Elezanumab(Elezanumab) - 药物靶点：RGMa_在研适应症：急性缺血性卒中，急性脊髓损伤_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Elezanumab (USAN/INN)

+ [1]

靶点

RGMa

作用机制

RGMa抑制剂(排斥性导向分子a抑制剂)、免疫调节剂、髓磷脂蛋白刺激剂

治疗领域

在研适应症

非在研适应症

原研机构

在研机构

非在研机构-

最高研发阶段临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 13225718H

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Sequence Code 13225715L

来源: *****

关联

7

项与 Elezanumab 相关的临床试验

NCT04309474 / Active, not recruiting临床2期

A Randomized, Double-Blind, Placebo-Controlled Proof-of-Concept Study to Assess the Safety and Efficacy of Elezanumab in Acute Ischemic Stroke

Stroke is one of the leading causes death and major functional disability worldwide. Treatment options for acute stroke are limited with many patients having residual neurologic impairment. The purpose of this study is to evaluate the safety and efficacy of elezanumab and assess change in neurologic function in participants following an acute ischemic stroke.
Elezanumab is an investigational drug being developed for the treatment of acute ischemic stroke. This 52-week study is "double-blinded', which means that neither the participants nor the study doctors will know who will be given elezanumab and who will be given placebo (does not contain treatment drug). Participants will be assigned to one of two groups, called treatment arms. Participants in one arm will receive elezanumab and participants in the other arm will receive placebo. There is a 1 in 2 chance that participants will be assigned to placebo. Approximately 120 subjects will be enrolled in 45 sites worldwide.
Participants will be randomized to elezanumab or placebo by intravenous (IV) infusion within 24 hours of "last known normal" (time when the participant was last known to be without signs and symptoms of the current stroke) and every 4 weeks thereafter for 48 weeks for a total of 13 doses.
There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of elezanumab will be checked by medical assessments, blood tests, evaluation of side effects, and completion of questionnaires.

开始日期2020-11-09

申办/合作机构

AbbVie, Inc.

NCT04295538 / Active, not recruiting临床2期

A Randomized, Double-Blind, Placebo-Controlled Proof of Concept Study to Assess the Safety and Efficacy of Elezanumab in Acute Traumatic Cervical Spinal Cord Injury

Acute Spinal Cord Injury (SCI) is a rare injury that leads to permanent neuromotor impairment and sudden disability. Approximately 25,000 people experience cervical SCI in the United States, Europe, and Japan every year. The purpose of this study is to see if elezanumab is safe and assess change in Upper Extremity Motor Score (UEMS) in participants with acute traumatic cervical SCI.
Elezanumab is an investigational drug being developed for the treatment of SCI. Elezanumab is a monoclonal antibody, that binds to an inhibitor of neuronal regeneration and neutralizes the inhibitor, thus potentially promoting neuroregeneration. This study is "double-blinded", which means that neither trial participants nor the study doctors will know who will be given which study drug. Study doctors put the participants in 1 of 2 groups, called treatment arms. Each group receives a different treatment. There is a 1 in 3 chance that participants will be assigned to placebo. Participants 18-75 years of age with a SCI will be enrolled. Approximately 54 participants will be enrolled in the study in approximately 49 sites worldwide.
Participants will receive intravenous (IV) doses of elezanumab or placebo within 24 hours of injury and every 4 weeks thereafter through Week 48 for a total of 13 doses.
There may be a higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the course of the study at a hospital or clinic. The effect of the treatment will be checked by medical assessments, blood tests, checking for side effects and completing questionnaires.

开始日期2020-09-06

申办/合作机构

AbbVie, Inc.

NCT03737812 / Completed临床2期

A Randomized, Double-Blind, Placebo-Controlled, Multiple Dose Study to Assess the Safety and Efficacy of Elezanumab When Added to Standard of Care in Progressive Forms of Multiple Sclerosis

The purpose of this study is to evaluate the safety and efficacy of elezanumab in participants with progressive Multiple Sclerosis (PMS).

开始日期2019-02-27

申办/合作机构

AbbVie, Inc.

100 项与 Elezanumab 相关的临床结果

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100 项与 Elezanumab 相关的转化医学

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100 项与 Elezanumab 相关的专利（医药）

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6

项与 Elezanumab 相关的文献（医药）

2024-02-01·Clinical Pharmacology in Drug Development

Comparability of Elezanumab Safety, Tolerability, and Pharmacokinetics in Healthy Japanese, Chinese, and White Participants

Article

作者: Xiong, Hao ; Locke, Charles ; Boehm, Nils ; Ziemann, Adam ; Rosebraugh, Matthew R ; Kalluri, Hari V

AbstractElezanumab is a fully human monoclonal antibody, which is directed against repulsive guidance molecule A. The safety, tolerability, pharmacokinetics (PK), and immunogenicity of elezanumab were assessed in 2 Phase 1 clinical studies. The objective of this study was to assess the PK, safety, tolerability, and immunogenicity following intravenous infusion of elezanumab in healthy adult Japanese, Han Chinese, and Caucasian participants as well as Western participants from the single‐ascending‐dose study. Elezanumab exposures were approximately 20% higher in Japanese and Han Chinese participants compared to White participants without controlling for body weight. After statistically controlling for body weight by including it as a covariate, the PK of elezanumab in White participants were comparable to those in Japanese and Han Chinese participants. The clinical implications of these exposure differences are yet to be determined. All adverse events were assessed by the investigator as having no reasonable possibility of being related to the study drugs and were mild in severity. No positive immunogenicity effect was observed that impacted elezanumab exposure or safety.

