A Study to Evaluate Safety and Efficacy of ASP015K in Patients With Rheumatoid Arthritis (RA) Who Had an Inadequate Response to DMARDs

Phase 3

Completed

Conditions: Rheumatoid Arthritis

Interventions: Drug: Placebo
Drug: Peficitinib
Biological: Etanercept

Registration Number: NCT02308163

Lead Sponsor: Astellas Pharma Inc

Brief 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

Detailed Description: 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).

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 509

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Participants were assigned to receive placebo to peficitinib once a day until week 12.
Peficitinib 100 mg	Peficitinib	Participants were assigned to receive peficitinib 100 mg/day for 52 weeks.
Etanercept	Etanercept	Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
Peficitinib 150 mg	Peficitinib	Participants were assigned to receive peficitinib 150 mg/day for 52 weeks.

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
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	The ACR50 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 50% reduction compared with baseline. 2. SJC : ≥ 50% reduction compared with baseline. 3. ≥ 50% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
Change From Baseline in Swollen Joint Count (SJC) (66 Joints) at Week 12	Baseline and Week 12/ET	The following 66 joints subjects to assessment were examined for swollen joints and the location was confirmed. Higher SJC66 indicated greater disease activity. Temporomandibular joints (2), sternoclavicular joints (2), acromioclavicular joints (2), shoulder joints (2), elbow joints (2), wrist joints (2), distal interphalangeal joints (8), proximal interphalangeal joints of both hands (10), metacarpophalangeal joints (10), knee joints (2), ankle joints (2), tarsal bones (2), metatarsophalangeal joints (10), interphalangeal joint joints of toes (2), proximal interphalangeal joints of both feet (8).
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	DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.
Percentage of Participants Achieving DAS28-ESR <= 3.2 at Week 12	Week 12/ET	DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.
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	DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.
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	Higher ESR indicates greater disease activity.
Percentage of Participants With an American College of Rheumatology 50% (ACR50)-CRP Response at Week 12	Baseline and Week 12/ET	The ACR50 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 50% reduction compared with baseline. 2. SJC : ≥ 50% reduction compared with baseline. 3. ≥ 50% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
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	DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. Higher DAS28 score indicated greater disease activity.
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	The following 68 joints subjects to assessment were examined for tender joints and the location was confirmed. Higher TJC68 indicated greater disease activity. Temporomandibular joints (2), sternoclavicular joints (2), acromioclavicular joints (2), shoulder joints (2), elbow joints (2), wrist joints (2), distal interphalangeal joints (8), proximal interphalangeal joints of both hands (10), metacarpophalangeal joints (10), hip joints (2), knee joints (2), ankle joints (2), tarsal bones (2), metatarsophalangeal joints (10), interphalangeal joint joints of toes (2), proximal interphalangeal joints of both feet (8).
Percentage of Participants Achieving DAS28-CRP < 2.6 at Week 12	Baseline and Week 12/ET	DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.
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	The ACR70 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 70% reduction compared with baseline. 2. SJC : ≥ 70% reduction compared with baseline. 3. ≥ 70% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
Change From Baseline in Disease Activity Score (DAS) 28-CRP at Week 12	Baseline and Week 12/ET	DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. Higher DAS28 score indicated greater disease activity.
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	DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. Higher DAS28 score indicated greater disease activity.
