An Efficacy, Safety and Tolerability Study of Ixmyelocel-T Administered Via Transendocardial Catheter-based Injections to Subjects With Heart Failure Due to Ischemic Dilated Cardiomyopathy (IDCM)

NCT ID: NCT01670981

Last Updated: 2021-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 114 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-20
• Study Completion Date: 2018-03-07

Brief Summary

This study is designed to assess the efficacy, safety and tolerability of ixmyelocel-T compared to placebo (vehicle control) when administered via transendocardial catheter-based injections to patients with end stage heart failure due to IDCM, who have no reasonable revascularization options (either surgical or percutaneous interventional) likely to provide clinical benefit.

Detailed Description

The primary objective of this study is to evaluate the efficacy of ixmyelocel-T compared to placebo (vehicle control) on the average per patient number of all-cause deaths, cardiovascular hospital admissions, and unplanned outpatient or emergency department visits to treat acute decompensated heart failure, over the 12 months following administration of investigational product (IP).

Conditions

Ischemic Dilated Cardiomyopathy (IDCM)

Study Design

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

Study Groups

ixmyelocel-T

Ixmyelocel-T delivered by catheter-based intramyocardial injection procedure.

Group Type: EXPERIMENTAL

ixmyelocel-T

Intervention Type: BIOLOGICAL

12-20 transendocardial injections of 0.4 mL of ixmyelocel-T per injection into the left ventricle.

Placebo

Placebo delivered by catheter-based intramyocardial injection procedure.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

12-20 transendocardial injections of 0.4 mL of vehicle control per injection into the left ventricle.

Interventions

ixmyelocel-T

12-20 transendocardial injections of 0.4 mL of ixmyelocel-T per injection into the left ventricle.

Intervention Type: BIOLOGICAL

Placebo

12-20 transendocardial injections of 0.4 mL of vehicle control per injection into the left ventricle.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Males and non-pregnant, non-lactating females;

2. Age 30 to 86 years of age;

3. Diagnosis of ischemic dilated cardiomyopathy;

4. LVEF ≤ 35% by echocardiogram;

5. Symptomatic heart failure in NYHA functional class III or IV;

6. Subject is not a candidate for reasonable revascularization procedures that will produce clinical improvement;

7. Subject is receiving appropriate clinical standard of care heart failure therapy, as tolerated and as dictated by a subject's current medical condition, for at least 30 days prior to screening;

8. Must have an automatic implantable cardioverter defibrillator (AICD);

9. Worsening heart failure hospitalization or equivalent within 6 months prior to screening, hospitalization equivalent defined as an unplanned outpatient/emergency department visit for treatment of acute decompensated heart failure; or have an N-terminal prohormone B-type natriuretic peptide (NT-proBNP) ≥2000 pg/mL or BNP ≥400 pg/mL within 30 days of screening (including screening); or have a 6-minute walk test (6MWT) distance of ≤400 meters at screening;

10. Life expectancy of at least 12 months in the opinion of the Investigator;

11. LV wall thickness ≥ 7mm (by echocardiogram) at anticipated target injection area;

12. Hemodynamic stability without IV vasopressors or support devices;

13. Given medical history and concurrent medication, subject is an acceptable candidate for bone marrow aspiration and cardiac catheterization and transendocardial injection procedures in the opinion of the Investigator;

14. Willing and able to comply scheduled visits and tolerate study procedures.

15. Voluntarily provide a personally-signed and dated informed consent.

Exclusion Criteria

Disease-specific:

1. Severe primary valvular heart disease including, but not limited to, aortic valve stenosis and insufficiency;

2. VAD implantation, heart transplantation, cardiomyoplasty, left ventricular reduction surgery, or cardiac shunt implantation;

3. Planned heart failure-related device interventions (e.g., VAD implantation, initial cardiac resynchronization therapy) or planned cardiac procedures (e.g., heart transplant, cardiomyoplasty, valvular repair);

4. Current arrhythmias that would prohibit accurate NOGA® electromechanical mapping and NOGA®-guided injections;

5. LV thrombus (as documented on echocardiography or LV angiography);

6. Myocardial infarction, stroke or transient ischemic attack within 3 months prior to screening;

7. Percutaneous coronary intervention, valvuloplasty, cardiac surgery, and other major cardiac procedure within 30 days prior to screening;

8. In the opinion of the Investigator, the subject's left ventricular wall is unsuitable for transendocardial injections (due to thickness or other reasons).

Medical History:

9. Stroke or transient ischemic attack (TIA) within 3 months of screening;

10. Hemoglobin A1c (HbA1c) ≥ 9% at screening;

11. Diabetic subjects with uncontrolled or untreated proliferative retinopathy as determined by dilated eye exam administered by a qualified eye care professional as per American Diabetes Association guidelines;

12. Blood clotting disorder not caused by medication (e.g., thrombophilia);

13. Active malignancy (non-basal cell) requiring surgery, chemotherapy, and/or radiation in the past 12 months;

14. Drug or alcohol abuse that would interfere with the subject's compliance with study procedures;

15. Allergies to any equine, porcine, or bovine products;

16. Body mass index (BMI) ≥ 40 kg/m2 at screening;

17. Established chronic kidney disease (CKD) requiring dialysis (Stage 5); estimated creatinine clearance < 15 mL/min at screening;

18. Subject has allergy or is unable to tolerate cardiac imaging contrast agents; also the inability to get a good quality echocardiogram image at screening (as determined by the imaging core lab).

