In December 2013, the Company completed enrollment in its PreSERVE AMI study, a multicenter randomized, double-blind, placebo-controlled U.S. Phase 2 clinical trial to evaluate the efficacy and safety of a single intra-coronary infusion of at least 10 million cells of AMR-001, in patients with an acute ST elevation myocardial infarction (“STEMI”), a particular type of AMI, who are shown to have reduced heart muscle function with ejection fractions of 48% or less as measured by cardiac magnetic resonance imaging (“CMR”).
The objective of the Phase 2 study is to determine the safety and the efficacy of AMR-001 in improving cardiac function and outcomes of patients after STEMI. The primary endpoint of the study is improvement in myocardial cardiac perfusion using the resting total severity score (“RTSS”), measured by gated single photon emission computed tomography (“SPECT”) myocardial perfusion imaging (“MPI”) at six months post randomization (MPI is a non-invasive imaging test that shows how well blood flows through your heart muscle), with secondary endpoints including the occurrence of major adverse cardiac events (“MACE”) at 6, 12, 18, 24 and 36 months. MACE includes: premature death; recurrent heart attack; chronic heart failure; significant arrhythmias; and acute coronary syndrome.
Additional secondary endpoints of the study are to determine preservation of cardiac function via CMR to measure left ventricular ejection fraction (LVEF), left ventricular end systolic volume (LVESV), left ventricular end diastolic volume (LVEDV), regional myocardial strain, infarct/peri-infarct regional wall motion abnormalities, and infarct size and Quality of Life measures questionnaires such as Kansas City Cardiomyopathy Questionnaire and Seattle Angina Questionnaire. Data from this study will be released in 2H 2014.
AMR-001 – Phase 1 Clinical Trial Summary
The Company reported results of a Phase 1 study of AMR-001 treating 31 patients with damaged heart muscle following AMI In December 2010. The completed Phase 1 study of AMR-001 showed a statistically significant dose-related improvement in myocardial perfusion (the flow of blood to the heart muscle). Patients who received 10 million cells (n=5) or 15 million cells (n=4) showed statistically significant improvement in resting perfusion rates at six months as compared to patients who received 5 million cells (n=6) or the control groups (n=15), as measured by single-photon emission computerized tomography (SPECT). The study data also showed a dose-related trend towards improvement in ejection fraction (the percentage of blood pumped out of the ventricles with each heart beat), end systolic volume (the blood volume remaining in a ventricle at the end of contraction and the beginning of filling, which can be used clinically as a measurement of the adequacy of cardiac emptying), and reduction in infarct size (dead tissue caused by shutting off the blood supply).
Pre-clinical animal models of induced AMI have demonstrated that CD34/CXCR4 expressing cells migrate naturally to oxygen-deprived locations. More specifically, these cells home to the viable tissue surrounding the infarcted (dead) myocardium, known as the peri-infarct zone. Moreover, CD34/CXCR4 expressing cells have been shown to be capable of inducing the development and formation of new blood vessels over time and preventing heart cell death due to chronic ischemia (chronic ischemia can occur when one’s coronary arteries may become so narrowed that they limit the flow of blood to one’s heart all the time, even when they are at rest). Other studies have demonstrated that the CD34/CXCR4 cells that take up residence in the peri-infarct zone are likely the cell type that affects angiogenesis (the development and formation of new blood vessels), relieves ischemia (restriction of blood supply) and prevents apoptosis (cell death). Collectively, these results provided the rationale for the clinical exploration of CD34/CXCR4 expressing cells to reduce the incidence and severity of MACE events after an extensive AMI.