Study of Safety and Efficacy of BCD-020 Comparing to MabThera in Patients With Rheumatoid Arthritis (BIORA)
Rheumatoid Arthritis
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, DMARDs, rituximab, biosimilar, interchangeability
Eligibility Criteria
Inclusion Criteria:
- Having signed a written informed consent form.
- Patients must be from 18 to 80 years of age (both ages inclusive)
- Rheumatoid arthritis confirmed according to ACR 1987 criteria.
- Seropositive rheumatoid arthritis.
- Active rheumatoid arthritis during the last 3 months.
- 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.
- Patient's functional status - class I-III according to ACR classification
- Inadequate response to DMARDs that include one or more TNF inhibitors, intolerance or contraindications to TNF inhibitors.
- Necessity of methotrexate treatment during the last 4 weeks prior to screening period with stable/consistent dosage of 7.5 - 20 mg per week.
- Patient's ability (in Investigator's opinion) to follow the protocol procedures;
- Willingness to use contraception during all study period.
Exclusion Criteria:
- Patients with Felty's syndrome (irrespectively to clinical form).
- Patient's functional status - class IV according to ACR classification .
- Rheumatoid arthritis low activity (less than 3.2 according to DAS28).
Concomitant therapy:
- 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 study's principal phase (treatment with rituximab).
- Intra-articular glucocorticosteroids within 4 weeks before the study'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 ≤10 mg per day in cases when this dose wasn't stable/consistent during last 4 weeks.
- 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.
- Pregnancy and breast-feeding.
Changes of laboratory values:
- Hemoglobin level is less than 100 g/l;
- Leucocyte level is less than 3,0×10e9/l;
- Absolute neutrophil count is less than 1,5×10e9/l;
- Thrombocyte level is less than 100×10e9/l.
- Confirmed chicken pox within 30 days before inclusion to the screening.
- Confirmed herpes zoster infection.
- Acute forms of any infectious diseases, history of chronic infections with severe clinical manifestations.
- Active tuberculosis, history of latent tuberculosis.
- 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).
- Juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis developed before the age of 16.
- Any determined immunodeficiency.
- Pernicious anemia.
- Confirmed cobalamine deficiency.
- 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;
- 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.
- Major surgery within 28 days prior to the trial principal phase (treatment with rituximab).
- 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.
- Unstable angina pectoris.
- Myocardial infarction within less than 1 year prior to participation in the study.
- Severe central or peripheral nervous system diseases.
- Drug addiction, alcoholism.
- 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.
- Presence of malignant neoplasm, with the exception of adequately treated basal cell carcinoma and cervical carcinoma in situ and any malignancy with complete remission of more than 5 years;
- 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.
Sites / Locations
- Gomel Regional Clinical Hospital
- City Clinical Hospital №1
- City Clinical Hospital №9
- Vitebsk Regional Clinical Hospital
- Satellite Orthopaedic Hospital & Research Centre Pvt Ltd
- Smt NHL Medical College and SethVS General Hospital
- Government Medical College and Hospital Panchakki Road
- Bangalore Medical College and Research Institute, Victoria Hospital
- Pristine Hospital and Research Center Pvt. Ltd
- Sapthagiri Institute of Medical Sciences and Research Centre#15
- Sri Venkateshwara Hospital
- Sri Ramachandra Medical Centre, No.1
- Swami Vivekananda National Institrute of Rehabilitation Training and research
- Gandhi Hospital, Department of Orthopedics
- Sri Sri Holistic Hospitals
- Sumana Hospitals, Research Department
- Yashoda Hospital
- Jaipur Hospital, Lal Kothi, Near SMS Stadium
- SMS Medical College & Hospital
- Calcutta national medical college, Kolkata
- Bhatia Hospital, Medical Research Society
- Government Medical College and Hospital
- Jawarlal Institute of Postgraduation Medical Education and Research
- B.J Medical college Sassoon General Hospital, Near Pune Railway Station
- Medipoint Hospitals Pvt Ltd
- Ruby Hall Clinic
- Christian Medical College
- Chelyabinsk Regional Clinical hospital
- Clinical Hospital at Chelyabinsk Railway Station
- Kursk regional hospital
- Research Institute of Rheumotology
- Nizhegorodskaya Regional Clinical Hospital named after N.A. Semashko
- Limited liability company Consultation and Diagnostic Center "Zdorovyye sustavy"
- Local hospital at the station Smolensk OAO RZD
- Smolensk State Medical Academy
- North-Western State Medical University n.a. I.I.Mechnikov
- Novgorod regional clinical hospital
- Kharkiv City Clinical Emergency Hospital n.a. O.I.Meschaninov
- National Research Center "Cardiology Institute n.a. M.D.Strazheska"
- Odessa Regional Cardiology Dispensary
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
MabThera (F. Hoffmann-La Roche Ltd.)
BCD-020 (CJSC BIOCAD)
Stage 1 (week 1 - week 24) MabThera will be administered at a dose of 1000 mg, IV (on day 1 and day 15). Stage 2 (week 24 - 48) If the disease activity remains on Week 24 the patient will undergo the second randomization (1:1 ratio): if he/she randomised into group A then he/she recieves BCD-020 at a dose f 1000 mg, IV, once in 2 weeks, 2 infusions per course (on day 1 and day 15); if he/she if he/she randomised into group B then he/she continues to recieve MabThera at a dose f 1000 mg, IV, once in 2 weeks, 2 infusions per course (on day 1 and day 15). MabThera/BCD-020 will be used in combination with methotrexate (irrespectively to study stage).
Stage 1 (week 1-week 24) BCD-020 will be administered at a dose of 1000 mg, IV (on day 1 and day 15). Stage 2 (week 24-48) If the disease activity remains on Week 24 the patient will undergo the second randomization (1:1 ratio): if he/she randomised into group A then he/she recieves MabThera at a dose f 1000 mg, IV, on day 1 and day 15; if he/she if he/she randomised into group B then he/she continues to recieve BCD-020 at a dose f 1000 mg, IV, on day 1 and day 15. MabThera/BCD-020 will be used in combination with methotrexate (irrespectively to study stage).