The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00106535




Registration number
NCT00106535
Ethics application status
Date submitted
25/03/2005
Date registered
28/03/2005
Date last updated
6/02/2014

Titles & IDs
Public title
A Study to Assess the Effect of Tocilizumab + Methotrexate on Prevention of Structural Joint Damage in Patients With Moderate to Severe Active Rheumatoid Arthritis (RA)
Scientific title
A Randomized, Double-blind Study of Safety and Prevention of Structural Joint Damage During Treatment With Tocilizumab Versus Placebo, in Combination With Methotrexate, in Patients With Moderate to Severe Rheumatoid Arthritis
Secondary ID [1] 0 0
WA17823
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Rheumatoid Arthritis 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Osteoarthritis
Inflammatory and Immune System 0 0 0 0
Rheumatoid arthritis

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - tocilizumab [RoActemra/Actemra]
Treatment: Drugs - Placebo
Treatment: Drugs - Methotrexate

Experimental: Tocilizumab 4 mg/kg + Methotrexate - Tocilizumab 4 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Experimental: Tocilizumab 8 mg/kg + Methotrexate - Tocilizumab 8 mg/kg IV every 4 weeks plus MTX 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.

Placebo Comparator: Placebo + Methotrexate - Placebo intravenously (IV) every 4 weeks plus methotrexate (MTX) 10-25 mg (oral or parenteral) weekly for 52 weeks. From Week 16 participants with < 20% improvement in swollen and tender joints counts were eligible for escape therapy with tocilizumab. After Week 52 participants were able to switch to open label treatment with tocilizumab 8 mg/kg every 4 weeks for 12 months in year 2 (except patients who had a >70% improvement in both swollen and tender joint counts who remained on blinded treatment). Participants who completed year 2 of the study were eligible to enter an optional open-label long-term extension period (Year 3 to 5) and received Tocilizumab 8 mg/kg every 4 weeks.


Treatment: Drugs: tocilizumab [RoActemra/Actemra]
4 mg/kg or 8 mg/kg IV/month every 4 weeks.

