Efficacy and Safety Study of Mizoribine in Active Rheumatoid (AMOLED)

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to access the efficacy and safety of Mizoribine 150mg qid and 50mg tid in active rheumatoid arthritis patients unsuccessfully treated with disease-modifying antirheumatic drug.

Detailed Description
-----------------
EULAR Response after 24weeks of treatment EULAR Response after 12weeks of treatment DAS28 value change KHAQ-20 value change

Official Title
-----------------
Open Label, Multicenter, Randomized Study to Assess the Efficacy and Safety of Mizoribine in Active Rheumatoid Arthritis Patients Unsuccessfully Treated With Disease-modifying Antirheumatic Drug

Conditions
-----------------
Rheumatoid Arthritis

Intervention / Treatment
-----------------
* Drug: Bredinin tablet 150mg
* Drug: Bredinin tablet 50mg


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female aged from 20 to 80 years old Signed and dated informed consent document indicating that the patient Patients must have a diagnosis of Rheumatoid Arthritis(RA) of at least 3months duration as defined by the 2010 American College of Rheumatology(ACR) Classification criteria. Patients should have a Disease Activity Score 28 greater than or equal to 3.2 (DAS28 ≥ 3.2) and have received treatment with more than 1 kind of disease-modifying antirheumatic drug(including MTX). ESR≥28mm/h or CRP≥1.0mg/dl at screening. Exclusion Criteria At screening, patients have laboratory result as defined by : white blood cell ≤ 3,000/mm3 , Hemoglobin < 8.5 g/dL, Platelet count < 100,000/mm3, Serum creatinine > 2.0 mg/dL, Aspartic Acid Transaminase/Alanine Transaminase ≥ 2*upper limit of normal , Uric acid ≥ 1.5*upper limit of normal Patient must not have bleeding disorder or taking anticoagulant. (But, lt is allowed to take 100mg/day of Asprin) 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. Patients have severe infection, including moderate respiratory disease and have received treatment with systemic antibiotics within 2 weeks. Patients have cardiovascular disease or associated disease which is not controlled. Patients have a history of malignancy within 5years. (But, basal cell or squamous cell carcinoma or carcinoma in situ of the uterine cervix have been treated is allowed) Patients have hypersensitivity reaction on this drug. Patients on any other clinical trial or experimental treatment in the past 3months. Female patients who are breast feeding, pregnant or plan to become pregnant during the trial or for two months following study termination. Not allowable medication recorded below ; Intra-articular injections within weeks at baseline visit, Patients taking oral steroid over 10mg /day or using new treatment or changing dosage within 4weeks at baseline visit, Using new nonsteroidal antiinflammatory drug within 4 weeks or changing nonsteroidal antiinflammatory drug dosage within 2 weeks at baseline visit. Having experience of use biologic agent, immunosuppressant, cytostatic preparations within 8weeks at baseline visit. (But, Rituximab is not allowed within 6months) Start to treatment new disease-modifying antirheumatic drug or need to change dosage of disease-modifying antirheumatic drug which is taking on the trial. (Leflunomide(ARAVA®) is not allowed within 12weeks, But, Cholestyramine is allowed after 48 hours later stopping. if it use three times a day, 8g, for 11days)

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bredinin tablet 150mg<br>dosage form: Tablet, dosage: 150mg qd, Duration: for 6months | Drug: Bredinin tablet 150mg<br>* Bredinin 150mg qd vs Bredinin 50mg tid<br>* Other names: Mizoribine;|
| Active Comparator: Bredinin tablet 50mg<br>dosage form: Tablet, dosage: 50mg tid, Duration: for 6months | Drug: Bredinin tablet 50mg<br>* Bredinin 150mg qd vs Bredinin 50mg tid<br>* Other names: Mizoribine;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all cause mortality |  | two years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
rheumatoid arthritis, RA, Mizoribine, DAS28, European League Against Rheumatism