Clinical trial NCT01458405: Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration
Official title: 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 a Myocardial Infarction and Ischemic Left Ventricular Dysfunction
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Myocardial Infarction
Keywords: Myocardial Infarction
Heart Attack
Stem cell
Left ventricular dysfunction
Congestive heart failure
Lead sponsor: Capricor Inc.
Sponsor class: INDUSTRY
Collaborators: name: National Institutes of Health (NIH)
name: National Heart, Lung, and Blood Institute (NHLBI)
name: California Institute for Regenerative Medicine (CIRM)
First posted: 2011-10-24
Enrollment: 135
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Experiencing Any of the Adjudicated Events
timeFrame: Within 1-month post-infusion
measure: Percent Change From Baseline in Myocardium Mass Infarct Size at Month 12
timeFrame: Baseline, Month 12
Secondary outcomes:
measure: Number of Participants Experiencing Any of the Adjudicated Events
timeFrame: Up to Month 12 post-infusion
measure: Absolute Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Left Ventricular Ejection Fraction (LVEF) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Left Ventricular End Systolic Volume (LVESV) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Myocardium Mass Infarct Size at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Infarct Size (Scar Tissue Mass) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Infarct Size (Scar Tissue Mass) at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Viable Mass at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Viable Mass at Month 6 and12
timeFrame: Baseline, Month 6 and Month 12
measure: Absolute Change From Baseline in Function of the Region Receiving CAP-1002 Therapy at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Percent Change From Baseline in Function of the Region Receiving CAP-1002 Therapy at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Six-Minute Walk Test at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Minnesota Living With Heart Failure Questionnaire (MLHFQ) Total Score at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Short Form (36) (SF-36) Scale Score at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Work Productivity and Activity Impairment: Specific Health Problem (WPAI:SHP) Score at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Number of Participants With Change From Baseline in Patient Global Assessment (PGA) Score at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Number of Participants With Change From Baseline in New York Heart Association (NYHA) Class at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in N-terminal Pro-hormone Brain Natriuretic Peptide (NT-proBNP) Biomarker at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
measure: Change From Baseline in Log Transformed N-terminal Pro-hormone Brain Natriuretic Peptide (NT-proBNP) Biomarker at Month 6 and 12
timeFrame: Baseline, Month 6 and Month 12
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology, P.C.
state: Alabama
city: Huntsville
country: United States
facility: Heart Center Research
state: Alabama
city: La Jolla
country: United States
facility: Scripps
state: California
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Gainesville
country: United States
facility: University of Florida - Shands Hospital
state: Florida
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Springfield
country: United States
facility: Prairie Heart - St. John's Hospital
state: Illinois
city: Kansas City
country: United States
facility: Kansas University Medical Center
state: Kansas
city: Lexington
country: United States
facility: University of Kentucky
state: Kentucky
city: Worcester
country: United States
facility: UMass Memorial Medical Center
state: Massachusetts
city: Saginaw
country: United States
facility: Michigan CardioVascular Institute
state: Michigan
city: Coon Rapids
country: United States
facility: Metropolitan Heart and Vascular Institute / Mercy Hospital
state: Minnesota
city: Minneapolis
country: United States
facility: Minneapolis Heart Institute Foundation
state: Minnesota
city: Buffalo
country: United States
facility: University at Buffalo
state: New York
city: New York
country: United States
facility: Lenox Hill Hospital
state: New York
city: Charlotte
country: United States
facility: Carolinas HealthCare System
state: North Carolina
city: Durham
country: United States
facility: Duke University Hospital
state: North Carolina
city: Raleigh
country: United States
facility: NC Heart & Vascular Research
state: North Carolina
city: Akron
country: United States
facility: SUMMA Health System
state: Ohio
city: Cincinnati
country: United States
facility: Lindner Center for Research and Education at the Christ Hospital
state: Ohio
city: Columbus
country: United States
facility: Ohio State University
state: Ohio
city: Columbus
country: United States
facility: OhioHealth Research Institute
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Providence
country: United States
facility: The Miriam Hospital
state: Rhode Island
city: Austin
country: United States
facility: Austin Heart
state: Texas
city: Houston
country: United States
facility: University of Texas Memorial Hermann Hospital
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Burlington
country: United States
facility: University of Vermont Medical Center
state: Vermont
city: Seattle
country: United States
facility: Swedish Medical Center - Heart and Vascular Research
state: Washington
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Milwaukee
country: United States
facility: Aurora Research Institute
state: Wisconsin
Study officials:
affiliation: Capricor Inc.
name: Frank Litvack, MD
role: STUDY_DIRECTOR
References:
citation: Ostovaneh MR, Makkar RR, Ambale-Venkatesh B, Ascheim D, Chakravarty T, Henry TD, Kowalchuk G, Aguirre FV, Kereiakes DJ, Povsic TJ, Schatz R, Traverse JH, Pogoda J, Smith RD, Marban L, Marban E, Lima JAC. Effect of cardiosphere-derived cells on segmental myocardial function after myocardial infarction: ALLSTAR randomised clinical trial. Open Heart. 2021 Jul;8(2):e001614. doi: 10.1136/openhrt-2021-001614.
citation: Makkar RR, Kereiakes DJ, Aguirre F, Kowalchuk G, Chakravarty T, Malliaras K, Francis GS, Povsic TJ, Schatz R, Traverse JH, Pogoda JM, Smith RR, Marban L, Ascheim DD, Ostovaneh MR, Lima JAC, DeMaria A, Marban E, Henry TD. Intracoronary ALLogeneic heart STem cells to Achieve myocardial Regeneration (ALLSTAR): a randomized, placebo-controlled, double-blinded trial. Eur Heart J. 2020 Sep 21;41(36):3451-3458. doi: 10.1093/eurheartj/ehaa541.