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

Phase 2
Completed
Conditions
Rheumatoid Arthritis
Interventions
Registration Number
NCT02884635
Lead Sponsor
Astellas Pharma Inc
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
72
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboPlacebo will be orally administered for 12 weeks.
PlaceboMethotrexatePlacebo will be orally administered for 12 weeks.
ASP1707ASP1707ASP1707 will be orally administered for 12 weeks.
ASP1707MethotrexateASP1707 will be orally administered for 12 weeks.
Primary Outcome Measures
NameTimeMethod
ACR20 response rateWeek 12

ACR20: American College of Rheumatology 20

Secondary Outcome Measures
NameTimeMethod
ACR50 response rateUp 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
Change from baseline in CRPBaseline and Up to Week 12
Percentage of subjects achieving EULAR response criterion of "Good Response"Up to Week 12

EULAR: European league Against Rheumatism

ACR20 response rateUp to Week 8
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
ACR70 response rateUp to Week 12
Change from baseline in ESRBaseline and Up to Week 12
Safety assessed by incidence of adverse eventsUp to Week 13
Safety assessed by pulse rateUp to Week 13
Safety assessed by laboratory tests: HematologyUp to Week 13
Safety assessed by laboratory tests: BiochemistryUp to Week 13
Safety assessed by laboratory tests: UrinalysisUp to Week 13
Change from baseline in DAS28-CRP scoreBaseline and Up to Week 12

DAS28-CRP: Disease Activity Score28 - C-reactive protein

Change from baseline in DAS28-ESR scoreBaseline and Up to Week 12

DAS28-ESR: Disease Activity Score28 - Erythrocyte sedimentation rate

Change from baseline in the SDAI scoreBaseline and Up to Week 12
Safety assessed by body temperatureUp to Week 13
Safety assessed by standard 12-lead electrocardiogramUp to Week 13
Safety assessed by weightUp to Week 13
Pharmacodynamics assessed by plasma concentration of TNF-αUp to Week 13

TNF: Tumor Necrosis Factor

Percentage of subjects achieving ACR/EULAR score for remissionUp to Week 12
Percentage of subjects achieving SDAI score ≦ 3.3 (SDAI remission)Up to Week 12

SDAI: Simplified Disease Activity Index

Plasma concentration of metabolite of ASP1707Up to Week 12
Pharmacodynamics assessed by endocrinology testsUp to Week 13
Percentage of subjects achieving EULAR response criterion of "Good Response" or "Moderate Response"Up to Week 12
Change from baseline for the HAQ-DIBaseline and Up to Week 12

HAQ-DI: Health Assessment Questionnaire - Disability Index

Safety assessed by blood pressure in sitting positionUp to Week 13
Pharmacodynamics assessed by plasma concentration of MMP3Up to Week 13

MMP3: Matrix metalloproteinase 3

Plasma concentration of ASP1707Up to Week 12
Pharmacodynamics assessed by plasma concentration of IL-6Up to Week 13

IL-6: Interleukin-6

Trial Locations

Locations (27)

Site JP00010

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Hiroshima, Japan

Site JP00022

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Aichi, Japan

Site JP00023

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Aichi, Japan

Site JP00006

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Gunma, Japan

Site JP00024

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Gunma, Japan

Site JP00011

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Hiroshima, Japan

Site JP00018

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Fukuoka, Japan

Site JP00019

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Fukuoka, Japan

Site JP00021

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Kanagawa, Japan

Site JP00020

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Oita, Japan

Site JP00015

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Kumamoto, Japan

Site JP00013

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Nagasaki, Japan

Site JP00009

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Shizuoka, Japan

Site JP00004

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Iwate, Japan

Site JP00026

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Ehime, Japan

Site JP00001

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Hokkaido, Japan

Site JP00008

🇯🇵

Shizuoka, Japan

Site JP00002

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Hokkaido, Japan

Site JP00016

🇯🇵

Kagoshima, Japan

Site JP00007

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Kanagawa, Japan

Site JP00014

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Kumamoto, Japan

Site JP00017

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Chiba, Japan

Site JP00012

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Fukuoka, Japan

Site JP00025

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Fukui, Japan

Site JP00005

🇯🇵

Iwate, Japan

Site JP00003

🇯🇵

Hokkaido, Japan

Site JP00027

🇯🇵

Tokyo, Japan

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