Safety Study of Allogeneic Mesenchymal Precursor Cells (MPCs) in Subjects With Recent Acute Myocardial Infarction

Sponsor

Angioblast Systems (Industry)

Overall Status

Unknown status

CT.gov ID

NCT00555828

Collaborator

(none)

Enrollment

Locations

Arms

Duration (Months)

12.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Primary Objective The primary objective of this study is to evaluate the safety and feasibility of transendocardial injection using the Cordis Biosense NogaStarTM Mapping Catheter with the Biosense MyostarTM Left Ventricular Injection Catheter of 25 M, 75 M, and 150 M allogeneic mesenchymal precursor cells (MPCs) in subjects with AMI.

SecondaryObjective

The secondary objectives are to explore functional efficacy for subsequent study design, as well as late-term dose related tolerance, by:

Evaluating the effect of allogeneic MPCs on exploratory efficacy endpoints related to cardiac function on Days 90, 180, and 1 year
Evaluating the change from baseline in the Medical Outcome Study Short Form (SF-36), Kansas City Cardiomyopathy Questionnaire, Seattle Angina Questionnaire, and the New York Heart Association Classification at 30 days, 3 and 6 months, and 1, 2, and 3 years
Evaluating follow-up safety through Day 360
Providing preliminary data to support dose selection for future studies

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Genetic: Allogeneic Mesenchymal Precursor Cells (MPCs) Procedure: Standard-of-care treatment with NOGA® mapping and staged injections. Genetic: Allogeneic Mesenchymal Precursor Cells (MPCs) Procedure: Standard-of-care treatment with NOGA® mapping and staged injections. Genetic: Allogeneic Mesenchymal Precursor Cells (MPCs) Procedure: Standard-of-care treatment with NOGA® mapping and staged injections.	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

A Phase 1b/2a Dose Escalation Study to Assess the Safety and Feasibility of Transendocardial Delivery of 3 Different Doses of Allogeneic Mesenchymal Precursor Cells (MPCs) in Subjects With Recent Acute Myocardial Infarction

Study Start Date :

Mar 1, 2008

Anticipated Primary Completion Date :

Dec 1, 2013

Anticipated Study Completion Date :

Dec 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: A1 5 subjects randomized to receive 25 M allogeneic MPCs by transendocardial injection	Genetic: Allogeneic Mesenchymal Precursor Cells (MPCs) 25 M allogeneic MPCs by transendocardial injection
Other: A2 5 subjects randomized to receive standard-of-care treatment with NOGA® mapping and staged injections.	Procedure: Standard-of-care treatment with NOGA® mapping and staged injections. Standard-of-care treatment with NOGA® mapping and staged injections.
Experimental: B1 5 subjects randomized to receive 75 M allogeneic MPCs by transendocardial injection	Genetic: Allogeneic Mesenchymal Precursor Cells (MPCs) 75 M allogeneic MPCs by transendocardial injection
Other: B2 3 subjects randomized to receive standard-of-care treatment with NOGA® mapping and staged injections.	Procedure: Standard-of-care treatment with NOGA® mapping and staged injections. Standard-of-care treatment with NOGA® mapping and staged injections.
Experimental: C1 5 subjects randomized to receive 150 M allogeneic MPCs by transendocardial injection	Genetic: Allogeneic Mesenchymal Precursor Cells (MPCs) 150 M allogeneic MPCs by transendocardial injection
Other: C2 2 subjects randomized to receive standard-of-care treatment with NOGA® mapping and staged injections.	Procedure: Standard-of-care treatment with NOGA® mapping and staged injections. Standard-of-care treatment with NOGA® mapping and staged injections.

