Prezalumab(Prezalumab) - 药物靶点：ICOSLG_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-B7RP1-MAb

+ [2]

靶点

ICOSLG

作用机制

ICOS配体抑制剂

治疗领域

免疫系统疾病眼部疾病口颌疾病+ [3]

在研适应症-

非在研适应症

关节炎皮肤红斑狼疮寻常狼疮+ [3]

原研机构

Amgen, Inc.

在研机构-

非在研机构

Amgen, Inc.

MedImmune LLC

最高研发阶段终止临床2期

首次获批日期-

最高研发阶段(中国)-

特殊审评-

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结构/序列

Sequence Code 9697699H

来源: *****

Sequence Code 78566L

来源: *****

关联

6

项与 Prezalumab 相关的临床试验

NCT02334306

/ Completed临床2期

A Phase 2a, Randomized, Placebo Controlled, Proof of Mechanism Study to Evaluate the Safety and Efficacy of AMG 557/MEDI5872 in Subjects With Primary Sjögren's Syndrome

A Phase 2a study to evaluate the efficacy and safety of AMG 557/MEDI5872 in Primary Sjögren's Syndrome

开始日期2015-06-08

申办/合作机构

MedImmune LLC

[+1]

NCT01683695

/ Completed临床1期

A Randomized, Double-blind, Parallel, Placebo-controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of AMG 557 in Systemic Lupus Erythematosus (SLE) Subjects With Active Lupus Arthritis

This is a multicenter, randomized, double-blind, parallel, placebo-controlled, multiple dose study that will enroll approximately 40 systemic lupus erythematosus subjects with active lupus arthritis.

开始日期2012-06-01

申办/合作机构

Amgen, Inc.

NCT01493518

/ Terminated临床1期

A Randomized, Double-blind, Placebo-controlled, Multiple-dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Clinical Effects of AMG 557 in Subjects With Moderate to Severe Psoriasis

The purpose of this study is to study the safety, tolerability and immunogenicity of AMG 557 following multiple subcutaneous dose administration in adults with moderate to severe psoriasis.

开始日期2011-11-01

申办/合作机构

Amgen, Inc.

100 项与 Prezalumab 相关的临床结果

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100 项与 Prezalumab 相关的转化医学

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100 项与 Prezalumab 相关的专利（医药）

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12

项与 Prezalumab 相关的文献（医药）

2023-08-01·Arthritis & Rheumatology

Non‐Redundant Roles of T Cell Costimulation Pathways in Inflammatory Arthritis Revealed by Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN‐101)

Article

作者: Kleist, Kayla ; Blair, Tiffany C ; Wolfson, Martin F ; Lewis, Katherine E ; Peng, Stanford L ; Mudri, Sherri ; Debrot, Susan ; Levin, Steven D ; Rixon, Mark W ; Holland, Pamela M ; Dillon, Stacey R ; Evans, Lawrence S ; Garrett, Logan ; Bhandari, Janhavi G

ObjectiveCD28 and inducible T cell costimulator (ICOS) appear to have nonredundant roles in T cell activation and adaptive immunity. We undertook this study to characterize in vitro and in vivo the therapeutic potential of acazicolcept (ALPN‐101), an Fc fusion protein of a human variant ICOS ligand (ICOSL) domain designed to inhibit both CD28 and ICOS costimulation, in inflammatory arthritis.MethodsAcazicolcept was compared in vitro with inhibitors of either the CD28 or ICOS pathways (abatacept and belatacept [CTLA‐4Ig], prezalumab [anti‐ICOSL monoclonal antibody]) in receptor binding and signaling assays, and in a collagen‐induced arthritis (CIA) model. Acazicolcept was also compared in cytokine and gene expression assays of peripheral blood mononuclear cells (PBMCs) from healthy donors or rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients stimulated with artificial antigen‐presenting cells (APCs) expressing CD28 and ICOS ligands*.ResultsAcazicolcept bound CD28 and ICOS, prevented ligand binding, and inhibited human T cell functional interactions, matching or exceeding the activity of CD28 or ICOS costimulatory single‐pathway inhibitors tested individually or in combination. Acazicolcept administration significantly reduced disease in the CIA model and more potently than abatacept. Acazicolcept also inhibited proinflammatory cytokine production from stimulated PBMCs in cocultures with artificial APCs and demonstrated unique effects on gene expression distinct from those induced by abatacept, prezalumab, or a combination of both.ConclusionBoth CD28 and ICOS signaling play critical roles in inflammatory arthritis. Therapeutic agents such as acazicolcept that coinhibit both ICOS and CD28 signaling may mitigate inflammation and/or disease progression in RA and PsA more effectively than inhibitors of either pathway alone.

