文摘
摘要目的:描述的安全性和有效性tolebrutinib复发多发性硬化症患者在72周(月18)在长期的安全(LTS) 2 b阶段试验的延伸。
背景:2 b阶段试验(NCT03889639)、tolebrutinib CNS-penetrant布鲁顿的酪氨酸激酶抑制剂,是良好的耐受性在12周剂量依赖性降低新钆增强T1和新/扩大T2病灶。
设计/方法:LTS扩展(NCT03996291)由2部分组成:病人继续他们的核心研究tolebrutinib剂量(5、15、30或60毫克/天)双盲,直到第三阶段研究剂量被选中(部分),目前收到tolebrutinib 60毫克/天开放(B部分)。长期安全性和耐受性是主要的目标。次级终点包括复发年率(ARR)和基线的变化扩大残疾状态量表(eds)评分。
结果:124年治疗的125例扩展完成部分A和B部分转换到一个病人(5毫克/天)停止部分由于进步的疾病和6 B部分停止由于各种原因,包括不良事件(AE;n = 2),缺乏有效性(n = 1),进步的疾病(n = 1),和移民(n = 2)。到目前为止,还没有观察到新的安全信号。最常见的治疗诱发的AEs(流泪)头痛(12.8% [16/125]),COVID-19(12.8%[16/125]),鼻咽炎(13/125)(10.4%),上呼吸道感染(8.0%[10/125]),和关节痛(5.6% [7/125])。没有建议的剂量效应TEAE或严重AE在某种程度上,没有出现新的安全信号切换到60 mg患者b部分ARR tolebrutinib 60毫克为0.17(95%置信区间CI: 0.11, 0.27);84.7%的患者无复发LTS一周72截止。意味着eds分数72 LTS周保持稳定。
结论:通过72年LTS周,tolebrutinib 60毫克继续表现出良好的安全性和耐受性,和较低的加勒比海盗。
披露:哦收到博士个人薪酬在5000 - 9999美元的范围为罗氏公司担任顾问。博士的机构哦收到个人薪酬在5000 - 9999美元的范围为Biogen-Idec担任顾问。哦收到博士个人薪酬在500 - 4999美元的范围为百时美施贵宝担任顾问。哦收到博士个人薪酬在5000 - 9999美元的范围为EMD-Serono担任顾问。哦收到博士个人薪酬在5000 - 9999美元的范围为Sanofi-Genzyme担任顾问。哦收到博士个人薪酬在500 - 4999美元的范围为诺华公司担任顾问。哦收到博士个人薪酬在500 - 4999美元的范围为Alexion担任顾问。博士哦收到个人补偿的范围0 - 499美元为在科学咨询服务或数据安全监测委员会罗氏。博士哦收到个人薪酬在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Biogen-Idec。博士哦收到个人薪酬在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Sanofi-Genzyme。 The institution of Dr. Oh has received research support from Biogen-Idec. The institution of Dr. Oh has received research support from EMD-Serono. The institution of Dr. Oh has received research support from Biogen-Idec. Dr. Syed has received personal compensation for serving as an employee of Sanofi US. Dr. Orogun has nothing to disclose. Deborah Dukovic has received personal compensation for serving as an employee of Sanofi. Deborah Dukovic has received stock or an ownership interest from Sanofi. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for AB Science. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Janssen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Celgene. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for EMD Serono. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Genentech. Dr. Fox has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Teva. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving as a Consultant for TG Therapeutics. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Immunic. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Fox has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Janssen. The institution of Dr. Fox has received research support from National Institutes of Health. Dr. Fox has received publishing royalties from a publication relating to health care.
