Safety of Allogeneic Cardiosphere-Derived Cells for Acute Myocardial Infarction

同种异体心肌球衍生细胞治疗急性心肌梗死的安全性

• 批准号: 8494382
• 负责人: Rachel Ruckdeschel Smith
• 金额: $ 99.99万
• 依托单位: CAPRICOR, INC.
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8494382
• 关键词: Acute; Acute myocardial infarction; Adenosine; Affect; Aftercare; Allogenic; American; Animal Model; Anterior; Arrhythmia; Attenuated; Autologous; Award; Biological Assay; Blood flow; Businesses; Cardiac; Cardiotonic Agents; Cardiovascular Diseases; Cause of Death; Cell Therapy; Cells; Chronic; Cicatrix; Clinical; Clinical Data; Clinical Protocols; Clinical Trials; Coronary artery; Cryopreservation; Cyclosporine; Data; Development; Disease; Double-Blind Method; EFRAC; Enrollment; Ensure; Enzymes; Event; Funding; Future; Glean; Goals; Gold; HLA Antigens; Heart failure; Hour; Immune; Immunosuppression; Infarction; Inflammation; Infusion procedures; Injury; Intervention; Investigational New Drug Application; Lead; Left; Left Ventricular Dysfunction; Left Ventricular Remodeling; Licensing; Life; Magnetic Resonance Imaging; Marketing; Myocardial; Myocardial Infarction; Myocardial perfusion; Myocardium; National Heart, Lung, and Blood Institute; Natural regeneration; Patients; Phase I Clinical Trials; Placebo Control; Population; Positioning Attribute; Preclinical Testing; Prevention; Process; Product Approvals; Protocols documentation; Quality Control; Randomized; Reaction; Reperfusion Therapy; Resolution; Safety; Secure; Series; Small Business Innovation Research Grant; Source; Surrogate Endpoint; Symptoms; System; Testing; Time; Tissues; United States; United States Food and Drug Administration; United States National Institutes of Health; Ventricular; abstracting; base; clinical research site; cohort; commercialization; design; effective therapy; experience; falls; immunological status; man; manufacturing process; meetings; mortality; open label; patient population; percutaneous coronary intervention; pre-clinical; public health relevance; regenerative; regenerative agent; regenerative therapy; response; restoration; safety testing; scale up; sound; standard care; success

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.

描述（由申请人提供）：项目摘要：Capricor，Inc。具有同种异体细胞治疗产品，CAP-1002，目前在临床开发中。 CAP-1002由心圈衍生的细胞（CDC）组成，该细胞是从与接受者无关的供体生长的，使用专有的过程，专有授予Capricor。自体CDC已证明其作为再生剂的实用性：能够降低梗塞大小（又称疤痕尺寸），增加可行的组织质量，并减轻对心肌梗死（MI）几个月后给患者施用时降低不良的左心室（LV）重塑。在经CDC处理的患者中看到的好处的大小可以预示将来的不良临床事件减少。当前，在随机，双盲，安慰剂对照，多中心的安全性和有效性研究中，在类似的MI后人群中进行了同种异体CDC。当前的提案旨在测试 CAP-1002在急性MI设置中施用，对金标准治疗的辅助（即PCI [经皮冠状动脉干预]），恢复血流（或再灌注）后迅速作为心脏保护剂。 Capricor具有经过批准的IND（研究新药应用），用于在MI后使用CAP-1002在治疗和/或预防LV功能障碍中，并且拟议的临床试验属于此适应症的保护。王状会数据支持在急性MI中安全使用CAP-1002，并揭示产品限制梗塞的能力 大小并减少急性心肌损伤。 CAP-1002是在现有的GMP（符合制造实践）设施中制造的，并将存储在临床现场以立即可用。配制了CAP-1002，以便可以在几分钟内准备就绪并在几分钟内进行管理。在成功再灌注后数小时内，将用CAP-1002对患者进行开放标签。安全终点将包括评估冠状动脉的血流和微脉管系统，心肌损伤的分辨率，免疫反应，心律不齐和狼牙棒（主要心脏不良事件）。功效评估将检查MRI（磁共振成像）的梗塞大小，LV体积和射血分数。将同时进行后续审判的资金。代言人对下一项研究的融资良好，尤其是在互补的患者人群中使用相同产品的一项持续的多中心研究。该公司具有合理的监管策略和顾问，以指导与FDA（食品和药物管理局）的互动，因为CAP-1002已获得批准。当前的制造规模和设施将足以通过早期商业化来实现，并且计划扩大计划。 Capricor已经确定了进入公共市场并维持积极业务发展工作的几种潜在途径。该公司预计将在项目完成后的几年内产生收入。持续的和拟议的临床试验系列涵盖了MI后几乎全部疾病状态的连续体。 CAP-1002为所有MI患者成功开发，将根据需要提供心脏保护和再生疗法。