Phase 2 Study of Hemin for Treatment and Prevention of Porphyria Attacks

项目摘要/总结 注射用氯化血红素（Panhematin，Lundbeck）是第一种根据《孤儿药法》批准的药物。其 1971年批准用于改善急性间歇性卟啉病的急性发作是基于公开的 在许多个体病例和病例系列中报告了生化疗效和明显获益， 充分把握度的随机对照研究。因此，它的有效性仍然存在疑问 尤其是在这个循证医学的时代。此外，狭窄的批准适应症（仅女性 周期性发作），需要葡萄糖负荷的初始试验，1-4 mg/kg的宽剂量范围，以及 用无菌水重构冻干产品的方法已经损害了其临床用途。是 越来越多的人认识到需要更多的临床研究来解决这些长期存在的问题， 产品标签和当前专家建议之间存在相当大的差异。一项2期研究将 由Porphyrias Consortium中的至少5个中心进行（由NIDDK和NIH Rare的一部分支持） 疾病临床研究网络- RDCRN）旨在改善这种治疗急性 斑岩攻击这项随机、设盲、安慰剂对照研究将比较 在30-40例原发性高血压患者中，“泛血红素”4 mg/kg/d+葡萄糖治疗4天与单用葡萄糖治疗相比， 卟啉症的急性发作联合体研究者具有开展对照研究的经验， 卟啉症，包括急性发作患者的研究。RDCRN支持研究的发展 材料、基于网络的数据输入、数据仓库和多个研究中心的监测， 建立了数据和安全监测委员会。生产商已承诺将药物用于研究。的 美国卟啉病基金会，一个长期有效的病人支持小组，也是 财团将协助患者招募。所有研究中心的基础设施将包括NIH资助的设施 临床和转化科学奖。研究者IND申请（IND #13，929）已获得批准。 一项镇痛研究正在开发中，以评估使用泛血红素”预防卟啉病发作， 因为这种药物的使用证据更少。此外，单患者对照交叉 计划进行研究以解决对预防方案的反应是可变的、不可预测的 并且难以对个体患者进行评估。该项目将提供第一个高质量的疗效证据 和安全性的药物被视为最重要的可用治疗急性发作的卟啉症。

PROJECT ABSTRACT/SUMMARY Hemin for injection (Panhematin", Lundbeck) was the first drug approved under the Orphan Drug Act. Its approval in 1971 for the amelioration of acute attacks of acute intermittent porphyria was based on published reports of biochemical efficacy and evident benefit in numerous individual cases and case series rather than adequately powered, randomized, controlled studies. Therefore its efficacy has remained in question especially in an era of evidence-based medicine. Moreover, the narrow approved indications (only women with cyclic attacks), a requirement for an initial trial of glucose loading, a wide dose range of 1-4 mg/kg, and a method for reconstitution of the lyophilized product with sterile water have impaired its clinical usefullness. It is increasingly recognized that additional clinical studies are needed to address these longstanding issues and considerable disparities between product labeling and current expert recommendations. A Phase 2 study to be conducted by at least 5 centers in the Porphyrias Consortium (supported by NIDDK and part of the NIH Rare Diseases Clinical Research Network - RDCRN) aims to improve the evidence base for this treatment for acute porphyric attacks. This randomized, blinded placebo-controlled study will compare treatment with Panhematin" 4 mg/kg daily plus glucose for 4 days to treatment with glucose alone in 30-40 patients with acute attacks of porphyria. The consortium investigators have experience in conducting controlled studies in porphyrias, including studies in patients with acute attacks. The RDCRN supports development of study materials, web-based data entry, data warehousing, and monitoring at multiple study sites, and has established a data and safety monitoring board. The manufacturer has committed drug for the study. The American Porphyria Foundation, a longstanding and effective patient support group that is also part of the Consortium, will assist with patient recruitment. Infrastructure at all sites will include facilities of NIH-funded Clinical and Translational Science Awards. An investigator IND application (IND#13,929) has been approved. An analgous study is being developed to assess the use of Panhematin" for prevention of porphyric attacks, since there is even less evidence for this use of the drug. Additionally, single-patient controlled crossover studies are planned to address the problem that response to a preventive regimen is variable, unpredictable and difficult to assess for individual patients. This project will provide the first high quality evidence for efficacy and safety of the drug viewed as the most important available treatment for acute attacks of porphyria.