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

Astellas Pharma Inc519 enrolled

Overview

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

This study was a multi-center, randomized, placebo-controlled, double-blind, parallel-group, confirmatory study to evaluate the efficacy and safety of ASP015K (100 and 150 mg/day) administered in combination with MTX in participants with RA who had an inadequate response to MTX. Participants orally received ASP015K 100 mg, ASP015K 150 mg or placebo once daily (QD) in combination with MTX after breakfast for 52 weeks. At Week 12, inadequate responders in the placebo group, as determined by a \< 20% improvement from baseline (i.e., treatment initiation day) in tender or painful joint count (TJC) and swollen joint count (SJC), were switched to either ASP015K 100 mg or ASP015K 150 mg, and the dosage was maintained until the end of treatment (EOT). In addition, participants who received placebo at Week 28 were switched to either ASP015K 100 mg or ASP015K 150 mg, and the dosage was maintained until the EOT. The ASP015K dose that was started for placebo group participants at Week 12 or Week 28 was randomly chosen at baseline. The dose was switched under the blinded condition. Participants who completed this study were eligible for participation in the open-label extension study (015K-CL-RAJ2). Participants made a follow-up visit after the week 52 visit if they did not enroll into the extension study on the day of the week 52 visit.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

519

Conditions

Rheumatoid Arthritis

Interventions

PeficitinibDRUG

oral tablet

PlaceboDRUG

oral tablet

MethotrexateDRUG

Oral tablet/capsule

Eligibility

Sex: ALLMin age: 20 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Subject has RA of \< 10 years duration at baseline that was diagnosed according to the 1987 American College of Rheumatology (ACR) criteria or the 2010 American College of Rheumatology/European League against Rheumatism (ACR/EULAR) criteria * Subject who did not receive the following drugs, or received the drugs with stable dosage for at least 28 days prior to the baseline (start of treatment) for RA treatment: * Non-steroidal anti-inflammatory drugs (NSAIDs; excluding topical formulations with a local action), oral morphine or equivalent opioid analgesics (≤ 30 mg/day), acetaminophen, or oral corticosteroids (≤ 10 mg/day in prednisolone equivalent) * At screening subject has active RA as evidenced by both of the following: * ≥ 6 tender/painful joints (using 68-joint assessment) * ≥ 6 swollen joints (using 66-joint assessment) * CRP (latex agglutination test) of ≥ 1.00 mg/dL at screening. * Subject meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class I, II or, III at screening * Inadequate responders to MTX which was continuously administered for at least 90 days prior to screening and MTX ≥ 8 mg/week for at least 28 days prior to baseline. However, inadequate responder to MTX \< 8 mg/week is eligible if intolerance precludes dose increase and defined as MTX-IR * Subject is able to continue stable dose of MTX (a maximum of 16 mg/week) from at least 28 days prior to screening until the end of treatment * Subject has bone erosion at the joint (as evidenced by x-rays of hands and feet) assessed in mTSS and any of the following apply at screening. Bone erosion may be evidenced by x-rays within 90 days prior to baseline. * Positive anti-CCP antibody: ≥ 4.5 U/mL * Positive rheumatoid factor: \> 15 IU/mL Exclusion Criteria: * Subject has received a biologic DMARD within the specified period * Inadequate responders to biologic DMARD as determined by investigator/sub-investigator * Subject has received intra-articular, intravenous, intramuscular or endorectal (excluding suppositories for anal diseases) corticosteroid within 28 days prior to baseline * Subject has participated in any study of ASP015K and has received ASP015K or placebo * Subject has received other investigational drugs within 90 days or within 5 half-lives, whichever is longer, prior to baseline * Subject has received plasma exchange therapy within 60 days prior to baseline * Subject has undergone joint drainage, has received local anesthesia and nerve block, or has received articular cartilage protectant at the assessed joint within 28 days prior to baseline * Subject has undergone surgery and has residual effects in the assessed joints at the discretion of investigator/sub-investigator, or is scheduled to undergo surgery that may affect the study evaluation of the assessed joints at the discretion of investigator/sub-investigator * A diagnosis of inflammatory arthritis (psoriatic arthritis, ankylosing spondylitis, SLE, sarcoidosis, etc.) other than RA * Any of the following laboratory values at screening: * Hemoglobin \< 9.0 g/dL * Absolute neutrophil count \< 1000/μL * Absolute lymphocyte count \< 800/μL * Platelet count \< 75000/μL * ALT ≥ 2 ×ULN * AST ≥ 2 × ULN * Total bilirubin (TBL) ≥ 1.5 × ULN * Estimated GFR ≤ 40 mL/min as measured by the MDRD method * β-D-glucan ≥ 11 pg/mL * Positive HBs antigen, HBc antibody, HBs antibody or HBV-DNA quantitation (However, subject with negative HBs antigen and HBV-DNA quantitation, and positive HBc antibody and/or HBs antibody is eligible if HBV-DNA is monitored by HBV-DNA quantitation at every scheduled visit after initiation of study drug administration.) * Positive HCV antibody * Subject has a history of or concurrent active tuberculosis (TB) * Subject has a history of or concurrent interstitial pneumonia and investigator/sub-investigator judges that it is inappropriate for the subject to participate in this study * Subject has a history of or concurrent malignant tumor (except for successfully treated basal cell carcinoma) * Subject has received live or live attenuated virus vaccination within 56 days prior to baseline. (Inactivated vaccines including influenza and pneumococcal vaccines are allowed.) * Subject has any ongoing severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, infectious, or autoimmune disease except for RA (excluding Sjogren's syndrome and chronic thyroiditis), or any ongoing illness which would make the subject unsuitable for the study as determined by the investigator/sub-investigator * Subject has a history of clinically significant allergy. (Clinically significant allergy includes allergies such as systemic urticaria induced by specific antigens and drugs, anaphylaxis, and allergy associated with shock necessitating hospitalized treatment.) * Subject has concurrent cardiac failure, defined as NYHA classification Class III or higher, or a history of it * Subject has concurrent prolonged QT syndrome or a history of it. Subject has prolonged QT interval (defined as QTc ≥ 500 msec. Subject has QTc ≥ 500 msec at retest will be excluded) at screening * Subject has a history of positive HIV infection * Subject has congenital short QT syndrome or a history of it. Subject has shortened QT interval (defined as QTc \< 330 msec. Subject has QTc \< 330 msec at retest will be excluded) at screening.

