Health Condition 1: null- Patients with rheumatoid arthritis who had an inadequate response or intolerance to other DMARDs including one or more TNF inhibitor therapies
Conditions
Interventions
Intervention1: BCD-020 â?? Rituximab (INN: rituximab), concentrate for solution for infusion: This study is designed to be double blind, therefore neither the patient nor the study doctor should know
Sponsors
BIOCAD INDIA PVT LTD
Eligibility
Inclusion criteria
Inclusion criteria: 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. Patientâ??s functional status â?? 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 â?? 20 mg per week. 10. Patientâ??s ability (in Investigatorâ??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
Exclusion criteria
Exclusion criteria: 1. Patients with Feltyâ??s syndrome complicated by severe skin vasculitis (ulcerative-necrotic form). 2. Patientâ??s functional status â?? 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. • Treatment with azathioprine within 28 days before the study initiation and with leflunomide within 8 weeks before the studyâ??s principal phase (treatment with rituximab). • Intra-articular glucocorticosteroids within 4 weeks before the studyâ??s principal phase (treatment with rituximab). • Necessity for prednisone or its equivalent administration at dose more than 10 mg per day. • Necessity for prednisone or its equivalent administration at dose • 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: ï?¼ Hemoglobin level is less than 100 g/l; ï?¼ Leucocyte level is less than 3,0Ã?109/l; ï?¼ Absolute neutrophil count is less than 1,5Ã?109/l; ï?¼ Thrombocyte level is less than 100Ã?109/l. 7. Confirmed chicken pox within 30 days before inclusion to the screening. 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, Crohnâ??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 16. 13. Any determined immunodeficiency. 14. Pernicious anemia. 15. Confirmed cobalamine deficiency. 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. <b
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| â?¢Percentage of patients in each group that have reached ACR20 within 24 weeks after the treatment initiation. â?¢Safety and efficacy evaluation. Timepoint: 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Assessment of Safety parameters after one dose of one of the investigational drugs during the study â?¢ AEs and SAEs incidence Secondary study endpoints for pharmacokinetics assessment 2. Secondary study endpoints for pharmacodynamic assessment: 3.Secondary study endpoints for efficacy assessmentTimepoint: As defined in protocol | — |
Countries
India
Contacts
Public ContactDr Mrutyunjaya Ganiger
BIOCAD INDIA PVT LTD,
Outcome results
None listed