Efficacy and Safety Study of Tacrobell to Treat Rheumatoid Arthritis

Study Overview
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Brief Summary
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The aims of this study are to assess the efficacy and safety of tacrolimus in patients with active rheumatoid arthritis(RA). EULAR(European League Against Rheumatism) response at week 24 compared to baseline will be evaluated to assess the efficacy of Tacrolimus.

Detailed Description
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A Phase IV, Open labeled, Multi-Center Trial to Assess the Efficacy and Safety of Tacrolimus(Tacrobell®)in patients with active rheumatoid arthritis(RA).

Official Title
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Phase IV STudy of Tacrobell in Active Rheumatoid Arthritis

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: Tacrolimus with Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged ≥20years Signed and dated informed consent document indicating that the patient Women of childbearing potential must have a negative serum or urine pregnancy test at the screening visit. Except in the case of surgically sterile or amenorrhea for one year. Female patients must agree to use adequate contraception measures during the period of therapy which should be continued for 4 weeks. have RA and meet all of the following criteria; RA occurring ≥ 3months and less than 15 years and diagnosed based on 1987 ACR classification criteria for rheumatoid arthritis; Active RA patients with MTX and among them who has insufficiency response to DMARDs as defined DAS28>3.2 in active RA patient. Insufficiency response is defined despite MTX therapy for > 12 weeks, RA activity≥ more than moderate and confirmable during 12 weeks, sequence of taking MTX >7.5mg/week for more than 6 weeks; ESR≥28mm/h or CRP≥1.0mg/dl; Tender Joint Counts must be more than 6 and Swollen Joint Counts must be more than 3 Exclusion Criteria: Inflammatory joint diseases, Systematic inflammatory disease Prosthesis and had an event of infected in it. Medical history of chronic infection, moderate infection or possibly to life threatening or signs and symptoms of serious infection. Patients have received treatment with a live vaccine from baseline within 8 weeks. HBsAg positive and hepatitis C virus positive patient. Patients have a history of malignancy. (But, carcinoma in situ of the uterine cervix or basal cell carcinoma have been treated is allowed within 5years) Patients have cardiovascular disease or associated disease which is not controlled. uncontrollable blood sugar(HbA1C ≥8%) or required insulin. Patients with a history of operation on index knee joint which could have influence on the result and need to have surgery as determined by investigator. At screening, patients have laboratory result as defined by ; white blood cell(WBC) < 3,500/mm3, Absolute Neutrophil Count(ANC) < 1,500/mm3, Hemoglobin < 8.5g/dl, Platelet count(PLT) < 100,000/mm3, Serum creatinine >1.5*upper limit of normal or 2mg/dl, Total bilirubin > 2*upper limit of normal, aspartate aminotransferase(AST) > 2*upper limit of normal, alanine aminotransferase(ALT) > 2*upper limit of normal, alkaline phosphatase(ALP) > 2*upper limit of normal Patients on any other clinical trial or experimental treatment in the past 8weeks An impossible one who participates in clinical trial by investigator's decision

Ages Eligible for Study
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Minimum Age: 20 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus with Methotrexate<br>Subjects have tacrolimus per oral once daily with methotrexate for 24weeks. Tacrolimus increased dosing regimen: 1mg for 0 4 weeks, 2mg for 4 weeks 8 weeks, 3mg for 8 weeks 24 weeks | Drug: Tacrolimus with Methotrexate<br>* Tacrolimus 1 mg for 0 week4, 2mg for week4 week8, 3mg for week8 week24 with MTX ≤20mg/week<br>* Other names: TacroBell® with MTX;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline European League Against Rheumatism(EULAR) response at 24weeks |  | baseline, 24weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Simplified Disease Activity Index(SDAI) at 24weeks |  | baseline, 24weeks | 
| Change from baseline Korean Health Assessment Questionnaire(KHAQ-20) at 24weeks |  | baseline, 24weeks | 
| Change from baseline Erythrocyte Sedimentation Rate(ESR) at 16weeks |  | baseline, 16weeks | 
| Change from baseline Erythrocyte Sedimentation Rate(ESR) at 24weeks |  | baseline, 24eeks | 
| Change from baseline C-Reactive Protein(CRP) at 16weeks |  | baseline, 16weeks | 
| Change from baseline C-Reactive Protein(CRP) at 24weeks |  | baseline, 24weeks | 
| Change from baseline European League Against Rheumatism(EULAR) response at 16weeks |  | baseline, 16weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA, rheumatoid arthritis, tacrolimus, Disease Activity Score 28, EULAR