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: 9338040
• 负责人: KARL ELMO ANDERSON
• 金额: $ 20.76万
• 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 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9338040
• 关键词: Phase; Study; Hemin; Treatment; Prevention

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.

描述（由申请人提供）： 这是一项2期，随机，盲目的对照研究，可将每天4 mg/kg的HEMIN治疗加4天，以在30-40例卟啉症患者中单独使用葡萄糖治疗。 该研究将在卟啉菌联盟的多个地点进行，旨在改善此治疗急性斑岩攻击的证据基础。财团研究人员具有进行卟啉症进行对照研究的经验，包括对急性发作的患者进行的研究。美国国家卫生研究院（NIH）罕见疾病临床研究网络支持研究材料的开发，基于Web的数据输入，数据仓库以及在多个研究地点进行监测，并建立了数据和安全监测委员会。制造商已将药物用于研究。美国斑岩基金会（American Porphyria Foundation）是一个长期有效的患者支持小组，也是该财团的一部分，将有助于患者招募。所有站点的基础设施都将包括NIH资助的临床和转化科学奖。该提案的具体目的是：1）通过在30-40例急性急性卟啉症患者中进行双盲安慰剂对照2期临床试验，提供人体Hemin对卟啉症急性发作的有效性的证据； 2）获得一项研究的样品，该研究旨在通过研究血红素途径酶的基因调节，并在急性治疗前后治疗急性卟啉患者中获得的外周血单核细胞（PBMC）中的热休克和应激反应基因，以更好地理解卟啉症的有益作用的机制。这将与北卡罗来纳州夏洛特市卡罗尼努斯医疗中心的赫伯特·邦科夫斯基博士合作； 3）通过在20名有据可查的急性斑岩症患者中进行双盲安慰剂对照的2期临床试验，以提供预防孢子症的疗效和安全性的证据； 4）探索盲人安慰剂对照跨界方法的可行性和效用，以评估HEMIN在急性卟啉症患者中的疗效。 第二和探索性目标将包括比较泛素和葡萄糖的生化作用，以评估临床特征的影响，例如性别，年龄以及静态症状攻击对泛毒素和葡萄糖的反应的因素，从患有卟啉症急性攻击的患者的人白蛋白25％。