A Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy, safety and pharmacokinetics of ASP5094 in patients with rheumatoid arthritis (RA) treated with background methotrexate (MTX).

Detailed Description
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The study drug will be intravenously administered.

Official Title
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A Phase 2a, Randomized, Placebo-Controlled, Double-Blind, Parallel Group Study to Evaluate the Efficacy and Safety of ASP5094 in Patients With Rheumatoid Arthritis on Methotrexate

Conditions
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Rheumatoid Arthritis (RA)

Intervention / Treatment
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* Drug: ASP5094
* Drug: Placebo
* Other: Methotrexate therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 ACR/European League Against Rheumatism (EULAR) criteria at least 6 months prior to screening. Subject meets the 1991 ACR Revised Criteria for the Classification of Global Functional Status in RA Class I, II, or III at screening. At screening and baseline, subject has active RA as evidenced by both of the following: ≥ 6 tender/painful joints (using 68-joint assessment) ≥ 6 swollen joints (using 66-joint assessment) Subject meets the criterion for a CRP level (Latex Agglutination method) at screening. Subject who has continuously received Methotrexate for at least 90 days prior to screening and who is able to continue a stable dose of Methotrexate from at least 28 days prior to screening throughout the study period. Exclusion Criteria: Subject has deviated from the criteria for previous and concomitant treatment before baseline. Subject has an ongoing infection requiring antibiotics. Subject is determined to be an inadequate responder to a prior biologic disease modifying antirheumatic drugs (DMARDs) or Janus kinase (JAK) inhibitors. Subject has participated in previous ASP5094 clinical trial. Subject has participated in a clinical trial or post-marketing clinical study of another ethical drug or medical device within 12 weeks (84 days). Subject has another inflammatory arthritis than RA, or any other articular symptom which may affect on joint assessment. Subject meets any of the criteria for laboratory values at screening. Subject has a positive T-SPOT or QuantiFERON Gold test within 90 days prior to screening or at screening. Subject has a history of or concurrent malignant tumor. Subject has autoimmune disease except for RA or any severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, or mental illness. Subject has a history of clinically significant allergy. Subject has clinically significant abnormalities on 12-lead electrocardiogram (ECG) at screening. Subject has a history of Human Immunodeficiency Virus (HIV) infection. Subject had surgery within 30 days prior to screening or has a planned elective surgery. Subject has a wound that is currently healing at baseline.

