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

Randomized Double Blind Phase I Trial Comparing Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety of Rituximab (Mabscale LLC, Russia)+ Methotrexate+ Folic Acid and MabThera® Methotrexate+ Folic Acid in Adult Patients With Moderate or Severe Rheumatoid Arthritis With Insufficient Response to Treatment Tumor Necrosis Factor (TNF-α)

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.

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.