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

Sponsor
Astellas Pharma Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT02308163
Collaborator
(none)
509
Enrollment
153
Locations
4
Arms
39.5
Actual Duration (Months)
3.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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

Condition or Disease Intervention/Treatment Phase
Phase 3

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).

Study Design

Study Type:
Interventional
Actual Enrollment :
509 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Aug 8, 2014
Actual Primary Completion Date :
Jan 23, 2017
Actual Study Completion Date :
Nov 22, 2017

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Placebo

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

Drug: Placebo
oral
Experimental: Peficitinib 100 mg

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

Drug: Peficitinib
oral
Other Names:
  • ASP015K

    		•
    Experimental: Peficitinib 150 mg

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

    Drug: Peficitinib
    oral
    Other Names:
  • ASP015K

    		•
    Active Comparator: Etanercept

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

    Biological: Etanercept
    subcutaneous injection

    Outcome Measures

    Primary Outcome Measures

    1. 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. Tender joint count (TJC) : ≥ 20% reduction compared with baseline. Swollen joint count (SJC) : ≥ 20% reduction compared with baseline. ≥ 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

    1. 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. TJC : ≥ 20% reduction compared with baseline. SJC : ≥ 20% reduction compared with baseline. ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

    2. 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. TJC : ≥ 50% reduction compared with baseline. SJC : ≥ 50% reduction compared with baseline. ≥ 50% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

    3. 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. TJC : ≥ 50% reduction compared with baseline. SJC : ≥ 50% reduction compared with baseline. ≥ 50% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

    4. 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. TJC : ≥ 70% reduction compared with baseline. SJC : ≥ 70% reduction compared with baseline. ≥ 70% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

    5. 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. TJC : ≥ 70% reduction compared with baseline. SJC : ≥ 70% reduction compared with baseline. ≥ 70% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.

    6. 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.

    7. 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.

    8. 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.

    9. 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.

    10. 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).

    11. 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).

    12. 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).

    13. 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).

    14. 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.

    15. 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.

    16. 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.

    17. 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.

    18. 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.

    19. 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.

    20. 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.

    21. 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.

    22. Change From Baseline in CRP at Week 12 [Baseline and Week 12/ET]

      Higher CRP indicates greater disease activity.

    23. 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.

    24. Change From Baseline in ESR at Week 12 [Baseline and Week 12/ET]

      Higher ESR indicates greater disease activity.

    25. 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.

    26. 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.

    27. 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.

    28. 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.

    29. 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.

    30. 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.

    31. 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.

    32. 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.

    33. 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.

    34. 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.

    35. 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).

    36. 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.

    37. 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.

    38. 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.

    39. 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.

    40. 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.

    41. 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.

    42. 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.

    43. 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.

    44. 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.

    45. 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.

    46. 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.

    47. 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.

    48. 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.

    49. 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.

    50. 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.

    51. 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.

    52. 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.

    53. 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.

    54. 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.

    55. 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.

    56. 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.

    57. 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.

    58. 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.

    59. 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).

    60. 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).

    61. 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.

    62. 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.

    63. 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)].

    64. 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)].

    65. 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.

    66. 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.

    67. 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.

    68. 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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    20 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 JP00037 Nagoya Aichi Japan
    2 JP00109 Nagoya Aichi Japan
    3 JP00130 Nagoya Aichi Japan
    4 JP00066 Okazaki Aichi Japan
    5 JP00140 Toyoake Aichi Japan
    6 JP00108 Toyohashi Aichi Japan
    7 JP00156 Toyota Aichi Japan
    8 JP00068 Yatomi Aichi Japan
    9 JP00102 Kamagaya Chiba Japan
    10 JP00127 Matsudo Chiba Japan
    11 JP00115 Narashino Chiba Japan
    12 JP00138 Yotsukaido Chiba Japan
    13 JP00120 Iizuka Fukuoka Japan
    14 JP00040 Kitakyushu Fukuoka Japan
    15 JP00119 Kitakyushu Fukuoka Japan
    16 JP00071 Kurume Fukuoka Japan
    17 JP00097 Kurume Fukuoka Japan
    18 JP00106 Kurume Fukuoka Japan
    19 JP00033 Takasaki Gunma Japan
    20 JP00026 Asahikawa Hokkaido Japan
    21 JP00090 Hakodate Hokkaido Japan
    22 JP00125 Kushiro Hokkaido Japan
    23 JP00001 Sapporo Hokkaido Japan
    24 JP00002 Sapporo Hokkaido Japan
    25 JP00003 Sapporo Hokkaido Japan
    26 JP00031 Sapporo Hokkaido Japan
    27 JP00038 Sapporo Hokkaido Japan
    28 JP00114 Sapporo Hokkaido Japan
    29 JP00158 Sapporo Hokkaido Japan
    30 JP00056 Akashi Hyogo Japan
    31 JP00069 Himeji Hyogo Japan
    32 JP00113 Kakogawa Hyogo Japan
    33 JP00041 Kato Hyogo Japan
    34 JP00042 Kobe Hyogo Japan
    35 JP00092 Kobe Hyogo Japan
    36 JP00154 Kobe Hyogo Japan
    37 JP00117 Nishinomiya Hyogo Japan
    38 JP00107 Hitachi Ibaraki Japan
    39 JP00073 Koga Ibaraki Japan
    40 JP00054 Mito Ibaraki Japan
    41 JP00049 Morioka Iwate Japan
    42 JP00084 Isehara Kanagawa Japan
    43 JP00048 Kawasaki Kanagawa Japan
    44 JP00058 Kawasaki Kanagawa Japan
    45 JP00141 Sagamihara Kanagawa Japan
    46 JP00096 Yokohama Kanagawa Japan
    47 JP00128 Yokosuka Kanagawa Japan
    48 JP00057 Tamana Kumamoto Japan
    49 JP00004 Sendai Miyagi Japan
    50 JP00027 Sendai Miyagi Japan
    51 JP00036 Sendai Miyagi Japan
    52 JP00105 Sendai Miyagi Japan
    53 JP00151 Sendai Miyagi Japan
    54 JP00050 Hyuga Miyazaki Japan
    55 JP00162 Isehaya Nagasaki Japan
    56 JP00101 Omura Nagasaki Japan
    57 JP00103 Omura Nagasaki Japan
    58 JP00153 Sasebo Nagasaki Japan
    59 JP00094 Kashihara Nara Japan
    60 JP00025 Nagaoka Niigata Japan
    61 JP00144 Shibata Niigata Japan
    62 JP00064 Beppu Oita Japan
    63 JP00051 Setouchi Okayama Japan
    64 JP00011 Hannan Osaka Japan
    65 JP00134 Higashiosaka Osaka Japan
    66 JP00078 Kawachinagano Osaka Japan
    67 JP00137 Sakai Osaka Japan
    68 JP00070 Suita Osaka Japan
    69 JP00086 Suita Osaka Japan
    70 JP00061 Toyonaka Osaka Japan
    71 JP00075 Ureshino Saga Japan
    72 JP00126 Gyoda Saitama Japan
    73 JP00007 Hiki Saitama Japan
    74 JP00082 Iruma Saitama Japan
    75 JP00060 Kawagoe Saitama Japan
    76 JP00161 Kawagoe Saitama Japan
    77 JP00062 Kawaguchi Saitama Japan
    78 JP00052 Sayama Saitama Japan
    79 JP00008 Tokorozawa Saitama Japan
    80 JP00133 Kakegawa Shizuoka Japan
    81 JP00077 Kanuma Tochigi Japan
    82 JP00024 Bunkyo Tokyo Japan
    83 JP00043 Bunkyo Tokyo Japan
    84 JP00149 Bunkyo Tokyo Japan
    85 JP00152 Bunkyo Tokyo Japan
    86 JP00095 Chiyoda Tokyo Japan
    87 JP00099 Chiyoda Tokyo Japan
    88 JP00142 Chuo Tokyo Japan
    89 JP00063 Hachioji Tokyo Japan
    90 JP00053 Kiyose Tokyo Japan
    91 JP00072 Meguro Tokyo Japan
    92 JP00083 Meguro Tokyo Japan
    93 JP00148 Ota Tokyo Japan
    94 JP00100 Setagaya Tokyo Japan
    95 JP00032 Shinjuku Tokyo Japan
    96 JP00010 Takaoka Toyama Japan
    97 JP00155 Nishimuro Wakayama Japan
    98 JP00104 Shimonoseki Yamaguchi Japan
    99 JP00047 Shunan Yamaguchi Japan
    100 JP00018 Fukuoka Japan
    101 JP00020 Fukuoka Japan
    102 JP00035 Fukuoka Japan
    103 JP00059 Fukuoka Japan
    104 JP00067 Fukuoka Japan
    105 JP00076 Fukuoka Japan
    106 JP00131 Fukuoka Japan
    107 JP00164 Fukuoka Japan
    108 JP00013 Hiroshima Japan
    109 JP00014 Hiroshima Japan
    110 JP00015 Hiroshima Japan
    111 JP00016 Hiroshima Japan
    112 JP00055 Hiroshima Japan
    113 JP00065 Kagoshima Japan
    114 JP00074 Kagoshima Japan
    115 JP00093 Kochi Japan
    116 JP00022 Kumamoto Japan
    117 JP00046 Kumamoto Japan
    118 JP00123 Kyoto Japan
    119 JP00159 Kyoto Japan
    120 JP00023 Miyagi Japan
    121 JP00122 Miyazaki Japan
    122 JP00080 Nagano Japan
    123 JP00098 Nagasaki Japan
    124 JP00112 Nagasaki Japan
    125 JP00147 Nagasaki Japan
    126 JP00017 Oita Japan
    127 JP00118 Okayama Japan
    128 JP00150 Osaka Japan
    129 JP00157 Osaka Japan
    130 JP00089 Shizuoka Japan
    131 JP00135 Shizuoka Japan
    132 JP00139 Toyama Japan
    133 KR00504 Daegu Korea, Republic of
    134 KR00510 Daegu Korea, Republic of
    135 KR00505 Gwangju Korea, Republic of
    136 KR00506 Incheon Korea, Republic of
    137 KR00508 Jeonju Korea, Republic of
    138 KR00501 Seoul Korea, Republic of
    139 KR00502 Seoul Korea, Republic of
    140 KR00503 Seoul Korea, Republic of
    141 KR00509 Seoul Korea, Republic of
    142 KR00511 Seoul Korea, Republic of
    143 KR00507 Suwon Korea, Republic of
    144 TW00708 Kaohsiung Taiwan
    145 TW00709 Kaohsiung Taiwan
    146 TW00704 Taichung Taiwan
    147 TW00705 Taichung Taiwan
    148 TW00710 Taichung Taiwan
    149 TW00712 Tainan Taiwan
    150 TW00701 Taipei Taiwan
    151 TW00702 Taipei Taiwan
    152 TW00711 Taipei Taiwan
    153 TW00703 Taoyuan Taiwan

    Sponsors and Collaborators

    • Astellas Pharma Inc

    Investigators

    • Study Director: Medical Director, Astellas Pharma Inc

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Astellas Pharma Inc
    ClinicalTrials.gov Identifier:
    NCT02308163
    Other Study ID Numbers:
    • 015K-CL-RAJ3
    First Posted:
    Dec 4, 2014
    Last Update Posted:
    Mar 16, 2020
    Last Verified:
    Feb 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Keywords provided by Astellas Pharma Inc
    Rheumatoid Arthritis
    ASP015K
    Additional relevant MeSH terms:
    Arthritis
    Arthritis, Rheumatoid
    Etanercept
    Peficitinib

    Study Results

    Participant Flow

    Recruitment Details Participants with rheumatoid arthritis (RA) who had an inadequate response to disease-modifying antirheumatic drugs (DMARDs) were enrolled in 142 sites in Japan, 11 sites in Korea and 12 sites in Taiwan.
    Pre-assignment Detail Participants were randomized in a 1:1:1:2 ratio to peficitinib 100 mg, 150 mg, placebo or etanercept groups at baseline. At week 12, participants in the placebo group were switched to receive either peficitinib at a dose of 100 mg or 150 mg. The dose of peficitinib administered to the placebo group from week 12 was determined in advance randomly.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Period Title: Overall Study
    STARTED 104 102 50 52 201
    COMPLETED 73 84 36 39 167
    NOT COMPLETED 31 18 14 13 34

    Baseline Characteristics

    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept Placebo Total
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12. Total of all reporting groups
    Overall Participants 104 102 200 101 507
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    54.1
    (12.2)
    55
    (12.8)
    55.5
    (11.6)
    56.3
    (11.7)
    55.3
    (12)
    Sex: Female, Male (Count of Participants)
    Female
    77
    74%
    78
    76.5%
    138
    69%
    73
    72.3%
    366
    72.2%
    Male
    27
    26%
    24
    23.5%
    62
    31%
    28
    27.7%
    141
    27.8%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    104
    100%
    102
    100%
    200
    100%
    101
    100%
    507
    100%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    White
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Tender Joint Count (68 Joints) (tender joints) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [tender joints]
    15
    (9.4)
    15.4
    (9.5)
    14.9
    (9.3)
    16.2
    (10.7)
    15.3
    (9.6)
    Swollen Joint Count (66 Joints) (swollen joints) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [swollen joints]
    12.4
    (6.3)
    12.8
    (7.1)
    11.9
    (6.8)
    12.9
    (7.2)
    12.4
    (6.8)
    Subject's Global Assessment of Arthritis Pain (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    57.31
    (26.71)
    58.02
    (25.66)
    55.79
    (26.54)
    57.56
    (25.07)
    56.9
    (26.05)
    Subject's Global Assessment of Arthritis (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    57.54
    (24.78)
    59.52
    (25.73)
    57.52
    (26.92)
    58.99
    (25.7)
    58.22
    (25.95)
    Physician's Global Assessment of Arthritis (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    60.21
    (20.11)
    58.46
    (19.35)
    58.17
    (19.87)
    61.93
    (19.35)
    59.39
    (19.71)
    Health Assessment Questionnaire - Disability Index (HAQ-DI) (units on a scale) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [units on a scale]
    0.92
    (0.69)
    1.03
    (0.67)
    1.03
    (0.75)
    1
    (0.66)
    1
    (0.7)
    C-Reactive Protein (CRP) (mg/dL) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mg/dL]
    2.296
    (2.566)
    2.561
    (2.597)
    2.055
    (2.144)
    2.258
    (2.224)
    2.247
    (2.346)
    Erythrocyte Sedimentation Rate (ESR) (mm/h) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [mm/h]
    49.6
    (27.4)
    50.6
    (29.7)
    47.4
    (29.8)
    47.9
    (27.6)
    48.6
    (28.8)
    Prior Biologic Disease-modifying Antirheumatic Drug-inadequate Response (DMARD-IR) (Count of Participants)
    No
    95
    91.3%
    95
    93.1%
    185
    92.5%
    96
    95%
    471
    92.9%
    Yes
    9
    8.7%
    7
    6.9%
    15
    7.5%
    5
    5%
    36
    7.1%
    Concomitant DMARD at Baseline (Count of Participants)
    No
    13
    12.5%
    13
    12.7%
    24
    12%
    14
    13.9%
    64
    12.6%
    Yes
    91
    87.5%
    89
    87.3%
    176
    88%
    87
    86.1%
    443
    87.4%
    Study Region (Count of Participants)
    Japan
    85
    81.7%
    83
    81.4%
    164
    82%
    83
    82.2%
    415
    81.9%
    Korea
    11
    10.6%
    11
    10.8%
    22
    11%
    10
    9.9%
    54
    10.7%
    Taiwan
    8
    7.7%
    8
    7.8%
    14
    7%
    8
    7.9%
    38
    7.5%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With an American College of Rheumatology 20% (ACR20) C-Reactive Protein (CRP) Response at Week 12
    Description The ACR20 response required that all criteria from (1) to (3) below be met. Tender joint count (TJC) : ≥ 20% reduction compared with baseline. Swollen joint count (SJC) : ≥ 20% reduction compared with baseline. ≥ 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).
    Time Frame Baseline and Week 12/early termination (ET)

