NCT03660059已完成3 期
A Randomized, Double-Blind, Placebo-Controlled Confirmatory Study of the Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response or Intolerance to MTX
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 385
- 试验地点
- 43
- 主要终点
- American College of Rheumatology (ACR)20 response rate at Week 24
研究概览
简要总结
The purpose of this study is to verify the superiority of ASP015K in combination with MTX or with other disease-modifying antirheumatic drugs (DMARDs) over placebo in terms of efficacy in participants with rheumatoid arthritis (RA) who had an inadequate response or intolerance to MTX, as measured by the American College of Rheumatology (ACR) 20 response rate at Week 24.
This study will also evaluate the pharmacokinetics and safety of ASP015K as well as efficacy and safety of long-term treatment with ASP015K (52 weeks).
详细描述
Participants will be randomized in a 1:1:1 ratio to the ASP015K dose-A group, ASP015K dose-B group or placebo group at Week 0.
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject is a man or woman and considered to be an adult, according to the local legal definition, at the time of informed consent.
- •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 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).
- •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 has CRP > 0.50 mg/dL. The re-test of CRP will be allowed, if the subject's CRP value at the time of screening test is more than 0.30 mg/dL and also his/her most recent CRP value which was carried out up to 90 days before the date of screening test was more than 0.5 mg/dL.
- •Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II, or III.
- •Subject has inadequate response or intolerance for MTX.
- •For inadequate responder to MTX, subject has had regular use of MTX for at least 90 days prior to screening at a dose that, in accordance with local clinical practice, is considered acceptable to adequately assess clinical response. The dose of MTX must have been a stable, unchanging oral dose of 7.5 to 20 mg/week (or the equivalent injectable dose) for at least the 28 days prior to screening. Subject is able to continue stable dose of MTX from at least 28 days prior to screening until the end of the administration period of study drug.
- •For subject who is intolerant of MTX, subject has had regular use of the following DMARDs, and when the following DMARDs are concomitantly administered to subject, the drugs must be administered for at least 90 days prior to screening, and must be stable from at least 28 days prior to screening until the end of the administration period of study drug.
- •Hydroxychloroquine
- •Salazosulfapyridine
- •D-penicillamine
- •Lobenzarit
- •Bucillamine
- •Iguratimod
排除标准
- •Subject has received a biologic DMARD within the specified period:
- •Anakinra: within 28 days prior to baseline
- •Etanercept: within 28 days prior to baseline
- •Adalimumab, infliximab: within 56 days prior to baseline
- •Golimumab, certolizumab pegol: within 70 days prior to baseline
- •Abatacept, tocilizumab: within 84 days prior to baseline
- •Denosumab: within 150 days prior to baseline
- •Rituximab: within 180 days prior to baseline
- •Subject has inadequate response to at least 3 biologic DMARDs.
- •Subject has received a non-biologic DMARD listed below or other drugs used in the treatment of RA within 28 days prior to baseline. Leflunomide is prohibited within 90 days prior to baseline. Alternatively, leflunomide is prohibited at least 28 days prior to baseline if washout with cholestyramine for at least 17 days is completed within 28 days prior to baseline. However, topical drugs other than those for the treatment of RA may be used concomitantly.
- •Leflunomide
- •Tacrolimus
- •Cyclosporine
- •Cyclophosphamide
- •Azathioprine
- •Minocycline
- •Mizoribine
- •Subject has received Chinese herbal medicines listed below or other herbal drugs used in the treatment of RA within 28 days prior to baseline.
- •Tripterygium wilfordii
- •Total glucosides of paeony
- •Tsuduranine
- •Subject has received tofacitinib, baricitinib or other JAK inhibitor (including other investigational drugs).
- •Subject has received intra-articular, intravenous, intramuscular, or endorectal (including 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 (such as glucosamine sulfate, chondroitin sulfate these DMORD medicine) at the assessed joint within 28 days prior to baseline.
