Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration

NCT ID: NCT01458405

Last Updated: 2024-04-09

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 135 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-13
• Study Completion Date: 2019-02-28

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.

Conditions

Myocardial Infarction

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Single, blinded, intracoronary infusion of a placebo solution

CAP-1002 Allogeneic Cardiosphere-Derived Cells

Group Type: ACTIVE_COMPARATOR

CAP-1002 Allogeneic Cardiosphere-Derived Cells

Intervention Type: BIOLOGICAL

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

Interventions

CAP-1002 Allogeneic Cardiosphere-Derived Cells

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

Intervention Type: BIOLOGICAL

Placebo

Single, blinded, intracoronary infusion of a placebo solution

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institutes of Health (NIH)

NIH

Sponsor Role: collaborator

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

California Institute for Regenerative Medicine (CIRM)

OTHER

Sponsor Role: collaborator

Capricor Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Frank Litvack, MD

Role: STUDY_DIRECTOR

Capricor Inc.

Locations

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

Michigan CardioVascular Institute

Saginaw, Michigan, United States

Metropolitan Heart and Vascular Institute / Mercy Hospital

Coon Rapids, Minnesota, United States

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, United States

University at Buffalo

Buffalo, New York, United States

Lenox Hill Hospital

New York, New York, United States

Carolinas HealthCare System

Charlotte, North Carolina, United States

Duke University Hospital

Durham, North Carolina, United States

NC Heart & Vascular Research

Raleigh, North Carolina, United States

SUMMA Health System

Akron, Ohio, United States

Lindner Center for Research and Education at the Christ Hospital

Cincinnati, Ohio, United States

Ohio State University

Columbus, Ohio, United States

OhioHealth Research Institute

Columbus, Ohio, United States

Oregon Health & Science University

Portland, Oregon, United States

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

The Miriam Hospital

Providence, Rhode Island, United States

Austin Heart

Austin, Texas, United States

University of Texas Memorial Hermann Hospital

Houston, Texas, United States

University of Utah

Salt Lake City, Utah, United States

University of Vermont Medical Center

Burlington, Vermont, United States

Swedish Medical Center - Heart and Vascular Research

Seattle, Washington, United States

University of Washington

Seattle, Washington, United States

Aurora Research Institute

Milwaukee, Wisconsin, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 34233913 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32749459 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

RC3HL103356-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1002-01

Identifier Type: -

Identifier Source: org_study_id