Change From Baseline in TJC (68 Joints) at Week 12	Baseline and Week 12/ET	The following 68 joints subjects to assessment were examined for tender joints and the location was confirmed. Higher TJC68 indicated greater disease activity. Temporomandibular joints (2), sternoclavicular joints (2), acromioclavicular joints (2), shoulder joints (2), elbow joints (2), wrist joints (2), distal interphalangeal joints (8), proximal interphalangeal joints of both hands (10), metacarpophalangeal joints (10), hip joints (2), knee joints (2), ankle joints (2), tarsal bones (2), metatarsophalangeal joints (10), interphalangeal joint joints of toes (2), proximal interphalangeal joints of both feet (8).
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	The ACR20 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 20% reduction compared with baseline. 2. SJC : ≥ 20% reduction compared with baseline. 3. ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
Percentage of Participants With an American College of Rheumatology 70% (ACR70)-CRP Response at Week 12	Baseline and Week 12/ET	The ACR70 response required that all criteria from (1) to (3) below be met. 1. TJC : ≥ 70% reduction compared with baseline. 2. SJC : ≥ 70% reduction compared with baseline. 3. ≥ 70% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (ESR) at Week 12	Baseline and Week 12/ET	DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. Higher DAS28 score indicated greater disease activity.
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	The following 66 joints subjects to assessment were examined for swollen joints and the location was confirmed. Higher SJC66 indicated greater disease activity. Temporomandibular joints (2), sternoclavicular joints (2), acromioclavicular joints (2), shoulder joints (2), elbow joints (2), wrist joints (2), distal interphalangeal joints (8), proximal interphalangeal joints of both hands (10), metacarpophalangeal joints (10), knee joints (2), ankle joints (2), tarsal bones (2), metatarsophalangeal joints (10), interphalangeal joint joints of toes (2), proximal interphalangeal joints of both feet (8).
Percentage of Participants Achieving DAS28-ESR < 2.6 at Week 12	Week 12/ET	DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.
Change From Baseline in CRP at Week 12	Baseline and Week 12/ET	Higher CRP indicates greater disease activity.
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	Higher CRP indicates greater disease activity.
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	Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.
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	DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.70 ln ESR + 0.014 × SGA. DAS28-ESR scores range from 0 to approximately 10. If the DAS28 score was less than 2.6, the participant was considered to be in DAS28 remission.
Percentage of Participants Achieving DAS28-CRP <= 3.2 at Week 12	Week 12/ET	DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.
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	DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to below description. DAS28 = 0.56√(TJC) + 0.28√(SJC) + 0.36 ln (CRP + 1) + 0.014 × SGA + 0.96. DAS28-CRP scores range from 0.96 to approximately 10. DAS28 score of less than or equal to 3.2 was considered to be low disease activity.
Change From Baseline in ESR at Week 12	Baseline and Week 12/ET	Higher ESR indicates greater disease activity.
Percentage of Participants With a European League Against Rheumatism (EULAR) Good Response Using DAS28-CRP at Week 12	Week 12/ET	Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.
Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR at Week 12	Week 12/ET	Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.
Percentage of Participants With a Good EULAR Response Using DAS28-ESR at Week 12	Week 12/ET	Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.
Percentage of Participants Achieving ACR / EULAR Remission at Week 12	Week 12/ET	ACR/EULAR Remission was defined as TJC (68 joints) ≤ 1, SJC (66 joints) ≤ 1, CRP ≤ 1 mg/dL, and subject's global assessment of arthritis ≤ 1 cm (on a visual analog scale (VAS) of 0 - 100 mm). Statistical analysis of treatment difference vs placebo was not estimable for either peficitinib 100 mg or peficitinib 150 mg reporting groups.
Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP at Week 12	Week 12/ET	Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.
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	Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.
