(Evobrutinib) - 药物靶点：BTK_专利_临床

概要

基本信息

药物类型

小分子化药

别名

+ [2]

靶点

BTK

作用机制

BTK抑制剂(酪氨酸蛋白激酶BTK抑制剂)

治疗领域

肿瘤免疫系统疾病神经系统疾病+ [3]

在研适应症-

非在研适应症

肝病复发性多发性硬化复发-缓解型多发性硬化+ [3]

原研机构

Merck Serono SA

在研机构

Merck Healthcare KGaA

非在研机构

EMD Serono Research & Development Institute, Inc.Merck Serono SAMerck KGaA

最高研发阶段临床1期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

结构

分子式C25H27N5O2

InChIKeyQUIWHXQETADMGN-UHFFFAOYSA-N

CAS号1415823-73-2

关联

31

项与 Evobrutinib 相关的临床试验

NCT05245396 / Completed临床1期

A Phase I, Single-site, Open-label, Partially Randomized Study to Evaluate the Relative Bioavailability and Pharmacokinetics of Evobrutinib Following Administration of Different Formulations in Healthy Participants

The purpose of this study is to evaluate the pharmacokinetic (PK), pharmacodynamic (PD), and safety and tolerability of evobrutinib after oral administration of immediate release (IR) and modified release (MR) formulations in healthy participants.

开始日期2022-02-02

申办/合作机构

Merck Healthcare KGaA

[+1]

NCT05248945 / Completed临床1期

Phase I, Open-Label, Single-Sequence Study of the Effect of Multiple Doses of Carbamazepine on Single-Dose Evobrutinib Pharmacokinetics in Healthy Participants

The purpose of this study is to investigate the effect of multiple doses of carbamazepine on two single doses of evobrutinib pharmacokinetics (PK) in healthy participants. Study details include:
Study Duration: up to 54 days. Treatment Duration: 25 days. Visit Frequency: Participants will be resident in the Clinical Research Unit from Day 1 to Day 20 and return on Day 26 for a Safety Follow-Up visit.

开始日期2022-01-13

申办/合作机构

Merck Healthcare KGaA

NCT05064488 / Completed临床1期

A Phase I, Open-Label, Two-Part Study of the Effect of Multiple-Dose Evobrutinib on Transporter Substrates Digoxin, Metformin, Rosuvastatin, and Sumatriptan Pharmacokinetics in Healthy Participants

This study consists of 2 parts: Part 1 and 2. The purpose of this study is to evaluate the pharmacokinetic, safety and tolerability of multiple doses of evobrutinib on single doses of digoxin, metformin and rosuvastatin in Part-1 and sumatriptan in Part-2 of the study.

开始日期2021-10-04

申办/合作机构

Merck Healthcare KGaA

100 项与 Evobrutinib 相关的临床结果

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100 项与 Evobrutinib 相关的转化医学

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100 项与 Evobrutinib 相关的专利（医药）

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37

项与 Evobrutinib 相关的文献（医药）

2024-03-12·Neurology

Effect of Evobrutinib on Slowly Expanding Lesion Volume in Relapsing Multiple Sclerosis: A Post Hoc Analysis of a Phase 2 Trial.

Article

作者: Douglas L Arnold ; Colm Elliott ; Emily C Martin ; Yann Hyvert ; Davorka Tomic ; Xavier Montalban

BACKGROUND AND OBJECTIVES:

Chronic active lesions (CALs) are demyelinated multiple sclerosis (MS) lesions with ongoing microglia/macrophage activity, resulting in irreversible neuronal damage and axonal loss. Evobrutinib is a highly selective, covalent, CNS-penetrant, Bruton tyrosine kinase inhibitor. This post hoc analysis evaluated the effect of evobrutinib on slowly expanding lesion (SEL) volume, an MRI marker of CALs, assessed baseline-week 48 in a phase 2, double-blind, randomized trial (NCT02975349) in relapsing MS (RMS).

