Prevention of Delayed Cerebral Vasospasm Associated with Subarachnoid Hemorrhage

蛛网膜下腔出血相关迟发性脑血管痉挛的预防

• 批准号: 7537956
• 负责人: Craig Sherman
• 金额: $ 10万
• 依托单位: HOPE PHARMACEUTICALS
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-02-15 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7537956
• 关键词: Accounting; Acidosis; Admission activity; Affect; Agreement; Alternative Therapies; Applications Grants; Area; Blood flow; Businesses; Cerebrovascular Spasm; Cessation of life; Chemistry; Clinical; Clinical Research; Clinical Trials; Cognitive; Complication; Continuous Intravenous Infusion; Development; Documentation; Dose; Drug Approval Processes; Drug Kinetics; Enrollment; Evaluation; Glass; Goals; Grant; Hour; Hypotension; Hypoxia; Incidence; Infusion procedures; Injection of therapeutic agent; Institutes; Intensive Care; Intravenous; Intravenous infusion procedures; Investigational Drugs; Left; Legal patent; Length of Stay; Licensing; Life; Marketing; Maximum Tolerated Dose; Medical; Monitor; Morbidity - disease rate; Neurologic; Neurological outcome; Neurological status; Neurology; Nitrites; Obstruction; Orphan; Outcome; Patients; Pharmacologic Substance; Phase; Phase I Clinical Trials; Phase II Clinical Trials; Prevention; Property; Reporting; Research Personnel; Rights; Risk; Safety; Saline; Severities; Sodium Nitrite; Solutions; Sterility; Stroke; Subarachnoid Hemorrhage; Suggestion; Survivors; Time; Treatment Efficacy; Treatment Protocols; United States; United States Food and Drug Administration; United States National Institutes of Health; Vasodilation; Vasodilator Agents; Vasospasm; Vial device; clinical efficacy; design; disability; experience; functional disability; healthy volunteer; insight; meetings; mortality; nervous system disorder; outcome forecast; pre-clinical; prevent; public health relevance; research and development; therapy design; treatment duration; volunteer

DESCRIPTION (provided by applicant): Hope Pharmaceuticals (Hope) is a Small Business that distributes a limited line of proprietary pharmaceuticals. In 2007, Hope licensed from the National Institutes of Health (NIH) exclusive, worldwide rights to two pending patent applications for recently discovered clinical uses for Sodium Nitrite, including in the area of neurology. Since it currently markets Sodium Nitrite Injection, Hope has the immediate advantage of existing pre-clinical information along with trade secrets about the product chemistry and manufacture. Hope's goal is to leverage this expertise in order to obtain regulatory approval for new treatments as quickly as possible. Using Hope's product in several of its studies, researchers at the NIH discovered that the administration of Sodium Nitrite can achieve localized vasodilation precisely in areas where blood flow has been compromised. No targeted vasodilator exists on the market at present. All current vasodilators act systemically and must be monitored carefully to prevent life-threatening hypotension. Sodium Nitrite may be especially beneficial for conditions that involve focal obstructions of blood flow, that are associated with high mortality, and that have no existing treatments such as cerebral vasospasm associated with subarachnoid hemorrhage. Subarachnoid hemorrhage (SAH) accounts for approximately 5% of all new strokes. In the United States, it affects approximately 33,000 people each year and is associated with high rates of mortality ranging between 30 and 70% depending on severity. It is also associated with significant morbidity in survivors with nearly 50% of survivors experiencing cognitive and/or functional impairments. Cerebral vasospasm is a common complication following SAH. The outcome for those with symptomatic vasospasm is horrific. As many as one-third of these patients die and another third are left with permanent and severe disabilities. Acknowledging the serious unmet medical needs associated with this condition, the Food and Drug Administration (FDA) granted "Fast Track" status and "Orphan Product" designation to Hope's development of Sodium Nitrite Injection for the treatment of cerebral vasospasm associated with SAH. Hope and the National Institute of Neurological Diseases and Stroke (NINDS) executed a Collaborative Research and Development Agreement to conduct clinical development. Under Investigational New Drug (IND) #77,633, the parties initiated a Phase 1 clinical study in July 2007 to investigate the safety and pharmacokinetics of a 48-hour intravenous nitrite infusion in healthy volunteers. As of December 1, 2007, the clinical component of this study will be completed with the enrollment and dosing of five additional patients. Using the insights gained from the Phase 1 study, Hope and NINDS are planning Phase 2 clinical trials as further evaluation of the safety and efficacy of Sodium Nitrite Injection for the prevention of delayed cerebral vasospasm and the improvement of neurological outcomes after subarachnoid hemorrhage. This grant application is intended to support these Phase 2 clinical trials. PUBLIC HEALTH RELEVANCE: Delayed cerebral vasospasm (DCV) is a serious complication associated with subarachnoid hemorrhage (SAH). DCV occurs in over half of the patients that survive SAH and frequently causes significant disability or death. Hope Pharmaceuticals' objective is to conduct clinical studies to confirm the safety and efficacy of Sodium Nitrite as a new, safe, inexpensive, and rationally designed therapy to prevent this condition and thereby reduce the horrific morbidity and mortality sustained by patients who suffer a subarachnoid hemorrhage.

