Study of the Efficacy and Safety of BCD-089 in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis

Inclusion Criteria:

1. Signed informed consent form (ICF).
2. Men and women aged 18 years or older on the day of signing the ICF.
3. Verified rheumatoid arthritis according to the ACR 2010 criteria diagnosed at least 24weeks before signing the ICF .
4. Use of methotrexate for the last 12 weeks before signing the ICF.
5. Use of a stable dose of methotrexate for the last 4 weeks before signing the ICF (thedose of methotrexate should be 15 to 25 mg per week). Methotrexate can be used at adose of 10 mg in the case of intolerability/toxicity of higher doses.
6. Inefficacy of methotrexate used for the last 12 weeks before signing the ICF (in theopinion of the Investigator).
7. Active rheumatoid arthritis at randomization in the study.
8. The ability of the patient (in the Investigator's opinion) to follow the Protocolprocedures.
9. Patients and their sexual partners of childbearing potential agree to use reliablecontraceptive methods starting from signing the ICF, during the study and for 8 weeksfrom the last injection of the investigational product. This requirement does notapply to patients and their partners who underwent surgical sterilization and to womenwho are post-menopausal for at least 2 years. Reliable contraceptive methods includeone barrier method in combination with one of the following: spermicides, intrauterinedevice/oral contraceptives.

Exclusion Criteria:

1. Previous exposure to tocilizumab or other anti-IL6 or anti-IL-6R monoclonalantibodies.
2. Previous exposure to JAK inhibitors.
3. Previous exposure to rituximab or other B-cell depleting/suppressing agents.
4. Felty's syndrome (regardless of clinical form).
5. Patient's functional status: class IV according to the ACR 1991 classification.
6. Known allergy to or intolerance of any ingredients of BCD-089 or placebo.
7. Use of any of the following concomitant therapies:

• Oral prednisolone or its equivalent in a dose more than 10 mg/day;
• Need in oral prednisolone (or its equivalent) ≤ 10 mg if its dose was not stableduring the last 4 weeks before signing the ICF (patients who used topicalglucocorticoids are allowed to participate in the study);
• Need in NSAIDs if the dose was not stable during the last 4 weeks before signingthe ICF (patients who have occasionally used NSAIDs for fever or allergy syndromeassociated with an intercurrent disease can be included in the study);
• Use of alkylating agents any time within 12 months before signing the ICF.
• Intra-articular use of corticosteroids within 4 weeks before signing the ICF.
• Vaccination with live or attenuated vaccines any time within 8 weeks beforesigning the ICF.
• Use of leflunomide within 8 weeks before signing the ICF.
• Use of TNFα inhibitors or T-cell costimulation blockers within 8 weeks beforesigning the ICF.

8. Any of the following laboratory values at screening:

• Hemoglobin level < 80 g/L;
• Leukocyte count < 3.0 × 109/L;
• Platelet count < 100 × 109/L;
• Neutrophil count < 2 × 109/L;
• AST and ALT ≥ 1.5×ULN (based on the reference limits used by the laboratory);
• Serum creatinine ≥ 1.7 × ULN (based on the reference limits used by thelaboratory).

9. Positive pregnancy urine test in female subjects at screening (no test is required inwomen who are post-menopausal for at least 2 years and in surgically sterile women).
10. Current diagnosis or a history of a severe immunodeficiency of any other origin.
11. Diagnosed HIV, hepatitis B, hepatitis C, or syphilis ;
12. Tuberculosis now or in the past.
13. Latent TB forms (positive Diaskintest®, QuantiFERON®-TB Gold or T-SPOT.TB test with noradiographic signs of pulmonary TB).
14. Herpes zoster infection now or in the past .
15. Documented chickenpox within 30 days before signing the ICF.
16. Definite diagnosis of any other chronic infection (e.g. sepsis, invasive mycoses,histoplasmosis, etc.) that, in the Investigator's opinion, can increase the risk ofinfectious complications.
17. Any acute infection or aggravation of a chronic infection within 30 days beforesigning the ICF if this condition may, in the Investigator's opinion, increase therisk of infectious complications.
18. Severe infections (including those that required hospitalization or parenteralantibacterial/antimycotic/antiprotozoal treatment) within 6 months before signing theICF.
19. Systemic antibacterial/antimycotic/antiprotozoal treatments used within 8 weeks beforethe signing the ICF.
20. More than 4 episodes of respiratory infections within 6 months before signing the ICF.
21. A major surgery within 30 days before signing the ICF or a major surgery scheduled atany time during the study.
22. History of epileptic attacks or seizures.
23. History of severe depression, suicidal thoughts or suicide attempts .
24. Diverticulosis and/or diverticulitis .
25. Alcohol, drug or psychoactive substance dependence or medication abuse now or in thepast, signs of alcohol/drug dependence.
26. Other documented medical conditions that can increase a risk of adverse events duringthe study treatment, affect the assessment of the main disease severity, mask,aggravate, affect symptoms of the main disease, or result in the same clinical andlaboratory instrumental symptoms as those of rheumatoid arthritis:

• Diabetes mellitus with inadequate glycemic control ;
• Severe treatment-resistant hypertension ;
• Current or a history of inflammatory joint diseases other than rheumatoidarthritis (including ankylosing spondylitis, gout, psoriatic arthritis, Lymedisease etc. ) or other systemic autoimmune diseases (including systemic lupuserythematosus, Crohn's disease, non-specific ulcerative colitis, systemicscleroderma, inflammatory myopathy, mixed connective tissue disease, overlapsyndrome, fibromyalgia etc.);
• Malignant neoplasms except for cured basal-cell carcinoma and cancer of thecervix in situ (complete remission ≥ 5 years); cured basal-cell carcinoma of theskin (complete remission ≥ 5 years); cured ductal breast cancer (completeremission ≥ 5 years);
• Decompensated liver or kidney diseases;
• Unstable angina;
• Chronic heart failure of NYHA class III-IV;
• Myocardial infarction within 1 year before signing the ICF;
• History of organ transplantation;
• History of angioedema;
• Respiratory system disorders with decompensated respiratory insufficiency;
• Definite diagnosis of multiple sclerosis, Devic's disease, or Guillain-Barresyndrome;
• Nervous system disorders with motor and/or sensitivity abnormalities.

27. Pregnancy , planned pregnancy less than 8 weeks after the last injection of theinvestigational product; lactation.
28. Current participation in other clinical studies; previous participation in otherclinical studies within 3 calendar months before signing the ICF (except forscreenouts); previous participation in this study (except for screenouts).