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临床试验/NCT02308163
NCT02308163已完成3 期

Phase 3 Study of ASP015K - A Randomized, Double-blind, Placebo-controlled Confirmatory Study of the Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis Who Had an Inadequate Response to DMARDs

Astellas Pharma Inc153 个研究点 分布在 1 个国家目标入组 509 人开始时间: 2014年8月8日最近更新:
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适应症
干预措施

试验速览

阶段
3 期
状态
已完成
入组人数
509
试验地点
153
主要终点
Percentage of Participants With an American College of Rheumatology 20% (ACR20) C-Reactive Protein (CRP) Response at Week 12
研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

The objective of this study was to verify the superiority of ASP015K alone or in combination with disease-modifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response to DMARDs

详细描述

This was a multi-center, randomized, placebo-controlled, double-blind, parallel-group, confirmatory study to evaluate the efficacy and safety of ASP015K alone or in combination with DMARDs in participants with RA who had an inadequate response to DMARDs.

Etanercept was also administered as the reference drug in an open-label manner. The study drug was orally administered once daily (QD) after breakfast for 52 weeks. Etanercept was administered subcutaneously QD for 52 weeks. At Week 12, participants in the placebo group were switched to ASP015K.

The dose of ASP015K to be started at Week 12 for the placebo group was determined randomly at baseline in advance and switched in a blinded manner.

Participants in ASP015K group or placebo groups who had completed the study were eligible for participation in an open-label extension study (015K-CL-RAJ2).

研究设计

研究类型
Interventional
分配方式
Randomized
干预模型
Parallel
主要目的
Treatment
盲法
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

入排标准

年龄范围
20 Years 至 —（Adult, Older Adult）
性别
All
接受健康志愿者
否

入选标准

  • •Subject has RA diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria
  • •Subject who did not receive the following drugs, or received the drugs with stable dosage for at least 28 days prior to the baseline (start of treatment) for RA treatment:
  • •Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations), oral morphine or equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, or oral corticosteroids (≤ 10 mg/day in prednisolone equivalent)
  • •At screening 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)
  • •CRP > 0.50 mg/dL at screening
  • •Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II or, III at screening.
  • •Inadequate responder to (including subjects who were intolerant of) at least one DMARD administered for at least 90 days prior to screening