2023-02-01·Annals of Neurology

Phase 1 Evaluation of Elezanumab (Anti–Repulsive Guidance Molecule A Monoclonal Antibody) in Healthy and Multiple Sclerosis Participants

Article

作者: Misko, Thomas P. ; Liu, Wei ; Rosebraugh, Matthew R. ; Kalluri, Hari V. ; Cree, Bruce A. C. ; Ziemann, Adam

ObjectiveThis study was undertaken to describe the safety, tolerability, pharmacokinetics, and immunogenicity of elezanumab (ABT‐555), a fully human monoclonal antibody (mAb) directed against repulsive guidance molecule A (RGMa), in healthy and multiple sclerosis (MS) study participants.MethodsThe single‐center, first‐in‐human, single ascending dose (SAD) study evaluated elezanumab (50–1,600mg intravenous [IV] and 150mg subcutaneous) in 47 healthy men and women. The multicenter multiple ascending dose (MAD; NCT02601885) study evaluated elezanumab (150mg, 600mg, and 1,800mg) in 20 adult men and women with MS, receiving either maintenance or no immunomodulatory treatment.ResultsNo pattern of study drug‐related adverse events was identified for either the SAD or MAD elezanumab regimens. Across both studies, the Tmax occurred within 4 hours of elezanumab IV infusion, and the harmonic mean of t1/2 ranged between 18.6 and 67.7 days. Following multiple dosing, elezanumab Cmax, area under the curve, and Ctrough increased dose‐proportionally and resulted in dose‐dependent increases in elezanumab cerebrospinal fluid (CSF) concentrations. Elezanumab CSF penetration was 0.1% to 0.4% across both studies, with CSF levels of free RGMa decreased by >40%. Changes in CSF interleukin‐10 (IL‐10) and free RGMa demonstrated dose/exposure‐dependence.InterpretationThe elezanumab pharmacokinetic profile supports monthly, or bimonthly, administration of up to 1,800mg with the option of a loading dose of 3,600mg. Elezanumab partitioning into CSF is within the range expected for mAbs. Reduced CSF levels of free RGMa demonstrate central nervous system target binding of elezanumab with an apparent maximal effect at 1,800mg IV. Exposure‐associated increases in CSF IL‐10, an anti‐inflammatory cytokine with neuroprotective/neurorestorative properties, support potential pathway modulation in MS participants. ANN NEUROL 2023;93:285–296

2022-10-01·Neurobiology of Disease

Delayed administration of elezanumab, a human anti-RGMa neutralizing monoclonal antibody, promotes recovery following cervical spinal cord injury

Article

作者: Jacobson, Peer B ; Tator, Charles H ; Ulndreaj, Antigona ; Rahemipour, Radmehr ; Fehlings, Michael G ; Mothe, Andrea J ; Huang, Lili ; Monnier, Philippe P ; Caprelli, Mitchell

Spinal cord injury (SCI) elicits a cascade of degenerative events including cell death, axonal degeneration, and the upregulation of inhibitory molecules which limit repair. Repulsive guidance molecule A (RGMa) is an axon growth inhibitor which is also involved in neuronal cell death and differentiation. SCI causes upregulation of RGMa in the injured rodent, non-human primate, and human spinal cord. Recently, we showed that delayed administration of elezanumab, a high affinity human RGMa-specific monoclonal antibody, promoted neuroprotective and regenerative effects following thoracic SCI. Since most human traumatic SCI is at the cervical level, and level-dependent anatomical and molecular differences may influence pathophysiological responses to injury and treatment, we examined the efficacy of elezanumab and its therapeutic time window of administration in a clinically relevant rat model of cervical impact-compression SCI. Pharmacokinetic analysis of plasma and spinal cord tissue lysate showed comparable levels of RGMa antibodies with delayed administration following cervical SCI. At 12w after SCI, elezanumab promoted long term benefits including perilesional sparing of motoneurons and increased neuroplasticity of key descending pathways involved in locomotion and fine motor function. Elezanumab also promoted growth of corticospinal axons into spinal cord gray matter and enhanced serotonergic innervation of the ventral horn to form synaptic connections caudal to the cervical lesion. Significant recovery in grip and trunk/core strength, locomotion and gait, and spontaneous voiding ability was found in rats treated with elezanumab either immediately post-injury or at 3 h post-SCI, and improvements in specific gait parameters were found when elezanumab was delayed to 24 h post-injury. We also developed a new locomotor score, the Cervical Locomotor Score, a simple and sensitive measure of trunk/core and limb strength and stability during dynamic locomotion.