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	Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline \> 1.2.
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	Good and moderate response was defined as DAS28 after treatment ≤ 5.1 and improvement from baseline \> 0.6, or DAS28 after treatment \> 5.1 and improvement from baseline \> 1.2.
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	ACR/EULAR Remission was defined as TJC (68 joints) ≤ 1, SJC (66 joints) ≤ 1, CRP ≤ 1 mg/dL, and subject's global assessment of arthritis ≤ 1 cm (on a VAS of 0 - 100 mm).
Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Remission at Week 12	Week 12/ET	SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to below description. SDAI = TJC + SJC + SGA + PGA + CRP. SDAI Remission was defined as SDAI score ≤ 3.3. Statistical analysis of treatment difference vs placebo was not estimable for either peficitinib 100 mg or peficitinib 150 mg reporting groups.
Percentage of Participants Achieving SDAI Remission Through Week 52	Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52	SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to below description. SDAI = TJC + SJC + SGA + PGA + CRP. SDAI Remission was defined as SDAI score ≤ 3.3.
Change From Baseline in SDAI Score at Week 12	Baseline and Week 12/ET	SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to below description. SDAI = TJC + SJC + SGA + PGA + CRP. The SDAI score ranges from 0 to approximately 86. Higher SDAI indicates greater disease activity.
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	SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to below description. SDAI = TJC + SJC + SGA + PGA + CRP. The SDAI score ranges from 0 to approximately 86. Higher SDAI indicates greater disease activity.
Change From Baseline in CDAI Score at Week 12	Baseline and Week 12/ET	CDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, and calculated according to below description. CDAI = TJC + SJC + SGA + PGA. The CDAI score ranges from 0 to approximately 76. Higher CDAI indicates greater disease activity.
Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Score <= 2.8 at Week 12	Week 12/ET	CDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, and calculated according to below description. CDAI = TJC + SJC + SGA + PGA. CDAI. Remission was defined as CDAI score ≤ 2.8. Statistical analysis of treatment difference vs placebo was not estimable for either peficitinib 100 mg or peficitinib 150 mg reporting groups.
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	CDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, and calculated according to below description. CDAI = TJC + SJC + SGA + PGA. CDAI. Remission was defined as CDAI score ≤ 2.8.
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	CDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, and calculated according to below description. CDAI = TJC + SJC + SGA + PGA. The CDAI score ranges from 0 to approximately 76. Higher CDAI indicates greater disease activity.
Change From Baseline in Physician's Global Assessment of Arthritis (PGA) at Week 12	Baseline and Week 12/ET	The investigator assessed the participants' disease activity on a VAS of 0-100 mm on the physician assessment table. Higher PGA (100 mm VAS) scores indicate greater activity impairment.
Change From Baseline in Subject's Assessment of Pain at Week 12	Baseline and Week 12/ET	The participant assessed his/her own pain severity on a VAS from 0-100 mm on the questionnaire form. Higher SGA of pain (100 mm VAS) scores indicate greater activity pain.
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	The participant assessed his/her own pain severity on a VAS from 0-100 mm on the questionnaire form. Higher SGA of pain (100 mm VAS) scores indicate greater activity pain.
Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12	Baseline and Week 12/ET	The HAQ-DI (range 0 - 3) was composed of 20 items in 8 categories (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities). Each category has at least two questions. Within each category, participants reported the amount of difficulty they have in performing the specific question items. Higher HAQ-DI score indicates greater disease activity.
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	The HAQ-DI (range 0 - 3) was composed of 20 items in 8 categories (Dressing and Grooming, Arising, Eating, Walking, Hygiene, Reach, Grip, and Activities). Each category has at least two questions. Within each category, participants reported the amount of difficulty they have in performing the specific question items. Higher HAQ-DI score indicates greater disease activity.
