安全性和有效性的ozanimod和干扰素beta-1a复发多发性硬化症(光辉):多中心,随机,24个月,3期临床试验。

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科恩JA, Comi G, Selmaj千瓦,酒吧或,阿诺DL,斯坦曼L,哈惠普,好吃的X, Kubala Havrdova E,克里族BAC,谢菲尔德JK,明顿N, Raghupathi K,黄V,卡波斯L

安全性和有效性的ozanimod和干扰素beta-1a复发多发性硬化症(光辉):多中心,随机,24个月,3期临床试验。

柳叶刀神经。2019年11月18日(11):1021 - 1033。doi: 10.1016 / s1474 - 4422 (19) 30238 - 8。Epub 2019年9月3。

PubMed ID

31492652 (在PubMed

]

文摘

背景:Ozanimod鞘氨醇1-phosphate受体调制器,它选择性地结合鞘氨醇1-phosphate与高亲和力受体亚型1和5。在光辉的第二阶段研究参与者与复发多发性硬化症、ozanimod与MRI措施疗效优于安慰剂,耐受性良好。光辉第三阶段研究旨在证实的安全性和有效性ozanimod与干扰素beta-1a复发多发性硬化症患者。方法:我们做了24个月的、多中心、双盲、double-dummy 3期临床试验参与者的复发多发性硬化症在21个国家147个医疗中心和临床实践。参与者18-55岁,多发性硬化症根据2010年麦当劳标准,复发的临床过程,脑MRI病灶与多发性硬化相一致,扩大残疾状态量表得分为0.0 - -5.0,和至少一个在12个月内复发前筛选或者至少有一个在24个月内复发前钆增强病变筛查+至少一个随机前12个月内。参与者被随机分配(比)通过一个交互式语音应答系统每日口服ozanimod 1.0毫克或0.5毫克或每周肌内干扰素beta-1a 30杯。参与者、调查人员和研究人员都戴面具的治疗分配。主要终点是年复发率(ARR)超过24个月。主要分析了所有参与者的意向处理人口接受研究药物和安全评估在所有接受研究药物的受试者随机分配,按最高剂量的ozanimod收到分组。这个试验在ClinicalTrials.gov注册,NCT02047734, EudraCT, 2012-002714-40。 FINDINGS: Between Dec 27, 2013, and March 31, 2015, we screened 1695 participants, of which 375 did not meet inclusion criteria. 1320 participants were enrolled and randomly assigned to a group, of whom 1313 received study drug (433 assigned to ozanimod 1.0 mg, 439 assigned to ozanimod 0.5 mg, and 441 assigned to interferon beta-1a) and 1138 (86.7%) completed 24 months of treatment. Adjusted ARRs were 0.17 (95% CI 0.14-0.21) with ozanimod 1.0 mg, 0.22 (0.18-0.26) with ozanimod 0.5 mg, and 0.28 (0.23-0.32) with interferon beta-1a, with rate ratios versus interferon beta-1a of 0.62 (95% CI 0.51-0.77; p<0.0001) for ozanimod 1.0 mg and 0.79 (0.65 to 0.96; p=0.0167) for ozanimod 0.5 mg. The incidence of treatment-emergent adverse events was higher in the interferon beta-1a group (365 [83.0%] of 440 participants) than in the ozanimod 1.0 mg group (324 [74.7%] of 434) or the ozanimod 0.5 mg group (326 [74.3%] of 439). More participants in the interferon beta-1a group had treatment-emergent adverse events leading to treatment discontinuation than in the ozanimod groups. Incidences of infections and serious treatment-emergent adverse events were similar across treatment groups. No cases of ozanimod-related symptomatic reduction in heart rate and no second-degree or third-degree cases of atrioventricular block were reported. INTERPRETATION: In this 24-month phase 3 study in participants with relapsing multiple sclerosis, ozanimod was well tolerated and associated with a significantly lower rate of clinical relapses than intramuscular interferon beta-1a. These findings show the potential of ozanimod as an effective oral therapy for individuals with relapsing multiple sclerosis. FUNDING: Celgene International II.

DrugBank数据引用了这篇文章

药物

Ozanimod

药物靶点

药物	目标	类	生物	药理作用	行动
Ozanimod	鞘氨醇1-phosphate受体1	蛋白质	人类	是的	受体激动剂	细节
Ozanimod	鞘氨醇1-phosphate受体5	蛋白质	人类	是的	受体激动剂	细节