乐维利单抗(Levilimab) - 药物靶点：IL-6RA_在研适应症：类风湿关节炎，新型冠状病毒感染_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

Ilsira

靶点

IL-6RA

作用机制

IL-6RA拮抗剂(白细胞介素-6受体α亚基拮抗剂)

治疗领域

免疫系统疾病感染呼吸系统疾病+ [1]

在研适应症

类风湿关节炎新型冠状病毒感染

非在研适应症-

原研机构

Biocad Medical, Inc.

在研机构

Biocad CJSC

非在研机构-

最高研发阶段批准上市

首次获批日期

俄罗斯 (2020-06-04),

新型冠状病毒感染

最高研发阶段(中国)-

特殊审评-

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序列信息

Sequence Code 432066943L

来源: *****

Sequence Code 432066942H

来源: *****

关联

5

项与乐维利单抗相关的临床试验

NCT05800327 / Active, not recruiting临床3期

A Two-Stage Study of the Efficacy, Safety, Pharmacokinetics, Pharmacodynamics and Immunogenicity of Various Doses of Levilimab When Administered Intravenously and Subcutaneously to Healthy Subjects and Subjects With Active Rheumatoid Arthritis

This is a two-stage study of efficacy, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of various doses of levilimab when administered intravenously and subcutaneously to healthy subjects and subjects with active rheumatoid arthritis resistant to methotrexate monotherapy.
Aim of the Stage 1 is to study the tolerability, safety, immunogenicity, and main pharmacokinetic and pharmacodynamic parameters of levilimab after its single subcutaneous or intravenous administration at ascending doses to healthy subjects.
Aim of the Stage 2 is to confirm the efficacy and safety of levilimab 648 mg IV Q4W in combination with methotrexate and levilimab 324 mg SC Q2W in combination with methotrexate in subjects with active rheumatoid arthritis, resistant to methotrexate monotherapy.

开始日期2022-12-07

申办/合作机构

Biocad CJSC

NCT04397562 / Completed临床3期

A Multicenter, Randomized, Double-blind, Placebo-controlled, Adaptively Designed Clinical Trial of the Efficacy and Safety of Levilimab (BCD-089) in Patients With Severe COVID-19

The objective: to study the efficacy and safety of levilimab in subjects with severe COVID-19.

开始日期2020-04-29

申办/合作机构

Biocad CJSC

NCT04227366 / Completed临床3期

An International, Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Study of the Efficacy and Safety of BCD-089 (JSC BIOCAD, Russia) in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis

BCD-089 is the original therapeutic monoclonal antibody binding the alpha subunit of the IL-6 receptor.
The aim of the study is to demonstrate the efficacy and safety of BCD-089 in combination with methotrexate in patients with active rheumatoid arthritis resistant to monotherapy with methotrexate.

开始日期2019-11-19

申办/合作机构

Biocad CJSC

100 项与乐维利单抗相关的临床结果

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100 项与乐维利单抗相关的转化医学

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100 项与乐维利单抗相关的专利（医药）

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9

项与乐维利单抗相关的文献（医药）

2023-01-01·Annals of the Rheumatic Diseases

Efficacy of synthetic and biological DMARDs: a systematic literature review informing the 2022 update of the EULAR recommendations for the management of rheumatoid arthritis

Review

作者: Edwards, Christopher John ; van der Heijde, Désirée ; de Souza, Savia ; Stamm, Tanja A ; Caporali, Roberto ; Verschueren, Patrick ; Sepriano, Alexandre ; Schoones, Jan W ; Smolen, Josef S ; Hyrich, Kimme L ; Aletaha, Daniel ; Winthrop, Kevin L ; Pope, Janet E ; Takeuchi, Tsutomu ; Kerschbaumer, Andreas ; Bergstra, Sytske Anne ; Landewé, Robert B M

ObjectivesTo update the evidence on efficacy of DMARDs (disease-modifying antirheumatic drugs) and inform the taskforce of the 2022 update of the European Alliance of Associations for Rheumatology (EULAR) recommendations for management of rheumatoid arthritis (RA).MethodsThis systematic literature review (SLR) investigated the efficacy of conventional synthetic (cs), biological (b), biosimilar and targeted synthetic (ts)DMARDs in patients with RA. Medline, EMBASE, Cochrane CENTRAL and Web of Science were used to identify all relevant articles published since the previous update in 2019 to 14 January 2022.ResultsOf 8969 search results, 169 articles were selected for detailed review and 47 were finally included. Trials investigated the efficacy of csDMARDs, bDMARDs and tsDMARDs, DMARD switching, tapering and trials investigating different treatment strategies. The compounds investigated were csDMARDs (methotrexate (MTX), leflunomide, sulfasalazine, hydroxychloroquine), bDMARDs (abatacept, adalimumab, certolizumab-pegol, denosumab, etanercept, infliximab, levilimab, olokizumab, opineracept, rituximab, sarilumab, tocilizumab) and tsDMARDs (baricitinib, filgotinib, tofacitinib, upadacitinib). The efficacy of csDMARDs+ short-term glucocorticoids in early RA was confirmed and similar to bDMARD+MTX combination therapy. Interleukin-6 pathway inhibition was effective in trials on olokizumab and levilimab. Janus kinase inhibitor (JAKi) was efficacious in different patient populations. After insufficient response to JAKi, patients could respond to TNFi treatment. Tapering of DMARDs was feasible for a proportion of patients, who were able to taper therapy while remaining in low disease activity or remission.ConclusionThe results of this SLR, together with one SLR on safety of DMARD and one on glucocorticoids, informed the taskforce of the 2022 update of the EULAR recommendations for pharmacological management of RA.