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	The SF-36v2 was scored for the 8 subscales (each range: 0-100 scale): 1. physical functioning, 2. role physical, 3. bodily pain, 4. general health, 5. vitality, 6. social functioning, 7. role-emotional, and 8. mental health. Physical Component Summary Score, Mental Component Summary Score and Roll/Social Component Summary Score were calculated based on the 2007 General Japanese Population Means and Standard Deviations and coefficient. Component summary measures had means of 50 in 2007 General Japanese Population and deviation was expressed by the scale of 10. Higher score indicated better health state.
Change From Baseline in SF-36v2 Physical Component Summary Score Through Week 52	Baseline and Week 4, 8, 12, 28, and 52	The SF-36v2 was scored for the 8 subscales (each range: 0-100 scale): 1. physical functioning, 2. role physical, 3. bodily pain, 4. general health, 5. vitality, 6. social functioning, 7. role-emotional, and 8. mental health. Physical Component Summary Score, Mental Component Summary Score and Roll/Social Component Summary Score were calculated based on the 2007 General Japanese Population Means and Standard Deviations and coefficient. Component summary measures had means of 50 in 2007 General Japanese Population and deviation was expressed by the scale of 10. Higher score indicated better health state.
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	The investigator assessed the participants' disease activity on a VAS of 0-100 mm on the physician assessment table. Higher PGA (100 mm VAS) scores indicate greater activity impairment.
Change From Baseline in Subject's SGA at Week 12	Baseline and Week 12/ET	The participant assessed his/her own disease activity on a VAS of 0-100 mm on the questionnaire form. Higher SGA (100 mm VAS) scores indicate greater activity impairment.
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	The participant assessed his/her own disease activity on a VAS of 0-100 mm on the questionnaire form. Higher SGA (100 mm VAS) scores indicate greater activity impairment.
Number of Participants Who Withdrew Due to Lack of Efficacy	Up to week 12	The number of participants who withdrew due to lack of efficacy up to week 12 was calculated.
Change From Baseline in SF-36v2 Mental Component Summary Score at Week 12	Baseline and Week 12/ET	The SF-36v2 was scored for the 8 subscales (each range: 0-100 scale): 1. physical functioning, 2. role physical, 3. bodily pain, 4. general health, 5. vitality, 6. social functioning, 7. role-emotional, and 8. mental health. Physical Component Summary Score, Mental Component Summary Score and Roll/Social Component Summary Score were calculated based on the 2007 General Japanese Population Means and Standard Deviations and coefficient. Component summary measures had means of 50 in 2007 General Japanese Population and deviation was expressed by the scale of 10. Higher score indicated better health state.
Change From Baseline in SF-36v2 Role/Social Component Summary Score Through Week 52	Baseline and Week 4, 8, 12, 28, and 52	The SF-36v2 was scored for the 8 subscales (each range: 0-100 scale): 1. physical functioning, 2. role physical, 3. bodily pain, 4. general health, 5. vitality, 6. social functioning, 7. role-emotional, and 8. mental health. Physical Component Summary Score, Mental Component Summary Score and Roll/Social Component Summary Score were calculated based on the 2007 General Japanese Population Means and Standard Deviations and coefficient. Component summary measures had means of 50 in 2007 General Japanese Population and deviation was expressed by the scale of 10. Higher score indicated better health state.
Change From Baseline in WPAI Percent Overall Work Impairment Through Week 52	Baseline and Week 4, 8, 12, 28, and 52	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent overall work impairment due to problem: Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4))x(Q5/10)\].
