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This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3\u00a0mg\/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12\u00a0weeks in HAM\/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a \u2265\u20091-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (\u2212\u200959.39\u2009\u00b1\u200929.91% vs. placebo 2.32\u2009\u00b1\u200936.31%) and CSF neopterin (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001)\/CXCL10 levels (<jats:italic>p<\/jats:italic>\u2009=\u20090.004). The baseline OMDS pattern and the 60\u201380% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1\/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin\/CXCL10 levels are associated with long-term prognosis in HAM\/TSP.<\/jats:p><jats:p>Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).<\/jats:p>","DOI":"10.1007\/s00415-024-12239-x","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T14:02:00Z","timestamp":1709388120000},"page":"3471-3485","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy"],"prefix":"10.1007","volume":"271","clinical-trial-number":[{"clinical-trial-number":"nct03191526","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Tomoo","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nagai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osamu","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuro","family":"Misu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norihiro","family":"Takenouchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryuichi","family":"Ohkubo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Ishihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshio","family":"Tsuboi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahisa","family":"Katsuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanori","family":"Nakagawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Matsushita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhiro","family":"Aso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eiji","family":"Matsuura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Tokashiki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Mukaino","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Adachi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaoru","family":"Nakanishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saaya","family":"Yamaguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-0345","authenticated-orcid":false,"given":"Yoshihisa","family":"Yamano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,3,2]]},"reference":[{"key":"12239_CR1","doi-asserted-by":"publisher","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","volume":"3","author":"A Gessain","year":"2012","unstructured":"Gessain A, Cassar O (2012) Epidemiological aspects and world distribution of HTLV-1 infection. 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We thank the patients who participated in this study as well as the investigators and site staff members who provided support. We thank ASCA Corporation for providing medical writing support, which was funded by Kyowa Kirin Co., Ltd., in accordance with Good Publication Practice guidelines (). T. Sato and Y. Yamano received grants and consulting fees\/honoraria from Kyowa Kirin Co., Ltd. for this study. M. Nagai, O. Watanabe, T. Misu, N. Takenouchi, R. Ohkubo, S. Ishihara, Y. Tsuboi, M. Katsuno, M. Nakagawa, Y. Aso, E. Matsuura, T. Tokashiki, A. Mukaino, and H. Adachi received grants from Kyowa Kirin Co., Ltd. for this study. T. Matsushita received grant from Kyowa Kirin Co., Ltd. for this study and lecture fees\/speaker\u2019s bureaus from Takeda Pharmaceutical Company Ltd., Chugai Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, and Alexion Pharmaceuticals, Inc. outside the study. K. Nakanishi, Y. Yamaguchi, and S. Yamaguchi are employees of Kyowa Kirin Co., Ltd.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflicts of interest"}},{"value":"This study was performed in accordance with the ethical standards of the Declaration of Helsinki and in compliance with the Ministerial Ordinance on Good Clinical Practice for Drugs (Ordinance of the Ministry of Health and Welfare No. 28, 1997), the Pharmaceutical Affairs Law, the Ministerial Ordinance on the Partial Revision of the Ordinance, and other related notifications. This study was approved by the internal review board at each study site, and the study was registered at Japanese Pharmaceutical Information as JapicCTI-173608.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Written informed consent was obtained from all participating patients prior to the study initiation.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"The authors affirm that human research participants provided informed consent for publication of data from the clinical trial.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to publish"}}]}}