UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

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

Denton, Christopher P; del Galdo, Francesco; Khanna, Dinesh; Vonk, Madelon C; Chung, Lorinda; Johnson, Sindhu R; Varga, John; ... Reid, Juliet; + view all (2023) Biological and clinical insights from a randomised phase II study of an anti-oncostatin M monoclonal antibody in systemic sclerosis. Rheumatology , 62 (1) pp. 234-242. 10.1093/rheumatology/keac300. Green open access

[thumbnail of Denton_keac300.pdf]
Preview
Text
Denton_keac300.pdf

Download (459kB) | Preview

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.

Type: Article
Title: Biological and clinical insights from a randomised phase II study of an anti-oncostatin M monoclonal antibody in systemic sclerosis
Open access status: An open access version is available from UCL Discovery
DOI: 10.1093/rheumatology/keac300
Publisher version: https://doi.org/10.1093/rheumatology/keac300
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Biomarkers, Fibrosis, GSK2330811, Inflammation, Monoclonal antibody, Placebo-controlled trial, Safety
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inflammation
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10149171
Downloads since deposit
6Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item