Study of Iguratimod Plus Methotrexate Compared to Leflunomid Plus Methotrexate in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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This study is intended to evaluate the efficacy and safety of Iguratimod Plus Methotrexate Compared to Leflunomid Plus Methotrexate in patients with active Rheumatoid Arthritis (RA).

Official Title
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A Randomized, Double-blind Study to Evaluate the Efficacy and Safety of Iguratimod or Leflunomide in Combination With Methotrexate in Patients With Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Iguratimod
* Drug: Leflunomide
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a diagnosis of RA according to the diagnostic criteria of the American College of Rheumatology (ACR) (revised in 1987) Rheumatoid Arthritis for more than 3 months from the time of the initial diagnosis Functional Class II-III Subjects have active RA at the time of screening Subjects with inadequate response to biologics should have a washout period before the initiation of study. For etanercept, washout period should be 2-week, and 8-week for infliximab and adalimumab. For firstly diagnostic RA patients, the disease activity should be moderate to severe, with DAS28>3.2 Must have at least 4 tender joints (66 join count) and 8 swollen joints( 68 join count) at screening and baseline Has a C-reactive protein ≥ 10 mg/L(or 1.0 mg/dL) OR Erythrocyte Sedimentation Rate (ESR) ≥ 28 mm/hr Must have a negative Pregnancy test and use adequate method of contraception throughout the trial Written informed consent Exclusion Criteria: Preceding treatment with DMARDs, immunosuppressants (cyclophosphamide, cyclosporine, azathioprine, etc.), or Tripterygium within 4 weeks prior to study entry Subjects have been treated with iguratimod or leflunomide combined with MTX before screening. Subjects combined with other autoimmune disease, such as systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), scleriasis and polymyositis, except for Sjögren syndrome. Chest x-ray abnormalities, such as tuberculosis, interstitial pulmonary fibrosis, etc. ALT >1.5×ULN, AST >1.5×ULN, Cr >135umol/L, total bilirubin>1.5×ULN WBC<4×109/L，HGB<85g/L，PLT<100×109/L Subjects with serious cardiovascular, renal, hematologic, endocrine diseases or malignant Women of Pregnant or breastfeeding, and male or female with recent plan to conception Subjects with immunodeficiency, uncontrolled infection and active gastrointestinal disease Allergic to any of the study drugs History of alcoholism Subjects with mental illness Subjects receiving live vaccines recently Subjects participating in other clinical study within 3 months prior to study entry

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Iguratimod and MTX combination<br>Drug:Iguratimod 25 mg/tablet, taken orally, 2 tablets/day (bid) Drug:MTX 2.5 mg/tablet, taken orally once a week, 4 tablets/week | Drug: Iguratimod<br>* Iguratimod 25 mg/tablet, taken orally, 2 tablets/day (bid),52 weeks<br>* Other names: Iremod;Drug: Methotrexate<br>* Methotrexate 2.5 mg/tablet, taken orally once a week, 4 tablets/week,52 weeks<br>|
| Active Comparator: Leflunomide and MTX combination<br>Drug: Leflunomide 10 mg/tablet, taken orally, 2 tablets/day (bid) Drug: Methotrexate 2.5 mg/tablet, taken orally once a week, 4 tablets/week | Drug: Leflunomide<br>* Leflunomide 10 mg/tablet, taken orally, 2 tablets/day (bid),52 weeks<br>Drug: Methotrexate<br>* Methotrexate 2.5 mg/tablet, taken orally once a week, 4 tablets/week,52 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with ACR 20 response and Change in Disease Activity as measured by the DAS28 |  | week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in modified Total Sharp Score (mTSS) |  | week 52 | 
| Percentage of patients with ACR 50 response and ACR70 response |  | week 24,week 52 | 
| Change from baseline in number of swollen and tender joins, Erythrocyte sedimentation rate (ESR) ,C-reactive protein (CRP),anti-citrullinated-protein antibody (ACPA) and heumatoid factor(RF) |  | week 24, week 52 | 
| Time to achieve the ACR20, ACR50 and ACR70 |  | week 12, week 24, week 40, week 52 | 
| Percentage of patients with Simplified Disease Activity Index (SDAI) ≤ 3.3 and change from baseline in Health Assessment Questionnaire (HAQ) |  | week 12, week 24, week 40, week 52 | 
| Incidence of adverse events |  | up to 52 weeks |