SAN-300(SAN-300) - 药物靶点：α1β1_在研适应症：类风湿关节炎_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Anti-VLA-1 antibody、Anti-VLA-1 mAb

+ [1]

靶点

α1β1

作用机制

α1β1拮抗剂(整合素α-1/β-1复合体拮抗剂)

治疗领域

免疫系统疾病皮肤和肌肉骨骼疾病

在研适应症

类风湿关节炎

非在研适应症-

原研机构

Biogen, Inc.

在研机构

Biogen, Inc.

非在研机构

Salix Pharmaceuticals, Inc.

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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关联

2

项与 SAN-300 相关的临床试验

NCT02047604 / Completed临床2期

A Randomized, Double-blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Escalating Doses of SAN-300 in Patients With Active Rheumatoid Arthritis With Inadequate Response to Disease-Modifying Anti-rheumatic Drug(s).

A Study to Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy of Escalating Doses of SAN-300 in Patients with Active Rheumatoid Arthritis with Inadequate Response to Disease-Modifying Anti-rheumatic Drug(s).

开始日期2013-12-01

申办/合作机构

Bausch Health Americas, Inc.

ACTRN12611000123943 / Completed临床1期

A phase 1 study of healthy subjects and patients with rheumatoid arthritis receiving single doses of SAN-300 or placebo to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of SAN-300

开始日期2011-03-07

申办/合作机构

Santarus, Inc.

100 项与 SAN-300 相关的临床结果

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100 项与 SAN-300 相关的转化医学

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100 项与 SAN-300 相关的专利（医药）

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40

项与 SAN-300 相关的文献（医药）

2023-06-01·British journal of anaesthesia

Anti-high-mobility group box-1 treatment strategies improve trauma-induced coagulopathy in a mouse model of trauma and shock.

Article

作者: Maas, M. Adrie W. ; Kleinveld, Derek J. B. ; Meijers, Joost C. M. ; Juffermans, Nicole P. ; Roelofs, Joris J. T. H. ; Sloos, Pieter H. ; Nieuwland, Rienk

BACKGROUNDTrauma-induced coagulopathy is associated with platelet dysfunction and contributes to early mortality after traumatic injury. Plasma concentrations of the damage molecule high-mobility group box-1 (HMGB-1) increase after trauma, which may contribute to platelet dysfunction. We hypothesised that inhibition of HMGB-1 with a monoclonal antibody (mAb) or with recombinant thrombomodulin (rTM) improves trauma-induced coagulopathy in a murine model of trauma and shock.METHODSMale 129S2/SvPasOrlRJ mice were anaesthetised, mechanically ventilated, and randomised into five groups: (i) ventilation control (VENT), (ii) trauma/shock (TS), (iii) TS+anti-HMGB-1 mAb (TS+AB), (iv) TS+rTM (TS+TM), and (v) TS+anti-HMGB-1 mAb+rTM (TS+COMBI). Primary outcome was rotational thromboelastometry EXTEM. Secondary outcomes included tail bleeding time, platelet count, plasma HMGB-1 concentration, and platelet activation.RESULTSTrauma and shock resulted in a hypocoagulable thromboelastometry profile, increased plasma HMGB-1, and increased platelet activation markers. TS+AB was associated with improved clot firmness after 5 min compared with TS (34 [33-37] vs 32 [29-34] mm; P=0.043). TS+COMBI was associated with decreased clot formation time (98 [92-125] vs 122 [111-148] s; P=0.018) and increased alpha angle (77 [72-78] vs 69 [64-71] degrees; P=0.003) compared with TS. TS+COMBI also reduced tail bleeding time compared with TS (P=0.007). The TS+TM and TS+COMBI groups had higher platelet counts compared with TS (P=0.044 and P=0.041, respectively).CONCLUSIONSInhibition of HMGB-1 early after trauma in a mouse model improves clot formation and strength, preserves platelet count, and decreases bleeding time.

2023-01-01·Folia neuropathologica

Osteopontin expression and the effect of anti-VLA-4 mAb treatment in experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis.

