Study of Tocilizumab in Combination With Methotrexate for Treatment of Moderate to Severe Rheumatoid Arthritis Patients

Study Overview
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Brief Summary
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This is a Phase III study to evaluate efficacy and safety of Tocilizumab in patients with Rheumatoid Arthritis.

Official Title
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Randomized, Placebo-controlled Study of Tocilizumab in Combination With Methotrexate for Treatment of Moderate to Severe Rheumatoid Arthritis Patients

Conditions
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Rheumatoid Arthritis (RA)

Intervention / Treatment
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* Drug: Tocilizumab + methotrexate(MTX)
* Drug: Tocilizumab placebo + methotrexate(MTX)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients diagnosed with history of moderate-to- severe rheumatoid arthritis for more than 6 months according to the American College of Rheumatology (ACR) 1987 revised criteria for the classification of RA. Patients who failed to achieve clinical response to treatment of at least 2 DMARDs(disease modifying anti-rheumatic drug) (including MTX) for at least 12 weeks within 12 months prior to screening, of which MTX must have been at a stable dose of 10-20 mg/wk for at least 12 weeks prior to screening. All other DMARDs should be given at standard therapeutic dose. Patients who satisfy swollen joint count (SJC) ≥ 6 (66 joint count) and tender joint count (TJC) ≥ 8 (68 joint count) at screening and baseline. C-reactive protein (CRP) level ≥ 1 mg/dl or an erythrocyte sedimentation rate (ESR) ≥ 28 mm/hour at screening and at baseline. Exclusion Criteria: Patients who have received a major surgery including joint surgery 8 weeks prior to the screening or are scheduled to be operated within 6 months after the enrolment. Patients with rheumatoid autoimmune disease other than RA, including but not limited to SLE(system lupus erythematosus), or significant systemic involvement secondary to RA. Patients who belong to the Class IV of the ACR classification criteria for functional status of RA. (ACR Amended Criteria for the Classification of Functional Capacity in Rheumatoid Arthritis; Class IV: Largely or wholly incapacitated with patient bedridden or confined to wheel chair, permitting little or no self-care). Patients with a history of hypersensitivity to human, humanized or murine monoclonal antibodies or patients with contraindication for them. Patients who currently have or have a history of recurrence of bacterial, viral,fungal, or mycobacterial infections or other infectious diseases; tuberculosis(TB),atypical mycobacterial disease, clinically significant granulomatous disease on chest radiograph, hepatitis B, hepatitis C, or herpes zoster and etc. However, a patient with hand & foot fungal infections can participate.

Ages Eligible for Study
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Minimum Age: 20 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br> | Drug: Tocilizumab + methotrexate(MTX)<br>* Tocilizumab:8 mg/kg every4weeks,IV infusion methotrexate:10-20 mg/week<br>|
| Placebo Comparator: 2<br> | Drug: Tocilizumab placebo + methotrexate(MTX)<br>* Tocilizumab placebo:8 mg/kg every 4 weeks,IV infusion methotrexate:10-20 mg/week<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with an American College of Rheumatology 20(ACR20) response |  | at baseline and week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with ACR50 response |  | at baseline and week 24 | 
| Proportion of patients with ACR70 response |  | at baseline and week 24 | 
| Mean change from baseline of Swollen joint count(SJC) and Tender joint count(TJC) respectively |  | at baseline and week 24 | 
| Mean change from baseline in disease activity using 28-joint modified disease activity score (DAS28) |  | at baseline and week 24 | 
| Proportion of patients achieving DAS28 remission (DAS28 < 2.6) |  | at week 24 | 
| Adverse event incidence |  | from baseline to week 24 | 
| Mean change from baseline to evaluation visits in vital signs |  | from baseline to week 24 | 
| Result of Electrocardiogram. From baseline to evaluation visits |  | from baseline to week 24 | 
| Mean change from baseline visit to evaluation visits in quantitative hematological exam results (including Hb, Ht, RBC, WBC & differential, platelet counts). |  | from baseline to week 24 | 
| Mean change from baseline visit to evaluation visits in quantitative Biochemical exam of blood results (including AST, ALT, Alk-p, γ-GTP, LDH, total protein, albumin, total bilirubin, BUN, uric acid, creatinine, glucose, ferritin, K, Na, Cl, Ca, P.). |  | from baseline to week 24 | 
| Mean change from baseline visit to evaluation visits in quantitative serum lipid exam results. |  | from baseline to week 24 | 
| Mean change from baseline visit to evaluation visits in quantitative urinalysis results. |  | from baseline to week 24 |