ALLSTAR: Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration

• Sponsor: Capricor Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT01458405
• Collaborator: National Institutes of Health (NIH) (NIH), National Heart, Lung, and Blood Institute (NHLBI) (NIH), California Institute for Regenerative Medicine (CIRM) (Other)
• Enrollment: 156
• Locations: 32
• Arms: 2
• Actual Duration (Months): 75.5
• Patients Per Site: 4.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Biological: CAP-1002 Allogeneic Cardiosphere-Derived Cells; Drug: Placebo	Phase 1/Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 156 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 13, 2012
• Actual Primary Completion Date: Jul 3, 2017
• Actual Study Completion Date: Feb 28, 2019

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo	Drug: Placebo; Single, blinded, intracoronary infusion of a placebo solution
Active Comparator: CAP-1002 Allogeneic Cardiosphere-Derived Cells	Biological: CAP-1002 Allogeneic Cardiosphere-Derived Cells; Single dose, blinded, intracoronary infusion of 25 Million cardiosphere-derived cells

Outcome Measures

Primary Outcome Measures

1. Infarct size assessed by MRI [12 Months]

   The primary safety endpoint is the proportion of patients that experience active myocarditis possibly attributable to treatment accompanied by the presence of circulating antibodies specific to the CAP-1002 CDC donor, death due to ventricular tachycardia or ventricular fibrillation, sudden unexpected death, or a major adverse cardiac event (MACE). The primary efficacy endpoint is relative percentage improvement in infarct size assessed by MRI for the CAP-1002 group compared to the placebo group at 12 months post-infusion.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

1. 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.

2. No further revascularization clinically indicated at the time the subject is assessed for participation in the clinical trial.

3. Ability to provide informed consent and follow-up with protocol procedures.

4. 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.

1. 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.

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

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

1. Estimated glomerular filtration rate < 30 mL/min.

2. Participation in an on-going protocol studying an experimental drug or device, or participation in an interventional clinical trial within the last 30 days.

3. Diagnosis of arrhythmogenic right ventricular cardiomyopathy.

4. Current alcohol or drug abuse.

5. 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).

6. Human Immunodeficiency Virus (HIV) infection.

7. Viral hepatitis.

8. Uncontrolled diabetes (HbA1c>9%).

9. 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.

10. 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.

11. Ventricular fibrillation not associated with a new acute ischemic episode.

12. New York Heart Association (NYHA) Class IV congestive heart failure.

13. Evidence of tumor on screening chest/abdominal/pelvic (body) CT scan.

14. Any prior transplant.

15. Known hypersensitivity to dimethyl sulfoxide (DMSO).

16. Known hypersensitivity to bovine products.

17. Any malignancy within 5 years (except for in-situ non-melanoma skin cancer and in-situ cervical cancer) of signing the ICF.

18. Any condition or other reason that, in the opinion of the Investigator or Medical Monitor, would render the subject unsuitable for the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cardiology, P.C.	Birmingham	Alabama	United States	35211
2	Heart Center Research	Huntsville	Alabama	United States	35801
3	Scripps	La Jolla	California	United States	92037
4	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
5	University of Florida - Shands Hospital	Gainesville	Florida	United States	32610
6	Rush University Medical Center	Chicago	Illinois	United States	60612
7	Prairie Heart - St. John's Hospital	Springfield	Illinois	United States	62712
8	Kansas University Medical Center	Kansas City	Kansas	United States	66160
9	University of Kentucky	Lexington	Kentucky	United States	40536
10	UMass Memorial Medical Center	Worcester	Massachusetts	United States	01655
11	Michigan CardioVascular Institute	Saginaw	Michigan	United States	48602
12	Metropolitan Heart and Vascular Institute / Mercy Hospital	Coon Rapids	Minnesota	United States	55433
13	Minneapolis Heart Institute Foundation	Minneapolis	Minnesota	United States	55407
14	University at Buffalo	Buffalo	New York	United States	14203
15	Lenox Hill Hospital	New York	New York	United States	10075
16	Carolinas HealthCare System	Charlotte	North Carolina	United States
17	Duke University Hospital	Durham	North Carolina	United States	27710
18	NC Heart & Vascular Research	Raleigh	North Carolina	United States	27607
19	SUMMA Health System	Akron	Ohio	United States	44304
20	Lindner Center for Research and Education at the Christ Hospital	Cincinnati	Ohio	United States	45219
21	Ohio State University	Columbus	Ohio	United States	43201
22	OhioHealth Research Institute	Columbus	Ohio	United States	43214
23	Oregon Health & Science University	Portland	Oregon	United States	97239
24	University of Pittsburgh Medical Center	Pittsburgh	Pennsylvania	United States	15213
25	The Miriam Hospital	Providence	Rhode Island	United States	02906
26	Austin Heart	Austin	Texas	United States	78756
27	University of Texas Memorial Hermann Hospital	Houston	Texas	United States	77030
28	University of Utah	Salt Lake City	Utah	United States	84132
29	University of Vermont Medical Center	Burlington	Vermont	United States	05401
30	Swedish Medical Center - Heart and Vascular Research	Seattle	Washington	United States	98122
31	University of Washington	Seattle	Washington	United States	98195
32	Aurora Research Institute	Milwaukee	Wisconsin	United States	53233

Sponsors and Collaborators

• Capricor Inc.
• National Institutes of Health (NIH)
• National Heart, Lung, and Blood Institute (NHLBI)
• California Institute for Regenerative Medicine (CIRM)

Investigators

• Study Director: Frank Litvack, MD, Capricor Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Capricor Inc.
• ClinicalTrials.gov Identifier: NCT01458405
• Other Study ID Numbers: 1002-01; RC3HL103356-01
• First Posted: Oct 24, 2011
• Last Update Posted: Apr 9, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Capricor Inc.: Myocardial Infarction; Heart Attack; Stem cell; Left ventricular dysfunction; Congestive heart failure
• Additional relevant MeSH terms: Myocardial Infarction; Ventricular Dysfunction; Infarction

Study Results

No Results Posted as of Apr 9, 2019