A Dose Response Study of E6011 in Participants With Rheumatoid Arthritis Inadequately Responding to Methotrexate

Study Overview
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Brief Summary
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This study is a multicenter, randomized, double-blind, placebo-controlled, parallel-group comparison study in rheumatoid arthritis participants inadequately responding to methotrexate.

Official Title
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A Dose Response Study of E6011 in Subjects With Rheumatoid Arthritis Inadequately Responding to Methotrexate

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Drug: E6011
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria Aged greater than or equal to (>=) 18 and less than (<)75 years old at the time of informed consent Diagnosed with rheumatoid arthritis (RA) under the 1987 American College of Rheumatology (ACR) or 2010 ACR/European League Against Rheumatism (EULAR) criteria >=12 weeks before informed consent Received methotrexate (MTX) treatment at 6 to 16 milligram (mg)/week for >=12 weeks before screening and presented ≥6 tender joints (out of 68 joints) and >=6 swollen joints (out of 66 joints) in the Screening and Observation Phases Can continue stable dose regimen of MTX at 6 to 16 mg/week from 4 weeks before starting the study treatment until completion of the Extension Phase (or until study discontinuation) C-reactive protein (CRP) level >=0.6 mg/deciliter (dL) or erythrocyte sedimentation rate (ESR) >=28 millimeters per hour (mm/hr) in the Screening Phase Erosions at >=3 sites in radiographic image in the Screening Phase, or those with erosions at >=1 site and either positive for rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP) antibody in the Screening Phase Weighs >=30 kilograms (kg) and ≤100 kg in the Screening Phase Has voluntarily consented, in writing, to participate in this study. If a participant is below the age of 20, also consented, in writing, by a legally acceptable representative. Has been thoroughly briefed on the conditions for participation in the study, is able to understand, and is willing and able to comply with all aspects of the protocol Exclusion Criteria: Any history or complication of inflammatory arthritic disorder other than RA or Sjogren's syndrome Meets the ACR 1991 Revised Criteria for the Classification of Global Functional Status in RA Class IV in the Screening Phase Received immunoglobulin preparations or blood products within 24 weeks before starting the study treatment Received a live vaccine within 12 weeks before starting the study treatment, or is planning to receive Evidence of clinically significant disease (example, cardiac, respiratory, gastrointestinal, or renal disease) that could affect the participant's safety or interfere with the study assessments in the opinion of the investigator or subinvestigator Complication of uncontrolled disorders such as acute cardiac infarction, unstable angina, brain infarct, or symptomatic intracerebral hemorrhage History of severe allergy (shock or anaphylactoid symptoms) History or current clinical condition of malignant tumor, lymphoma, leukemia, or lymphoproliferative disease, except for skin carcinoma (epithelial carcinoma or basal cell carcinoma) and cervix carcinoma which has completely excised and without metastasis or recurrence for more than 5 years before informed consent Immunodeficiency or history of human immunodeficiency virus (HIV) infection Infection requiring hospitalization or intravenous administration of antibiotics or disease requiring administration of antivirus drugs (example, herpes zoster) within 4 weeks before starting the study treatment History of tuberculosis or current complication of active tuberculosis History of clinically important vasculitis Tested positive for any of the following in the Screening Phase: HIV, hepatitis B virus surface antigen (HBs antigen), hepatitis B virus surface antibody (HBs antibody), hepatitis B virus core antibody (HBc antibody), hepatitis B virus deoxyribonucleic acid (HBV DNA), hepatitis C virus antibody (HCV antibody), human T-lymphotrophic virus Type I antibody (HTLV-1 antibody), or syphilis Positive in tuberculosis test (QuantiFERON®TB Gold Test or T-SPOT®.TB Test) in the Screening Phase Findings indicating a history of tuberculosis on chest x-ray in the Screening Phase Neurological findings such as paralysis, visual impairment, or language disorder in the Screening Phase Demonstrated prolonged QTcF interval (>450 milliseconds [ms]) in repeated electrocardiogram examinations Females of childbearing potential who have a positive pregnancy test in the Screening or Observation Phase or are breastfeeding Females of