Safety of Allogeneic Cardiosphere-Derived Cells for Acute Myocardial Infarction

描述（由申请人提供）：项目摘要：Capricor，Inc.拥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由心球衍生细胞（CDC）组成，使用Capricor独家许可的专有工艺从与受体无关的供体中生长。自体CDC已被证明可作为一种再生剂：在心肌梗死（MI）后数月给予患者时，能够缩小梗死面积（也称为瘢痕大小），增加活组织质量，并减弱不良左心室（LV）重塑。CDC治疗患者的获益程度可能预示着未来不良临床事件的减少。同种异体CDC目前正在一项随机、双盲、安慰剂对照、多中心安全性和疗效研究中，在类似的MI后人群中进行测试。目前的建议旨在测试 CAP-1002在急性MI环境中给药，在血流恢复（或再灌注）后快速进行金标准治疗（即PCI [经皮冠状动脉介入治疗]），作为心脏保护剂。Capricor已获得CAP-1002用于治疗和/或预防MI后LV功能障碍的IND（研究性新药申请）批准，拟定的临床试验福尔斯属于该适应症范围。临床前数据支持CAP-1002在急性MI中的安全使用，并揭示了该产品限制梗死的能力。 并减少急性心肌损伤。CAP-1002在现有的GMP（符合药品生产质量管理规范）设施中生产，并将储存在临床研究中心，以供立即使用。CAP-1002的配制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的数小时内用CAP-1002进行开放标签治疗。安全性终点将包括冠状动脉和微血管中的血流评估、心肌损伤的消退、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）检查梗死面积、LV体积和射血分数。将同时为证明疗效的后续试验提供资金。Capricor有能力为下一项研究获得资金，特别是正在进行的多中心研究，该研究在互补的患者人群中使用相同的产品。该公司有一个健全的监管策略和顾问到位，以指导与FDA（食品和药物管理局）的互动，因为CAP-1002是先进的批准。目前的生产规模和设施将足以通过早期商业化，并计划扩大规模正在进行中。Capricor已经确定了几个进入公共市场的潜在途径，并保持积极的业务发展努力。该公司预计在项目完成后的几年内产生收入。正在进行的和拟议的临床试验系列几乎涵盖了MI后疾病状态的完整连续体。CAP-1002开发成功的所有MI患者将提供心脏保护和再生治疗，根据需要进行管理。

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.