    Outcome Measure Data

    Analysis Population Description
    The analysis population consisted of the Full Analysis Set (FAS). Last observation carried forward (LOCF) was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 101 104 102 200
    Number [Percentage of Participants]
    30.7
    29.5%
    57.7
    56.6%
    74.5
    37.3%
    83.5
    82.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Closed testing procedure was used for multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.13
    Confidence Interval (2-Sided) 95%
    1.76 to 5.58
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: ACR20-CRP response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments Closed testing procedure was used for multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.59
    Confidence Interval (2-Sided) 95%
    3.56 to 12.20
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: ACR20-CRP response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    2. Secondary Outcome
    Title Percentage of Participants With an ACR20-CRP Response Through Week 52
    Description The ACR20 response required that all criteria from (1) to (3) below be met. TJC : ≥ 20% reduction compared with baseline. SJC : ≥ 20% reduction compared with baseline. ≥ 20% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    43.9
    42.2%
    45.0
    44.1%
    21.4
    10.7%
    19.1
    18.9%
    61.0
    12%
    Week 8
    51.0
    49%
    68.7
    67.4%
    38.1
    19.1%
    25.5
    25.2%
    80.5
    15.9%
    Week 12
    59.4
    57.1%
    77.2
    75.7%
    31.7
    15.9%
    34.0
    33.7%
    84.8
    16.7%
    Week 16
    64.5
    62%
    79.6
    78%
    58.5
    29.3%
    61.7
    61.1%
    86.7
    17.1%
    Week 20
    64.1
    61.6%
    81.5
    79.9%
    51.2
    25.6%
    71.7
    71%
    88.5
    17.5%
    Week 24
    63.2
    60.8%
    85.6
    83.9%
    61.5
    30.8%
    71.1
    70.4%
    90.1
    17.8%
    Week 28
    72.3
    69.5%
    87.6
    85.9%
    60.0
    30%
    67.4
    66.7%
    92.7
    18.3%
    Week 32
    76.5
    73.6%
    88.4
    86.7%
    63.9
    32%
    73.3
    72.6%
    88.1
    17.4%
    Week 36
    72.2
    69.4%
    90.7
    88.9%
    66.7
    33.4%
    76.7
    75.9%
    92.0
    18.1%
    Week 40
    73.7
    70.9%
    90.7
    88.9%
    67.6
    33.8%
    83.3
    82.5%
    92.5
    18.2%
    Week 44
    74.7
    71.8%
    88.2
    86.5%
    79.4
    39.7%
    84.6
    83.8%
    91.2
    18%
    Week 48
    74.3
    71.4%
    90.5
    88.7%
    73.5
    36.8%
    82.1
    81.3%
    90.5
    17.9%
    Week 52
    73.2
    70.4%
    90.1
    88.3%
    79.4
    39.7%
    81.6
    80.8%
    90.7
    17.9%
    End of Treatment (EOT)
    65.4
    62.9%
    84.3
    82.6%
    67.4
    33.7%
    74.5
    73.8%
    86.5
    17.1%
    3. Secondary Outcome
    Title Percentage of Participants With an American College of Rheumatology 50% (ACR50)-CRP Response at Week 12
    Description The ACR50 response required that all criteria from (1) to (3) below be met. TJC : ≥ 50% reduction compared with baseline. SJC : ≥ 50% reduction compared with baseline. ≥ 50% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 101 104 102 200
    Number [Percentage of Participants]
    8.9
    8.6%
    30.8
    30.2%
    42.2
    21.1%
    52.5
    52%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.79
    Confidence Interval (2-Sided) 95%
    2.14 to 10.75
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: ACR50-CRP response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 7.86
    Confidence Interval (2-Sided) 95%
    3.53 to 17.50
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: ACR50-CRP response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    4. Secondary Outcome
    Title Percentage of Participants With an ACR50-CRP Response Through Week 52
    Description The ACR50 response required that all criteria from (1) to (3) below be met. TJC : ≥ 50% reduction compared with baseline. SJC : ≥ 50% reduction compared with baseline. ≥ 50% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    8.2
    7.9%
    14.0
    13.7%
    4.8
    2.4%
    2.1
    2.1%
    29.5
    5.8%
    Week 8
    25.0
    24%
    35.4
    34.7%
    4.8
    2.4%
    6.4
    6.3%
    47.2
    9.3%
    Week 12
    32.3
    31.1%
    45.7
    44.8%
    7.3
    3.7%
    12.8
    12.7%
    55.0
    10.8%
    Week 16
    43.0
    41.3%
    45.2
    44.3%
    31.7
    15.9%
    25.5
    25.2%
    60.6
    12%
    Week 20
    41.3
    39.7%
    54.3
    53.2%
    22.0
    11%
    43.5
    43.1%
    66.5
    13.1%
    Week 24
    43.7
    42%
    62.2
    61%
    38.5
    19.3%
    44.4
    44%
    64.8
    12.8%
    Week 28
    44.6
    42.9%
    60.7
    59.5%
    40.0
    20%
    50.0
    49.5%
    69.5
    13.7%
    Week 32
    50.6
    48.7%
    65.1
    63.8%
    52.8
    26.4%
    44.4
    44%
    70.5
    13.9%
    Week 36
    53.2
    51.2%
    68.6
    67.3%
    47.2
    23.6%
    44.2
    43.8%
    70.3
    13.9%
    Week 40
    47.4
    45.6%
    69.8
    68.4%
    45.9
    23%
    52.4
    51.9%
    73.4
    14.5%
    Week 44
    50.7
    48.8%
    69.4
    68%
    50.0
    25%
    53.8
    53.3%
    70.2
    13.8%
    Week 48
    48.6
    46.7%
    73.8
    72.4%
    58.8
    29.4%
    69.2
    68.5%
    75.6
    14.9%
    Week 52
    49.3
    47.4%
    75.3
    73.8%
    47.1
    23.6%
    65.8
    65.1%
    77.2
    15.2%
    EOT
    43.3
    41.6%
    66.7
    65.4%
    41.9
    21%
    55.3
    54.8%
    69.0
    13.6%
    5. Secondary Outcome
    Title Percentage of Participants With an American College of Rheumatology 70% (ACR70)-CRP Response at Week 12
    Description The ACR70 response required that all criteria from (1) to (3) below be met. TJC : ≥ 70% reduction compared with baseline. SJC : ≥ 70% reduction compared with baseline. ≥ 70% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 101 104 102 200
    Number [Percentage of Participants]
    1.0
    1%
    13.5
    13.2%
    27.5
    13.8%
    30.5
    30.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo. Difference vs. Peficitinib 100mg was not estimable.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 39.93
    Confidence Interval (2-Sided) 95%
    5.29 to 301.61
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: ACR70-CRP response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    6. Secondary Outcome
    Title Percentage of Participants With an ACR70-CRP Response Through Week 52
    Description The ACR70 response required that all criteria from (1) to (3) below be met. TJC : ≥ 70% reduction compared with baseline. SJC : ≥ 70% reduction compared with baseline. ≥ 70% improvement in 3 or more of the following 5 parameters compared with baseline: Subject's assessment of pain, SGA, PGA, HAQ-DI, CRP.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    1.0
    1%
    2.0
    2%
    0.0
    0%
    0.0
    0%
    14.5
    2.9%
    Week 8
    11.5
    11.1%
    14.1
    13.8%
    0.0
    0%
    2.1
    2.1%
    20.5
    4%
    Week 12
    14.6
    14%
    29.3
    28.7%
    0.0
    0%
    2.1
    2.1%
    31.9
    6.3%
    Week 16
    23.7
    22.8%
    28.0
    27.5%
    7.3
    3.7%
    8.5
    8.4%
    37.8
    7.5%
    Week 20
    26.1
    25.1%
    30.4
    29.8%
    7.3
    3.7%
    19.6
    19.4%
    41.8
    8.2%
    Week 24
    28.7
    27.6%
    40.0
    39.2%
    15.4
    7.7%
    22.2
    22%
    44.5
    8.8%
    Week 28
    25.3
    24.3%
    38.2
    37.5%
    20.0
    10%
    17.4
    17.2%
    48.0
    9.5%
    Week 32
    28.4
    27.3%
    39.5
    38.7%
    25.0
    12.5%
    24.4
    24.2%
    47.7
    9.4%
    Week 36
    31.6
    30.4%
    43.0
    42.2%
    27.8
    13.9%
    18.6
    18.4%
    44.6
    8.8%
    Week 40
    28.9
    27.8%
    47.7
    46.8%
    27.0
    13.5%
    35.7
    35.3%
    49.7
    9.8%
    Week 44
    30.7
    29.5%
    49.4
    48.4%
    41.2
    20.6%
    28.2
    27.9%
    52.0
    10.3%
    Week 48
    33.8
    32.5%
    51.2
    50.2%
    32.4
    16.2%
    38.5
    38.1%
    54.2
    10.7%
    Week 52
    35.2
    33.8%
    48.1
    47.2%
    38.2
    19.1%
    42.1
    41.7%
    56.2
    11.1%
    EOT
    31.7
    30.5%
    42.2
    41.4%
    34.9
    17.5%
    34.0
    33.7%
    48.0
    9.5%
    7. Secondary Outcome
    Title Change From Baseline in Disease Activity Score (DAS) 28-CRP at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 101 101 200
    Mean (Standard Deviation) [Units on a Scale]
    -0.64
    (1.20)
    -1.62
    (1.41)
    -2.17
    (1.14)
    -2.42
    (1.11)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -1.06
    Confidence Interval (2-Sided) 95%
    -1.41 to -0.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments Based on analysis of covariance model: DAS28 Change = Treatment + Baseline DAS28 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -1.55
    Confidence Interval (2-Sided) 95%
    -1.86 to -1.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.16
    Estimation Comments Based on analysis of covariance model: DAS28 Change = Treatment + Baseline DAS28 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    8. Secondary Outcome
    Title Change From Baseline DAS28-CRP Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -1.11
    (0.97)
    -1.29
    (0.83)
    -0.49
    (0.78)
    -0.56
    (0.86)
    -1.89
    (1.05)
    Week 8
    -1.48
    (1.24)
    -1.92
    (0.96)
    -0.70
    (1.02)
    -0.65
    (1.00)
    -2.27
    (1.03)
    Week 12
    -1.66
    (1.34)
    -2.27
    (1.12)
    -0.70
    (1.23)
    -0.82
    (1.15)
    -2.49
    (1.06)
    Week 16
    -1.96
    (1.37)
    -2.40
    (1.26)
    -1.60
    (1.29)
    -1.92
    (1.25)
    -2.61
    (1.01)
    Week 20
    -2.01
    (1.41)
    -2.57
    (1.20)
    -1.58
    (1.42)
    -2.15
    (1.22)
    -2.73
    (1.04)
    Week 24
    -2.06
    (1.39)
    -2.68
    (1.24)
    -1.60
    (1.34)
    -2.28
    (1.30)
    -2.79
    (1.04)
    Week 28
    -2.12
    (1.37)
    -2.80
    (1.27)
    -1.90
    (1.50)
    -2.35
    (1.31)
    -2.90
    (0.97)
    Week 32
    -2.26
    (1.30)
    -2.77
    (1.29)
    -1.98
    (1.47)
    -2.22
    (1.35)
    -2.94
    (1.05)
    Week 36
    -2.31
    (1.34)
    -2.87
    (1.22)
    -2.21
    (1.40)
    -2.26
    (1.35)
    -2.91
    (1.03)
    Week 40
    -2.31
    (1.36)
    -2.88
    (1.27)
    -2.17
    (1.46)
    -2.47
    (1.48)
    -2.99
    (0.97)
    Week 44
    -2.34
    (1.29)
    -2.86
    (1.37)
    -2.39
    (1.35)
    -2.47
    (1.42)
    -2.97
    (0.95)
    Week 48
    -2.26
    (1.31)
    -2.98
    (1.27)
    -2.58
    (1.32)
    -2.73
    (1.29)
    -3.03
    (1.01)
    Week 52
    -2.28
    (1.38)
    -2.99
    (1.26)
    -2.51
    (1.29)
    -2.73
    (1.30)
    -3.04
    (1.08)
    EOT
    -2.01
    (1.63)
    -2.75
    (1.36)
    -2.11
    (1.59)
    -2.50
    (1.41)
    -2.80
    (1.19)
    9. Secondary Outcome
    Title Change From Baseline in DAS28-Erythrocyte Sedimentation Rate (ESR) at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 98 102 101 198
    Mean (Standard Deviation) [Units on a Scale]
    -0.62
    (1.17)
    -1.60
    (1.39)
    -2.24
    (1.23)
    -2.51
    (1.27)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -1.03
    Confidence Interval (2-Sided) 95%
    -1.38 to -0.67
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.18
    Estimation Comments Based on analysis of covariance model: DAS28 Change = Treatment + Baseline DAS28 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -1.64
    Confidence Interval (2-Sided) 95%
    -1.96 to -1.31
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.17
    Estimation Comments Based on analysis of covariance model: DAS28 Change = Treatment + Baseline DAS28 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    10. Secondary Outcome
    Title Change From Baseline in DAS28-ESR Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -1.13
    (0.94)
    -1.26
    (0.84)
    -0.46
    (0.74)
    -0.63
    (0.87)
    -1.90
    (1.12)
    Week 8
    -1.50
    (1.20)
    -1.96
    (1.04)
    -0.68
    (0.99)
    -0.57
    (0.92)
    -2.33
    (1.12)
    Week 12
    -1.65
    (1.33)
    -2.35
    (1.21)
    -0.66
    (1.18)
    -0.80
    (1.13)
    -2.58
    (1.22)
    Week 16
    -1.95
    (1.40)
    -2.50
    (1.36)
    -1.53
    (1.33)
    -1.84
    (1.20)
    -2.68
    (1.15)
    Week 20
    -2.06
    (1.44)
    -2.65
    (1.29)
    -1.57
    (1.43)
    -2.15
    (1.20)
    -2.76
    (1.15)
    Week 24
    -2.11
    (1.47)
    -2.79
    (1.39)
    -1.60
    (1.37)
    -2.25
    (1.16)
    -2.86
    (1.18)
    Week 28