childbearing potential who: Had unprotected sexual intercourse within 30 days before study entry and who do not agree to use a highly effective method of contraception (e.g., total abstinence, an intrauterine device, a double-barrier method [such as condom plus diaphragm with spermicide], a contraceptive implant, an oral contraceptive, or have a vasectomized partner with confirmed azoospermia) throughout the entire study period or for 28 days after study drug discontinuation Are currently abstinent, and do not agree to use a double-barrier method (as described above) or refrain from being sexually active during the study period or for 28 days after study drug discontinuation Are using hormonal contraceptives but are not on a stable dose of the same hormonal contraceptive product for at least 4 weeks before dosing and who do not agree to use the same contraceptive during the study or for 28 days after study drug discontinuation (NOTE: All females will be considered to be of childbearing potential unless they are postmenopausal [amenorrheic for at least 12 consecutive months, in the appropriate age group, and without other known or suspected cause] or have been sterilized surgically [i.e., bilateral tubal ligation, total hysterectomy, or bilateral oophorectomy, all with surgery at least 1 month before dosing]). Males who have not had a successful vasectomy (confirmed azoospermia) or they and their female partners do not meet the criteria above (i.e., not of childbearing potential or practicing highly effective contraception throughout the study period or for 28 days after study drug discontinuation). No sperm donation is allowed during the study period or for 28 days after study drug discontinuation. Scheduled for surgery during the study Currently enrolled in another clinical study or used any investigational drug or device within 28 days (or 5* the half-life, whichever is longer) before informed consent Has been treated with E6011 or any biologics for use in RA that has not been approved Use of a psychotropic agent as recreational purpose other than therapeutic purpose Any history of a medical condition or a concomitant medical condition that in the opinion of the investigator or subinvestigator would compromise the participant's ability to safely complete the study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E6011 100 milligrams (mg)<br>In the Treatment Phase, E6011 100 mg will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102. | Drug: E6011<br>* subcutaneous administration<br>|
| Experimental: E6011 200 mg<br>In the Treatment Phase, E6011 200 mg will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102. | Drug: E6011<br>* subcutaneous administration<br>|
| Experimental: E6011 400 mg<br>In the Treatment Phase, E6011 400 mg will be subcutaneously administered at Weeks 0, 1, 2, 4, 6, 8, and 10, and then E6011 200 mg will be subcutaneously administered every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102. | Drug: E6011<br>* subcutaneous administration<br>|
| Placebo Comparator: Placebo<br>In the Treatment Phase, placebo will be subcutaneously administered at Weeks 0, 1, and 2, and then every 2 weeks up to Week 22. In the Extension Phase, E6011 200 mg will be subcutaneously administered every 2 weeks until Week 102. | Drug: Placebo<br>* subcutaneous administration<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Phase: Percentage of Participants Who Achieved an American College of Rheumatology 20 (ACR20) Response at Week 12 Based on Non-responder Imputation (NRI) | The ACR20 response was defined as if the following 3 criteria (ACR components) were met: Greater than or equal to (>=) 20 percent (%) reduction from baseline in the tender joint count (TJC) in 68 joints (TJC68); >=20% reduction from baseline in the swollen joint count (SJC) in 66 joints (SJC66); >=20% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (visual analog scale [VAS]) , Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), Health Assessment Questionnaire disability index (HAQ-DI), and C-reactive protein (CRP). | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment Phase: Percentage of Participants Who Achieved an ACR20 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI | The ACR20 response was defined as if the following 3 criteria (ACR components) were met: >=20% reduction from baseline in the TJC in 68 joints (TJC68); >=20% reduction from baseline in the SJC in 66 joints (SJC66); >=20% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (VAS), Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), HAQ-DI, and CRP. | Weeks 2, 4, 8, 16, 20, and 24 | 
