GSK-2330811(GSK-2330811) - 药物靶点：OSM_专利_临床

概要

基本信息

药物类型

单克隆抗体

别名

GSK 2330811、GSK2330811

靶点

OSM

作用方式

抑制剂、调节剂

作用机制

OSM抑制剂(肿瘤抑制因子抑制剂)、免疫调节剂

治疗领域

免疫系统疾病消化系统疾病皮肤和肌肉骨骼疾病+ [1]

在研适应症-

非在研适应症

克罗恩病弥漫性硬皮病

原研机构

GSK Plc

在研机构-

非在研机构

GSK Plc

权益机构-

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 67977L

Sequence Code 67982H

关联

4

项与 GSK-2330811 相关的临床试验

NCT04151225

/ Withdrawn临床2期

A Multicentre, Randomised, Double-blind, Placebo-controlled, Repeat Dose, Dose-ranging Phase 2a/2b Study to Evaluate the Safety, Tolerability and Efficacy of an Anti-oncostatin M Monoclonal Antibody (GSK2330811) in Patients With Moderate to Severe Crohn's Disease

The study will include participants with moderate to severe Crohn's disease. The aim is to evaluate the safety, tolerability, and efficacy of anti-oncostatin M monoclonal antibody (mAb) GSK2330811. This is a parallel group study with Induction and Maintenance periods. During Induction, the first 100 participants randomised will receive a 450mg GSK2330811 SC loading dose followed by 150mg weekly (Q1W), or placebo for 12 weeks. Additional dose-ranging arms will open after the 100th participant is randomized and in addition to placebo and the highest dose arms will also include a 300mg subcutaneous (SC) loading dose followed by 150mg SC every 2 weeks (Q2W) arm, a 300mg loading dose followed by 150mg SC every 4 weeks (Q4W) arm and a 150mg SC every 8 weeks (Q8W) arm. Participants with a clinical response at Week 12 will continue into a 40-week blinded maintenance period and will receive either 150mg SC Q2W, 150mg SC Q4W, 150mg SC Q8W or placebo. Participants without a clinical response at Week 12 will be offered up to 40 weeks of open label treatment with GSK2330811. Approximately 560 participants will be screened to randomize 280.

开始日期2021-04-05

申办/合作机构

GSK Plc

NCT04138043

/ Completed临床1期

A Phase 1, Randomised, Double-blind, Placebo-controlled Study of the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Subcutaneous Doses of GSK2330811 in Healthy Japanese Participants

This is a randomized, double-blind (sponsor-open), placebo-controlled, single-center study involving Japanese participants. The purpose of the study is to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity after a single subcutaneous (SC) dose of GSK2330811 in healthy Japanese participants. GSK2330811 is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that binds and inhibits the action of Oncostatin M (OSM) and is being developed for the treatment of Crohn's disease (CD) and Systemic sclerosis (SSc). Participants will be randomized to receive either GSK2330811 (450 milligram [mg]) or placebo in an approximate ratio of 7:3.

开始日期2019-12-05

申办/合作机构

GSK Plc

NCT03041025

/ Completed临床2期

A Multi-center, Randomized, Double-blind (Sponsor Open), Placebo-controlled, Repeat-dose, Proof of Mechanism Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Explore Efficacy of GSK2330811 in Participants With Diffuse Cutaneous Systemic Sclerosis