METHODS:

In the 48-week, double-blind trial, adult patients received evobrutinib (25 mg once daily [QD], 75 mg QD, or 75 mg twice daily [BID]), placebo (switched to evobrutinib 25 mg QD after week 24), or open-label dimethyl fumarate (DMF) 240 mg BID. SELs were defined as slowly and consistently radially expanding areas of preexisting T2 lesions of ≥10 contiguous voxels (∼30 mm³) over time. SELs were identified by MRI and assessed by the Jacobian determinant of the nonlinear deformation from baseline to week 48. SEL volume analysis, stratified by baseline T2 lesion volume tertiles, was based on week 48/end-of-treatment status (completers/non-completers). Treatment effect was analyzed using the stratified Hodges-Lehmann estimate of shift in distribution and stratified Wilcoxon rank-sum test. Comparisons of evobrutinib and DMF vs placebo/evobrutinib 25 mg QD were made. Subgroup analyses used pooled treatment groups (evobrutinib high dose [75 mg QD/BID] vs low dose [placebo/evobrutinib 25 mg QD]).

RESULTS:

The SEL analysis set included 223 patients (mean [SD] age: 42.4 [10.7] years; 69.3% female; 87.4% relapsing/remitting MS). Mean (SD) SEL volume was 2,099 (2,981.0) mm³ with evobrutinib 75 mg BID vs 2,681 (3,624.2) mm³ with placebo/evobrutinib 25 mg QD. Median number of SELs/patient ranged from 7 to 11 across treatments. SEL volume decreased with increasing evobrutinib dose vs placebo/evobrutinib 25 mg QD, and no difference with DMF vs placebo/evobrutinib 25 mg QD was noted. SEL volume significantly decreased with evobrutinib 75 mg BID vs placebo/evobrutinib 25 mg QD (-474.5 mm³ [-1,098.0 to -3.0], p = 0.047) and vs DMF (-711.6 [-1,290.0 to -149.0], p = 0.011). SEL volume was significantly reduced for evobrutinib high vs low dose within baseline Expanded Disability Status Scale ≥3.5 and longer disease duration (≥8.5 years) subgroups.

DISCUSSION:

Evobrutinib reduced SEL volume in a dose-dependent manner in RMS, with a significant reduction with evobrutinib 75 mg BID. This is evident that evobrutinib affects brain lesions associated with chronic inflammation and tissue loss.

TRIAL REGISTRATION INFORMATION:

ClinicalTrials.gov number: NCT02975349. Submitted to ClinicalTrials.gov on November 29, 2016. First patient enrolled: March 7, 2017.

CLASSIFICATION OF EVIDENCE:

This study provides Class II evidence that evobrutinib reduces the volume of SELs assessed on MRI comparing baseline with week 48, in patients with RMS.

2024-01-22·Brain pathology (Zurich, Switzerland)

The relation between BTK expression and iron accumulation of myeloid cells in multiple sclerosis.

Article

作者: Anja Steinmaurer ; Christian Riedl ; Theresa König ; Giulia Testa ; Ulrike Köck ; Jan Bauer ; Hans Lassmann ; Romana Höftberger ; Thomas Berger ; Isabella Wimmer ; Simon Hametner

Activation of Bruton's tyrosine kinase (BTK) has been shown to play a crucial role in the proinflammatory response of B cells and myeloid cells upon engagement with B cell, Fc, Toll-like receptor, and distinct chemokine receptors. Previous reports suggest BTK actively contributes to the pathogenesis of multiple sclerosis (MS). The BTK inhibitor Evobrutinib has been shown to reduce the numbers of gadolinium-enhancing lesions and relapses in relapsing-remitting MS patients. In vitro, BTK inhibition resulted in reduced phagocytic activity and modulated BTK-dependent inflammatory signaling of microglia and macrophages. Here, we investigated the protein expression of BTK and CD68 as well as iron accumulation in postmortem control (n = 10) and MS (n = 23) brain tissue, focusing on microglia and macrophages. MS cases encompassed active, chronic active, and inactive lesions. BTK⁺ and iron⁺ cells positively correlated across all regions of interests and, along with CD68, revealed highest numbers in the center of active and at the rim of chronic active lesions. We then studied the effect of BTK inhibition in the human immortalized microglia-like HMC3 cell line in vitro. In particular, we loaded HMC3 cells with iron-dextran and subsequently administered the BTK inhibitor Evobrutinib. Iron treatment alone induced a proinflammatory phenotype and increased the expression of iron importers as well as the intracellular iron storage protein ferritin light chain (FTL). BTK inhibition of iron-laden cells dampened the expression of microglia-related inflammatory genes as well as iron-importers, whereas the iron-exporter ferroportin was upregulated. Our data suggest that BTK inhibition not only dampens the proinflammatory response but also reduces iron import and storage in activated microglia and macrophages with possible implications on microglial iron accumulation in chronic active lesions in MS.

