A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Peficitinib; Placebo; Etanercept
Intervention description: oral; oral; subcutaneous injection
Intervention MeSH terms: Etanercept; Peficitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 509.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: Rheumatoid Arthritis; ASP015K

Summary:

      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
    

Eligibility criteria:

        Inclusion Criteria:

          -  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

        Exclusion Criteria:

          -  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.