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

血红素治疗和预防卟啉症发作的 2 期研究

• 批准号: 8569008
• 负责人: KARL ELMO ANDERSON
• 金额: $ 33.95万
• 依托单位: UNIVERSITY OF TEXAS MED BR GALVESTON
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-16 至 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8569008
• 关键词: Phase; Study; Hemin; Treatment; Prevention

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.

项目摘要/摘要 注射Hemin（Panhematin”，Lundbeck）是根据《孤儿药物法》批准的第一个药物。 1971年批准急性间歇性卟啉症的急性攻击是基于发表的 在许多个别情况和病例系列中，生化疗效和明显利益的报告，而不是 足够的动力，随机，对照研究。因此，其功效仍然存在 特别是在循证医学时代。此外，批准的迹象狭窄（只有 循环攻击），对葡萄糖负荷初步试验的要求，1-4 mg/kg的宽剂量范围和A 用无菌水重构冻干产物的方法损害了其临床用途。这是 越来越认识到需要其他临床研究来解决这些长期存在的问题和 产品标签与当前专家建议之间的差异很大。 2期研究是 由卟啉财团中的至少5个中心进行（由NIDDK支持和NIH的一部分稀有 疾病临床研究网络-RDCRN）旨在改善这种急性治疗方法的证据基础 斑岩攻击。这项随机，盲目的安慰剂对照研究将将治疗与 PANHEMATIN“每天4 mg/kg加葡萄糖4天，仅在30-40例患者中单独用葡萄糖治疗 卟啉症的急性攻击。财团调查员有进行对照研究的经验 卟啉症，包括对急性攻击患者的研究。 RDCRN支持研究的发展 材料，基于Web的数据输入，数据仓库和在多个研究站点进行监视，并具有 建立了数据和安全监控委员会。制造商已将药物用于研究。这 American Porphyria Foundation是一个长期有效的患者支持小组，也是该基金会的一部分 财团将有助于患者招募。所有站点的基础设施都将包括NIH资助的设施 临床和转化科学奖。研究人员的IND申请（IND＃13,929）已批准。 正在开发一项肛门研究，以评估全甲蛋白的使用“用于预防斑岩攻击， 由于这种使用该药物的证据甚至更少。另外，单人受控跨界 计划研究对预防疗法的反应是可变的，不可预测的问题 很难评估个别患者。该项目将为功效提供第一个高质量证据 该药物的安全性被视为卟啉症急性攻击的最重要的治疗方法。