Double-blind Multicenter Randomized Study of the Effectiveness and Safety of Tocilizumab Biosimilar (Complarate®) and Actemra® in Parallel Groups in Patients With Rheumatoid Arthritis With Repeated Intravenous Administration
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AO GENERIUM
- 入组人数
- 465
- 试验地点
- 55
- 主要终点
- Proportion of Participants with an American College of Rheumatology 20% (ACR20) response
研究概览
简要总结
This is a randomized double-blind comparative parallel group study of the efficacy and safety of tocilizumab biosimilar Complarate® and Actemra® in the treatment of patients with rheumatoid arthritis with moderate to high disease activity. Participants received an intravenous dose of tocilizumab 8 mg/kg once 4 weeks. The time on study treatment was 24 weeks.
详细描述
Complarate® (INN: tocilizumab) is being developed as a biosimilar to the drug Actemra®, a concentrate for the preparation of a solution for infusion.
Tocilizumab is a recombinant humanized monoclonal antibody to the human interleukin-6 (IL-6) receptor from the immunoglobulin G1 (IgG1) subclass of immunoglobulins. Tocilizumab binds to and inhibits both soluble and membrane IL-6 receptors.
This III phase study is aimed to compare the effectiveness, safety and immunogenicity of Complarate® and Actemra®. The study included patients aged 18-75 years at the time of signing the informed consent form with a documented diagnosis of rheumatoid artritis, established according to the 2010 ACR/EULAR classification criteria, at least 6 months before screening, with moderate or high degree of disease activity and insufficient response to methotrexate monotherapy (preservation of moderate/high disease activity for at least 3 months) and/or poor tolerability of methotrexate (including the subcutaneous form of the drug) and/or insufficient response to or intolerance to other synthetic disease-modifying anti-inflammatory drugs (sDMARDs) with or without methotrexate inclusive, who meet all criteria for participation in the study. The study included a screening period and a treatment period. Allocation of patients to treatment groups was carried out by randomization in a ratio of 2:1 to the study drug (Complarate®) and comparator drug (Actemra®). 465 patients (310 to the study drug group and 155 to the comparator drug group) were randomized.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
盲法说明
Throughout the study neither the investigators nor the patients knew which drug was being administered until the end of the comparative treatment study period
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Availability of written informed consent obtained from the patient before the start of any procedures related to the study.
- •Men and women 18-75 years of age, inclusive, at the time of signing the informed consent form.
- •Patients with a documented diagnosis of rheumatoid artritis (RA), established according to the 2010 ACR/EULAR classification criteria at least 6 months before screening, with moderate to high disease activity and an insufficient response to methotrexate monotherapy (maintaining moderate/high disease activity for at least 3 months) and/or poor tolerability of methotrexate (including the subcutaneous form of the drug) and/or insufficient response to or intolerance to other synthetic disease-modifying anti-inflammatory drugs (sDMARDs) in combination with methotrexate or without methotrexate.
- •The number of swollen and/or painful joints is 6 or more.
- •No changes in the dosage regimen of standard RA therapy with oral glucocorticosteroids and NSAIDs for ≥ 4 weeks before screening.
- •No changes in the dosing regimen of standard RA sDMARD therapy for ≥ 4 weeks before screening.
- •Agreement to adhere to adequate methods of contraception throughout the study and for 3 months after the end of tocilizumab therapy.
排除标准
- •A history of rheumatic autoimmune disease other than rheumatoid arthritis.
- •Functional Class IV according to the ACR Functional Status Classification or wheelchair/bedridden.
- •Development of pronounced extra-articular (systemic) manifestations of the disease and complications (rheumatoid vasculitis, amyloidosis, Felty's syndrome, neuropathy, damage to the organ of vision).
- •Use of oral corticosteroids in doses greater than >10 mg daily prednisolone equivalent, or change in oral corticosteroid dose within 4 weeks before or during screening.
- •Use of injectable corticosteroids (including intra-articular corticosteroids) or intra-articular hyaluronic acid injections within 4 weeks before or during screening.
- •Therapy with tumor necrosis factor-alfa (TNF-alpha) inhibitors or any other genetically engineered biological drugs within 1 month before screening.
- •History of tocilizumab therapy.
- •Major surgery (including joint surgery) within 8 weeks before the start of the study or elective surgery within 6 months after the start of the study.
- •A history of an adverse drug reaction to any of the components of the study drug or a reference drug.
- •Immunization with any live or live attenuated vaccine within 1 month before the first dose of the study or comparator drug.
- •A history of a disease associated with the accumulation of immune complexes (including serum sickness).
- •Concomitant diseases and conditions that, in the opinion of the Investigator and/or Sponsor, jeopardize the safety of the patient during participation in the study, or which will influence the analysis of safety data.
- •Active systemic infection (bacterial, viral or fungal) within 14 days before signing the informed consent form or at the time of screening.
- •Blood donation or blood loss (450 ml of blood or more) less than 2 months before the start of the study.
- •Pregnancy or breastfeeding.
- •History of demyelinating disease of the central nervous system.
- •History of diverticulosis/intestinal diverticulitis or chronic ulcerative diseases of the lower gastrointestinal tract, such as Crohn's disease, ulcerative colitis.
- •History of tuberculosis.
- •Positive/doubtful test with tuberculosis allergen.
- •Participation in clinical trials of drugs less than 3 months before signing the informed consent form.
- •Positive tests for hepatitis B or C, HIV or syphilis.
- •Unwillingness or inability to comply with the recommendations prescribed by this protocol.
- •Identification during screening of other diseases/conditions not listed above that, in the opinion of the physician-researcher, prevent the inclusion of the patient in the study.
结局指标
主要结局
Proportion of Participants with an American College of Rheumatology 20% (ACR20) response
时间窗: week 24
The ACR 20 response: greater than or equal to (\>/=) 20 percent (%) improvement in TJC and SJC (28 assessed joints), and 20% improvement in 3 of the following 5 criteria, respectively: 1) PGDA, 2) PtGDA, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) CRP or ESR at week 24
次要结局
- Proportion of Participants with an American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response(week 24)
- Time to ACR20 response(week 24)
- Proportion of Participants who achieved remission in accordance with the ACR remission criteria(week 24)
- Change in Disease Activity Score Based on 28-Joints Count (DAS28)(week 24)
- Area under the curve (AUC) of the disease activity index (DAS28)(week 24)
- Proportion of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28(week 24)
- Change in Simplified Disease Activity Index (SDAI)(week 24)
- Change in Clinical Disease Activity Index (CDAI)(week 24)
- Proportion of Participants who dropped out of the study due to insufficient treatment effectiveness(week 24)