2023-12-19·Pharmaceutics

Update and Application of a Deep Learning Model for the Prediction of Interactions between Drugs Used by Patients with Multiple Sclerosis.

Article

作者: Michael Hecker ; Niklas Frahm ; Uwe Klaus Zettl

Patients with multiple sclerosis (MS) often take multiple drugs at the same time to modify the course of disease, alleviate neurological symptoms and manage co-existing conditions. A major consequence for a patient taking different medications is a higher risk of treatment failure and side effects. This is because a drug may alter the pharmacokinetic and/or pharmacodynamic properties of another drug, which is referred to as drug-drug interaction (DDI). We aimed to predict interactions of drugs that are used by patients with MS based on a deep neural network (DNN) using structural information as input. We further aimed to identify potential drug-food interactions (DFIs), which can affect drug efficacy and patient safety as well. We used DeepDDI, a multi-label classification model of specific DDI types, to predict changes in pharmacological effects and/or the risk of adverse drug events when two or more drugs are taken together. The original model with ~34 million trainable parameters was updated using >1 million DDIs recorded in the DrugBank database. Structure data of food components were obtained from the FooDB database. The medication plans of patients with MS (n = 627) were then searched for pairwise interactions between drug and food compounds. The updated DeepDDI model achieved accuracies of 92.2% and 92.1% on the validation and testing sets, respectively. The patients with MS used 312 different small molecule drugs as prescription or over-the-counter medications. In the medication plans, we identified 3748 DDIs in DrugBank and 13,365 DDIs using DeepDDI. At least one DDI was found for most patients (n = 509 or 81.2% based on the DNN model). The predictions revealed that many patients would be at increased risk of bleeding and bradycardic complications due to a potential DDI if they were to start a disease-modifying therapy with cladribine (n = 242 or 38.6%) and fingolimod (n = 279 or 44.5%), respectively. We also obtained numerous potential interactions for Bruton's tyrosine kinase inhibitors that are in clinical development for MS, such as evobrutinib (n = 434 DDIs). Food sources most often related to DFIs were corn (n = 5456 DFIs) and cow's milk (n = 4243 DFIs). We demonstrate that deep learning techniques can exploit chemical structure similarity to accurately predict DDIs and DFIs in patients with MS. Our study specifies drug pairs that potentially interact, suggests mechanisms causing adverse drug effects, informs about whether interacting drugs can be replaced with alternative drugs to avoid critical DDIs and provides dietary recommendations for MS patients who are taking certain drugs.

