文摘
摘要目的:的疗效和安全性risdiplam (RG7916)在婴儿1型脊髓性肌萎缩(SMA)治疗12个月期间FIREFISH确认第2部分的研究。
背景:SMA是一种严重的进行性减少引起的神经肌肉疾病水平的运动神经元的生存(SMN)蛋白质由于删除和/或突变的SMN1基因。第二个基因,SMN2,只有低水平的功能性SMN蛋白。Risdiplam是一个口头管理、集中和外围地分布SMN2pre-mRNA拼接修饰符增加功能性SMN蛋白的水平。
设计/方法:FIREFISH (NCT02913482)是一个持续的、多中心、非盲risdiplam研究婴儿1 - 7月入学1型SMA和两个SMN2基因复制。FIREFISH第1部分(n = 21)评估安全,耐受性,不同的药代学和药效学risdiplam剂量水平(加上探索性功效的结果)。在FIREFISH第1部分没有毒品安全研究发现导致退出≤30(平均19)个月的治疗后(数据削弱:2019年7月2日)。的主要目标确认第2部分(n = 41)调查risdiplam的功效在第1部分中剂量选择。主要疗效端点是婴儿坐的比例支持5秒后12个月治疗,所评估的22项的粗大运动规模婴儿和幼儿发展的量表,第三版(BSID-III)。附加二次端点也将被测量。
结果:这里我们将报告有效性和安全性的数据确认第2部分FIREFISH研究的参与者收到risdiplam治疗至少12个月的剂量选择第1部分中。
结论:FIREFISH的第2部分将提供重要的数据的有效性和安全性risdiplam在婴儿1型SMA。
披露:Servais博士已经收到个人赔偿咨询、担任科学顾问委员会说,与Avexis或其他活动,Inc .)生原体,Biophytis, Cytokinetics, Dynacure,罗氏,Santhera, Sarepta疗法。Servais博士已经收到Avexis研究支持,Inc .)生原体,Dynacure,罗氏。Baranello博士已经收到个人赔偿咨询、担任科学顾问委员会说,或其他活动AveXis和罗氏。马森博士没有披露。Mazurkiewicz-Beldzin博士已经收到个人赔偿咨询、担任科学顾问委员会说,生原体和Biomarin或其他活动。罗斯博士没有披露。Vlodavets博士已经收到个人赔偿咨询、担任科学顾问委员会说,与PTC疗法或其他活动,罗氏、诺华、Sarepta疗法,Avexus Jannses,马林生物技术。熊博士没有披露。Zanotelli博士没有披露。El-Khairi博士已经收到个人赔偿咨询、担任科学顾问委员会,与罗氏产品来说,或其他活动有限。 Dr. El-Khairi holds stock and/or stock options in Roche Holding AG. Dr. Fuerst-Recktenwald has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd.. Dr. Fuerst-Recktenwald holds stock and/or stock options in F. Hoffmann-La Roche Ltd. which sponsored research in which Dr. Fuerst-Recktenwald was involved as an investigator. Dr. Fuerst-Recktenwald holds stock and/or stock options in F. Hoffmann-La Roche Ltd.. Dr. Gerber has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Gerber has received compensation for serving on the Board of Directors of Sponsor. Dr. Gerber holds stock and/or stock options in Hoffmann-La Roche which sponsored research in which Dr. Gerber was involved as an investigator. Dr. Gerber holds stock and/or stock options in Hoffmann-La Roche. Dr. Gorni has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F.Hoffmann-La Roche. Dr. Kletzl has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Kletzl holds stock and/or stock options in Hoffmann-La Roche which sponsored research in which Dr. Kletzl was involved as an investigator. Dr. Kletzl holds stock and/or stock options in Hoffmann-La Roche. Dr. Kletzl has received research support from Hoffmann-La Roche. Dr. Scalco has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Hoffmann-La Roche. Dr. Scalco holds stock and/or stock options in Hoffmann-La Roche which sponsored research in which Dr. Scalco was involved as an investigator. Dr. Scalco has received research support from Hoffmann-La Roche. Dr. Darras has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with AveXis, Biogen, Bristol-Myers Squibb, Cytokinetics, Marathon, PTC Therapeutics, Roche, Santhera, and Sarepta. Dr. Darras has received research support from the National Institutes of Health/National Institute of Neurological Disorders and Stroke, the Slaney Family Fund for SMA, Working on Walking Fund, the SMA Foundation; CureSMA, Ionis Pharmaceuticals, Inc. and Biogen, AveXis, Cytokinetics, Fibrogen, PTC Th.
