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: 8010936
• 负责人: Craig Sherman
• 金额: $ 100万
• 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 2012-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8010936
• 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; Health; 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; Regimen; Reporting; Research Personnel; Rights; Risk; Safety; Saline; Severities; Sodium Nitrite; Solutions; Sterility; Stroke; Subarachnoid Hemorrhage; Suggestion; Survivors; Time; Treatment Efficacy; 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; phase 1 study; phase 2 study; pre-clinical; prevent; 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）： Hope Pharmaceuticals (Hope) 是一家小型企业，经销有限系列的专有药品。 2007 年，Hope 获得了美国国立卫生研究院 (NIH) 的全球独家权利，获得两项正在申请的专利，这些专利申请涉及最近发现的亚硝酸钠的临床用途，包括在神经病学领域的用途。由于目前销售亚硝酸钠注射液，Hope 可以立即利用现有的临床前信息以及有关产品化学和制造的商业秘密。 Hope 的目标是利用这些专业知识，尽快获得新疗法的监管批准。美国国立卫生研究院的研究人员在多项研究中使用了 Hope 的产品，发现使用亚硝酸钠可以在血流受损的区域精确地实现局部血管舒张。目前市场上尚无靶向血管扩张剂。目前所有的血管扩张剂都是系统性作用的，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血流局灶性阻塞、与高死亡率相关且尚无现有治疗方法（例如与蛛网膜下腔出血相关的脑血管痉挛）的疾病特别有益。蛛网膜下腔出血 (SAH) 约占所有新发中风的 5%。在美国，它每年影响约 33,000 人，根据严重程度，死亡率高达 30% 至 70%。它还与幸存者的显着发病率相关，近 50% 的幸存者出现认知和/或功能障碍。脑血管痉挛是 SAH 后常见的并发症。对于有症状的血管痉挛患者来说，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的残疾。认识到与这种情况相关的严重未满足的医疗需求，美国食品和药物管理局 (FDA) 授予 Hope 开发的亚硝酸钠注射液用于治疗 SAH 相关脑血管痉挛的“快速通道”地位和“孤儿产品”称号。 Hope 和国家神经疾病和中风研究所 (NINDS) 签署了一项合作研究和开发协议来进行临床开发。根据研究性新药 (IND) #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 小时静脉注射亚硝酸盐的安全性和药代动力学。截至 2007 年 12 月 1 日，该研究的临床部分将随着另外 5 名患者的入组和给药而完成。利用第一阶段研究获得的见解，Hope 和 NINDS 正在计划第二阶段临床试验，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系统结局的安全性和有效性。该拨款申请旨在支持这些二期临床试验。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。 DCV 发生在超过一半的 SAH 存活患者中，并且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型、安全、廉价且设计合理的疗法的安全性和有效性，以预防这种情况，从而减少蛛网膜下腔出血患者的可怕发病率和死亡率。