A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE)

Study KIN-1901-2001 is a multi-center, adaptive, randomized, double-blind, placebo-controlled study to assess the efficacy and safety of gimsilumab in subjects with lung injury or acute respiratory distress syndrome (ARDS) secondary to COVID-19.

开始日期2020-04-15

申办/合作机构

Kinevant Sciences GmbH

[+1]

NCT04205851

/ Completed临床1期

An Ascending Single- and Multiple-Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Gimsilumab in Healthy Subjects and Subjects With Ankylosing Spondylitis

This study is intended to treat ankylosing spondylitis (AS). AS is a form of arthritis that primarily affects the spine. It is characterized by inflammation of the spinal joints that can lead to severe pain, and in more advanced cases, ankylosis (sections of the spine fuse in a fixed, immobile position). The study will be an ascending single and multiple-dose study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of subcutaneous KIN-1901 in healthy subjects and subjects with AS.

开始日期2019-11-12

申办/合作机构

Kinevant Sciences GmbH

NCT01357759

/ Completed临床1期

A Randomized, Double-Blind, Placebo-Controlled, Single-Dose, Dose-Escalation Trial of MORAb-022 in Healthy Subjects and Subjects With Rheumatoid Arthritis

This is a randomized, double-blind, placebo-controlled, single-dose, dose escalation study in healthy male and or female subjects and subjects with Rheumatoid Arthritis (RA) to determine the safety and tolerability of MORAb-022.

开始日期2013-05-01

申办/合作机构

Morphotek, Inc.

100 项与 Gimsilumab 相关的临床结果

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100 项与 Gimsilumab 相关的转化医学

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100 项与 Gimsilumab 相关的专利（医药）

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项与 Gimsilumab 相关的文献（医药）

2022-09-15·American Journal of Respiratory and Critical Care Medicine

Erratum: Anti-Granulocyte–Macrophage Colony–Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial

2022-06-01·American Journal of Respiratory and Critical Care Medicine

Anti-Granulocyte–Macrophage Colony–Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial

Article

作者: Abbasi, Jamil A. ; Mathews, Kusum S. ; Lyon, George Marshall ; DiMaio, J. Michael ; Ahmad, Kareem ; Case, Amy H. ; Sherman, Lisa ; Shen, Steven ; Gottlieb, Robert L. ; Wang, Tisha S. ; Mendelson, Robert ; Tran, MaryAnn P. ; Criner, Gerard J. ; Jeanfreau, Robert ; Bellam, Shashi ; Spak, Cedric W. ; Madduri, Deepu ; Ghamande, Shekhar ; Rice, Todd W. ; Glassberg, Marilyn K. ; Lang, Frederick M. ; Davis, Steven G. ; Lowry, Simon

Rationale: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). Objectives: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. Methods: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. Measurements and Main Results: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [-6 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. Conclusions: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. Clinical trial registered with www.clinicaltrials.gov (NCT04351243).

2021-09-01·The Journal of Clinical Pharmacology3区 · 医学

Therapeutic Application of Corticosteroids in COVID‐19: A Focus on Optimum Dose and Duration of Therapy

3区 · 医学

Article

作者: Entezari‐Maleki, Taher ; Khiali, Sajad

The pandemic of coronavirus disease 2019 (COVID-19) has resulted in a global health crisis.Pathophysiol., the disease has the initial phase of viral replication that could be followed by an immunol. phase, which is characterized by a systemic inflammatory response, cytokine release syndrome, acute respiratory distress syndrome (ARDS), and multisystem organ dysfunction, and associated with a considerable rate of mortality.The critical condition of the immunol. phase of the disease has raised many studies investigating the efficacy and safety of a series of anti-inflammatory agents, including proinflammatory cytokine inhibitors (anakinra, tocilizumab, sarilumab, adalimumab, infliximab), Janus kinase inhibitors (baricitinib, tofacitinib, ruxolitinib), convalescent plasma, and granulocyte-macrophage colony-stimulating factors (gimsilumab, lenzilumab, namilumab), as well as nonspecific immune modulators such as corticosteroids in patients with COVID-19.It seems that, due to the substantial heterogeneity of the disease, ongoing RCTs should incorporate plans for understanding heterogeneity and identifying patients who are responsive to corticosteroids and appropriate dose of the medicines considering the burden of lung injury, inflammatory markers such as neutrophil-to-lymphocyte ratio, sedimentation rate, levels of interleukins, presence of poor prognosis risk factors, and other clin. and paraclin. data.Finally, the pharmacokinetics, glucocorticoids/mineralocorticoids ratios, and equivalent doses of corticosteroids, as well as dose and duration of the drugs in similar situations like the classic ARDS, should be considered in the clin. trials and treatment centers.

