Safety of Allogeneic Cardiosphere-Derived Cells for Acute Myocardial Infarction

描述(由申请人提供)：项目摘要：Capricor，Inc.有一种同种异体细胞治疗产品CAP-1002，目前正在临床开发中。CAP-1002由心脏圈来源的细胞(CDCs)组成，这些细胞来自与接受者无关的捐赠者，使用Capricor独家许可的专利过程。自体CDCs作为一种再生剂已被证明是有用的：在心肌梗死(MI)几个月后给患者使用时，能够缩小梗死范围(也就是疤痕大小)，增加存活的组织块，并减轻不利的左心室(LV)重构。在接受CDC治疗的患者中看到的益处的大小可能预示着未来不良临床事件的减少。同种异体疾控细胞目前正在类似的心肌梗死后人群中进行随机、双盲、安慰剂对照、多中心安全性和有效性研究。目前的提案旨在测试以下设备的安全性 CAP-1002在急性心肌梗死情况下，作为黄金标准治疗(即经皮冠状动脉介入治疗)的补充，在血流恢复(或再灌流)后迅速给予，作为心脏保护剂。Capricor拥有批准的IND(研究新药申请)，用于使用CAP-1002治疗和/或预防心肌梗塞后的左心功能障碍，拟议的临床试验属于这一适应症的范畴。临床前数据支持CAP-1002在急性心肌梗死中的安全使用，并揭示了该产品限制梗塞的能力 大小和减少急性心肌损伤。CAP-1002是在现有的GMP(符合良好制造规范)设施中制造的，将储存在临床现场立即可用。CAP-1002的配方使得它可以在几分钟内准备好使用，并在几分钟内给药。患者将在成功再灌注后数小时内接受CAP-1002的开放标签治疗。安全终点将包括评估冠状动脉和微血管中的血流、解决心肌损伤、免疫反应、心律失常和MACE(主要不良心脏事件)。疗效评估将通过MRI(磁共振成像)检查梗塞范围、左室容量和射血分数。将同时为证明疗效的后续试验提供资金。Capricor处于有利地位，可以为下一项研究获得资金，特别是正在进行的一项在互补患者群体中使用相同产品的多中心研究。随着CAP-1002获得批准，该公司拥有完善的监管战略和顾问，以指导与FDA(食品和药物管理局)的互动。目前的制造规模和设施通过早期商业化就足够了，扩大规模的计划正在进行中。Capricor已经确定了进入公开市场的几个潜在途径，并保持着积极的业务发展努力。该公司预计在项目完成后几年内就能产生收入。正在进行的和拟议的临床试验系列几乎涵盖了心肌梗塞后的所有疾病状态。为所有心肌梗死患者成功开发的CAP-1002将提供心脏保护和再生治疗，根据需要给予治疗。

DESCRIPTION (provided by applicant): Project Abstract: Capricor, Inc. has an allogeneic cell therapy product, CAP-1002, presently in clinical development. CAP-1002 consists of cardiosphere-derived cells (CDCs), grown from a donor unrelated to the recipient, using a proprietary process exclusively licensed to Capricor. Autologous CDCs have demonstrated their utility as a regenerative agent: able to reduce infarct size (a.k.a scar size), add viable tissue mass, and attenuate adverse left ventricular (LV) remodeling when administered to patients several months after a myocardial infarction (MI). The magnitude of benefit seen in CDC-treated patients could foreshadow a reduction in future adverse clinical events. Allogeneic CDCs are currently being tested in a similar post-MI population in a randomized, double-blinded, placebo-controlled, multi-center safety and efficacy study. The current proposal aims to test the safety of CAP-1002 administered in the acute MI setting, adjunctive to the gold-standard treatment (i.e. PCI [percutaneous coronary intervention]), rapidly after restoration of blood flow (or reperfusion), as a cardioprotective agent. Capricor has an approved IND (Investigational New Drug application) for the use of CAP-1002 in the treatment and/or prevention of LV dysfunction following MI, and the proposed clinical trial falls under the umbrella of this indication. Preclinial data support the safe use of CAP-1002 in acute MI and reveal the product's ability to limit infarct size and reduce acute myocardial damage. CAP-1002 is manufactured in an existing GMP (Good Manufacturing Practice compliant) facility and will be stored at the clinical site for immediate availability. CAP-1002 is formulated such that it can be prepared for use within minutes and administered within minutes. Patients will be treated open-label with CAP-1002 within hours of successful reperfusion. Safety endpoints will include assessments of blood flow in the coronary arteries and microvasculature, resolution of myocardial damage, immune reaction, arrhythmias, and MACE (major adverse cardiac events). Efficacy assessments will examine infarct size, LV volumes, and ejection fraction by MRI (magnetic resonance imaging). Funding for a follow-on trial that would demonstrate efficacy will be pursued concurrently. Capricor is well-positioned to secure financing for the next study, particularly with an ongoing multi-center study utilizing the same product in a complementary patient population. The company has a sound regulatory strategy and advisors in place to guide interactions with the FDA (Food and Drug Administration) as CAP-1002 is advanced toward approval. The current manufacturing scale and facility will suffice through early commercialization and plans to scale up are underway. Capricor has identified several potential avenues by which to enter the public market and maintains active business development efforts. The company anticipates being revenue generating within a few years of project completion. The ongoing and proposed clinical trial series encompass nearly the full continuum of disease states following MI. CAP-1002 developed successfully for all MI patients would offer both a cardioprotective and regenerative therapy, to be administered as needed.