Clinical Trial of Human Allogenic Culture-expanded Bone Marrow-derived Mesenchymal Stem Cells (CardiALLO)

Study Overview
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Brief Summary
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This clinical study will utilize allogenic bone marrow-derived culture-expanded MSC that are expanded from the NK1R+ Mesenchymal stem cells as a therapy for chronic ischemic left ventricular dysfunction delivered using the investigational Helix transendocardial delivery catheter.

Detailed Description
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Chronic heart failure is in need of new therapies. Over the past few years, cardiovascular regenerative medicine using bone marrow-derived cells has emerged as a new treatment strategy that could have tremendous benefit in treating heart failure. At present, several types of adult bone marrow derived stem cells hold great promise to treat heart failure. Allogenic culture-expanded bone marrow-derived human mesenchymal stem cells (MSC) are the subject of the current study as having potential to provide a safe and effective treatment for patients with ischemic heart failure. Mesenchymal stem cells are multipotent stromal cells that can differentiate into a variety of cell types, including osteoblasts (bone cells), chondrocytes (cartilage cells), myocytes (muscle cells) and adipocytes (fat cells which give rise to marrow adipose tissue). The CardiALLO cell therapy is an allogenic bone marrow-derived NK1R+ selected and culture-expanded mesenchymal stem cells that will be delivered intramyocardially using the investigational Helix delivery catheter. The purpose of this study is to determine the safety, optimal dose and efficacy of CardiALLO cell therapy system in patients with post-myocardial infarction heart failure.

Official Title
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Phase I/II Clinical Trial of Human Allogenic Culture-expanded Bone Marrow-derived Mesenchymal Stem Cells in Patients With Post-Myocardial Infarction Heart Failure

Conditions
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Heart Failure, Systolic

Intervention / Treatment
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* Combination Product: CardiALLO™ Human Allogenic Culture-expanded Bone marrow-derived Mesenchymal Stem Cells (hMSCs)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New York Heart Association (NYHA) Class II or III Diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction Left ventricular ejection fraction between 20% and 40% On stable, guideline-directed medical and device therapy, as appropriate Exclusion Criteria: Other cardiovascular or medical history parameters, as appropriate, that may preclude safe administration of the study treatment.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Interventional Model Description: Phase I: Dose escalation, safety study consisting of 3 cell doses of 20million, 100 million and 200 million allogeneic hMSC. Each dose cohort will consist of 3 patients.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Cohort<br>The study will utilize a dose escalation study design with three patients at 20 million MSCs, three patients at 100 million MSC, and three patients at 200 million MSC to identify dose for Phase II. Prespecified DSMB review after each dose cohort of the Phase I, before moving to higher dose. | Combination Product: CardiALLO™ Human Allogenic Culture-expanded Bone marrow-derived Mesenchymal Stem Cells (hMSCs)<br>* CardiALLO™ Human Allogenic Culture-expanded Bone marrow-derived Mesenchymal Stem Cells (hMSCs) delivered with the Helix transendocardial delivery catheter (treatment)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent serious adverse events | Incidence of TE-SAE defined as a composite of death, non-fatal MI, stroke, worsening HF (requiring admission, iv diuretics and/or inotropics), myocardial perforation (with tamponade), ventricular arrythmias >15 seconds | Through 30 days post-procedure. | 
| Composite endpoint consisting of all cause or cardiac death, non-fatal cardiac-related hospitalizations and functional capacity measured using the 6 minute walk distance. | The primary efficacy endpoint is a composite endpoint based on a 3-tiered Finkelstein-Schoenfeld (FS) hierarchical analysis. The tiers, starting with the most serious events, would be (1) all cause death, including cardiac death equivalents such as heart transplant or left ventricular assist device placement, ordered by time to event; (2) non-fatal MACCE events excluding those deemed procedure related occurring within the first 7 days (heart failure hospitalization, stroke or MI) ordered by time to event, and (3) change for 6MWD. | Through Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival | Overall survival time | Through 12 months | 
| Major Adverse Cardiac Events (MACE) | A composite of all-cause death, hospitalization for worsening heart failure, nonfatal recurrent myocardial infarction, placement of a left ventricular assist device [LVAD], or heart transplantation) | Through 12 months | 
| Minnesota Living with Heart Failure Questionnaire | Self-reported questionnaire asking about heart failure symptoms with lower score being better | Through 12 months |