项与 Gimsilumab 相关的新闻（医药）

2022-11-08

·生物制药小编

迷茫的GM-CSF单抗

此前，葛兰素史克(GSK)（10月27日）宣布，由于一种治疗类风湿性关节炎（RA）的实验性单克隆抗体疗法Otilimab在三期临床试验ContRAst-3中的未能达到主要终点后，该公司将终止该疗法的开发。事实上对于近一年多以来GM-CSF单抗的失败，这已经不是第一次。被诅咒的GM-CSFGM-CSF抗体目前主要应用于治疗COVID-19的细胞因子风暴和RA这两项疾病，而此前对于Otilimab的临床开发也主打这两个方向。先前的临床ContRAst-1和ContRAst-2虽然到达了ACR20的主要终点但不足以改变患者的治疗方案，而此次ContRAst-3则在目前针对大分子DMARD和/或JAK抑制剂没有足够响应的患者也失败了，这意味着在RA临床中较为彻底的失败。考虑到此前Otilimab已经在新冠上未达统计学意义的主要终点，此次放弃RA基本等于放弃Otilimab了。事实上，这一现象不仅仅在Otilimab这一家的GM-CSF抗体上。目前除了两家国内公司的STSA-1005和TJM2(TJ003234)之外，GM-CSF抗体在这两项适应症上的临床几乎沦陷。就比如Mavrilimumab，目前Kiniksa Pharmaceuticals只打算开发其罕见心血管疾病中的应用，尽管在RA和巨细胞动脉炎中的效果都不错，都在II期到达了终点，然而这家公司也没有将其推进到III期的打算。而拥有KB003的KaloBios不仅临床失败，就连KaloBios这家公司本身都因为很著名的Martin Shkreli案件而破产了。图：Martin ShkreliMORAb-022（Gimsilumab）的命运较为坎坷，最开始由Morphotek研发，但随后被卫材收购，而卫材又将商业权限交给了Roivant Sciences，Roivant Sciences曾试图将新冠和强直性脊柱炎作为适应症，但在新冠II期临床没有披露结果后，在该公司的官网上就找不到Gimsilumab的管线了，很可能已经被雪藏或弃用。同样曾在安进、武田分别接手过的Namilumab（MT-203; AMG-203; IZN-101），目前的开发公司Kinevant Sciences仅将结节病作为适应症开发方向发展。预计2024年将获得营业数据。Humanigen公司的Lenzilumab在胸科发表同行评审的出版物上的数据曾一度表明，支持在新冠早期治疗中应用Lenzilumab，但最终其临床结果仍旧认为无法证实其新冠上的临床益处。目前其临床适应症已经改为相当偏门的NRAS、KRAS和CBL基因突变的高危慢性粒单核细胞白血病。而受此影响，Humanigen公司的股价已经从巅峰时期的23美元跌至现在的0.14$，市值仅为1450多万美元，面临摘牌的风险，更因证券欺诈而被投资者集体诉讼至法院。那么如果抛开新冠和RA这两项适应症，在其他领域也可能有GM-CSF的用武之地。GM-CSF还有哪些可能应用？如果从机制入手，GM-CSF的异常表达会导致过度的炎症、疼痛、趋化和组织损伤，并促进其他致病细胞因子的产生，“GM-CSF网络”通过持续和过度活跃的炎症反应，促进疾病。该网络是一个正反馈回路，涉及单核核细胞/巨噬细胞、TH细胞和邻近细胞群体之间，相互分泌GM-CSF和促炎细胞因子/趋化因子，该网络的细胞因子中最显著的是IL-1、IL-6和TNF，它们已成功地靶向于各种炎症性疾病。GM-CSF促炎症效应参与了一些列炎症性疾病：COVID-19 的急性呼吸窘迫，CRS，噬血细胞淋巴组织细胞增生症（PHP），移植物抗宿主病(GVHD)，心血管疾病。产生GM-CSF的Th细胞被发现参与了多种自身免疫性疾病。既然抛开了COVID-19，那么剩下的炎症相关疾病仍然有可以用武之地。扩展阅读：GM-CSF：风湿性疾病、新冠CRS、抗体药物从CRS方面来看，将GM-CSF抗体应用于CAR-T临床，以减少CRS的尝试并非没有，此前Yescarta（Axi-Cel）就与mavrilimumab展开了协同临床，虽然因为Kite投资组合策略审查影响了计划的试验而导致合作中止，但其可行性仍然存在。例如，近期Humanigen也宣布正在探索lenzilumab作为CD19靶向CAR-T细胞疗法相关炎症的治疗方法，并正在探索lenzilumab在其他炎症疾病中的有效性，如接受异基因造血干细胞移植、嗜酸性哮喘和类风湿性关节炎患者的急性移植物抗宿主病。小编总结总体而言，GM-CSF需要找到一个合适的定位，例如和其他药物联用等等，寻找到贴合GM-CSF的正确定位。参考来源：葛兰素史克：GM-CSF抗体三期临床疗效有限，终止开发医药笔记GM-CSF功能、炎症、抗体药物Achuthan AA, Lee KMC, Hamilton JA. Targeting GM-CSF in inflammatory and autoimmune disorders. Semin Immunol. 2021 Apr;54:101523. doi: 10.1016/j.smim.2021.101523. Epub 2021 Nov 12. PMID: 34776300.各个公司财报

