ACT34-CMI -- Adult Autologous CD34+ Cells

A DB, Randomized, Placebo-controlled Study of the Tolerability, Efficacy, Safety, and Dose Range of Intramyocardial CLBS14 for Reduction of Angina Episodes in Patients With Refractory Chronic Myocardial Ischemia (ACT34-CMI)

The purpose of this study is to evaluate the efficacy and safety of intramyocardial injections of CLBS14 in patients with refractory chronic myocardial ischemia.

This is a double-blind, prospective, randomized, placebo-controlled trial to determine the tolerability, efficacy, safety and dose range of intramyocardial injections of adult autologous CD34+ cells mobilized with granulocyte colony stimulating factor (G-CSF) for the reduction of angina episodes in patients with refractory chronic myocardial ischemia.

Inclusion Criteria:

• Canadian Cardiovascular Society (CCS) functional class III or IV chronic refractory angina
• subjects without control of their angina symptoms, in spite of maximal tolerated doses of anti-anginal drugs, must be on optimal therapy for their angina and on a stable anti-anginal medication regimen for at least 1 month prior to entering the screening period of the study
• identified as unsuitable for conventional revascularization
• recent coronary angiogram (within the last 12 months) to document the coronary anatomy and to verify the revascularization procedures
• subjects must have objective evidence of inducible ischemia or viable myocardium in the potential target injection zone
• a left ventricular ejection fraction equal to or greater than 25% by ECHO or single photon emission computed tomography (SPECT) at screening
• subjects must experience at minimum an average of 7 angina or anginal equivalent episodes per week
• subjects must be able to complete a minimum of 3 minutes but nor more than 10 minutes on a treadmill following the Modified Bruce Protocol
• subjects must experience angina or anginal equivalent episodes during the screening exercise treadmill test
• female subjects must either be no longer capable of reproduction or using medically valid contraception to prevent pregnancy during the study
• subjects must be willing and able to comply with specified follow-up evaluations

Exclusion Criteria:

• predominant congestive heart failure
• myocardial infarction within 60 days of treatment
• successful or partially successful coronary revascularization procedures (any vessel) within 6 months of study enrollment
• placement of a bi-ventricular pacemaker for cardiac resynchronization therapy (CRT) for heart failure in the past 90 days
• documented stroke or transient ischemic attack (TIA) within 60 days of study enrollment
• history of moderate to severe aortic stenosis or severe aortic insufficiency; severe mitral stenosis or severe mitral insufficiency
• prosthetic aortic valve replacement
• evidence of any life-threatening arrhythmia that requires intervention on the 24-hour Holter monitor. Life-threatening arrhythmia that is successfully treated with an implantable cardioverter defibrillator (ICD) is not exclusionary.
• splenomegaly and/or severe co-morbidity associated with a reduction in life expectancy of less than 1 year, such as chronic medical illness (ie, severe chronic obstructive pulmonary disease, renal failure or cancer [exceptions: in-situ skin cancer or fully removed skin cancer other than melanoma, in-situ cervical cancer, or cancer free for 5 years with no history of a stem cell transplant])
• sickle cell disease or sickle cell trait
• platelet count greater than 10% above the upper limit of normal or a platelet count below 100,000 if on Clopidogrel or 50,000 without Clopidogrel
• hematocrit <30%
• serum creatinine >2.5 mg/dL
• any clinically significant laboratory abnormality on screening laboratories
• currently enrolled in another IDE or IND that has not completed the protocol required primary follow-up period (excludes 15 year follow up of gene therapy trials)
• history of alcohol or drug abuse within 3 months of screening
• joint or peripheral vascular disease or neurologic disease that severely limits treadmill walking
• chronic obstructive pulmonary disease that severely limits walking or FEV1 <30% predicted
• females who are pregnant or lactating
• female subjects who are capable of reproduction and will not use medically valid contraception to prevent pregnancy during the study
• subjects who test positive for HIV, hepatitis B or hepatitis C, or are on chronic immunosuppressive medications or have had a prior stem cell transplant
• subjects with a known hypersensitivity to E. coli-derived proteins, or to any component of Neupogen (Filgrastim) or G-CSF
• subjects who have a significant psychiatric disorder or mental disability that could interfere with the subject´s ability to provide informed consent and/or comply with protocol procedures