{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T00:48:43Z","timestamp":1775695723173,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,11,26]],"date-time":"2024-11-26T00:00:00Z","timestamp":1732579200000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Neuromyelitis optica spectrum disorder (NMOSD) is a rare debilitating autoimmune disease of the central nervous system (CNS). This is the first\u2010in\u2010human dose\u2010escalation Phase I clinical study of BAT4406F, an antibody\u2010dependent cell\u2010mediated cytotoxicity (ADCC)\u2010enhanced fully humanized anti\u2010CD20 monoclonal antibody, in Chinese NMOSD patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Using a \u201c3\u2009+\u20093\u201d design and based on the planned algorithm of dose escalation, the enrolled NMOSD patients were sequentially assigned to one of the five dose\u2010escalation cohorts of BAT4406F with a single intravenous dose, and were then followed for a 6\u2010month observation period. The maximum tolerated dose (MTD) and dose\u2010limiting toxicity (DLT), safety, pharmacokinetics (PK), pharmacodynamics, and immunogenicity of BAT4406F were investigated, and the efficacy of BAT4406F in NMOSD was also preliminarily explored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifteen Chinese NMOSD patients were enrolled to receive BAT4406F of escalated doses ranging from 20 to 750\u2009mg. No subjects experienced DLT at the studied doses. BAT4406F injection exhibited favorable safety, with most of the adverse events (AE) of CTCAE Grade 1 or 2 in severity, and no Grade \u2265\u20093 adverse drug reactions (ADR) or serious adverse reactions occurred in any subjects. With the dose increase of BAT4406F, the maximum plasma concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>), area under concentration\u2010time curve from 0 to the last measurable timepoint (AUC<jats:sub>0\u2010t<\/jats:sub>) and area under concentration\u2010time curve from 0 to infinity (AUC<jats:sub>0\u2010inf<\/jats:sub>) showed an increasing trend, whereas the mean clearance (CL<jats:sub>t<\/jats:sub>), terminal elimination rate (<jats:italic>\u03bb<\/jats:italic><jats:sub>Z<\/jats:sub>), and apparent volume of distribution (<jats:italic>V<\/jats:italic><jats:sub>d<\/jats:sub>) decreased. The mean elimination half\u2010life (<jats:italic>T<\/jats:italic><jats:sub>1\/2<\/jats:sub>) was ranged from 9.0\u201316.4\u2009days. PK profile of BAT4406F was generally nonlinear. BAT4406F led to a rapid and significant B\u2010cell depletion in all dose groups. Single administration of 500\u2009mg or 750\u2009mg maintains the CD19<jats:sup>+<\/jats:sup> B lymphocyte count below 10\/\u03bcL within the whole 6\u2010month observation period. Three subjects were antidrug antibody (ADA) positive and all of them were neutralizing antibody (NAb)\u2010negative. On day 99\/180 postdose, several groups had decreased expanded disability status scale (EDSS) scores compared to baseline. During the observation period, NMOSD relapse occurred in two patients (13.3%) and the other 13 (86.7%) subjects remained relapse free.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>BAT4406F was well tolerated at doses up to 750\u2009mg and showed an expected pharmacodynamic effect of significant and long\u2010term depletion of CD19<jats:sup>+<\/jats:sup> B lymphocytes. It has also shown preliminary evidence of activity in NMOSD maintenance treatment, warranting further investigations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link> identifier: NCT04146285<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70126","type":"journal-article","created":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T04:25:19Z","timestamp":1732681519000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["First\u2010in\u2010Human Study of <scp>BAT4406F<\/scp>, an <scp>ADCC<\/scp>\u2010Enhanced Fully Humanized Anti\u2010<scp>CD20<\/scp> Monoclonal Antibody in Patients With Neuromyelitis Optica Spectrum Disorders"],"prefix":"10.1111","volume":"30","author":[{"given":"Hai","family":"Yu","sequence":"first","affiliation":[{"name":"Department of Neurology, Huashan Hospital, Fudan University and Institute of Neurology Fudan University  Shanghai China"},{"name":"National Center for Neurological Disorders  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuancheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital Fudan University  Shanghai China"},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital Fudan University  Shanghai China"},{"name":"Research Ward of Huashan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunpeng","family":"Qi","sequence":"additional","affiliation":[{"name":"Bio\u2010Thera Solutions Ltd  Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haijing","family":"Yang","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital Fudan University  Shanghai China"},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital Fudan University  Shanghai China"},{"name":"Research Ward of Huashan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guoying","family":"Cao","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Research Center, Huashan Hospital Fudan University  Shanghai China"},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital Fudan University  Shanghai China"},{"name":"Research Ward of Huashan Hospital Fudan University  Shanghai China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenbo","family":"Yang","sequence":"additional","affiliation":[{"name":"Department 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