% PEP. PEP dose will be infused immediately distal to the newly placed stent over approximately 5 minutes.
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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 (during PCI for AMI) for the treatment of downstream sequela of AMI. [Days 1-14 of the study period for each study participant.]
DLTs are possibly, probably or definitely related to PEP and are defined as: Signs of infection present in the judgement of a reviewing MD. CTCAE Grade 2 or higher bronchial stricture. CTCAE Grade 3 or higher: New or reoccurring angina after infusion with PEP. Elevated ALT, AST, total or direct bilirubin, unless due to procedural complications or complications of 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. Any patient enrolled with unknown COVID-19 status or previously negative COVID-19 status and subsequently found to be positive by SARS-Cov-2 PCR testing at visit 1, visit 4, visit 6, or any unscheduled visit within the first 14 days after receiving the study drug, will be excluded from the primary endpoint analysis.
Secondary Outcome Measures
- Infarction scar size [Day 7 and Day 40 of the study period for each study participant.]
Cardiac MRI will be used to assess myocardial infarction scar size. In the event there are patients enrolled with unknown COVID-19 status or previously negative COVID-19 status and subsequently found to be positive by SARS-Cov-2 PCR testing at visit 1, visit 4, visit 6, or any unscheduled visit within 40 days after receiving the study drug, then those patients will be excluded from the secondary endpoint analysis.
- Ejection fraction [Day 7 and Day 40 of the study period for each study participant.]
Cardiac MRI will be used to assess ejection fraction. In the event there are patients enrolled with unknown COVID-19 status or previously negative COVID-19 status and subsequently found to be positive by SARS-Cov-2 PCR testing at visit 1, visit 4, visit 6, or any unscheduled visit within 40 days after receiving the study drug, then those patients will be excluded from the secondary endpoint analysis.
- Abdominal abnormalities [Day 7 and Day 365 of the study period for each study participant.]
Complete abdominal ultrasound will be conducted to evaluate for abnormalities. In the event there are patients enrolled with unknown COVID-19 status or previously negative COVID-19 status and subsequently found to be positive by SARS-Cov-2 PCR testing at visit 1, visit 4, visit 6, or any unscheduled visit within 40 days after receiving the study drug, then those patients will be excluded from the secondary endpoint analysis.
- Alloimmune Response [Day 1 (Baseline/Screening) visit, Day 40 and Day 365]
Class I & II Antibody Single Antigen Bead testing will be completed. Changes will be documented and evaluated. In the event there are patients enrolled with unknown COVID-19 status or previously negative COVID-19 status and subsequently found to be positive by SARS-Cov-2 PCR testing at visit 1, visit 4, visit 6, or any unscheduled visit within 40 days after receiving the study drug, then those patients will be excluded from the secondary endpoint analysis.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Ages 21-85
-
Males and females
-
Acute myocardial infarction (ST elevation at the J point in at least 2 contiguous leads of
≥2 mm (0.2 mV) in men or ≥1.5 mm (0.15 mV) in women in leads V2-V3 and/or of ≥1 mm (0.1 mV) in other contiguous chest leads or the limb leads)
-
Successful stent implantation within 4 and 12 hours from onset of AMI symptoms
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Angiographic evidence of TIMI 0 or TIMI 1 flow through culprit lesion prior to stent placement
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Angiographic evidence of residual stenosis visually <30% after stent placement
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Willing and able to provide signed informed consent
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Lives within 90 mile radius of study site
Exclusion Criteria:
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Prior cardiovascular history of systolic or diastolic dysfunction or acute myocardial infarction
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Received fibrinolytic therapy (i.e. tPA (tissue plasminogen activator)), prior to PCI
-
Known history of stroke or TIA within the past 6 months
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Prior solid organ transplantation at any time
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Pregnant or lactating at screening
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Known presence of chronic systemic inflammatory disorder that requires ongoing therapy with immunosuppressive agents
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Known immune system compromise including but not limited to human immunodeficiency virus (HIV), hepatitis A, hepatitis B (HBV) or hepatitis C (HCV) infection
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Known history of malignancy of any type except non-melanoma skin cancer
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Known serum creatinine >2 mg/dL or GFR ≤30 mL/min within the last twelve months
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Known AST, ALT, and/or bilirubin (total) elevated twice the upper limit of normal for age & gender within the last twelve months
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Known Hemoglobin lower than 8.0 g/dL within the last twelve months
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Known current illicit drug use at screening
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Other major surgical procedure or major trauma within the previous 14 days prior to enrollment
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Female of child bearing potential who is unwilling to agree to use acceptable contraception methods for 3 months after receiving the investigational drug
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ICD implant in place
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Adult lacking decision-making capacity
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Prisoner
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Non-English speaking
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English-speaking but illiterate
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Legally blind
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Known allergy to heparin or heparin-induced thrombocytopenia
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Known history of positive SARS-CoV2 PCR nasal swab test
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Prior history of cardiac stent placement
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DNR/DNI status prior to PCI procedure or planned DNR/DNI status after PCI procedure
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
Sponsors and Collaborators
- Christopher J. McLeod
- Rion LLC
Investigators
- Principal Investigator: Guy S Reeder, MD, Mayo Clinic
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 18-011636