抗体免疫疗法细胞疗法并购合作

2021-06-18

·GlobeNewswire

Axial Spondyloarthritis Pipeline: Drug Pipeline, Regulatory Events and Clinical Trials in the Spotlight| Insights by DelveInsight

Los Angeles, June 17, 2021 (GLOBE NEWSWIRE) -- Axial Spondyloarthritis Pipeline: Drug Pipeline, Regulatory Events and Clinical Trials in the Spotlight| Insights by DelveInsight The report offers the most up-to-date information on Axial Spondyloarthritis pipeline products being developed by notable companies such as Pfizer, Suzhou Zelgen Biopharmaceuticals, Clover Biopharmaceuticals, FunPep Co Ltd., Kinevant Sciences, Izana Bioscience, Mycenax Biotech, and UCB Biopharma, among others. DelveInsight’s ‘Axial Spondyloarthritis (axSpA) Pipeline Insights’ report offers exhaustive coverage of the emerging therapies in different stages of development from pre-clinical till late-stage, along with dormant, inactive, and abandoned therapeutic agents. Some of the important takeaways from the Axial Spondyloarthritis Pipeline report: Request for Sample to know more about the therapies expected to make grab the maximum patient pool @ Axial Spondyloarthritis Emerging Therapies and Forecast The Axial Spondyloarthritis Pipeline reports lay down a thorough coverage of the ongoing clinical trials, collaborations taking place in the domain, recent happenings in the Axial Spondyloarthritis pipeline space, and growth prospects across the Axial Spondyloarthritis domain. Axial Spondyloarthritis: Overview Axial Spondyloarthritis is a chronic, inflammatory rheumatic disease that affects primarily the axial joints leading to severe pain, stiffness, and fatigue. It starts with an early inflammatory phase in which there is no structural damage in the sacroiliac joints (non-radiographic disease) progressing to later stages in which structural damage is visible on X‑ray scans of the sacroiliac joints as erosions, sclerosis, or bony bridges (radiographic disease; also known as Ankylosing Spondylitis). Discover more about the disease, treatments, and pipeline therapies @ axSpA Pipeline Assessment Axial Spondyloarthritis Pipeline Drugs Request for Sample to know more @ Axial Spondyloarthritis Pipeline Analysis, Key Companies, and Futuristic Trends Axial Spondyloarthritis Therapeutics Assessment The Axial Spondyloarthritis Pipeline report presents a kaleidoscopic view of the axSpA emerging novel therapies segmented by Stage, Product Type, Route of Administration (RoA), Molecule Type, Target, and Mechanism of Action. By Product Type By Stage By Molecule Type By Route of Administration By Mechanism of Action By Targets For rich insights into merging therapies and assessment, visit Axial Spondyloarthritis Pipeline: Emerging Novel Therapies Scope of the Axial Spondyloarthritis Pipeline Report Coverage: GlobalKey Players: Izana Bioscience, UCB, Sun Pharma Global, Akeso Biopharma, Kinevant Sciences, Jiangsu Hengrui Medicine Co., Suzhou Zelgen Biopharmaceuticals, Clover Biopharmaceuticals, Mycenax Biotech, Boehringer Ingelheim, and Qyuns Therapeutics among others.Key Axial Spondyloarthritis Pipeline Therapies: Namilumab , Bimekizumab, Tofacitinib, Tildrakizumab, AK-111, NDI 031232, Gimsilumab, QX002N, SHR-0302, Jaktinib, SCB-808, FPP003, KIN-1901, ENIA11, BI 730357, and QX002N among others. Discover more about the report offerings @ axSpA Emerging Therapies, Treatments, and Ongoing Clinical Trials Table of Contents Get in touch with our Business executive for Regulatory Analysis, Licensing Services, and Consulting Solutions Related Reports Axial Spondyloarthritis MarketDelveInsight's "Axial Spondyloarthritis Market Insights, Epidemiology, and Market Forecast-2030" report. Non-Radiographic Axial Spondyloarthritis MarketDelveInsight's "Non-Radiographic Axial Spondyloarthritis (nr-AxSpA) Market Insights, Epidemiology, and Market Forecast-2030" report. Spondylolisthesis Market InsightsDelveInsight's “Spondylolisthesis Market Insights, Epidemiology, and Market Forecast-2030" report. Ankylosing Spondylitis MarketDelveInsight’s ‘Ankylosing Spondylitis Market Insights, Epidemiology, and Market Forecast–2030’ report. Global Kinase Inhibitor In Autoimmune Diseases MarketDelveInsight’s ‘Global Kinase Inhibitor in Autoimmune Diseases Market Insights and Market Forecast – 2030’ report. Adenosine Deaminase Severe Combined Immunodeficiency MarketDelveInsight's "Adenosine Deaminase-Severe Combined Immunodeficiency Market Insights, Epidemiology, and Market Forecast-2030" report. Adult-Onset Still Disease MarketDelveInsight’s “Adult-onset Still’s Disease Market Insights, Epidemiology, and Market Forecast – 2030” report. Browse through our posts ABSSSI Pipeline Analysis Parkinson's Disease Risk FactorsWearable Healthcare Devices Market About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports Pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve. For more insights, visit Pharma, Healthcare, and Biotech News

