Allogeneic Heart Stem Cells to Achieve Myocardial Regeneration

NCT01458405 | Terminated Phase 1 Results DMC

• 2 other identifiers: 1002-01RC3HL103356-01
• Study Type: interventional
• Target: 135
• Locations: 1 country
• Sites: 32

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

Keywords

Myocardial Infarction; Heart Attack; Stem cell; Left ventricular dysfunction; Congestive heart failure

Outcome Measures

Primary Outcomes (2)

• 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).

  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%.

  Baseline, Month 12

Secondary Outcomes (22)

• Number of Participants Experiencing Any of the Adjudicated Events

  Up to Month 12 post-infusion

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

  Baseline, Month 6 and Month 12

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

  Baseline, Month 6 and Month 12

• Absolute Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 6 and 12

  Baseline, Month 6 and Month 12

• Percent Change From Baseline in Left Ventricular End Diastolic Volume (LVEDV) at Month 6 and 12

  Baseline, Month 6 and Month 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

CAP-1002 Allogeneic Cardiosphere-Derived Cells

ACTIVE COMPARATOR

Biological: CAP-1002 Allogeneic Cardiosphere-Derived Cells

Interventions

CAP-1002 Allogeneic Cardiosphere-Derived Cells BIOLOGICAL

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

CAP-1002 Allogeneic Cardiosphere-Derived Cells

Placebo DRUG

Single, blinded, intracoronary infusion of a placebo solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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.
• 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.
• No further revascularization clinically indicated at the time the participants is assessed for participation in the clinical trial.
• Ability to provide informed consent and follow-up with protocol procedures.
• Age \>= 18 years.

You may not qualify if:

• 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.
• Diagnosed or suspected myocarditis.
• History of cardiac tumor, or cardiac tumor demonstrated on screening MRI.
• History of acute coronary syndrome in the 4 weeks prior to study infusion.
• History of previous stem cell therapy.
• History of radiation treatment to the central or left side of thorax.
• 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.
• 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.
• 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.
• Estimated glomerular filtration rate \< 30 mL/min.
• Participation in an on-going protocol studying an experimental drug or device, or participation in an interventional clinical trial within the last 30 days.
• Diagnosis of arrhythmogenic right ventricular cardiomyopathy.

Sponsors & Collaborators

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

Study Sites (32)

Cardiology, P.C.

Birmingham, Alabama, 35211, United States

Location

Heart Center Research

Huntsville, Alabama, 35801, United States

Location

Scripps

La Jolla, California, 92037, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of Florida - Shands Hospital

Gainesville, Florida, 32610, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Prairie Heart - St. John's Hospital

Springfield, Illinois, 62712, United States

Location

Kansas University Medical Center

Kansas City, Kansas, 66160, United States

Location

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

UMass Memorial Medical Center

Worcester, Massachusetts, 01655, United States

Location

Michigan CardioVascular Institute

Saginaw, Michigan, 48602, United States

Location

Metropolitan Heart and Vascular Institute / Mercy Hospital

Coon Rapids, Minnesota, 55433, United States

Location

Minneapolis Heart Institute Foundation

Minneapolis, Minnesota, 55407, United States

Location

University at Buffalo

Buffalo, New York, 14203, United States

Location

Lenox Hill Hospital

New York, New York, 10075, United States

Location

Carolinas HealthCare System

Charlotte, North Carolina, United States

Location

Duke University Hospital

Durham, North Carolina, 27710, United States

Location

NC Heart & Vascular Research

Raleigh, North Carolina, 27607, United States

Location

SUMMA Health System

Akron, Ohio, 44304, United States

Location

Lindner Center for Research and Education at the Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Ohio State University

Columbus, Ohio, 43201, United States

Location

OhioHealth Research Institute

Columbus, Ohio, 43214, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

The Miriam Hospital

Providence, Rhode Island, 02906, United States

Location

Austin Heart

Austin, Texas, 78756, United States

Location

University of Texas Memorial Hermann Hospital

Houston, Texas, 77030, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

University of Vermont Medical Center

Burlington, Vermont, 05401, United States

Location

Swedish Medical Center - Heart and Vascular Research

Seattle, Washington, 98122, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Aurora Research Institute

Milwaukee, Wisconsin, 53233, United States

Location

Related Publications (2)

• 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.

  PMID: 34233913 DERIVED

• 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.

  PMID: 32749459 DERIVED

MeSH Terms

Conditions

Myocardial Infarction; Ventricular Dysfunction, Left; Heart Failure

Condition Hierarchy (Ancestors)

Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Infarction; Ischemia; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Necrosis; Ventricular Dysfunction

Limitations and Caveats

Based on available clinical data at time of the analysis, the Sponsor decided not to pursue development of CAP-1002 in this indication; hence the trial was stopped.

Results Point of Contact

• Title: Vice President of Clinical Research and Development Operations
• Organization: Capricor, Inc.

clinicaltrialsgov@capricor.com

858-727-1755

Study Officials

• Frank Litvack, MD

  Capricor Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2011
• First Posted: October 24, 2011
• Study Start: November 13, 2012
• Primary Completion: July 3, 2017
• Study Completion: February 28, 2019
• Last Updated: April 9, 2024
• Results First Posted: April 9, 2024

Record last verified: 2024-02

Locations

US (32)