Randomized, Double-Blind, Placebo-Controlled Phase I/II Study of the Safety and Efficacy of Intracoronary Delivery of Allogeneic Cardiosphere-Derived Cells in Patients With an Anterior Myocardial Infarction and Ischemic Left Ventricular Dysfunction (ALLogeneic Heart STem Cells to Achieve Myocardial Regeneration, ALLSTAR)

Trial ID:
IRB-13-6175
Richard Schatz
The purpose of this study is to determine whether Allogeneic Cardiosphere-Derived Cells (CAP-1002) is safe and effective in decreasing infarct...

Inclusion Criteria:

  • 1. History of MI (STEMI or NSTEMI) within the prior 12 months due to a coronary artery event and evidenced by at least two of the following: typical ischemic symptoms, serial ST-T changes (new ST elevation or new left bundle block) and/or elevated troponin or CK-MB >5 times the upper limit of normal. Also at least one of the following: development of pathological Q wave ECG changes, imaging evidence of new loss of viable myocardium, or new regional wall motion abnormalities.
  • 2. History of percutaneous coronary intervention (PCI), with stent placement resulting in TIMI flow = 3, in the coronary artery supplying the infarcted, dysfunctional territory and through which the treatment will be infused.
  • 3. At least one assessment of left ventricular ejection function (LVEF) ≤0.45 as determined by any one of the standard modalities (echocardiography, ventriculography, nuclear imaging, CT and/or MRI) prior to or during the screening period.
    • For subjects that fulfill the criteria of Recent MI (i.e., within 90 days of MI) at time of screening visit: assessment must be post-reperfusion after index MI and the most recent test prior to or during the screening period.
    • For subjects that fulfill the criteria of Chronic MI (i.e., greater than 90 days from MI) at the time of screening visit: assessment must be at least 21 days post-reperfusion after index MI and the most recent test prior to or during the screening period.

    Note: subjects may screen as a Recent MI but be randomized into the Chronic MI strata if the infusion date is > 90 days post-MI.

  • 4. Left ventricular infarct size of ≥ 15% of left ventricular mass in the qualifying infarct-related region to be infused as determined by centrally read screening MRI, with associated thinning and/or hypokinesis, akinesis, or dyskinesis, with no large aneurysmal area in the infarcted regions.
  • 5. No further revascularization clinically indicated at the time the subject is assessed for participation in the clinical trial.
  • 6. Ability to provide informed consent and follow-up with protocol procedures.
  • 7. Age ≥ 18 years.
  • Exclusion Criteria:

    • 1. Subjects with a history of coronary artery bypass surgery, and a patent graft (arterial or saphenous vein graft) attached to the coronary artery to be infused.
    • 2. Diagnosed or suspected myocarditis.
    • 3. History of cardiac tumor, or cardiac tumor demonstrated on screening MRI.
    • 4. History of acute coronary syndrome in the 4 weeks prior to study infusion.
    • 5. History of previous stem cell therapy.
    • 6. History of radiation treatment to the central or left side of thorax.
    • 7. Current or history (within the previous 5 years) of systematic auto-immune or connective tissue disease including, but not limited to, giant cell myocarditis, cardiac or systemic sarcoidosis, Dressler's syndrome, chronic recurrent or persistent pericarditis.
    • 8. History of or current treatment with immunosuppressive , anti-inflammatory, or other agents to treat manifestations of systemic immunologic reactions, including chronic systemic corticosteroids, biologic agents targeting the immune system, anti-tumor and anti-neoplastic drugs, anti-VEGF, or chemotherapeutic agents within 3 months prior to enrollment.
    • 9. Prior ICD and/or pacemaker placement where study imaging site has not been trained and certified specifically for this protocol to conduct cardiac MRI in subjects with ICD and/or pacemaker placement.
      • a. Presence of a pacemaker and/or ICD generator with any of the following limitations/conditions are excluded: i. Manufactured before the year 2000, ii. Leads implanted < 6 weeks prior to signing informed consent, iii. Non-transvenous epicardial, abandoned, or no-fixation leads, iv. Subcutaneous ICDs, v. Leadless pacemakers, vi. Any other condition that, in the judgement of device-trained staff, would deem an MRI contraindicated.

        b. Pacemaker dependence with an ICD (Note: pacemaker-dependent candidates without an ICD are not excluded).

        c. A cardiac resynchronization therapy (CRT) device implanted < 3 months prior to signing informed consent.

    • 10. Estimated glomerular filtration rate < 30 mL/min.
    • 11. Participation in an on-going protocol studying an experimental drug or device, or participation in an interventional clinical trial within the last 30 days.
    • 12. Diagnosis of arrhythmogenic right ventricular cardiomyopathy.
    • 13. Current alcohol or drug abuse.
    • 14. Pregnant/nursing women and women of child-bearing potential that do not agree to use at least two forms of active and highly reliable method(s) of contraception. Acceptable methods of contraception include contraceptive pills, depo-progesterone injections, a barrier contraceptive such as a condom with or without spermicide cream or gel, diaphragms or cervical cap with or without spermicide or gel, or an intrauterine device (IUD).
    • 15. Human Immunodeficiency Virus (HIV) infection.
    • 16. Viral hepatitis.
    • 17. Uncontrolled diabetes (HbA1c>9%).
    • 18. Abnormal liver function (SGPT/ALT > 3 times the upper reference range) and/or abnormal hematology (hematocrit < 25%, WBC < 3000 µl, platelets < 100,000 µl) studies without a reversible, identifiable cause.
    • 19. Sustained ventricular tachycardia (VT) or non-sustained ventricular tachycardia > 30 beats, not associated with the acute phase of a previous MI (> 48 hours after the MI onset) or a new acute ischemic episode.
    • 20. Ventricular fibrillation not associated with a new acute ischemic episode.
    • 21. New York Heart Association (NYHA) Class IV congestive heart failure.
    • 22. Evidence of tumor on screening chest/abdominal/pelvic (body) CT scan.
    • 23. Any prior transplant.
    • 24. Known hypersensitivity to dimethyl sulfoxide (DMSO).
    • 25. Known hypersensitivity to bovine products.
    • 26. Any malignancy within 5 years (except for in-situ non-melanoma skin cancer and in-situ cervical cancer) of signing the ICF.
    • 27. Any condition or other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for the study.