Ocrelizumab治疗效果在项目组合管理系统对上肢功能障碍:患者群清唱剧研究结果通知ORATORIO-HAND研究设计(p3.2 - 091)

摘要目的:评估ocrelizumab功效在更多的残疾/老年患者上肢功能与主要进展型多发性硬化症(项目组合管理系统)三期清唱剧研究(NCT01194570)通知希望具有ORATORIO-HAND研究的设计阶段。

背景:Ocrelizumab演示效果和安慰剂在减少上肢功能障碍(9洞桩测试[9 hpt])在清唱剧(扩大残疾状态量表(eds)≤6.5)。Ocrelizumab受益更多的残疾人专业患者不能列入清唱剧将实现一个未满足的需求。

设计/方法:清唱剧专业患者(N = 732;eds 3.0 - -6.5;18-55岁)被随机分配(2:1)为≥120周ocrelizumab或安慰剂,直到一个预先确定的eds进展事件发生。功效ocrelizumab预防进展的上肢功能恶化以12周证实20% 9 hpt双手的(平均)在基线调查子组:eds≥6.0 (N = 220),年龄> 45年(N = 384)、和9成时间> 25秒(N = 434)。

结果:Ocrelizumab减少上肢残疾发展更多/老专业患者禁用。风险降低和安慰剂在9 hpt过程类似患者基线eds得分< 6.0和≥6.0(40%比38%,p = 0.92),和基线9 hpt时间≤25 s和> 25 s(49%比44%,p = 0.82)。发展事件主要发生在患者9 hpt > 25和≤25年代(安慰剂:34.3% vs 17.8%;ocrelizumab: 21.5% vs 9.9%);疲软的趋势更大功效≤45年的病人与观察> 45年(p = 0.29)。

结论:ORATORIO-HAND旨在进一步研究ocrelizumab对上肢功能的功效。基于9 hpt进展率在清唱剧,1000名符合条件的患者(eds 3.0─8.0, 18 - 65岁,9成> 25 s),随机(1:1)为≥120周ocrelizumab或安慰剂(直到预先确定数量的发展事件发生时)将使ocrelizumab疗效的评估确认9 hpt进展(主要终点)。筛选将2019年一季度开始。

披露:Giovannoni博士已经收到个人赔偿咨询、担任科学顾问委员会说,与AbbVie或其他活动,生原体,诺华,Teva神经科学和罗氏诊断公司。他还收到咨询费用为Merck-Serono顾问委员会会议,Genzyme-Sanofi,合成纤维BV,医生峰会和几个医学教育会议。Giovannoni博士已经收到了个人在一篇社论中补偿能力多发性硬化和相关疾病(爱思唯尔)。Giovannoni博士收到武田制药公司的研究支持。Airas博士已经收到个人赔偿咨询、担任科学顾问委员会说,或其他活动与罗氏公司,默克公司。Airas博士接到Sanofi-Genzyme研究支持。Bove博士已经收到个人赔偿咨询、担任科学顾问委员会说,或其他的活动与罗氏公司基因泰克和Genzyme赛诺菲。Bove博士接到Akili互动研究支持。Boyko博士已经收到个人赔偿咨询、担任科学顾问委员会说,与生原体或其他活动,先灵葆雅,默克公司TEVA,诺华Sanofi-Genzyme, Actelion股价,Biocad Generium。刀已经收到个人赔偿咨询博士担任科学顾问委员会说,与AMO制药或其他活动,Biolinerx,地平线制药、海蜃制药、默克公司,默克和辉瑞,Opko生物制剂,Neurim,诺华,Ophazyme,赛诺菲-安万特(sanofi - aventis)套索制药、Receptos / Celgene公司,梯瓦制药、NHLBI,美国儿童健康与人类发展研究所Atara Biotherapeutics,轴突,生原体,Argenix,头脑风暴细胞疗法,查尔斯顿实验室公司,点击疗法,Genzyme,基因泰克,瓦制药,Klein-Buendel合并,落实Medday,诺华,罗氏,Scifluor, Somahlution,梯瓦制药、TG疗法,但休斯顿。 Dr. Cutter has received personal compensation in an editorial capacity for Statistical editor for the Journal of the American Society of Nephrology. Dr. Cutter has received research support from Via MGFA. Dr. Hobart has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Acorda, Asubio, Bayer Schering, Biogen Idec, F. Hoffmann-La Roche Ltd, Genzyme, Merck Serono, Novartis, Oxford PharmaGenesis, Oxford Health Policy Forum and Teva. Dr. Kuhle’s institution has received compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Novartis Pharmaceuticals, Protagen AG, Roche, Teva, Sanofi Genzyme, Swiss MS Society, and Merck Serono,. Dr. Kuhle has received research support from ECTRIMS Research Fellowship Programme, Bayer AG, Biogen, Sanofi Genzyme, Merck, Novartis Pharmaceuticals, Roche, Swiss MS Society, Swiss National Research Foundation, and University of Basel. Dr. Oh has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with EMD-Serono, Novartis, Biogen-Idec, Sanofi-Genzyme, Roche, Celgene. Dr. Oh has received research support from Biogen-Idec, Sanofi-Genzyme. Dr. Tur has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Biogen, Bayer, F. Hoffmann-La Roche Ltd, Ismar Healthcare, Merck Serono, Novartis, Sanofi and Teva. Dr. Tur has received research support from Postdoctoral research ECTRIMS Fellowships. Dr. Garas has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Model has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd. Dr. Manfrini has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with F. Hoffmann-La Roche Ltd as an employee. Dr. Wolinsky has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Alkermes, Actelion, Acorda Therapeutics, Celgene, EMD Serono, GeNeuro, GW Pharma, MedDay Pharmaceuticals, Novartis, Otsuka, PTC Therapeutics, Roche/Genentech, Sanofi Genzyme, PlatformQ Health Education, PRIME, and Strategic Consultants Intl. Dr. Wolinsky has received royalty, license fees, or contractual rights payments from UTHealth to Millipore (Chemicon International) Corporation.