    -2.14
    (1.43)
    -2.87
    (1.37)
    -1.94
    (1.51)
    -2.31
    (1.29)
    -2.97
    (1.14)
    Week 32
    -2.28
    (1.41)
    -2.88
    (1.41)
    -1.98
    (1.46)
    -2.26
    (1.44)
    -3.01
    (1.13)
    Week 36
    -2.38
    (1.43)
    -3.00
    (1.36)
    -2.18
    (1.39)
    -2.28
    (1.35)
    -3.00
    (1.14)
    Week 40
    -2.38
    (1.44)
    -3.02
    (1.38)
    -2.12
    (1.44)
    -2.49
    (1.60)
    -3.10
    (1.06)
    Week 44
    -2.40
    (1.39)
    -3.02
    (1.51)
    -2.39
    (1.34)
    -2.55
    (1.38)
    -3.05
    (1.04)
    Week 48
    -2.32
    (1.40)
    -3.09
    (1.44)
    -2.67
    (1.39)
    -2.79
    (1.28)
    -3.16
    (1.09)
    Week 52
    -2.35
    (1.48)
    -3.06
    (1.40)
    -2.45
    (1.30)
    -2.67
    (1.23)
    -3.10
    (1.16)
    EOT
    -2.06
    (1.70)
    -2.81
    (1.47)
    -2.06
    (1.56)
    -2.44
    (1.44)
    -2.86
    (1.27)
    11. Secondary Outcome
    Title Change From Baseline in TJC (68 Joints) at Week 12
    Description 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).
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Tender Joints]
    -4.3
    (9.2)
    -8.2
    (8.8)
    -9.9
    (8.0)
    -10.7
    (7.8)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -4.6
    Confidence Interval (2-Sided) 95%
    -6.8 to -2.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.1
    Estimation Comments Based on analysis of covariance model: TJC68 Change = Treatment + Baseline TJC68 + the prior biologic - DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -6.1
    Confidence Interval (2-Sided) 95%
    -8.1 to -4.0
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.0
    Estimation Comments Based on analysis of covariance model: TJC68 Change = Treatment + Baseline TJC68 + the prior biologic - DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    12. Secondary Outcome
    Title Change From Baseline in TJC (68 Joints) Through Week 52
    Description 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).
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -5.9
    (8.0)
    -5.4
    (6.0)
    -3.9
    (8.1)
    -4.3
    (6.4)
    -8.3
    (7.7)
    Week 8
    -7.8
    (7.6)
    -8.6
    (7.1)
    -4.4
    (8.4)
    -3.9
    (8.3)
    -10.3
    (7.1)
    Week 12
    -8.6
    (8.8)
    -10.3
    (8.0)
    -5.0
    (9.7)
    -5.5
    (7.6)
    -11.0
    (7.6)
    Week 16
    -9.2
    (9.2)
    -10.3
    (8.8)
    -7.7
    (10.2)
    -9.6
    (7.5)
    -11.5
    (7.6)
    Week 20
    -9.8
    (9.2)
    -11.3
    (8.6)
    -8.1
    (10.8)
    -10.3
    (7.9)
    -12.0
    (7.9)
    Week 24
    -9.4
    (9.4)
    -11.3
    (9.7)
    -7.6
    (9.9)
    -11.7
    (7.9)
    -12.2
    (8.2)
    Week 28
    -9.7
    (8.8)
    -12.0
    (9.3)
    -8.4
    (10.3)
    -11.5
    (8.2)
    -12.6
    (8.6)
    Week 32
    -10.4
    (8.5)
    -12.2
    (8.6)
    -9.2
    (10.3)
    -11.1
    (8.5)
    -12.4
    (8.9)
    Week 36
    -10.2
    (8.6)
    -11.7
    (8.4)
    -10.1
    (9.5)
    -11.5
    (8.1)
    -12.6
    (8.6)
    Week 40
    -10.5
    (8.5)
    -11.8
    (8.8)
    -9.9
    (9.6)
    -12.2
    (8.4)
    -12.9
    (8.8)
    Week 44
    -10.6
    (8.2)
    -12.0
    (8.7)
    -10.7
    (10.0)
    -12.5
    (7.8)
    -12.8
    (9.0)
    Week 48
    -10.1
    (7.1)
    -12.4
    (9.5)
    -11.3
    (9.6)
    -13.2
    (7.7)
    -12.8
    (8.7)
    Week 52
    -10.1
    (7.6)
    -12.8
    (9.3)
    -11.4
    (10.1)
    -12.9
    (7.9)
    -12.8
    (8.9)
    EOT
    -9.1
    (9.7)
    -11.5
    (9.9)
    -9.6
    (10.7)
    -11.9
    (8.5)
    -11.9
    (8.8)
    13. Secondary Outcome
    Title Change From Baseline in Swollen Joint Count (SJC) (66 Joints) at Week 12
    Description 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).
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Tender Joints]
    -3.2
    (6.0)
    -6.0
    (6.4)
    -8.4
    (5.9)
    -8.3
    (5.5)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -3.0
    Confidence Interval (2-Sided) 95%
    -4.6 to -1.4
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.8
    Estimation Comments Based on analysis of covariance model: TJC68 Change = Treatment + Baseline TJC68 + the prior biologic - DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -5.3
    Confidence Interval (2-Sided) 95%
    -6.8 to -3.9
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.7
    Estimation Comments Based on analysis of covariance model: TJC68 Change = Treatment + Baseline TJC68 + the prior biologic - DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    14. Secondary Outcome
    Title Change From Baseline in SJC (66 Joints) Through Week 52
    Description 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).
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Lacebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -4.5
    (4.9)
    -4.7
    (4.2)
    -2.5
    (6.0)
    -2.2
    (4.5)
    -6.3
    (5.8)
    Week 8
    -5.6
    (5.6)
    -7.1
    (5.2)
    -2.8
    (5.8)
    -3.4
    (4.7)
    -7.6
    (5.2)
    Week 12
    -6.4
    (5.8)
    -8.7
    (6.0)
    -3.3
    (6.7)
    -3.9
    (5.6)
    -8.3
    (5.5)
    Week 16
    -7.7
    (6.0)
    -8.7
    (6.0)
    -6.4
    (6.3)
    -6.3
    (5.3)
    -8.7
    (5.3)
    Week 20
    -7.6
    (6.3)
    -9.1
    (6.2)
    -6.6
    (6.4)
    -7.8
    (6.9)
    -9.2
    (5.5)
    Week 24
    -7.9
    (6.0)
    -9.7
    (6.5)
    -6.5
    (6.2)
    -8.2
    (7.6)
    -9.1
    (5.3)
    Week 28
    -8.2
    (5.6)
    -10.4
    (5.7)
    -6.7
    (7.5)
    -8.7
    (7.4)
    -9.7
    (5.9)
    Week 32
    -8.2
    (6.3)
    -10.4
    (5.7)
    -5.9
    (8.3)
    -8.2
    (7.5)
    -9.8
    (6.1)
    Week 36
    -8.4
    (6.1)
    -10.4
    (6.1)
    -7.6
    (7.1)
    -8.5
    (7.7)
    -9.8
    (6.0)
    Week 40
    -8.4
    (5.7)
    -10.4
    (6.3)
    -7.6
    (7.0)
    -9.1
    (8.0)
    -10.0
    (6.2)
    Week 44
    -8.8
    (5.5)
    -10.5
    (6.2)
    -8.0
    (8.0)
    -9.3
    (8.0)
    -9.9
    (6.4)
    Week 48
    -8.6
    (5.8)
    -10.8
    (6.4)
    -8.0
    (7.2)
    -9.1
    (8.1)
    -9.9
    (6.0)
    Week 52
    -8.7
    (5.9)
    -11.0
    (6.0)
    -8.2
    (8.7)
    -9.4
    (8.0)
    -10.2
    (6.5)
    EOT
    -7.7
    (7.1)
    -10.0
    (6.5)
    -6.7
    (9.7)
    -8.6
    (8.0)
    -9.7
    (6.4)
    15. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-CRP < 2.6 at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 102 101 200
    Number [Percentage of Participants]
    5.0
    4.8%
    24.5
    24%
    34.7
    17.4%
    45.5
    45%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.40
    Confidence Interval (2-Sided) 95%
    2.31 to 17.67
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: DAS28-CRP score < 2.6 (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 10.13
    Confidence Interval (2-Sided) 95%
    3.76 to 27.27
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: DAS28-CRP score < 2.6 (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    16. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-CRP < 2.6 Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    10.2
    9.8%
    5.0
    4.9%
    0.0
    0%
    2.1
    2.1%
    26.0
    5.1%
    Week 8
    19.8
    19%
    23.5
    23%
    9.3
    4.7%
    2.1
    2.1%
    37.4
    7.4%
    Week 12
    25.0
    24%
    37.0
    36.3%
    7.1
    3.6%
    4.3
    4.3%
    47.6
    9.4%
    Week 16
    35.5
    34.1%
    39.8
    39%
    21.4
    10.7%
    23.4
    23.2%
    53.2
    10.5%
    Week 20
    37.0
    35.6%
    51.1
    50.1%
    16.7
    8.4%
    32.6
    32.3%
    59.3
    11.7%
    Week 24
    37.9
    36.4%
    51.7
    50.7%
    25.0
    12.5%
    33.3
    33%
    59.9
    11.8%
    Week 28
    36.1
    34.7%
    55.1
    54%
    34.1
    17.1%
    41.3
    40.9%
    61.6
    12.1%
    Week 32
    38.3
    36.8%
    55.8
    54.7%
    37.8
    18.9%
    37.8
    37.4%
    68.2
    13.5%
    Week 36
    49.4
    47.5%
    54.7
    53.6%
    43.2
    21.6%
    39.5
    39.1%
    61.7
    12.2%
    Week 40
    45.3
    43.6%
    53.5
    52.5%
    36.8
    18.4%
    45.2
    44.8%
    68.8
    13.6%
    Week 44
    46.7
    44.9%
    57.6
    56.5%
    48.6
    24.3%
    41.0
    40.6%
    69.6
    13.7%
    Week 48
    43.2
    41.5%
    61.9
    60.7%
    51.4
    25.7%
    56.4
    55.8%
    70.8
    14%
    Week 52
    43.7
    42%
    66.7
    65.4%
    45.7
    22.9%
    55.3
    54.8%
    67.9
    13.4%
    EOT
    39.2
    37.7%
    59.4
    58.2%
    41.9
    21%
    51.1
    50.6%
    61.5
    12.1%
    17. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-ESR < 2.6 at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 103 101 199
    Number [Percentage of Participants]
    1.0
    1%
    11.7
    11.5%
    17.8
    8.9%
    31.7
    31.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo. Difference vs. Peficitinib 100mg was not estimable.
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.003
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 21.72
    Confidence Interval (2-Sided) 95%
    2.83 to 166.66
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: DAS28-ESR score < 2.6 (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    18. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-ESR < 2.6 Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    2.0
    1.9%
    4.0
    3.9%
    0.0
    0%
    2.1
    2.1%
    14.5
    2.9%
    Week 8
    8.4
    8.1%
    13.3
    13%
    0.0
    0%
    0.0
    0%
    27.7
    5.5%
    Week 12
    11.5
    11.1%
    19.6
    19.2%
    2.4
    1.2%
    0.0
    0%
    33.2
    6.5%
    Week 16
    18.3
    17.6%
    26.1
    25.6%
    11.9
    6%
    14.9
    14.8%
    35.1
    6.9%
    Week 20
    22.0
    21.2%
    28.6
    28%
    14.6
    7.3%
    19.6
    19.4%
    38.1
    7.5%
    Week 24
    23.0
    22.1%
    34.1
    33.4%
    15.4
    7.7%
    17.8
    17.6%
    41.4
    8.2%
    Week 28
    27.7
    26.6%
    34.8
    34.1%
    26.8
    13.4%
    21.7
    21.5%
    39.8
    7.9%
    Week 32
    22.2
    21.3%
    30.2
    29.6%
    19.4
    9.7%
    24.4
    24.2%
    43.4
    8.6%
    Week 36
    25.3
    24.3%
    41.2
    40.4%
    25.0
    12.5%
    18.6
    18.4%
    40.0
    7.9%
    Week 40
    28.9
    27.8%
    44.2
    43.3%
    32.4
    16.2%
    28.6
    28.3%
    43.9
    8.7%
    Week 44
    32.0
    30.8%
    48.2
    47.3%
    35.3
    17.7%
    28.2
    27.9%
    43.3
    8.5%
    Week 48
    24.3
    23.4%
    39.3
    38.5%
    37.1
    18.6%
    38.5
    38.1%
    47.6
    9.4%
    Week 52
    25.4
    24.4%
    34.6
    33.9%
    29.4
    14.7%
    28.9
    28.6%
    43.2
    8.5%
    EOT
    23.3
    22.4%
    28.7
    28.1%
    26.2
    13.1%
    27.7
    27.4%
    39.5
    7.8%
    19. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-CRP <= 3.2 at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 102 101 200
    Number [Percentage of Participants]
    11.0
    10.6%
    40.2
    39.4%
    53.5
    26.8%
    68.0
    67.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 5.80
    Confidence Interval (2-Sided) 95%
    2.74 to 12.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: DAS28-CRP score ≤ 3.2 (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 9.66
    Confidence Interval (2-Sided) 95%
    4.57 to 20.41
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: DAS28-CRP score ≤ 3.2 (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    20. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-CRP <= 3.2 Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    18.4
    17.7%
    21.0
    20.6%
    4.7
    2.4%
    4.3
    4.3%
    47.0
    9.3%
    Week 8
    32.3
    31.1%
    40.8
    40%
    11.6
    5.8%
    12.8
    12.7%
    59.5
    11.7%
    Week 12
    41.7
    40.1%
    55.4
    54.3%
    14.3
    7.2%
    10.6
    10.5%
    70.2
    13.8%
    Week 16
    52.7
    50.7%
    64.5
    63.2%
    33.3
    16.7%
    44.7
    44.3%
    73.4
    14.5%
    Week 20
    55.4
    53.3%
    67.4
    66.1%
    45.2
    22.6%
    47.8
    47.3%
    75.8
    15%
    Week 24
    50.6
    48.7%
    74.2
    72.7%
    35.0
    17.5%
    62.2
    61.6%
    77.5
    15.3%
    Week 28
    55.4
    53.3%
    76.4
    74.9%
    41.5
    20.8%
    63.0
    62.4%
    81.9
    16.2%
    Week 32
    58.0
    55.8%
    70.9
    69.5%
    51.4
    25.7%
    55.6
    55%
    83.0
    16.4%
    Week 36
    63.3
    60.9%
    75.6
    74.1%
    56.8
    28.4%
    67.4
    66.7%
    83.4
    16.4%
    Week 40
    62.7
    60.3%
    76.7
    75.2%
    57.9
    29%
    71.4
