CardiAMP™ Cell Therapy for Heart Failure Trial

Study Overview
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Brief Summary
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This is a prospective, multi-center, randomized, controlled, patient- and evaluator-blinded study comparing treatment with the CardiAMP cell therapy to a sham control treatment. A roll-in phase with a maximum of 10 subjects may occur.

Detailed Description
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Heart failure is a clinical condition in which the output of blood from the heart is insufficient to meet the metabolic demands of the body. In 2015, the American Heart Association, or AHA, report on heart disease statistics estimated that there are 5.7 million Americans over the age of 20 that have heart failure. Heart failure is increasingly prevalent due to the aging population and the increase in major cardiovascular risk factors, including obesity and diabetes. The AHA also estimates that one in five adults will develop heart failure after the age of 40. During heart failure progression, the heart steadily loses its ability to respond to increased metabolic demand, and mild exercise soon exceeds the heart's ability to maintain adequate output. Towards the end stage of the disease, the heart cannot pump enough blood to meet the body's needs at rest. At this stage, fluids accumulate in the extremities or in the lungs making the patient bedridden and unable to perform the activities of daily living. The long-term prognosis associated with heart failure is approximately 50% mortality at five years following the initial diagnosis. CardiAMP cell therapy is a comprehensive therapeutic treatment that comprises (i) a point of care cell processing platform and (ii) a biotherapeutic delivery system. CardiAMP cell therapy is the first comprehensive therapeutic treatment utilizing a patient's own cells for the treatment of ischemic heart failure with reduced ejection fraction. In the screening process, the physician extracts a small sample of the patient's bone marrow in an outpatient procedure performed under local anesthesia. The clinic sends the sample to a central diagnostic lab, which tests the sample. For the study treatment, a clinician collects and then prepares the patient's own bone marrow mononuclear cells, or autologous cells, using the CardiAMP point of care cell processing platform, which a cardiologist then delivers into the heart using the Helix biotherapeutic delivery system. BioCardia intends to submit data obtained from this clinical trial in a Pre-Market Approval Application to the United States Food and Drug Administration

Official Title
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Randomized Controlled Pivotal Trial of Autologous Bone Marrow Mononuclear Cells Using the CardiAMP Cell Therapy System in Patients With Ischemic Heart Failure (CardiAMP Heart Failure Trial)

Conditions
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Heart Failure, Systolic

Intervention / Treatment
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* Biological: Autologous cell therapy
* Other: Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New York Heart Association (NYHA) Class II or III A diagnosis of chronic ischemic left ventricular dysfunction secondary to myocardial infarction (MI) as defined by selected criteria. On stable evidence-based medical and device therapy for ischemic etiology heart failure, per the ACC/AHA Heart Failure guidelines, for at least three (3) months prior to randomization. Left ventricular ejection fraction between 20% and 40%. Qualification of a pre-procedure screening of the patient's bone-marrow characteristics Exclusion Criteria: • Other cardiac or vascular system or other health-related criteria which may be seen in a patient's history and physical examination.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 90 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CardiAMP cell therapy<br>Placement of an introducer guidewire, performance of a left ventriculogram, and treatment with autologous cell therapy. | Biological: Autologous cell therapy<br>* Autologous cell therapy delivered into the heart muscle using the CardiAMP Cell Therapy System. The CardiAMP Cell Therapy System consists of the CardiAMP Cell Separator, a cardiac delivery catheter, and flexible tip guide catheter.<br>|
| Sham Comparator: Sham Comparator<br>Placement of an introducer guidewire and performance of a left ventriculogram with no autologous cell therapy treatment. | Other: Sham<br>* An introducer guidewire is placed into the heart and left ventriculography is performed just like it is in the Experimental Arm but no autologous cell therapy is delivered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A composite endpoint based on a 3-tiered Finkelstein-Schoenfeld (FS) hierarchical analysis. | The tiers include (1) all-cause death, (2) non-fatal MACCE events, and (3) change for 6MWD from baseline to month 12. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Minnesota Living with Heart Failure Questionnaire (MLHFQ) | Mean change in quality of life score as measured by the MLHFQ at 12 months compared to baseline (superiority, treatment vs sham) | 12 months | 
| Survival | Overall survival compared between both study arms (non-inferiority, treatment vs sham) | 12 Months | 
| Time to first Major Adverse Cardiac Events (MACE) | Time to first MACE, defined as the 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 (non-inferiority, treatment vs sham) | 12 months |