BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) causes the debilitating 
neuroinflammatory disease HTLV-1-associated myelopathy-tropical spastic 
paraparesis (HAM-TSP) as well as adult T-cell leukemia-lymphoma (ATLL). In 
patients with HAM-TSP, HTLV-1 infects mainly CCR4+ T cells and induces 
functional changes, ultimately causing chronic spinal cord inflammation. We 
evaluated mogamulizumab, a humanized anti-CCR4 monoclonal antibody that targets 
infected cells, in patients with HAM-TSP.
METHODS: In this uncontrolled, phase 1-2a study, we assessed the safety, 
pharmacokinetics, and efficacy of mogamulizumab in patients with 
glucocorticoid-refractory HAM-TSP. In the phase 1 dose-escalation study, 21 
patients received a single infusion of mogamulizumab (at doses of 0.003 mg per 
kilogram of body weight, 0.01 mg per kilogram, 0.03 mg per kilogram, 0.1 mg per 
kilogram, or 0.3 mg per kilogram) and were observed for 85 days. Of those 
patients, 19 continued on to the phase 2a study and received infusions, over a 
period of 24 weeks, of 0.003 mg per kilogram, 0.01 mg per kilogram, or 0.03 mg 
per kilogram at 8-week intervals or infusions of 0.1 mg per kilogram or 0.3 mg 
per kilogram at 12-week intervals.
RESULTS: The side effects of mogamulizumab did not limit administration up to 
the maximum dose (0.3 mg per kilogram). The most frequent side effects were 
grade 1 or 2 rash (in 48% of the patients) and lymphopenia and leukopenia (each 
in 33%). The dose-dependent reduction in the proviral load in peripheral-blood 
mononuclear cells (decrease by day 15 of 64.9%; 95% confidence interval [CI], 
51.7 to 78.1) and inflammatory markers in cerebrospinal fluid (decrease by day 
29 of 37.3% [95% CI, 24.8 to 49.8] in the CXCL10 level and of 21.0% [95% CI, 
10.7 to 31.4] in the neopterin level) was maintained with additional infusions 
throughout the phase 2a study. A reduction in spasticity was noted in 79% of the 
patients and a decrease in motor disability in 32%.
CONCLUSIONS: Mogamulizumab decreased the number of HTLV-1-infected cells and the 
levels of inflammatory markers. Rash was the chief side effect. The effect of 
mogamulizumab on clinical HAM-TSP needs to be clarified in future studies. 
(Funded by the Japan Agency for Medical Research and Development and the 
Ministry of Health, Labor, and Welfare; UMIN trial number, UMIN000012655 .).