Safety Study of AMI MultiStem® to Treat Heart Attacks

Acute Myocardial Infarction Clinical Trial

Official title:

A Phase I, Multicenter, Dose-Escalation Trial Evaluating the Safety of Allogeneic AMI MultiStem® in Patients With Acute Myocardial Infarction

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00677222
• Other study ID #: AMI-07-001
• Status: Completed
• Phase: Phase 1
• First received: May 12, 2008
• Last updated: May 10, 2012
• Start date: May 2008
• Est. completion date: February 2012

Study information

• Verified date: May 2012
• Source: Athersys, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine if escalating doses of AMI MultiStem® delivered by catheter can safely be given to patients that have had a recent heart attack treated with stent implantation.

Description:

The mortality rates associated with acute myocardial infarction (AMI) have significantly decreased over the past 2 decades. Beginning first with thrombolytic therapy for AMI, and more recently with growing acceptance and availability of primary percutaneous coronary intervention (PCI) for ST-elevation AMI, the mortality rates of this devastating ischemic event have decreased from almost 15% in clinical trials in the late 1980's to <5% in recent primary percutaneous coronary intervention trials. Though AMI-related mortality has been reduced, AMI survival is often accompanied by significant loss of function that may lead to subsequent treatments, congestive heart failure (CHF) and reduction in quality of life. A cell therapy that could reduce the damage associated with AMI and positively affect heart function would provide substantial benefits to the AMI patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: February 2012
• Est. primary completion date: March 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

• Patients of either sex 18-85 years of age

• Women of childbearing potential or less than 2 years postmenopausal agree to use of adequate contraception during the study

• Patients with the first time diagnosis of ST elevation myocardial infarction

• Acute myocardial infarction (ST elevation in at least two leads >0.2 mV in V1, V2 or V3 or >0.1 mV in other leads), treated by one of the following: either

• Acute PCI with stent implantation

• With thrombolysis within 12 hr of symptom onset followed by PCI with stent implantation within 24 hr after Thrombolysis

• Maximal creatine kinase elevation >400 U/l with significant membrane-bound fraction (>6%)or troponin >2X ULN

• Decreasing levels of CK/CK-MB or troponin following reperfusion

• Successful acute PCI/stent implantation (residual stenosis visually <30% and TIMI flow >2). Absence of severe disorder of the microcirculation (e.g. pulsatile flow pattern, systolic flow reversal) at the time of administration of the trial therapy

• Significant regional wall motion abnormality in left ventricular angiogram or transthoracic echocardiogram =48 hours post PCI

• LVEF between 30 and 45% by LV gram after the primary PCI or transthoracic echocardiogram =48 hours post PCI

• Willing and able to comply with the scheduled visits, treatment, laboratory tests and other study related procedures.

• Signed informed consent

Exclusion Criteria:

• Prior cardiovascular history

• Mechanical complications of the index acute myocardial infarction including but not limited to rupture of the mitral valve with resultant development of mitral regurgitation, rupture of the left ventricular free wall and rupture of the interventricular septum

• Pregnant or lactating

• Known allergy to contrast agents

• Known allergy or religious objections to bovine or porcine products

• History of malignancy of any type except non-melanoma skin cancer

• Presence of major hematological conditions or laboratory abnormalities (low hemoglobin (<10 gm/dl), - WBC (<3,000 cells/mm2) or platelet count (<100,000 cells/mm3))

• Prothrombin time (PT) > 1x ULN

• Partial thromboplastin time (PTT) > 1x ULN

• Presence of chronic systemic inflammatory disorders that requires ongoing therapy

• Previous autologous, allogeneic bone marrow or peripheral stem cell transplant

• Prior solid organ transplantation

• Immune system compromise including but not limited to history of human immunodeficiency virus (HIV), hepatitis B (HBV) and hepatitis C (HCV) infection.

• Prior participation in any other study involving investigational pharmacological agents(s), devices or marketed products within 30 days prior to planned AMI MultiStem® administration

• Life expectancy of six months or less

• Current alcohol or substance abuse

• Ongoing systemic infection

• Renal function: Serum creatinine >2 mg/dL or creatinine clearance =50 mL/min

• Hepatic function: Screening ALT and AST =3x upper limit of normal for the laboratory or total bilirubin =2.0 mg/dL (exception: acceptable if patient is identified with pre existing condition e.g. Gilbert's disease that will contribute to baseline elevations of bilirubin)

• Other serious medical or psychiatric illness that, in the investigator's opinion, would not permit the patient to be managed according to the protocol.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Myocardial Infarction
• Infarction
• Myocardial Infarction

Intervention

Biological:
• AMI MultiStem®
AMI MultiStem® administered via catheter into peri-vascular space of the target vessel, 2-5 days post PCI. There will be 3 dose escalation cohorts, 6 patients per cohort.

Locations

Country	Name	City	State
United States	Cardiology PC	Birmingham	Alabama
United States	Cleveland Clinic	Cleveland	Ohio
United States	Metro Health	Cleveland	Ohio
United States	Henry Ford Hospital	Detroit	Michigan
United States	Hamot Medical Center	Erie	Pennsylvania
United States	The Care Group	Indianapolis	Indiana
United States	Columbia University Medical Center	New York	New York

Sponsors (3)

Lead Sponsor	Collaborator
Athersys, Inc	Angiotech Pharmaceuticals, PPD

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of adverse events during the first 24 hours after administration of AMI MultiStem® and post acute adverse events up to 30 days following AMI		30 days	Yes
Secondary	Evaluation of longer term safety and cardiac function over 12 months following AMI		12 months	Yes