Denton, C.P. orcid.org/0000-0003-3975-8938, del Galdo, F. orcid.org/0000-0002-8528-2283, Khanna, D. et al. (12 more authors) (2023) Biological and clinical insights from a randomized phase 2 study of an anti-oncostatin M monoclonal antibody in systemic sclerosis. Rheumatology, 62 (1). pp. 234-242. ISSN 1462-0324
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (https://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
Keywords: | biomarkers; fibrosis; GSK2330811; inflammation; monoclonal antibody; placebo-controlled trial; safety |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Institute of Rheumatology & Musculoskeletal Medicine (LIRMM) (Leeds) > Inflammatory Arthritis (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 15 Nov 2023 12:51 |
Last Modified: | 15 Nov 2023 12:51 |
Status: | Published |
Publisher: | Oxford University Press |
Identification Number: | 10.1093/rheumatology/keac300 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:205298 |