Prochymal® (Human Adult Stem Cells) Intravenous Infusion Following Acute Myocardial Infarction (AMI)

Study Overview
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Brief Summary
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The objective of the present study is to establish the safety and efficacy of Prochymal® following first acute myocardial infarction.

Detailed Description
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The standard of care treatment for acute myocardial infarction (AMI) usually includes immediate perfusion, optimal pain relief, oxygen, aspirin or other anti-coagulants, Beta-Blockers, nitrates and Ace-inhibitors. However, because salvaging the viable myocardium is dependent on early reperfusion, only a minority of participants will reach the hospital within the time-window for myocardial rescue. Thus, even if the participant manages their tobacco use, hypertension, lipid levels, diabetes, weight and exercise, many participants will go on to develop Congestive Heart Failure (CHF). Though the medical management for CHF may improve symptoms and slow disease progression, such treatment cannot restore a functioning myocardium. A therapy that could improve the myocardial remodeling process and reduce the incidence or severity of CHF following acute MI would provide a significant benefit. The characteristics and biologic activity of Prochymal®, along with a good safety profile in human trials to date, suggest that Prochymal® may be a good candidate for addressing this unmet medical need.

Official Title
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A Phase II, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of PROCHYMAL® (Ex Vivo Cultured Adult Human Mesenchymal Stem Cells) Intravenous Infusion Following Acute Myocardial Infarction

Conditions
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Myocardial Infarction

Intervention / Treatment
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* Drug: Prochymal®
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female between 21 and 85 years old, inclusive First heart attack within 7 days prior to randomization and drug infusion Baseline left ventricular ejection fraction (LVEF) 20-45% Hemodynamically stable within 24 hours prior to randomization Adequate pulmonary function Exclusion Criteria: Previous medical history of heart attack, heart failure, significant valvular heart disease, aortic dissection Pacemaker or other device Pregnant, breast-feeding, or intends to become pregnant during the study Allergy to cow or pig derived products Evidence of active malignancy or prior history of active malignancy Major surgical procedure or major trauma within the past 14 days Autoimmune disease (e.g., Lupus, Multiple Sclerosis) Any medical condition, which in the opinion of the Investigator, renders participation unsuitable Undergone pharmacologic cardioversion or external defibrillation within 24 hours of randomization. Experienced cardiac arrest more than 36 hours after presentation to site or within 24 hours of randomization.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 85 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: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prochymal®<br>Participants will receive Prochymal® single intravenous (IV) infusion at a dose of 200 x 10^6 human mesenchymal stem cells (hMSC), reconstituted in 80 mL, delivered at a rate of 2 mL/min, with a maximum rate of 5.0 x 10^6 hMSC/minute, and the participants will be followed for 24 months and remain in the study for up to 60 months. | Drug: Prochymal®<br>* Intravenous infusion of ex vivo cultured adult human mesenchymal stem cells<br>* Other names: Remestemcel-L;|
| Placebo Comparator: Placebo<br>Participants will receive Prochymal® placebo-matching single IV infusion at a dose of of 200 x 10^6 hMSC, reconstituted in 80 mL, delivered at a rate of 2 mL/min, with a maximum rate of 5.0 x 10^6 hMSC/minute, and the participants will be followed for 24 months and remain in the study for up to 60 months. | Drug: Placebo<br>* Intravenous infusion of excipients of Prochymal®<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Cardiac Magnetic Resonance (CMR) imaging-determined End Systolic Volume (ESV) at Month 3 |  | Baseline, Month 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricular End Systolic Volume |  | 6 months | 
| Infarct Size |  | 3 and 6 months | 
| Left Ventricular Ejection Fraction |  | 3 and 6 months | 
| Left Ventricular End Diastolic Volume |  | 3 and 6 months | 
| Number of Participants with Ventricular Arrhythmias |  | 3 and 6 months | 
| Duke Activity Status Index (DASI) Assessment | The Duke Activity Status Index (DASI) is a brief, self-administered questionnaire that provides a standardized assessment of functional status and quality-of-life that correlates well with an objective measure of maximal exercise capacity. The scale ranges from 0 (unable to perform any tasks) to 58.20 (able to perform all tasks). Higher scores indicate a greater ability to perform daily activities. | 6, 12, and 24 months | 
| New York Heart Association (NYHA) Congestive Heart Failure Classification Status |  | 6, 12, 24, and 60 months | 
| Maximal Symptom-limited Exercise Test (Treadmill) |  | 6 and 12 months | 
| Number of Participants with Major Adverse Cardiac Events (MACE) |  | 6, 12, 24, and 60 months | 
| Overall Survival |  | 60 months | 
| Number of Participants with Adverse Events |  | 3,6,12,24,60 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute myocardial infarction, AMI, Myocardial infarction, Heart attack, Mesenchymal stem cells, MSC, Adult human stem cells, Osiris