92

项与 Evobrutinib 相关的新闻（医药）

2024-03-29

·精准药物

默克BTK抑制剂 evobrutinib终止开发，MUCI/EGFR双抗ADC消失

默克公司在周四的 2023 年第四季度业绩中指出，该公司已取消用于治疗多发性硬化症的 BTK 抑制剂evobrutinib。首席执行官贝伦·加里霍（Belén Garijo）在投资者电话会议上表示，该计划已正式终止。2023年12月，该公司宣布其两项研究 evobrutinib 安全性和有效性的 III 期试验并未达到降低多发性硬化症 (MS) 患者年复发率的主要终点。然而，终止合同似乎并没有阻止加里霍参加电话会议。她指出，尽管 evobrutinib 遇到了挫折，但该公司“对我们在医疗保健领域的定位相当稳固和良好”。加里霍提到，解约成本为 9500 万欧元（1.038 亿美元）。然而，这是一次性付款。她还表示，evobrutinib 不会像去年那样产生上市前费用。Merck KGaA 在其 BTK 抑制剂方面曾遇到过障碍。2023 年 4 月，在两名多发性硬化症患者出现肝损伤迹象后，FDA 暂停了 III 期试验。当时，不允许该公司招募新患者参加试验，并且已停止接受该药物治疗不到70天的参与者的给药。BTK 抑制剂作为一类药物也遇到了障碍。就在默克公司 III 期试验失败之前，罗氏用于治疗多发性硬化症的 BTK 抑制剂因一些潜在的肝损伤病例而被 FDA 暂停临床。具体来说，参与罗氏 III 期研究的两名患者在接受剂量后出现肝转氨酶水平异常升高。FDA 已对其他 BTK 抑制剂进行了部分临床搁置。与此同时，默克公司一直在研究其他领域。2023 年 1 月，该公司通过预付 4500 万美元从 Inspirna 获得两项资产许可，扩大了其结直肠癌产品组合。周一，这家德国公司还向 C4 Therapeutics 预付了 1600 万美元，后者可能获得超过 7.4 亿美元的潜在里程碑付款，以建立研究合作，发现两种针对“关键致癌蛋白”的靶向蛋白质降解剂.现在，evobrutinib也已经消失了在管线中而且多日不追踪，那个曾经的MUCI/EGFR双抗ADC药物M1231同样也已经在两家管线中消失不见。2023年9月份，这个产品还是在的2021年，就写过这个品种，大家不妨看看当时就提出了EGFR/双抗，包括Met声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