Treatment: Drugs: Placebo
IV/month

Treatment: Drugs: Methotrexate
10-25 mg/week

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With American College of Rheumatology-ACR20 Response - ACR20 response is defined as a = 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [1] 0 0
Baseline, Week 24
Primary outcome [2] 0 0
Change From Baseline in Modified Total Sharp-Genant Score at Week 52 - Radiographs were taken of each hand and foot at Baseline and Week 52 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 (normalized from 98) and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 (normalized from 104) and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Timepoint [2] 0 0
Baseline, Week 52
Primary outcome [3] 0 0
Change in Physical Function as Measured by the Area Under the Curve (AUC) for the Change From Baseline in the Health Assessment Questionnaire (HAQ) Disability Index at Week 52 - HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 1 year by using the AUC of the change from baseline in HAQ-DI score through week 52. Decreases in AUC of change from baseline in HAQ-DI indicate a greater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 52 HAQ-DI score, the AUC of the change from baseline was standardized to 52 weeks using the latest timepoint available for calculation of the AUC. The mean was adjusted for region. A negative change from baseline indicated improvement.
Timepoint [3] 0 0
Baseline to Week 52
Primary outcome [4] 0 0
Change From Baseline in the Modified Total Sharp-Genant Score at Week 104 - Radiographs of each hand and foot were taken at Baseline and Week 104 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Timepoint [4] 0 0
Baseline, Week 104
Primary outcome [5] 0 0
Change in Physical Function as Measured by the Area Under the Curve for the Change From Baseline in the Health Assessment Questionnaire- Disability Index (HAQ-DI) at Week 104 - HAQ-DI consisted of 20 questions in 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities rated on a 4-point scale where 0=without any difficulty to 3=unable to do. The sum of scores was divided by the number of domains with a score for a total possible score of 0 (best) to 3 (worst). Functional disability was determined as a cumulative measure of HAQ-DI over 2 years by using the AUC of the change from baseline in HAQ-DI score through week 104. Decreases in AUC of change from baseline in HAQ-DI indicated a gr eater average improvement in physical function over time and represent a decrease in sustained impairment. For patients with missing week 104 HAQ-DI score, the AUC of the change from baseline was standardized to 104 weeks using the latest timepoint available for calculation of the AUC. A negative change from baseline indicated improvement.
Timepoint [5] 0 0
Baseline to Week 104
Secondary outcome [1] 0 0
Percentage of Participants With ACR50 Response - ACR50 response is defined as a = 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Percentage of Participants With ACR70 Response - ACR70 response is defined as a = 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant [either C-reactive protein or Erythrocyte Sedimentation Rate].
Timepoint [2] 0 0
Baseline,Week 24
Secondary outcome [3] 0 0
Swollen Joint Count (66 Joint Count): Mean Change From Baseline at Week 24 - 66 joints were assessed for swelling and joints are classified as swollen/not swollen giving a total possible swollen joint count score of 0 to 66.
Timepoint [3] 0 0
Baseline, Week 24
Secondary outcome [4] 0 0
Tender Joint Count (68 Joint Count): Mean Change From Baseline at Week 24 - 68 joints are assessed for tenderness and joints are classified as tender/not tender giving a total possible tender joint count score of 0 to 68.
Timepoint [4] 0 0
Baseline, Week 24
Secondary outcome [5] 0 0
Patient's Global Visual Analog Scale (VAS): Mean Change From Baseline at Week 24 - The patient's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Physician's Global VAS: Mean Change From Baseline at Week 24 - The physician's global assessment of disease activity is assessed on a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm as "maximum disease activity" (maximum arthritis disease activity).
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Patient's Pain VAS: Mean Change From Baseline at Week 24 - The patient assessed their pain on a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change indicated improvement.
Timepoint [7] 0 0
Baseline and Week 24
Secondary outcome [8] 0 0
C-Reactive Protein (CRP): Mean Change From Baseline at Week 24 - The serum concentration of C-Reactive Protein (CRP) is measured in mg/dL. A reduction in the level is considered an improvement.
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24 - The Erythrocyte Sedimentation Rate (ESR) was measured in mm/hr. A reduction in the level is considered an improvement.
Timepoint [9] 0 0
Baseline, Week 24
Secondary outcome [10] 0 0
Health Assessment Questionnaire Disability Index (HAQ-DI): Mean Change From Baseline at Week 24 - HAQ-DI is a self-completed patient questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Timepoint [10] 0 0
Baseline, Week 24
Secondary outcome [11] 0 0
Percentage of Participants With American College of Rheumatology (ACR20) Response at Week 52 - ACR20 response is defined as a = 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [11] 0 0
Baseline, Week 52
Secondary outcome [12] 0 0
Percentage of Participants With ACR20 Response at Week 104 - ACR20 response is defined as a = 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [12] 0 0
Baseline, Week 104
Secondary outcome [13] 0 0