2021-12-01·Inflammation Research3区 · 医学

The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study

3区 · 医学

Article

作者: Gordeev, Ivan G ; Mazurov, Vadim I ; Pasechnik, Elena S ; Dokukina, Ekaterina A ; Eremeeva, Anna V ; Bakirov, Bulat A ; Lomakin, Nikita V ; Lutckii, Anton A ; Linkova, Yulia N ; Smolyarchuk, Elena A ; Fomina, Darya S ; Gilyarov, Mikhail Yu ; Seleznev, Anton I ; Morozova, Maria A ; Musaev, Gaziyavdibir H ; Moiseeva, Olga M ; Zinkina-Orikhan, Arina V ; Popov, Vladimir V ; Protsenko, Denis N ; Pukhtinskaia, Polina S

AbstractObjective and designThe aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19.SubjectsThe study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia.Treatment206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy.MethodsThe primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders.Results63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups.ConclusionIn patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate.Trail registrationThe trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).

2021-03-18·The Cochrane database of systematic reviews

Interleukin-6 blocking agents for treating COVID-19: a living systematic review.

Review

作者: Boutron, Isabelle ; Davidson, Mauricia ; Ferrand, Gabriel ; Sguassero, Yanina ; Riveros, Carolina ; Henschke, Nicholas ; Ghosn, Lina ; Schmucker, Christine ; Nguyen, Thu Van ; Kapp, Philipp ; Tovey, David ; Rada, Gabriel ; Ravaud, Philippe ; Ávila, Camila ; Hróbjartsson, Asbjørn ; Chaimani, Anna ; Grasselli, Giacomo ; Bollig, Claudia ; Devane, Declan ; Nejstgaard, Camilla Hansen ; Graña, Carolina ; Menon, Sonia ; Evrenoglou, Theodoros ; Meerpohl, Joerg J