引进/卖出临床3期抗体药物偶联物医药出海

2024-03-11

·药时代

默克终止BTK抑制剂开发！啃不动“自免”的骨头，肝损伤风险谁来验证……

血液瘤王者，自免碰壁相同的靶点因为赛道的差异，可能造就完全不同的命运。对于血液瘤领域的王牌治疗药物BTK抑制剂而言特别如此。尽管很早之前学界就已阐明BTK在自免疾病的致病通路中可能存在重要作用，但进入成药阶段，BTK抑制剂在自免领域的推进举步维艰。作为近年来最热门的血液瘤赛道之一，根据智慧芽情报库数据，全球有46款BTK抑制剂进入临床阶段，竞争热烈。但BTK抑制剂在B细胞相关恶性血液肿瘤中的成功，似乎难以复制到自免疾病领域中。德国默克的Evobrutinib曾是BTK抑制剂在自免领域闯荡的领头羊。但去年年末，默克宣布研究性BTK抑制剂Evobrutinib在复发性多发性硬化症 (RMS)的III期evolutionRMS 1和evolutionRMS 2试验中均未达到降低年复发率的主要终点，带来了巨大的不确定性。在昨日的2023年第四季度业绩披露会上，默克CEO Belén Garijo表示，已正式终止Evobrutinib的开发。两年间，多款在研BTK抑制剂在自免领域的试探碰壁，默克并非孤例，怀疑重点主要建立在其安全性问题之上。2023年4月，Evobrutinib因两名受试者出现肝损伤，临床试验被FDA一度叫停。2023年2月，赛诺菲终止BTK抑制剂Tolebrutinib治疗全身性重症肌无力的Ⅲ期临床研究URSA研究，该药物曾在2022年因肝损伤被暂停部分研究。在2023年12月7日，默克宣布临床试验失败的两天前，罗氏（基因泰克）的BTK抑制剂Fenebrutinib则在MS的Ⅲ期FENhance研究中发现药物肝损伤风险，导致临床试验暂停。疗效不佳、安全性成疑，Follower想要在自免领域大展身手，就必须交出更令人信服的答案。强有力的对照组多发性硬化症是最常见的中枢神经系统疾病，成因复杂。患者的中枢神经髓鞘受到破坏，并因此导致患者的神经信号传导受损。研究发现B细胞可能在MS的致病机制中起到重要作用，且部分抗B细胞疗法，如CD20抗体等，已展示出了一定缓解MS的作用。那么理论上能够阻止B细胞扩增，就有可能在一定程度上阻止神经系统被进一步破坏。而BTK作为B细胞受体信号通路中的关键激酶，可调控B细胞的增殖，乃至抗体和细胞因子的释放，并可调节巨噬细胞、小胶质细胞的活化。但EvolutionRMS 1和EvolutionRMS 2并未证明与特立氟胺（Aubagio）相比，使用Evobrutinib的患者年化复发率（ARR）存在统计学差异。此前默克在公告中表示，对照组的ARR数据显著低于近期的其他研究，也就是说，可能这一批受试者和特立氟胺的“适配程度”特别好。和诺华的CD20单抗奥法妥木单抗（Ofatumumab，商品名Kesimpta）中的对照组相比，同样是治疗MS，确实出现了不足以以试验设计解释的，较为明显的对照组数据差异。所以默克当时表示将会重新评估临床试验数据。没想到，评估评估，最后把自己评估没了……此外，自Ⅱ期临床试验以来，Evobrutinib一直表现出较强的肝毒性，Ⅱ期临床试验中26%的受试者出现转氨酶升高，11%的受试者退出临床试验。可能终止开发与毒副作用也不无关系。肝损伤原因成谜根据以往我们在BTK抑制剂在血液瘤领域中总结的经验，BTK抑制剂依然存在相对难以克服的药物副作用。而自免类疾病往往需要患者长期服药，因此如肝损伤等不良事件很可能是难以接受的。但在不同的适应症中，同一款BTK抑制剂所呈现的肝毒性不尽相同。尽管部分BTK抑制剂本身具有肝毒性，大多数情况下，患者暂停药物使用即可恢复。但MS患者本身就可能会存在肝损伤，或者肝脏更加敏感，二者相互作用导致毒副作用进一步增强，不过这一观点目前还需要更多数据佐证。这某种程度上既意味着BTK抑制剂可能会在MS适应症上出现阻力，亦代表着在MS之外的其他自免疾病中BTK抑制剂仍旧存在开发价值。诺华的BTK抑制剂Remibrutinib的临床试验或许可以验证这一猜想。目前诺华已完成该药物治疗慢性自发性荨麻疹的两项Ⅲ期临床试验。在相关研究中，活性药物组和安慰剂组的肝功能检查结果无显著差异，可证实Remibrutinib安全性良好。目前诺华已开展Remibrutinib用于治疗MS的Ⅲ期临床试验，如在MS适应症开发的后续数据中再次出现肝损伤风险提示，或许就意味着存在短期内难以解决的共性问题……BTK适应症开发，MS并不是一个常见项数据来源：智慧芽新药情报库坦诚来讲，哪怕说能挺进自免领域适应症的Ⅲ期临床试验，对于BTK抑制剂来说都已经是一个不小的突破，MS的进展已经比之前的适应症开发乐观太多。在BTK-自免赛道中，MS既不是最早被开发的适应症，也不是目前最常见的在研适应症。更多在研药物实际上栽在了系统性红斑狼疮、类风湿性关节炎、特应性皮炎、银屑病等适应症开发中，普遍在Ⅲ期阶段之前夭折。封面图来源：Pixabay版权声明/免责声明本文为药时代团队原创。本文仅作信息交流之目的，不提供任何商用、医用、投资用建议。文中图片、视频、字体、音乐等素材或为药时代购买的授权正版作品，或来自微信公共图片库，或取自公司官网/网络，部分素材根据CC0协议使用，版权归拥有者，药时代尽力注明来源。如有任何问题，请与我们联系。衷心感谢!药时代官方网站:www.drugtimes.cn联系方式:电话:13651980212微信:27674131邮箱:contact@drugtimes.cnFerring首席科学家杨翼博士：肥胖症疫苗离我们还有多远？礼来D药推迟上市，FDA的B面下一代GLP-1类药物早期临床数据读出，直接推动诺和诺德成为6000亿美元市值药企！点击这里，欣赏更多精彩内容！