描述（由申请人提供）：希望制药（希望）是一家小型企业，分销有限的专利药品。2007年，Hope从美国国立卫生研究院（NIH）获得了两项正在申请的专利申请的独家全球权利，这些专利申请是最近发现的亚硝酸钠临床用途，包括神经病学领域。由于Hope目前销售亚硝酸钠注射液，因此Hope具有现有临床前信息的直接优势，沿着有关于产品化学和生产的商业机密。Hope的目标是利用这些专业知识，尽快获得监管机构对新疗法的批准。在几项研究中使用Hope的产品，NIH的研究人员发现，亚硝酸钠的施用可以在血流受损的区域精确地实现局部血管舒张。目前市场上没有靶向血管扩张剂。目前所有的血管扩张剂都是全身性的，必须仔细监测，以防止危及生命的低血压。亚硝酸钠可能对涉及局灶性血流阻塞、与高死亡率相关以及没有现有治疗方法的疾病（如与蛛网膜下腔出血相关的脑血管痉挛）特别有益。蛛网膜下腔出血（SAH）约占所有新发卒中的5%。在美国，它每年影响大约33，000人，并与高死亡率相关，根据严重程度，死亡率在30%至70%之间。它还与幸存者的显著发病率相关，近50%的幸存者经历认知和/或功能障碍。脑血管痉挛是蛛网膜下腔出血后常见的并发症。症状性血管痉挛的结果是可怕的。这些患者中有多达三分之一死亡，另外三分之一留下永久性和严重残疾。认识到与这种情况相关的严重未满足的医疗需求，美国食品药品监督管理局（FDA）授予Hope开发的亚硝酸钠注射液治疗SAH相关脑血管痉挛的“快速通道”状态和“孤儿产品”称号。Hope和国家神经疾病和中风研究所（NINDS）执行了一项合作研究和开发协议，以进行临床开发。根据新药临床试验（IND）编号77，633，双方于2007年7月启动了一项1期临床研究，以调查健康志愿者48小时静脉输注亚硝酸盐的安全性和药代动力学。截至2007年12月1日，本研究的临床部分将完成，另外5例患者将入组和给药。利用从1期研究中获得的见解，Hope和NINDS正在计划2期临床试验，以进一步评估亚硝酸钠注射液预防迟发性脑血管痉挛和改善蛛网膜下腔出血后神经功能结局的安全性和有效性。该资助申请旨在支持这些2期临床试验。公共卫生相关性：迟发性脑血管痉挛（DCV）是与蛛网膜下腔出血（SAH）相关的严重并发症。超过一半的SAH患者发生DCV，并经常导致严重残疾或死亡。Hope Pharmaceuticals的目标是进行临床研究，以确认亚硝酸钠作为一种新的，安全的，廉价的，合理设计的治疗方法的安全性和有效性，以预防这种情况，从而降低蛛网膜下腔出血患者的可怕发病率和死亡率。