Laboratory Parameters:

19. Abnormal laboratory values (performed at central lab) at screening:

• Platelets < 50,000 μL;
• Hemoglobin < 9.0 g/dL;
• Aspartate aminotransferase/alanine aminotransferase (AST/ALT) > 3 times the upper limit of normal (ULN);
• Human immunodeficiency virus 1 (HIV 1), HIV 2, or syphilis positive (rapid plasma reagin [RPR]);
• Active hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies;
• NOTE: Additional lab tests may be performed per local requirements including but not limited to: hepatitis B core antibody, human T lymphotropic virus I/II.

Exclusionary Procedures, Devices, or Medication:

20. Subjects receiving anti-angiogenic drugs (e.g., anti-vascular endothelial growth factor [VEGF]);

21. Chronic exposure to cytotoxic therapy for oncologic or chronic non-oncologic reasons in the prior 3 months or expected requirement over the course of the study;

22. Concurrent participation in another interventional clinical trial or receiving experimental intervention within 30 days of screening or having previously been exposed to Aastrom's ixmyelocel T product or previously received allogeneic cell therapy, autologous cell therapy cultured with animal proteins.

23. In the opinion of the Investigator, the subject is unsuitable for cellular therapy or has a food/drug allergy, surgical or medical condition, clinically significant psychiatric disorders, poor nutritional status, or lab abnormality requiring further medical evaluation that may interfere with the investigational product, interfere with the study results' interpretation, interfere with the subject's ability to complete the study or compromise the subject's safety.

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 86 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Vericel Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Cardiology, P.C. & Center for Therapeutic Angiogenesis

Birmingham, Alabama, United States

University of Alabama at Birmingham

Birmingham, Alabama, United States

Mercy Gilbert Medical Center

Gilbert, Arizona, United States

Mayo Clinic Arizona

Phoenix, Arizona, United States

Scripps Clinic

La Jolla, California, United States

UCSD Medical Center

La Jolla, California, United States

Cedars-Sinai Heart and Lung Institute

Los Angeles, California, United States

University of California Los Angeles (UCLA)

Los Angeles, California, United States

St. John's Regional Medical Center

Oxnard, California, United States

Stanford University

Stanford, California, United States

Cardiology Research Associates

Daytona Beach, Florida, United States

University of Florida - Division of Cardiology

Gainesville, Florida, United States

Mayo Clinic Florida (Jacksonville)

Jacksonville, Florida, United States

University of Miami - Miller School of Medicine

Miami, Florida, United States

Emory University Hospital

Atlanta, Georgia, United States

Georgia Regents University

Augusta, Georgia, United States

Rush University Medical Center

Chicago, Illinois, United States

Ochsner Clinic Foundation

New Orleans, Louisiana, United States

Massachusetts General Hospital, Division of Cardiology

Boston, Massachusetts, United States

Michigan CardioVascular Institute

Saginaw, Michigan, United States

Mayo Clinic

Rochester, Minnesota, United States

Newark Beth Israel Hospital

Newark, New Jersey, United States

Columbia University Medical Center

New York, New York, United States

The Carl and Edyth Linder Center for Research & Education at The Christ Hospital

Cincinnati, Ohio, United States

University Hospitals - Case Medical Center

Cleveland, Ohio, United States

Temple University

Philadelphia, Pennsylvania, United States

UPMC Cardiovascular Institute

Pittsburgh, Pennsylvania, United States

Veterans Administration Healthcare System

Pittsburgh, Pennsylvania, United States

Stern Cardiovascular Foundation, Inc.

Germantown, Tennessee, United States

Soltero Cardiovascular Research Center

Dallas, Texas, United States

Methodist DeBakey Heart and Vascular Center

Houston, Texas, United States

University of Utah Health Services Center

Salt Lake City, Utah, United States

Swedish Medical Center - Cherry Hill Professional Building

Seattle, Washington, United States

University of Wisconsin-Madison Cardiovascular Medicine

Madison, Wisconsin, United States

University of Alberta Hospital

Edmonton, Alberta, Canada

Montreal Heart Institute

Montreal, Quebec, Canada

Countries

United States; Canada

References

Patel AN, Henry TD, Quyyumi AA, Schaer GL, Anderson RD, Toma C, East C, Remmers AE, Goodrich J, Desai AS, Recker D, DeMaria A; ixCELL-DCM Investigators. Ixmyelocel-T for patients with ischaemic heart failure: a prospective randomised double-blind trial. Lancet. 2016 Jun 11;387(10036):2412-21. doi: 10.1016/S0140-6736(16)30137-4. Epub 2016 Apr 5.

Reference Type: DERIVED

PMID: 27059887 (View on PubMed)

Related Links

http://www.vcel.com/

Vericel Corporation Homepage

Other Identifiers

ABI 55-1202-1

Identifier Type: -

Identifier Source: org_study_id