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

NCT ID: NCT06175338

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 208 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-14
• Study Completion Date: 2025-04-30

Brief 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.

Detailed Description

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.

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: TRIPLE

Study Groups

Rituximab (manufactured by Mabscale, LLC)

Eligible subjects (104 patients) will receive Rituximab 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml) twice: on Visit 1 and 5. The following visits are the visits of safety and PK, PD and immunogenicity and also preliminary effectiveness). Patients will also receive background treatment Methotrexate+ Folic acid.

Group Type: EXPERIMENTAL

Rituximab

Intervention Type: DRUG

Rituximab 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)

MabThera®

Eligible subjects (104 patients) will receive MabThera® 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml) twice: on Visit 1 and 5. The following visits are the visits of safety and PK, PD and immunogenicity and also preliminary effectiveness). Patients will also receive background treatment Methotrexate+ Folic acid.

Group Type: ACTIVE_COMPARATOR

MabThera®

Intervention Type: DRUG

MabThera® 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)

Interventions

Rituximab

Rituximab 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)

Intervention Type: DRUG

MabThera®

MabThera® 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mabscale, LLC

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Immanuel Kant Baltic Federal University

Kaliningrad, , Russia

Scientific-Research Medical Complex Your Health

Kazan', , Russia

LLC "Medical Center Revma-Med"

Kemerovo, , Russia

LLC "Korolev Family Clinic №4"

Korolyov, , Russia

Moscow City Clinical Hospital №1

Moscow, , Russia

V.A. Nasonova Research Institute of Rheumatology

Moscow, , Russia

Orenburg State Medical University

Orenburg, , Russia

JSC "Northwestern Center for Evidence-Based Medicine"

Saint Petersburg, , Russia

LLC "Interleukin"

Saint Petersburg, , Russia

Medical center "Capital-Polis"

Saint Petersburg, , Russia

Saratov State Medical University

Saratov, , Russia

LLC "Biomed"

Vladimir, , Russia

Countries

Russia

Other Identifiers

RIT-1/01092021

Identifier Type: -

Identifier Source: org_study_id