Ages Eligible for Study
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Minimum Age: 20 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: ASP5094 Group<br>To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate. | Drug: ASP5094<br>* intravenously administration<br>Other: Methotrexate therapy<br>* MTX must have been continuously orally administered for at least 90 days prior to screening, with stable dosage for at least 28 days prior to screening, and will be continuously administered with the same dosage throughout the study period.<br>|
| Placebo Comparator: Placebo Group<br>To be intravenously administered ASP5094 in patients with rheumatoid arthritis (RA) treated with methotrexate. | Drug: Placebo<br>* intravenously administration<br>Other: Methotrexate therapy<br>* MTX must have been continuously orally administered for at least 90 days prior to screening, with stable dosage for at least 28 days prior to screening, and will be continuously administered with the same dosage throughout the study period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR50 response rate | To assess ACR (American College of Rheumatology) 50 for efficacy | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR50 response rate | To assess ACR (American College of Rheumatology) 50 for efficacy | Up to Week 16 | 
| ACR20 response rate | To assess ACR (American College of Rheumatology) 20 for efficacy | Up to Week 16 | 
| ACR70 response rate | To assess ACR (American College of Rheumatology) 70 for efficacy | Up to Week 16 | 
| Change from baseline in DAS28-CRP score | To assess DAS28-CRP (Disease Activity Score28 - C-reactive protein) for efficacy | Baseline and Up to Week 16 | 
| Change from baseline in DAS28-ESR score | To assess DAS28-ESR (Disease Activity Score28 - Erythrocyte sedimentation rate) for efficacy | Baseline and Up to Week 16 | 
| Change from baseline in Tender Joint Count (68 joints) | To assess Tender Joint Count for efficacy | Baseline and Up to Week 16 | 
| Change from baseline in Swollen Joint Count (66 joints) | To assess Swollen Joint Count for efficacy | Baseline and Up to Week 16 | 
| Percentage of subjects achieving DAS28-CRP score for remission (<2.6) | To assess DAS28-CRP score for efficacy | Up to Week 16 | 
| Percentage of subjects achieving DAS28-ESR score for remission (<2.6) | To assess DAS28-ESR score for efficacy | Up to Week 16 | 
| Percentage of subjects achieving DAS28-CRP score for low disease activity (≦3.2) | To assess DAS28-CRP score for efficacy | Up to Week 16 | 
| Percentage of subjects achieving DAS28-ESR score for low disease activity (≦3.2) | To assess DAS28-ESR score for efficacy | Up to Week 16 | 
| Change from baseline in CRP | To assess CRP (C-reactive protein) for efficacy | Baseline and Up to Week 16 | 
| Change from baseline in ESR | To assess ESR (Erythrocyte sedimentation rate) for efficacy | Baseline and Up to Week 16 | 
| Percentage of subjects achieving EULAR response criteria of Good Response | To assess EULAR (European league Against Rheumatism) response criteria for efficacy | Up to Week 16 | 
| Percentage of subjects achieving EULAR response criteria of Good Response or Moderate Response | To assess EULAR response criteria for efficacy | Up to Week 16 | 
| Percentage of subjects achieving ACR/EULAR score for remission | To assess ACR/EULAR remission for efficacy | Up to Week 16 | 
| Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission) | To assess SDAI (Simplified Disease Activity Index) score for efficacy | Up to Week 16 | 
| Percentage of subjects achieving CDAI score ≦ 2.8 (CDAI remission) | To assess CDAI (Clinical Disease Activity Index) score for efficacy | Up to Week 16 | 
| Change from baseline for the HAQ-DI | To assess HAQ-DI (Health Assessment Questionnaire - Disability Index) for efficacy | Baseline to Up to Week 16 | 
| Safety assessed by incidence of adverse events | Adverse events will be coded using Medical Dictionary for Regulatory Activities (MedDRA). | Up to Week 16 | 
| Safety assessed by laboratory tests: Hematology | To assess hematology as a criteria of safety variables. | Up to Week 16 | 
| Safety assessed by laboratory tests: Biochemistry | To assess Biochemistry as a criteria of safety variables. | Up to Week 16 | 
| Safety assessed by laboratory tests: Urinalysis | To assess Urinalysis as a criteria of safety variables. | Up to Week 16 | 
| Safety assessed by vital signs: Body temperature | To assess the vital sign as a criteria of safety variables. | Up to Week 16 | 
| Safety assessed by vital signs: Sitting blood pressure | To assess the vital sign as a criteria of safety variables. | Up to Week 16 | 
| Safety assessed by vital signs: pulse rate | To assess the vital sign as a criteria of safety variables. | Up to Week 16 | 
| Safety assessed by weight | To assess the weight as a criteria of safety variables. | Up to Week 16 | 
| Safety assessed by standard 12-lead electrocardiogram | To assess the cardiovascular system functioning as a criteria of safety variables. | Up to Week 16 | 
| Serum concentration of ASP5094 | To assess Serum concentration of ASP5094 for pharmacokinetics | Up to Week 16 | 
| Serum concentration of TNF-α | To assess TNF-α (Tumor Necrosis Factor-α) for pharmacodynamics | Up to Week 16 | 
| Serum concentration of MMP3 | To assess MMP3 (Matrix metalloproteinase 3) for pharmacodynamics | Up to Week 16 | 
| Serum concentration of IL-6 | To assess IL-6 (Interleukin-6) for pharmacodynamics | Up to Week 16 | 
| Anti-ASP5094 anti-bodies | To assess Anti-ASP5094 anti-bodies for immunogenicity | Up to Week 16 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methotrexate, Arthritis, Rheumatoid, ASP5094