排除标准

  • •Subject has received a biologic DMARD within the specified period
  • •Subject has received etanercept
  • •Inadequate responder to at least 3 biologic DMARDs as determined by investigator/sub-investigator
  • •Subject has received intra-articular, intravenous, intramuscular or endorectal (excluding suppositories for anal diseases) corticosteroid within 28 days prior to baseline
  • •Subject has participated in any study of ASP015K and has received ASP015K or placebo
  • •Subject has received other investigational drugs within 90 days or within 5 half-lives, whichever is longer, prior to baseline
  • •Subject has received plasma exchange therapy within 60 days prior to baseline
  • •Subject has undergone joint drainage, has received local anesthesia and nerve block, or has received articular cartilage protectant at the assessed joint within 28 days prior to baseline
  • •Subject has undergone surgery and has residual effects in the assessed joints at the discretion of investigator/sub-investigator, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints at the discretion of investigator/sub-investigator
  • •A diagnosis of inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis, SLE, sarcoidosis, etc.) other than RA
  • •Any of the following laboratory values at screening:
  • •Hemoglobin < 9.0 g/dL
  • •Absolute neutrophil count < 1000/μL
  • •Absolute lymphocyte count < 800/μL
  • •Platelet count < 75000/μL
  • •ALT ≥ 2 ×ULN
  • •AST ≥ 2 × ULN
  • •Total bilirubin (TBL) ≥ 1.5 × ULN
  • •Estimated GFR ≤ 40 mL/min as measured by the MDRD method
  • •β-D-glucan > ULN [in case of Japan: ≥ 11 pg/mL]
  • •Positive HBs antigen, HBc antibody, HBs antibody or HBV-DNA quantitation (However, subject with negative HBs antigen and HBV-DNA quantitation, and positive HBc antibody and/or HBs antibody is eligible if HBV-DNA is monitored by HBV-DNA quantitation at every scheduled visit after initiation of study drug or reference drug administration.)
  • •Positive HCV antibody
  • •Subject has a history of or concurrent active tuberculosis (TB)
  • •Subject has a history of or concurrent interstitial pneumonia and investigator/sub-investigator judges that it is inappropriate for the subject to participate in this study
  • •Subject has a history of or concurrent malignant tumor (except for successfully treated basal cell carcinoma)
  • •Subject has received live or live attenuated virus vaccination within 56 days prior to baseline. (Inactivated vaccines including influenza and pneumococcal vaccines are allowed.)
  • •Subject has a history of or concurrent demyelinating disorders
  • •Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA (excluding Sjogren's syndrome and chronic thyroiditis), or any ongoing illness which would make the subject unsuitable for the study as determined by the investigator/sub-investigator
  • •Subject has a history of clinically significant allergy. (Clinically significant allergy includes allergies such as systemic urticaria induced by specific antigens and drugs, anaphylaxis, and allergy associated with shock necessitating hospitalized treatment.)
  • •Subject has concurrent cardiac failure, defined as NYHA classification Class III or higher, or a history of it
  • •Subject has concurrent prolonged QT syndrome or a history of it. Subject has prolonged QT interval (defined as QTc ≥ 500 msec. Subject has QTc ≥ 500 msec at retest will be excluded) at screening
  • •Subject has a history of positive HIV infection
  • •Subject has congenital short QT syndrome or a history of it. Subject has shortened QT interval (defined as QTc < 330 msec. Subject has QTc < 330 msec at retest will be excluded) at screening.

研究组 & 干预措施

Placebo

Placebo Comparator

Participants were assigned to receive placebo to peficitinib once a day until week 12.

干预措施: Placebo (Drug)

Peficitinib 100 mg

Experimental

Participants were assigned to receive peficitinib 100 mg/day for 52 weeks.

干预措施: Peficitinib (Drug)

Peficitinib 150 mg

Experimental

Participants were assigned to receive peficitinib 150 mg/day for 52 weeks.

干预措施: Peficitinib (Drug)

Etanercept

Active Comparator

Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.

干预措施: Etanercept (Biological)

结局指标

主要结局

Percentage of Participants With an American College of Rheumatology 20% (ACR20) C-Reactive Protein (CRP) Response at Week 12

时间窗: Baseline and Week 12/early termination (ET)

The ACR20 response required that all criteria from (1) to (3) below be met. 1. Tender joint count (TJC) : ≥ 20% reduction compared with baseline. 2. Swollen joint count (SJC) : ≥ 20% reduction compared with baseline. 3. ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline (3) ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, Subject's Global Assessment of Arthritis (SGA), Physician's Global Assessment of Arthritis (PGA), Health Assessment Questionnaire - Disability Index (HAQ-DI), C-Reactive Protein (CRP).

