A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Combination Therapy of T-614 and Methotrexate in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of T-614 versus placebo when added to ongoing, stable-dose methotrexate therapy in patients with persistently active rheumatoid arthritis

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled Study of the Combination Therapy of T-614 and Methotrexate in Rheumatoid Arthritis Patients With an Inadequate Response to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: T-614
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Subjects who have a diagnosis of Rheumatoid Arthritis by the ACR criteria Age greater or 20 years and less than 70 years old Exclusion criteria: Subject who is considered by the investigator, for any reason, to be an unsuitable candidate for the study Women of childbearing potential who are not practicing a successful method of contraception, or wish to become pregnant

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 69 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: T-614<br>* T-614 is administered twice daily in combination with methotrexate. The daily dose of T-614 is 25 mg for the first 4 weeks and 50 mg for subsequent weeks.<br>|
| Placebo Comparator: 2<br> | Drug: Placebo<br>* Placebo is administered twice daily in combination with methotrexate. In placebo group, patients will receive T-614 after completing 28 weeks of treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of American College of Rheumatology [ACR] 20 Criteria Responders | ACR20 response is defined as at least a 20% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant [erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)]. | Week 24 Last Observation Carried Forward (LOCF) (for T-614 arm and placebo arm) and Week 52 LOCF (for T-614 arm and placebo/T614 arm) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Tender Joint Counts and Swollen Joint Counts | Assessment of individual ACR core components like Tender Joint Counts (TJC) and Swollen Joint Counts (SJC) | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | 
| Change From Baseline in PAP, PtGADA and PyGADA | Patient's assessment of pain (PAP), patient's global assessment of disease activity (PtGADA) and physician's global assessment of disease activity (PyGADA) each was assessed on a visual analog scale ranging from 0-100 mm, with higher scores indicating severe disease. | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | 
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) | HAQ-DI was a participant assessed measure of health assessment, measured on a single scale ranging from 0 (no difficulty) to 3 (unable to do), with higher scores indicating severe disease. | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | 
| Change From Baseline in C-reactive Protein (CRP) | Assessment of individual ACR core components i.e. CRP | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | 
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) | Assessment of individual ACR core components i.e. ESR | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | 
| Disease Activity Score in 28 Joints (DAS28): The Rates of Remission (DAS28-CRP Less Than 2.6), and Low Disease Activity (DAS28-CRP Less Than 3.2) | The DAS28 is a composite score derived from 4 of these measures i.e count of 28 swollen joints, 28 tender joints, measure erythrocyte sedimentation rate (ESR) or C reactive protein (CRP) and to make a 'global assessment of health' (indicated by marking a 10 cm line between very good and very bad). DAS28 is assessed as score on scale from 0 to 10 indicating current rheumatoid arthritis (RA) disease activity (0= low disease activity and 10 = high disease activity). | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | 
| Percentage of ACR 50 Criteria Responders | ACR50 response is defined as at least a 50% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant [erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)]. | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) | 
| Percentage of ACR 70 Criteria Responders | ACR70 response is defined as at least a 70% improvement in tender joint count and swollen joint count, and in three of five of the following measures: patient pain intensity assessment, patient global assessment, physician global assessment, Health assessment questionnaire disability index (HAQ-DI), and an acute phase reactant [erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP)]. | Week 24 LOCF (for T-614 arm and placebo arm) and Week 52 LOCF (for T614 arm and placebo/T614 arm) |