Rheumatoid Arthritis
Conditions
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.
Interventions
DRUGRituximab
Rituximab 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)
DRUGMabThera®
MabThera® 1000 mg in 150 ml 0,9 % NaCl (total volume of infusion 250 ml)
Sponsors
Mabscale, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Ctrough | Day 1 to Day 15 | Residual concentration (Ctrough) before the second infusion on Day 15 |
| 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) |
| 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) |
Countries
Russia
Outcome results
None listed