Article

作者: Lis, Grzegorz J ; Litwin, Jan A ; Pyka-Fościak, Grażyna

INTRODUCTIONOsteopontin (OPN) is involved in the pathogenesis of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis (EAE). The aim of this study was to investigate the expression of OPN in spinal cords of mice in the successive phases of EAE, to compare it with the density of inflammatory cells, oligodendrocytes and with the expression of interleukin (IL)-17A and to assess the effect of anti-α4β1 integrin (VLA-4) treatment.MATERIAL AND METHODSExperimental autoimmune encephalomyelitis (EAE) mice were injected with anti-VLA-4 antibodies or, as treatment control, with immunoglobulin G (IgG). Spinal cords were sectioned and immunostained for OPN, CD45 (overall leukocytes), CD3 (T cells), Iba1 (activated macrophages/microglia), IL-17A, and CNP1 (oligodendrocytes). Microscopic images were analysed and the percentage of immunopositive areas encompassing the whole spinal cord cross-sectional area were assessed in images for each antigen.RESULTSOsteopontin was expressed by inflammatory cells and by a minority of neurons and blood vessels. Most of the studied parameters followed the temporal pattern of clinical scores: increase in the peak phase and decrease in the chronic phase. Only OPN and IL-17A remained at a high level in the chronic phase, while CNP1 expression gradually decreased in the successive phases. Anti-VLA-4 treatment lowered the expression of the studied antigens in the peak and chronic phases with the exception of oligodendrocyte marker CNP1 which in both phases showed an increased expression.CONCLUSIONSInvolvement of OPN is particularly significant in advanced EAE. Anti-VLA-4 treatment not only inhibits migration of myelin-reactive T cells, but also downregulates OPN and inhibits loss of oligodendrocytes.

2022-10-01·Archives of Biochemistry and Biophysics

Biomechanical changes in the liver tissue induced by a mouse model of multiple sclerosis (EAE) and the effect of anti-VLA-4 mAb treatment

Article

作者: Zemła, J ; Lekki, J ; Pyka-Fościak, G ; Wójcik, B ; Lekka, M ; Lis, G J ; Litwin, J A

Experimental autoimmune encephalomyelitis (EAE) is a mouse model of demyelinating diseases, such as multiple sclerosis (MS). MS can be accompanied by autoimmune hepatitis. In this study, nanomechanical, biorheological and histological examinations were carried out by atomic force microscopy (AFM), rheology, and immunofluorescence microscopy to investigate changes in the liver tissue of EAE mice and the effect of natalizumab, a monoclonal antibody against α4-integrin (VLA-4) cell adhesion molecule, used in MS therapy. Liver samples collected from EAE mice in three successive phases of the disease showed inflammatory changes manifested by leukocyte infiltrations and elevated levels of proinflammatory cytokine IL-1β. Liver stiffness and viscoelasticity increased in the onset phase of EAE, decreased in the peak phase and increased again in the chronic phase to reach the highest values. These changes were not associated with inflammation parameters which increased in the peak phase and decreased to the lowest values in the chronic phase. Moreover, anti-VLA treatment, which reduced the inflammation parameters, had an ambiguous effect on stiffness and viscoelasticity: it increased them in the peak phase but decreased in the chronic phase. The observed discrepancies can result from a complex network of interactions between inflammation and fibrosis, as well as between liver cells and the extracellular matrix influencing the biomechanical properties of the liver tissue.

100 项与 SAN-300 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
类风湿关节炎	临床2期	-	Biogen, Inc.	-

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临床结果

适应症

分期

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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


NCT02047604 (C2013-0302, CTgov)	临床2期	类风湿关节炎	41	SAN-300 0.5 mg/kg QW (Cohort A - SAN-300 0.5 mg/kg QW)	憲選餘廠餘淵襯構鹹積(築壓齋糧願鏇顧齋積製) = 選餘願觸積鑰衊膚繭淵築顧築遞簾憲鏇淵願積 (積齋鹽簾繭選鹹壓鹹糧, 鬱鏇鹹鬱繭鑰膚衊範膚 ~ 遞廠觸築繭廠齋憲網衊) 更多	-	2021-06-21
				SAN-300 1.0 mg/kg QW (Cohort B - SAN-300 1.0 mg/kg QW)	憲選餘廠餘淵襯構鹹積(築壓齋糧願鏇顧齋積製) = 繭鑰艱鏇鬱蓋繭構網鏇築顧築遞簾憲鏇淵願積 (積齋鹽簾繭選鹹壓鹹糧, 淵鏇獵獵窪選艱鑰獵憲 ~ 鑰夢廠構遞築鏇壓鏇鑰) 更多