文摘
摘要目的:确定疗效、安全性、药物动力学(PK)和药效学的risdiplam婴儿发生前症状与基因诊断和脊髓性肌萎缩(SMA)。
背景:SMA是一种严重的进步,基因水平降低引起的神经肌肉疾病的生存运动神经元(SMN)蛋白质由于删除和/或突变的SMN1基因。第二个SMN的基因,SMN2,只有低水平的功能性SMN蛋白。Risdiplam集中和外围分布式口服SMN2pre-mRNA拼接修饰符增加功能性SMN蛋白的水平。Risdiplam (EVRYSDI™)已经被FDA批准用于治疗SMA患者,年龄在2个月以上。
设计/方法:RAINBOWFISH (NCT03779334)是一个非盲、随访时间、多中心、全球临床研究招收birth-6周的婴儿年龄(第一次剂量),不管SMN2拷贝数。婴儿会收到risdiplam为24个月,紧随其后的是提供3年的扩展。主要分析将在12个月的治疗有两个婴儿SMN2副本和复合肌肉动作电位振幅城市规划机构(CMAP)≥1.5 mv基准。
结果:主要终点是婴儿坐在没有支持的比例至少12个月的治疗后5秒(评估量表的婴儿和幼儿发展,第三版)。二次端点包括临床表现SMA的发展,生存和永久通风,实现电机的里程碑,运动机能,增长措施,营养状况,提出、PK、安全监控、和其他临床参数。
年龄中位数在第剂量(范围)的七个登记婴儿35(16-40)天。我们将报告更新基线人口统计学和基线SMN蛋白数据登记婴儿发生前症状与SMA。额外的初步数据也将呈现。
结论:RAINBOWFISH将提供有价值的信息关于risdiplam治疗的效果与SMA在婴幼儿阶段发生前症状。全球招聘研究正在进行。
披露:芬克尔博士已经收到个人薪酬在500 - 4999美元的范围为Neurogene担任顾问。芬克尔博士已经收到个人薪酬在10000 - 49999美元的范围为在科学咨询服务或数据安全监测委员会AveXis。芬克尔博士已经收到个人薪酬在10000 - 49999美元的范围为在科学咨询服务或数据安全监测委员会生原体。芬克尔博士已经收到个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会的缓解期。芬克尔博士已经收到个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会Capricor。芬克尔博士已经收到个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会ReveraGen。芬克尔博士已经收到个人薪酬在5000 - 9999美元的范围为在科学咨询服务或数据安全监测委员会罗氏。芬克尔博士已经收到个人薪酬在500 - 4999美元的范围为在科学咨询服务或数据安全监测委员会学者岩石。芬克尔博士已经收到个人薪酬在500 - 4999美元的范围作为一个编辑,副主编,或为爱思唯尔编辑顾问委员会成员。芬克尔博士的机构已经接到AveXis研究支持。 The institution of Dr. Finkel has received research support from Biogen. The institution of Dr. Finkel has received research support from Capricor. The institution of Dr. Finkel has received research support from Catabasis. The institution of Dr. Finkel has received research support from ReveraGen. The institution of Dr. Finkel has received research support from Roche. The institution of Dr. Finkel has received research support from Scholar Rock. Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. An immediate family member of Dr. Finkel has received intellectual property interests from a discovery or technology relating to health care. Dr. Finkel has a non-compensated relationship as a advisor with n-Lorem Foundation that is relevant to AAN interests or activities. Dr. Finkel has a non-compensated relationship as a Board Member with Every Life Foundation that is relevant to AAN interests or activities. Dr. Al-Muhaizea has nothing to disclose. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Michelle Farrar has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen. Michelle Farrar has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Leslie Nelson, PT, MPT, OCS has received personal compensation for serving as an employee of UT Southwestern Medical Center. Leslie Nelson, PT, MPT, OCS has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Leslie Nelson, PT, MPT, OCS has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Avexis. Leslie Nelson, PT, MPT, OCS has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Audentes. Leslie Nelson, PT, MPT, OCS has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen, Inc. Leslie Nelson, PT, MPT, OCS has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Scholar Rock. Manickvasagam Janarthanam has nothing to disclose. Yi Wang has nothing to disclose. Edmar Zanoteli has nothing to disclose. Laura Palfreeman has received personal compensation for serving as an employee of Roche. Muna El-Khairi has received personal compensation for serving as an employee of Roche Products Limited. Dr. Gorni has received personal compensation for serving as an employee of Hoffman La Roche. Heidemarie Kletzl has received personal compensation for serving as an employee of Hoffmann-La Roche. Marianne Gerber has received personal compensation for serving as an employee of Roche. Marianne Gerber has received stock or an ownership interest from F Hoffmann La Roche . Dr. Bertini has nothing to disclose.