    70.7%
    85.0
    16.8%
    Week 44
    61.3
    58.9%
    75.3
    73.8%
    57.1
    28.6%
    74.4
    73.7%
    83.0
    16.4%
    Week 48
    64.9
    62.4%
    81.0
    79.4%
    60.0
    30%
    79.5
    78.7%
    86.3
    17%
    Week 52
    63.4
    61%
    84.0
    82.4%
    54.3
    27.2%
    81.6
    80.8%
    89.5
    17.7%
    EOT
    54.9
    52.8%
    77.2
    75.7%
    48.8
    24.4%
    76.6
    75.8%
    81.5
    16.1%
    21. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-ESR <= 3.2 at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 103 101 199
    Number [Percentage of Participants]
    7.0
    6.7%
    19.4
    19%
    37.6
    18.8%
    49.7
    49.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.012
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.24
    Confidence Interval (2-Sided) 95%
    1.29 to 8.12
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: DAS28-ESR score ≤ 3.2 (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 8.19
    Confidence Interval (2-Sided) 96%
    3.42 to 19.63
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: DAS28-ESR score ≤ 3.2 (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    22. Secondary Outcome
    Title Percentage of Participants Achieving DAS28-ESR <= 3.2 Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    9.2
    8.8%
    10.0
    9.8%
    0.0
    0%
    4.3
    4.3%
    33.0
    6.5%
    Week 8
    20.0
    19.2%
    24.5
    24%
    9.3
    4.7%
    2.2
    2.2%
    42.6
    8.4%
    Week 12
    19.8
    19%
    39.1
    38.3%
    7.1
    3.6%
    8.5
    8.4%
    51.1
    10.1%
    Week 16
    32.3
    31.1%
    42.4
    41.6%
    21.4
    10.7%
    25.5
    25.2%
    53.7
    10.6%
    Week 20
    36.3
    34.9%
    51.6
    50.6%
    19.5
    9.8%
    34.8
    34.5%
    56.9
    11.2%
    Week 24
    37.9
    36.4%
    50.0
    49%
    23.1
    11.6%
    37.8
    37.4%
    58.6
    11.6%
    Week 28
    36.1
    34.7%
    59.6
    58.4%
    36.6
    18.3%
    41.3
    40.9%
    60.8
    12%
    Week 32
    42.0
    40.4%
    54.7
    53.6%
    38.9
    19.5%
    40.0
    39.6%
    65.7
    13%
    Week 36
    48.1
    46.3%
    61.2
    60%
    41.7
    20.9%
    37.2
    36.8%
    62.3
    12.3%
    Week 40
    51.3
    49.3%
    59.3
    58.1%
    43.2
    21.6%
    47.6
    47.1%
    67.1
    13.2%
    Week 44
    48.0
    46.2%
    60.0
    58.8%
    50.0
    25%
    46.2
    45.7%
    64.3
    12.7%
    Week 48
    45.9
    44.1%
    61.9
    60.7%
    54.3
    27.2%
    53.8
    53.3%
    72.6
    14.3%
    Week 52
    45.1
    43.4%
    69.1
    67.7%
    41.2
    20.6%
    52.6
    52.1%
    62.3
    12.3%
    EOT
    38.8
    37.3%
    61.4
    60.2%
    38.1
    19.1%
    46.8
    46.3%
    58.0
    11.4%
    23. Secondary Outcome
    Title Change From Baseline in CRP at Week 12
    Description Higher CRP indicates greater disease activity.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 101 101 200
    Mean (Standard Deviation) [mg/dL]
    0.022
    (1.498)
    -1.056
    (1.908)
    -1.734
    (1.906)
    -1.207
    (2.694)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS Mean
    Estimated Value -1.112
    Confidence Interval (2-Sided) 95%
    -1.546 to -0.679
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.220
    Estimation Comments Based on analysis of covariance model: CRP Change = Treatment + Baseline CRP + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -1.677
    Confidence Interval (2-Sided) 95%
    -2.114 to -1.241
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.221
    Estimation Comments Based on analysis of covariance model: CRP Change = Treatment + Baseline CRP + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    24. Secondary Outcome
    Title Change From Baseline in CRP Through Week 52
    Description Higher CRP indicates greater disease activity.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -0.817
    (1.566)
    -1.359
    (1.575)
    0.013
    (1.070)
    0.073
    (1.643)
    -1.360
    (1.511)
    Week 8
    -0.967
    (1.877)
    -1.664
    (1.768)
    0.198
    (1.662)
    -0.076
    (0.930)
    -1.337
    (1.822)
    Week 12
    -1.045
    (1.827)
    -1.810
    (1.908)
    0.026
    (1.852)
    -0.142
    (1.076)
    -1.205
    (2.735)
    Week 16
    -1.083
    (2.062)
    -1.849
    (2.099)
    -0.802
    (2.127)
    -1.180
    (1.109)
    -1.383
    (1.639)
    Week 20
    -0.964
    (2.551)
    -1.819
    (2.156)
    -0.581
    (2.471)
    -1.294
    (1.152)
    -1.525
    (1.643)
    Week 24
    -1.225
    (2.168)
    -1.824
    (2.200)
    -0.434
    (2.251)
    -1.318
    (1.486)
    -1.473
    (1.847)
    Week 28
    -1.323
    (1.976)
    -1.904
    (2.197)
    -1.013
    (2.247)
    -1.266
    (1.635)
    -1.611
    (2.000)
    Week 32
    -1.200
    (1.973)
    -1.979
    (2.223)
    -1.239
    (2.227)
    -0.975
    (3.345)
    -1.593
    (1.886)
    Week 36
    -1.310
    (1.874)
    -2.043
    (2.202)
    -1.084
    (2.460)
    -1.192
    (1.453)
    -1.467
    (2.233)
    Week 40
    -1.199
    (2.011)
    -2.019
    (2.240)
    -1.325
    (2.566)
    -1.232
    (1.609)
    -1.594
    (2.146)
    Week 44
    -1.202
    (1.961)
    -1.978
    (2.221)
    -1.292
    (2.366)
    -1.225
    (1.729)
    -1.627
    (1.810)
    Week 48
    -0.964
    (2.074)
    -1.833
    (2.882)
    -1.610
    (2.103)
    -1.407
    (1.747)
    -1.611
    (1.858)
    Week 52
    -1.138
    (2.056)
    -2.068
    (2.228)
    -1.566
    (2.034)
    -1.534
    (1.589)
    -1.595
    (1.873)
    EOT
    -0.949
    (2.368)
    -1.832
    (2.221)
    -0.797
    (2.879)
    -0.987
    (3.366)
    -1.326
    (2.724)
    25. Secondary Outcome
    Title Change From Baseline in ESR at Week 12
    Description Higher ESR indicates greater disease activity.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 199
    Mean (Standard Deviation) [mm/hour]
    -1.96
    (17.82)
    -12.96
    (21.51)
    -23.92
    (21.26)
    -20.92
    (21.66)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -10.90
    Confidence Interval (2-Sided) 95%
    -15.95 to -5.84
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.56
    Estimation Comments Based on analysis of covariance model: ESR Change = Treatment + Baseline ESR + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -21.14
    Confidence Interval (2-Sided) 95%
    -26.01 to -16.27
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.47
    Estimation Comments Based on analysis of covariance model: ESR Change = Treatment + Baseline ESR + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    26. Secondary Outcome
    Title Change From Baseline in ESR Through Week 52
    Description Higher ESR indicates greater disease activity.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -9.98
    (15.44)
    -14.99
    (15.90)
    -0.63
    (11.77)
    -3.87
    (12.99)
    -19.20
    (17.51)
    Week 8
    -15.27
    (19.29)
    -21.59
    (19.81)
    -0.95
    (12.47)
    -2.07
    (14.31)
    -20.88
    (19.43)
    Week 12
    -13.49
    (21.25)
    -25.26
    (21.22)
    -2.62
    (18.31)
    -4.43
    (17.07)
    -21.74
    (20.67)
    Week 16
    -15.34
    (20.98)
    -28.32
    (21.66)
    -11.76
    (19.87)
    -16.89
    (17.70)
    -22.05
    (19.53)
    Week 20
    -16.77
    (21.88)
    -27.34
    (21.95)
    -12.69
    (23.03)
    -20.62
    (17.65)
    -21.91
    (20.59)
    Week 24
    -17.61
    (22.60)
    -27.02
    (26.00)
    -13.18
    (21.90)
    -20.04
    (18.45)
    -22.20
    (23.87)
    Week 28
    -16.47
    (21.90)
    -27.21
    (23.97)
    -16.29
    (17.77)
    -18.02
    (24.26)
    -23.52
    (22.35)
    Week 32
    -16.35
    (23.09)
    -27.02
    (23.81)
    -19.54
    (21.98)
    -19.93
    (25.80)
    -24.75
    (21.27)
    Week 36
    -18.67
    (23.77)
    -29.50
    (25.26)
    -19.65
    (22.64)
    -21.99
    (21.52)
    -24.66
    (22.32)
    Week 40
    -17.74
    (25.65)
    -29.79
    (24.00)
    -19.45
    (23.06)
    -21.71
    (25.48)
    -25.87
    (24.84)
    Week 44
    -17.77
    (25.35)
    -29.07
    (24.47)
    -21.43
    (24.12)
    -22.31
    (23.12)
    -25.73
    (21.09)
    Week 48
    -15.43
    (25.70)
    -28.70
    (24.69)
    -23.40
    (23.87)
    -25.66
    (22.30)
    -25.98
    (22.00)
    Week 52
    -16.77
    (26.05)
    -28.59
    (24.97)
    -21.03
    (19.81)
    -23.24
    (24.28)
    -24.23
    (21.70)
    EOT
    -14.94
    (27.20)
    -26.15
    (25.02)
    -15.37
    (24.27)
    -18.61
    (27.67)
    -20.75
    (26.25)
    27. Secondary Outcome
    Title Percentage of Participants With a European League Against Rheumatism (EULAR) Good Response Using DAS28-CRP at Week 12
    Description Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline > 1.2.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 101 101 200
    Number [Percentage of Participants]
    9.1
    8.8%
    38.6
    37.8%
    51.5
    25.8%
    65.5
    64.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 6.64
    Confidence Interval (2-Sided) 95%
    2.98 to 14.83
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 10.86
    Confidence Interval (2-Sided) 95%
    4.91 to 24.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    28. Secondary Outcome
    Title Percentage of Participants With a EULAR Good Response Using DAS28-CRP Through Week 52
    Description Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline > 1.2.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    17.3
    16.6%
    16.0
    15.7%
    4.8
    2.4%
    2.1
    2.1%
    44.5
    8.8%
    Week 8
    28.1
    27%
    39.8
    39%
    11.9
    6%
    6.4
    6.3%
    56.4
    11.1%
    Week 12
    39.6
    38.1%
    53.3
    52.3%
    12.2
    6.1%
    8.5
    8.4%
    67.5
    13.3%
    Week 16
    48.4
    46.5%
    60.2
    59%
    34.1
    17.1%
    40.4
    40%
    72.9
    14.4%
    Week 20
    51.1
    49.1%
    65.2
    63.9%
    46.3
    23.2%
    43.5
    43.1%
    75.8
    15%
    Week 24
    47.1
    45.3%
    71.9
    70.5%
    33.3
    16.7%
    57.8
    57.2%
    76.4
    15.1%
    Week 28
    50.6
    48.7%
    74.2
    72.7%
    40.0
    20%
    58.7
    58.1%
    80.8
    15.9%
    Week 32
    54.3
    52.2%
    68.6
    67.3%
    50.0
    25%
    46.7
    46.2%
    83.0
    16.4%
    Week 36
    59.5
    57.2%
    74.4
    72.9%
    55.6
    27.8%
    62.8
    62.2%
    83.4
    16.4%
    Week 40
    58.7
    56.4%
    75.6
    74.1%
    54.1
    27.1%
    66.7
    66%
    84.4
    16.6%
    Week 44
    58.7
    56.4%
    74.1
    72.6%
    55.9
    28%
    71.8
    71.1%
    82.5
    16.3%
    Week 48
    60.8
    58.5%
    79.8
    78.2%
    55.9
    28%
    79.5
    78.7%
    85.1
    16.8%
    Week 52
    59.2
    56.9%
    81.5
    79.9%
    52.9
    26.5%
    78.9
    78.1%
    88.3
    17.4%
    EOT
    52.5
    50.5%
    75.2
    73.7%
    47.6
    23.8%
    72.3
    71.6%
    80.0
    15.8%
    29. Secondary Outcome
    Title Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 101 101 200
    Number [Percentage of Participants]
    41.4
    39.8%
    75.2
    73.7%
    92.1
    46.1%
    92.5
    91.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.37
    Confidence Interval (2-Sided) 95%
    2.38 to 8.04
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good or Moderate Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 16.78
    Confidence Interval (2-Sided) 95%
    7.31 to 38.51
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good or Moderate Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    30. Secondary Outcome
    Title Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    63.3
    60.9%
    72.0
    70.6%
    31.0
    15.5%
    40.4
    40%
    87.5
    17.3%
    Week 8
    76.0
    73.1%
    86.7
    85%
    47.6
    23.8%
    40.4
    40%
    92.3
    18.2%
    Week 12
    77.1
    74.1%
    94.6
    92.7%
    41.5
    20.8%
    48.9
    48.4%
    94.2
    18.6%
    Week 16
    81.7
    78.6%
    92.5
    90.7%
    73.2
    36.6%
    85.1
    84.3%
    96.8
    19.1%
    Week 20
    79.3
    76.3%
    96.7
    94.8%
    78.0
    39%
    91.3
    90.4%
    95.6
    18.9%
    Week 24
    85.1
    81.8%
    96.6
    94.7%
    71.8
    35.9%
    91.1
    90.2%
    97.3
    19.2%
    Week 28
    89.2
    85.8%
    95.5
    93.6%
    80.0
    40%
    87.0
    86.1%
    99.4
    19.6%
    Week 32
    91.4
    87.9%
    96.5
    94.6%
    83.3
    41.7%
    82.2
    81.4%
    98.3
    19.4%
    Week 36
    87.3
    83.9%
    96.5
    94.6%
    86.1
    43.1%
    86.0
    85.1%
    97.7
    19.3%
    Week 40
