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

项目摘要/摘要 注射用氯化血红素(Panhematin，Lundbeck)是根据《孤儿药品法》批准的第一种药物。其 1971年批准的改善急性间歇性卟啉病急性发作的批准是基于发表的 在许多个别病例和病例系列中关于生化疗效和明显益处的报道，而不是 充足的、随机、对照的研究。因此，它的有效性一直存在疑问。 尤其是在循证医学的时代。此外，狭隘的批准适应症(仅限患有 循环攻击)，葡萄糖负荷初始试验的要求，1-4毫克/公斤的宽剂量范围，以及 用无菌水重建冻干品的方法影响了其临床应用。它是 越来越认识到，需要更多的临床研究来解决这些长期存在的问题，并 产品标签与目前的专家建议之间存在相当大的差距。第二阶段研究将进行 由Porporrias 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白血病的证据基础 门静脉性发作。这项随机、盲目、安慰剂对照的研究将比较治疗和 泛血定每日4 mg/kg加葡萄糖治疗30~40例 卟啉症的急性发作。财团调查人员有在以下方面进行对照研究的经验 卟啉症，包括对急性发作患者的研究。RDCRN支持研究的发展 材料、基于Web的数据输入、数据仓库和多个研究站点的监控，并具有 建立了数据和安全监测委员会。制造商已承诺为这项研究提供药物。这个 美国卟啉症基金会，一个长期而有效的患者支持组织，也是 财团将协助招募病人。所有地点的基础设施将包括由NIH资助的设施 临床和翻译科学奖。调查员IND申请(IND编号13,929)已获批准。 正在进行一项分析研究，以评估Panhematin在预防门脉性疾病发作中的使用。 因为使用这种药物的证据更少。此外，单患者控制的交叉 计划进行研究以解决这样一个问题，即对预防方案的反应是可变的、不可预测的 而且很难对个别患者进行评估。该项目将提供首个高质量的疗效证据。 和安全性被认为是最重要的可用的治疗急性卟啉发作的药物。

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.