In December 2013, the Company completed enrollment in its PreSERVE AMI study. PreSERVE AMI is a randomized, double-blind, placebo-controlled clinical trial of intracoronary infusion of autologous CD34 cells in patients with left ventricular dysfunction post-ST elevation myocardial infarction (STEMI). The trial included 161 subjects at 60 sites in the United States, randomized 1:1 between treatment and placebo arms.
Eligible patients presented with acute STEMI, had successful stenting of the infarct-related artery and had left ventricular dysfunction 4 days after AMI.
Primary endpoints include occurrence of SAEs and MACE (defined as cardiovascular death, re-infarction, heart failure hospitalization, and
coronary revascularization) through 3 year follow-up, occurrence of SAEs through 3 year follow-up, and 6-month change in myocardial perfusion (RTSS) measured quantitatively by gated SPECT myocardial perfusion imaging. Other endpoints include cardiovascular magnetic imaging resonance (CMR) to measure left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), left ventricular end-systolic diameter (LVEDV), regional myocardial strain, infarct/peri-infarct regional wall motion abnormalities and infarct size (baseline and six months) and quality of life measures (KCCQ and SAQ). While all 6 month data has been collected, it is subject to ongoing analysis, and results reported at this time, although promising, are preliminary. There can be no assurance that further analysis may not reveal negative, or less promising, results.
NBS10 – Phase 1 Clinical Trial Summary
The Company reported results of a Phase 1 study of NBS10 treating 31 patients with damaged heart muscle following AMI In December 2010. The completed Phase 1 study of NBS10 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.