A MULTI-CENTER, DOUBLE-BLIND, RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。急性间歇性卟啉病(AIP)是由于胆汁酸原脱氨酶(PBGD)缺乏引起的一种遗传性(常染色体显性)疾病。过量的胆红素和其他血红素生物合成途径的中间产物在肝脏和血浆中积累，并通过尿液排泄。症状大多是由于对神经系统的影响而出现的急性发作。标准疗法包括静脉注射葡萄糖和氯化血红素(血红素、血红素白蛋白或血红素精氨酸)，但这些方法并不总是有效的。这项多中心、双盲、随机、安慰剂对照、平行组II-III期试验的主要目的是观察重组人胆红素脱氨酶对急性间歇性卟啉(AIP)发作期患者血浆胆红素原(PBG)的生化疗效。次要目标包括评估重组人PBGD在血浆中的临床疗效和药代动力学。至少有36名受试者将在欧洲和美国参加试验，其中包括UTMB的多达12名受试者。可能反复发作的潜在患者会被提前告知这项研究，并鼓励他们在发作时尽早来医院就诊。在尽可能短的筛查期(4小时)之后，登记参加试验的受试者将被随机分成两组，分别使用PorPhozym？或安慰剂以及葡萄糖进行治疗。如果在治疗过程中，卟啉症的症状恶化，试验药物可能会被停止，患者可以使用氯化血红素进行治疗。用试验药物治疗超过48小时，之后如果临床指征，可以给予标准治疗，包括氯化血红素。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Acute intermittent porphyria (AIP) is a genetic (autosomal dominant) disease due to a deficiency of porphobilinogen deaminase (PBGD). Excess porphobilinogen and other heme biosynthetic pathway intermediates accumulate in liver and plasma and are excreted in urine. Symptoms occur mostly as acute attacks due to effects on the nervous system. Standard therapies include intravenous glucose and hemin (hematin, heme albumin or heme arginate), but these are not always effective. The primary objective of this multi-center, double-blind, randomized, placebo-controlled, parallel group, Phase II-III trial is to investigate the biochemical efficacy of Porphozym(recombinant human porphobilinogen deaminase) on plasma porphobilinogen (PBG) in subjects with acute intermittent porphyria (AIP) during an attack. Secondary objectives include assessments of clinical efficacy and pharmacokinetics of rhPBGD in plasma. At least 36 subjects will be enrolled in the trial, both in Europe and the U.S., including up to 12 at UTMB. Potential patients who are likely to have recurrent attacks are informed of the study in advance and encouraged to come to the hospital early in an attack. After a screening period that is as short as possible (4 hours) subjects enrolled in the trial will be randomized to treatment with either Porphozym¿ or placebo, as well as glucose. If the symptoms of porphyria become worse during treatment the trial drug may be discontinued and the patient treated with hemin. Treatment with trial drug is given over 48 hours, after which standard treatment, including hemin, may be given if clinically indicated.