STUDY OF THE SAFETY AND EFFICACY OF FABRAZYME IN PATIENTS WITH FABRY DISEASE

FABRAZYME 对法布瑞病患者的安全性和有效性研究

• 批准号: 7380535
• 负责人: MARYAM BANIKAZEMI
• 金额: $ 3万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-17 至 2007-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7380535
• 关键词: autonomic nervous system; blood vessels; emotions; enzymes; glycosphingolipids; human; hyperthermia; kidney; lead; pharmacokinetics; placebos; reduction; success; tissues; urinalysis

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. The common element in the manifestations of Fabry disease is severe endothelial dysfunction affecting the structure, vasoreactivity and integrity of blood vessels. Ultimately, failure of endothelial vascular beds result in the myriad pathophysiologic events leading to central, peripheral and autonomic nervous system disease, cardiac and renal disease. Genzyme Corporation has manufactured a recombinant form of human a-galactosidase A (r-ha-GAL; Fabrazyme) to provide replacement enzyme to patients with Fabry disease. A Phase 1-2 single center, open label, dose finding, safety and pharmacokinetic studies have been completed. This study provided evidence of pharmacodynamic clearance of stored glycosphingolipid from target tissues, suggesting physiologic improvement and potential for clinical benefit. A multi-national, randomized, double blind placebo controlled pivotal Phase 3 study has also been completed. The most frequent adverse events for those patients who received Fabrazyme compared to placebo were infusion-associated reactions including rigors and fever. In addition, laboratory studies including clinical chemistry, hematology, and urinalysis did not show that treatment with Fabrazyme had any toxic effects. Both trials have demonstrated pharmacodynamic reduction to normal or near-normal levels of stored glycospingolipids from vascular endothelial beds as surrogate endpoints likely to predict clinical benefit in Fabry patients.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。法布里疾病表现的共同元素是严重的内皮功能障碍，影响血管的结构，血管反应性和完整性。最终，内皮血管床的失败导致无数的病理生理事件导致中枢，周围和自主神经系统疾病，心脏和肾脏疾病。 Genzyme Corporation已经生产了一种重组形式的人类A-半乳糖苷酶A（R-HA-GAL； Fabrazyme），为Fabry病患者提供替代酶。 1-2阶段单中心，开放标签，剂量发现，安全性和药代动力学研究已完成。这项研究提供了靶组织中储存的糖磷脂的药效学清除的证据，这表明生理改善和临床益处的潜力。一项跨国，随机的，双盲安慰剂控制的关键阶段3研究也已完成。与安慰剂相比，那些接受Fabrazyme的患者最常见的不良事件是输液相关的反应，包括严格和发烧。此外，包括临床化学，血液学和尿液分析在内的实验室研究并未表明用木氮治疗具有任何毒性作用。这两项试验均表明，从血管内皮床中的药效学降低到正常或近非正常水平的糖叠脂质，因为替代端点可能可以预测Fabry患者的临床益处。