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.

Start Date07 Dec 2022

Sponsor / Collaborator

Biocad CJSC

NCT04397562 / CompletedPhase 3

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.

Start Date29 Apr 2020

Sponsor / Collaborator

Biocad CJSC

NCT04227366 / CompletedPhase 3

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.

Start Date19 Nov 2019

Sponsor / Collaborator

Biocad CJSC

100 Clinical Results associated with Levilimab

100 Translational Medicine associated with Levilimab

100 Patents (Medical) associated with Levilimab

Literatures (Medical) associated with Levilimab

01 Jan 2023·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

Author: 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.

01 Dec 2021·Inflammation ResearchQ3 · MEDICINE

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

Q3 · MEDICINE

Article

Author: 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).

18 Mar 2021·The Cochrane database of systematic reviews

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

Review

Author: 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 Deals associated with Levilimab

External Link

KEGG	Wiki	ATC	Drug Bank
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R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Rheumatoid Arthritis	RU	Biocad CJSC	08 Jun 2021
COVID-19	RU	Biocad CJSC	04 Jun 2020

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04397562 (SOLAR, EULAR2022)	Phase 3	Rheumatoid Arthritis	154	Levilimab 162 mg, SC + MTX	egrbprmtqy(ytgfwivbep) = oigqlugsrw izufpjcpba (rdirkxwkav ) View more	Positive	01 Jun 2022
NCT04397562 (CORONA, Pubmed) Manual	Phase 3	COVID-19	217	SOC+levilimab	(yrbqdwjszv) = xkbhchszcx ikitwsfaah (mjkzncyixf )	Positive	01 Dec 2021
				Placebo+SOC	(yrbqdwjszv) = vdermxsvjr ikitwsfaah (mjkzncyixf )
NCT04397562 (SOLAR, EULAR2021)	Phase 3	Rheumatoid Arthritis	154	Levilimab + MTX	(pvkdlcsmza) = qhocbzvqcr cezhhzeosw (mxrlpvqoqd ) View more	Positive	02 Jun 2021
				Placebo + MTX	(pvkdlcsmza) = offhbguwea cezhhzeosw (mxrlpvqoqd ) View more
NCT04397562 (CORONA, EULAR2021)	Phase 3	COVID-19 Erythrocyte sedimentation rate (ESR) \| C-reactive protein (CRP) \| IL-6	217	Levilimab	(uompcmrsrg) = bcoiuaunbu cnyqdszedc (qgiwdifydg ) View more	Positive	02 Jun 2021
				Placebo	(uompcmrsrg) = wthhbytlii cnyqdszedc (qgiwdifydg ) View more
NCT03103438 (CTgov)	Phase 1	Autoimmune Diseases \| Rheumatoid Arthritis	19	BCD-089 (Cohort 1)	evqyecvysm(izsermdmme) = gbrwpqfnfz ihhfcguwcf (feqzyjnpeu, orbobwgqgp - gfekacdhct) View more	-	26 Feb 2021
				BCD-089 (Cohort 2)	evqyecvysm(izsermdmme) = nstktdcbab ihhfcguwcf (feqzyjnpeu, uzykpglvvz - oiasclotxu) View more
NCT03455842 (EULAR2020)	Phase 2	Rheumatoid Arthritis	105	Levilimab + Methotrexate (QW)	(wocfyptcti) = lsrwchghdc ldwlhlxukn (vmvcvjyyea ) View more	-	03 Jun 2020
				Levilimab + Methotrexate (Q2W)	(wocfyptcti) = ijqnxkjrca ldwlhlxukn (vmvcvjyyea ) View more
NCT03455842 (AURORA, EULAR2019)	Phase 2	Rheumatoid Arthritis	105	BCD-089 QW+MTX	(uflhhuusek) = njikkgvxbp ttqmypphcd (oixcczqmat ) View more	Positive	12 Jun 2019
				BCD-089 Q2W+MTX	(uflhhuusek) = xukqrtpeut ttqmypphcd (oixcczqmat ) View more

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