- •Subject has undergone surgery and has residual effects in the assessed joints or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints.
- •Subject is diagnosed as inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis, SLE, sarcoidosis, etc.) other than RA.
- •Subject has any of the following laboratory values:
- •Hemoglobin < 9.0 g/dL
- •Absolute neutrophil count < 1000/μL
- •Absolute lymphocyte count < 800/μL
- •Platelet count < 75000/μL
- •Alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN)
- •Aspartate aminotransferase (AST) ≥ 2 × ULN
- •Total bilirubin (TBL) ≥ 1.5 × ULN
- •Estimated glomerular filtration rate (eGFR) ≤ 40 mL/min as measured by the MDRD method
- •β-D-glucan > ULN
- •Subject has a history of or concurrent active tuberculosis (TB). Eligibility criteria for TB are tabulated below:
- •Subject meets any of the following in terms of infection except for TB:
- •History of or concurrent severe herpes zoster (associated with Hunt syndrome or having ulcerative lesions) or disseminated herpes zoster
- •History of multiple recurrences (at least twice) of localized herpes zoster
- •Serious infection requiring hospitalization within 90 days prior to baseline
- •Subject has received intravenous antibiotics within 90 days prior to baseline. (However, prophylactic antibiotics are allowed.)
- •Subject with high risk of infection (e.g., subject with urinary catheter)
- •Subject has a history of or concurrent interstitial pneumonia and inappropriate 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 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.
- 另有 10 项未显示
研究组 & 干预措施
ASP015K 100 mg
Experimental
Participants will receive 100 milligrams (mg) of ASP015K once daily after breakfast for 52 weeks.
干预措施: Peficitinib (Drug)
ASP015K 100 mg
Experimental
Participants will receive 100 milligrams (mg) of ASP015K once daily after breakfast for 52 weeks.
干预措施: Disease-modifying antirheumatic drugs (DMARDs) (Drug)
ASP015K 150 mg
Experimental
Participants will receive 150 mg of ASP015K once daily after breakfast for 52 weeks.
干预措施: Peficitinib (Drug)
ASP015K 150 mg
Experimental
Participants will receive 150 mg of ASP015K once daily after breakfast for 52 weeks.
干预措施: Disease-modifying antirheumatic drugs (DMARDs) (Drug)
Placebo/ASP015K
Placebo Comparator
Participants will receive placebo for 24 weeks, then either 100 mg or 150 mg of ASP015K for 28 weeks as determined randomly at Week 0 in advance.
干预措施: Peficitinib (Drug)
Placebo/ASP015K
Placebo Comparator
Participants will receive placebo for 24 weeks, then either 100 mg or 150 mg of ASP015K for 28 weeks as determined randomly at Week 0 in advance.
干预措施: Plaebo (Drug)
Placebo/ASP015K
Placebo Comparator
Participants will receive placebo for 24 weeks, then either 100 mg or 150 mg of ASP015K for 28 weeks as determined randomly at Week 0 in advance.
干预措施: Disease-modifying antirheumatic drugs (DMARDs) (Drug)
结局指标
主要结局
American College of Rheumatology (ACR)20 response rate at Week 24
时间窗: At Week 24
The ACR20 response requires that all criteria from (1) to (3) be met compared with Week 0 (baseline); (1), Tender Joint Count (TJC) \>= 20% reduction; (2), Swollen Joint Count (SJC) \>= 20% reduction;(3) \>= 20% improvement in three or more of the following five parameters - \[1\] subject's assessment of pain, \[2\] Subject's Global Assessment of Arthritis (SGA), \[3\] Physician's Global Assessment of Arthritis (PGA), \[4\] health assessment questionnaire-disability index (HAQ-DI), \[5\] acute phase reactant (C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR)).