| Treatment Phase: Percentage of Participants Who Achieved an ACR50 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI | The ACR50 response was defined as if the following 3 criteria (ACR components) were met: >=50% reduction from baseline in the TJC in 68 joints (TJC68); >=50% reduction from baseline in the SJC in 66 joints (SJC66); >=50% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (VAS), Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), HAQ-DI, and CRP. | Weeks 2, 4, 8, 16, 20, and 24 | 
| Treatment Phase: Percentage of Participants Who Achieved an ACR70 Response at Weeks 2, 4, 8, 16, 20 and 24 Based on NRI | The ACR70 response was defined as if the following 3 criteria (ACR components) were met: >=70% reduction from baseline in the TJC in 68 joints (TJC68); >=70% reduction from baseline in the SJC in 66 joints (SJC66); >=70% reduction from baseline in at least 3 of the following 5 assessments: Physician's Global Assessment of Disease Activity (VAS), Participant's Global Assessment of Disease Activity (VAS), Participant's Assessment of Pain (VAS), HAQ-DI, and CRP. | Weeks 2, 4, 8, 16, 20, and 24 | 
| Change From Baseline in Tender Joint Counts (TJC) at Each Visit Based on Last Observation Carried Forward (LOCF) | A total of 68 joints were examined for tenderness by applying pressure to the joint line or by moving joints through their respective ranges of motion. Joints were examined for tenderness by applying pressure to the joint line or by moving joints through their respective ranges of motion. Tender joints were marked with tick or cross in corresponding frames of the Assessment Sheet for Tender Joint Counts. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Swollen Joint Counts (SJC) at Each Visit Based on LOCF | A total of 66 joints (minus 2 hip joints from evaluated tender joints) were examined for swollen joints. Swollen joints were marked with open circles in corresponding frames of the Assessment Sheet for Swollen Joint Counts. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Participant's Assessment of Pain Based on VAS Score at Each Visit Based on LOCF | Intensity and severity of pain associated with rheumatoid arthritis (RA) were indicated by the participant on a score sheet, Pain/disease activity assessments reported by the participant, by placing a mark on a 100 millimeter (mm) horizontal VAS. The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity). Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Participant's Global Assessment of Disease Activity Based on VAS Score at Each Visit Based on LOCF | Participants were evaluated on their disease activity of RA, and entered the result on the score sheet, disease activity assessments reported by the participant, by placing a mark on a 100 mm horizontal VAS. The scale ranged from 0-100 mm, where 0 indicated no disease activity (symptom free and no arthritis symptoms) and 100 represented maximum disease activity (maximum arthritis disease activity). Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Physician's Global Assessment of Disease Activity Scale Based on VAS Score at Each Visit Based on LOCF | The Physician's Global Assessment of Disease Activity was recorded using the 100 mm horizontal VAS. Physician rated participant's RA disease activity on a scale ranged from 0-100 mm, where 0 indicated no disease activity (no arthritis) and 100 represented maximum disease activity (maximum arthritis). Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Health Assessment Questionnaire Disability Index (HAQ-DI) at Each Visit Based on LOCF | The degree of disability was self-evaluated by the participant using the HAQ-DI. The assessment was made based on the activities capable without any aids or devices. The 20-question instrument assessed the degree of difficulty a person had in accomplishing tasks in 8 functional areas (dressing, arising, eating, walking, hygiene, reaching, gripping, and activities of daily living). Responses in each functional area were scored from 0, indicated no difficulty, to 3, indicated inability to perform a task in that area. 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. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in C-reactive Protein (CRP) Values at Each Visit Based on LOCF | CRP of each participants was measured as a part of blood biochemical tests. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Erythrocyte Sedimentation Rate (ESR) Values at Each Visit Based on LOCF | ESR were a type of blood test. An ESR was used to monitor the arthritis condition. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80,and 84 | 
