International multicentre double blind randomized clinical study evaluating the efficacy and safety of BCD-020 (CJSC BIOCAD, Russia) and MabThera® (F. Hoffmann-La Roche Ltd., Switzerland) in patients with rheumatoid arthritis who had an inadequate response or intolerance to other DMARDs including one or more TNF inhibitor therapies
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 308
- 试验地点
- 18
- 主要终点
- •Percentage of patients in each group that have reached ACR20 within 24 weeks after the treatment initiation.
研究概览
简要总结
This study is multicentre double blind randomized clinical study evaluating the efficacy and safety of BCD-020 (CJSC BIOCAD, Russia) and MabThera® (F. Hoffmann-La Roche Ltd., Switzerland) in patients with rheumatoid arthritis who had an inadequate response or intolerance to other DMARDs including one or more TNF inhibitor therapies.
The main objective of the study is to compare the efficacy, safety, pharmacokinetics and pharmacodynamics of the drug BCD-020 (CJSC BIOCAD, Russia) and MabThera® (F. Hoffmann-La Roche Ltd., Switzerland) when using in combination with methotrexate in patients with rheumatoid arthritis and also to evaluate the diversity, frequency, severity and duration of adverse events in patients.
The study will be conducted at 18 sites of India and 60 patients after completing the screening period and obtaining the Investigator’s positive decision on participation in the study, each patient should be stratified according to age (younger than 40 years of age, 40 years of age or over), ACPA-positive or negative, necessity of taking oral glucocorticosteroids. After stratification, patients will be centrally randomized into one of the two study groups.This study is designed to be double blind, therefore neither the patient nor the study doctor should know which rituximab drug product the patient receives.
he drug Rituximab based on monoclonal antibodies a surface receptor of pre-B and mature B-lymphocytes, rituximab, which is a biological equivalent (Biosimilar) of MabThera® (F. Hoffmann-La Roche Ltd., Switzerland) a drug that is well known and widely used in rheumatology and oncology. Rituximab manufactured by CJSC BIOCAD (BCD-020) had undergone a series of comparative physical-chemical and preclinical studies (including animal studies) that showed a complete equivalence of the biological effects of BCD-020 and MabThera®.
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 80.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Having signed a written informed consent form.
- •2.Patients must be from 18 to 80 years of age (both ages inclusive) 3.Rheumatoid arthritis confirmed according to ACR 1987 criteria.
- •4.Seropositive rheumatoid arthritis .
- •5.Active rheumatoid arthritis during the last 3 months.
- •6.Disease score according to DAS28 of 3.2 or more, TJC≥8 (68), SJC≥8 (66), hsCRP≥6 mg/l, ESR≥28 mm/hr (by Westergren) at the moment of screening.
- •7.Patient’s functional status – class I-III according to ACR classification 8.Inadequate response to DMARDs that include one or more TNF inhibitors, intolerance or contraindications to TNF inhibitors.
- •9.Necessity of methotrexate treatment during the last 4 weeks prior to screening period with stable/consistent dosage of 7.5 – 20 mg per week.
- •10.Patient’s ability (in Investigator’s opinion) to follow the protocol procedures; 11.Male and female patients with normal reproductive function and their sexual partners are aware and willing to use voluntarily reliable methods of contraception during the whole period of the study including the screening period.
- •This requirement does not apply to patients who underwent operative sterilization or those defined as post-menopausal (documentally confirmed) within last 2 years.
- •Reliable methods of contraception suggest using 1 barrier method in combination with 1 of the following methods: spermicides, intra-uterine device etc.
排除标准
- •1.Patients with Felty’s syndrome complicated by severe skin vasculitis (ulcerative-necrotic form).
- •2.Patient’s functional status – class IV according to ACR classification .
- •3.Rheumatoid arthritis low activity (less than 3.2 according to DAS28).
- •4.Taking medications : •Previous treatment with any biological drug products causing CD20+ lymphocyte depletion, including biological investigational drugs.
- •â€¢Treatment with azathioprine within 28 days before the study initiation and with leflunomide within 8 weeks before the study’s principal phase (treatment with rituximab).