GSK2330811 is a humanized monoclonal antibody which is in development for systemic sclerosis (SSc), a rare autoimmune disease with high morbidity and mortality. Currently, there are no approved disease modifying therapies and it is an area of high unmet medical need. GSK2330811 has been shown to bind and neutralize Oncostatin M (OSM) that has been associated with fibrosis, vasculopathy and inflammation in a number of diseases. This multi-center, randomized, double-blind (sponsor open), placebo controlled, proof of mechanism study will be the first study to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of repeat subcutaneous (SC) doses of GSK2330811 in male and female participants with diffuse cutaneous SSc (dcSSc). Participants with active disease and a disease duration of <= 60 months will be enrolled. Approximately 24 to 40 participants will be randomized across two sequential cohorts. Cohort 1 will evaluate a repeat-dose predicted to provide sub-maximal inhibition of OSM, leading to a dose escalation decision. Cohort 1 is planned to consist of at least 4 participants, randomized such that 3 participants will receive GSK2330811 100 milligram (mg) and 1 will receive placebo. Cohort 2 is planned to consist of at least 20 participants, randomized such that participants will receive GSK2330811 300 mg and placebo in a 3:1 ratio respectively. The duration of the study is up to 34 weeks including a screening period of up to 6 weeks, treatment period of 12 weeks and follow-up period of 16 weeks.

开始日期2017-06-05

申办/合作机构

GSK Plc

100 项与 GSK-2330811 相关的临床结果

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100 项与 GSK-2330811 相关的转化医学

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100 项与 GSK-2330811 相关的专利（医药）

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2

项与 GSK-2330811 相关的文献（医药）

2022-12-23·Rheumatology (Oxford, England)

Biological and clinical insights from a randomized phase 2 study of an anti-oncostatin M monoclonal antibody in systemic sclerosis

Article

作者: Wisniacki, Nicolas ; Khanna, Dinesh ; Denton, Christopher P ; Csomor, Eszter ; Flint, Shaun M ; Varga, John ; Temple, Jane ; Reid, Juliet ; Lee, Amy ; del Galdo, Francesco ; Vonk, Madelon C ; Furst, Daniel E ; Johnson, Sindhu R ; Zecchin, Chiara ; Chung, Lorinda

Abstract:

Objectives:

The cytokine oncostatin M (OSM) is implicated in the pathology of SSc. Inhibiting OSM signalling using GSK2330811 (an anti-OSM monoclonal antibody) in patients with SSc has the potential to slow or stop the disease process.

Methods:

This multicentre, randomized, double-blind, placebo-controlled study enrolled participants ≥18 years of age with active dcSSc. Participants were randomized 3:1 (GSK2330811:placebo) in one of two sequential cohorts to receive GSK2330811 (cohort 1: 100 mg; cohort 2: 300 mg) or placebo s.c. every other week for 12 weeks. The primary endpoint was safety; blood and skin biopsy samples were collected to explore mechanistic effects on inflammation and fibrosis. Clinical efficacy was an exploratory endpoint.

Results:

Thirty-five participants were randomized to placebo (n = 8), GSK2330811 100 mg (n = 3) or GSK2330811 300 mg (n = 24). Proof of mechanism, measured by coordinate effects on biomarkers of inflammation or fibrosis, was not demonstrated following GSK2330811 treatment. There were no meaningful differences between GSK2330811 and placebo for any efficacy endpoints. The safety and tolerability of GSK2330811 were not favourable in the 300 mg group, with on-target, dose-dependent adverse events related to decreases in haemoglobin and platelet count that were not observed in the 100 mg or placebo groups.

Conclusion:

Despite a robust and novel experimental medicine approach and evidence of target engagement, anticipated SSc-related biologic effects of GSK2330811 were not different from placebo and safety was unfavourable, suggesting OSM inhibition may not be a useful therapeutic strategy in SSc.

Trial registration number:

ClinicalTrials.gov, NCT03041025; EudraCT, 2016-003417-95.

2018-10-01·British journal of clinical pharmacology2区 · 医学

In vivo affinity and target engagement in skin and blood in a first‐time‐in‐human study of an anti‐oncostatin M monoclonal antibody

2区 · 医学

Article

作者: Fernando, Disala ; Feeney, Maria ; Reid, Juliet ; Edwards, Ken ; Zamuner, Stefano ; Nevin, Katherine ; Zecchin, Chiara ; Wisniacki, Nicolas ; Rumley, Sally‐Anne

Aims:

The oncostatin M (OSM) pathway drives fibrosis, inflammation and vasculopathy, and is a potential therapeutic target for inflammatory and fibrotic diseases. The aim of this first‐time‐in‐human experimental medicine study was to assess the safety, tolerability, pharmacokinetics and target engagement of single subcutaneous doses of GSK2330811, an anti‐OSM monoclonal antibody, in healthy subjects.