| Change From Baseline in Disease Activity Score 28 (DAS28)-ESR Values at Each Visit Based on LOCF | The DAS28 index was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and ESR value. Total score ranged between 0-10. A DAS28-ESR score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value <2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in DAS28-CRP Values at Each Visit Based on LOCF | The DAS28 index was a composite score of weighted components including tender joint counts of 28, swollen joint counts of 28, participant global assessment of disease activity score, and CRP value. Total score ranged between 0-10. A DAS28-CRP score of 5.1 or above = high disease activity, a value between 3.2 and 5.1 = moderate disease activity and value between 2.6 and 3.2 = low disease activity, value <2.6 = disease remission. A positive change in score indicates worsening, and a negative change indicates improvement. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Simple Disease Activity Index (SDAI) Values at Each Visit Based on LOCF | The SDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-86. SDAI score of 26 or above = high disease activity, a value between 11 and 26 = moderate disease activity and value less than or equal to (<=) 11 = low disease activity, value <=33 = disease remission. Higher scores indicated higher disease activity. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Clinical Disease Activity Index (CDAI) Values at Each Visit Based on LOCF | The CDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-76. CDAI score of 22 or above = high disease activity, a value between 10 and 22 = moderate disease activity and value less than or equal to <=10 = low disease activity, value <=2.8 = disease remission. Higher scores indicated higher disease activity. Data reported for the Extension Phase from Baseline to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Number of Participants With a European League Against Rheumatism (EULAR) Good, Moderate or No Response Using DAS28-ESR at Each Visit Based on NRI | 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. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Number of Participants With a EULAR Good or Moderate Response Using DAS28-CRP at Each Visit Based on NRI | 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. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Percentage of Participants Who Achieved SDAI Remission at Each Visit Based on NRI | The SDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-86. SDAI score of 26 or above = high disease activity, a value between 11 and 26 = moderate disease activity and value <=11 = low disease activity. Higher scores indicated higher disease activity. SDAI Remission was defined as SDAI score <=3.3. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, 84, 88, 92, 96, 100, and 104 | 
| Percentage of Participants Who Achieved CDAI Remission at Each Visit Based on NRI | The CDAI was calculated from tender joint counts of 28, swollen joint counts of 28, participant's global assessment of disease activity, physician global assessment of disease activity score, and CRP value. Total score ranged between 0-76. CDAI score of 22 or above = high disease activity, a value between 10 and 22 = moderate disease activity and value less than or equal to <=10 = low disease activity. Higher scores indicated higher disease activity. CDAI Remission was defined as CDAI score <=2.8. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Percentage of Participants Who Achieved Boolean Remission at Each Visit Based on NRI | Boolean remission criteria was defined as: tender joint count 68 <=1; swollen joint count 68 <=1; CRP <=1 mg/dL; and disease activity assessments VAS (mm) by participants <=1. Data reported for the Extension Phase from Week 2 to Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Weeks 2, 4, 8, 12, 16, 20, and 24; Extension Phase: Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, 64, 68, 72, 76, 80, and 84 | 
| Change From Baseline in Modified Total Sharp Score (mTSS) at Each Visit Based on Observed Cases (OC) | The mTSS was a measure of change in joint health. X-rays of hands, wrists, and feet (including distal interphalangeal joints) were obtained. Totals for hands and feet for erosion scores (range 0 to 320) and joint space narrowing scores (range 0 to 208) were calculated and added to obtain the mTSS (range = 0 [normal] to 528 [maximal disease]). An increase in mTSS from Baseline represents disease progression and/or joint worsening; no progression was defined as a change of <=0.5. Data reported for the Extension Phase from Baseline and Week 24, is the same data for the Treatment Phase, but excluding the participants who did not gave consent to participate in Extension Phase. | Treatment Phase: Baseline and Week 24; Extension Phase: Baseline, Weeks 24, 52, 76, and 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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E6011, rheumatoid arthritis