次要结局

  • Percentage of Participants With an ACR50-CRP Response Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in Swollen Joint Count (SJC) (66 Joints) at Week 12(Baseline and Week 12/ET)
  • Percentage of Participants Achieving DAS28-CRP < 2.6 Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants Achieving DAS28-ESR <= 3.2 at Week 12(Week 12/ET)
  • Percentage of Participants Achieving DAS28-ESR <= 3.2 Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in ESR Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants With an American College of Rheumatology 50% (ACR50)-CRP Response at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in DAS28-ESR Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in TJC (68 Joints) Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants Achieving DAS28-CRP < 2.6 at Week 12(Baseline and Week 12/ET)
  • Percentage of Participants With an ACR70-CRP Response Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in Disease Activity Score (DAS) 28-CRP at Week 12(Baseline and Week 12/ET)
  • Change From Baseline DAS28-CRP Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in TJC (68 Joints) at Week 12(Baseline and Week 12/ET)
  • Percentage of Participants With an ACR20-CRP Response Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants With an American College of Rheumatology 70% (ACR70)-CRP Response at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (ESR) at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in SJC (66 Joints) Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants Achieving DAS28-ESR < 2.6 at Week 12(Week 12/ET)
  • Change From Baseline in CRP at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in CRP Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants With a EULAR Good Response Using DAS28-CRP Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants Achieving DAS28-ESR < 2.6 Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants Achieving DAS28-CRP <= 3.2 at Week 12(Week 12/ET)
  • Percentage of Participants Achieving DAS28-CRP <= 3.2 Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in ESR at Week 12(Baseline and Week 12/ET)
  • Percentage of Participants With a European League Against Rheumatism (EULAR) Good Response Using DAS28-CRP at Week 12(Week 12/ET)
  • Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR at Week 12(Week 12/ET)
  • Percentage of Participants With a Good EULAR Response Using DAS28-ESR at Week 12(Week 12/ET)
  • Percentage of Participants Achieving ACR / EULAR Remission at Week 12(Week 12/ET)
  • Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP at Week 12(Week 12/ET)
  • Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants With a Good EULAR Response Using DAS28-ESR Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants Achieving ACR / EULAR Remission Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Remission at Week 12(Week 12/ET)
  • Percentage of Participants Achieving SDAI Remission Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in SDAI Score at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in SDAI Score Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in CDAI Score at Week 12(Baseline and Week 12/ET)
  • Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Score <= 2.8 at Week 12(Week 12/ET)
  • Percentage of Participants Achieving CDAI Score <= 2.8 Through Week 52(Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in CDAI Score Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in Physician's Global Assessment of Arthritis (PGA) at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in Subject's Assessment of Pain at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in Subject's Assessment of Pain Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in HAQ-DI Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in Short Form Health Survey - 36 Questions, Version 2 (SF-36v2) Physical Component Summary Score at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in SF-36v2 Physical Component Summary Score Through Week 52(Baseline and Week 4, 8, 12, 28, and 52)
  • Change From Baseline in PGA Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Change From Baseline in Subject's SGA at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in SGA Through Week 52(Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52)
  • Number of Participants Who Withdrew Due to Lack of Efficacy(Up to week 12)
  • Change From Baseline in SF-36v2 Mental Component Summary Score at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in SF-36v2 Role/Social Component Summary Score Through Week 52(Baseline and Week 4, 8, 12, 28, and 52)
  • Change From Baseline in WPAI Percent Overall Work Impairment Through Week 52(Baseline and Week 4, 8, 12, 28, and 52)
  • Number of Participants With Adverse Events During the First 12 Weeks(Week 0 to Week 12)
  • Number of Participants With Adverse Events From Week 12(Week 12 to week 52, plus 28 days after the week 52 visit for participants who did not enroll in the extension study)
  • Change From Baseline in SF-36v2 Mental Component Summary Score Through Week 52(Baseline and Week 4, 8, 12, 28, and 52)
  • Change From Baseline in SF-36v2 Role/Social Component Summary Score at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Percent Work Time Missed at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in WPAI Percent Work Time Missed Through Week 52(Baseline and Week 4, 8, 12, 28, and 52)
  • Change From Baseline in WPAI Percent Impairment While Working at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in WPAI Percent Activity Impairment at Week 12(Baseline and Week 12/ET)
  • Change From Baseline in WPAI Percent Activity Impairment Through Week 52(Baseline and Week 4, 8, 12, 28, and 52)
  • Change From Baseline in WPAI Percent Impairment While Working Through Week 52(Baseline and Week 4, 8, 12, 28, and 52)
  • Change From Baseline in Percent Overall Work Impairment at Week 12(Baseline and Week 12/ET)

研究者

申办方类型
Industry
责任方
Sponsor

研究点 (153)

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