Locations (146)

Outcomes

Primary Outcomes

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

ACR20 response: greater than and equal to (≥) 20 percent (%) improvement in tender and swollen joint count; and ≥ 20% improvement in at least 3 of the following 5 criteria compared with baseline: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit.

Time frame: Baseline and week 12/Early termination (ET)

Change From Baseline in mTSS at Week 28

mTSS was defined as the sum of joint erosion scores graded by assessing erosion severity in 44 joints (16 per hand and 6 per feet) and JSN scores graded by assessing narrowing of joint spaces in 42 joints (15 per hand and 6 per feet). Erosion score was scored from 0 (no erosion) to 5 (complete collapse of bone) and the score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). JSN including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change from baseline was calculated as score at week 28 (ET) minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

Time frame: Baseline and week 28/ET

Secondary Outcomes

Percentage of Participants With an ACR20-CRP Response Through Week 52

ACR20 response:≥ 20% improvement in tender and swollen joint count; and ≥ 20% improvement in at least 3 of the following 5 criteria compared with baseline: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional disability via a health assessment questionnaire, and 5) C-reactive protein at each visit. EOT was defined as end of treatment i.e, either early termination or week 52.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

JP00037

Nagoya, Aichi-ken, Japan

JP00109

Nagoya, Aichi-ken, Japan

JP00130

Nagoya, Aichi-ken, Japan

JP00175

Nagoya, Aichi-ken, Japan

JP00066

Okazaki, Aichi-ken, Japan

JP00108

Toyohashi, Aichi-ken, Japan

JP00170

Toyohashi, Aichi-ken, Japan

JP00156

Toyota, Aichi-ken, Japan

JP00068

Yatomi, Aichi-ken, Japan

JP00180

Asahi, Chiba, Japan

...and 136 more locations

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants With an ACR50-CRP Response at Week 12

ACR50 response: ≥50% improvement in tender and swollen joint counts and 50% improvement in 3 of the following 5 criteria compared with baseline: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional ability via a health assessment questionnaire-Disability Index, and 5) C-reactive protein at each visit.

Time frame: Baseline and week 12/ET

Percentage of Participants With an ACR50-CRP Response Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants With an ACR70-CRP Response at Week 12

ACR70 response: ≥ 70% improvement in tender and swollen joint counts and 70% improvement in 3 of the following 5 criteria compared with baseline: 1) physician's global assessment of disease activity, 2) participant's assessment of disease activity, 3) participant's assessment of pain, 4) participant's assessment of functional ability via a health assessment questionnaire-Disability Index, and 5) C-reactive protein at each visit.