100 项与 Elezanumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11355	-	-	DB15240

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
急性缺血性卒中	临床2期	美国	AbbVie, Inc.	2020-11-09
急性脊髓损伤	临床2期	日本	AbbVie, Inc.	2020-09-06
急性脊髓损伤	临床2期	以色列	AbbVie, Inc.	2020-09-06
急性脊髓损伤	临床2期	韩国	AbbVie, Inc.	2020-09-06
急性脊髓损伤	临床2期	美国	AbbVie, Inc.	2020-09-06
急性脊髓损伤	临床2期	西班牙	AbbVie, Inc.	2020-09-06
急性脊髓损伤	临床2期	澳大利亚	AbbVie, Inc.	2020-09-06
急性脊髓损伤	临床2期	加拿大	AbbVie, Inc.	2020-09-06
多发性硬化症	药物发现	美国	AbbVie, Inc.	2018-12-11
多发性硬化症	药物发现	加拿大	AbbVie, Inc.	2018-12-11

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临床结果

适应症

分期

评价

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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


NCT03737851 (RADIUS-R, CTgov)	临床2期	多发性硬化症	208	placebo (Placebo)	觸製醖鑰醖廠膚淵積艱(夢醖鹽鹽簾觸構遞餘鏇) = 簾鹹鹹鹽簾蓋壓獵範廠繭選築顧網簾餘顧夢醖 (積鹽觸構襯構範膚築選, 鹽鹹鹽餘窪衊鏇範糧鑰 ~ 蓋窪齋鏇醖糧顧窪遞繭) 更多	-	2023-12-22
				elezanumab (Elezanumab Dose 1)	觸製醖鑰醖廠膚淵積艱(夢醖鹽鹽簾觸構遞餘鏇) = 鑰繭範構襯餘膚構選壓繭選築顧網簾餘顧夢醖 (積鹽觸構襯構範膚築選, 遞壓壓遞網築鏇醖積醖 ~ 選鹹壓簾壓壓選艱鬱餘) 更多
NCT03737812 (RADIUS-P, CTgov)	临床2期	多发性硬化症	123	placebo (Placebo)	築夢鹹壓遞鏇糧構獵願(選網蓋範壓構積鬱襯鹹) = 蓋選艱艱糧築構製鏇製齋夢範築淵構鹽憲窪簾 (膚顧選網襯顧築願願壓, 廠構糧廠膚願糧鬱網鹹 ~ 憲蓋蓋選築鹽簾繭積願) 更多	-	2023-12-21
				elezanumab (Elezanumab 400mg Dose)	築夢鹹壓遞鏇糧構獵願(選網蓋範壓構積鬱襯鹹) = 糧膚壓衊齋選範鏇鹹鹽齋夢範築淵構鹽憲窪簾 (膚顧選網襯顧築願願壓, 膚廠夢範積網壓憲遞範 ~ 顧願獵醖膚窪蓋窪襯醖) 更多
NCT02601885 (Pubmed) 人工标引	临床1期	多发性硬化症	47	Elezanumab (multiple ascending dose)	(窪選淵繭繭積壓壓廠製) = 積鑰觸淵鑰遞網築衊鬱憲糧醖觸艱鑰選窪蓋蓋 (積選餘衊網製艱壓鏇襯 ) 更多	积极	2022-09-12
NCT03737812 \| NCT03737851 (RADIUS-P, ECTRIMS2020)	临床2期	多发性硬化症	-	Elezanumab	選範鏇範憲襯憲憲壓艱(鑰襯選齋廠夢網蓋願鹹) = 夢廠鬱齋積鬱憲製壓繭蓋繭醖憲衊簾鹽淵鹽鹽 (願鑰獵網範構顧積鑰衊 )	-	2020-12-07
				Placebo	選範鏇範憲襯憲憲壓艱(鑰襯選齋廠夢網蓋願鹹) = 膚製夢鏇範蓋築齋積壓蓋繭醖憲衊簾鹽淵鹽鹽 (願鑰獵網範構顧積鑰衊 )
Phase 1, multiple-dose study of elezanumab (ABT-555) (ECTRIMS2018)	临床1期	复发性多发性硬化 repulsive guidance molecule A (RGMa) \| Interleukin-10	20	Elezanumab 150 mg	(鏇蓋製蓋鹽蓋簾顧糧築) = 25% of all patients 窪願夢觸網鹹淵選鹹艱 (簾鹽蓋構願繭構膚繭繭 )	积极	2018-10-09
				Elezanumab 600 mg