Study, Evaluating Pharmacokinetics, Pharmacodynamics, Immunogenicity and Safety Profiles of Rituximab Compared to MabThera® in Patients With Rheumatoid Arthritis
- Conditions
- Rheumatoid Arthritis
- Interventions
- Registration Number
- NCT06175338
- Lead Sponsor
- Mabscale, LLC
- 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 208
-
Male and Female 18-65 y.o. with body weight 50-120 kg
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Patients with active rheumatoid arthritis with disease duration minimum 6 months prior to screening visit per ACR/EULAR 2019 criteria classification.
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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).
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Received treatment for RA and experienced an inadequate response or intolerance to treatment with at least 1 anti-TNF alpha therapy;
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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;
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description MabThera® 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. Rituximab (manufactured by Mabscale, LLC) Rituximab 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.
- Primary Outcome Measures
Name Time Method AUC(w2-24) Day 1 to Week 24 Area Under the Concentration Time Curve predose Day 1 to Week 24 (AUC(w2-24).
AUC0-inf Day 1 to Week 24 Area Under the Concentration Time Curve extrapolated from 0 to infinity (AUC0-inf)
Cmax Dose 2 to the end of the study or Week 24 Maximum Plasma Concentration (Cmax) after Dose 2
- Secondary Outcome Measures
Name Time Method Ctrough Day 1 to Day 15 Residual concentration (Ctrough) before the second infusion on Day 15
AUC0-d15 Day 1 - Day 15 (before infusion) Area under the concentration-time curve from 0 (directly pre-infusion on Day 1) before pre-infusion measurement on Day 15 (AUC0-d15)
AUC0-w12 Day 1 - Week 12 (before infusion) Area under the concentration-time curve from 0 and before measurement at Week 12 (AUC0-w12)
AUCd15-n24 Day 15 - Week 24 Area under the concentration-time curve from measurement immediately before the second infusion (Day 15) before measuring in point Week 24 (AUCd15-n24)
Trial Locations
- Locations (12)
LLC "Medical Center Revma-Med"
🇷🇺Kemerovo, Russian Federation
LLC "Korolev Family Clinic №4"
🇷🇺Korolev, Russian Federation
JSC "Northwestern Center for Evidence-Based Medicine"
🇷🇺Saint-Petersburg, Russian Federation
V.A. Nasonova Research Institute of Rheumatology
🇷🇺Moscow, Russian Federation
Scientific-Research Medical Complex Your Health
🇷🇺Kazan, Russian Federation
Moscow City Clinical Hospital №1
🇷🇺Moscow, Russian Federation
LLC "Interleukin"
🇷🇺Saint-Petersburg, Russian Federation
Saratov State Medical University
🇷🇺Saratov, Russian Federation
Immanuel Kant Baltic Federal University
🇷🇺Kaliningrad, Russian Federation
Orenburg State Medical University
🇷🇺Orenburg, Russian Federation
Medical center "Capital-Polis"
🇷🇺Saint-Petersburg, Russian Federation
LLC "Biomed"
🇷🇺Vladimir, Russian Federation