Outcome Measures

Primary Outcome Measures

Evaluate the safety and feasibility of transendocardial injection using the Cordis Biosense NogaStarTM Mapping Catheter with the Biosense MyostarTM Left Ventricular Injection Catheter of allogeneic mesenchymal precursor cells (MPCs) in subjects with AMI. [30 days]

Secondary Outcome Measures

Explore efficacy for subsequent study design and dose related tolerance: •Effect related to cardiac function.•Change from baseline in SF-36, KCCQ, SAQ, and the NYHA Classification.•Follow-up safety through Day 360 • Dose selection for future stu [3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Age 18 years or older.
An ST-elevation MI (STEMI) within 2 to 10 days of study enrollment. The STEMI must be documented by ECG with ST-segment elevation >1 mm in at least 2 contiguous precordial leads or in at least 2 adjacent limb leads. If there is a history of a previous AMI prior to the qualifying MI, then there must be a documented EF ≥ 50% by 2D echocardiogram within 12 months of enrollment.
Successful percutaneous revascularization with Thrombolysis in Myocardial Infarction (TIMI)-3 flow of the infarct-related artery.
A baseline 2D echocardiogram with EF ≥ 30 and ≤ 50% following PCI.
Creatinine level ≤ 1.5mg/dL within 24 hours of study procedure.
Hematocrit ≥ 30% within 24 hours of study procedure.
White Blood Cell count < 20k/mm3 within 24 hours of study procedure.
Platelet count ≥ 100k/mm3 within 24 hours of study procedure.
INR ≤ 1.7 within 24 hours of study procedure.
Total bilirubin <3 mg/dL, albumin >2.8 g/dL, aspartate aminotransferase(AST) ≤ 2.5x the upper limit of normal, gamma glutamyltranspeptidase (GGT) ≤ 1.5 x the upper limit of normal.
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 surgery.
Female subjects of childbearing potential must have a negative serum pregnancy test at screening (within 2 weeks of enrollment) and a negative serum or urine pregnancy test on the day of cell implantation.
Willing and able to understand, sign, and date the Informed Consent Form (ICF).
Must be willing to return for required follow-up visits.
Must be able to follow postoperative management program.

Exclusion Criteria:

Subject is hemodynamically unstable at Day 5 post-AMI as demonstrated by any of the following:
Killip Class 4 indicative of cardiogenic shock.
Requirement of intra-aortic balloon pump or IV inotropic support for the maintenance of mean arterial blood pressure ≥ 60 mmHg.
Sustained ventricular tachycardia as demonstrated by QRS complexes wider than 120 msec, lasting >30 secs, and >100 bpm occurring >48 hours following PCI without any identifiable, reversible cause (ie, electrolyte imbalance).
Further revascularization planned for the next 30 days.
Chronic atrial fibrillation.
A wall thickness in the target region <8 mm as determined by 2D echocardiography(the target region is defined at the time of NOGA® mapping).
An LV thrombus.
Severe peripheral vascular disease precluding femoral artery access as determined at time of original catheterization.
Aortic stenosis as determined as valve area less than 1 cm2 that prohibits catheter access to the LV.
Echocardiographic evidence of hypertrophic cardiomyopathy indicating heart muscle thickness >15 mm.
Human immunodeficiency virus (HIV)
Serum glucose level ≥ 400 mg/dl within 24 hours of study procedure
Serum glucose level 300-400 mg/dl and presence of urine ketones within 24 hours of study procedure.
Claustrophobic, or with medical conditions or contradictions that impede performing baseline MRI study.
An active uncontrolled infection.
A prosthetic aortic valve.
Presence of ≥ 20% anti-HLA antibody titers and/or having antibody specificities to donor HLA antigens.
A current or prior history within the last 3 years of neoplasm (excluding basal cell) and/or any active neoplasm within the last 24 months.
A known hypersensitivity to dimethyl sulfoxide (DMSO), murine and/or bovine products.
Pregnancy or breastfeeding.
Imprisoned at the time of enrollment.
A treatment and/or an uncompleted follow-up treatment of any investigational therapy within 6 months before implantation surgery and intent to participate in any other investigational drug or cell therapy study during the 3-year follow-up period of this study.
Active participation in other research therapy for cardiovascular repair/regeneration.
A prior recipient of stem precursor cell therapy for cardiac repair.
Any medical condition that would affect the investigator's ability to evaluate the subject's condition or could compromise the subject's safety.
Any condition that, in the judgment of the investigator, would prohibit the subject from participating in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Minnesota/Minneapolis Heart Institute	Minneapolis	Minnesota	United States	55407-1139
2	Texas Heart Institute/St. Luke's Hospital	Houston	Texas	United States	77030