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)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 208
- 试验地点
- 12
- 主要终点
- AUC(w2-24)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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;
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Rituximab (Drug)
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.
干预措施: MabThera® (Drug)
结局指标
主要结局
AUC(w2-24)
时间窗: Day 1 to Week 24
Area Under the Concentration Time Curve predose Day 1 to Week 24 (AUC(w2-24).
AUC0-inf
时间窗: Day 1 to Week 24
Area Under the Concentration Time Curve extrapolated from 0 to infinity (AUC0-inf)
Cmax
时间窗: Dose 2 to the end of the study or Week 24
Maximum Plasma Concentration (Cmax) after Dose 2
次要结局
- 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)