Yoshiya Tanaka1, Tsutomu Takeuchi2, Hisanori Umehara3, Toshihiro Nanki4, Nobuyuki Yasuda5, Fumitoshi Tago6, Makoto Kawakubo6, Yasumi Kitahara6, Seiichiro Hojo6, Tetsu Kawano5, Toshio Imai5. 1. a First Department of Internal Medicine , University of Occupational and Environmental Health , Kitakyushu , Japan. 2. b Division of Rheumatology, Department of Internal Medicine , Keio University School of Medicine , Tokyo , Japan. 3. c Division of Rheumatology and Immunology , Nagahama City Hospital , Shiga , Japan. 4. d Division of Rheumatology, Department of Internal Medicine , Toho University School of Medicine , Tokyo , Japan. 5. e KAN Research Institute, Inc. , Kobe , Japan. 6. f Eisai Co., Ltd. , Tokyo , Japan.
Abstract
OBJECTIVE: Fractalkine (CX3CL1/FKN) is a chemokine that regulates chemotaxis and adhesion of CX3C chemokine receptor 1 (CX3CR1)-expressing inflammatory cells. We conducted the first phase 1/2, open-label, multiple ascending dose study of E6011, a humanized anti-FKN monoclonal antibody, in Japanese rheumatoid arthritis (RA) patients (clinicaltrial.gov identifier: NCT02196558). METHODS: Active RA patients with an inadequate response or intolerance to methotrexate or tumor necrosis factor (TNF) inhibitor received E6011 at week 0, 1, 2, and thereafter every 2 weeks for 12 weeks. RESULTS: Twelve, 15, and 10 subjects were enrolled in the 100, 200, and 400 mg cohorts, respectively. No severe adverse events (AEs) or deaths occurred, and no major differences were observed in the incidence or severity of AEs across the cohorts. Serum E6011 concentrations increased dose dependently. American College of Rheumatology (ACR) 20, 50, and 70 responses at week 12 were 75.0%, 33.3%, and 8.3% in the 100 mg cohort; 66.7%, 20.0%, and 13.3% in the 200 mg cohort; and 60.0%, 30.0%, and 20.0% in the 400 mg cohort, respectively. CONCLUSIONS: E6011 appeared to be safe and well tolerated in RA patients during this 12-week treatment period, suggesting that E6011 has an effective clinical response in active RA patients.
OBJECTIVE:Fractalkine (CX3CL1/FKN) is a chemokine that regulates chemotaxis and adhesion of CX3C chemokine receptor 1 (CX3CR1)-expressing inflammatory cells. We conducted the first phase 1/2, open-label, multiple ascending dose study of E6011, a humanized anti-FKN monoclonal antibody, in Japanese rheumatoid arthritis (RA) patients (clinicaltrial.gov identifier: NCT02196558). METHODS: Active RApatients with an inadequate response or intolerance to methotrexate or tumor necrosis factor (TNF) inhibitor received E6011 at week 0, 1, 2, and thereafter every 2 weeks for 12 weeks. RESULTS: Twelve, 15, and 10 subjects were enrolled in the 100, 200, and 400 mg cohorts, respectively. No severe adverse events (AEs) or deaths occurred, and no major differences were observed in the incidence or severity of AEs across the cohorts. Serum E6011 concentrations increased dose dependently. American College of Rheumatology (ACR) 20, 50, and 70 responses at week 12 were 75.0%, 33.3%, and 8.3% in the 100 mg cohort; 66.7%, 20.0%, and 13.3% in the 200 mg cohort; and 60.0%, 30.0%, and 20.0% in the 400 mg cohort, respectively. CONCLUSIONS:E6011 appeared to be safe and well tolerated in RApatients during this 12-week treatment period, suggesting that E6011 has an effective clinical response in active RApatients.