Time frame: Baseline and week 12/ET

Percentage of Participants With an ACR70-CRP Response Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in mTSS at Week 52

mTSS was defined as the sum of joint erosion scores graded by assessing erosion severity in 44 joints (16 per hand and 6 per feet) and JSN scores graded by assessing narrowing of joint spaces in 42 joints (15 per hand and 6 per feet). Erosion score was scored from 0 (no erosion) to 5 (complete collapse of bone) and the score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). JSN including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. mTSS scores ranged from 0 (normal) to 448 (worst possible total score). Change from baseline was calculated as score at week 52 (ET) minus score at baseline. An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

Time frame: Baseline and week 52/ET

Change From Baseline in JSN Score at Week 28 and Week 52

JSN was defined as narrowing in joint space width over the course of the study. The JSN score summarizes the severity of JSN in 30 joints of the hands and 12 joints of the feet. JSN, including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. Higher scores indicate greater disease activity.

Time frame: Baseline and weeks 28/ET and 52/ET

Change From Baseline in Erosion Score at Week 28 and Week 52

The joint erosion score was a summary of erosion severity in 32 joints of the hands and 12 joints of the feet. Each joint in the hand is scored from 0-5 and each joint in the foot is scored from 0-10. The score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet. By summing these score, the range of total erosion score is 0-280. Higher erosion score indicates greater disease activity.

Time frame: Baseline and weeks 28/ET and 52/ET

Percentage of Participants Achieving Change From Baseline in mTSS <= 0.5 at Week 28 and Week 52

mTSS was defined as the sum of joint erosion scores graded by assessing erosion severity in 44 joints (16 per hand and 6 per feet) and JSN scores graded by assessing narrowing of joint spaces in 42 joints (15 per hand and 6 per feet). Erosion score was scored from 0 (no erosion) to 5 (complete collapse of bone) and the score for erosion ranges from 0 to 160 in the hands and from 0 to 120 in the feet (the maximum erosion score for a joint in the foot is 10). JSN including subluxation, was scored from 0 (normal) to 4 (complete loss of joint space, bony ankylosis, or luxation), with a maximum JSN score of 168. mTSS scores ranged from 0 (normal) to 448 (worst possible total score). An increase in mTSS from baseline represented disease progression and/or joint worsening, no change represented halting of disease progression, and a decrease represented improvement.

Time frame: Baseline and week 28/ET and 52/ET

Change From Baseline in Disease Activity Score (DAS) 28-CRP at Week 12

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to 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

Change From Baseline in DAS28-CRP Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in DAS28-ESR at Week 12

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to 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

Change From Baseline in DAS28-ESR Score Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in TJC (68 Joints) at Week 12

The participants were examined for the tender joints and the location was confirmed by the investigator who assessed the following 68 joints which included 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). Higher TJC indicated greater disease activity.

Time frame: Baseline and week 12/ET

Change From Baseline in TJC (68 Joints) Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in SJC (66 Joints) at Week 12

The participants were examined for the swollen joints and the location was confirmed by the investigator who assessed the following 66 joints which included 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). Higher SJC indicated greater disease activity.

Time frame: Baseline and week 12/ET

Change From Baseline in SJC (66 Joints) Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants Achieving DAS28-CRP Score < 2.6 at Week 12

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to 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: Week 12/ET

Percentage of Participants Achieving DAS28-CRP Score < 2.6 Through Week 52

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to 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, 52 and EOT

Percentage of Participants Achieving DAS28-ESR Score < 2.6 at Week 12

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to 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

Percentage of Participants Achieving DAS28-ESR Score < 2.6 Through Week 52

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to 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, 52 and EOT

Percentage of Participants Achieving DAS28-CRP Score <= 3.2 at Week 12

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to 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

Percentage of Participants Achieving DAS28-CRP Score <= 3.2 Through Week 52

DAS28-CRP response consisted of following parameters: TJC (28 joints), SJC (28 joints), CRP, SGA, and calculated according to 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, 52 and EOT

Percentage of Participants Achieving DAS28-ESR Score <= 3.2 at Week 12

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to 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

Percentage of Participants Achieving DAS28-ESR Score <= 3.2 Through Week 52

DAS28-ESR response consisted of following parameters: TJC (28 joints), SJC (28 joints), ESR, SGA , and calculated according to 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, 52 and EOT

Change From Baseline in CRP at Week 12

Higher CRP indicates greater disease activity.

