A Study to Evaluate Efficacy and Safety of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to Methotrexate (MTX) Treatment
Condition: Rheumatoid Arthritis
MeSH terms: Arthritis; Arthritis, Rheumatoid
Intervention: Peficitinib; Placebo; Methotrexate
Intervention description: oral tablet; oral tablet; Oral tablet/capsule
Intervention MeSH terms: Methotrexate; 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: 519.0
Sex: All
Minimum age: 20 Years
Healthy volunteers: No
Keywords: ASP015K; Rheumatoid Arthritis

Summary:

      The objective of this study was to verify the efficacy of ASP015K versus placebo
      administrated in combination with methotrexate (MTX) over placebo in terms of efficacy in
      participants with rheumatoid arthritis (RA) who had an inadequate response to MTX
    

Eligibility criteria:

        Inclusion Criteria:

          -  Subject has RA of < 10 years duration at baseline that was 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
                  with a local action), 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 (latex agglutination test) of ≥ 1.00 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 responders to MTX which was continuously administered for at least 90 days
             prior to screening and MTX ≥ 8 mg/week for at least 28 days prior to baseline.
             However, inadequate responder to MTX < 8 mg/week is eligible if intolerance precludes
             dose increase and defined as MTX-IR

          -  Subject is able to continue stable dose of MTX (a maximum of 16 mg/week) from at least
             28 days prior to screening until the end of treatment

          -  Subject has bone erosion at the joint (as evidenced by x-rays of hands and feet)
             assessed in mTSS and any of the following apply at screening. Bone erosion may be
             evidenced by x-rays within 90 days prior to baseline.

               -  Positive anti-CCP antibody: ≥ 4.5 U/mL

               -  Positive rheumatoid factor: > 15 IU/mL

        Exclusion Criteria:

          -  Subject has received a biologic DMARD within the specified period

          -  Inadequate responders to biologic DMARD 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 ≥ 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
                  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 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.