临床3期临床1期细胞疗法引进/卖出临床2期

2024-03-11

·BioSpace

FDA Rejects Viatris, Mapi’s Long-Acting Multiple Sclerosis Injection

Pictured: A nerve cell attacked by the immune system/iStock, peterschreiber.media The FDA has rejected Viatris and Mapi Pharma’s investigational formulation of glatiramer acetate, dubbed GA Depot 40, for the treatment of relapsing forms of multiple sclerosis, the companies announced on Monday. Details of the FDA’s rejection were scant and the partners only said that they are currently reviewing the Complete Response Letter to better determine the “appropriate next steps” for GA Depot 40. “The companies continue to believe in the potential of the product to provide an important new treatment advancement for patients with multiple sclerosis,” according to the announcement. Glatiramer acetate, the active ingredient of GA Depot 40 is an immunomodulator that targets the inflammatory pathways underpinning multiple sclerosis (MS). The drug itself cannot cross the blood-brain barrier but exerts its effects through peripheral helper cells, which can then potentially enter the brain and reduce inflammation within the central nervous system. Originally developed by Teva Pharmaceuticals, glatiramer acetate was first approved in the U.S. in 1996 for the treatment of relapsing forms of MS. It carries the brand name Copaxone. Viatris and Israel-based partner Mapi were proposing their investigational long-acting formulation of glatiramer acetate, which is designed to be given via an intramuscular injection every four weeks. The partners supported their New Drug Application, which the FDA accepted in August 2023, with Phase III data obtained from more than 1,000 patients who received a total of 13 doses of either 40-mg GA Depot or placebo. Results showed that the long-acting formulation could cut the annualized relapse rate by 30.1% versus placebo, an effect that was statistically significant with a p-value of 0.0066. GA Depot also offered patients a preferable dosing schedule and elicited fewer injection site reactions as compared with other products. At the time, Viatris President Rajiv Malik said in a statement that GA depot, if approved, could “improve patient experience through fewer injections, greater tolerability and increased compliance.” Monday’s rejection continues biopharma’s losing streak in the MS space. Last week, Merck KGaA announced that it was abandoning the development of its BTK inhibitor evobrutinib in MS. The decision comes after the candidate failed two Phase III trials in December 2023, unable to significantly reduce annualized relapse rate versus teriflunomide. Other BTK inhibitors have also stumbled in MS. Sanofi’s tolebrutinib was put under partial clinical hold in June 2022 due to drug-induced liver injury. Roche’s candidate fenebrutinib ran into the same problem in December 2023, when the FDA also put a regulatory pause on the BTK inhibitor for potential liver injury. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床3期上市批准临床结果

100 项与 Evobrutinib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB15170

研发状态

适应症	最高研发状态	国家/地区	公司
复发性多发性硬化	临床3期	罗马尼亚更多	Merck Healthcare KGaA 更多
多发性硬化症	临床3期	德国更多	Merck Serono SA 更多
复发-缓解型多发性硬化	临床2期	俄罗斯更多	EMD Serono Research & Development Institute, Inc. 更多
类风湿关节炎	终止	美国更多	Merck Serono SA 更多
系统性红斑狼疮	终止	中国台湾更多	-

