A Study is to Assess Efficacy and Safety of Tacrolimus in Active Rheumatoid Arthritis Patients Who Showed Unsuccessful Response to Existing Disease Modifying Antirheumatic Drugs (DMARDs)

Study Overview
=================
Brief Summary
-----------------
This study is to assess efficacy and safety of tacrolimus in active rheumatoid arthritis patients who showed unsuccessful response to existing DMARDs.

Official Title
-----------------
An Open- Label, Single-arm, Phase 4 Study to Assess the Efficacy and Safety of Tacrolimus in Active Rheumatoid Arthritis Patients Shown Unsuccessful Response Against DMARDs

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

Intervention / Treatment
-----------------
* Drug: Tacrolimus


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subjects who have rheumatoid arthritis for 6 months or longer based on American College of Rheumatology (ACR) diagnostic criteria Subjects who used more than 1 Disease Modifying Antirheumatic Drug (DMARD) including MTX (methotrexate) for 6 months or longer Subjects with ESR (erythrocyte sedimentation rate) ≥ 28mm/h or CRP (C-reactive protein)≥ 1.0 mg/dL Subjects with ≥ 3 swollen joints out of 66 joints assessed Subjects with ≥ 6 tender joints out of 68 joints assessed Exclusion Criteria: Pregnant or nursing women, or subjects who plan to become pregnant within 6 months or whose screening test results show pregnancy cannot be ruled out Subjects with previous experience of tacrolimus (excluding external preparations) Subjects with renal dysfunction or with serum creatinin > 1.4 mg/dL at screening Following subjects with hepatic dysfunction: viral infection, non-viral infection, hepatic cirrhosis, and Serum Glutamic Oxaloacetic Transaminase / Serum Glutamic Pyruvic Transaminase (SGOT/SGPT) exceeding twice the upper limit of normal at screening Subjects with pancreatitis, uncontrolled diabetes or complication(s) or with HbA1c > 6.4% at screening Subjects complicated with hyperkalemia or with serum potassium level >5.5 mEq/L at screening Subjects with history of heart disease (ischemic heart disease, arrhythmia requiring treatment, and heart failure), etc or complications Subjects complicated with severe respiratory disease and infection Subjects with history of malignant tumor or complication(s) (However, the subjects who are considered to have no risk of recurrence with malignant tumor untreated for 5 years or longer can enter the study. The subjects who succeeded in treatment for basal cell or squamous cell carcinoma of skin can also enter the study.) Subjects who were treated with other investigational product(s) within 3 months before screening Other subjects who are considered ineligible for the study by the investigator

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 75 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Tacrolimus group<br>oral | Drug: Tacrolimus<br>* oral<br>* Other names: Prograf;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 response rate 6 months post dose | ACR20 is 20% improvement in ACR (American College of Rheumatology) core set | Baseline and 6 months post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR50 response rates at month 6 | ACR50 is 50% improvement in ACR (American College of Rheumatology) core set | Baseline and at month 6 | 
| ACR70 response rates at month 6 | ACR70 is 70% improvement in ACR (American College of Rheumatology) core set | Baseline and at month 6 | 
| Change in DAS28 from baseline to 6 months | DAS (Disease Activity Score in Rheumatoid Arthritis) | Baseline and at month 6 | 
| Change in bone loss rate from baseline to 6 months | comparative factors for bone loss rate: bone mineral densitometry [BMD], bone turnover marker test | Baseline and at month 6 | 
| Safety assessed by the incidence of adverse events, vital signs and lab-tests |  | For 6 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
calcineurin inhibitor, Prograf, Rheumatoid arthritis (RA), Tacrolimus