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2020-06-01·Journal of Autoimmunity1区 · 医学

Sjögren's syndrome: Old and new therapeutic targets

1区 · 医学

Review

作者: Mavragani, Clio P ; Moutsopoulos, Haralampos M

Sjögren's syndrome (SS) is a prototype autoimmune disease characterized by oral and ocular mucosal dryness following chronic inflammation of salivary and lachrymal glands, respectively. Profound B cell hyperactivity along with systemic manifestations including fatigue, musculoskeletal complaints, features related to hepatic, pulmonary, renal and nervous system involvement, as well as lymphoma development can be also present. Despite that activation of both innate and adaptive immune pathways has been long well documented in SS pathogenesis, systemic immunosuppression in SS, in contrast to other autoimmune diseases, has been largely inefficacious. Biological agents previously implemented in successful therapeutic outcomes in rheumatoid arthritis (RA), such as anti-TNF agents, anakinra, tocilizumab and rituximab failed to reach primary outcomes in randomized double-blind controlled trials in the context of SS. Abatacept and belimumab, already licensed for the treatment of RA and lupus respectively, as well combination regimens of both rituximab and belimumab hold some promise in alleviation of SS-specific complaints, but data from large controlled trials are awaited. Recent advances in dissecting the molecular pathways underlying SS pathogenesis led to an expanding number of novel biological compounds directed towards type I interferon system, antigen presentation, costimulatory pathways, B and T cell activation, as well as germinal center formation. While targeting of cathepsin-S (Petesicatib), inducible costimulator of T cells ligand (prezalumab), and lymphotoxin beta receptor (baminercept) failed to fulfil the primary outcome measures, preliminary results from two randomized placebo controlled trials on CD40 blockade (Iscalimab) and B-cell activating factor receptor (Ianalumab) inhibition resulted in significant reduction of SS disease activity, with a favorable so far safety profile. Results from administration of other kinase inhibitors, a transmembrane activator and calcium-modulator and cytophilin ligand interactor TACI fusion protein (RC18), as well as low dose recombinant interleukin-2 to expand T-regulatory cells are currently awaited.

2018-07-01·Arthritis & Rheumatology1区 · 医学

Brief Report: A Randomized, Double‐Blind, Parallel‐Group, Placebo‐Controlled, Multiple‐Dose Study to Evaluate AMG 557 in Patients With Systemic Lupus Erythematosus and Active Lupus Arthritis

1区 · 医学

Article

作者: Tsuji, Wayne H. ; Sullivan, Barbara A. ; Zhou, Lei ; Cheng, Laurence E. ; Amoura, Zahir ; Cheah, Benjamin ; Chung, James B. ; Hiepe, Falk ; Merrill, Joan T. ; Arnold, Gregory E.

