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

描述（由申请人提供）： 这是一项2期、随机、盲法对照研究，在30-40例卟啉症急性发作患者中比较每日4 mg/kg氯化血红素加葡萄糖治疗4天与单独葡萄糖治疗。 该研究将在卟啉病联盟的多个地点进行，旨在改善这种治疗急性卟啉病发作的证据基础。该联盟的研究人员有进行卟啉病对照研究的经验，包括对急性发作患者的研究。美国国立卫生研究院（NIH）罕见病临床研究网络支持研究材料的开发，基于网络的数据输入，数据仓库和多个研究中心的监测，并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。美国卟啉病基金会是一个长期有效的患者支持团体，也是该联盟的一部分，将协助招募患者。所有研究中心的基础设施将包括NIH资助的临床和转化科学奖的设施。该提案的具体目的是：1）通过在30-40例有充分记录的急性卟啉症患者中进行双盲安慰剂对照的2期临床试验，为人氯化血红素治疗卟啉症急性发作的疗效提供证据;（二）为了获得研究样本，旨在通过研究更好地了解氯化血红素在卟啉症中的有益作用机制，血红素途径酶基因和热休克及应激反应基因在急性卟啉病患者治疗前后的调节。这将是与北卡罗来纳州夏洛特的Broninus医学中心的赫伯特邦科夫斯基博士合作进行的; 3）通过在20名有充分记录的急性卟啉症患者中进行双盲安慰剂对照的2期临床试验，为氯高铁血红素预防卟啉症复发的有效性和安全性提供证据; 4）探索盲法安慰剂对照交叉方法评估氯化血红素对急性卟啉症个体患者疗效的可行性和实用性。 次要和探索性目的将包括比较Panhematin和葡萄糖的生化作用，以评价临床特征（如性别、年龄和促使卟啉病发作的因素）对Panhematin和葡萄糖反应的影响，以评价遗传特征（包括性质或潜在突变）对Panhematin治疗反应的影响，探讨25%人血白蛋白重组血红素在卟啉病急性发作中的应用。

DESCRIPTION (provided by applicant): This is a Phase 2, randomized, blinded controlled study to compare treatment with Hemin 4 mg/kg daily plus glucose for 4 days to treatment with glucose alone in 30-40 patients with acute attacks of porphyria. The study will be conducted at multiple sites in the Porphyrias Consortium and aims to improve the evidence base for this treatment for acute porphyric attacks. The consortium investigators have experience in conducting controlled studies in porphyrias, including studies in patients with acute attacks. The National Institutes of Health (NIH) Rare Disease Clinical Research Network 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 facilitis of NIH-funded Clinical and Translational Science Awards. The specific aims of this proposal are: 1) To provide evidence for efficacy of human hemin for treatment of acute attacks of porphyria by conducting a double-blind placebo-controlled Phase 2 clinical trial in 30-40 patients with well documented acute porphyria; 2) To obtain samples for a study that aims for a better understanding of the mechanism of the beneficial effects of hemin administered in porphyria by studying regulation of genes for heme pathway enzymes and heat shock and stress response genes in peripheral blood mononuclear cells (PBMCs) obtained from acute porphyria patients before and after treatment with hemin. This will be in collaboration with Dr.Herbert Bonkovsky at Carolinus Medical Center in Charlotte, NC; 3) To provide evidence for efficacy and safety of hemin for prevention of recurring attacks of porphyria by conducting a double-blind placebo-controlled Phase 2 clinical trial in 20 patients with well documented acute porphyria; 4) To explore the feasibility and utility of a blinded placebo-controlled crossover approach to assessing the efficacy of hemin in individual patients with acute porphyria. Secondary and exploratory objectives will include a comparison of the biochemical effects of Panhematin and glucose, to evaluate effects of clinical features, such as sex, age and the factors that precipitat attacks of porphyria on response to Panhematin and glucose, to evaluate effects of genetic features, including the nature or the underlying mutation on treatment response to Panhematin, and to evaluate the use of Panhematin reconstituted with 25% human albumin in patients with acute attacks of porphyria.