Phase I Clinical Trial for BB3

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Percutaneous coronary intervention has become the mainstay for treatment of ST-segment elevation myocardial infarction (STEMI). Whereas early recanalization undoubtedly salvages myocardial tissue, reperfusion following prolonged ischemia exacerbates injury. Infarct size needs to be limited, because in patients with acute myocardial infarction (AMI) who do not die of out-of-hospital arrhythmias, long-term prognosis is dependent on the amount of myocardium that is lost. These patients could potentially benefit from use of adjuvant cardioprotective strategies during recanalization. Hepatocyte growth factor (HGF), also know as scatter factor (SF), is an endogenous cell survival factor that exerts cardioprotective effects and can potentially be harnessed for salvaging the ischemic myocardium. The feasibility of SF/HGF as gene or protein therapy however is limited by issues relating to immune and inflammatory responses evoked by adenoviral proteins, inherent instability of proteins in solution, their limited tissue half-life and the exorbitant costs associated with such therapy. We have identified and developed BB3, a novel small molecule HGF mimetic. BB3 duplicates the bioactivities of the native protein in every assay tested to date. In single cardiocyte models simulating ischemia-reperfusion injury, BB3 attenuates apoptotic and necrotic death. In the isolated perfused heart, BB3 improves postischemic function and in in vivo experimental normothermic myocardial ischemia-reperfusion, systemic BB3 administration attenuates infarct size when administered 3 hours following onset of reperfusion. BB3 also confers functional and infarct-sparing benefit in renal, hepatic and cerebral models of ischemic and/or traumatic injury, preventing transition of these organs to failure. Supported by the SBIR program, a comprehensive panel of preclinical regulatory studies comprising genotoxicology, in vivo toxicology and safety pharmacology studies for BB3 has been completed. An IND application incorporating the efficacy and safety data was submitted and approved by FDA. Based on these data, the present application is designed to determine the effects of BB3, a small molecule scatter factor/hepatocyte growth factor mimetic in a Phase I, Randomized, Single-Blind, Placebo-Controlled, Single Dose, Dose-Escalating Study in Healthy Subjects.