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.

Study Overview

• Status: Active, not recruiting
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Drug: Rituximab; Drug: MabThera®

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.

• Study Type: Interventional
• Enrollment (Actual): 208
• Phase: Phase 1

Contacts and Locations

Study Locations

• Russian Federation
  • Kaliningrad, Russian Federation
    • Immanuel Kant Baltic Federal University
  • Kazan, Russian Federation
    • Scientific-Research Medical Complex Your Health
  • Kemerovo, Russian Federation
    • LLC "Medical Center Revma-Med"
  • Korolev, Russian Federation
    • LLC "Korolev Family Clinic №4"
  • Moscow, Russian Federation
    • Moscow City Clinical Hospital №1
  • Moscow, Russian Federation
    • V.A. Nasonova Research Institute of Rheumatology
  • Orenburg, Russian Federation
    • Orenburg State Medical University
  • Saint-Petersburg, Russian Federation
    • JSC "Northwestern Center for Evidence-Based Medicine"
  • Saint-Petersburg, Russian Federation
    • LLC "Interleukin"
  • Saint-Petersburg, Russian Federation
    • Medical center "Capital-Polis"
  • Saratov, Russian Federation
    • Saratov State Medical University
  • Vladimir, Russian Federation
    • LLC "Biomed"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: Rituximab; Rituximab 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)
Active Comparator: 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.	Drug: MabThera®; MabThera® 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC(w2-24)	Area Under the Concentration Time Curve predose Day 1 to Week 24 (AUC(w2-24).	Day 1 to Week 24
AUC0-inf	Area Under the Concentration Time Curve extrapolated from 0 to infinity (AUC0-inf)	Day 1 to Week 24
Cmax	Maximum Plasma Concentration (Cmax) after Dose 2	Dose 2 to the end of the study or Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ctrough	Residual concentration (Ctrough) before the second infusion on Day 15	Day 1 to Day 15
AUC0-d15	Area under the concentration-time curve from 0 (directly pre-infusion on Day 1) before pre-infusion measurement on Day 15 (AUC0-d15)	Day 1 - Day 15 (before infusion)
AUC0-w12	Area under the concentration-time curve from 0 and before measurement at Week 12 (AUC0-w12)	Day 1 - Week 12 (before infusion)
AUCd15-n24	Area under the concentration-time curve from measurement immediately before the second infusion (Day 15) before measuring in point Week 24 (AUCd15-n24)	Day 15 - Week 24

Collaborators and Investigators

• Sponsor: Mabscale, LLC

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): April 1, 2025

Study Registration Dates

• First Submitted: December 7, 2023
• First Submitted That Met QC Criteria: December 14, 2023
• First Posted (Actual): December 18, 2023

Study Record Updates

• Last Update Posted (Actual): June 6, 2024
• Last Update Submitted That Met QC Criteria: June 5, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: RIT-1/01092021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No