Methods:

This was a phase I, randomized, double‐blind, placebo‐controlled, single‐dose escalation, first‐time‐in‐human study of subcutaneously administered GSK2330811 in healthy adults (NCT02386436). Safety and tolerability, GSK2330811 pharmacokinetic profile, OSM levels in blood and skin, and the potential for antidrug antibody formation were assessed. The in vivo affinity of GSK2330811 for OSM and target engagement in serum and skin blister fluid (obtained via a skin suction blister model) were estimated using target‐mediated drug disposition (TMDD) models in combination with compartmental and physiology‐based pharmacokinetic (PBPK) models.

Results:

Thirty subjects were randomized to receive GSK2330811 and 10 to placebo in this completed study. GSK2330811 demonstrated a favourable safety profile in healthy subjects; no adverse events were serious or led to withdrawal. There were no clinically relevant trends in change from baseline in laboratory values, with the exception of a reversible dose‐dependent reduction in platelet count. GSK2330811 exhibited linear pharmacokinetics over the dose range 0.1–6 mg kg–1. The estimated in vivo affinity (nM) of GSK2330811 for OSM was 0.568 [95% confidence interval (CI) 0.455, 0.710] in the compartmental with TMDD model and 0.629 (95% CI 0.494, 0.802) using the minimal PBPK with TMDD model.

Conclusions:

Single subcutaneous doses of GSK2330811 were well tolerated in healthy subjects. GSK2330811 demonstrated sufficient affinity to achieve target engagement in systemic circulation and target skin tissue, supporting the progression of GSK2330811 clinical development.

100 项与 GSK-2330811 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
克罗恩病	临床2期	-	GSK Plc	2021-04-05
弥漫性硬皮病	临床2期	美国	GSK Plc	2017-06-05
弥漫性硬皮病	临床2期	加拿大	GSK Plc	2017-06-05
弥漫性硬皮病	临床2期	荷兰	GSK Plc	2017-06-05
弥漫性硬皮病	临床2期	英国	GSK Plc	2017-06-05

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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


NCT04138043 (CTgov)	临床1期	系统性硬皮病 \| 克罗恩病	9	Placebo (Placebo)	鹽鹹醖廠簾蓋糧鹽鏇遞 = 壓網廠觸艱憲簾壓糧襯選顧簾衊淵築夢廠網範 (選淵艱築簾積網鬱鹹積, 窪壓夢簾構膚壓簾簾壓 ~ 遞鬱鏇淵齋繭壓夢鹽選) 更多	-	2021-05-24
				GSK2330811 (GSK2330811 450 mg)	鹽鹹醖廠簾蓋糧鹽鏇遞 = 膚繭範艱餘鬱憲顧獵觸選顧簾衊淵築夢廠網範 (選淵艱築簾積網鬱鹹積, 窪選繭憲願壓廠壓積選 ~ 遞艱醖繭顧選觸憲憲淵) 更多
NCT03041025 (CTgov)	临床2期	弥漫性硬皮病	35	placebo (Placebo)	簾範窪繭憲選淵築網夢 = 繭顧廠蓋選觸繭鏇選襯範築憲淵壓鬱糧選簾壓 (獵糧淵繭顧夢選襯壓構, 鹹艱廠鏇網醖憲襯觸築 ~ 選糧襯觸艱壓蓋構願糧) 更多	-	2021-05-24
				GSK2330811 (GSK2330811 100 mg)	簾範窪繭憲選淵築網夢 = 鏇簾齋選壓廠廠壓艱窪範築憲淵壓鬱糧選簾壓 (獵糧淵繭顧夢選襯壓構, 製製網壓糧窪繭觸獵膚 ~ 製築糧蓋網範壓簾構鹹) 更多