ObjectiveTo evaluate the safety and potential efficacy of AMG 557, a fully human antibody directed against the inducible T cell costimulator ligand (ICOSL) in patients with systemic lupus erythematosus (SLE) with arthritis.MethodsIn this phase Ib, randomized, double‐blind, placebo‐controlled study, patients received AMG 557 210 mg (n = 10) or placebo (n = 10) weekly for 3 weeks, then every other week for 10 additional doses. The corticosteroid dosage was tapered to ≤7.5 mg/day by day 85, and immunosuppressants were discontinued by day 29. Primary end points on day 169 were safety, immunogenicity, the Lupus Arthritis Response Index (LARI; defined by a reduction in the tender and swollen joint counts), ≥1‐letter improvement in the musculoskeletal domain of the British Isles Lupus Assessment Group (BILAG) index, and medication discontinuation. The secondary/exploratory end points were changes in the tender and swollen joint counts, BILAG index scores (musculoskeletal, global), and the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI).ResultsThe incidence of adverse events, most of which were mild, was similar between groups. LARI responses occurred in 3 of 10 patients receiving AMG 557 and 1 of 10 patients receiving placebo (P = 0.58). More patients in the AMG 557 group achieved a ≥4‐point improvement in the SLEDAI score on day 169 (7 of 10 patients) compared with the placebo group (2 of 10 patients) (P = 0.07). Patients treated with AMG 557 (versus placebo) had greater improvements from baseline in the global BILAG index scores (–36.3% versus –24.7%) and the SLEDAI score (–47.8% versus –10.7%) and in tender (–22.8% versus –13.5%) and swollen (–62.1% versus –7.8%) joint counts on day 169.ConclusionAMG 557 showed safety and potential efficacy, supporting further evaluation of the clinical efficacy of ICOSL blockade in patients with SLE.

100 项与 Prezalumab 相关的药物交易

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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
原发性干燥综合征	临床2期	法国	MedImmune LLC	2015-06-08
原发性干燥综合征	临床2期	美国	Amgen, Inc.	2015-06-08
原发性干燥综合征	临床2期	瑞典	Amgen, Inc.	2015-06-08
原发性干燥综合征	临床2期	英国	Amgen, Inc.	2015-06-08
原发性干燥综合征	临床2期	美国	MedImmune LLC	2015-06-08
原发性干燥综合征	临床2期	英国	MedImmune LLC	2015-06-08
原发性干燥综合征	临床2期	法国	Amgen, Inc.	2015-06-08
原发性干燥综合征	临床2期	瑞典	MedImmune LLC	2015-06-08
系统性红斑狼疮	临床2期	-	MedImmune LLC	-
系统性红斑狼疮	临床2期	-	MedImmune LLC	-

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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


NCT02334306 (CTgov)	临床2期	原发性干燥综合征	32	AMG 557/MEDI5872	窪窪鑰齋蓋願襯顧膚構(鑰蓋廠憲齋鹽觸遞構鬱) = 憲觸廠願淵窪齋範鏇觸窪積製鏇觸憲醖齋獵積 (簾築積壓衊網築窪鑰衊, 夢築獵廠醖簾蓋繭鹽憲 ~ 鏇壓餘獵夢夢觸鑰鑰鏇) 更多	-	2019-03-19
NCT01683695 (Pubmed \| Arthritis Rheumatol) 人工标引	临床1期	关节炎 \| 系统性红斑狼疮	20	AMG 557	積範網壓繭遞顧鬱鹽齋(製艱構衊淵遞憲蓋鑰構) = 餘襯積構淵夢鑰膚餘襯簾餘壓膚選鑰艱糧築蓋 (範築網範獵憲積艱襯選 ) 更多	积极	2018-07-01
				Placebo	積範網壓繭遞顧鬱鹽齋(製艱構衊淵遞憲蓋鑰構) = 鹽廠蓋繭醖餘積鑰壓淵簾餘壓膚選鑰艱糧築蓋 (範築網範獵憲積艱襯選 ) 更多
EULAR2017	临床1期	红斑狼疮	20	AMG 557 210 mg	鏇齋廠糧鹹鏇憲積觸願(觸遞夢壓淵夢衊艱獵齋) = Treatment-emergent adverse events (AEs) were similar between placebo and AMG 557 arms; most commonly headache and upper respiratory tract infection 鏇築獵壓遞襯網憲鹹鹽 (淵鏇夢鏇鹽鬱鹹範鹹鏇 )	积极	2017-06-14
				Placebo