Journal Article

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

Watanabe, Osamu, Yamaguchi, Saaya, Katsuno, Masahisa, Tokashiki, Takashi, Ohkubo, Ryuichi, Sato, Tomoo, Nakanishi, Kaoru, Yamaguchi, Yusuke, Adachi, Hiroaki, Nakagawa, Masanori, Matsuura, Eiji, Nagai, Masahiro, Misu, Tatsuro, Aso, Yasuhiro, Ishihara, Satoshi, Takenouchi, Norihiro, Matsushita, Takuya, Mukaino, Akihiro, Tsuboi, Yoshio, Yamano, Yoshihisa

2024

Overview

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).

• Publisher: Springer Berlin Heidelberg,Springer Nature B.V
• Subject: Central nervous system diseases / Cerebrospinal fluid / Chemokine receptors / Chemokines / Clinical trials / CXCL10 protein / Disease progression / Hereditary spastic paraplegia / Immunotherapy / Leukemia / Lymphocytes T / Medicine / Medicine & Public Health / Monoclonal antibodies / NCT / NCT03191526 / Neopterin / Neurodegenerative diseases / Neurology / Neuroradiology / Neurosciences / Original Communication / Patients / Placebos / Safety / Spinal cord / Targeted cancer therapy / Tropical spastic paraparesis