Study, Evaluating Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety Profiles of Rituximab Compared to MabThera® in Patients With Rheumatoid Arthritis

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.