Number of Participants With Adverse Events During the First 12 Weeks	Week 0 to Week 12	Treatment-emergent adverse events (TEAEs) were defined as any AE that started or worsened in severity after initial dose of study drug or reference drug through week 52 or withdrawal. TEAEs were summarized using MedDRA (Version 11.1) by System Organ Class (SOC) and Preferred Term (PT). Participants reporting more than 1 AE for a given MedDRA PT were counted only once for that term. Participants reporting more than 1 AE within a SOC were counted only once for the SOC total. Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade: grade 3 = severe or medically significant, grade 4 = life threatening, grade 5 = death related to AE.
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	Treatment-emergent adverse events (TEAEs) were defined as any AE that started or worsened in severity after initial dose of study drug or reference drug through week 52 or withdrawal. TEAEs were summarized using MedDRA (Version 11.1) by SOC and PT. Participants reporting more than 1 AE for a given MedDRA PT were counted only once for that term. Participants reporting more than 1 AE within a SOC were counted only once for the SOC total. Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade: grade 3 = severe or medically significant, grade 4 = life threatening, grade 5 = death related to AE.
Change From Baseline in SF-36v2 Mental Component Summary Score Through Week 52	Baseline and Week 4, 8, 12, 28, and 52	The SF-36v2 was scored for the 8 subscales (each range: 0-100 scale): 1. physical functioning, 2. role physical, 3. bodily pain, 4. general health, 5. vitality, 6. social functioning, 7. role-emotional, and 8. mental health. Physical Component Summary Score, Mental Component Summary Score and Roll/Social Component Summary Score were calculated based on the 2007 General Japanese Population Means and Standard Deviations and coefficient. Component summary measures had means of 50 in 2007 General Japanese Population and deviation was expressed by the scale of 10. Higher score indicated better health state.
Change From Baseline in SF-36v2 Role/Social Component Summary Score at Week 12	Baseline and Week 12/ET	The SF-36v2 was scored for the 8 subscales (each range: 0-100 scale): 1. physical functioning, 2. role physical, 3. bodily pain, 4. general health, 5. vitality, 6. social functioning, 7. role-emotional, and 8. mental health. Physical Component Summary Score, Mental Component Summary Score and Roll/Social Component Summary Score were calculated based on the 2007 General Japanese Population Means and Standard Deviations and coefficient. Component summary measures had means of 50 in 2007 General Japanese Population and deviation was expressed by the scale of 10. Higher score indicated better health state.
Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Percent Work Time Missed at Week 12	Baseline and Week 12/ET	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent work time missed due to problem: Q2/(Q2+Q4).
Change From Baseline in WPAI Percent Work Time Missed Through Week 52	Baseline and Week 4, 8, 12, 28, and 52	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent work time missed due to problem: Q2/(Q2+Q4).
Change From Baseline in WPAI Percent Impairment While Working at Week 12	Baseline and Week 12/ET	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent impairment while working due to problem: Q5/10.
Change From Baseline in WPAI Percent Activity Impairment at Week 12	Baseline and Week 12/ET	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent activity impairment due to problem: Q6/10.
Change From Baseline in WPAI Percent Activity Impairment Through Week 52	Baseline and Week 4, 8, 12, 28, and 52	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent activity impairment due to problem: Q6/10.
Change From Baseline in WPAI Percent Impairment While Working Through Week 52	Baseline and Week 4, 8, 12, 28, and 52	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent impairment while working due to problem: Q5/10.
Change From Baseline in Percent Overall Work Impairment at Week 12	Baseline and Week 12/ET	WPAI consisted of 6 questions (Q1=Employment status; Q2=Hours absent from work due to the rheumatoid arthritis; Q3=Hours absent from work due to other reasons; Q4=Hours actually worked; Q5=Impact of the rheumatoid arthritis on productivity while working; Q6=Impact of the rheumatoid arthritis on productivity while doing regular daily activities other than work) and a 1-week recall period. Higher WPAI scores indicate greater activity impairment. Multiply scores by 100 to express in percentages. Percent overall work impairment due to problem: Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4))x(Q5/10)\].

