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) (ixCELL DCM)

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Aastrom Biosciences
Sponsor:
Information provided by (Responsible Party):
Aastrom Biosciences
ClinicalTrials.gov Identifier:
NCT01670981
First received: August 20, 2012
Last updated: September 3, 2014
Last verified: September 2014
  Purpose

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.


Condition Intervention Phase
Ischemic Dilated Cardiomyopathy (IDCM)
Biological: ixmyelocel-T
Other: Vehicle Control
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, PARALLEL GROUP STUDY TO EVALUATE THE EFFICACY, SAFETY AND TOLERABILITY OF TRANSENDOCARDIAL INJECTION OF IXMYELOCEL-T IN SUBJECTS WITH HEART FAILURE DUE TO ISCHEMIC DILATED CARDIOMYOPATHY (IDCM).

Resource links provided by NLM:


Further study details as provided by Aastrom Biosciences:

Primary Outcome Measures:
  • Average number of clinical events over 12 months post-treatment. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    The primary endpoint will assess the efficacy of ixmyelocel-T compared to placebo (vehicle control) on the average number of events per patient over 12 months post-treatment in each treatment arm (total number events in each arm/total number of patients in each arm). The events include: all-cause deaths, cardiovascular hospitalizations, and unplanned outpatient or emergency department visits to treat acute decompensated heart failure. The clinical events used in this endpoint will be adjudicated by an independent clinical endpoint committee who are blinded to treatment.


Secondary Outcome Measures:
  • Change from baseline to 12 months post-treatment in 6-minute walk test. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    A secondary objective will be to evaluate the changes from baseline to 12 months post-treatment in the distance walked as measured by the 6-minute walk test.

  • Change from baseline to 12 months post-treatment in left ventricular function as evaluated by echocardiography. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    A secondary objective will be to evaluate the change in left ventricular function as measured by echocardiography for left ventricular ejection fraction (LVEF).

  • Change from baseline to 12 months post-treatment in quality of life. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    A secondary objective will be to evaluate the change in quality of life (total score) in patients treated with ixmyelocel-T compared to placebo using the Minnesota Living with Heart Failure Questionnaire.

  • Change from baseline to 12 months post-treatment in NYHA Classification. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    A secondary objective will be to evaluate the change from baseline to Month 12 in NYHA Classification in patients treated with ixmyelocel-T compared to placebo.

  • Percent of patients with adverse events. [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    A secondary objective will be to evaluate the overall safety and tolerability of ixmyelocel-T versus placebo in patients with DCM from time of aspiration through 12 months post-treatment/follow-up by % of patients with adverse events.

  • Percent of patients with major adverse cardiac events (MACE). [ Time Frame: 12 Months ] [ Designated as safety issue: No ]
    A secondary objective will be to evaluate the overall safety and tolerability of ixmyelocel-T versus placebo in patients with DCM by the percentage of patients who experience MACE events. MACE events include: unstable angina requiring hospitalization, myocardial infarction, stroke, worsening heart failure requiring hospitalization, VAD implantation, heart transplant, resuscitated sudden death, and cardiovascular death.


Estimated Enrollment: 108
Study Start Date: October 2012
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: ixmyelocel-T
Ixmyelocel-T delivered by catheter-based intramyocardial injection procedure.
Biological: ixmyelocel-T
12-20 transendocardial NOGA® -guided injections of 0.4 mL of ixmyelocel-T per injection into the left ventricle.
Placebo Comparator: Vehicle Control
Placebo delivered by catheter-based intramyocardial injection procedure.
Other: Vehicle Control
12-20 transendocardial NOGA® -guided injections of 0.4 mL of vehicle control per injection into the left ventricle.

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).

  Eligibility

Ages Eligible for Study:   30 Years to 86 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01670981

