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- 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.
- Authors
Sato, Tomoo; Nagai, Masahiro; Watanabe, Osamu; Misu, Tatsuro; Takenouchi, Norihiro; Ohkubo, Ryuichi; Ishihara, Satoshi; Tsuboi, Yoshio; Katsuno, Masahisa; Nakagawa, Masanori; Matsushita, Takuya; Aso, Yasuhiro; Matsuura, Eiji; Tokashiki, Takashi; Mukaino, Akihiro; Adachi, Hiroaki; Nakanishi, Kaoru; Yamaguchi, Yusuke; Yamaguchi, Saaya; Yamano, Yoshihisa
- Abstract
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks 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 ≥ 1-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 (− 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60–80% 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. Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
- Subjects
HTLV; PARAPARESIS; HTLV-I; SPINAL cord diseases
- Publication
Journal of Neurology, 2024, Vol 271, Issue 6, p3471
- ISSN
0340-5354
- Publication type
Article
- DOI
10.1007/s00415-024-12239-x