Delving into the Latest Updates on GSK-2330811 with Synapse

Overview

Basic Info

Drug Type

Monoclonal antibody

Synonyms

GSK 2330811, GSK2330811

Target

OSM

Action

inhibitors, modulators

Mechanism

OSM inhibitors(Oncostatin M inhibitors), Immunomodulators

Therapeutic Areas

Immune System DiseasesDigestive System DisordersSkin and Musculoskeletal Diseases+ [1]

Active Indication-

Inactive Indication

Crohn DiseaseScleroderma, Diffuse

Originator Organization

GSK Plc

Active Organization-

Inactive Organization

GSK Plc

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure/Sequence

Sequence Code 67977L

Sequence Code 67982H

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.

Start Date05 Apr 2021

Sponsor / Collaborator

GSK Plc

NCT04138043

/ CompletedPhase 1

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.

Start Date05 Dec 2019

Sponsor / Collaborator

GSK Plc

NCT03041025

/ CompletedPhase 2

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.

Start Date05 Jun 2017

Sponsor / Collaborator

GSK Plc

100 Clinical Results associated with GSK-2330811

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100 Translational Medicine associated with GSK-2330811

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100 Patents (Medical) associated with GSK-2330811

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2

Literatures (Medical) associated with GSK-2330811

23 Dec 2022·Rheumatology (Oxford, England)

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

Article

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

01 Oct 2018·British journal of clinical pharmacologyQ2 · MEDICINE

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

Q2 · MEDICINE

Article

Author: Feeney, Maria ; Fernando, Disala ; Reid, Juliet ; Edwards, Ken ; Zamuner, Stefano ; Nevin, Katherine ; Wisniacki, Nicolas ; Zecchin, Chiara ; 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 Deals associated with GSK-2330811

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R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Crohn Disease	Phase 2	-	GSK Plc	05 Apr 2021
Scleroderma, Diffuse	Phase 2	United States	GSK Plc	05 Jun 2017
Scleroderma, Diffuse	Phase 2	Canada	GSK Plc	05 Jun 2017
Scleroderma, Diffuse	Phase 2	Netherlands	GSK Plc	05 Jun 2017
Scleroderma, Diffuse	Phase 2	United Kingdom	GSK Plc	05 Jun 2017

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04138043 (CTgov)	Phase 1	Scleroderma, Systemic \| Crohn Disease	9	Placebo (Placebo)	vmbscjnynh = xsjhcaxscv mffkpntslw (pjmffepgsl, eurutpyztl - kchuopvpzk) View more	-	24 May 2021
				GSK2330811 (GSK2330811 450 mg)	vmbscjnynh = ttfqtmphpr mffkpntslw (pjmffepgsl, uwbvyeqazs - bqyidxakfh) View more
NCT03041025 (CTgov)	Phase 2	Scleroderma, Diffuse	35	placebo (Placebo)	djvnhidbbr = mjujcgxfyj egbgxvptma (ssruthltzk, rcphclkfgk - wtbzuzuypd) View more	-	24 May 2021
				GSK2330811 (GSK2330811 100 mg)	djvnhidbbr = dqmilzgrxk egbgxvptma (ssruthltzk, eyxxqcabho - iqzibennsq) View more

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Biosimilar

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