PATIENTS WITH TRANSFUSION DEPENDANT (PNH)

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。假设：Eculizumab是一种人源化的单抗，专门结合末端补体蛋白C5，将在输血依赖型溶血性阵发性睡眠性血红蛋白尿症(PNH)患者中进行长期安全性评估。这是一项针对已完成凯旋(GCRC协议#853)、SHEPEND(GCRC协议#899)或X03-001试验的患者的开放标签研究。目的：PNH是一种获得性造血干细胞克隆性疾病，以血管内溶血、血红蛋白尿、贫血和血栓形成为特征(1)。在美国，这是一种罕见的疾病，发病率为每百万人中有2到6人，患病率在10,000到30,000人之间。确诊后的PNH患者估计10年存活率为50%，25年存活率为28%，大部分死亡是由血栓形成或骨髓发育不良引起的。实验设计：这是一项为期约2年(104周)的开放式研究。完成Shepherd或X03-001试验的患者将直接进入这一延期的开放标签阶段。为了保留Triumph研究的盲性，完成Triumph研究的患者在进入该试验的开放标签阶段之前将经历一个盲诱导期。开放标签治疗阶段：患者将每两周静脉滴注900 mg eculizumab。

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. Hypothesis: The long-term safety of Eculizumab, a humanized monoclonal antibody that specifically binds the terminal complement protein C5, will be evaluated in patients with transfusion-dependent hemolytic paroxysmal nocturnal hemoglobinuria (PNH). This is an open-label study of patients who have completed the TRIUMPH (GCRC Protocol #853), SHEPHERD (GCRC Protocol #899) or X03-001 trials. Goals: PNH is an acquired clonal disorder of the hematopoietic stem cell, characterized by intravascular hemolysis, hemoglobinuria, anemia, and thrombosis (1). It is a rare condition with an incidence of 2 to 6 per million and a prevalence between 10,000 and 30,000 in the United States. The estimated survival of PNH patients after diagnosis is 50% at 10 yrs and 28% at 25 yrs, with a majority of the deaths resulting from thrombosis or bone marrow hypoplasia. Experimental Design: This is an open-label study of approximately 2 yrs (104 weeks). Patients who have completed the SHEPHERD or X03-001 trials will directly enter the open-label phase of this extension. To preserve the blinded nature of the TRIUMPH study, patients who have completed the TRIUMPH study will undergo a blind induction period prior to entering the open-label phase of this trial. Open-Label Treatment Phase: Patients will receive 900 mg eculizumab via IV infusion every 2 weeks.