Time frame: Baseline and week 12/ET

Change From Baseline in CRP Through Week 52

Higher CRP indicates greater disease activity.

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in ESR at Week 12

Higher ESR indicates greater disease activity.

Time frame: Baseline and week 12/ET

Change From Baseline in ESR Through Week 52

Higher ESR indicates greater disease activity.

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants With a European League Against Rheumatism (EULAR) Good Response Using DAS28-CRP at Week 12

The Disease Activity Score Based on 28-joints Count based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1. Percentage of participants with good response have been reported in this outcome measure.

Time frame: Week 12/ET

Percentage of Participants With a EULAR Good Response Using DAS28-CRP Through Week 52

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP at Week 12

The Disease Activity Score Based on 28-joints Count based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1. Percentage of participants with good or moderate response have been reported in this outcome measure.

Time frame: Week 12/ET

Percentage of Participants With a Good or Moderate EULAR Response Using DAS28-CRP Through Week 52

The Disease Activity Score Based on 28-joints Count based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1. Percentage of participants with good or moderate response have been reported in this outcome measure.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants With a EULAR Good Response Using DAS28-ESR at Week 12

Time frame: Week 12/ET

Percentage of Participants With a EULAR Good Response Using DAS28-ESR Through Week 52

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants With a EULAR Good or Moderate Response Using DAS28-ESR at Week 12

The Disease Activity Score Based on 28-joints Count based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1. Percentage of participants with good or moderate response have been reported in this outcome measure.

Time frame: Week 12/ET

Percentage of Participants With a EULAR Good or Moderate Response Using DAS28-ESR Through Week 52

The Disease Activity Score Based on 28-joints Count based EULAR response criteria were used to measure individual response as none, good, and moderate, depending on the extent of change from baseline and the level of disease activity reached. Good responders: change from baseline \>1.2 with DAS28 =\< 3.2; moderate responders: change from baseline \>1.2 with DAS28 \>3.2 to =\<5.1 or change from baseline \>0.6 to =\<1.2 with DAS28 =\<5.1; non-responders: change from baseline =\< 0.6 or change from baseline \>0.6 and =\<1.2 with DAS28 \>5.1. Percentage of participants with good or moderate response have been reported in this outcome measure.

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants Achieving ACR / EULAR Remission at Week 12

ACR/EULAR Remission was defined as TJC (68 joints) ≤ 1, SJC (66 joints) ≤1, CRP ≤1 mg/dL, and participant's global assessment of arthritis ≤ 1 cm (on a visual analog scale (VAS) of 0 - 100 mm).

Time frame: Week 12/ET

Percentage of Participants Achieving ACR / EULAR Remission Through Week 52

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Percentage of Participants Achieving Simplified Disease Activity Index (SDAI) Remission <=3.3 at Week 12

SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to description. SDAI = TJC + SJC + SGA + PGA + CRP. SDAI Remission was defined as SDAI score ≤ 3.3.

Time frame: Week 12/ET

Percentage of Participants Achieving SDAI Remission Score <=3.3 Through Week 52

Time frame: Weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in SDAI Score at Week 12

SDAI score consisted of following parameters: TJC (28 joints), SJC (28 joints), SGA, PGA, CRP (mg/dL), and calculated according to 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

Change From Baseline in SDAI Score Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in PGA at Week 12

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

Change From Baseline in PGA Through Week 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.

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in SGA at Week 12

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

Change From Baseline in SGA Through Week 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.

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in SGAP at Week 12

The participant assessed his/her own pain severity on a visual analog scale (VAS) of 0-100 mm on the questionnaire form. Higher SGA of pain (100 mm VAS) scores indicated greater activity pain.

Time frame: Baseline and week 12/ET

Change From Baseline in SGAP Through Week 52

The participant assessed his/her own pain severity on a visual analog scale (VAS) of 0-100 mm on the questionnaire form. Higher SGA of pain (100 mm VAS) scores indicated greater activity pain.

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Number of Participants Who Withdrew Due to Lack of Efficacy

Participants who discontinued due to lack of efficacy have been reported.

Time frame: Up to week 52

Change From Baseline in HAQ-DI at Week 12

Participant-reported assessment of ability to perform tasks in 8 categories of daily living activities: dress/groom; arise; eat; walk; reach; grip; hygiene; and common activities over past week. Each item was scored on 4-point scale from 0 to 3: 0=no difficulty; 1=some difficulty; 2=much difficulty; 3=unable to do. Overall score was computed as the sum of domain scores and divided by the number of domains answered. Total possible score range 0-3 where 0 = least difficulty and 3 = extreme difficulty.

