A Phase II Dose-escalation Study to Assess the Feasibility and Safety of Transendocardial Delivery of Three Different Doses of Allogeneic Mesenchymal Precursor Cells (MPCs)in Subjects With Heart Failure

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Angioblast Systems
ClinicalTrials.gov Identifier:
NCT00721045
First received: July 21, 2008
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

This is a dose-ranging clinical study to evaluate the feasibility, safety, and tolerability of 3 different doses of immunoselected, culture expanded, nucleated, allogeneic MPCs in subjects who have cardiomyopathy of both ischemic and idiopathic etiology.


Condition Intervention Phase
Heart Failure
Biological: Mesenchymal Precursor Cells (MPCs)
Procedure: standard-of-care treatment with mock mapping and injection procedures.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: Single Blind (Subject)
Primary Purpose: Treatment
Official Title: A Phase II Dose-escalation Study to Assess the Feasibility and Safety of Transendocardial Delivery of Three Different Doses of Allogeneic Mesenchymal Precursor Cells (MPCs)in Subjects With Heart Failure

Resource links provided by NLM:


Further study details as provided by Angioblast Systems:

Primary Outcome Measures:
  • The primary objective of this study is to evaluate the feasibility and safety of transendocardial injection using mapping Catheter with the Left Ventricular Injection Catheter of 25 M, 75 M, and 150 M allogeneic MPCs in subjects with heart failure. [ Time Frame: 3 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objectives are to explore functional efficacy for subsequent study design. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 60
Study Start Date: August 2008
Estimated Study Completion Date: July 2013
Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: A1
15 subjects randomized to receive 25 M allogeneic MPCs by transendocardial injection and mapping.
Biological: Mesenchymal Precursor Cells (MPCs)
25 M allogeneic MPCs by transendocardial injection and mapping.
Other Name: Revascor
Sham Comparator: A2
5 subjects randomized to receive standard-of-care treatment with mock mapping and injection procedures.
Procedure: standard-of-care treatment with mock mapping and injection procedures.
Mock
Active Comparator: B1
15 subjects randomized to receive 75 M allogeneic MPCs by transendocardial injection and mapping.
Biological: Mesenchymal Precursor Cells (MPCs)
75 M allogeneic MPCs by transendocardial injection and mapping.
Other Name: Revascor
Sham Comparator: B2
5 subjects randomized to receive standard-of-care treatment with mock mapping and injection procedures.
Procedure: standard-of-care treatment with mock mapping and injection procedures.
Mock
Active Comparator: C1
15 subjects randomized to receive 150 M allogeneic MPCs by transendocardial injection and mapping.
Biological: Mesenchymal Precursor Cells (MPCs)
150 M allogeneic MPCs by transendocardial injection
Other Name: Revascor
Sham Comparator: C2
5 subjects randomized to receive standard-of-care treatment with mock mapping and injection procedures.
Procedure: standard-of-care treatment with mock mapping and injection procedures.
Mock

Detailed Description:

Heart failure subjects recruited will include those who have advanced heart failure NYHA (New York Heart Association) class II to IV and a depressed ejection fraction (EF < 40%). Baseline eligibility testing assessments will be completed within 28 days prior to cell delivery. Efficacy will be explored at 3, 6, and 12 months.

This will be a single-blinded, dose-escalation, cohort study in 60 subjects allocated sequentially to 1 of 3 cohorts A, B, or C. Forty-five subjects will be randomized to receive transendocardial delivery of MPC treatment, and 15 subjects will be randomized to receive standard-of-care treatment without MPC administration. The fifteen subjects randomized to receive standard of care without needle injection will serve as the study's control population and will undergo mock mapping and verbal injection scripts.

  Eligibility

Ages Eligible for Study:   20 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. NYHA ≥ 2.
  2. Age >20 and <80.
  3. Cardiomyopathy of ischemic or idiopathic etiology.
  4. Subject is not a candidate for either percutaneous intervention or cardiac surgery as determined by both an interventional cardiologist and a cardiac surgeon.
  5. LVEF (Left ventricular ejection fraction) < 40% via 2-D Echocardiogram within 28 days of study procedure.
  6. On stable maximal, tolerable dosages of heart failure therapies including betablockers,ace inhibitors and/or diuretics with no interruption or change in medical therapy for at least 28 days prior to study enrollment.
  7. Left Ventricle wall thickness ≥ 8mm at target site by echo within 28 days of study procedure.
  8. If the subject or partner is of childbearing potential, he or she must be willing to use adequate contraception (hormonal or barrier method or abstinence) from the time of screening and for a period of at least 16 weeks after procedure.
  9. Female subjects of childbearing potential must have a negative serum pregnancy test at screening.
  10. Willing and able to understand, sign, and date the Informed Consent Form (ICF).
  11. Must be willing to return for required follow-up visits.
  12. Must be able to follow postoperative management program.

