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

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。急性间歇性卟啉症（AIP）是一种遗传性（常染色体显性）疾病，由于缺乏卟胆色素原脱氨酶（PBGD）。过量的卟啉胆色素原和其他血红素生物合成途径中间体在肝脏和血浆中积累，并随尿液排出。由于对神经系统的影响，症状大多以急性发作的形式出现。标准的治疗方法包括静脉注射葡萄糖和血红素（血红素、血红蛋白或精氨酸血红素），但这些方法并不总是有效。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研究重组人卟啉原脱氨酶（Porphozym）对急性间歇性卟啉症（AIP）患者发作期间血浆卟啉原（PBG）的生化影响。次要目的包括评估rhPBGD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12名受试者。有可能反复发作的潜在患者提前被告知这项研究，并鼓励他们在发作时尽早到医院就诊。在尽可能短的筛选期（4小时）后，参加试验的受试者将被随机分配到Porphozym¿或安慰剂以及葡萄糖治疗组。如果在治疗期间卟啉症的症状恶化，可以停药，病人用血红素治疗。试验药物治疗超过48小时，在此之后，如果临床指征，可以给予标准治疗，包括血红素。

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.