TY -的T1 RA101495补充组件5的皮下注射肽抑制剂(C5)广义重症肌无力的治疗(gMG):第一阶段的结果和第二阶段设计(S31.006) JF -神经学乔-神经学六世- 90 - 15补充SP - S31.006盟詹姆斯·f·霍华德,小非盟-亨利·j·卡明斯基盟理查德•j•诺瓦克AU -吉尔。沃尔夫盟迈克尔·g·贝纳塔尔AU -阿隆索里卡多盟米歇尔·d·Hoarty AU -史蒂芬·j·德马科盟Ramin Fa首页rzaneh-Far AU -佩特拉·w·杜达Y1 - 2018/04/10 UR - //www.ez-admanager.com/content/90/15_Supplement/S31.006.abstract N2 -目的:评估安全,耐受性、药代动力学、药效学和RA101495健康志愿者(阶段1)——设计的第二阶段研究的gMG patientsBackground RA101495:乙酰胆碱受体抗体(乙酰胆碱受体)激活的gMG的古典补体级联,并诱导膜攻击复杂(MAC)神经肌肉接头的形成和组织损伤。抑制C5治疗目标是一个强大的生物AChR-antibody积极的gMG的理由。RA101495有力、subcutaneously-administered大环肽结合C5和抑制其解理C5a C5b,防止生产MAC。RA101495在第二阶段临床开发治疗阵发性夜间血红蛋白尿和gMG。设计/方法:在第一阶段,受试者被随机分配接受单(n = 14)和多个(n = 4)剂量的RA101495或安慰剂(n = 10), 7天。补体抑制是评估使用antibody-sensitized绵羊红细胞试验进行验证。基于这些数据,多中心,随机,双盲,安慰剂对照的第二阶段研究AChR-antibody积极gMG病人已经启动。结果:在第一阶段,药物水平在健康志愿者从in-silico建模与预测一致,与终端半衰期约为7天。因此,与多个剂量暴露稳步增长超过7天。补充活动几乎完全抑制(≥95%)后3小时内实现第一剂量和维护在24小时在高剂量组。未发现安全隐患。三个RA101495-treated学科经历了瞬态和自限性温和注射部位红斑。 The design of the ongoing Phase 2 study in gMG will also be presented.Conclusions: Phase 1 data support the evaluation of RA101495 in a Phase 2 study in gMG. Subcutaneous self-administration of RA101495, if shown effective, may not only enable a broader population of gMG patients to potentially benefit from targeted C5 inhibitor therapy but also ease the treatment-related burden of intravenous options.Study Supported by: Ra PharmaceuticalsDisclosure: Dr. Howard has nothing to disclose. Dr. Kaminski has nothing to disclose. Dr. Nowak has nothing to disclose. Dr. Wolfe has nothing to disclose. Dr. Benatar has nothing to disclose. Dr. Ricardo has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ra Pharmaceuticals. Dr. Ricardo holds stock and/or stock options in Ra Pharmaceuticals. Dr. Hoarty has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ra Pharmaceuticals. Dr. Hoarty holds stock and/or stock options in Ra Pharmaceuticals. Dr. DeMarco has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ra Pharmaceuticals. Dr. DeMarco holds stock and/or stock options in Ra Pharmaceuticals. Dr. Farzaneh-Far has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ra Pharmaceuticals. Dr. Farzaneh-Far holds stock and/or stock options in Ra Pharmaceuticals. Dr. Duda has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ra Pharmaceuticals. Dr. Duda holds stock and/or stock options in Ra Pharmaceuticals. ER -