    89.3
    85.9%
    96.5
    94.6%
    86.5
    43.3%
    85.7
    84.9%
    100.0
    19.7%
    Week 44
    93.3
    89.7%
    94.1
    92.3%
    88.2
    44.1%
    87.2
    86.3%
    99.4
    19.6%
    Week 48
    90.5
    87%
    97.6
    95.7%
    94.1
    47.1%
    89.7
    88.8%
    98.2
    19.4%
    Week 52
    91.5
    88%
    98.8
    96.9%
    94.1
    47.1%
    92.1
    91.2%
    98.8
    19.5%
    EOT
    78.2
    75.2%
    93.1
    91.3%
    83.3
    41.7%
    85.1
    84.3%
    95.5
    18.8%
    31. Secondary Outcome
    Title Percentage of Participants With a Good EULAR Response Using DAS28-ESR at Week 12
    Description Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline > 1.2.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 98 102 101 198
    Number [Percentage of Participants]
    5.1
    4.9%
    18.6
    18.2%
    36.6
    18.3%
    49.0
    48.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.006
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 4.29
    Confidence Interval (2-Sided) 95%
    1.52 to 12.08
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio, log
    Estimated Value 11.01
    Confidence Interval (2-Sided) 95%
    4.07 to 29.74
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    32. Secondary Outcome
    Title Percentage of Participants With a Good EULAR Response Using DAS28-ESR Through Week 52
    Description Good response was defined as DAS28 after treatment ≤ 3.2 and improvement from baseline > 1.2.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    8.2
    7.9%
    10.0
    9.8%
    0.0
    0%
    2.2
    2.2%
    31.7
    6.3%
    Week 8
    16.8
    16.2%
    24.5
    24%
    9.5
    4.8%
    0.0
    0%
    41.2
    8.1%
    Week 12
    18.8
    18.1%
    38.0
    37.3%
    4.9
    2.5%
    6.5
    6.4%
    50.0
    9.9%
    Week 16
    31.2
    30%
    40.2
    39.4%
    22.0
    11%
    21.7
    21.5%
    52.7
    10.4%
    Week 20
    34.1
    32.8%
    51.6
    50.6%
    20.0
    10%
    31.1
    30.8%
    56.4
    11.1%
    Week 24
    35.6
    34.2%
    50.0
    49%
    21.1
    10.6%
    34.1
    33.8%
    56.4
    11.1%
    Week 28
    32.5
    31.3%
    59.6
    58.4%
    35.0
    17.5%
    37.8
    37.4%
    59.7
    11.8%
    Week 32
    39.5
    38%
    54.7
    53.6%
    37.1
    18.6%
    36.4
    36%
    63.4
    12.5%
    Week 36
    44.3
    42.6%
    60.0
    58.8%
    40.0
    20%
    33.3
    33%
    62.3
    12.3%
    Week 40
    47.4
    45.6%
    59.3
    58.1%
    41.7
    20.9%
    43.9
    43.5%
    67.1
    13.2%
    Week 44
    45.3
    43.6%
    60.0
    58.8%
    48.5
    24.3%
    43.6
    43.2%
    63.7
    12.6%
    Week 48
    41.9
    40.3%
    61.9
    60.7%
    52.9
    26.5%
    52.6
    52.1%
    72.6
    14.3%
    Week 52
    43.7
    42%
    69.1
    67.7%
    39.4
    19.7%
    48.6
    48.1%
    61.7
    12.2%
    EOT
    38.2
    36.7%
    61.4
    60.2%
    36.6
    18.3%
    43.5
    43.1%
    57.3
    11.3%
    33. Secondary Outcome
    Title Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 98 102 101 198
    Number [Percentage of Participants]
    37.8
    36.3%
    69.6
    68.2%
    88.1
    44.1%
    90.9
    90%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 3.82
    Confidence Interval () 95%
    2.11 to 6.93
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good or Moderate Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Wald's chi-squared test
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value 13.65
    Confidence Interval (2-Sided) 95%
    6.39 to 29.17
    Parameter Dispersion Type:
    Value:
    Estimation Comments Based on logistic regression model: Good or Moderate Response (responder, non-responder) = Treatment + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    34. Secondary Outcome
    Title Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-ESR Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    56.1
    53.9%
    65.0
    63.7%
    31.0
    15.5%
    23.9
    23.7%
    81.9
    16.2%
    Week 8
    66.3
    63.8%
    84.7
    83%
    45.2
    22.6%
    33.3
    33%
    92.8
    18.3%
    Week 12
    70.8
    68.1%
    90.2
    88.4%
    39.0
    19.5%
    43.5
    43.1%
    92.6
    18.3%
    Week 16
    76.3
    73.4%
    88.0
    86.3%
    73.2
    36.6%
    76.1
    75.3%
    94.7
    18.7%
    Week 20
    79.1
    76.1%
    96.7
    94.8%
    72.5
    36.3%
    86.7
    85.8%
    93.9
    18.5%
    Week 24
    82.8
    79.6%
    95.5
    93.6%
    73.7
    36.9%
    90.9
    90%
    96.1
    19%
    Week 28
    84.3
    81.1%
    92.1
    90.3%
    77.5
    38.8%
    88.9
    88%
    97.7
    19.3%
    Week 32
    90.1
    86.6%
    94.2
    92.4%
    77.1
    38.6%
    86.4
    85.5%
    97.1
    19.2%
    Week 36
    83.5
    80.3%
    95.3
    93.4%
    85.7
    42.9%
    83.3
    82.5%
    96.6
    19.1%
    Week 40
    89.5
    86.1%
    95.3
    93.4%
    83.3
    41.7%
    85.4
    84.6%
    98.3
    19.4%
    Week 44
    90.7
    87.2%
    92.9
    91.1%
    84.8
    42.4%
    87.2
    86.3%
    98.2
    19.4%
    Week 48
    86.5
    83.2%
    95.2
    93.3%
    88.2
    44.1%
    89.5
    88.6%
    98.2
    19.4%
    Week 52
    84.5
    81.3%
    97.5
    95.6%
    84.8
    42.4%
    89.2
    88.3%
    98.1
    19.3%
    EOT
    74.5
    71.6%
    94.1
    92.3%
    75.6
    37.8%
    82.6
    81.8%
    93.5
    18.4%
    35. Secondary Outcome
    Title Percentage of Participants Achieving ACR / EULAR Remission at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 102 101 200
    Number [Percentage of Participants]
    2.0
    1.9%
    5.9
    5.8%
    5.9
    3%
    13.5
    13.4%
    36. Secondary Outcome
    Title Percentage of Participants Achieving ACR / EULAR Remission Through Week 52
    Description 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).
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    1.0
    1%
    0.0
    0%
    0.0
    0%
    0.0
    0%
    7.0
    1.4%
    Week 8
    2.1
    2%
    1.0
    1%
    2.3
    1.2%
    0.0
    0%
    11.8
    2.3%
    Week 12
    6.3
    6.1%
    6.5
    6.4%
    0.0
    0%
    4.3
    4.3%
    14.1
    2.8%
    Week 16
    11.8
    11.3%
    8.6
    8.4%
    4.8
    2.4%
    2.1
    2.1%
    18.6
    3.7%
    Week 20
    12.0
    11.5%
    13.0
    12.7%
    4.8
    2.4%
    6.5
    6.4%
    20.9
    4.1%
    Week 24
    13.8
    13.3%
    10.1
    9.9%
    5.0
    2.5%
    8.9
    8.8%
    28.0
    5.5%
    Week 28
    12.0
    11.5%
    18.0
    17.6%
    9.8
    4.9%
    10.9
    10.8%
    24.3
    4.8%
    Week 32
    13.6
    13.1%
    20.9
    20.5%
    10.8
    5.4%
    11.1
    11%
    25.0
    4.9%
    Week 36
    16.5
    15.9%
    18.6
    18.2%
    8.1
    4.1%
    7.0
    6.9%
    22.3
    4.4%
    Week 40
    16.0
    15.4%
    19.8
    19.4%
    7.9
    4%
    14.3
    14.2%
    24.3
    4.8%
    Week 44
    16.0
    15.4%
    24.7
    24.2%
    20.0
    10%
    7.7
    7.6%
    25.1
    5%
    Week 48
    17.6
    16.9%
    25.0
    24.5%
    25.7
    12.9%
    15.4
    15.2%
    27.4
    5.4%
    Week 52
    18.3
    17.6%
    18.5
    18.1%
    22.9
    11.5%
    10.5
    10.4%
    30.2
    6%
    EOT
    14.7
    14.1%
    15.8
    15.5%
    20.9
    10.5%
    8.5
    8.4%
    25.0
    4.9%
    37. Secondary Outcome
    Title Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Remission at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 102 101 200
    Number [Percentage of Participants]
    0.0
    0%
    8.8
    8.6%
    8.9
    4.5%
    18.5
    18.3%
    38. Secondary Outcome
    Title Percentage of Participants Achieving SDAI Remission Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    1.0
    1%
    1.0
    1%
    0.0
    0%
    0.0
    0%
    10.0
    2%
    Week 8
    4.2
    4%
    6.1
    6%
    0.0
    0%
    0.0
    0%
    16.9
    3.3%
    Week 12
    9.4
    9%
    9.8
    9.6%
    0.0
    0%
    0.0
    0%
    19.4
    3.8%
    Week 16
    12.9
    12.4%
    15.1
    14.8%
    2.4
    1.2%
    8.5
    8.4%
    23.9
    4.7%
    Week 20
    17.4
    16.7%
    18.5
    18.1%
    4.8
    2.4%
    15.2
    15%
    29.7
    5.9%
    Week 24
    18.4
    17.7%
    18.0
    17.6%
    10.0
    5%
    17.8
    17.6%
    34.1
    6.7%
    Week 28
    19.3
    18.6%
    29.2
    28.6%
    17.1
    8.6%
    17.4
    17.2%
    33.9
    6.7%
    Week 32
    16.0
    15.4%
    27.9
    27.4%
    13.5
    6.8%
    13.3
    13.2%
    35.2
    6.9%
    Week 36
    21.5
    20.7%
    27.9
    27.4%
    18.9
    9.5%
    4.7
    4.7%
    30.9
    6.1%
    Week 40
    24.0
    23.1%
    36.0
    35.3%
    10.5
    5.3%
    19.0
    18.8%
    33.5
    6.6%
    Week 44
    22.7
    21.8%
    38.8
    38%
    20.0
    10%
    15.4
    15.2%
    34.5
    6.8%
    Week 48
    18.9
    18.2%
    38.1
    37.4%
    28.6
    14.3%
    25.6
    25.3%
    39.3
    7.8%
    Week 52
    21.1
    20.3%
    29.6
    29%
    20.0
    10%
    21.1
    20.9%
    39.5
    7.8%
    EOT
    17.6
    16.9%
    25.7
    25.2%
    18.6
    9.3%
    17.0
    16.8%
    33.5
    6.6%
    39. Secondary Outcome
    Title Change From Baseline in SDAI Score at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 101 101 200
    Mean (Standard Deviation) [Units on a Scale]
    -7.22
    (14.11)
    -16.08
    (14.37)
    -20.93
    (11.32)
    -21.94
    (11.21)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS Mean
    Estimated Value -9.94
    Confidence Interval (2-Sided) 95%
    -13.66 to -6.22
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.89
    Estimation Comments Based on analysis of covariance model: SDAI Change = Treatment + Baseline SDAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter Odds Ratio (OR)
    Estimated Value -14.43
    Confidence Interval (2-Sided) 95%
    -17.71 to -11.15
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.66
    Estimation Comments Based on analysis of covariance model: SDAI Change = Treatment + Baseline SDAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    40. Secondary Outcome
    Title Change From Baseline in SDAI Score Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -11.83
    (9.97)
    -12.78
    (9.06)
    -5.57
    (9.50)
    -7.21
    (9.35)
    -17.09
    (10.83)
    Week 8
    -14.71
    (12.53)
    -18.66
    (9.73)
    -7.07
    (12.26)
    -8.43
    (11.37)
    -20.64
    (10.09)
    Week 12
    -16.59
    (13.47)
    -21.62
    (11.48)
    -7.48
    (14.80)
    -10.18
    (11.82)
    -22.54
    (10.79)
    Week 16
    -19.25
    (13.76)
    -21.90
    (12.19)
    -15.20
    (14.25)
    -18.90
    (12.08)
    -23.46
    (10.37)
    Week 20
    -19.47
    (14.16)
    -23.37
    (11.94)
    -15.67
    (15.41)
    -20.61
    (12.44)
    -24.44
    (10.15)
    Week 24
    -20.14
    (13.96)
    -24.40
    (12.00)
    -16.13
    (14.40)
    -22.25
    (13.22)
    -24.78
    (10.14)
    Week 28
    -20.29
    (12.71)
    -25.29
    (12.32)
    -17.75
    (15.21)
    -22.74
    (13.00)
    -25.70
    (10.51)
    Week 32
    -21.72
    (12.82)
    -25.28
    (12.07)
    -17.71
    (15.34)
    -21.14
    (14.69)
    -25.84
    (10.79)
    Week 36
    -21.34
    (12.65)
    -25.62
    (11.95)
    -20.57
    (14.03)
    -22.02
    (13.54)
    -25.77
    (11.33)
    Week 40
    -21.55
    (13.04)
    -25.78
    (12.54)
    -20.34
    (14.90)
    -23.09
    (14.63)
    -26.46
    (11.11)
    Week 44
    -21.54
    (12.22)
    -25.82
    (12.92)
    -22.65
    (13.74)
    -23.23
    (14.31)
    -26.17
    (11.06)
    Week 48
    -21.11
    (12.13)
    -26.33
    (12.58)
    -23.21
    (13.47)
    -24.61
    (13.35)
    -26.57
    (11.02)
    Week 52
    -21.19
    (12.83)
    -26.99
    (12.52)
    -23.04
    (13.57)
    -25.20
    (13.91)
    -26.77
    (11.57)
    EOT
    -18.92
    (15.76)
    -24.95
    (12.77)
    -18.76
    (16.83)
    -22.38
    (15.91)
    -24.85
    (12.19)
    41. Secondary Outcome
    Title Percentage of Participants Achieving Clinical Disease Activity Index (CDAI) Score <= 2.8 at Week 12
    Description 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.
    Time Frame Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 100 103 101 200
    Number [Percentage of Participants]
    0.0
    0%
    8.7
    8.5%
    9.9
    5%
    19.0
    18.8%
    42. Secondary Outcome
    Title Percentage of Participants Achieving CDAI Score <= 2.8 Through Week 52
    Description 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.
    Time Frame Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    1.0
    1%
    2.0
    2%
    0.0
    0%
    0.0
    0%
    9.0
