Comparative Clinical Trial of Efficacy and Safety of BCD-055 and Remicade® in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis

Study Overview
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Brief Summary
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BCD-055-3 is international multi-center comparative double-blind randomized clinical trial of efficacy and safety of BCD-055 (JSC BIOCAD, Russia) and Remicade® in combination with methotrexate in patients with active rheumatoid arthritis.

Official Title
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International Multi-center Comparative Double-blind Randomized Clinical Trial of Efficacy and Safety of BCD-055 (JSC BIOCAD, Russia) and Remicade® in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Biological: BCD-055
* Biological: Remicade®
* Drug: Methotrexate
* Drug: Folic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Active rheumatoid arthritis according to criteria of American College of Rheumatologists (2010), that was diagnosed at least 6 months prior to screening. Active rheumatoid arthritis at screening despite of therapy with methotrexate for 3 last months. Use of methotrexate in stable dose for at least 4 weeks before screening (10-25 mg per week). History of ineffective treatment with basic antiinflammatory drugs (including methotrexate). Exclusion Criteria: Previous therapy of rheumatoid arthritis with monoclonal antibodies (including anti-tumor necrosis factor drugs) Felty's syndrome Functional status - class IV according to ACR classification (1991) Low activity of rheumatoid arthritis (DAS28-CRP(4) index less than 3.2) Patient needs corticosteroids in a dose more than 10 mg (recalculated to prednisolone) before signing informed consent. Patients needs equal of less than 10 mg prednisolone but the dose was not stable for last 4 weeks prior to infliximab treatment Prior use of disease-modifying antirheumatic drugs including methotrexate, sulfasalazin, chloroquine or hydroxychloroquine for up to 4 weeks before randomization. Prior use of alkylating agents for up to 12 months prior to signing informed consent. Intraarticular use of corticosteroids for up to 4 weeks before randomization. Prior use of live or attenuated vaccines for up to 8 weeks before signing informed consent. Diagnosis of tuberculosis. Body mass more than 130 kg.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-055<br>Patients in this group will receive BCD-055 in a dose of 3 mg/kg on Week 0, Week 2, Week 6, Week 14, Week 22, Week 30, Week 38, Week 46, Week 54. | Biological: BCD-055<br>* BCD-055 is infliximab biosimilar<br>* Other names: infliximab;Drug: Methotrexate<br>* All patients will receive methotrexate in a dose from 10 to 25 mg per week.<br>Drug: Folic acid<br>* All patients will receive folic acid in a dose of 5 mg per week.<br>|
| Active Comparator: Remicade®<br>Patients in this group will receive Remicade® in a dose of 3 mg/kg on Week 0, Week 2, Week 6, Week 14, Week 22, Week 30, Week 38, Week 46, Week 54. | Biological: Remicade®<br> <br> * Other names: infliximab;Drug: Methotrexate<br>* All patients will receive methotrexate in a dose from 10 to 25 mg per week.<br>Drug: Folic acid<br>* All patients will receive folic acid in a dose of 5 mg per week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of patients with ACR20 response after 14 weeks of therapy | Ratio of patients who developed a decrease in American College of Rheumatologists (ACR) score by 20% or more after 14 weeks of therapy with study drug | Week 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratio of patients with ACR20 response after 30 and 54 weeks of therapy | Ratio of patients who developed a decrease in American College of Rheumatologists (ACR) score by 20% or more after 30 and 54 weeks of therapy with study drug | Week 30, Week 54 | 
| Ratio of patients with ACR50 and 70 response after 14, 30 and 54 weeks of therapy | Ratio of patients who developed a decrease in American College of Rheumatologists (ACR) score by 50% or more and by 70% or more after 14, 30 and 54 weeks of therapy with study drug | Week 14, Week 30, Week 54 | 
| Ratio of patients with low activity of rheumatoid arthritis according to index DAS28-CRP(4) after 14, 30 and 54 weeks of therapy | Ratio of patients with low activity of rheumatoid arthritis according to index Disease Activity Score 28 - C-reactive protein (DAS28-CRP(4), score 2.6-3.2) after 14, 30 and 54 weeks of therapy. | Week 14, Week 30, Week 54 | 
| Ratio of patients with low activity of rheumatoid arthritis according to index CDAI after 14, 30 and 54 weeks of therapy | Ratio of patients with low activity of rheumatoid arthritis according to Clinical Disease Activity Index (CDAI, score 2.9-10.0) after 14, 30 and 54 weeks of therapy. | Week 14, Week 30, Week 54 | 
| Ratio of patients with low activity of rheumatoid arthritis according to index SDAI after 14, 30 and 54 weeks of therapy | Ratio of patients with low activity of rheumatoid arthritis according to Simplified Disease Activity Index (SDAI, score 3.4-11.0) after 14, 30 and 54 weeks of therapy. | Week 14, Week 30, Week 54 | 
| Ratio of patients with remission of rheumatoid arthritis according to index DAS28 after 14, 30 and 54 weeks of therapy | Ratio of patients with remission of rheumatoid arthritis according to index Disease Activity Score 28 (DAS28, score less than 2.6) after 14, 30 and 54 weeks of therapy. | Week 14, Week 30, Week 54 | 
| Ratio of patients with remission of rheumatoid arthritis according to index CDAI after 14, 30 and 54 weeks of therapy | Ratio of patients with remission of rheumatoid arthritis according to Clinical Disease Activity Index (CDAI, score 0.0-2.8) after 14, 30 and 54 weeks of therapy. | Week 14, Week 30, Week 54 | 
| Ratio of patients with remission of rheumatoid arthritis according to index SDAI after 14, 30 and 54 weeks of therapy | Ratio of patients with remission of rheumatoid arthritis according to Simplified Disease Activity Index (SDAI, score 0.0-3.3) after 14, 30 and 54 weeks of therapy. | Week 14, Week 30, Week 54 | 
| Ratio of patients with remission of rheumatoid arthritis according to ACR-EULAR criteria after 14, 30 and 54 weeks of therapy | Ratio of patients with low activity of rheumatoid arthritis according to American College of Rheumatologists (ACR)/ European league Against Rheumatism (EULAR) after 14, 30 and 54 weeks of therapy. | Week 14, Week 30, Week 54 | 
| Mean SF-36 score at screening and after 14, 30 and 54 weeks of therapy | Mean score of quality of life as assessed by Short Form-36 (SF-36) at screening and after 14, 30 and 54 weeks of therapy. | Screening, Week 14, Week 30, Week 54 | 
| CRP | Dynamics of blood level of C-reactive protein (CRP) | Screening, Week 14, Week 30, Week 54 | 
| ESR | Dynamics of Erythrocyte Sedimentation Rate | Screening, Week 14, Week 30, Week 54 | 
| Roentgenologic characteristics of abnormal joints after 54 weeks of therapy |  | Week 54 | 
| Frequency of AE/SAE |  | 54 weeks | 
| Frequency of AE 3-4 grade CTCAE |  | 54 weeks | 
| Frequency of early withdrawals due to AE/SAE |  | 54 weeks | 
| Percentage of patients who developed binding and neutralizing antibodies to infliximab |  | Screening, Week 14, Week 30, Week 54 |