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Thomas P Frazier    205-934-8767    tpfrazie@uab.edu   
Principal Investigator: Sumanth Prabhu, MD         
Cardiology, P.C. & Center for Therapeutic Angiogenesis Not yet recruiting
Birmingham, Alabama, United States, 35211
Contact: Susan DeRamus, RN, CCRC    205-780-4330 ext 338    sderamus@cardiologypc.com   
Principal Investigator: Farrell O Mendelsohn, MD         
United States, Arizona
Mercy Gilbert Medical Center Recruiting
Gilbert, Arizona, United States, 85297
Contact: Jennifer Vermillion, CCRC    480-728-9973    jennifer.vermillion@dignityhealth.org   
Principal Investigator: Nabil Dib, MD         
Mayo Clinic Arizona Recruiting
Phoenix, Arizona, United States, 85054
Contact: Barbara Knight    480-342-2545    knight.barbara@mayo.edu   
Principal Investigator: David Fortuin, MD         
United States, California
Scripps Clinic Recruiting
La Jolla, California, United States, 92037
Contact: Heather Catchpole, MS, CCRC    858-554-5258    catchpole.heather@scrippshealth.org   
Principal Investigator: Richard Schatz, MD         
UCSD Medical Center Recruiting
La Jolla, California, United States, 92037
Contact: Cassie Gustafson    858-657-5170    csgustafson@ucsd.edu   
Principal Investigator: Anthony DeMaria, MD         
University of California Los Angeles (UCLA) Not yet recruiting
Los Angeles, California, United States, 90095
Contact: Rubine Gevorgyan    310-794-4797    rgevorgyan@mednet.ucla.edu   
Principal Investigator: A Nsair, MD         
Cedars-Sinai Heart and Lung Institute Recruiting
Los Angeles, California, United States, 90048
Contact: Michelle Domingo    424-315-4458    michelle.domingo@cshs.org   
Contact: Joseph Cosico       joseph.cosico@cshs.org   
Principal Investigator: Timothy Henry, MD         
St. John's Regional Medical Center Recruiting
Oxnard, California, United States, 93030
Contact: Lindsey McFarland    805-988-7086    Lindsey.McFarland@dignityhealth.org   
Principal Investigator: David Schmidt, MD         
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Ed Finn    650-724-6167    efinn@stanford.edu   
Principal Investigator: Joseph Wu, MD         
United States, Florida
Cardiology Research Associates Recruiting
Daytona Beach, Florida, United States, 32117
Contact: Lauraine Crandall    386-677-6672    cardioinc2@aol.com   
Principal Investigator: David Henderson, MD         
University of Florida - Division of Cardiology Recruiting
Gainesville, Florida, United States, 32610
Contact: Dana Leach    352-273-8945    dana.leach@medicine.ufl.edu   
Principal Investigator: David Anderson, MD         
Mayo Clinic Florida (Jacksonville) Recruiting
Jacksonville, Florida, United States, 32224
Contact: Estela Staggs    904-953-8509    staggs.estela@mayo.edu   
Principal Investigator: Issam Moussa, MD         
University of Miami - Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Darcy DiFede    305-243-9106    dvelazqu@med.miami.edu   
Principal Investigator: Joshua Hare, MD         
United States, Georgia
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30322
Contact: Salman Sher    404-712-0170      
Contact: Khuram Ashraf    4047127762    khuram.ashraf@emory.edu   
Principal Investigator: Arshed Quyyumi, MD         
Georgia Regents University Recruiting
Augusta, Georgia, United States, 30912
Contact: Carol Smith    706-721-0193    csmith@gru.edu   
Principal Investigator: Adam E Berman, MD         
United States, Illinois
Rush University Medical Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Jennifer McDonald    312-942-8239    jennifer_mcdonald@rush.edu   
Principal Investigator: Gary Schaer, MD         
United States, Louisiana
Ochsner Clinic Foundation Recruiting
New Orleans, Louisiana, United States, 70121
Contact: Monica Pellegrin    504-842-2690    mopellegrin@ochsner.org   
Principal Investigator: Rajan Patel, MD         
United States, Massachusetts
Massachusetts General Hospital, Division of Cardiology Recruiting
Boston, Massachusetts, United States, 02114
Contact: Alexandra Miller    617-643-1372    AMILLER18@partners.org   
Principal Investigator: Kimberly Parks, MD         
United States, Michigan
Michigan CardioVascular Institute Recruiting
Saginaw, Michigan, United States, 48602
Contact: Valerie Bitzer, RN    989-583-6372    vbitzer@mcvi.com   
Principal Investigator: Safwan Kassas, MD         
United States, Minnesota
Mayo Clinic Recruiting
Rochester, Minnesota, United States, 55905