Exclusion Criteria:

  1. Acute Myocardial Infarction in past 30 days.
  2. Discharge of subject's ICD within 28 days of study procedure.
  3. Sustained Ventricular Tachycardia as demonstrated by QRS complexes wider than 120 msec, lasting >30 secs, and >100 bpm documented in screening ECG or 24 hour Holter monitoring.
  4. Unstable angina.
  5. LV thrombus by echocardiogram or angiogram with 28 days prior to and up to the time of cell injection.
  6. Aortic stenosis as determined by echocardiography as valve area less than 1 cm2 that prohibits NOGA catheter access to LV.
  7. Cardiogenic shock defined as the need for intravenous inotropic support, an intraaortic balloon pump, or mechanical circulatory support at the time of cell injections.
  8. Chronic AF or AF at the time of cell injections.
  9. Unprotected left main coronary artery disease >50%.
  10. Ischemic or hemorrhagic stroke as diagnosed by CT/MRI events within the last 3 months prior to enrollment.
  11. Bleeding diathesis disorder such as abnormal coagulation profile precluding performing of mapping/injection procedure.
  12. Serum glucose level > 400 mg/dl within 28 days of study procedure.
  13. Serum glucose level 300 to 400 mg/dl and presence of urine ketones within 28 days of study procedure.
  14. Creatinine level ≥ 2.5 mg/dL within 28 days of study procedure.
  15. Hematocrit ≤ 32% within 28 days of study procedure.
  16. White Blood Cell count > 12 x 106/mm3 within 28 days of study procedure.
  17. Platelet count ≤100 x106/mm3 within 28 days of study procedure.
  18. Total bilirubin >3 mg/dL, albumin <2.8 g/dL, aspartate aminotransferase (AST) ≥ 2.5x the upper limit of normal, gamma glutamyltranspeptidase (GGT) ≥ 1.5x the upper limit of normal within 28 days of study procedure.
  19. Presence of ≥ 20% anti-HLA antibody titers and/or having antibody specificities to donor HLA antigens.
  20. A known hypersensitivity to dimethyl sulfoxide (DMSO), murine and/or bovine products.
  21. History of cancer prior to screening (excluding basal cell carcinoma).
  22. Acute or chronic infectious disease, including but not limited to human immunodeficiency virus (HIV).
  23. Any concurrent disease or condition that, in the opinion of the investigator, would make the subject unsuitable for participation in the study.
  24. Treatment and/or an uncompleted follow-up treatment of any investigational. therapy within 6 months before procedure and intent to participate in any other investigational drug or cell therapy study during the 3-year follow-up period of this study.
  25. Active participation in other research therapy for cardiovascular repair/regeneration.
  26. Prior recipient of stem precursor cell therapy for cardiac repair.
  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: NCT00721045

Locations
United States, Arizona
Mercy Gilbert Medical Center
Gilbert, Arizona, United States, 85297
United States, California
University of California, San Diego
La Jolla, California, United States, 92037-1300
United States, Minnesota
Minneapolis Heart Institute 920 East 28th St, Suite 300
Minneapolis, Minnesota, United States, 55407-1139
United States, Pennsylvania
UPMC
Pittsburgh, Pennsylvania, United States, 15213
United States, Texas
Texas Heart Institue
Houston, Texas, United States, 77030
United States, Washington
Swedish Heart and Vascular Institute
Seattle, Washington, United States, 98122
Sponsors and Collaborators
Angioblast Systems
Investigators
Principal Investigator: Emerson Perin, MD Texas Heart Institute
  More Information

No publications provided

Responsible Party: Angioblast Systems
ClinicalTrials.gov Identifier: NCT00721045     History of Changes
Other Study ID Numbers: HF-AB002
Study First Received: July 21, 2008
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Angioblast Systems:
Heart Failure
Congestive Heart Failure

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on July 24, 2014