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

NCT ID: NCT00721045

Last Updated: 2020-03-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2008-08-31

Study Completion Date

2013-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Heart Failure

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

FACTORIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

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A1

15 subjects randomized to receive 25 M allogeneic MPCs by transendocardial injection and mapping.

Group Type ACTIVE_COMPARATOR

Mesenchymal Precursor Cells (MPCs)

Intervention Type BIOLOGICAL

25 M allogeneic MPCs by transendocardial injection and mapping.

A2

5 subjects randomized to receive standard-of-care treatment with mock mapping and injection procedures.

Group Type SHAM_COMPARATOR

standard-of-care treatment with mock mapping and injection procedures.

Intervention Type PROCEDURE

Mock

B1

15 subjects randomized to receive 75 M allogeneic MPCs by transendocardial injection and mapping.

Group Type ACTIVE_COMPARATOR

Mesenchymal Precursor Cells (MPCs)

Intervention Type BIOLOGICAL

75 M allogeneic MPCs by transendocardial injection and mapping.

B2

5 subjects randomized to receive standard-of-care treatment with mock mapping and injection procedures.

Group Type SHAM_COMPARATOR

standard-of-care treatment with mock mapping and injection procedures.

Intervention Type PROCEDURE

Mock

C1

15 subjects randomized to receive 150 M allogeneic MPCs by transendocardial injection and mapping.

Group Type ACTIVE_COMPARATOR

Mesenchymal Precursor Cells (MPCs)

Intervention Type BIOLOGICAL

150 M allogeneic MPCs by transendocardial injection

C2

5 subjects randomized to receive standard-of-care treatment with mock mapping and injection procedures.

Group Type SHAM_COMPARATOR

standard-of-care treatment with mock mapping and injection procedures.

Intervention Type PROCEDURE

Mock

Interventions

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Mesenchymal Precursor Cells (MPCs)

25 M allogeneic MPCs by transendocardial injection and mapping.

Intervention Type BIOLOGICAL

Mesenchymal Precursor Cells (MPCs)

75 M allogeneic MPCs by transendocardial injection and mapping.

Intervention Type BIOLOGICAL

Mesenchymal Precursor Cells (MPCs)

150 M allogeneic MPCs by transendocardial injection

Intervention Type BIOLOGICAL

standard-of-care treatment with mock mapping and injection procedures.

Mock

Intervention Type PROCEDURE

standard-of-care treatment with mock mapping and injection procedures.

Mock

Intervention Type PROCEDURE

standard-of-care treatment with mock mapping and injection procedures.

Mock

Intervention Type PROCEDURE

Other Intervention Names

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Revascor Revascor Revascor

Eligibility Criteria

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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.
Minimum Eligible Age

20 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Mesoblast, Ltd.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Emerson Perin, MD

Role: PRINCIPAL_INVESTIGATOR

Texas Heart Institute

Locations

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Mercy Gilbert Medical Center

Gilbert, Arizona, United States

Site Status

University of California, San Diego

La Jolla, California, United States

Site Status

Minneapolis Heart Institute 920 East 28th St, Suite 300

Minneapolis, Minnesota, United States

Site Status

UPMC

Pittsburgh, Pennsylvania, United States

Site Status

Texas Heart Institue

Houston, Texas, United States

Site Status

Swedish Heart and Vascular Institute

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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HF-AB002

Identifier Type: -

Identifier Source: org_study_id

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