International comparative multicenter double-blind randomized clinical study of efficacy and safety of BCD-055 (CJSC BIOCAD, Russia) and Remicade® in combination with methotrexate in patients with active rheumatoid arthritis
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 426
- 试验地点
- 16
- 主要终点
- Proportion of patients with rheumatoid arthritis in each group who achieve improvement in disease according to ACR20 at Week 14 from the time of the first infliximab infusion.
研究概览
简要总结
It is an International comparative multicenter double-blind randomized clinical study of efficacy and safety of BCD-055 (CJSC BIOCAD, Russia) and Remicade® in combination with methotrexate in patients with active rheumatoid arthritis, Phase III study. Patients of both genders aged 18 to 75 years inclusive, with diagnosis of active1 rheumatoid arthritis established at least 6 months prior to screening. the main objective is to establish the equivalence of efficacy and equal safety of BCD-055 and Remicade® when used in patients with active rheumatoid arthritis, Determine the proportion of patients in each group who reached 20%, 50% and 70% improvement in activity parameters of rheumatoid arthritis according to ACR criteria in 14, 30 and 54 weeks after start of therapy, Determine the proportion of patients in each group who reached remission and low disease activity according to DAS28-CRP (4), SDAI, CDAI criteria in 14, 30 and 54 weeks after start of therapy, Determine the proportion of patients in each group with persistent medium and high disease activity according to DAS28-CRP (4), SDAI, CDAI criteria in 14, 30 and 54 weeks after start of therapy, Determine the proportion of patients in each group with the appearance of binding antibodies to infliximab, as well as the number of cases of the appearance of neutralizing antibodies to infliximab. Identify the presence/absence of correlation between the development of immune response and drug efficacy, Determine the range, frequency and severity of adverse events in repeated administration of BCD-055 or Remicade® to patients with active rheumatoid arthritis.comparative evaluation of safety in patients with active rheumatoid arthritis. The statistical sample calculation showed that in order to prove the hypothesis of equivalence at α level of 0.05 and power of 80%, the study should include 140 patients (93 patients – into the main group, 47 patients – into the reference group).
After signing the informed consent to participate in the study and completion of all screening procedures, eligible patients will be stratified according to country of residence (CIS countries other countries), age (younger than 40 years, 40 years and older), degree of disease activity at the time of screening (moderate activity of the disease – 3.2 5.1) and applied methotrexate dose (less than 20 mg/25 mg and more), and then randomly assigned (randomized) into one of two groups in the ratio of 2:1.
All patients will additionally receive methotrexate in a stable dose of 15 to 25 mg per week orally or parenterally, as well as folic acid in a dose of 5 mg per week. The study will involve 10 visits, including 9 visits for study drug/comparator infusion.The participation of one patient in the study involves treatment and observation in the period from the beginning of screening to Visit at Week 58 (i.e., maximum 62 weeks).
研究设计
- 研究类型
- Interventional
- 分配方式
- Computer generated randomization
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 18.00 Year(s) 至 75.00 Year(s)（—）
- 性别
- All
入选标准
- •Signed informed consent to participate in the study;
- •Men and women aged 18-75 years inclusive;
- •Confirmed diagnosis of rheumatoid arthritis according to ACR criteria 2010 set at least 6 months prior to screening;
- •Active rheumatoid arthritis at the time of screening despite methotrexate therapy which lasted for the past 3 months;
- •The use of methotrexate in a stable dose for the past 4 weeks prior to the screening period (15-25 mg range per week);
- •Ineffectiveness of previous therapy by disease-modifying antirheumatic drugs (including methotrexate);
- •Consent of a patient with preserved childbearing potential during the period of study to use reliable methods of contraception40 from the date of IC signature and up to 8 weeks after the last dose of study drug/comparator;
- •Adequate kidney and liver function determined at screening under the following parameters: a.
- •ALT level ≤ ULN adopted in the center laboratory; c.
- •AST level ≤ ULN adopted in the center laboratory.
- •Absence of clinically significant abnormalities in complete blood count conducted at screening, determined as: a.
- •Hemoglobin level ≥120 g/l for males and ≥100 g/l for females; b.
- •White blood cell count ≥3.5 × 109/l; c.
- •Absolute neutrophil count ≥1.5 × 109/l; d.
- •Platelet count ≥100 × 109 platelets/l.
- •Ability of the patient to follow the protocol procedures, according to the investigator.
排除标准
- •Prior use of any products based on monoclonal antibodies (including tumor necrosis factor alpha inhibitors) for the treatment of rheumatoid arthritis;
- •Felty’s syndrome (irrespectively to clinical form);
- •Functional status of the patient.
- •Class IV according to ACR 1991 classification;
- •Low activity of rheumatoid arthritis (according to DAS28-CRP(4) index of less than 3.2 points);
- •The use of the following medicinal products as concomitan therapy The need for administration of prednisolone or its equivalent in a dose of more than 10 mg orally daily; a. The need for oral administration of prednisone or its equivalent in a dose of ≤10 mg daily, if the dose was not stable for the last 4 weeks before infliximab therapy (it is permitted to include the patients receiving topical glucocorticosteroids); b. The use of other disease-modifying antirheumatic drugs besides methotrexate, including hydroxychloroquine, chloroquine, sulfasalazine within 4 weeks prior to screening. If a patient took leflunomide, his screening period should be extended to 12 weeks during which leflunomide administration is prohibited (washout period); c. Acceptance of alkylating agents at any time during 12 months before screening; d. Intra-articular administration of corticosteroids for less than 4 weeks prior to randomization; e. Vaccination with live or attenuated vaccines at any time during the 8 weeks prior to screening.
- •Determined hypersensitivity to murine proteins or any components of the study drugs, methotrexate, folic acid, as well as the drugs being a part of premedication;
- •Hepatitis B, active hepatitis C, HIV, syphilis;
- •Determined diagnosis of tuberculosis;
- •Latent tuberculosis (positive Diaskintest®/PPD test with 5TU/QuantiFERON®-TB Gold test in the absence of pulmonary tuberculosis in the chest radiography). It is permitted to include the patients with suspicious Diaskintest®/PPD test with 5TU/QuantiFERON®-TB Gold test result after consulting with a phthisiatrician who confirmed that latent tuberculosis is absent in this patient;
- •The established diagnosis of other acute or severe chronic infection (sepsis, abscesses, invasive mycoses, histoplasmosis) at screening or in history;
- •Patients with the diagnosed bacterial infection that required oral administration of antibacterial drugs during the two weeks preceding the time of signing the informed consent; patients with the diagnosed bacterial infection that required parenteral administration of antibacterial drugs during four weeks prior to screening;
- •Patients with the established diagnosis of herpes zoster;
- •Drug abuse, alcoholism (including history);
- •Other documented diseases that increase the risk of adverse events in a patient during the study treatment or that mayaffect the assessment of symptoms of the underlying disease; mask, increase, modify the symptoms of the underlying disease or cause clinical, laboratory and instrumental symptoms similar to those of rheumatoid arthritis
- •Body mass of more than 130 kg;
- •Pregnancy, pregnancy planning less than 8 weeks after the end of participation in the study, breastfeeding.
- •Simultaneous participation in any other clinical trial, as well as former participation in other clinical trials within 3 months before this study initiation; previous participation in this study.
结局指标
主要结局
Proportion of patients with rheumatoid arthritis in each group who achieve improvement in disease according to ACR20 at Week 14 from the time of the first infliximab infusion.
时间窗: Week 14 from the time of the first infliximab infusion according to ACR20 criteria
次要结局
- Efficacy evaluation;(Safety evaluation;)