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，目的是在30-40例急性卟啉症患者中比较氯化高铁血红素每天4 mg/kg加葡萄糖治疗4天与单独使用葡萄糖治疗的疗效。这项研究将在卟啉联合体的多个地点进行，旨在改善这种治疗急性卟啉发作的证据基础。该联盟的研究人员在进行门静脉症对照研究方面有经验，包括对急性发作患者的研究。美国国立卫生研究院(NIH)罕见疾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地点的监测，并建立了一个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。美国门户病基金会是一个长期有效的患者支持组织，也是该联盟的一部分，将帮助招募患者。所有地点的基础设施都将包括NIH资助的临床和翻译科学奖的设施。这项建议的具体目的是：1)通过在30-40名有良好记录的急性卟啉患者中进行双盲安慰剂对照2期临床试验，为人类氯化血红素治疗急性卟啉病发作的疗效提供证据；2)为一项研究获取样本，该研究旨在通过研究氯化高铁血红素治疗前后外周血单核细胞(PBMC)中的血红素途径酶基因以及热休克和应激反应基因的调控，以更好地了解氯化血红素治疗门静脉高压症的益处机制。这将与北卡罗来纳州夏洛特卡罗林斯医学中心的Herbert Bonkovsky博士合作；3)通过对20名有充分记录的急性卟啉症患者进行双盲安慰剂对照2期临床试验，为氯化血红素预防卟啉症复发的有效性和安全性提供证据；4)探索用盲法安慰剂对照交叉方法评估氯化血红素对个别急性卟啉病患者疗效的可行性和实用性。次要和探索性目标将包括比较泛血红素和葡萄糖的生化效应，评估临床特征，如性别、年龄和导致卟啉病发作的因素对泛血红素和葡萄糖反应的影响，评估遗传特征(包括本质或潜在突变)对泛血红素治疗反应的影响，以及评价由25%人白蛋白重组的泛血红素在门脉症急性发作患者中的应用。

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.