Trial Locations

Locations (153): JP00099
🇯🇵
Chiyoda, Tokyo, Japan
JP00018
🇯🇵
Fukuoka, Japan
JP00078
🇯🇵
Kawachinagano, Osaka, Japan
JP00090
🇯🇵
Hakodate, Hokkaido, Japan
JP00101
🇯🇵
Omura, Nagasaki, Japan
JP00103
🇯🇵
Omura, Nagasaki, Japan
JP00092
🇯🇵
Kobe, Hyogo, Japan
JP00120
🇯🇵
Iizuka, Fukuoka, Japan
JP00040
🇯🇵
Kitakyushu, Fukuoka, Japan
JP00119
🇯🇵
Kitakyushu, Fukuoka, Japan
JP00097
🇯🇵
Kurume, Fukuoka, Japan
JP00031
🇯🇵
Sapporo, Hokkaido, Japan
JP00041
🇯🇵
Kato, Hyogo, Japan
JP00162
🇯🇵
Isehaya, Nagasaki, Japan
JP00153
🇯🇵
Sasebo, Nagasaki, Japan
JP00093
🇯🇵
Kochi, Japan
JP00138
🇯🇵
Yotsukaido, Chiba, Japan
JP00026
🇯🇵
Asahikawa, Hokkaido, Japan
JP00142
🇯🇵
Chuo, Tokyo, Japan
JP00010
🇯🇵
Takaoka, Toyama, Japan
JP00147
🇯🇵
Nagasaki, Japan
JP00113
🇯🇵
Kakogawa, Hyogo, Japan
JP00042
🇯🇵
Kobe, Hyogo, Japan
JP00054
🇯🇵
Mito, Ibaraki, Japan
JP00046
🇯🇵
Kumamoto, Japan
JP00118
🇯🇵
Okayama, Japan
JP00036
🇯🇵
Sendai, Miyagi, Japan
JP00144
🇯🇵
Shibata, Niigata, Japan
JP00077
🇯🇵
Kanuma, Tochigi, Japan
JP00122
🇯🇵
Miyazaki, Japan
JP00074
🇯🇵
Kagoshima, Japan
JP00066
🇯🇵
Okazaki, Aichi, Japan
JP00109
🇯🇵
Nagoya, Aichi, Japan
JP00130
🇯🇵
Nagoya, Aichi, Japan
JP00037
🇯🇵
Nagoya, Aichi, Japan
JP00140
🇯🇵
Toyoake, Aichi, Japan
JP00108
🇯🇵
Toyohashi, Aichi, Japan
JP00156
🇯🇵
Toyota, Aichi, Japan
JP00068
🇯🇵
Yatomi, Aichi, Japan
JP00102
🇯🇵
Kamagaya, Chiba, Japan
JP00127
🇯🇵
Matsudo, Chiba, Japan
JP00115
🇯🇵
Narashino, Chiba, Japan
JP00033
🇯🇵
Takasaki, Gunma, Japan
JP00106
🇯🇵
Kurume, Fukuoka, Japan
JP00071
🇯🇵
Kurume, Fukuoka, Japan
JP00002
🇯🇵
Sapporo, Hokkaido, Japan
JP00003
🇯🇵
Sapporo, Hokkaido, Japan
JP00038
🇯🇵
Sapporo, Hokkaido, Japan
JP00114
🇯🇵
Sapporo, Hokkaido, Japan
JP00158
🇯🇵
Sapporo, Hokkaido, Japan
JP00125
🇯🇵
Kushiro, Hokkaido, Japan
JP00001
🇯🇵
Sapporo, Hokkaido, Japan
JP00056
🇯🇵
Akashi, Hyogo, Japan
JP00069
🇯🇵
Himeji, Hyogo, Japan
JP00049
🇯🇵
Morioka, Iwate, Japan
JP00154
🇯🇵
Kobe, Hyogo, Japan
JP00117
🇯🇵
Nishinomiya, Hyogo, Japan
JP00107
🇯🇵
Hitachi, Ibaraki, Japan
JP00073
🇯🇵
Koga, Ibaraki, Japan
JP00048
🇯🇵
Kawasaki, Kanagawa, Japan
JP00084
🇯🇵
Isehara, Kanagawa, Japan
JP00058
🇯🇵
Kawasaki, Kanagawa, Japan
JP00141
🇯🇵
Sagamihara, Kanagawa, Japan
JP00096
🇯🇵
Yokohama, Kanagawa, Japan
JP00128
🇯🇵
Yokosuka, Kanagawa, Japan
JP00004
🇯🇵
Sendai, Miyagi, Japan
JP00057
🇯🇵
Tamana, Kumamoto, Japan
JP00027
🇯🇵
Sendai, Miyagi, Japan
JP00105
🇯🇵
Sendai, Miyagi, Japan
JP00151
🇯🇵
Sendai, Miyagi, Japan
JP00050
🇯🇵
Hyuga, Miyazaki, Japan
JP00064
🇯🇵
Beppu, Oita, Japan
JP00051
🇯🇵
Setouchi, Okayama, Japan
