文摘
摘要目的:报告tolebrutinib的安全性和有效性在120周(2.5年)2 b阶段试验(NCT03889639)长期安全性(LTS)扩展(NCT03996291)。
背景:2 b阶段试验结果显示brain-penetrant布鲁顿的酪氨酸激酶抑制剂tolebrutinib耐受性良好,引发剂量依赖性降低新钆增强T1和新参与者/扩大T2病灶复发多发性硬化症。
设计/方法:在一个LTS一部分,参与者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选择(60毫克/天)。在B部分中,参与者开放tolebrutinib 60毫克/天。安全评估通过不良事件(AE)。疗效结果包括年复发率(ARR)和规模在扩大残疾状态变化(eds)得分从基线。
结果:LTS扩展,107年(85.6%)截至2022年7月7日参与者进行治疗。治疗中止的原因是:缺乏功效(n = 5),进步的疾病(n = 4),参与者的决定(n = 3), AEs (n = 3),移民(n = 2),计划怀孕(n = 1)。LTS周120年,还没有观察到新的安全信号。最常见的治疗诱发的AEs(流泪)COVID-19[31/125](24.8%),头痛(13.6%[17/125]),鼻咽炎(16/125)(12.8%),上呼吸道感染(11.2%[14/125]),细菌性膀胱炎,关节痛和背痛(各占7.2%(9/125)),和咽炎(6.4% [8/125])。没有观察到tolebrutinib剂量效应部分流泪或严重AEs和不安全信号出现参与者转向tolebrutinib 60毫克/天在b部分参与者收到tolebrutinib 60毫克/天≥8周(n = 124),加勒比海盗是0.20(95%置信区间CI: 0.14, 0.28)和73.4%仍不复发。意味着eds保持稳定到120周。
结论:通过LTS周120,tolebrutinib 60毫克/天继续展示出良好的安全性,并与低加勒比海盗和稳定的残疾。
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美元的范围为礼来公司担任顾问。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. Li has received personal compensation for serving as an employee of Sanofi. Dr. Salloum has received personal compensation for serving as an employee of Sanofi. Dr. Salloum has received personal compensation for serving as an employee of Biogen. Dr. Salloum has stock in Biogen. Timothy J. Turner has received personal compensation for serving as an employee of Sanofi. Timothy J. Turner has received stock or an ownership interest from Sanofi. Timothy J. Turner has received intellectual property interests from a discovery or technology relating to health care. 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 $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 as a Consultant for Genzyme. 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. Dr. Fox has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for AB Science. 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.
