study, evaluating pharmacokinetics, pharmacodynamics, immunogenicity and safety profiles of rituximab compared to mabthera® in patients with rheumatoid arthritis

Conditions: Rheumatoid Arthritis

Summary: a randomised, double blind, parallel group, multicentre study to compare the pharmacokinetics, pharmacodynamics, immunogenicity and safety of rituximab (mabscale llc, russia) versus mabthera® in patients with rheumatoid arthritis.

rit-1/01092021 is a double-blind randomized, parallel group, multicenter clinical trial comparing pharmacokinetics, pharmacodynamics, immunogenicity and safety of rituximab (mabscale llc, russia) and mabthera® in adult patients with moderate or severe rheumatoid arthritis with insufficient response to treatment tumor necrosis factor (tnf-α) inhibitors receiving background treatment with methotrexate. the purpose of the study is to demonstrate equivalence of pharmacokinetics, pharmacodynamics, immunogenicity and safety of rituximab (mabscale llc, russia) and mabthera®. the study will take place across approximately 30 study sites in russia in order to randomize 208 patients. rituximab is a monoclonal antibody currently being developed by mabscale llc, as a proposed biosimilar to mabthera®, which is approved as treatment in case of insufficient response or toxicity to treatment tumor necrosis factor (tnf-α) inhibitors receiving background treatment with methotrexate. this randomized equivalence study is designed to meet the regulatory requirement for approval of a biosimilar product.

Eligibility criteria:
inclusion criteria: * male and female 18-65 y.o. with body weight 50-120 kg * patients with active rheumatoid arthritis with disease duration minimum 6 months prior to screening visit per acr/eular 2019 criteria classification. * moderate or severe active course of rheumatoid arthritis, which is defined as the fulfillment of all of the following conditions: * ≥6 tender joints (based on a score of 68 joints) at screening and baseline; and * ≥6 swollen joints (based on a score of 66 joints) at screening and at baseline; and * level of c-reactive protein is not less than 10 mg/l or esr is not less than 28 mm/hour at screening. * positive result of the analysis for antibodies to cyclic citrullinated peptide (≥10 units/ml) and / or the presence of rheumatoid factor (≥ 20 units/ml) at screening (see section). * received treatment for ra and experienced an inadequate response or intolerance to treatment with at least 1 anti-tnf alpha therapy; * must have received mtx for a minimum of 12 weeks, with the last 4 weeks, prior to screening at a stable dose 10-25 mg/week; exclusion criteria: * contraindications according to the mabthera smpc and every serious coexisting diseases which, in the investigator's opinion, would preclude subject participation * history of current rheumatic autoimmune disease other than ra and current inflammatory joint disease other than ra * positive tests for hiv, hepatitis b surface antigen (hbsag) anti-hbc antibody, hepatitis c antibody * prior treatment with rituximab, other anti-cd20 mab * pregnancy or lactation or women planning to get pregnant during the course of the study and/or within 12 months post last study drug infusion * covid prior 8 weeks prior to screening visit or other acute systemic infection within 4 weeks prior to day 1 * allergic reaction or intolerance to rituximab, mabioncd20 or any of their components * severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies or previous treatment of any lymphocyte-depleting therapies * confirmed current active tuberculosis (tb). * any significant cardiac disease * history of a severe allergic reaction or anaphylactic reaction to a biological agent or history of hypersensitivity to any component of the study drug including known hypersensitivity or allergy to a murine product.