- •â€¢Intra-articular glucocorticosteroids within 4 weeks before the study’s principal phase (treatment with rituximab).
- •â€¢Necessity for prednisone or its equivalent administration at dose more than 10 mg per day.
- •â€¢Necessity for prednisone or its equivalent administration at dose ≤10 mg per day in cases when this dose wasn’t stable/consistent during last 4 weeks.
- •â€¢Necessity for administration of non-steroidal anti-inflammatory drugs for arthritis treatment in cases when its doses were not stable/consistent during last 4 weeks.
- •5.Pregnancy and breast-feeding.
- •6.Changes of laboratory values: Hemoglobin level is less than 100 g/l; Leucocyte level is less than 3,0×109/l; Absolute neutrophil count is less than 1,5×109/l; Thrombocyte level is less than 100×109/l.
- •8.Confirmed herpes zoster infection.
- •9.Acute forms of any infectious diseases, history of chronic infections with severe clinical manifestations.
- •10.Active tuberculosis, history of latent tuberculosis.
- •11.Inflammatory disease of the joints (present or in anamnesis) not related to rheumatoid arthritis (including gout, reactive arthritis, psoriatic arthritis, seronegative spondyloarthropathy, Lyme disease and others) or other systemic autoimmune disease (including systemic lupus erythematosus, Crohn’s disease, ulcerative colitis, systemic scleroderma, inflammatory myopathy, mixed forms of connective tissue inflammatory diseases, cross-syndrome and others).
- •12.Juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis developed before the age of
- •13.Any determined immunodeficiency.
- •14.Pernicious anemia.
- •16.Other somatic diseases (apart from rheumatoid arthritis) that can increase the probability of adverse events during the study or can influence the estimation of symptom manifestation of RA ; mask, enhance or alter the symptoms of RA or cause clinical or laboratory symptoms similar to that of RA; ï€Severe hypertonic disease resistant to treatment ; ï€Decompensated heart (CHF III, NYHA class IV), liver or kidney diseases (creatinine level >133 µM/l, AST, ALT and bilirubin levels 3 and more times higher than normal), except for the cases when the symptom is caused by rheumatoid arthritis; ï€Decompensated forms of respiratory insufficiency; ï€Severe diabetes mellitus resistant to treatment; 17.Positive results of serological test of Hepatitis B surface antigen (HbsAg) or presence of Hbc IgM together with positive results of HBV PCR test, presence of antibodies to Hepatitis C virus, syphilis or HIV.
- •19.Any mental disorder, including major depression and/or suicidal thoughts in anamnesis that can, in Investigator’s opinion, create a risk for the patient or influence the patient’s ability to follow the study protocol.
- •20.Unstable angina pectoris.
- •21.Myocardial infarction within less than 1 year prior to participation in the study.
- •22.Severe central or peripheral nervous system diseases.
- •23.Drug addiction, alcoholism.
- •24.Known hypersensitivity to murine proteins or any other components of the medications used in the treatment, methotrexate, folic acid and any drugs used in premedication.
- •25.Presence of malignant neoplasm, with the exception of: Adequately treated basal cell carcinoma and cervical carcinoma in situ; Any malignancy with complete remission of more than 5 years; 26.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
•Percentage of patients in each group that have reached ACR20 within 24 weeks after the treatment initiation.
时间窗: Prior to first infusion, 3hr after the infusion initiation, immediately after infusion termination, 6 hr after the infusion initiation, 48 hr after Second infusion, prior to the second infusion,immediately after infusion termination, 6 hr after the infusion initiation, 48 hr after Second infusion,336 hrs after initiation of second infusion and 744 hrs after initiation of second infusion.
•Safety and efficacy evaluation.
时间窗: Prior to first infusion, 3hr after the infusion initiation, immediately after infusion termination, 6 hr after the infusion initiation, 48 hr after Second infusion, prior to the second infusion,immediately after infusion termination, 6 hr after the infusion initiation, 48 hr after Second infusion,336 hrs after initiation of second infusion and 744 hrs after initiation of second infusion.
次要结局
- 1. Assessment of Safety parameters after one dose of one of the investigational drugs during the study(• AEs and SAEs incidence)