Percentage of Participants With ACR50 Response at Week 52 - ACR50 response is defined as a = 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [13] 0 0
Baseline, Week 52
Secondary outcome [14] 0 0
Percentage of Participants With ACR50 Response at Week 104 - ACR50 response is defined as a = 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [14] 0 0
Baseline, Week 104
Secondary outcome [15] 0 0
Percentage of Participants With ACR70 Response at Week 52 - ACR70 response is defined as a = 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [15] 0 0
Baseline, Week 52
Secondary outcome [16] 0 0
Percentage of Participants With ACR70 Response at Week 104 - ACR50 response is defined as a = 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [16] 0 0
Baseline, Week 104
Secondary outcome [17] 0 0
Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months - ACR70 response is defined as a = 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [17] 0 0
104 Weeks
Secondary outcome [18] 0 0
Change From Baseline in Swollen Joint Count at Week 52 - 66 joints were assessed at Baseline and Week 52 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Timepoint [18] 0 0
Baseline, Week 52
Secondary outcome [19] 0 0
Change From Baseline in Tender Joint Count at Week 52 - 68 joints were assessed at Baseline and Week 52 for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Timepoint [19] 0 0
Baseline, Week 52
Secondary outcome [20] 0 0
Change From Baseline in Patient's Global Assessment of Disease Activity at Week 52 - The patient's global assessment of disease activity is assessed at Baseline and Week 52 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Timepoint [20] 0 0
Baseline, Week 52
Secondary outcome [21] 0 0
Change From Baseline in Physicians Global Assessment of Disease Activity at Week 52 - The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Timepoint [21] 0 0
Baseline, Week 52
Secondary outcome [22] 0 0
Change From Baseline in the Patient's Pain VAS at Week 52 - The patient assessed their pain at Baseline and Week 52 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Timepoint [22] 0 0
Baseline, Week 52
Secondary outcome [23] 0 0
Change From Baseline in C-Reactive Protein (CRP) at Week 52 - Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 52 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Timepoint [23] 0 0
Baseline, Week 52
Secondary outcome [24] 0 0
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52 - Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 52 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.
Timepoint [24] 0 0
Baseline, Week 52
Secondary outcome [25] 0 0
Change From Baseline in Swollen Joint Count at Week 104 - 66 joints were assessed at Baseline and Week 104 for swelling and joints were classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Timepoint [25] 0 0
Baseline, Week 104
Secondary outcome [26] 0 0
Change From Baseline in Tender Joint Count at Week 104 - 68 joints were assessed for tenderness and joints were classified as tender/not tender for a total possible tender joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Timepoint [26] 0 0
Baseline, Week 104
Secondary outcome [27] 0 0
Change From Baseline in Patient's Global Assessment of Disease Activity at Week 104 - The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Timepoint [27] 0 0
Baseline, Week 104
Secondary outcome [28] 0 0
Change From Baseline in Physicians Global Assessment of Disease Activity at Week 104 - The physician's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Timepoint [28] 0 0
Baseline, Week 104
Secondary outcome [29] 0 0
Change From Baseline in the Patient's Pain VAS at Week 104 - The patient assessed their pain at Baseline and Week 104 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Timepoint [29] 0 0
Baseline, Week 104
Secondary outcome [30] 0 0
Change From Baseline in C-Reactive Protein (CRP) at Week 104 - Blood was collected for C-Reactive Protein (CRP) at Baseline and Week 104 and was analyzed at a central laboratory. The serum concentration of CRP was measured in milligrams/deciliter (mg/dL). A reduction in the level is considered an improvement.
Timepoint [30] 0 0
Baseline, Week 104
Secondary outcome [31] 0 0
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104 - Blood was collected for Erythrocyte Sedimentation Rate (ESR) at Baseline and Week 104 and was analyzed at a local laboratory. ESR was measured in millimeters/hour (mm/hr). A reduction in the level is considered an improvement.
Timepoint [31] 0 0
Baseline, Week 104
Secondary outcome [32] 0 0
Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 52 - The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do). HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst).
Timepoint [32] 0 0
Baseline, Week 52
Secondary outcome [33] 0 0
Percentage of Participants Who Achieve an Improvement of at Least 0.3 Units From Baseline in the HAQ Disability Index at Week 104 - The Stanford Health Assessment Questionnaire disability index (HAQ-DI) is a patient completed questionnaire specific for rheumatoid arthritis. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip and common daily activities. Each domain has at least two component questions. There are four possible responses for each component ranging from 0 (without any difficulty) to 3 (unable to do).HAQ-DI=sum of worst scores in each domain divided by the number of domains answered for a total possible score of 0 (best) to 3 (worst).
.
Timepoint [33] 0 0
Baseline, Week 104
Secondary outcome [34] 0 0