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适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04338061 \| NCT04338022 (evolutionRMS 2 \| evolutionRMS 1, Biospace) 人工标引	临床3期	复发性多发性硬化	-	Evobrutinib (evolutionRMS 1)	(選鬱顧醖遞遞廠齋鹽鏇) = 築積選網構壓願蓋遞餘襯鑰襯積構廠艱選衊鏇 (廠簾窪鏇構窪膚窪鏇齋 ) 未达到	不佳	2023-12-05
				teriflunomide (evolutionRMS 1)	(選鬱顧醖遞遞廠齋鹽鏇) = 簾顧觸餘遞鏇簾窪顧夢襯鑰襯積構廠艱選衊鏇 (廠簾窪鏇構窪膚窪鏇齋 ) 未达到
NCT04032171 (CTgov)	临床3期	复发-缓解型多发性硬化 \| 横纹肌肉瘤	1	Avonex® matched Placebo+Evobrutinib (Evobrutinib + Avonex® Matched Placebo)	(構醖夢構鏇廠艱獵鏇鏇) = 繭齋襯蓋窪願繭夢艱顧鹽鏇淵醖廠夢範餘構廠 (築構艱醖淵夢淵選夢積, 鏇壓夢獵製範構鬱齋範 ~ 鏇網簾顧範鏇鑰醖餘獵) 更多	-	2021-08-05
				Evobrutinib matched Placebo+Avonex® (Avonex® + Evobrutinib Matched Placebo)	夢簾醖鏇艱衊醖鑰築廠(觸餘鏇鏇網壓窪膚衊繭) = 製鹹簾築獵構顧膚夢獵襯餘鏇淵艱餘齋簾網選 (願觸遞窪獵餘餘觸鹽遞, 遞膚製鑰繭範選繭鏇憲 ~ 獵憲醖觸觸衊選鹽餘積) 更多
NCT02784106 (CTgov)	临床2期	类风湿关节炎	65	Placebo (Placebo: Double-Blind Treatment Period)	願襯艱齋衊壓襯窪廠製(鬱憲鹽築鹽製淵鏇齋鹽) = 餘艱鬱鹽齋願襯製範遞淵積簾簾鏇構願顧鬱淵 (選衊糧壓遞構鹽獵製醖, 觸醖觸蓋襯選願鹽網鏇 ~ 廠蓋醖鏇鑰憲糧範積觸) 更多	-	2018-05-30
				M2951 (M2951: Double-Blind Treatment Period)	願襯艱齋衊壓襯窪廠製(鬱憲鹽築鹽製淵鏇齋鹽) = 膚憲壓繭遞窪築製遞鏇淵積簾簾鏇構願顧鬱淵 (選衊糧壓遞構鹽獵製醖, 夢艱醖製獵壓鏇簾壓顧 ~ 鬱衊糧積壓衊選廠壓築) 更多
NCT03233230 \| NCT02975349 \| NCT02975336 (Pubmed)	临床2期	多发性硬化症 \| 类风湿关节炎 \| 系统性红斑狼疮	1,083	Evobrutinib	(襯願範夢積醖夢艱願衊) = 襯構壓憲選簾壓選齋齋膚衊蓋範齋窪鬱願壓網 (蓋鏇繭夢鹹選簾願網觸 ) 更多	-	2022-11-23
				Placebo	(襯願範夢積醖夢艱願衊) = 淵夢襯糧蓋鑰範鬱窪憲膚衊蓋範齋窪鬱願壓網 (蓋鏇繭夢鹹選簾願網觸 ) 更多
AAN2023	N/A	神经炎症	-	Evobrutinib	願膚選範顧餘網獵鑰膚(壓積觸顧衊製衊鑰鹹糧) = 鬱鑰艱膚觸願廠襯範鹹願淵膚淵築壓繭鑰艱膚 (鑰網窪願淵獵網製鹽襯 ) 更多	积极	2023-04-25
