[Results of a phase 1 clinical study of anti-CD20 monoclonal antibody (BCD-132): pharmacokinetics, pharmacodynamics and safety]. / Rezul'taty I fazy klinicheskogo issledovaniia monoklonal'nogo antitela protiv CD20 (BCD-132): farmakokinetika, farmakodinamika i bezopasnost'.

ABSTRACT

AIM: To study the pharmacokinetics, pharmacodynamics, and immunogenicity of two intravenous dosing regimens of the new anti-B-cells drug BCD-132 (JSC BIOCAD, Russia) at ascending doses in patients with remitting multiple sclerosis. MATERIAL AND METHODS: Twenty-four patients with multiple sclerosis were sequentially randomized in the multicenter open-label uncontrolled multicohort phase I study (3+3 design) and assigned to 4 cohorts (8 groups). Patients in each cohort received an intravenous infusion of BCD-132 at a predefined dose ranging from 100 to 1000 mg based on the planned algorithm of dose escalation if no dose-limiting toxicities occurred. RESULTS: The assessment of the number of cells positive for the main B-cell antigens over time demonstrated a direct effect of BCD-132 on B lymphocytes when used at a wide range of doses (100 to 1000 mg) in patients with remitting multiple sclerosis. No significant variation of the number of T-cells was observed, which clearly proves strict specificity of BCD-132 exclusively to B lymphocytes. CONCLUSION: BCD-132 has an expected pharmacodynamic effect of long-term depletion of CD19+ and CD20+ B lymphocytes and an acceptable safety profile when used to treat patients with remitting multiple sclerosis at all tested doses.