    1.8%
    Week 8
    4.2
    4%
    6.1
    6%
    0.0
    0%
    0.0
    0%
    14.4
    2.8%
    Week 12
    9.4
    9%
    10.9
    10.7%
    0.0
    0%
    0.0
    0%
    19.9
    3.9%
    Week 16
    14.0
    13.5%
    16.1
    15.8%
    2.4
    1.2%
    6.4
    6.3%
    23.9
    4.7%
    Week 20
    18.5
    17.8%
    17.4
    17.1%
    2.4
    1.2%
    10.9
    10.8%
    28.0
    5.5%
    Week 24
    16.1
    15.5%
    15.6
    15.3%
    7.5
    3.8%
    15.6
    15.4%
    31.9
    6.3%
    Week 28
    20.5
    19.7%
    27.0
    26.5%
    14.6
    7.3%
    17.4
    17.2%
    31.6
    6.2%
    Week 32
    17.3
    16.6%
    27.9
    27.4%
    16.2
    8.1%
    13.3
    13.2%
    32.4
    6.4%
    Week 36
    19.0
    18.3%
    26.7
    26.2%
    18.9
    9.5%
    7.0
    6.9%
    30.3
    6%
    Week 40
    22.4
    21.5%
    29.1
    28.5%
    13.2
    6.6%
    21.4
    21.2%
    31.8
    6.3%
    Week 44
    21.3
    20.5%
    36.5
    35.8%
    25.7
    12.9%
    15.4
    15.2%
    33.3
    6.6%
    Week 48
    23.0
    22.1%
    34.5
    33.8%
    28.6
    14.3%
    23.1
    22.9%
    36.3
    7.2%
    Week 52
    21.1
    20.3%
    27.2
    26.7%
    22.9
    11.5%
    18.4
    18.2%
    38.3
    7.6%
    EOT
    18.4
    17.7%
    23.8
    23.3%
    20.9
    10.5%
    17.0
    16.8%
    32.5
    6.4%
    43. Secondary Outcome
    Title Change From Baseline in CDAI Score at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    -7.25
    (13.42)
    -14.91
    (13.46)
    -19.20
    (11.04)
    -20.74
    (10.64)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -8.69
    Confidence Interval (2-Sided) 95%
    -12.19 to -5.20
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.77
    Estimation Comments Based on ANCOVA Model: CDAI Change = Treatment + Baseline CDAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method ANCOVA
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -12.83
    Confidence Interval (2-Sided) 95%
    -15.96 to -9.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.58
    Estimation Comments Based on ANCOVA Model: CDAI Change = Treatment + Baseline CDAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    44. Secondary Outcome
    Title Change From Baseline in CDAI Score Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -11.01
    (9.47)
    -11.42
    (8.99)
    -5.61
    (9.16)
    -7.28
    (8.76)
    -15.73
    (10.51)
    Week 8
    -13.74
    (11.77)
    -17.06
    (9.58)
    -7.29
    (11.46)
    -8.35
    (11.10)
    -19.31
    (9.69)
    Week 12
    -15.55
    (12.71)
    -19.81
    (11.21)
    -7.52
    (13.88)
    -10.04
    (11.47)
    -21.21
    (10.39)
    Week 16
    -18.17
    (12.81)
    -20.06
    (11.91)
    -14.40
    (13.13)
    -17.72
    (11.75)
    -22.08
    (10.12)
    Week 20
    -18.51
    (13.13)
    -21.55
    (11.42)
    -15.08
    (14.22)
    -19.31
    (12.30)
    -22.92
    (10.04)
    Week 24
    -18.92
    (12.65)
    -22.28
    (11.75)
    -15.71
    (13.08)
    -20.93
    (12.88)
    -23.30
    (9.93)
    Week 28
    -18.97
    (12.06)
    -23.38
    (11.76)
    -16.74
    (14.06)
    -21.48
    (12.70)
    -24.09
    (10.26)
    Week 32
    -20.52
    (12.07)
    -23.30
    (11.53)
    -16.46
    (14.45)
    -20.17
    (13.87)
    -24.25
    (10.38)
    Week 36
    -20.03
    (12.22)
    -23.58
    (11.41)
    -19.48
    (12.86)
    -20.83
    (13.10)
    -24.30
    (10.86)
    Week 40
    -20.41
    (12.12)
    -23.76
    (12.03)
    -19.00
    (13.77)
    -21.86
    (14.11)
    -24.87
    (10.76)
    Week 44
    -20.34
    (11.43)
    -23.84
    (12.25)
    -21.34
    (12.56)
    -22.00
    (13.79)
    -24.54
    (10.81)
    Week 48
    -20.11
    (11.47)
    -24.50
    (11.77)
    -21.58
    (12.56)
    -23.20
    (13.03)
    -24.96
    (10.70)
    Week 52
    -20.05
    (11.94)
    -24.93
    (11.90)
    -21.44
    (12.72)
    -23.67
    (13.42)
    -25.17
    (11.14)
    EOT
    -17.82
    (14.69)
    -23.12
    (12.04)
    -17.96
    (15.14)
    -21.39
    (14.85)
    -23.52
    (11.45)
    45. Secondary Outcome
    Title Change From Baseline in Physician's Global Assessment of Arthritis (PGA) at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    -13.94
    (24.85)
    -27.69
    (25.39)
    -34.65
    (21.19)
    -37.40
    (20.69)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -15.20
    Confidence Interval (2-Sided) 95%
    -21.40 to -9.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.14
    Estimation Comments Based on analysis of covariance model: PGA (100 mm VAS) Change = Treatment + Baseline PGA (100 mm VAS) + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -23.14
    Confidence Interval (2-Sided) 95%
    -28.78 to -17.51
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 2.86
    Estimation Comments Based on analysis of covariance model: PGA (100 mm VAS) Change = Treatment + Baseline PGA (100 mm VAS) + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    46. Secondary Outcome
    Title Change From Baseline in PGA Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -18.71
    (17.32)
    -19.49
    (18.14)
    -8.77
    (17.97)
    -12.37
    (16.60)
    -27.48
    (20.10)
    Week 8
    -25.92
    (23.49)
    -30.55
    (21.05)
    -11.70
    (20.42)
    -16.04
    (22.64)
    -33.80
    (19.61)
    Week 12
    -28.91
    (25.08)
    -35.53
    (21.28)
    -14.85
    (24.59)
    -18.99
    (23.44)
    -37.99
    (20.16)
    Week 16
    -34.84
    (23.77)
    -34.68
    (22.76)
    -26.10
    (22.44)
    -31.35
    (20.54)
    -39.20
    (20.77)
    Week 20
    -34.83
    (24.45)
    -38.65
    (21.19)
    -28.43
    (22.91)
    -33.80
    (21.18)
    -41.10
    (20.77)
    Week 24
    -36.67
    (23.23)
    -38.50
    (23.05)
    -30.62
    (21.72)
    -37.43
    (21.86)
    -41.18
    (20.68)
    Week 28
    -37.17
    (22.57)
    -39.29
    (21.74)
    -31.69
    (24.41)
    -37.90
    (22.50)
    -41.51
    (20.87)
    Week 32
    -39.14
    (22.04)
    -40.49
    (21.08)
    -30.22
    (21.37)
    -37.27
    (23.10)
    -41.95
    (20.76)
    Week 36
    -38.29
    (23.55)
    -40.76
    (21.04)
    -35.44
    (22.26)
    -38.90
    (21.79)
    -41.27
    (21.41)
    Week 40
    -39.95
    (23.16)
    -41.88
    (21.29)
    -36.31
    (23.59)
    -38.83
    (22.58)
    -42.93
    (20.16)
    Week 44
    -38.53
    (22.64)
    -42.16
    (21.19)
    -38.01
    (23.72)
    -37.74
    (23.46)
    -42.65
    (20.13)
    Week 48
    -38.29
    (22.29)
    -43.41
    (20.74)
    -39.09
    (20.99)
    -41.99
    (22.00)
    -43.71
    (20.63)
    Week 52
    -37.85
    (23.45)
    -44.02
    (22.47)
    -39.43
    (21.85)
    -43.24
    (24.17)
    -44.11
    (20.69)
    EOT
    -34.09
    (25.92)
    -40.56
    (22.93)
    -33.01
    (25.17)
    -39.28
    (24.37)
    -41.07
    (22.71)
    47. Secondary Outcome
    Title Change From Baseline in Subject's SGA at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    -7.87
    (25.15)
    -23.74
    (32.14)
    -31.59
    (27.41)
    -32.43
    (27.39)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -16.88
    Confidence Interval (2-Sided) 95%
    -23.81 to -9.95
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.51
    Estimation Comments Based on analysis of covariance model: SGA (100 mm VAS) Change = Treatment + Baseline SGA (100 mm VAS) + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -23.56
    Confidence Interval (2-Sided) 95%
    -29.83 to -17.28
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.18
    Estimation Comments Based on analysis of covariance model: SGA (100 mm VAS) Change = Treatment + Baseline SGA (100 mm VAS) + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    48. Secondary Outcome
    Title Change From Baseline in SGA Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -14.66
    (24.11)
    -18.30
    (24.25)
    -1.83
    (18.03)
    -6.59
    (21.35)
    -24.38
    (25.81)
    Week 8
    -21.29
    (30.24)
    -29.55
    (26.34)
    -5.71
    (22.02)
    -8.78
    (21.39)
    -29.31
    (26.07)
    Week 12
    -25.09
    (31.56)
    -32.75
    (27.51)
    -6.93
    (22.74)
    -8.85
    (27.24)
    -33.14
    (27.23)
    Week 16
    -29.98
    (30.36)
    -34.37
    (28.43)
    -21.29
    (24.56)
    -21.98
    (25.10)
    -34.88
    (25.91)
    Week 20
    -29.82
    (32.87)
    -36.21
    (26.97)
    -17.76
    (26.75)
    -24.53
    (24.24)
    -36.10
    (26.28)
    Week 24
    -30.09
    (31.93)
    -37.51
    (29.32)
    -25.96
    (25.72)
    -25.42
    (26.02)
    -37.12
    (26.33)
    Week 28
    -31.19
    (33.76)
    -37.91
    (27.72)
    -25.66
    (27.71)
    -26.01
    (26.63)
    -37.75
    (26.52)
    Week 32
    -34.49
    (30.49)
    -38.71
    (28.92)
    -27.97
    (28.37)
    -26.17
    (28.46)
    -38.02
    (27.74)
    Week 36
    -32.11
    (30.55)
    -39.08
    (26.81)
    -31.56
    (25.36)
    -26.64
    (26.00)
    -37.54
    (27.65)
    Week 40
    -34.66
    (32.19)
    -40.85
    (28.00)
    -30.76
    (27.65)
    -28.80
    (28.13)
    -38.42
    (26.72)
    Week 44
    -34.87
    (32.36)
    -39.51
    (29.51)
    -36.01
    (27.49)
    -28.19
    (26.52)
    -39.01
    (26.58)
    Week 48
    -35.53
    (32.53)
    -41.60
    (27.74)
    -34.09
    (26.60)
    -31.05
    (27.81)
    -39.47
    (26.06)
    Week 52
    -35.61
    (33.45)
    -41.54
    (28.60)
    -32.06
    (28.15)
    -32.91
    (27.33)
    -40.36
    (27.01)
    EOT
    -28.52
    (35.62)
    -38.84
    (29.05)
    -26.80
    (30.15)
    -28.71
    (27.54)
    -37.09
    (27.62)
    49. Secondary Outcome
    Title Change From Baseline in Subject's Assessment of Pain at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    -6.64
    (24.61)
    -23.78
    (30.75)
    -30.65
    (27.91)
    -30.82
    (27.68)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -17.58
    Confidence Interval (2-Sided) 95%
    -24.36 to -10.81
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.44
    Estimation Comments Based on analysis of covariance model: SGA of pain (100 mm VAS) Change = Treatment + Baseline SGA of pain (100 mm VAS) + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -23.90
    Confidence Interval (2-Sided) 95%
    -30.24 to -17.57
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.21
    Estimation Comments Based on analysis of covariance model: SGA of pain (100 mm VAS) Change = Treatment + Baseline SGA of pain (100 mm VAS) + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    50. Secondary Outcome
    Title Change From Baseline in Subject's Assessment of Pain Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -14.80
    (29.58)
    -18.36
    (24.49)
    -2.00
    (18.75)
    -8.23
    (25.32)
    -22.24
    (25.57)
    Week 8
    -22.45
    (31.06)
    -29.58
    (26.18)
    -4.11
    (21.26)
    -9.17
    (22.75)
    -27.43
    (26.90)
    Week 12
    -25.02
    (30.64)
    -31.83
    (28.13)
    -5.40
    (24.28)
    -9.15
    (25.80)
    -31.37
    (27.66)
    Week 16
    -28.58
    (31.83)
    -34.41
    (27.22)
    -20.93
    (25.76)
    -21.20
    (23.95)
    -32.48
    (26.22)
    Week 20
    -29.68
    (32.42)
    -35.83
    (28.40)
    -16.21
    (28.27)
    -24.63
    (26.52)
    -34.76
    (26.53)
    Week 24
    -29.78
    (32.23)
    -37.78
    (28.87)
    -22.64
    (26.09)
    -26.51
    (25.46)
    -35.45
    (27.27)
    Week 28
    -31.66
    (31.61)
    -36.48
    (29.18)
    -22.63
    (28.92)
    -24.93
    (26.19)
    -36.23
    (27.15)
    Week 32
    -34.15
    (30.84)
    -37.65
    (28.66)
    -25.53
    (27.07)
    -27.09
    (26.20)
    -37.20
    (27.18)
    Week 36
    -32.44
    (30.76)
    -38.48
    (27.27)
    -28.38
    (25.68)
    -26.79
    (25.38)
    -36.31
    (26.59)
    Week 40
    -35.06
    (31.74)
    -40.67
    (27.68)
    -26.65
    (28.10)
    -29.48
    (26.77)
    -36.45
    (26.58)
    Week 44
    -34.59
    (30.82)
    -38.76
    (29.25)
    -32.32
    (27.16)
    -28.55
    (25.32)
    -36.24
    (25.37)
    Week 48
    -34.87
    (31.77)
    -40.27
    (28.71)
    -31.57
    (27.05)
    -30.73
    (27.45)
    -37.03
    (26.66)
    Week 52
    -33.24
    (34.91)
    -42.01
    (28.18)
    -29.57
    (26.98)
    -32.11
    (27.54)
    -38.47
    (26.45)
    EOT
    -28.49
    (34.27)
    -38.03
    (29.14)
    -24.18
    (28.11)
    -28.51
    (27.74)
    -35.47
    (27.47)
    51. Secondary Outcome
    Title Number of Participants Who Withdrew Due to Lack of Efficacy
    Description The number of participants who withdrew due to lack of efficacy up to week 12 was calculated.
    Time Frame Up to week 12

