文摘
摘要目的:确定和安全容许剂量的ap - 101。
背景:Mis-folded SOD1可以发现在大多数ALS患者表明SOD1是一种常见的致病性司机在家族和零星的形式的肌萎缩性侧索硬化症。ap - 101是一个完整的人IgG1抗体亲和力和选择性高的绑定错误折叠SOD1蛋白质。ALS在转基因小鼠模型,小鼠的版本ap - 101能够减弱脊髓运动神经元和延长总生存期。
设计/方法:鉴于迅速致命的自然ALS的有效剂量升级加速研究是使用一个开放标签执行肿瘤学样式3 + 3设计(ClinicalTrials.gov标识符:NCT03981536)。ap - 101管理通过静脉输液患者在1小时增加剂量水平的100,500或2500毫克。哨兵病人观察之前招聘额外的患者群体。观察3周后和没有任何药物相关毒性的下一个剂量组开了招聘。如果任何安全信号被观察到在第一3例,另有3例被招募在同一剂量水平。2个或更多的患者的剂量限制毒性在任何剂量水平将导致最大耐受剂量的宣言。总体目标是评估其安全,耐受性,静脉注射后ap - 101的药物动力学。脑脊髓液也收集了病人
结果:迄今为止,没有dose-limiting毒性效应或任何安全性和耐受性的担忧与ap - 101曾被观察到。最常见的不良事件相关的腰椎穿刺病人筛查。
结论:结果将用于指导的设计概念验证研究检查功效潜力ap - 101。
披露:其全称博士已经收到个人薪酬在10000 - 49999美元的范围为地基制药公司担任顾问。其全称博士已经收到个人薪酬在10000 - 49999美元的范围作为顾问生原体。其全称博士已经收到个人薪酬在10000 - 49999美元的范围为Cytokinetics担任顾问。其全称博士已经收到个人薪酬在500 - 4999美元的范围为Amylyx担任顾问。其全称博士已经收到个人薪酬在10000 - 49999美元的范围为Quralis担任顾问。其全称博士已经收到个人薪酬在10000 - 49999美元的范围为Alexion担任顾问。其全称博士已经收到个人薪酬在10000 - 49999美元的范围作为顾问。其全称博士已经收到个人薪酬在500 - 4999美元的范围作为顾问波。Berube-Desrosiers博士没有披露。Zinman博士已经收到个人薪酬在500 - 4999美元的范围作为生原体和MTP的顾问。 Dr. Zinman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen and MTP. An immediate family member of Dr. Shoesmith has received personal compensation for serving as an employee of Roche Pharmaceuticals. Dr. Shoesmith has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Orion pharmaceuticals. Dr. Shoesmith has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Mitsubishi Tanabe Pharma Canada. The institution of Dr. Shoesmith has received research support from AL-Pharma. The institution of Dr. Shoesmith has received research support from Orphazyme. Dr. Shoesmith has received personal compensation in the range of $0-$499 for serving as a Drug application review with CADTH (Government of Canada). Michael Salzmann has received personal compensation in the range of $50,000-$99,999 for serving as an officer or member of the Board of Directors for AL-S Pharma AG. Rob Schott has received stock or an ownership interest from Eli Lilly. PAULE CLERMONT has nothing to disclose. An immediate family member of Justus Bingham has received personal compensation for serving as an employee of Saltzman & Johnson. Justus Bingham has received personal compensation in the range of $50,000-$99,999 for serving as a Consultant for Eli Lily and Co.. Emma Bowden has received personal compensation for serving as an employee of Eli Lilly.
