Efficacy and Safety Study of TAS5315 Compared With Placebo in Participants With Rheumatoid Arthritis.

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to assess the efficacy and safety of TAS5315 in combination with methotrexate in a 12 week or 36 week in participants with rheumatoid arthritis with inadequate response to methotrexate.

Official Title
-----------------
An Early Phase-II, Randomized, Double-blind, Study of TAS5315 in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

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

Intervention / Treatment
-----------------
* Drug: TAS5315 low dose
* Drug: TAS5315 high dose
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Have a diagnosis of RA according to 2010 ACR/ EULAR rheumatoid arthritis (RA) classification criteria Have been treated with methotrexate (MTX) for at least 90 days prior to screening, and must be on a stable dose between 8 and 16 mg/week for at least 56 days prior to screening. Have an inadequate response to MTX Have a minimum of 6 swollen and 6 tender joints from 66/68 joint count Have hsCRP of ≥ 0.6 mg/dL Exclusion Criteria: Have been treated with conventional synthetic disease-modifying anti-rheumatic drug, except for MTX, within 28 days prior to randomization Have an inadequate response to biologic disease-modifying anti-rheumatic drug or Have been treated with 2 biologic treatment Have been treated with Janus Kinase inhibitors or other Bruton's Tyrosine Kinase inhibitors Have a positive result for hepatitis B surface antigen/antibody, hepatitis B core antibody, hepatitis C virus antibody or human immunodeficiency virus antigen/antibody at screening Have been treated with Oral steroids at dose above 10 mg/day of prednisone or prednisone equivalents Have a diagnosis of Felty's syndrome Have a positive result of the QuantiFERON®-tuberculosis (TB) Gold test or a T-spot ®-TB test at screening Have a positive result of β-D-glucan at screening

Ages Eligible for Study
-----------------
Minimum Age: 20 Years
Maximum Age: 64 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAS5315 low dose group<br>TAS5315 low dose and Methotrexate as specified | Drug: TAS5315 low dose<br>* Oral administration for 12 or 36 weeks<br>|
| Experimental: TAS5315 high dose group<br>TAS5315 high dose and Methotrexate as specified | Drug: TAS5315 high dose<br>* Oral administration for 12 or 36 weeks<br>|
| Placebo Comparator: Placebo group<br>Placebo and Methotrexate as specified | Drug: Placebos<br>* Oral administration for 12 weeks (At Week 12, participants in the placebo group will be assigned to TAS5315 low or high dose group)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants achieving American College of Rheumatology 20% (ACR20) response |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants who achieve ACR20 response |  | Up to Week 36, except for Week 12 | 
| Proportion of participants achieving American College of Rheumatology 50% (ACR50) and American College of Rheumatology 70% (ACR70) response |  | Up to Week 36 | 
| Proportion of participants who achieve DAS28-hs C-ReactivePprotein (CRP) and DAS28-Erythrocyte Sedimentation Rate (ESR) for remission |  | Baseline, Week 12 | 
| Change from baseline in DAS28-CRP and DAS28-ESR score |  | Up to Week 36 | 
| Proportion of participants who achieve Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) for remission |  | Baseline, Week 12 | 
| Change from baseline in CDAI and SDAI score |  | Up to Week 36 | 
| Change from baseline in patient assessment score of arthritis pain |  | Up to Week 36 | 
| Change from baseline in patient global assessment score of arthritis |  | Up to Week 36 | 
| Change from baseline in physician's global assessment score of arthritis |  | Up to Week 36 | 
| Change from baseline in modified total sharp score |  | Baseline, Week 2, 4, 12 | 
| Change from baseline in Anti-cyclic Citrullinated Peptide antibody levels |  | Up to Week 36 | 
| Change from baseline in rheumatoid factor levels |  | Up to Week 36 | 
| Maximum observed plasma concentration for TAS5315 |  | Baseline, Week 2, 4, 12 | 
| Time to reach the maximum plasma concentration for TAS5315 |  | Baseline, Week 2, 4, 12 | 
| Area under the plasma concentration-time curve from time 0 to the time of the last quantifiable concentration for TAS5315 |  | Baseline, Week 2, 4, 12 | 
| Incidence of adverse events and side effects as safety |  | Up to Week 36 |