Area Under Curve (AUC) of the ACRn to Week 24 - The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 24. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Timepoint [34] 0 0
24 Weeks
Secondary outcome [35] 0 0
Area Under Curve (AUC) of the ACRn to Week 52 - The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 52. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Timepoint [35] 0 0
52 Weeks
Secondary outcome [36] 0 0
Area Under Curve (AUC) of the ACRn Score at Week 104 - The ACRn is defined as each patient's lowest percent improvement from Baseline of 3 measures: tender joint count (68 joints), swollen joint count (66 joints), and the improved score achieved in at least 3 of the 5 remaining ACR core components (physician global assessment, patient global assessment, pain, HAQ, and C-reactive protein or ESR, respectively). AUC of ACRn, a continuous variable, was calculated from Baseline to Week 104. A positive score change from Baseline indicated an improvement. The higher the ACRn score the better.
Timepoint [36] 0 0
104 Weeks
Secondary outcome [37] 0 0
Change From Baseline in Disease Activity Score (DAS28) at Week 24 - The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Timepoint [37] 0 0
Baseline, Week 24
Secondary outcome [38] 0 0
Change From Baseline in Disease Activity Score (DAS28) at Week 52 - The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Timepoint [38] 0 0
Baseline, Week 52
Secondary outcome [39] 0 0
Change From Baseline in Disease Activity Score (DAS28) at Week 104 - The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity], and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
Timepoint [39] 0 0
Baseline, Week 104
Secondary outcome [40] 0 0
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 24 - The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
European League Against Rheumatism (EULAR) Good response: DAS28 = 3.2 and a change from Baseline < -1.2.
EULAR Moderate response: DAS28 >3.2 to = 5.1 or a change from Baseline < -0.6 to = -1.2.
Timepoint [40] 0 0
Baseline, Week 24
Secondary outcome [41] 0 0
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 52 - The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
European League Against Rheumatism (EULAR) Good response: DAS28 = 3.2 and a change from Baseline < -1.2.
EULAR Moderate response: DAS28 >3.2 to = 5.1 or a change from Baseline < -0.6 to = -1.2.
Timepoint [41] 0 0
Baseline, Week 52
Secondary outcome [42] 0 0
Percentage of Participants With DAS28 Good or Moderate EULAR Response at Week 104 - The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm) [visual analog scale: 0=no disease activity to 100=maximum disease activity] , and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement.
European League Against Rheumatism (EULAR) Good response: DAS28 = 3.2 and a change from Baseline < -1.2.
EULAR Moderate response: DAS28 >3.2 to = 5.1 or a change from Baseline < -0.6 to = -1.2.
Timepoint [42] 0 0
Baseline, Week 104
Secondary outcome [43] 0 0
Percentage of Participants With DAS28 Remission at Week 24 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 remission is defined as a DAS28 score <2.6.
Timepoint [43] 0 0
Week 24
Secondary outcome [44] 0 0
Percentage of Participants With DAS28 Remission at Week 52 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control.DAS28 Remission is defined as a DAS28 score <2.6.
Timepoint [44] 0 0
Week 52
Secondary outcome [45] 0 0
Percentage of Participants With DAS28 Remission at Week 104 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.
Timepoint [45] 0 0
Week 104
Secondary outcome [46] 0 0
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Timepoint [46] 0 0
24 Weeks
Secondary outcome [47] 0 0
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Timepoint [47] 0 0
52 Weeks
Secondary outcome [48] 0 0
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. Higher calculated AUC values are worse (indicate higher disease activity).
Timepoint [48] 0 0
104 Weeks
Secondary outcome [49] 0 0
Change From Baseline in Modified Total Sharp-Genant Score at Week 24 - Radiographs were taken of each hand and foot at Baseline and Week 24 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Timepoint [49] 0 0
Baseline, Week 24
Secondary outcome [50] 0 0
Change From Baseline in Modified Total Sharp-Genant Score at Week 80 - Radiographs were taken of each hand and foot at Baseline and Week 80 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint). The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score.
Timepoint [50] 0 0
Baseline, Week 80
Secondary outcome [51] 0 0
Change From Baseline in Erosion Score at Week 24 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Timepoint [51] 0 0
Baseline, Week 24
Secondary outcome [52] 0 0
Change From Baseline in Erosion Score at Week 52 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Timepoint [52] 0 0
Baseline, Week 52
Secondary outcome [53] 0 0
Change From Baseline in Erosion Score at Week 80 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Timepoint [53] 0 0
Baseline, Week 80
Secondary outcome [54] 0 0
Change From Baseline in Erosion Score at Week 104 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). A lower number change from Baseline indicated a better score.
Timepoint [54] 0 0
Baseline, Week 104
Secondary outcome [55] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 24 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower change from Baseline indicated a better score.
Timepoint [55] 0 0
Baseline, Week 24
Secondary outcome [56] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 52 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Timepoint [56] 0 0
Baseline, Week 52