合作

100 项与 Gimsilumab 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11121	-	-	DB15280

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
风湿性疾病	临床2期	加拿大	Kinevant Sciences GmbH	2019-11-12
类风湿关节炎	临床2期	荷兰	Morphotek, Inc.	2013-05-01
类风湿关节炎	临床2期	美国	Morphotek, Inc.	2013-05-01
鼻咽肿瘤	临床2期	-	Morphotek, Inc.	-
新型冠状病毒感染	临床1期	美国	Kinevant Sciences GmbH	2020-04-15
新型冠状病毒感染	临床1期	美国	Roivant Sciences, Inc.	2020-04-15
成人呼吸窘迫综合征	临床1期	美国	Roivant Sciences, Inc.	2020-04-15
成人呼吸窘迫综合征	临床1期	美国	Kinevant Sciences GmbH	2020-04-15
肺损伤	药物发现	美国	Kinevant Sciences GmbH	2020-04-15
肺损伤	药物发现	美国	Roivant Sciences, Inc.	2020-04-15

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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


NCT04351243 (Pubmed \| Am J Respir Crit Care Med) 人工标引	临床2期	新型冠状病毒感染	225	Gimsilumab	(糧餘鹽壓餘齋願鏇廠夢) = 範餘餘鹽繭窪衊餘蓋獵積糧獵築觸鹹壓獵齋簾 (鑰鬱鹹顧艱鏇構遞範簾 )	不佳	2022-03-15
				Placebo	(糧餘鹽壓餘齋願鏇廠夢) = 構鏇壓顧遞淵願淵餘廠積糧獵築觸鹹壓獵齋簾 (鑰鬱鹹顧艱鏇構遞範簾 )
NCT04351243 (BREATHE, CTgov)	临床2期	新型冠状病毒感染 \| 成人呼吸窘迫综合征 \| 肺损伤	227	Gimsilumab (Gimsilumab)	蓋醖鹽鏇糧簾構壓齋鹽(憲壓蓋齋夢鏇鬱構鬱齋) = 積醖蓋糧餘壓襯淵夢願廠選網衊壓網餘餘壓積 (淵蓋衊構鏇願範衊醖簾, 壓鬱憲窪鹽築積範顧願 ~ 觸膚鬱鏇獵壓鹹襯鹹膚) 更多	-	2021-12-10
				Placebo (Placebo)	蓋醖鹽鏇糧簾構壓齋鹽(憲壓蓋齋夢鏇鬱構鬱齋) = 膚齋積壓醖遞網鹽廠衊廠選網衊壓網餘餘壓積 (淵蓋衊構鏇願範衊醖簾, 蓋積鑰糧積鏇壓鏇鬱蓋 ~ 憲選繭膚蓋鑰衊繭構獵) 更多
NCT01357759 (Biospace) 人工标引	临床1期	类风湿关节炎	51	MORAb-022-001	(艱淵齋鬱艱蓋淵鹽醖願) = 襯糧艱顧觸積衊繭淵餘鏇簾鑰糧壓艱範糧遞網 (醖鏇蓋鑰鏇積顧構選壓 ) 更多	积极	2015-12-07