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

Rheumatoid Arthritis Clinical Trial

Official title:

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)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06175338
• Other study ID #: RIT-1/01092021
• Status: Recruiting
• Phase: Phase 1
• Start date: June 14, 2023
• Est. completion date: April 2025

Study information

• Verified date: February 2024
• Source: Mabscale, LLC
• Contact: Sofia Ermolenko, MD
• Phone: +74997149289
• Email: Ermolenko.s[@]benerix.ru
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 208
• Est. completion date: April 2025
• Est. primary completion date: November 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

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

Locations

Country	Name	City	State
Russian Federation	Immanuel Kant Baltic Federal University	Kaliningrad
Russian Federation	Scientific-Research Medical Complex Your Health	Kazan
Russian Federation	LLC "Medical Center Revma-Med"	Kemerovo
Russian Federation	LLC "Korolev Family Clinic ?4"	Korolev
Russian Federation	Moscow City Clinical Hospital ?1	Moscow
Russian Federation	V.A. Nasonova Research Institute of Rheumatology	Moscow
Russian Federation	Orenburg State Medical University	Orenburg
Russian Federation	JSC "Northwestern Center for Evidence-Based Medicine"	Saint-Petersburg
Russian Federation	LLC "Interleukin"	Saint-Petersburg
Russian Federation	Medical center "Capital-Polis"	Saint-Petersburg
Russian Federation	Saratov State Medical University	Saratov
Russian Federation	LLC "Biomed"	Vladimir

Sponsors (1)

Lead Sponsor	Collaborator
Mabscale, LLC

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	AUC(w2-24)	Area Under the Concentration Time Curve predose Day 1 to Week 24 (AUC(w2-24).	Day 1 to Week 24
Primary	AUC0-inf	Area Under the Concentration Time Curve extrapolated from 0 to infinity (AUC0-inf)	Day 1 to Week 24
Primary	Cmax	Maximum Plasma Concentration (Cmax) after Dose 2	Dose 2 to the end of the study or Week 24
Secondary	Ctrough	Residual concentration (Ctrough) before the second infusion on Day 15	Day 1 to Day 15
Secondary	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)
Secondary	AUC0-w12	Area under the concentration-time curve from 0 and before measurement at Week 12 (AUC0-w12)	Day 1 - Week 12 (before infusion)
Secondary	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