    Outcome Measure Data

    Analysis Population Description
    Initial Randomization Set
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 101 104 102 200
    Count of Participants [Participants]
    7
    6.7%
    1
    1%
    1
    0.5%
    1
    1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.033
    Comments No Multiplicity Adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Fisher Exact
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.035
    Comments No Multiplicity Adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Fisher Exact
    Comments
    52. Secondary Outcome
    Title Change From Baseline in Health Assessment Questionnaire - Disability Index (HAQ-DI) at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    0.03
    (0.55)
    -0.28
    (0.55)
    -0.37
    (0.50)
    -0.39
    (0.48)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -0.34
    Confidence Interval (2-Sided) 95%
    -0.48 to -0.20
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.07
    Estimation Comments Based on analysis of covariance model: HAQ-DI Change = Treatment + Baseline HAQ-DI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea., and Taiwan)
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -0.40
    Confidence Interval (2-Sided) 95%
    -0.53 to -0.26
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.07
    Estimation Comments Based on analysis of covariance model: HAQ-DI Change = Treatment + Baseline HAQ-DI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea., and Taiwan)
    53. Secondary Outcome
    Title Change From Baseline in HAQ-DI Through Week 52
    Description 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.
    Time Frame Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 43 47 200
    Week 4
    -0.10
    (0.35)
    -0.19
    (0.40)
    -0.04
    (0.32)
    0.01
    (0.38)
    -0.24
    (0.43)
    Week 8
    -0.25
    (0.48)
    -0.31
    (0.48)
    -0.07
    (0.45)
    0.02
    (0.39)
    -0.35
    (0.45)
    Week 12
    -0.30
    (0.55)
    -0.38
    (0.50)
    -0.09
    (0.55)
    0.03
    (0.50)
    -0.39
    (0.47)
    Week 16
    -0.36
    (0.58)
    -0.41
    (0.48)
    -0.21
    (0.49)
    -0.12
    (0.48)
    -0.44
    (0.50)
    Week 20
    -0.34
    (0.56)
    -0.46
    (0.53)
    -0.22
    (0.58)
    -0.21
    (0.47)
    -0.46
    (0.52)
    Week 24
    -0.35
    (0.58)
    -0.46
    (0.53)
    -0.33
    (0.59)
    -0.26
    (0.45)
    -0.47
    (0.53)
    Week 28
    -0.35
    (0.58)
    -0.49
    (0.59)
    -0.33
    (0.53)
    -0.23
    (0.49)
    -0.47
    (0.51)
    Week 32
    -0.41
    (0.56)
    -0.50
    (0.54)
    -0.36
    (0.54)
    -0.29
    (0.46)
    -0.47
    (0.56)
    Week 36
    -0.40
    (0.56)
    -0.50
    (0.58)
    -0.36
    (0.51)
    -0.25
    (0.52)
    -0.47
    (0.55)
    Week 40
    -0.42
    (0.60)
    -0.51
    (0.57)
    -0.35
    (0.50)
    -0.28
    (0.47)
    -0.48
    (0.54)
    Week 44
    -0.39
    (0.58)
    -0.51
    (0.58)
    -0.42
    (0.63)
    -0.27
    (0.51)
    -0.49
    (0.55)
    Week 48
    -0.34
    (0.56)
    -0.52
    (0.57)
    -0.40
    (0.59)
    -0.31
    (0.50)
    -0.51
    (0.53)
    Week 52
    -0.36
    (0.57)
    -0.54
    (0.56)
    -0.46
    (0.57)
    -0.29
    (0.51)
    -0.51
    (0.53)
    EOT
    -0.30
    (0.60)
    -0.50
    (0.57)
    -0.37
    (0.64)
    -0.24
    (0.50)
    -0.47
    (0.53)
    54. Secondary Outcome
    Title Change From Baseline in Short Form Health Survey - 36 Questions, Version 2 (SF-36v2) Physical Component Summary Score at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 m Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    1.95
    (12.20)
    8.36
    (14.05)
    8.81
    (10.54)
    8.53
    (10.61)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value 6.87
    Confidence Interval (2-Sided) 95%
    3.69 to 10.05
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.61
    Estimation Comments Based on analysis of covariance model: SF-36v2 Change = Treatment + Baseline SF-36v2 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value 6.98
    Confidence Interval (2-Sided) 95%
    4.11 to 9.85
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.45
    Estimation Comments Based on analysis of covariance model: SF-36v2 Change = Treatment + Baseline SF-36v2 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    55. Secondary Outcome
    Title Change From Baseline in SF-36v2 Physical Component Summary Score Through Week 52
    Description 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.
    Time Frame Baseline and Week 4, 8, 12, 28, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit. The focus of data collection after Week 12 for participants transitioned from Placebo to Peficitinib was safety. Long term efficacy was not evaluated by the SF-36 questionnaire for them. These assessments were only conducted at Weeks 28 and 52 after transitioning to Peficitinib.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.New Group 3 Description
    Measure Participants 104 102 200
    Week 4
    3.82
    (10.21)
    3.20
    (10.49)
    6.10
    (10.07)
    Week 8
    6.43
    (10.98)
    6.78
    (9.99)
    7.35
    (10.23)
    Week 12
    9.93
    (12.38)
    9.63
    (10.33)
    8.40
    (10.51)
    Week 28
    10.85
    (12.79)
    10.95
    (12.04)
    10.28
    (10.67)
    Week 52
    13.07
    (12.41)
    9.88
    (12.51)
    11.18
    (11.77)
    56. Secondary Outcome
    Title Change From Baseline in SF-36v2 Mental Component Summary Score at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    0.00
    (8.65)
    2.70
    (7.59)
    3.69
    (8.23)
    3.23
    (8.24)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.004
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value 2.89
    Confidence Interval (2-Sided) 95%
    0.91 to 4.87
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.00
    Estimation Comments Based on analysis of covariance model: SF-36v2 Change = Treatment + Baseline SF-36v2 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value 3.25
    Confidence Interval (2-Sided) 95%
    1.30 to 5.19
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 0.98
    Estimation Comments Based on analysis of covariance model: SF-36v2 Change = Treatment + Baseline SF-36v2 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    57. Secondary Outcome
    Title Change From Baseline in SF-36v2 Mental Component Summary Score Through Week 52
    Description 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.
    Time Frame Baseline and Week 4, 8, 12, 28, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit. The focus of data collection after Week 12 for participants transitioned from Placebo to Peficitinib was safety. Long term efficacy was not evaluated by the SF-36 questionnaire for them. These assessments were only conducted at Weeks 28 and 52 after transitioning to Peficitinib.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 200
    Week 4
    1.53
    (7.19)
    1.72
    (7.58)
    2.85
    (8.07)
    Week 8
    2.91
    (7.39)
    3.55
    (9.08)
    3.56
    (8.49)
    Week 12
    2.38
    (7.53)
    4.01
    (8.17)
    3.63
    (7.95)
    Week 28
    2.95
    (8.07)
    3.52
    (8.14)
    3.80
    (7.66)
    Week 52
    4.23
    (8.17)
    4.39
    (8.08)
    3.79
    (8.38)
    58. Secondary Outcome
    Title Change From Baseline in SF-36v2 Role/Social Component Summary Score at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Units on a Scale]
    0.17
    (15.12)
    1.24
    (14.40)
    7.04
    (14.56)
    7.16
    (13.23)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.210
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value 2.27
    Confidence Interval (2-Sided) 95%
    -1.29 to 5.83
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.80
    Estimation Comments Based on analysis of covariance model: SF-36v2 Change = Treatment + Baseline SF-36v2 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value 6.23
    Confidence Interval (2-Sided) 95%
    2.74 to 9.71
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 1.77
    Estimation Comments Based on analysis of covariance model: SF-36v2 Change = Treatment + Baseline SF-36v2 + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    59. Secondary Outcome
    Title Change From Baseline in SF-36v2 Role/Social Component Summary Score Through Week 52
    Description 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.
    Time Frame Baseline and Week 4, 8, 12, 28, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit. The focus of data collection after Week 12 for participants transitioned from Placebo to Peficitinib was safety. Long term efficacy was not evaluated by the SF-36 questionnaire for them. These assessments were only conducted at Weeks 28 and 52 after transitioning to Peficitinib.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 200
    Week 4
    0.40
    (12.75)
    4.27
    (12.02)
    4.06
    (13.08)
    Week 8
    3.80
    (13.23)
    5.96
    (14.60)
    6.51
    (12.54)
    Week 12
    1.68
    (14.33)
    7.82
    (14.66)
    7.49
    (13.04)
    Week 28
    4.18
    (14.21)
    8.78
    (14.20)
    7.31
    (14.74)
    Week 52
    3.88
    (15.12)
    9.15
    (13.39)
    8.36
    (14.03)
    60. Secondary Outcome
    Title Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Percent Work Time Missed at Week 12
    Description 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).
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 48 57 49 99
    Mean (Standard Deviation) [Percent Work Time]
    6.78
    (25.76)
    -2.14
    (18.47)
    -6.80
    (19.40)
    -5.60
    (20.63)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.027
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -8.55
    Confidence Interval (2-Sided) 95%
    -16.11 to -1.00
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.81
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.010
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -10.17
    Confidence Interval (2-Sided) 95%
    -17.88 to -2.47
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.88
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    61. Secondary Outcome
    Title Change From Baseline in WPAI Percent Work Time Missed Through Week 52
    Description 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).
    Time Frame Baseline and Week 4, 8, 12, 28, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit. The focus of data collection after Week 12 for participants transitioned from Placebo to Peficitinib was safety. Long term efficacy was not evaluated by the WPAI questionnaire for them. These assessments were only conducted at Weeks 28 and 52 after transitioning to Peficitinib.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 200
    Week 4
    -0.56
    (20.13)
    -6.35
    (15.94)
    -3.71
    (17.34)
    Week 8
    -2.38
    (16.15)
    -6.10
    (19.30)
    -4.33
    (15.57)
    Week 12
    -1.38
    (18.13)
    -6.69
    (19.78)
    -4.73
    (18.54)
    Week 28
    -3.14
    (24.48)
    -6.46
    (20.29)
    -5.03
    (18.18)
    Week 52
    -6.76
    (22.20)
    -6.35
    (16.57)
    -4.52
    (14.91)
    62. Secondary Outcome
    Title Change From Baseline in WPAI Percent Impairment While Working at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 46 56 49 97
    Mean (Standard Deviation) [Percent Impairment]
    4.13
    (30.15)
    -13.04
    (30.45)
    -16.12
    (31.94)
    -24.43
    (25.82)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -20.67
    Confidence Interval (2-Sided) 95%
    -30.44 to -10.89
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 4.92
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -22.01
    Confidence Interval (2-Sided) 95%
    -32.06 to -11.97
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.06
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    63. Secondary Outcome
    Title Change From Baseline in WPAI Percent Impairment While Working Through Week 52
    Description 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.
    Time Frame Baseline and Week 4, 8, 12, 28, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit. The focus of data collection after Week 12 for participants transitioned from Placebo to Peficitinib was safety. Long term efficacy was not evaluated by the WPAI questionnaire for them. These assessments were only conducted at Weeks 28 and 52 after transitioning to Peficitinib.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 200
    Week 4
    -6.42
    (22.28)
    -6.46
    (27.48)
    -18.33
    (26.34)
    Week 8
    -14.31
    (26.10)
    -15.42
    (27.75)
    -20.52
    (25.31)
    Week 12
    -13.33
    (30.96)
    -19.77
    (31.66)
    -24.11
    (25.95)
    Week 28
    -17.35
    (34.63)
    -25.85
    (28.10)
    -29.53
    (26.78)
    Week 52
    -20.79
    (36.27)
    -23.89
    (30.55)
    -31.36
    (31.18)
    64. Secondary Outcome
    Title Change From Baseline in Percent Overall Work Impairment at Week 12
    Description 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)].
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 46 55 49 97
    Mean (Standard Deviation) [Percent iImpairment]
    3.62
    (30.49)
    -12.20
    (31.39)
    -18.68
    (33.81)
    -24.68
    (26.54)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -20.22
    Confidence Interval (2-Sided) 95%
    -30.38 to -10.06
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.12
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments
    Method Covariance model
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -23.67
    Confidence Interval (2-Sided) 95%
    -34.16 to -13.17
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 5.28
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    65. Secondary Outcome
    Title Change From Baseline in WPAI Percent Overall Work Impairment Through Week 52
    Description 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)].
    Time Frame Baseline and Week 4, 8, 12, 28, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit. The focus of data collection after Week 12 for participants transitioned from Placebo to Peficitinib was safety. Long term efficacy was not evaluated by the WPAI questionnaire for them. These assessments were only conducted at Weeks 28 and 52 after transitioning to Peficitinib.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 200
    Week 4
    -5.72
    (21.61)
    -8.67
    (28.20)
    -18.20
    (26.96)
    Week 8
    -14.16
    (27.22)
    -17.44
    (29.05)
    -20.94
    (25.88)
    Week 12
    -13.16
    (32.11)
    -22.84
    (33.22)
    -25.35
    (26.68)
    Week 28
    -17.48
    (34.87)
    -28.68
    (29.66)
    -30.12
    (28.21)
    Week 52
    -21.53
    (35.95)
    -24.75
    (31.45)
    -32.18
    (31.81)
    66. Secondary Outcome
    Title Change From Baseline in WPAI Percent Activity Impairment at Week 12
    Description 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.
    Time Frame Baseline and Week 12/ET

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with both baseline and available post-baseline data up to week 12. LOCF was used.
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 99 102 101 200
    Mean (Standard Deviation) [Percent Impairment]
    -4.65
    (26.39)
    -19.61
    (29.62)
    -24.65
    (28.27)
    -26.40
    (24.50)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 100 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -17.30
    Confidence Interval (2-Sided) 95%
    -24.00 to -10.61
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.39
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Placebo, Peficitinib 150 mg
    Comments Treatment Difference vs Placebo
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value <0.001
    Comments No multiplicity adjustment. Etanercept was open-label reference group and it was not included in statistical test.
    Method Covariance model
    Comments
    Method of Estimation Estimation Parameter LS mean
    Estimated Value -20.41
    Confidence Interval (2-Sided) 95%
    -26.59 to -14.24
    Parameter Dispersion Type: Standard Error of the Mean
    Value: 3.13
    Estimation Comments Based on analysis of covariance model: WPAI Change = Treatment + Baseline WPAI + the prior biologic-DMARD-IR (No, Yes) + concomitant DMARD use (No, Yes) + study region (Japan, Korea, and Taiwan).
    67. Secondary Outcome
    Title Change From Baseline in WPAI Percent Activity Impairment Through Week 52
    Description 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.
    Time Frame Baseline and Week 4, 8, 12, 28, and 52

    Outcome Measure Data

    Analysis Population Description
    FAS, number of participants with available data at each study visit. The focus of data collection after Week 12 for participants transitioned from Placebo to Peficitinib was safety. Long term efficacy was not evaluated by the WPAI questionnaire for them. These assessments were only conducted at Weeks 28 and 52 after transitioning to Peficitinib.
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 104 102 200
    Week 4
    -10.92
    (24.75)
    -11.30
    (21.82)
    -17.90
    (23.11)
    Week 8
    -20.10
    (26.89)
    -23.64
    (26.05)
    -25.33
    (23.95)
    Week 12
    -21.47
    (29.53)
    -26.74
    (28.48)
    -27.33
    (23.90)
    Week 28
    -25.18
    (31.40)
    -30.00
    (27.80)
    -30.34
    (26.86)
    Week 52
    -28.17
    (30.01)
    -34.07
    (27.69)
    -31.79
    (26.96)
    68. Secondary Outcome
    Title Number of Participants With Adverse Events During the First 12 Weeks
    Description 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.
    Time Frame Week 0 to Week 12

    Outcome Measure Data

    Analysis Population Description
    SAF
    Arm/Group Title Placebo Peficitinib 100 mg Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 101 104 102 200
    TEAEs
    54
    51.9%
    49
    48%
    55
    27.5%
    119
    117.8%
    Drug-related TEAEs
    29
    27.9%
    33
    32.4%
    38
    19%
    75
    74.3%
    TEAEs leading to death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Serious TEAEs
    4
    3.8%
    3
    2.9%
    2
    1%
    4
    4%
    Drug-related serious TEAEs
    3
    2.9%
    2
    2%
    1
    0.5%
    4
    4%
    ≥ Grade 3 TEAEs
    8
    7.7%
    6
    5.9%
    3
    1.5%
    6
    5.9%
    TEAEs leading to discontinuation
    4
    3.8%
    6
    5.9%
    3
    1.5%
    5
    5%
    Drug-related TEAEs leading to discontinuation
    1
    1%
    4
    3.9%
    2
    1%
    5
    5%
    Serious TEAEs leading to discontinuation
    2
    1.9%
    2
    2%
    2
    1%
    2
    2%
    Drug-related serious TEAEs leading to discont.
    1
    1%
    1
    1%
    1
    0.5%
    2
    2%
    69. Secondary Outcome
    Title Number of Participants With Adverse Events From Week 12
    Description 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.
    Time Frame Week 12 to week 52, plus 28 days after the week 52 visit for participants who did not enroll in the extension study

