Efficacy and Safety Study of MP-435 in Combination With Methotrexate (MTX) in Patients With Rheumatoid Arthritis

Study Overview
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Brief Summary
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The purpose of this study is to determine the Efficacy, Safety, and Pharmacokinetics of MP-435 administered for 12 weeks in subjects with rheumatoid arthritis (RA) on stable doses of Methotrexate.

Official Title
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A Multicenter Randomized, Double-blind, Placebo-controlled Study of MP-435 in Combination With MTX in Patients With Rheumatoid Arthritis - Exploratory Study

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: MP-435(dose1) + Methotrexate
* Drug: Placebo + Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects with a diagnosis of RA according to the diagnostic criteria of the American College of Rheumatology (ACR) (revised in 1987) for at least 6 months. Subjects who inadequately response for stable dose of MTX. Exclusion Criteria: Patients with Class IV functional activity by the Steinbrocker's scale. Patients who have received a biological agent in the past. Patients who have other rheumatic diseases, or who have other diseases with joint symptoms. Patients with severe or uncontrolled endocrine, psychiatric, cardiac, hematological, pulmonary, hepatic, kidney, gastrointestinal, or thyroid disease.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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>dose1 | Drug: MP-435(dose1) + Methotrexate<br>* MP-435 dose1 + stable weekly dose of Methotrexate<br>|
| Placebo Comparator: 2<br>Placebo | Drug: Placebo + Methotrexate<br>* Placebo + stable weekly dose of Methotrexate<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving American College of Rheumatology 20 (ACR 20) Response | ACR 20 response is a decrease of at least 20 per cent in both tender and swollen joint count [TJC and SJC] and in 3 to 5 assessments (participant's assessment of pain visual analog scale [VAS] with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; Health Assessment Questionnaire [HAQ-DI]: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; C-reactive protein[CRP]). | Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Achieving ACR 50 Response | ACR 50 response is a decrease of at least 50 per cent in both tender and swollen joint count and in 3 to 5 assessments (participant's assessment of pain VAS with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; HAQ-DI: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; CRP). | Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time) | 
| Percentage of Participants Achieving American College of Rheumatology 70 (ACR 70) Response | ACR 70 response is a decrease of at least 70 per cent in both tender and swollen joint count and in 3 to 5 assessments (participant's assessment of pain VAS with 0, no pain to 10, worst pain; patient's and physician's global assessment of disease activity VAS scales: overall disease activity [0, very well to 10, very poor and 0, no arthritis activity to 10, extremely active, respectively]; HAQ-DI: 20-questions on life activities [0, no difficulty to 3, inability to perform a task]; CRP). | Week 2, 4, 6, 8, 12, LOCF (Week 12 or discontinuation time) | 
| Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components | DAS28 (CRP) is calculated using TJC, SJC C-Reactive Protein ( CRP in mg/dL ), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.36 x log (CRP+1) + 0.014 x Global Assessment of Arthritis + 0.96 where 28 joints are examined and a lower score indicates less disease activity. DAS28 (ESR) is calculated using TJC, SJC erythrocyte sedimentation rate (ESR in mm/hour), and the Patient's Global Assessment of Disease Activity - Visual Analog Scale (VAS in mm) using the following formula: 0.56 x √(TJC) + 0.28 x √(SJC) + 0.70 x log (ESR) + 0.014 x Global Assessment of Arthritis where 28 joints are examined and a lower score indicates less disease activity. A negative change score indicates improvement. Higher score indicated more disease activity. DAS28 =<3.2 implied low disease activity, >3.2 to 5.1 implied moderate disease activity, >5.1 implied high disease activity. | LOCF (Week 12 or discontinuation time) | 
| Percent Changes From the Pretreatment Values in the Disease Activity Score (DAS) 28, and ACR Components | ACR components are tender joints count (TJC), swollen joints count (SJC), participant assessment of pain, participant global assessment of disease activity, physician global assessment of disease activity, self-assessed disability (disability index of the Health Assessment Questionnaire [HAQ-DI]); and C-Reactive Protein (CRP) or erythrocyte sedimentation rate (ESR). | LOCF (Week 12 or discontinuation time) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis