Phase I Clinical Trial for BB3

BB3的I期临床试验

• 批准号: 7790232
• 负责人: WEIZHONG CAI
• 金额: $ 8.2万
• 依托单位: ANGION BIOMEDICA CORPORATION
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-01-15 至 2009-07-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7790232
• 关键词: Acute myocardial infarction; Adjuvant; Apoptotic; Applications Grants; Arrhythmia; Attenuated; Biological Assay; Businesses; Cardiac Myocytes; Cell Survival; Cerebrum; Cessation of life; Clinic; Clinical; Clinical Research; Clinical Trials; Consult; Data; Development; Doctor of Philosophy; Dose; Drug Kinetics; FDA approved; Failure; Funding; Future; Genes; Grant; Half-Life; Heart; Hepatic; Hepatocyte Growth Factor; Hospitals; Hour; Immune; Infarction; Inflammatory Response; Infusion procedures; Injury; Ischemia; Kidney; Knowledge; Laboratories; Leadership; Letters; Liver diseases; Maximum Tolerated Dose; Measures; Medicine; Modeling; Myocardial Infarction; Myocardial Ischemia; Myocardial tissue; Myocardium; Necrosis; New York; Organ; Patients; Personnel Staffing; Pharmaceutical Preparations; Pharmacists; Pharmacology; Pharmacy facility; Phase; Phase I Clinical Trials; Placebo Control; Positioning Attribute; Program Development; Proteins; Randomized; Reperfusion Injury; Reperfusion Therapy; Research; Safety; Simulate; Solutions; Specific qualifier value; Testing; Tissues; Toxicology; Translational Research; United States National Institutes of Health; base; blind; cost; design; experience; improved; in vivo; innovation; medical schools; mimetics; novel; outcome forecast; percutaneous coronary intervention; pre-clinical; prevent; professor; programs; prophylactic; small molecule

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.

描述（申请人提供）：经皮冠状动脉介入治疗已成为st段抬高型心肌梗死（STEMI）的主流治疗方法。早期再通无疑可以挽救心肌组织，但长时间缺血后的再灌注会加重损伤。梗死面积需要限制，因为急性心肌梗死（AMI）患者如果没有死于院外心律失常，其长期预后取决于损失的心肌面积。在再通过程中，这些患者可能从辅助心脏保护策略中获益。