Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration (ALLSTAR)

• ClinicalTrials.gov Identifier: NCT01458405
• Recruitment Status: Terminated
• First Posted: October 24, 2011
• Last Update Posted: April 9, 2019
• Sponsor: Capricor Inc.
• Collaborators: National Institutes of Health (NIH); National Heart, Lung, and Blood Institute (NHLBI); California Institute for Regenerative Medicine (CIRM)
• Information provided by (Responsible Party): Capricor Inc.

Tracking Information

• First Submitted Date: October 20, 2011
• First Posted Date: October 24, 2011
• Last Update Posted Date: April 9, 2019
• Actual Study Start Date: November 13, 2012
• Actual Primary Completion Date: July 3, 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 13, 2016)

Infarct size assessed by MRI [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: October 21, 2011): Infarct size assessed by MRI
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Myocardial Infarction

Intervention

• Biological: CAP-1002 Allogeneic Cardiosphere-Derived Cells
  Single dose, blinded, intracoronary infusion of 25 Million cardiosphere-derived cells
• Drug: Placebo
  Single, blinded, intracoronary infusion of a placebo solution

Study Arms

• Placebo Comparator: Placebo
  Intervention: Drug: Placebo
• Active Comparator: CAP-1002 Allogeneic Cardiosphere-Derived Cells
  Intervention: Biological: CAP-1002 Allogeneic Cardiosphere-Derived Cells

Publications *

• 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, Marbán L, Marbán 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). pii: e001614. doi: 10.1136/openhrt-2021-001614.
• Makkar RR, Kereiakes DJ, Aguirre F, Kowalchuk G, Chakravarty T, Malliaras K, Francis GS, Povsic TJ, Schatz R, Traverse JH, Pogoda JM, Smith RR, Marbán L, Ascheim DD, Ostovaneh MR, Lima JAC, DeMaria A, Marbán 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.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: April 4, 2019): 156
• Original Enrollment: Not Provided
• Actual Study Completion Date: February 28, 2019
• Actual Primary Completion Date: July 3, 2017 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01458405
• Other Study ID Numbers: 1002-01; RC3HL103356-01 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Capricor Inc.
• Study Sponsor: Capricor Inc.

Collaborators

• 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.

• PRS Account: Capricor Inc.
• Verification Date: April 2019