Secondary outcome [57] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 80 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Timepoint [57] 0 0
Baseline, Week 80
Secondary outcome [58] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 104 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Timepoint [58] 0 0
Baseline, Week 104
Secondary outcome [59] 0 0
Percentage of Participants With no Progression of Erosion at Week 24 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Timepoint [59] 0 0
Baseline, Week 24
Secondary outcome [60] 0 0
Percentage of Participants With no Progression of Erosion at Week 52 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Timepoint [60] 0 0
Baseline, Week 52
Secondary outcome [61] 0 0
Percentage of Participants With no Progression of Erosion at Week 104 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best) to 142 (worst). No progression of Erosion score was defined as a change from Baseline of less than or equal to zero.
Timepoint [61] 0 0
Baseline, Week 104
Secondary outcome [62] 0 0
Percentage of Participants With no Progression of Joint Space Narrowing at Week 24 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score was defined as a change from Baseline of less than or equal to zero.
Timepoint [62] 0 0
Baseline, Week 24
Secondary outcome [63] 0 0
Percentage of Participants With no Progression of Joint Space Narrowing at Week 52 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.
Timepoint [63] 0 0
Baseline, Week 52
Secondary outcome [64] 0 0
Percentage of Participants With no Progression of Joint Space Narrowing at Week 104 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). No progression of Joint Space Narrowing score is defined as a change from Baseline of less than or equal to zero.
Timepoint [64] 0 0
Baseline, Week 104
Secondary outcome [65] 0 0
Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52 - HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from baseline indicated improvement.
Timepoint [65] 0 0
Baseline, Week 52
Secondary outcome [66] 0 0
Change From Baseline in HAQ Disability Index at Week 104 - HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8). Total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
Timepoint [66] 0 0
Baseline, Week 104
Secondary outcome [67] 0 0
Change From Baseline in Quality Life Short Form-36 (SF-36) Score at Week 24 - The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from baseline indicates improvement.
Timepoint [67] 0 0
Baseline, Week 24
Secondary outcome [68] 0 0
Change From Baseline in SF-36 Score at Week 52 - The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicates improvement.
Timepoint [68] 0 0
Baseline, Week 52
Secondary outcome [69] 0 0
Change From Baseline in SF-36 Score at Week 104 - The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. A positive change from Baseline indicated improvement.
Timepoint [69] 0 0
Baseline, Week 104
Secondary outcome [70] 0 0
Change From Baseline in Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F) Score at Week 24 - FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Timepoint [70] 0 0
Baseline, Week 24
Secondary outcome [71] 0 0
Change From Baseline in FACIT-F Score at Week 52 - FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Timepoint [71] 0 0
Baseline, Week 52
Secondary outcome [72] 0 0
Change From Baseline in FACIT-F Score at Week 104 - FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). A higher score reflects an improvement in the patient's health status.
Timepoint [72] 0 0
Baseline, Week 104
Secondary outcome [73] 0 0
Change From Baseline in Rheumatoid Factor (RF) at Week 24 in Those Patients With Positive RF - Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 24 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Timepoint [73] 0 0
Baseline, Week 24
Secondary outcome [74] 0 0
Change From Baseline in Rheumatoid Factor (RF) at Week 52 in Those Patients With Positive RF - Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 52 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Timepoint [74] 0 0
Baseline, Week 52
Secondary outcome [75] 0 0
Change From Baseline in Rheumatoid Factor (RF) at Week 104 in Those Patients With Positive RF - Blood was collected for Rheumatoid Factor (RF) at Baseline and Week 104 and was analyzed at a central laboratory. RF level was reported in international units/milliliter (IU/mL). A positive RF= >15 IU/mL. A lower number change from Baseline indicated a better result.
Timepoint [75] 0 0
Baseline, Week 104
Secondary outcome [76] 0 0
Time to Onset of ACR20 by Treatment Group - Time in days until ACR20 response. ACR20 response was defined as a = 20% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [76] 0 0
6 months
Secondary outcome [77] 0 0
Time to Onset of ACR50 by Treatment Group - Time in days until ACR50 response. ACR50 response was defined as a = 50% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [77] 0 0
6 months
Secondary outcome [78] 0 0
Time to Onset of ACR70 by Treatment Group - Time in days until ACR70 response. ACR70 response is defined as a = 70% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [78] 0 0
6 months
Secondary outcome [79] 0 0
Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response - Insufficient therapeutic response (patient not responding to the drug as assessed by the physician) was selected by the investigator as a reason that the patient withdrew from the study.
Timepoint [79] 0 0
104 Weeks
Secondary outcome [80] 0 0
Percentage of Participants in Each Treatment Group Who Receive Escape Therapy - In Escape 1, participants in the Tocilizumab 4 mg/kg + Methotrexate and Tocilizumab 8 mg/kg + Methotrexate groups received tocilizumab 8 mg/kg as escape therapy. Participants in the Placebo + Methotrexate group received tocilizumab 4 mg/kg as escape therapy.