JP00094
🇯🇵
Kashihara, Nara, Japan
JP00134
🇯🇵
Higashiosaka, Osaka, Japan
JP00011
🇯🇵
Hannan, Osaka, Japan
JP00137
🇯🇵
Sakai, Osaka, Japan
JP00070
🇯🇵
Suita, Osaka, Japan
JP00086
🇯🇵
Suita, Osaka, Japan
JP00075
🇯🇵
Ureshino, Saga, Japan
JP00061
🇯🇵
Toyonaka, Osaka, Japan
JP00126
🇯🇵
Gyoda, Saitama, Japan
JP00060
🇯🇵
Kawagoe, Saitama, Japan
JP00052
🇯🇵
Sayama, Saitama, Japan
JP00082
🇯🇵
Iruma, Saitama, Japan
JP00161
🇯🇵
Kawagoe, Saitama, Japan
JP00008
🇯🇵
Tokorozawa, Saitama, Japan
JP00133
🇯🇵
Kakegawa, Shizuoka, Japan
JP00043
🇯🇵
Bunkyo, Tokyo, Japan
JP00095
🇯🇵
Chiyoda, Tokyo, Japan
JP00152
🇯🇵
Bunkyo, Tokyo, Japan
JP00053
🇯🇵
Kiyose, Tokyo, Japan
JP00072
🇯🇵
Meguro, Tokyo, Japan
JP00148
🇯🇵
Ota, Tokyo, Japan
JP00083
🇯🇵
Meguro, Tokyo, Japan
JP00100
🇯🇵
Setagaya, Tokyo, Japan
JP00047
🇯🇵
Shunan, Yamaguchi, Japan
JP00032
🇯🇵
Shinjuku, Tokyo, Japan
JP00104
🇯🇵
Shimonoseki, Yamaguchi, Japan
JP00155
🇯🇵
Nishimuro, Wakayama, Japan
JP00076
🇯🇵
Fukuoka, Japan
JP00067
🇯🇵
Fukuoka, Japan
JP00035
🇯🇵
Fukuoka, Japan
JP00059
🇯🇵
Fukuoka, Japan
JP00013
🇯🇵
Hiroshima, Japan
JP00131
🇯🇵
Fukuoka, Japan
JP00164
🇯🇵
Fukuoka, Japan
JP00014
🇯🇵
Hiroshima, Japan
JP00023
🇯🇵
Miyagi, Japan
JP00016
🇯🇵
Hiroshima, Japan
JP00159
🇯🇵
Kyoto, Japan
JP00098
🇯🇵
Nagasaki, Japan
JP00017
🇯🇵
Oita, Japan
JP00055
🇯🇵
Hiroshima, Japan
JP00065
🇯🇵
Kagoshima, Japan
JP00123
🇯🇵
Kyoto, Japan
JP00112
🇯🇵
Nagasaki, Japan
JP00157
🇯🇵
Osaka, Japan
TW00705
🇨🇳
Taichung, Taiwan
TW00703
🇨🇳
Taoyuan, Taiwan
KR00504
🇰🇷
Daegu, Korea, Republic of
KR00510
🇰🇷
Daegu, Korea, Republic of
JP00089
🇯🇵
Shizuoka, Japan
JP00135
🇯🇵
Shizuoka, Japan
JP00139
🇯🇵
Toyama, Japan
KR00507
🇰🇷
Suwon, Korea, Republic of
TW00701
🇨🇳
Taipei, Taiwan
KR00511
🇰🇷
Seoul, Korea, Republic of
KR00505
🇰🇷
Gwangju, Korea, Republic of
JP00025
🇯🇵
Nagaoka, Niigata, Japan
JP00007
🇯🇵
Hiki, Saitama, Japan
JP00062
🇯🇵
Kawaguchi, Saitama, Japan
JP00024
🇯🇵
Bunkyo, Tokyo, Japan
JP00149
🇯🇵
Bunkyo, Tokyo, Japan
JP00063
🇯🇵
Hachioji, Tokyo, Japan
JP00020
🇯🇵
Fukuoka, Japan
JP00015
🇯🇵
Hiroshima, Japan
JP00022
🇯🇵
Kumamoto, Japan
JP00080
🇯🇵
Nagano, Japan
JP00150
🇯🇵
Osaka, Japan
KR00509
🇰🇷
Seoul, Korea, Republic of
KR00508
🇰🇷
Jeonju, Korea, Republic of
KR00501
🇰🇷
Seoul, Korea, Republic of
TW00710
🇨🇳
Taichung, Taiwan
KR00503
🇰🇷
Seoul, Korea, Republic of
KR00506
🇰🇷
Incheon, Korea, Republic of
KR00502
🇰🇷
Seoul, Korea, Republic of
TW00712
🇨🇳
Tainan, Taiwan
TW00708
🇨🇳
Kaohsiung, Taiwan
TW00709
🇨🇳
Kaohsiung, Taiwan
TW00704
🇨🇳
Taichung, Taiwan
TW00702
🇨🇳
Taipei, Taiwan
TW00711
🇨🇳
Taipei, Taiwan