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Lookup NU author(s): Professor Fai NgORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
© The Author(s) 2024.Sjögren’s disease (SjD) is a chronic, systemic autoimmune disease with no approved disease-modifying therapies. Dazodalibep (DAZ), a novel nonantibody fusion protein, is a CD40 ligand antagonist that blocks costimulatory signals between T and B cells and antigen-presenting cells, and therefore may suppress the wide spectrum of cellular and humoral responses that drive autoimmunity in SjD. This study was a phase 2, randomized, double-blinded, placebo (PBO)-controlled trial of DAZ with a crossover stage in two distinct populations of participants with SjD. Population 1 had moderate-to-severe systemic disease activity and population 2 had an unacceptable symptom burden and limited systemic organ involvement. All participants had a diagnosis of SjD, with 21.6% and 10.1% having an associated connective tissue disease (rheumatoid arthritis or systemic lupus erythematosus) in populations 1 and 2, respectively. The remaining participants would be considered as having primary Sjögren’s syndrome. The primary endpoint for population 1 (n = 74) was the change from baseline in the European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index at day 169. The primary endpoint for population 2 (n = 109) was the change from baseline in the European League Against Rheumatism Sjögren’s Syndrome Patient Reported Index at day 169. The primary endpoints (least squares mean ± standard error) were achieved with statistical significance for both population 1 (DAZ, −6.3 ± 0.6; PBO, −4.1 ± 0.6; P = 0.0167) and population 2 (DAZ, −1.8 ± 0.2; PBO, −0.5 ± 0.2; P = 0.0002). DAZ was generally safe and well tolerated. Among the most frequently reported adverse events were COVID-19, diarrhea, headache, nasopharyngitis, upper respiratory tract infection, arthralgia, constipation and urinary tract infection. In summary, DAZ appears to be a potential new therapy for SjD and its efficacy implies an important role for the CD40/CD40 ligand pathway in its pathogenesis. ClinicalTrials.gov identifier: NCT04129164.
Author(s): St Clair EW, Baer AN, Ng W-F, Noaiseh G, Baldini C, Tarrant TK, Papas A, Devauchelle-Pensec V, Wang L, Xu W, Pham T-H, Sikora K, Rees WA, Alevizos I
Publication type: Article
Publication status: Published
Journal: Nature Medicine
Year: 2024
Pages: epub ahead of print
Online publication date: 05/06/2024
Acceptance date: 18/04/2024
Date deposited: 17/06/2024
ISSN (print): 1078-8956
ISSN (electronic): 1546-170X
Publisher: Nature Research
URL: https://doi.org/10.1038/s41591-024-03009-3
DOI: 10.1038/s41591-024-03009-3
Data Access Statement: Data-sharing requests relating to data in this paper will be considered after the publication date and providing that either (1) this product and indication (or other new use) have been granted marketing authorization in both the United States and Europe or (2) clinical development discontinues and the data will not be submitted to the regulatory authorities. There is no end date for eligibility to submit a data-sharing request for these data. This may include deidentified individual patient data for variables necessary to address the specific research question in an approved data-sharing request; and also related data dictionaries, study protocol, statistical analysis plan, informed consent form and/or clinical study report. Qualified researchers may submit a request (the remainder of the data access statement can be found in the paper)
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