NCT03233230 (CTgov)	临床2期	类风湿关节炎	390	placebo (Placebo)	夢襯繭構襯顧範顧衊蓋(製鏇製鑰憲鹽廠範齋餘) = 鏇築襯願蓋醖艱繭壓簾繭鹽築壓構襯獵壓蓋鹹 (構顧製襯衊獵窪廠網艱, 淵製遞淵壓餘願觸選構 ~ 鹹網淵築壓醖齋壓壓願) 更多	-	2020-09-28
				M2591 25 mg QD (M2951 25 mg QD)	夢襯繭構襯顧範顧衊蓋(製鏇製鑰憲鹽廠範齋餘) = 齋夢餘簾醖壓醖製鹹獵繭鹽築壓構襯獵壓蓋鹹 (構顧製襯衊獵窪廠網艱, 鏇膚齋衊願艱壓積鬱膚 ~ 餘範簾壓襯築衊憲鏇積) 更多
S46.007 (AAN2023)	临床3期	多发性硬化症 BTK	-	Tolebrutinib	築網蓋築願鹽積糧簾遞(醖積鹽夢構憲襯積觸鹹) = 網製顧構鑰襯鏇構壓糧製餘艱鬱顧鏇鹽簾構醖 (餘製壓壓選選醖憲餘鹹, 0.40) 更多	积极	2023-04-25
				Evobrutinib	築網蓋築願鹽積糧簾遞(醖積鹽夢構憲襯積觸鹹) = 築窪構醖鹹顧壓築壓衊製餘艱鬱顧鏇鹽簾構醖 (餘製壓壓選選醖憲餘鹹, 0.13) 更多
NCT04032158 (CTgov)	临床3期	复发性多发性硬化 \| 复发-缓解型多发性硬化	3	Placebo+Avonex+Evobrutinib (Experimental: Evobrutinib + Avonex® Matched Placebo)	(願齋憲簾構淵鹽窪憲觸) = 憲簾顧觸鹹觸壓壓襯選鬱膚餘製觸壓艱膚襯簾 (簾選築願醖憲築鏇網遞, 艱壓遞製繭壓醖積淵選 ~ 構衊顧鹹觸糧糧艱窪壓) 更多	-	2021-08-05
				Placebo+Avonex+Evobrutinib (Active Comparator: Avonex® + Evobrutinib Matched Placebo)	(願齋憲簾構淵鹽窪憲觸) = 積鹹廠繭餘願鑰鹹齋窪鬱膚餘製觸壓艱膚襯簾 (簾選築願醖憲築鏇網遞, 淵鹹鹽繭築範憲選壓憲 ~ 構糧築淵鏇膚餘艱鏇鏇) 更多
NCT02975349 (CTgov)	临床2期	复发性多发性硬化 \| 复发-缓解型多发性硬化	267	Placebo (Placebo)	鹽選蓋憲醖蓋製窪壓廠(夢獵鏇鏇鏇窪壓衊獵選) = 夢顧鑰鏇構衊選鑰窪齋鏇淵製壓憲鏇繭憲齋壓 (築窪積餘繭醖糧繭壓鹽, 齋襯觸鑰壓範窪齋膚鏇 ~ 製觸衊糧艱窪襯夢鑰淵) 更多	-	2021-02-05
				Evobrutinib (Evobrutinib 25 mg QD)	鹽選蓋憲醖蓋製窪壓廠(夢獵鏇鏇鏇窪壓衊獵選) = 範簾窪糧醖廠構築鬱構鏇淵製壓憲鏇繭憲齋壓 (築窪積餘繭醖糧繭壓鹽, 鹽淵築鬱膚積齋淵構獵 ~ 選遞膚餘廠鏇製廠壓艱) 更多
NCT02975336 (CTgov)	临床2期	系统性红斑狼疮	469	M2951 (DBPC Period: M2951 25 mg QD)	衊廠鹹餘範簾製齋顧構(壓範鑰鏇蓋選製鏇獵顧) = 蓋網觸壓糧廠壓築衊鹽壓遞願壓衊淵積鏇遞醖 (淵繭襯憲願鑰糧鏇鏇製, 齋淵遞鬱簾積淵艱鑰積 ~ 膚齋構獵糧窪廠襯鑰製) 更多	-	2020-12-17
				M2951 (DBPC Period: M2951 75 mg QD)	衊廠鹹餘範簾製齋顧構(壓範鑰鏇蓋選製鏇獵顧) = 繭膚窪鬱艱膚蓋壓築憲壓遞願壓衊淵積鏇遞醖 (淵繭襯憲願鑰糧鏇鏇製, 齋醖憲選願膚淵鹹製鹹 ~ 鹽鑰淵膚鹽餘製觸齋選) 更多