Phase 2 Study of Deferiprone in the Treatment of NBIA

描述（由申请人提供）： 这是一项临床研究，旨在治疗一种罕见的遗传性运动障碍，称为神经变性与脑铁积累（NBIA）。其特征在于神经系统的进行性变性和铁在脑中的积累，主要是基底神经节。NBIA无法治愈，主要影响儿童。已经提出了铁螯合剂疗法，但由于缺乏有效穿过血脑屏障的铁螯合剂而没有系统地研究作为治疗。去铁酮是一种口服铁螯合剂，在国际上用于治疗全身性铁超载，可穿过血脑屏障。临床报告表明，约30 mg/kg/天的去铁酮在脑铁过量但无全身铁蓄积的症状性患者中具有放射学和临床疗效。本研究的主要目的是确定去铁酮在NBIA中的安全性，并证明去铁酮在减少张力障碍行为方面的疗效。拟议的研究将是一项设盲、安慰剂对照、随机试验，在40名患者中以2：1的比例进行药物与安慰剂的比较，为期4年。符合条件的患者将是NBIA/PKAN突变阳性，年龄超过8岁，治疗失败并且在过去6个月内显示临床进展而无改善。使用大脑R2的MRI协议将测量大脑铁含量的变化。结局指标将包括神经学和功能评估的改善。

DESCRIPTION (provided by applicant): This is a clinical study to treat patients with a rare genetic movement disorder known as neurodegeneration with brain iron accumulation (NBIA). It is characterized by the progressive degeneration of the nervous system and iron accumulation in the brain, primarily the basal ganglia. There is no cure for NBIA, which primarily affects children. Iron chelator therapy has been proposed, but not systematically studied as a treatment because of the lack of an iron chelator that effectively crosses the blood-brain barrier. Deferiprone, an oral iron chelator, used internationally for the treatment of systemic iron overload, crosses the blood-brain barrier. Clinical reports suggest deferiprone at approximately 30 mg/kg/day has radiographic and clinical efficacy in symptomatic patients with excess brain iron but no systemic iron accumulation. The primary aim of this study is to establish the safety of deferiprone in NBIA, and demonstrate efficacy of deferiprone in diminishing dystonic behaviors. The proposed research study will be a blinded, placebo-controlled, randomized trial of drug versus placebo in a 2:1 ratio in 40 patients over a four year period. Patients eligible will be NBIA/PKAN mutation positive, over 8 years of age, who have failed therapy and have shown clinical progression without improvement over the last six months. An MRI protocol using R2 of the brain will measure changes in brain iron content. Outcome measures will include improvement in neurologic and functional assessments.