BACKGROUNDInterleukin 6 (IL-6) blocking agents have been used for treating severe coronavirus disease 2019 (COVID-19). Their immunosuppressive effect might be valuable in patients with COVID-19 characterised by substantial immune system dysfunction by controlling inflammation and promoting disease tolerance.OBJECTIVESTo assess the effect of IL-6 blocking agents compared to standard care alone or with placebo on efficacy and safety outcomes in COVID-19. We will update this assessment regularly.SEARCH METHODSWe searched the World Health Organization (WHO) International Clinical Trials Registry Platform (up to 11 February 2021) and the L-OVE platform, and Cochrane COVID-19 Study Register to identify trials up to 26 February 2021.SELECTION CRITERIAWe included randomised controlled trials (RCTs) evaluating IL-6 blocking agents compared with standard care alone or with placebo for people with COVID-19, regardless of disease severity.DATA COLLECTION AND ANALYSISWe followed standard Cochrane methodology. The protocol was amended to reduce the number of outcomes considered. Two review authors independently collected data and assessed the risk of bias with the Cochrane Risk of Bias 2 tool. We rated the certainty of evidence with the GRADE approach for the critical outcomes such as clinical improvement (defined as hospital discharge or improvement on the scale used by trialists to evaluate clinical progression or recovery) (day (D) 28 / ≥ D60); WHO Clinical Progression Score of level 7 or above (i.e. the proportion of participants with mechanical ventilation +/- additional organ support OR death) (D28 / ≥ D60); all-cause mortality (D28 / ≥ D60); incidence of any adverse events; and incidence of serious adverse events.MAIN RESULTSWe identified 10 RCTs with available data including one platform trial comparing tocilizumab and sarilumab with standard of care. These trials evaluated tocilizumab (nine RCTs including two platform trials; seven were reported as peer-reviewed articles, two as preprints; 6428 randomised participants); and two sarilumab (one platform trial reported as peer reviewed article, one reported as preprint, 880 randomised participants). All trials included were multicentre trials. They were conducted in Brazil, China, France, Italy, UK, USA, and four were multi-country trials. The mean age range of participants ranged from 56 to 65 years; 4572 (66.3%) of trial participants were male. Disease severity ranged from mild to critical disease. The reported proportion of participants on oxygen at baseline but not intubated varied from 56% to 100% where reported. Five trials reported the inclusion of intubated patients at baseline. We identified a further 20 registered RCTs of tocilizumab compared to placebo/standard care (five completed without available results, five terminated without available results, eight ongoing, two not recruiting); 11 RCTs of sarilumab (two completed without results, three terminated without available results, six ongoing); six RCTs of clazakisumab (five ongoing, one not recruiting); two RCTs of olokizumab (one completed, one not recruiting); one of siltuximab (ongoing) and one RCT of levilimab (completed without available results). Of note, three were cancelled (2 tocilizumab, 1 clazakisumab). One multiple-arm RCT evaluated both tocilizumab and sarilumab compared to standard of care, one three-arm RCT evaluated tocilizumab and siltuximab compared to standard of care and consequently they appear in each respective comparison. Tocilizumab versus standard care alone or with placebo a. Effectiveness of tocilizumab for patients with COVID-19 Tocilizumab probably results in little or no increase in the outcome of clinical improvement at D28 (RR 1.06, 95% CI 1.00 to 1.13; I² = 40.9%; 7 RCTs, 5585 participants; absolute effect: 31 more with clinical improvement per 1000 (from 0 fewer to 67 more); moderate-certainty evidence). However, we cannot exclude that some subgroups of patients could benefit from the treatment. We did not obtain data for longer-term follow-up (≥ D60). The effect of tocilizumab on the proportion of participants with a WHO Clinical Progression Score of level of 7 or above is uncertain at D28 (RR 0.99, 95% CI 0.56 to 1.74; I² = 64.4%; 3 RCTs, 712 participants; low-certainty evidence). We did not obtain data for longer-term follow-up (≥ D60). Tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo (RR 0.89, 95% CI 0.82 to 0.97; I² = 0.0%; 8 RCTs, 6363 participants; absolute effect: 32 fewer deaths per 1000 (from 52 fewer to 9 fewer); high-certainty evidence). The evidence suggests uncertainty around the effect on mortality at ≥ D60 (RR 0.86, 95% CI 0.53 to 1.40; I² = 0.0%; 2 RCTs, 519 participants; low-certainty evidence). b. Safety of tocilizumab for patients with COVID-19 The evidence is very uncertain about the effect of tocilizumab on adverse events (RR 1.23, 95% CI 0.87 to 1.72; I² = 86.4%; 7 RCTs, 1534 participants; very low-certainty evidence). Nevertheless, tocilizumab probably results in slightly fewer serious adverse events than standard care alone or placebo (RR 0.89, 95% CI 0.75 to 1.06; I² = 0.0%; 8 RCTs, 2312 participants; moderate-certainty evidence). Sarilumab versus standard care alone or with placebo The evidence is uncertain about the effect of sarilumab on all-cause mortality at D28 (RR 0.77, 95% CI 0.43 to 1.36; 2 RCTs, 880 participants; low certainty), on all-cause mortality at ≥ D60 (RR 1.00, 95% CI 0.50 to 2.0; 1 RCT, 420 participants; low certainty), and serious adverse events (RR 1.17, 95% CI 0.77 to 1.77; 2 RCTs, 880 participants; low certainty). It is unlikely that sarilumab results in an important increase of adverse events (RR 1.05, 95% CI 0.88 to 1.25; 1 RCT, 420 participants; moderate certainty). However, an increase cannot be excluded No data were available for other critical outcomes.AUTHORS' CONCLUSIONSOn average, tocilizumab reduces all-cause mortality at D28 compared to standard care alone or placebo and probably results in slightly fewer serious adverse events than standard care alone or placebo. Nevertheless, tocilizumab probably results in little or no increase in the outcome clinical improvement (defined as hospital discharge or improvement measured by trialist-defined scales) at D28. The impact of tocilizumab on other outcomes is uncertain or very uncertain. With the data available, we were not able to explore heterogeneity. Individual patient data meta-analyses are needed to be able to identify which patients are more likely to benefit from this treatment. Evidence for an effect of sarilumab is uncertain and evidence for other anti-IL6 agents is unavailable. Thirty-nine RCTs of IL-6 blocking agents with no results are currently registered, of which nine are completed and seven trials were terminated with no results available. The findings of this review will be updated as new data are made available on the COVID-NMA platform (covid-nma.com).

