An Efficacy, Safety and Tolerability Study of Ixmyelocel-T Administered Via Transendocardial Catheter-based Injections to Subjects With Heart Failure Due to Ischemic Dilated Cardiomyopathy (IDCM) (ixCELL DCM)

Inclusion Criteria:

1. Males and non-pregnant, non-lactating females;
2. Age 30 to 85 years of age;

3. Diagnosis of ischemic dilated cardiomyopathy according to WHO criteria:

   • Ischemic dilated cardiomyopathy is defined as dilated cardiomyopathy in a subject with a history of myocardial infarction or evidence of clinically significant (≥ 70% narrowing of a major epicardial artery) coronary artery disease;

4. LVEF ≤ 30% by echocardiogram;
5. Symptomatic heart failure in NYHA functional class III or IV;
6. Subject is not a candidate for reasonable revascularization procedures that will produce clinical improvement, based on coronary angiography (angiography current within 12 months prior to screening);
7. Subject is receiving appropriate clinical standard of care heart failure therapy, as tolerated and as dictated by a subject's current medical condition, for at least 30 days prior to screening;
8. Must have an automatic implantable cardioverter defibrillator (AICD);
9. Worsening heart failure hospitalization or equivalent within 6 months prior to screening, hospitalization equivalent defined as an unplanned outpatient/emergency department visit for treatment with intravenous inotrope, vasoactive, or diuretic medication;
10. Life expectancy of at least 12 months in the opinion of the Investigator;
11. LV wall thickness ≥ 8mm (by echocardiogram) at anticipated target injection area;
12. Hemodynamic stability without IV vasopressors or support devices;
13. Given medical history and concurrent medication, subject is an acceptable candidate for bone marrow aspiration and cardiac catheterization and transendocardial injection procedures in the opinion of the Investigator;
14. Subject is willing and able to comply with scheduled study visits, and is able to tolerate study procedures;
15. Provide a personally-signed and dated informed consent document indicating that the subject (or a legally-acceptable representative, if permitted by the site's Investigational Review Board [IRB]) has been informed of all pertinent aspects of the study.

Exclusion Criteria:

Disease-specific:

1. Severe primary valvular heart disease including, but not limited to, aortic valve stenosis and insufficiency;
2. VAD implantation, heart transplantation, cardiomyoplasty, left ventricular reduction surgery, or cardiac shunt implantation;
3. Planned heart failure-related device interventions (e.g., VAD implantation, initial cardiac resynchronization therapy) or planned cardiac procedures (e.g., heart transplant, cardiomyoplasty, valvular repair);
4. Subject has any current arrhythmias that would prohibit accurate NOGA® electromechanical mapping and NOGA®-guided injections;
5. LV thrombus (as documented on echocardiography or LV angiography);
6. Myocardial infarction, stroke or transient ischemic attack within 3 months prior to screening;
7. Percutaneous coronary intervention, valvuloplasty, cardiac surgery, and other major cardiac procedure within 30 days prior to screening;

8. In the opinion of the Investigator, the subject's left ventricular wall is unsuitable for transendocardial injections (due to thickness or other reasons).

   Medical History:

9. Known history of severe chronic obstructive pulmonary disease (COPD) (defined as forced expiratory volume (FEV1) <30% predicted);
10. Hemoglobin A1c (HbA1c) ≥ 10% at screening;
11. Diabetic subjects with uncontrolled or untreated proliferative retinopathy as determined by dilated eye exam administered by a qualified eye care professional as per American Diabetes Association guidelines;
12. Blood clotting disorder not caused by medication (e.g., thrombophilia);
13. Active malignancy (non-basal cell) requiring surgery, chemotherapy, and/or radiation in the past 12 months;
14. Current documented drug or alcohol abuse that would interfere with the subject's compliance with study procedures;
15. Known allergies to any equine, porcine, or bovine products;
16. Body mass index (BMI) ≥ 40 kg/m2 at screening;
17. Established chronic kidney disease (CKD) requiring dialysis (Stage 5); estimated creatinine clearance < 15 mL/min at screening;

18. Subject has allergy or is unable to tolerate echocardiography contrast agent; also the inability to get a good quality echocardiogram image at screening (as determined by the imaging core lab).

    Laboratory Parameters:

19. Abnormal laboratory values (performed at central lab) at screening:

    • Platelets < 50,000 μL;
    • Hemoglobin < 9.0 g/dL;
    • Aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 3 times the upper limit of normal (ULN);
    • Human immunodeficiency virus 1 (HIV 1), HIV 2, or syphilis positive (rapid plasma reagin [RPR]);
    • Active hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies;
    • NOTE: Additional lab tests may be performed per local requirements including but not limited to: hepatitis B core antibody, human T lymphotropic virus I/II.

    Exclusionary Procedures, Devices, or Medication:

20. Subjects receiving anti-angiogenic drugs (e.g., anti-vascular endothelial growth factor [VEGF]);
21. Subjects receiving treatment with hematopoietic growth factors (e.g., erythropoietin [EPO], granulocyte colony-stimulating factor [G-CSF]);
22. Chronic exposure to immunosuppressive therapy for oncologic or chronic non-oncologic reasons in the prior 6 months or expected requirement over the course of the study;
23. Concurrent participation in another clinical trial or receiving experimental medication within 30 days of screening or having previously been exposed to Aastrom's ixmyelocel T product [previously known as tissue repair cells (TRC), cardiac repair cells (CRC), vascular repair cells (VRC)] or previously received intracoronary or intramyocardial injections of any other bone marrow therapies.