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Lookup NU author(s): Dr Faye WolstenhulmeORCiD, Irena Bibby, Mike Cole, Lydia Grixti, Dr Naomi McGregorORCiD, Penny Bradley, Rebecca Maier, Jenn Walker, Professor Simon PearceORCiD, Professor James WasonORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ. INTRODUCTION: Severe Graves' disease is a life-changing condition with poor outcomes from currently available treatments. It is caused by directly pathogenic thyroid-stimulating hormone receptor-stimulating antibodies (TRAb), which are secreted from plasma cells. The human anti-CD38 monoclonal antibody daratumumab was developed to target plasma cells which express high levels of CD38, and is currently licensed for treatment of the plasma cell malignancy, myeloma. However, it can also deplete benign plasma cells with the potential to reduce TRAb and alter the natural history of severe Graves' disease. This study aims to establish proof of concept that daratumumab has efficacy in patients with severe Graves' disease and will provide important data to inform a choice of dosing regimen for subsequent trials. METHODS AND ANALYSIS: The Graves-PCD trial aims to determine if daratumumab modulates the humoral immune response in patients with severe Graves' disease, and if so, over what time period, and to find an optimal dose. It is a single-blinded, randomised, dose-finding, adaptive trial using four different doses of daratumumab or placebo in 30 adult patients. Part 1 of the trial is dose-finding and, following an interim analysis, in part 2, the remaining patients will be randomised between the chosen dose(s) from the interim analysis or placebo. The primary outcome is the percentage change in serum TRAb from baseline to 12 weeks. ETHICS AND DISSEMINATION: The trial received a favourable ethical opinion from London-Hampstead Research Ethics Committee (reference 21/LO/0449). The results of this trial will be disseminated at international meetings, in the peer-reviewed literature and through partner patient group newsletters and presentations at patient education events. TRIAL REGISTRATION NUMBER: ISRCTN81162400.
Author(s): Wolstenhulme F, Bibby I, Cole M, Grixti L, McGregor N, Bradley P, Maier RH, Walker J, Pearce SH, Wason J
Publication type: Article
Publication status: Published
Journal: BMJ Open
Year: 2024
Volume: 14
Issue: 6
Online publication date: 12/06/2024
Acceptance date: 31/05/2024
Date deposited: 24/06/2024
ISSN (print): 2044-6055
ISSN (electronic): 2044-6055
Publisher: BMJ Publishing Group
URL: https://doi.org/10.1136/bmjopen-2023-079158
DOI: 10.1136/bmjopen-2023-079158
PubMed id: 38866568
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