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Review, Journal: Mast cell silencing: A novel therapeutic approach for urticaria and other mast cell-mediated diseases. (Pubmed Central) - Aug 22, 2023 MC silencers, such as agonist monoclonal antibodies that engage inhibitory receptors (e.g., sialic acid-binding immunoglobulin-like lectin8 -[Siglec-8] [lirentelimab/AK002], Siglec-6 [AK006], and CD200R [LY3454738]), have reached preclinical and clinical stages of development. In this review, we (1) describe the role of MCs in the pathogenesis of CU, highlighting similarities with other MC diseases in disease mechanisms and response to treatment; (2) explore current therapeutic strategies, categorized by nonspecific immunosuppression, targeted inhibition of MC activation or mediators, and targeted modulation of MC activity; and (3) introduce the concept of MC silencing as an emerging strategy that could selectively block activation of MCs without eliciting or exacerbating on- or off-target, immunosuppressive adverse effects.
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Trial completion, Enrollment change: A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - Oct 6, 2021 P1, N=128, Completed, In this review, we (1) describe the role of MCs in the pathogenesis of CU, highlighting similarities with other MC diseases in disease mechanisms and response to treatment; (2) explore current therapeutic strategies, categorized by nonspecific immunosuppression, targeted inhibition of MC activation or mediators, and targeted modulation of MC activity; and (3) introduce the concept of MC silencing as an emerging strategy that could selectively block activation of MCs without eliciting or exacerbating on- or off-target, immunosuppressive adverse effects. Active, not recruiting --> Completed | N=64 --> 128
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Journal: Biologics for the Use in Chronic Spontaneous Urticaria: When and Which. (Pubmed Central) - May 25, 2021 Guidelines for the treatment of chronic spontaneous urticaria (CSU) recommend the use of the IgE-targeted biologic omalizumab in patients with antihistamine-refractory disease...We provide information on the effects of the off-label use, in CSU, of biologics licensed for the treatment of other diseases, including dupilumab, benralizumab, mepolizumab, reslizumab, and secukinumab...These include IgE/ligelizumab, IgE/GI-310, thymic stromal lymphopoietin/tezepelumab, C5a receptor/avdoralimab, sialic acid-binding Ig-like lectin 8/lirentelimab, CD200R/LY3454738, and KIT/CDX-0159. Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future.
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Trial completion date, Trial termination: A Study of LY3454738 in Adults With Chronic Spontaneous Urticaria (clinicaltrials.gov) - May 19, 2021 P2, N=52, Terminated, Our aim is to provide updated information and guidance on the use of biologics in the treatment of patients with CSU, now and in the near future. Trial completion date: Sep 2021 --> Feb 2021 | Active, not recruiting --> Terminated; The study was terminated for lack of efficacy after an interim analysis was performed
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Enrollment closed: A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - May 5, 2021 P1, N=64, Active, not recruiting, Trial completion date: Sep 2021 --> Feb 2021 | Active, not recruiting --> Terminated; The study was terminated for lack of efficacy after an interim analysis was performed Recruiting --> Active, not recruiting
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[VIRTUAL] Development of LY3454738, an agonistic antibody to human CD200R () - Jul 1, 2020 - Abstract #SID2020SID_519; After demonstrating safety and tolerability in a phase 1 trial in healthy volunteers, LY3454738 is currently being studied in patients with atopic dermatitis and chronic spontaneous urticaria. The poster will describe properties and functional activities of the clinical drug candidate.
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Trial completion date, Trial primary completion date: A Study of LY3454738 in Healthy Participants and Participants With Atopic Dermatitis (clinicaltrials.gov) - Mar 17, 2020 P1, N=128, Recruiting, Trial completion date: Oct 2021 --> Jan 2022 | Recruiting --> Suspended | Trial primary completion date: Oct 2021 --> Jan 2022 Trial completion date: May 2020 --> Oct 2021 | Trial primary completion date: May 2020 --> Oct 2021
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