    Outcome Measure Data

    Analysis Population Description
    SAF
    Arm/Group Title Peficitinib 100 mg Peficitinib 150 mg Placebo / Peficitinib 100 mg Placebo / Peficitinib 150 mg Etanercept
    Arm/Group Description Participants were assigned to receive peficitinib 100 mg/day for 52 weeks. Participants were assigned to receive peficitinib 150 mg/day for 52 weeks. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly for 52 weeks.
    Measure Participants 96 93 43 47 191
    TEAEs
    78
    75%
    79
    77.5%
    41
    20.5%
    37
    36.6%
    156
    30.8%
    Drug-related TEAEs
    50
    48.1%
    47
    46.1%
    27
    13.5%
    26
    25.7%
    93
    18.3%
    TEAEs leading to death
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Serious TEAEs
    5
    4.8%
    6
    5.9%
    4
    2%
    5
    5%
    14
    2.8%
    Drug-related serious TEAEs
    2
    1.9%
    2
    2%
    2
    1%
    2
    2%
    5
    1%
    ≥ Grade 3 TEAEs
    9
    8.7%
    16
    15.7%
    2
    1%
    12
    11.9%
    23
    4.5%
    TEAEs leading to discontinuation
    7
    6.7%
    3
    2.9%
    2
    1%
    4
    4%
    8
    1.6%
    Drug-related TEAEs leading to discontinuation
    3
    2.9%
    2
    2%
    2
    1%
    4
    4%
    6
    1.2%
    Serious TEAEs leading to discontinuation
    4
    3.8%
    0
    0%
    1
    0.5%
    2
    2%
    3
    0.6%
    Drug-related serious TEAEs leading to discont.
    2
    1.9%
    0
    0%
    1
    0.5%
    2
    2%
    2
    0.4%

    Adverse Events

    Time Frame Week 0 to week 12, and from week 12 to week 52, plus 28 days after the week 52 visit for participants who did not enroll in the extension study.
    Adverse Event Reporting Description The safety analysis set (SAF) consisted of all participants who received at least one dose of study drugs.
    Arm/Group Title Weeks 0-12: Placebo Weeks 0-12: Peficitinib 100 mg Weeks 0-12: Peficitinib 150 mg Weeks 0-12: Etanercept Weeks 12-52: Peficitinib 100 mg Weeks 12-52: Peficitinib 150 mg Weeks 12-52: Placebo / Peficitinib 100 mg Weeks 12-52: Placebo / Peficitinib 150 mg Weeks 12-52: Etanercept
    Arm/Group Description Participants were assigned to receive placebo to peficitinib once a day until week 12. Participants were assigned to receive peficitinib 100 mg/day until 12 weeks. Participants were assigned to receive peficitinib 150 mg/day until 12 weeks. Participants were administered 50 mg of subcutaneous etanercept once weekly until 12 weeks. Participants were assigned to receive peficitinib 100 mg/day until 12 weeks and from week 12 to week 52. Participants were assigned to receive peficitinib 150 mg/day until 12 weeks and from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 100 mg/day from week 12 to week 52. Participants were assigned to receive placebo to peficitinib once a day until week 12 and peficitinib 150 mg/day from week 12 to week 52. Participants were administered 50 mg of subcutaneous etanercept once weekly until 12 weeks and from week 12 to week 52.
    All Cause Mortality
    Weeks 0-12: Placebo Weeks 0-12: Peficitinib 100 mg Weeks 0-12: Peficitinib 150 mg Weeks 0-12: Etanercept Weeks 12-52: Peficitinib 100 mg Weeks 12-52: Peficitinib 150 mg Weeks 12-52: Placebo / Peficitinib 100 mg Weeks 12-52: Placebo / Peficitinib 150 mg Weeks 12-52: Etanercept
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/101 (0%) 0/104 (0%) 0/102 (0%) 0/200 (0%) 0/96 (0%) 0/93 (0%) 0/43 (0%) 0/47 (0%) 0/191 (0%)
    Serious Adverse Events
    Weeks 0-12: Placebo Weeks 0-12: Peficitinib 100 mg Weeks 0-12: Peficitinib 150 mg Weeks 0-12: Etanercept Weeks 12-52: Peficitinib 100 mg Weeks 12-52: Peficitinib 150 mg Weeks 12-52: Placebo / Peficitinib 100 mg Weeks 12-52: Placebo / Peficitinib 150 mg Weeks 12-52: Etanercept
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 4/101 (4%) 3/104 (2.9%) 2/102 (2%) 4/200 (2%) 5/96 (5.2%) 6/93 (6.5%) 4/43 (9.3%) 5/47 (10.6%) 14/191 (7.3%)
    Blood and lymphatic system disorders
    Febrile neutropenia 1/101 (1%) 1 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Hypereosinophilic syndrome 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 1/200 (0.5%) 1 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Thrombocytopenia 1/101 (1%) 1 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Ear and labyrinth disorders
    Vertigo 1/101 (1%) 1 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 1/93 (1.1%) 1 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Gastrointestinal disorders
    Colitis 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 1/47 (2.1%) 1 0/191 (0%) 0
    Colonic polyp 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 1/43 (2.3%) 1 0/47 (0%) 0 0/191 (0%) 0
    Duodenal ulcer 0/101 (0%) 0 1/104 (1%) 1 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Gastric ulcer 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 1/96 (1%) 1 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Gastric ulcer haemorrhage 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 1/47 (2.1%) 1 0/191 (0%) 0
    General disorders
    Malaise 0/101 (0%) 0 1/104 (1%) 1 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Hepatobiliary disorders
    Hepatic function abnormal 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 1/200 (0.5%) 1 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Hepatic steatosis 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Immune system disorders
    Anaphylactic shock 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 1/93 (1.1%) 1 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Drug hypersensitivity 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 1/93 (1.1%) 1 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Infections and infestations
    Eczema herpeticum 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 1/43 (2.3%) 1 0/47 (0%) 0 0/191 (0%) 0
    Enteritis infectious 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Pharyngitis 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 1/93 (1.1%) 1 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Pharyngotonsillitis 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Pneumocystis jiroveci pneumonia 0/101 (0%) 0 0/104 (0%) 0 1/102 (1%) 1 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Pneumonia 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 1/200 (0.5%) 1 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 1/47 (2.1%) 1 1/191 (0.5%) 1
    Pneumonia pneumococcal 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 1/96 (1%) 1 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Injury, poisoning and procedural complications
    Foot fracture 0/101 (0%) 0 0/104 (0%) 0 1/102 (1%) 1 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Humerus fracture 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Patella fracture 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Radius fracture 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 1/96 (1%) 1 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Spinal compression fracture 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 2/93 (2.2%) 2 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Tendon rupture 1/101 (1%) 1 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Investigations
    Bronchoscopy 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 1/93 (1.1%) 1 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Hepatic enzyme increased 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 1/93 (1.1%) 1 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Rhabdomyolysis 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 1/200 (0.5%) 1 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Rheumatoid arthritis 1/101 (1%) 1 1/104 (1%) 1 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Spinal column stenosis 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Breast cancer 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 1/43 (2.3%) 1 0/47 (0%) 0 0/191 (0%) 0
    Colon cancer 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 1/96 (1%) 1 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Gastric cancer 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 1/96 (1%) 1 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Thyroid cancer 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Nervous system disorders
    Migraine 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 1/191 (0.5%) 1
    Renal and urinary disorders
    Renal disorder 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 1/47 (2.1%) 1 0/191 (0%) 0
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 1/96 (1%) 1 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Interstitial lung disease 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 1/200 (0.5%) 1 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 0/191 (0%) 0
    Organising pneumonia 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 2/191 (1%) 2
    Social circumstances
    Social stay hospitalisation 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 1/47 (2.1%) 2 0/191 (0%) 0
    Surgical and medical procedures
    Cataract operation 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 2/191 (1%) 2
    Prostatectomy 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 1/43 (2.3%) 1 0/47 (0%) 0 0/191 (0%) 0
    Vascular disorders
    Hypertension 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 1/43 (2.3%) 1 0/47 (0%) 0 0/191 (0%) 0
    Other (Not Including Serious) Adverse Events
    Weeks 0-12: Placebo Weeks 0-12: Peficitinib 100 mg Weeks 0-12: Peficitinib 150 mg Weeks 0-12: Etanercept Weeks 12-52: Peficitinib 100 mg Weeks 12-52: Peficitinib 150 mg Weeks 12-52: Placebo / Peficitinib 100 mg Weeks 12-52: Placebo / Peficitinib 150 mg Weeks 12-52: Etanercept
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 27/101 (26.7%) 30/104 (28.8%) 39/102 (38.2%) 63/200 (31.5%) 50/96 (52.1%) 42/93 (45.2%) 28/43 (65.1%) 23/47 (48.9%) 94/191 (49.2%)
    Gastrointestinal disorders
    Constipation 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 1/200 (0.5%) 1 3/96 (3.1%) 3 2/93 (2.2%) 2 3/43 (7%) 3 1/47 (2.1%) 1 3/191 (1.6%) 3
    Stomatitis 2/101 (2%) 2 2/104 (1.9%) 2 4/102 (3.9%) 4 4/200 (2%) 4 3/96 (3.1%) 3 1/93 (1.1%) 1 1/43 (2.3%) 1 3/47 (6.4%) 4 3/191 (1.6%) 4
    General disorders
    Injection site reaction 0/101 (0%) 0 0/104 (0%) 0 0/102 (0%) 0 25/200 (12.5%) 77 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 0/47 (0%) 0 9/191 (4.7%) 63
    Hepatobiliary disorders
    Hepatic function abnormal 3/101 (3%) 3 0/104 (0%) 0 7/102 (6.9%) 7 9/200 (4.5%) 9 2/96 (2.1%) 2 2/93 (2.2%) 3 2/43 (4.7%) 2 0/47 (0%) 0 3/191 (1.6%) 3
    Infections and infestations
    Bronchitis 1/101 (1%) 1 4/104 (3.8%) 4 1/102 (1%) 1 1/200 (0.5%) 1 4/96 (4.2%) 5 0/93 (0%) 0 1/43 (2.3%) 1 5/47 (10.6%) 5 7/191 (3.7%) 7
    Gastroenteritis 0/101 (0%) 0 0/104 (0%) 0 1/102 (1%) 1 1/200 (0.5%) 1 1/96 (1%) 1 2/93 (2.2%) 2 3/43 (7%) 3 0/47 (0%) 0 5/191 (2.6%) 5
    Herpes zoster 0/101 (0%) 0 1/104 (1%) 1 0/102 (0%) 0 2/200 (1%) 2 4/96 (4.2%) 4 4/93 (4.3%) 4 4/43 (9.3%) 4 1/47 (2.1%) 1 3/191 (1.6%) 6
    Influenza 2/101 (2%) 2 3/104 (2.9%) 3 1/102 (1%) 1 2/200 (1%) 2 4/96 (4.2%) 4 5/93 (5.4%) 5 2/43 (4.7%) 2 2/47 (4.3%) 2 8/191 (4.2%) 8
    Nasopharyngitis 6/101 (5.9%) 6 10/104 (9.6%) 11 19/102 (18.6%) 19 16/200 (8%) 17 21/96 (21.9%) 30 15/93 (16.1%) 21 13/43 (30.2%) 18 8/47 (17%) 11 49/191 (25.7%) 77
    Pharyngitis 1/101 (1%) 1 1/104 (1%) 1 1/102 (1%) 1 4/200 (2%) 5 7/96 (7.3%) 11 3/93 (3.2%) 4 0/43 (0%) 0 4/47 (8.5%) 4 6/191 (3.1%) 7
    Upper respiratory tract infection 2/101 (2%) 2 3/104 (2.9%) 3 3/102 (2.9%) 4 3/200 (1.5%) 3 3/96 (3.1%) 3 4/93 (4.3%) 5 4/43 (9.3%) 4 5/47 (10.6%) 7 3/191 (1.6%) 3
    Investigations
    Blood creatine phosphokinase increased 0/101 (0%) 0 4/104 (3.8%) 4 4/102 (3.9%) 4 1/200 (0.5%) 1 6/96 (6.3%) 9 7/93 (7.5%) 7 3/43 (7%) 3 3/47 (6.4%) 3 4/191 (2.1%) 4
    Musculoskeletal and connective tissue disorders
    Arthralgia 1/101 (1%) 1 0/104 (0%) 0 0/102 (0%) 0 0/200 (0%) 0 0/96 (0%) 0 0/93 (0%) 0 0/43 (0%) 0 3/47 (6.4%) 3 1/191 (0.5%) 1
    Rheumatoid arthritis 10/101 (9.9%) 17 2/104 (1.9%) 3 2/102 (2%) 12 3/200 (1.5%) 4 3/96 (3.1%) 3 3/93 (3.2%) 3 2/43 (4.7%) 3 0/47 (0%) 0 8/191 (4.2%) 10
    Respiratory, thoracic and mediastinal disorders
    Cough 4/101 (4%) 4 1/104 (1%) 1 3/102 (2.9%) 3 2/200 (1%) 2 5/96 (5.2%) 5 4/93 (4.3%) 5 1/43 (2.3%) 1 3/47 (6.4%) 3 8/191 (4.2%) 8
    Upper respiratory tract inflammation 1/101 (1%) 1 2/104 (1.9%) 2 3/102 (2.9%) 4 3/200 (1.5%) 3 3/96 (3.1%) 3 5/93 (5.4%) 5 1/43 (2.3%) 1 0/47 (0%) 0 9/191 (4.7%) 10

    Limitations/Caveats

    The focus of data collection after Week 12 for participants who transitioned from Placebo to Peficitinib was safety. Efficacy was not evaluated by the SF-36 and WPAI questionnaire after Week 12 for participants first assigned to placebo.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data. Sponsor must receive a site's manuscript prior to publication for review and comment as specified in the Investigator Agreement.

    Results Point of Contact

    Name/Title Clinical Trial Disclosure
    Organization Astellas Pharma Inc.
    Phone +81 3-3244-0512
    Email astellas.resultsdisclosure@astellas.com
    Responsible Party:
    Astellas Pharma Inc
    ClinicalTrials.gov Identifier:
    NCT02308163
    Other Study ID Numbers:
    • 015K-CL-RAJ3
    First Posted:
    Dec 4, 2014
    Last Update Posted:
    Mar 16, 2020
    Last Verified:
    Feb 1, 2020