In Escape 2, all participants received tocilizumab 8 mg/kg.
Timepoint [80] 0 0
104 Weeks
Secondary outcome [81] 0 0
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 24 - The percentage of participants, who achieved ACR remission at any study visit up to Week 24. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Timepoint [81] 0 0
24 Weeks
Secondary outcome [82] 0 0
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 52 - The percentage of participants, who achieved ACR remission at any study visit up to Week 52. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Timepoint [82] 0 0
52 Weeks
Secondary outcome [83] 0 0
Percentage of Participants Who Achieved Remission According to the ACR Remission Criteria by Week 104 - The percentage of participants who achieved ACR remission at any study visit up to Week 104. ACR remission required that all five of the following criteria were met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or pain on motion, no soft tissue swelling in joints or tendon sheaths, and ESR < 30 mm/hr for a female or 20 mm/hr for a male.
Timepoint [83] 0 0
104 Weeks
Secondary outcome [84] 0 0
Percentage of Participants Who Achieved Complete Clinical Response at Week 52 - Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline = 0 in the total Sharp-Genant score, erosion score, and JSN score]. Patients who achieve a complete clinical response at any time in the study are counted as responders, even if the response is not maintained.
Timepoint [84] 0 0
52 Weeks
Secondary outcome [85] 0 0
Percentage of Participants Who Achieved Complete Clinical Response at Week 104 - Complete clinical response is defined as a continuous 6-month period of remission by ACR criteria [defined as five of the following criteria are met for at least two consecutive months: morning stiffness < 15 minutes, no fatigue, no joint pain, no joint tenderness or swelling, and ESR < 30 mm/hr for a female or 20 mm/hr for a male] and no radiographic progression [defined as change from baseline = 0 in the total Sharp-Genant score, erosion score, and JSN score].
Timepoint [85] 0 0
104 Weeks
Secondary outcome [86] 0 0
End of Study: Percentage of Participants With ACR Response at Week 260 - ACR20/50/70/90 response is defined as a = 20/50/70/90% improvement (reduction) compared with baseline for both total joint count-68 joints (TJC68) and swollen joint count-66 joints (SJC66), as well as for three of the additional five ACR core set variables: Patient's Assessment of Pain over the previous 24 hours: using a Visual Analog Scale (VAS) left end of the line 0=no pain to right end of the line 100=unbearable pain; Patient's Global Assessment of Disease Activity and Physician's Global Assessment of Disease Activity over the previous 24 hours using a VAS where left end of the line 0=no disease activity to right end of the line 100=maximum disease activity; Health Assessment Questionnaire: 20 questions, 8 components: dressing/grooming, arising, eating, walking, hygiene, reach, grip and activities, 0=without difficulty to 3=unable to do; and acute-phase reactant, either C-reactive protein or Erythrocyte Sedimentation Rate.
Timepoint [86] 0 0
Baseline, Week 260
Secondary outcome [87] 0 0
End of Study: Percentage of Participants With DAS28 Remission at Week 260 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. DAS28 Remission is defined as a DAS28 score <2.6.
Timepoint [87] 0 0
Week 260
Secondary outcome [88] 0 0
End of Study: Percentage of Participants With DAS28 Low Disease Activity (LDA) at Week 260 - The DAS28 score is a measure of the patient's disease activity calculated using the tender joint count (TJC) [28 joints], swollen joint count (SJC) [28 joints], patient's global assessment of disease activity [visual analog scale: 0=no disease activity to 100=maximum disease activity] and the erythrocyte sedimentation rate (ESR). DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. LDA is defined as DAS28 =3.2.
Timepoint [88] 0 0
Week 260
Secondary outcome [89] 0 0
End of Study: Percentage of Participants With DAS28 European League Against Rheumatism (EULAR) Good or Moderate Response at Week 260 - The DAS28 score is a measure of the subject's disease activity. It is based on the tender joint count (28 joints), swollen joint count (28 joints), patient's global assessment of disease activity (mm), and ESR. DAS28 total scores range from 0 to approximately 10. Scores below 2.6 indicate best disease control and scores above 5.1 indicate worse disease control. A negative change from Baseline indicated improvement. EULAR Good response: DAS28 = 3.2 and a change from Baseline < -1.2. EULAR Moderate response: DAS28 >3.2 to = 5.1 or a change from Baseline < -0.6 to = -1.2.
Timepoint [89] 0 0
Baseline, Week 260
Secondary outcome [90] 0 0
End of Study: Change From Baseline in Swollen Joint Count at Week 260 - 66 joints were assessed at Baseline and Week 260 for swelling and joints are classified as swollen/not swollen for a total possible swollen joint count of 0 (best) to 66 (worst). A negative change from Baseline indicated improvement.
Timepoint [90] 0 0
Baseline, Week 260
Secondary outcome [91] 0 0
End of Study: Change From Baseline in Tender Joint Count at Week 260 - 68 joints were assessed at Baseline and Week 260 for tenderness and joints are classified as tender/not tender for a total possible swollen joint count of 0 (best) to 68 (worst). A negative change from Baseline indicated improvement.