Time frame: Baseline and week 12/ET

Change From Baseline in HAQ-DI Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52 and EOT

Change From Baseline in Short Form Health Survey - 36 Questions, Version 2 (SF-36v2) Physical Component Summary Score at Week 12

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

Change From Baseline in SF-36v2 Physical Component Summary Score Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 28, 52 and EOT

Change From Baseline in SF-36v2 Mental Component Summary Score at Week 12

Time frame: Baseline and week 12/ET

Change From Baseline in SF-36v2 Mental Component Summary Score Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 28, 52 and EOT

Change From Baseline in SF-36v2 Role/Social Component Summary Score at Week 12

Time frame: Baseline and week 12/ET

Change From Baseline in SF-36v2 Role/Social Component Summary Score Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 28, 52 and EOT

Change From Baseline in Work Productivity and Activity Impairment Questionnaire (WPAI) Percent Work Time Missed at Week 12

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). Higher WPAI scores indicated greater activity impairment. The scores were multiplied by 100 to express in percentages. Percent work time missed due to problem was calculated as Q2/(Q2+Q4). Negative values indicate improvement from baseline.

Time frame: Baseline and week 12/ET

Change From Baseline in WPAI Percent Work Time Missed Through Week 52

Time frame: Baseline, weeks 4, 8, 12, 28, 52 and EOT

Change From Baseline in WPAI Percent Impairment While Working at Week 12

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). Higher WPAI scores indicated greater activity impairment. The scores were multiplied by 100 to express in percentages. Percent impairment while working due to problem was calculated as Q5/10. Negative values indicate improvement from baseline.

Time frame: Baseline and week 12/ET

Change From Baseline in WPAI Percent Impairment While Working Through Week 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). Higher WPAI scores indicated greater activity impairment. The scores were multiplied by 100 to express in percentages. Percent impairment while working due to problem was calculates as Q5/10. Negative values indicate improvement from baseline.

Time frame: Baseline, weeks 4, 8, 12, 28, 52 and EOT

Change From Baseline in Percent Overall Work Impairment at Week 12

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). Higher WPAI scores indicated greater activity impairment. The scores were multiplied by 100 to express in percentages. Percent overall work impairment due to problem was calculated as Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4))x(Q5/10)\]. Negative values indicate improvement from baseline.

Time frame: Baseline and week 12/ET

Change From Baseline in WPAI Percent Overall Work Impairment Through Week 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). Higher WPAI scores indicated greater activity impairment. The scores were multiplied by 100 to express in percentages. Percent overall work impairment due to problem was calculated as Q2/(Q2+Q4)+\[(1-(Q2/(Q2+Q4))x(Q5/10)\]. Negative values indicate improvement from baseline.

Time frame: Baseline, weeks 4, 8, 12, 28, 52 and EOT

Change From Baseline in WPAI Percent Activity Impairment at Week 12

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 indicated greater activity impairment. The scores were multiplied by 100 to express in percentages. Percent activity impairment due to problem was calculated as Q6/10. Negative values indicate improvement from baseline.

Time frame: Baseline and week 12/ET

Change From Baseline in WPAI Percent Activity Impairment Through Week 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 indicated greater activity impairment. The scores were multiplied by 100 to express in percentages. Percent activity impairment due to problem was calculated as Q6/10. Negative values indicate improvement from baseline.

Time frame: Baseline, weeks 4, 8, 12, 28, 52 and EOT

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) During the First 12 Weeks

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), AEs were graded as grade 1=mild; grade 2=moderate: grade 3 = severe or medically significant, grade 4 = life threatening, grade 5 = death related to AE.

Time frame: Week 0 to week 12

Number of Participants With TEAEs From Week 12 to Week 28

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 NCI-CTCAE, AEs were graded as grade 1=mild; grade 2=moderate: grade 3 = severe or medically significant, grade 4 = life threatening, grade 5 = death related to AE

Time frame: Week 12 to week 28

Number of Participants With TEAEs From Week 28 to Week 52

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), AEs were graded as grade 1=mild; grade 2=moderate: grade 3 = severe or medically significant, grade 4 = life threatening, grade 5 = death related to AE.

Time frame: Week 28 to week 52, plus 28 days after the week 52 visit for participants who did not enroll in the extension study