Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration

Phase 2TerminatedNCT01458405

Capricor Inc.135 enrolled

Overview

The purpose of this study is to determine whether Allogeneic Cardiosphere-Derived Cells (CAP-1002) is safe and effective in decreasing infarct size in patients with a myocardial infarction.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

135

Conditions

Myocardial Infarction

Interventions

CAP-1002 Allogeneic Cardiosphere-Derived CellsBIOLOGICAL

Single dose, blinded, intracoronary infusion of 25 Million cardiosphere-derived cells

PlaceboDRUG

Single, blinded, intracoronary infusion of a placebo solution

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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 Creatine phosphokinase MB isoenzyme (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 Thrombolysis in Myocardial Infarction (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 participants 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 participants 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: participants 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 participants 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. Participants 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-vascular endothelial growth factor, or chemotherapeutic agents within 3 months prior to enrollment. 9. Prior implantable cardioverter defibrillator (ICD) and/or pacemaker placement where study imaging site has not been trained and certified specifically for this protocol to conduct cardiac MRI in participants 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 (Serum Glutamic Pyruvic Transaminase/Alanine aminotransferase \> 3 times the upper reference range) and/or abnormal hematology (hematocrit \< 25%, White Blood Cell \< 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 informed consent form. 27. Any condition or other reason that, in the opinion of the Investigator or Medical Monitor, would render the participants unsuitable for the study.

Locations (32)

Outcomes

Primary Outcomes

Number of Participants Experiencing Any of the Adjudicated Events

Adjudicated Events reported included: Acute myocarditis; Death due to ventricular tachycardia (VT) or ventricular fibrillation (VF); Sudden unexpected death (defined as occurring within one hour of symptom onset, or un- witnessed death); and Major adverse cardiac event (MACE) (defined as the composite incidence of death, non- fatal recurrent MI, hospitalization for heart failure, emergency room treatment for heart failure, left ventricular assist device \[LVAD\] placement or heart transplant).

Time frame: Within 1-month post-infusion

Percent Change From Baseline in Myocardium Mass Infarct Size at Month 12

Infarct size, expressed as a percentage, was calculated by dividing the sum of infarct areas from all sections by the sum of left ventricular (LV) areas from all sections (including those without infarct scar) and multiplying by 100. Percent improvement in infarct size defined by scar as a percent of LV mass was assessed by magnetic resonance imaging. Percent change from Baseline was calculated as: Percent change = (post-baseline value-Baseline value)/Baseline value \*100%.

Time frame: Baseline, Month 12

Secondary Outcomes

Number of Participants Experiencing Any of the Adjudicated Events

Adjudicated Events reported included: Acute myocarditis; Death due to VT or VF; Sudden unexpected death (defined as occurring within one hour of symptom onset, or un- witnessed death); MACE (defined as the composite incidence of death, non- fatal recurrent MI, hospitalization for heart failure, emergency room treatment for heart failure, LVAD placement or heart transplant); New cardiac tumor formation on MRI imaging; Any hospitalization due to cardiovascular cause; Any inter-current cardiovascular illness or one related to CAP-1002 or placebo infusion, which prolongs hospitalization; New thrombolysis in myocardial infarction (TIMI) flow \<=1; Development of, or an increase in frequency of VT; Development of increased anti-human leukocyte antigen (anti-HLA) antibody levels (mean fluorescence intensity \[MFI\] \>= 1000; 5000) with development of sensitization to HLA antigens specific to CAP-1002 cardiosphere-derived cells donor.

Data from ClinicalTrials.gov

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Cardiology, P.C.

Birmingham, Alabama, United States

Heart Center Research

Huntsville, Alabama, United States

Scripps

La Jolla, California, United States

Cedars-Sinai Medical Center

Los Angeles, California, United States

University of Florida - Shands Hospital

Gainesville, Florida, United States

Rush University Medical Center

Chicago, Illinois, United States

Prairie Heart - St. John's Hospital

Springfield, Illinois, United States

Kansas University Medical Center

Kansas City, Kansas, United States

University of Kentucky

Lexington, Kentucky, United States

UMass Memorial Medical Center

Worcester, Massachusetts, United States

...and 22 more locations

Time frame: Up to Month 12 post-infusion

Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 and 12

LVEF is the fraction of chamber volume ejected in systole (stroke volume) in relation to the volume of the blood in the ventricle at the end of diastole (end-diastolic volume). LVEF expressed as percentage ejection fraction was assessed by magnetic resonance imaging. Absolute change was calculated as: post-baseline value-Baseline value.