A Study to Evaluate the Efficacy and Safety of ASP1707 in Postmenopausal Female Patients With Rheumatoid Arthritis Taking Methotrexate

Study Overview
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Brief Summary
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The objective of this study is to evaluate the efficacy, pharmacokinetics, pharmacodynamics and safety of ASP1707 in combination with MTX in postmenopausal female patients with RA.

Official Title
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Phase IIa Study of ASP1707 A Randomized, Placebo-Controlled, Double-Blind, Parallel Group Phase 2a Study of ASP1707 in Postmenopausal Female Patients With Rheumatoid Arthritis (RA) Taking Methotrexate (MTX)

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: ASP1707
* Drug: Placebo
* Drug: Methotrexate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject has RA that was diagnosed according to the 1987 ACR criteria or the 2010 ACR/EULAR criteria. Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II or, III. subject has active RA as evidenced by both of the followings: ≥ 6 tender/painful joints (using 68-joint assessment) ≥ 6 swollen joints (using 66-joint assessment) CRP (C-reactive protein) of > 0.3 mg/dL or ESR (Erythrocyte sedimentation rate) of > 28 mm/hr at screening. Subject who continuously received MTX and who is able to continue stable dose of MTX. Subject who did not receive the following drugs, or received the drugs with stable dosage: Non-steroidal anti-inflammatory drugs, oral morphine or equivalent opioid analgesics, acetaminophen, or oral corticosteroids. Exclusion Criteria: Inadequate responders to a biologic DMARD (Disease-modifying antirheumatic drug). Subject has taken other investigational research products are prohibited within 12 weeks (84 days) or within 5 half-lives, whichever is longer, prior to screening. Subject has undergone surgery which has residual effects on the assessed joints, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints. Subject has another type of inflammatory arthritis other than RA. Subject who meets any of the following criteria of laboratory values at screening: White blood cell count <4000/μL Platelet count <100000/μL ALT (Alanine Aminotransferase) ≥ 2 x ULN (Upper Limit of Normal) AST (Aspartate Aminotransferase) ≥ 2 x ULN Total bilirubin ≥ 1.5 x ULN Positive Hepatitis B surface antigen, Hepatitis B virus-DNA quantitation, or Hepatitis C virus antibody Subject has a positive QuantiFERON-TB Gold test or T-spot. Subject has a history of or concurrent malignant tumor. Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA, or diseases which preclude the subject's participation in the study. Subject has a history of clinically significant allergy. Subject has clinically significant abnormalities on the 12-lead Electrocardiogram. Subject has a history of positive Human Immunodeficiency Virus infection.
Sexes Eligible for Study
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Female

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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ASP1707<br>ASP1707 will be orally administered for 12 weeks. | Drug: ASP1707<br>* Oral<br>Drug: Methotrexate<br>* Methotrexate will be orally administered at stable dose from at least 28 days prior to screening through the screening and treatment periods until the end of the follow-up period.<br>|
| Placebo Comparator: Placebo<br>Placebo will be orally administered for 12 weeks. | Drug: Placebo<br>* Oral<br>Drug: Methotrexate<br>* Methotrexate will be orally administered at stable dose from at least 28 days prior to screening through the screening and treatment periods until the end of the follow-up period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 response rate | ACR20: American College of Rheumatology 20 | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ACR20 response rate |  | Up to Week 8 | 
| ACR50 response rate |  | Up to Week 12 | 
| ACR70 response rate |  | Up to Week 12 | 
| Change from baseline in DAS28-CRP score | DAS28-CRP: Disease Activity Score28 - C-reactive protein | Baseline and Up to Week 12 | 
| Change from baseline in DAS28-ESR score | DAS28-ESR: Disease Activity Score28 - Erythrocyte sedimentation rate | Baseline and Up to Week 12 | 
| Change from baseline in Tender Joint Count (68 joints) |  | Baseline and Up to Week 12 | 
| Change from baseline in Swollen Joint Count (66 joints) |  | Baseline and Up to Week 12 | 
| Percentage of subjects achieving DAS28-CRP score and DAS28-ESR score for remission (<2.6) |  | Up to Week 12 | 
| Percentage of subjects achieving DAS28-CRP score and DAS28-ESR score for low disease activity (≤3.2) |  | Up to Week 12 | 
| Change from baseline in CRP |  | Baseline and Up to Week 12 | 
| Change from baseline in ESR |  | Baseline and Up to Week 12 | 
| Percentage of subjects achieving EULAR response criterion of Good Response | EULAR: European league Against Rheumatism | Up to Week 12 | 
| Percentage of subjects achieving EULAR response criterion of Good Response or Moderate Response |  | Up to Week 12 | 
| Percentage of subjects achieving ACR/EULAR score for remission |  | Up to Week 12 | 
| Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission) | SDAI: Simplified Disease Activity Index | Up to Week 12 | 
| Change from baseline in the SDAI score |  | Baseline and Up to Week 12 | 
| Change from baseline for the HAQ-DI | HAQ-DI: Health Assessment Questionnaire - Disability Index | Baseline and Up to Week 12 | 
| Safety assessed by incidence of adverse events |  | Up to Week 13 | 
| Safety assessed by body temperature |  | Up to Week 13 | 
| Safety assessed by pulse rate |  | Up to Week 13 | 
| Safety assessed by blood pressure in sitting position |  | Up to Week 13 | 
| Safety assessed by laboratory tests: Hematology |  | Up to Week 13 | 
| Safety assessed by laboratory tests: Biochemistry |  | Up to Week 13 | 
| Safety assessed by laboratory tests: Urinalysis |  | Up to Week 13 | 
| Safety assessed by standard 12-lead electrocardiogram |  | Up to Week 13 | 
| Safety assessed by weight |  | Up to Week 13 | 
| Plasma concentration of ASP1707 |  | Up to Week 12 | 
| Plasma concentration of metabolite of ASP1707 |  | Up to Week 12 | 
| Pharmacodynamics assessed by endocrinology tests |  | Up to Week 13 | 
| Pharmacodynamics assessed by plasma concentration of TNF-α | TNF: Tumor Necrosis Factor | Up to Week 13 | 
| Pharmacodynamics assessed by plasma concentration of MMP3 | MMP3: Matrix metalloproteinase 3 | Up to Week 13 | 
| Pharmacodynamics assessed by plasma concentration of IL-6 | IL-6: Interleukin-6 | Up to Week 13 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Methotrexate, ASP1707, Rheumatoid arthritis