Contact: Bola Aduloju, RN    507-255-2831    Aduloju.Omobolanle@mayo.edu   
Contact: Cindy M. Woltman, RN    507-266-4095    Woltman.cindy@mayo.edu   
Principal Investigator: Guy Reeder, MD         
Principal Investigator: Alfredo Clavell, MD         
United States, New Jersey
Newark Beth Israel Hospital Recruiting
Newark, New Jersey, United States, 07112
Contact: Elaine DeCarlo    973-926-8451    EDeCarlo@barnabashealth.org   
Principal Investigator: Mark Zucker, MD         
United States, New York
Columbia University Medical Center Recruiting
New York, New York, United States, 10032
Contact: Henry Arango    212-305-1368    ha2258@columbia.edu   
Contact: Mary Marks    212-305-1368    mc2228@columbia.edu   
Principal Investigator: Paul Christian Schulz, MD         
United States, Ohio
The Carl and Edyth Linder Center for Research & Education at The Christ Hospital Recruiting
Cincinnati, Ohio, United States, 45219
Contact: Christine Huber    513-585-1723    christine.huber@thechristhospital.com   
Principal Investigator: Eugene Chung, MD         
University Hospitals - Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Terence Semenec    216-983-4724    Terence.Semenec@UHhospitals.org   
Principal Investigator: Guilerme Oliveira, MD         
United States, Pennsylvania
Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Jennie Wong    215-707-5340    jennie.wong@tuhs.temple.edu   
Principal Investigator: Jon C George, MD         
UPMC Cardiovascular Institute Recruiting
Pittsburgh, Pennsylvania, United States, 15213
Contact: Laurie Dennis    412-647-6210    papugall@upmc.edu   
Principal Investigator: Catalin Toma, MD         
Veterans Administration Healthcare System Not yet recruiting
Pittsburgh, Pennsylvania, United States, 15240
Contact: Jennifer Carrick       jennifer.carrick@va.gov   
Principal Investigator: Nicole Lemieux, MD         
United States, Tennessee
Stern Cardiovascular Foundation, Inc. Recruiting
Germantown, Tennessee, United States, 38138
Contact: Barbara Hamilton    901-271-4063    barbara.hamilton@sterncardio.com   
Principal Investigator: Frank McGrew III, MD         
United States, Texas
Soltero Cardiovascular Research Center Recruiting
Dallas, Texas, United States, 75226
Contact: Wes Oglesby    214-820-2273    wesley.oglesby@baylorhealth.edu   
Principal Investigator: Cara East, MD         
Methodist DeBakey Heart and Vascular Center Recruiting
Houston, Texas, United States, 77030
Contact: Emily Taylor, RN, BSN, MS    713-441-3963    etaylor2@tmhs.org   
Principal Investigator: Barry H Tractenberg, MD         
United States, Utah
University of Utah Health Services Center Recruiting
Salt Lake City, Utah, United States, 84132
Contact: Michelle Esplin    801-585-5243    michelle.esplin@hsc.utah.edu   
Principal Investigator: Amit Patel, MD         
United States, Washington
Swedish Medical Center - Cherry Hill Professional Building Recruiting
Seattle, Washington, United States, 98122
Contact: Jennifer Nagel    206-386-6462    jennifer.nagel@swedish.org   
Principal Investigator: Paul Huang, MD         
United States, Wisconsin
University of Wisconsin-Madison Cardiovascular Medicine Recruiting
Madison, Wisconsin, United States, 53792
Contact: Cathlyn Leitzke, RN,MSN,CCRC    608-262-2290    cjl@medicine.wisc.edu   
Principal Investigator: Amish Raval, MD         
Canada, Alberta
University of Alberta Hospital Recruiting
Edmonton, Alberta, Canada, T6G 287
Contact: Suzanne Welsh    780-407-3572    Suzanne.Welsh@albertahealthservices.ca   
Principal Investigator: Robert Welsh, MD         
Canada, Quebec
Montreal Heart Institute Not yet recruiting
Montreal, Quebec, Canada, H1T 1C8
Contact: Nathalie St-Jean    514-376-3330 ext 3621    Nathalie.st-jean@icm-mhi.org   
Principal Investigator: Hung Ly, MD         
Sponsors and Collaborators
Aastrom Biosciences
  More Information

Additional Information:
No publications provided

Responsible Party: Aastrom Biosciences
ClinicalTrials.gov Identifier: NCT01670981     History of Changes
Other Study ID Numbers: ABI 55-1202-1
Study First Received: August 20, 2012
Last Updated: September 3, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Aastrom Biosciences:
Ischemic dilated cardiomyopathy
Heart failure
ixCELL
ixCELL DCM
IDCM
DCM
stem cells
MSC
cell therapy

Additional relevant MeSH terms:
Cardiomyopathies
Cardiomyopathy, Dilated
Heart Failure
Ischemia
Cardiomegaly
Cardiovascular Diseases
Heart Diseases
Pathologic Processes

ClinicalTrials.gov processed this record on October 30, 2014