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

NCT06175338 | Active Not Recruiting Phase 1

• 1 other identifier: RIT-1/01092021
• Study Type: interventional
• Target: 208
• Locations: 1 country
• Sites: 12

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.

Conditions

Rheumatoid Arthritis

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• Ctrough

  Day 1 to Day 15

• AUC0-d15

  Day 1 - Day 15 (before infusion)

• AUC0-w12

  Day 1 - Week 12 (before infusion)

• AUCd15-n24

  Day 15 - Week 24

Study Arms (2)

Rituximab (manufactured by Mabscale, LLC)

EXPERIMENTAL

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

MabThera®

ACTIVE COMPARATOR

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®

Interventions

Rituximab DRUG

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

Rituximab (manufactured by Mabscale, LLC)

MabThera® DRUG

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

MabThera®

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mabscale, LLC: lead

Study Sites (12)

Immanuel Kant Baltic Federal University

Kaliningrad, Russia

Location

Scientific-Research Medical Complex Your Health

Kazan', Russia

Location

LLC "Medical Center Revma-Med"

Kemerovo, Russia

Location

LLC "Korolev Family Clinic №4"

Korolyov, Russia

Location

Moscow City Clinical Hospital №1

Moscow, Russia

Location

V.A. Nasonova Research Institute of Rheumatology

Moscow, Russia

Location

Orenburg State Medical University

Orenburg, Russia

Location

JSC "Northwestern Center for Evidence-Based Medicine"

Saint Petersburg, Russia

Location

LLC "Interleukin"

Saint Petersburg, Russia

Location

Medical center "Capital-Polis"

Saint Petersburg, Russia

Location

Saratov State Medical University

Saratov, Russia

Location

LLC "Biomed"

Vladimir, Russia

Location

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Arthritis; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 7, 2023
• First Posted: December 18, 2023
• Study Start: June 14, 2023
• Primary Completion: November 1, 2024
• Study Completion: April 1, 2025
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

RU (12)