Timepoint [91] 0 0
Baseline, Week 260
Secondary outcome [92] 0 0
End of Study: Change From Baseline in Health Assessment Questionnaire-Disability Index (HAQ-DI) at Week 260 - HAQ-DI is a self-completed questionnaire specific for RA. It consists of 20 questions referring to 8 domains: dressing/grooming, arising, eating, walking, hygiene, reach, grip; common daily activities. Each domain has at least 2 component questions. There are 4 possible responses for each component 0=without any difficulty 1=with some difficulty 2=with much difficulty 3=unable to do. To Calculate HAQ-DI the patient must have a domain score for at least 6 of 8 domains. The HAQ-DI is the sum of the scores, divided by the number of domains that have a score (in range 6-8) for a total possible score minimum/maximum 0 (best) to 3 (worst). A negative change from Baseline indicated improvement.
Timepoint [92] 0 0
Baseline, Week 260
Secondary outcome [93] 0 0
End of Study: Change From Baseline in the Patient's Global Assessment of Disease Activity Visual Analog Scale (VAS) at Week 260 - The patient's global assessment of disease activity was assessed at Baseline and Week 104 using a 0 to 100 mm horizontal visual analogue scale (VAS) by the patient. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Timepoint [93] 0 0
Baseline, Week 260
Secondary outcome [94] 0 0
End of Study: Change From Baseline in the Physician's Global Assessment of Disease Activity VAS at Week 260 - The physician's global assessment of disease activity was assessed using a 0 to 100 mm horizontal visual analogue scale (VAS) by the physician. The left-hand extreme of the line equals 0 mm, and is described as "no disease activity" (symptom-free and no arthritis symptoms) and the right-hand extreme equals 100 mm, as "maximum disease activity" (maximum arthritis disease activity). A negative change from Baseline indicated improvement.
Timepoint [94] 0 0
Baseline, Week 260
Secondary outcome [95] 0 0
End of Study: Change From Baseline in the Patient's Pain VAS at Week 260 - The patient assessed their pain at Baseline and Week 260 using a 0 to 100 millimeter (mm) horizontal visual analogue scale (VAS). The left-hand extreme of the line equals 0 mm, and is described as "no pain" and the right-hand extreme equals 100 mm as "unbearable pain". A negative change from Baseline indicated improvement.
Timepoint [95] 0 0
Baseline, Week 260
Secondary outcome [96] 0 0
End of Study: Percentage of Participants With Clinical Improvement in the FACIT-Fatigue Score at Week 260 - FACIT-F is a 13-item questionnaire. Patients scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the patient's response to the questions (with the exception of 2 negatively stated), the greater the patient's fatigue. For all questions, except for the 2 negatively stated ones, the code was reversed and a new score was calculated as (4 minus the patient's response). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse score) to 52 (better score). Clinically relevant improvement is defined as a =5 change from Baseline.
Timepoint [96] 0 0
Baseline, Week 260
Secondary outcome [97] 0 0
End of Study: Percentage of Participants With Clinical Relevant Improvement in the SF-36 Score at Week 260 - The SF-36 is a questionnaire used to assess physical functioning and is made up of eight domains: Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional and Mental Health. Transforming and standardizing these domains leads to the calculation of the Physical (PCS) and Mental (MCS) Component Summary measures. Scores ranging from 0 to 100, with 0=worst score (or quality of life) and 100=best score. Clinically relevant improvement is defined as a =5 change from Baseline.
Timepoint [97] 0 0
Baseline, Week 260
Secondary outcome [98] 0 0
End of Study: Change From Baseline in Total Sharp-Genant Score at Week 260 - Radiographs were taken of each hand and foot at Baseline and Week 260 and evaluated at a central reading service by two independent radiologists using the Genant modified method according to Sharp. Erosion Score: A total of 14 locations in each hand and wrist and 6 joints in the foot were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion. Joint Narrowing Score: A total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint).The maximum total erosion score in the hands is 100 and in the feet 42, the maximum scores for joint space narrowing in the hands is 100 and in the feet 48. The maximum modified Sharp score achievable is 290. A lower number change from Baseline indicated a better score. The results were reported based on the treatment the patient was originally randomized to.
Timepoint [98] 0 0
Baseline, Week 260
Secondary outcome [99] 0 0
End of Study: Change From Baseline in Erosion Score at Week 260 - Radiographs were taken of a total of 14 locations in each hand and wrist and 6 joints in the foot and were evaluated for erosion using an 8-point scale where 0=Normal to 3.5=very severe erosion for a total possible score of 0 (best ) to 142 (worst). A lower number change from Baseline indicated a better score.
Timepoint [99] 0 0
Baseline, Week 260
Secondary outcome [100] 0 0
End of Study: Change From Baseline in Joint Space Narrowing Score at Week 260 - Radiographs were taken of a total of 13 locations in each hand and wrist and 6 joints in the foot were evaluated for joint narrowing score using a 9-point scale where 0=Normal to 4.0=definite ankylosis (stiffness or fixation of a joint) for a total possible score of 0 (best) to 148 (worst). A lower number change from Baseline indicated a better score.
Timepoint [100] 0 0
Baseline, Week 260