100 项与乐维利单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB16387

研发状态

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
类风湿关节炎	俄罗斯	Biocad CJSC	2021-06-08
新型冠状病毒感染	俄罗斯	Biocad CJSC	2020-06-04

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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


NCT04397562 (SOLAR, EULAR2022)	临床3期	类风湿关节炎	154	Levilimab 162 mg, SC + MTX	遞遞糧壓膚齋鑰願憲齋(繭選衊範壓鬱鏇鹽窪選) = 窪觸鬱蓋鑰淵艱鹽築鹹鏇壓淵齋膚壓淵鏇醖醖 (窪鹹餘壓窪顧憲蓋壓醖 ) 更多	积极	2022-06-01
NCT04397562 (CORONA, Pubmed) 人工标引	临床3期	新型冠状病毒感染	217	SOC+levilimab	(廠鹽艱積觸膚遞願憲鹽) = 積選鬱積簾鬱衊窪簾觸觸壓獵鏇範蓋蓋鏇糧簾 (襯顧製鏇壓築鹹繭窪糧 )	积极	2021-12-01
				Placebo+SOC	(廠鹽艱積觸膚遞願憲鹽) = 廠艱鏇選鹽窪觸鑰鹽鹹觸壓獵鏇範蓋蓋鏇糧簾 (襯顧製鏇壓築鹹繭窪糧 )
NCT04397562 (SOLAR, EULAR2021)	临床3期	类风湿关节炎	154	Levilimab + MTX	(觸餘憲簾願蓋膚築積衊) = 壓積膚獵遞窪夢構繭夢觸選繭選顧簾遞觸積餘 (遞醖構鬱網鏇蓋願醖鏇 ) 更多	积极	2021-06-02
				Placebo + MTX	(觸餘憲簾願蓋膚築積衊) = 襯顧製夢蓋簾鬱選鹹製觸選繭選顧簾遞觸積餘 (遞醖構鬱網鏇蓋願醖鏇 ) 更多
NCT04397562 (CORONA, EULAR2021)	临床3期	新型冠状病毒感染 Erythrocyte sedimentation rate (ESR) \| C-reactive protein (CRP) \| IL-6	217	Levilimab	(繭範壓簾繭鏇鬱積構鹽) = 鹹簾窪鹽齋廠壓蓋簾鹽鹽選憲淵範壓簾窪願衊 (繭廠淵襯夢顧簾選積網 ) 更多	积极	2021-06-02
				Placebo	(繭範壓簾繭鏇鬱積構鹽) = 憲簾齋構餘顧糧廠築糧鹽選憲淵範壓簾窪願衊 (繭廠淵襯夢顧簾選積網 ) 更多
NCT03103438 (CTgov)	临床1期	自身免疫性疾病 \| 类风湿关节炎	19	BCD-089 (Cohort 1)	淵襯窪網網壓繭鬱獵鏇(艱鬱繭觸鏇遞衊構範獵) = 簾願獵艱廠衊鹹願蓋積糧淵鏇壓鑰顧遞範鏇遞 (製齋積鬱構簾製鹽廠膚, 壓淵簾餘廠鹹蓋鏇醖願 ~ 艱構範淵艱蓋鏇鑰範膚) 更多	-	2021-02-26
				BCD-089 (Cohort 2)	淵襯窪網網壓繭鬱獵鏇(艱鬱繭觸鏇遞衊構範獵) = 觸膚網襯夢衊餘餘蓋網糧淵鏇壓鑰顧遞範鏇遞 (製齋積鬱構簾製鹽廠膚, 襯網積鹽簾鑰繭積廠憲 ~ 範膚蓋襯醖構夢簾繭淵) 更多
NCT03455842 (EULAR2020)	临床2期	类风湿关节炎	105	Levilimab + Methotrexate (QW)	(齋簾襯蓋鑰網鑰製襯選) = 簾構醖糧艱鹽製鏇鏇網衊壓糧遞願積構壓選構 (鹽簾鏇醖鑰範壓築觸製 ) 更多	-	2020-06-03
				Levilimab + Methotrexate (Q2W)	(齋簾襯蓋鑰網鑰製襯選) = 窪鹽觸顧糧夢膚夢積鹹衊壓糧遞願積構壓選構 (鹽簾鏇醖鑰範壓築觸製 ) 更多
NCT03455842 (AURORA, EULAR2019)	临床2期	类风湿关节炎	105	BCD-089 QW+MTX	(憲顧醖鹹網構製範艱糧) = 餘築鏇窪鏇選齋構範觸鏇蓋蓋蓋衊蓋築願構鑰 (壓繭鬱積鑰窪鹹鏇齋餘 ) 更多	积极	2019-06-12
				BCD-089 Q2W+MTX	(憲顧醖鹹網構製範艱糧) = 襯範襯鑰範糧艱網齋淵鏇蓋蓋蓋衊蓋築願構鑰 (壓繭鬱積鑰窪鹹鏇齋餘 ) 更多