次要结局
- ACR20 response rate(Up to Week 52)
- ACR50 response rate(Up to Week 52)
- ACR70 response rate(Up to Week 52)
- Change from baseline in disease activity score (DAS) 28-C-reactive protein (CRP) scores(From baseline (Week 0) to Week 52)
- Change from baseline in DAS28- erythrocyte sedimentation rate (ESR) scores(From baseline (Week 0) to Week 52)
- Change from baseline in Tender Joint Count (TJC) (68 joints)(From baseline (Week 0) to Week 52)
- Change from baseline in Swollen Joint Count (SJC) (66 joints)(From baseline (Week 0) to Week 52)
- Percentage of participants achieving DAS28-CRP scores for remission(Up to Week 52)
- Percentage of participants achieving DAS28-ESR scores for remission(Up to Week 52)
- Percentage of participants achieving low disease activity by DAS28-CRP(Up to Week 52)
- Percentage of participants achieving low disease activity by DAS28-ESR(Up to Week 52)
- Change from baseline in CRP(From baseline (Week 0) to Week 52)
- Change from baseline in ESR(From baseline (Week 0) to Week 52)
- Percentage of participants with good European League Against Rheumatism (EULAR) response(Up to Week 52)
- Percentage of participants with good or moderate EULAR response(At Week 52)
- Percentage of participants achieving ACR/EULAR remission(At Week 52)
- Percentage of participants achieving Simplified Disease Activity Index (SDAI) remission (SDAI score ≤ 3.3)(Up to Week 52)
- Change from baseline in SDAI score(From baseline (Week 0) to Week 52)
- Change from baseline in Physician's Global Assessment of Arthritis (PGA) (VAS)(From baseline (Week 0) to Week 52)
- Change from baseline in SGA (VAS)(From baseline (Week 0) to Week 52)
- Change from baseline in participant's assessment of pain (VAS)(From baseline (Week 0) to Week 52)
- Incidence of participant withdrawal due to the lack of efficacy(Up to Week 56)
- Change from baseline in health assessment questionnaire-disability index (HAQ-DI) score(From baseline (Week 0) to Week 52)
- Change from baseline in Short Form Health Survey - 36 questions, version 2 (SF-36v2)® score(From baseline (Week 0) to Week 52)
- Change from baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) score(From baseline (Week 0) to Week 52)
- Pharmacokinetics (PK) of ASP015K in plasma: post-dose concentration(2 hours post-dose at either Week 4 or Week 8)
- PK of ASP015K in plasma: trough concentration (Ctrough)(Up to Week 52)
- Safety assessed by incidence of adverse events (AEs)(Up to Week 56)
- Number of participants with vital sign abnormalities and/or AEs(Up to Week 56)
- Number of participants with body weight abnormalities and/or AEs(Up to Week 56)
- Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs(Up to Week 52)
- Number of participants with central ECG abnormalities and/or AEs(Up to Week 8)
- Number of participants with chest radiography abnormalities and/or AEs(Up to Week 52)
研究者
研究点 (43)
Loading locations...
相似试验
已完成
3 期
A Study to Evaluate Efficacy and Safety of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to Methotrexate (MTX) TreatmentRheumatoid ArthritisNCT02305849Astellas Pharma Inc519
已完成
3 期
A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDsRheumatoid ArthritisNCT02308163Astellas Pharma Inc509
已完成
2 期
A Study to Evaluate the Efficacy and Safety of ASP015K in Moderate to Severe Rheumatoid Arthritis SubjectsArthritis, RheumatoidNCT01649999Astellas Pharma Inc281
已完成
2 期
Efficacy and Safety Study of TAS5315 Compared With Placebo in Participants With Rheumatoid Arthritis.Rheumatoid ArthritisNCT03605251Taiho Pharmaceutical Co., Ltd.91
已完成
3 期
A Study to Evaluate a Therapeutic Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seropositive Recipients Undergoing Allogeneic, Hematopoietic Cell Transplant (HCT)Cytomegalovirus (CMV)-Positive RecipientsAllogeneic, Hematopoietic Cell Transplant (HCT)NCT01877655Astellas Pharma Global Development, Inc.514