Eligibility
Key inclusion criteria
- adult patients at least 18 years of age with moderate to severe active RA for at least
6 months;

- inadequate response to a stable dose of MTX;

- patients of reproductive potential must be using reliable methods of contraception.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- major surgery (including joint surgery) within 8 weeks before entering study, or
planned surgery within 6 months after entering study;

- prior treatment failure with an anti-tumor necrosis factor agent;

- women who are pregnant or breast-feeding.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
- Adelaide
Recruitment hospital [2] 0 0
- Malvern
Recruitment hospital [3] 0 0
- Melbourne
Recruitment hospital [4] 0 0
- New Lambton
Recruitment hospital [5] 0 0
- Shenton Park
Recruitment hospital [6] 0 0
- St. Leonards
Recruitment postcode(s) [1] 0 0
5011 - Adelaide
Recruitment postcode(s) [2] 0 0
3144 - Malvern
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment postcode(s) [4] 0 0
2305 - New Lambton
Recruitment postcode(s) [5] 0 0
6008 - Shenton Park
Recruitment postcode(s) [6] 0 0
2139 - St. Leonards
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
Country [4] 0 0
United States of America
State/province [4] 0 0
Colorado
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Idaho
Country [7] 0 0
United States of America
State/province [7] 0 0
Illinois
Country [8] 0 0
United States of America
State/province [8] 0 0
Indiana
Country [9] 0 0
United States of America
State/province [9] 0 0
Kentucky
Country [10] 0 0
United States of America
State/province [10] 0 0
Maryland
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
Montana
Country [13] 0 0
United States of America
State/province [13] 0 0
Nevada
Country [14] 0 0
United States of America
State/province [14] 0 0
New Hampshire
Country [15] 0 0
United States of America
State/province [15] 0 0
New Jersey
Country [16] 0 0
United States of America
State/province [16] 0 0
New York
Country [17] 0 0
United States of America
State/province [17] 0 0
North Carolina
Country [18] 0 0
United States of America
State/province [18] 0 0
Ohio
Country [19] 0 0
United States of America
State/province [19] 0 0
Oklahoma
Country [20] 0 0
United States of America
State/province [20] 0 0
Oregon
Country [21] 0 0
United States of America
State/province [21] 0 0
Pennsylvania
Country [22] 0 0
United States of America
State/province [22] 0 0
South Carolina
Country [23] 0 0
United States of America
State/province [23] 0 0
Tennessee
Country [24] 0 0
United States of America
State/province [24] 0 0
Texas
Country [25] 0 0
United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
United States of America
State/province [26] 0 0
Wisconsin
Country [27] 0 0
Brazil
State/province [27] 0 0
Porto Alegre
Country [28] 0 0
Brazil
State/province [28] 0 0
Rio de Janeiro
Country [29] 0 0
Brazil
State/province [29] 0 0
Sao Paulo
Country [30] 0 0
China
State/province [30] 0 0
Beijing
Country [31] 0 0
China
State/province [31] 0 0
Nanjing
Country [32] 0 0
China
State/province [32] 0 0
Shanghai
Country [33] 0 0
Denmark
State/province [33] 0 0
Hellerup
Country [34] 0 0
Denmark
State/province [34] 0 0
Odense
Country [35] 0 0
Finland
State/province [35] 0 0
Heinola
Country [36] 0 0
Finland
State/province [36] 0 0
Helsinki
Country [37] 0 0
Finland
State/province [37] 0 0
Oulu
Country [38] 0 0
Finland
State/province [38] 0 0
Vantaa
Country [39] 0 0
France
State/province [39] 0 0
Amiens
Country [40] 0 0
France
State/province [40] 0 0
Bobigny
Country [41] 0 0
France
State/province [41] 0 0
Bois Guillaume
Country [42] 0 0
France
State/province [42] 0 0
Bordeaux
Country [43] 0 0
France
State/province [43] 0 0
Le Kremlin Bicetre
Country [44] 0 0
France
State/province [44] 0 0
Lille
Country [45] 0 0
France
State/province [45] 0 0
Nice
Country [46] 0 0
France
State/province [46] 0 0
Orleans
Country [47] 0 0
France
State/province [47] 0 0
Paris
Country [48] 0 0
France
State/province [48] 0 0
Strasbourg
Country [49] 0 0
France
State/province [49] 0 0
Toulouse
Country [50] 0 0
France
State/province [50] 0 0
Vandoeuvre-les-nancy
Country [51] 0 0
Greece
State/province [51] 0 0
Athens
Country [52] 0 0
Greece
State/province [52] 0 0
Heraklion
Country [53] 0 0
Italy
State/province [53] 0 0
Brescia
Country [54] 0 0
Italy
State/province [54] 0 0
Coppito
Country [55] 0 0
Italy
State/province [55] 0 0
Firenze
Country [56] 0 0
Italy
State/province [56] 0 0
Genova
Country [57] 0 0
Italy
State/province [57] 0 0
Milano
Country [58] 0 0
Italy
State/province [58] 0 0
Napoli
Country [59] 0 0
Italy
State/province [59] 0 0
Padova
Country [60] 0 0
Italy
State/province [60] 0 0
Pavia
Country [61] 0 0
Italy
State/province [61] 0 0
Pisa
Country [62] 0 0
Italy
State/province [62] 0 0
Reggio Emilia
Country [63] 0 0
Italy
State/province [63] 0 0
Roma
Country [64] 0 0
Italy
State/province [64] 0 0
Torino
Country [65] 0 0
Italy
State/province [65] 0 0
Udine
Country [66] 0 0
Italy
State/province [66] 0 0
Valeggio Sul Mincio
Country [67] 0 0
Italy
State/province [67] 0 0
Varese
Country [68] 0 0
Italy
State/province [68] 0 0
Verona
Country [69] 0 0
Mexico
State/province [69] 0 0
Chihuahua
Country [70] 0 0
Mexico
State/province [70] 0 0
Mexico City
Country [71] 0 0
Mexico
State/province [71] 0 0
Monterrey
Country [72] 0 0
Mexico
State/province [72] 0 0
Obregon
Country [73] 0 0
Norway
State/province [73] 0 0
Haugesund
Country [74] 0 0
Norway
State/province [74] 0 0
Lillehammer
Country [75] 0 0
Norway
State/province [75] 0 0
Tromsø
Country [76] 0 0
Poland
State/province [76] 0 0
Bydgoszcz
Country [77] 0 0
Poland
State/province [77] 0 0
Dzialdowo
Country [78] 0 0
Poland
State/province [78] 0 0
Elblag
Country [79] 0 0
Poland
State/province [79] 0 0
Kalisz
Country [80] 0 0
Poland
State/province [80] 0 0
Krakow
Country [81] 0 0
Poland
State/province [81] 0 0
Poznan
Country [82] 0 0
Poland
State/province [82] 0 0
Szczecin
Country [83] 0 0
Poland
State/province [83] 0 0
Ustron
Country [84] 0 0
Poland
State/province [84] 0 0
Warszawa
Country [85] 0 0
Puerto Rico
State/province [85] 0 0
Ponce
Country [86] 0 0
Puerto Rico
State/province [86] 0 0
San Juan
Country [87] 0 0
South Africa
State/province [87] 0 0
Cape Town
Country [88] 0 0
South Africa
State/province [88] 0 0
Diepkloof
Country [89] 0 0
Spain
State/province [89] 0 0
Barcelona
Country [90] 0 0
Spain
State/province [90] 0 0
Cádiz
Country [91] 0 0
Spain
State/province [91] 0 0
Merida
Country [92] 0 0
Spain
State/province [92] 0 0
Sabadell
Country [93] 0 0
Spain
State/province [93] 0 0
Santander
Country [94] 0 0
Spain
State/province [94] 0 0
Sevilla
Country [95] 0 0
Switzerland
State/province [95] 0 0
Lausanne
Country [96] 0 0
Switzerland
State/province [96] 0 0
St. Gallen

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Hoffmann-La Roche
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This 3 arm study will compare the safety and efficacy, with respect to a reduction in signs
and symptoms and prevention of joint damage, of tocilizumab versus placebo, both in
combination with methotrexate (MTX) in patients with moderate to severe active rheumatoid
arthritis. Patients will be randomized to receive tocilizumab 4 mg/kg IV, tocilizumab 8 mg/kg
IV or placebo IV, every 4 weeks. All patients will also receive methotrexate, 10-25 mg/week.
The anticipated time on study treatment is 1-2 years and the target sample size is 500+
individuals. After completion of the 2 year study participants could participate in the
optional 3 year open label extension phase (year 3 to 5).
Trial website
https://clinicaltrials.gov/show/NCT00106535
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Clinical Trials
Address 0 0
Hoffmann-La Roche
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications