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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/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
Timepoint [1] 0 0
Baseline, Week 24
Primary outcome [2] 0 0
Change From Baseline in Modified Total Sharp-Genant Score at Week 52
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
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
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
Timepoint [5] 0 0
Baseline to Week 104
Secondary outcome [1] 0 0
Percentage of Participants With ACR50 Response
Timepoint [1] 0 0
Baseline, Week 24
Secondary outcome [2] 0 0
Percentage of Participants With ACR70 Response
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
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
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
Timepoint [5] 0 0
Baseline, Week 24
Secondary outcome [6] 0 0
Physician's Global VAS: Mean Change From Baseline at Week 24
Timepoint [6] 0 0
Baseline, Week 24
Secondary outcome [7] 0 0
Patient's Pain VAS: Mean Change From Baseline at Week 24
Timepoint [7] 0 0
Baseline and Week 24
Secondary outcome [8] 0 0
C-Reactive Protein (CRP): Mean Change From Baseline at Week 24
Timepoint [8] 0 0
Baseline, Week 24
Secondary outcome [9] 0 0
Erythrocyte Sedimentation Rate: Mean Change From Baseline at Week 24
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
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
Timepoint [11] 0 0
Baseline, Week 52
Secondary outcome [12] 0 0
Percentage of Participants With ACR20 Response at Week 104
Timepoint [12] 0 0
Baseline, Week 104
Secondary outcome [13] 0 0
Percentage of Participants With ACR50 Response at Week 52
Timepoint [13] 0 0
Baseline, Week 52
Secondary outcome [14] 0 0
Percentage of Participants With ACR50 Response at Week 104
Timepoint [14] 0 0
Baseline, Week 104
Secondary outcome [15] 0 0
Percentage of Participants With ACR70 Response at Week 52
Timepoint [15] 0 0
Baseline, Week 52
Secondary outcome [16] 0 0
Percentage of Participants With ACR70 Response at Week 104
Timepoint [16] 0 0
Baseline, Week 104
Secondary outcome [17] 0 0
Percentage of Participants With ACR70 Response Maintained for 6 Consecutive Months
Timepoint [17] 0 0
104 Weeks
Secondary outcome [18] 0 0
Change From Baseline in Swollen Joint Count at Week 52
Timepoint [18] 0 0
Baseline, Week 52
Secondary outcome [19] 0 0
Change From Baseline in Tender Joint Count at Week 52
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
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
Timepoint [21] 0 0
Baseline, Week 52
Secondary outcome [22] 0 0
Change From Baseline in the Patient's Pain VAS at Week 52
Timepoint [22] 0 0
Baseline, Week 52
Secondary outcome [23] 0 0
Change From Baseline in C-Reactive Protein (CRP) at Week 52
Timepoint [23] 0 0
Baseline, Week 52
Secondary outcome [24] 0 0
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 52
Timepoint [24] 0 0
Baseline, Week 52
Secondary outcome [25] 0 0
Change From Baseline in Swollen Joint Count at Week 104
Timepoint [25] 0 0
Baseline, Week 104
Secondary outcome [26] 0 0
Change From Baseline in Tender Joint Count at Week 104
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
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
Timepoint [28] 0 0
Baseline, Week 104
Secondary outcome [29] 0 0
Change From Baseline in the Patient's Pain VAS at Week 104
Timepoint [29] 0 0
Baseline, Week 104
Secondary outcome [30] 0 0
Change From Baseline in C-Reactive Protein (CRP) at Week 104
Timepoint [30] 0 0
Baseline, Week 104
Secondary outcome [31] 0 0
Change From Baseline in Erythrocyte Sedimentation Rate (ESR) at Week 104
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
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
Timepoint [33] 0 0
Baseline, Week 104
Secondary outcome [34] 0 0
Area Under Curve (AUC) of the ACRn to Week 24
Timepoint [34] 0 0
24 Weeks
Secondary outcome [35] 0 0
Area Under Curve (AUC) of the ACRn to Week 52
Timepoint [35] 0 0
52 Weeks
Secondary outcome [36] 0 0
Area Under Curve (AUC) of the ACRn Score at Week 104
Timepoint [36] 0 0
104 Weeks
Secondary outcome [37] 0 0
Change From Baseline in Disease Activity Score (DAS28) at Week 24
Timepoint [37] 0 0
Baseline, Week 24
Secondary outcome [38] 0 0
Change From Baseline in Disease Activity Score (DAS28) at Week 52
Timepoint [38] 0 0
Baseline, Week 52
Secondary outcome [39] 0 0
Change From Baseline in Disease Activity Score (DAS28) at Week 104
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
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
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
Timepoint [42] 0 0
Baseline, Week 104
Secondary outcome [43] 0 0
Percentage of Participants With DAS28 Remission at Week 24
Timepoint [43] 0 0
Week 24
Secondary outcome [44] 0 0
Percentage of Participants With DAS28 Remission at Week 52
Timepoint [44] 0 0
Week 52
Secondary outcome [45] 0 0
Percentage of Participants With DAS28 Remission at Week 104
Timepoint [45] 0 0
Week 104
Secondary outcome [46] 0 0
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 24
Timepoint [46] 0 0
24 Weeks
Secondary outcome [47] 0 0
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 52
Timepoint [47] 0 0
52 Weeks
Secondary outcome [48] 0 0
Area Under Curve (AUC) of Disease Activity Score (DAS28) at Week 104
Timepoint [48] 0 0
104 Weeks
Secondary outcome [49] 0 0
Change From Baseline in Modified Total Sharp-Genant Score at Week 24
Timepoint [49] 0 0
Baseline, Week 24
Secondary outcome [50] 0 0
Change From Baseline in Modified Total Sharp-Genant Score at Week 80
Timepoint [50] 0 0
Baseline, Week 80
Secondary outcome [51] 0 0
Change From Baseline in Erosion Score at Week 24
Timepoint [51] 0 0
Baseline, Week 24
Secondary outcome [52] 0 0
Change From Baseline in Erosion Score at Week 52
Timepoint [52] 0 0
Baseline, Week 52
Secondary outcome [53] 0 0
Change From Baseline in Erosion Score at Week 80
Timepoint [53] 0 0
Baseline, Week 80
Secondary outcome [54] 0 0
Change From Baseline in Erosion Score at Week 104
Timepoint [54] 0 0
Baseline, Week 104
Secondary outcome [55] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 24
Timepoint [55] 0 0
Baseline, Week 24
Secondary outcome [56] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 52
Timepoint [56] 0 0
Baseline, Week 52
Secondary outcome [57] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 80
Timepoint [57] 0 0
Baseline, Week 80
Secondary outcome [58] 0 0
Change From Baseline in Joint Space Narrowing Score at Week 104
Timepoint [58] 0 0
Baseline, Week 104
Secondary outcome [59] 0 0
Percentage of Participants With no Progression of Erosion at Week 24
Timepoint [59] 0 0
Baseline, Week 24
Secondary outcome [60] 0 0
Percentage of Participants With no Progression of Erosion at Week 52
Timepoint [60] 0 0
Baseline, Week 52
Secondary outcome [61] 0 0
Percentage of Participants With no Progression of Erosion at Week 104
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
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
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
Timepoint [64] 0 0
Baseline, Week 104
Secondary outcome [65] 0 0
Change From Baseline in HAQ Disability Index (HAQ-DI) at Week 52
Timepoint [65] 0 0
Baseline, Week 52
Secondary outcome [66] 0 0
Change From Baseline in HAQ Disability Index at Week 104
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
Timepoint [67] 0 0
Baseline, Week 24
Secondary outcome [68] 0 0
Change From Baseline in SF-36 Score at Week 52
Timepoint [68] 0 0
Baseline, Week 52
Secondary outcome [69] 0 0
Change From Baseline in SF-36 Score at Week 104
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
Timepoint [70] 0 0
Baseline, Week 24
Secondary outcome [71] 0 0
Change From Baseline in FACIT-F Score at Week 52
Timepoint [71] 0 0
Baseline, Week 52
Secondary outcome [72] 0 0
Change From Baseline in FACIT-F Score at Week 104
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
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
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
Timepoint [75] 0 0
Baseline, Week 104
Secondary outcome [76] 0 0
Time to Onset of ACR20 by Treatment Group
Timepoint [76] 0 0
6 months
Secondary outcome [77] 0 0
Time to Onset of ACR50 by Treatment Group
Timepoint [77] 0 0
6 months
Secondary outcome [78] 0 0
Time to Onset of ACR70 by Treatment Group
Timepoint [78] 0 0
6 months
Secondary outcome [79] 0 0
Percentage of Participants Who Withdraw Due to Lack of Sufficient Therapeutic Response
Timepoint [79] 0 0
104 Weeks
Secondary outcome [80] 0 0
Percentage of Participants in Each Treatment Group Who Receive Escape Therapy
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
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
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
Timepoint [83] 0 0
104 Weeks
Secondary outcome [84] 0 0
Percentage of Participants Who Achieved Complete Clinical Response at Week 52
Timepoint [84] 0 0
52 Weeks
Secondary outcome [85] 0 0
Percentage of Participants Who Achieved Complete Clinical Response at Week 104
Timepoint [85] 0 0
104 Weeks
Secondary outcome [86] 0 0
End of Study: Percentage of Participants With ACR Response at Week 260
Timepoint [86] 0 0
Baseline, Week 260
Secondary outcome [87] 0 0
End of Study: Percentage of Participants With DAS28 Remission at Week 260
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
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
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
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
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
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
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
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
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
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
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
Timepoint [98] 0 0
Baseline, Week 260
Secondary outcome [99] 0 0
End of Study: Change From Baseline in Erosion Score at Week 260
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
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
Sex
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
1/01/2005
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
1/07/2012
Sample size
Target
Accrual to date
Final
1196
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
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United States of America
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Nevada
Country [14] 0 0
United States of America
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New Hampshire
Country [15] 0 0
United States of America
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New Jersey
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United States of America
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New York
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United States of America
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North Carolina
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United States of America
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Ohio
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United States of America
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Oklahoma
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United States of America
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Oregon
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United States of America
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Pennsylvania
Country [22] 0 0
United States of America
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South Carolina
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
State/province [25] 0 0
Washington
Country [26] 0 0
United States of America
State/province [26] 0 0
Wisconsin
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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
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China
State/province [30] 0 0
Beijing
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China
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Nanjing
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China
State/province [32] 0 0
Shanghai
Country [33] 0 0
Denmark
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Hellerup
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Denmark
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Odense
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Finland
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Heinola
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Finland
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Helsinki
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Finland
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Oulu
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Finland
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Vantaa
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France
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Amiens
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France
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Bobigny
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France
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Bois Guillaume
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France
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Bordeaux
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France
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Le Kremlin Bicetre
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France
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Lille
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France
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Nice
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France
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Orleans
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France
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Paris
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France
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Strasbourg
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France
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Toulouse
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France
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Vandoeuvre-les-nancy
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Greece
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Athens
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Greece
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Heraklion
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Italy
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Brescia
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Italy
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Coppito
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Italy
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Firenze
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Italy
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Genova
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Italy
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Milano
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Italy
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Napoli
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Italy
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Padova
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Italy
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Pavia
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Italy
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Pisa
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Italy
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Reggio Emilia
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Italy
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Roma
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Italy
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Torino
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Italy
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Udine
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Italy
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Valeggio Sul Mincio
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Italy
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Varese
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Italy
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Verona
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Mexico
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Chihuahua
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Mexico
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Mexico City
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Mexico
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Monterrey
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Mexico
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Obregon
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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/study/NCT00106535
Trial related presentations / publications
Khawaja MN, Bergman MJ, Yourish J, Pei J, Reiss W, Keystone E. Routine Assessment of Patient Index Data 3 and the American College of Rheumatology/European League Against Rheumatism Provisional Remission Definitions as Predictors of Radiographic Outcome in a Rheumatoid Arthritis Clinical Trial With Tocilizumab. Arthritis Care Res (Hoboken). 2017 May;69(5):609-615. doi: 10.1002/acr.23008. Epub 2017 Apr 7.
Kremer JM, Blanco R, Halland AM, Brzosko M, Burgos-Vargas R, Mela CM, Rowell L, Fleischmann RM. Clinical efficacy and safety maintained up to 5 years in patients with rheumatoid arthritis treated with tocilizumab in a randomised trial. Clin Exp Rheumatol. 2016 Jul-Aug;34(4):625-33. Epub 2016 Apr 15.
Bay-Jensen AC, Platt A, Siebuhr AS, Christiansen C, Byrjalsen I, Karsdal MA. Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study. Arthritis Res Ther. 2016 Jan 20;18:13. doi: 10.1186/s13075-015-0913-x.
Keystone EC, Anisfeld A, Ogale S, Devenport JN, Curtis JR. Continued benefit of tocilizumab plus disease-modifying antirheumatic drug therapy in patients with rheumatoid arthritis and inadequate clinical responses by week 8 of treatment. J Rheumatol. 2014 Feb;41(2):216-26. doi: 10.3899/jrheum.130489. Epub 2014 Jan 15.
Siebuhr AS, Bay-Jensen AC, Leeming DJ, Plat A, Byrjalsen I, Christiansen C, van de Heijde D, Karsdal MA. Serological identification of fast progressors of structural damage with rheumatoid arthritis. Arthritis Res Ther. 2013 Aug 14;15(4):R86. doi: 10.1186/ar4266.
Fleischmann RM, Halland AM, Brzosko M, Burgos-Vargas R, Mela C, Vernon E, Kremer JM. Tocilizumab inhibits structural joint damage and improves physical function in patients with rheumatoid arthritis and inadequate responses to methotrexate: LITHE study 2-year results. J Rheumatol. 2013 Feb;40(2):113-26. doi: 10.3899/jrheum.120447. Epub 2013 Jan 15.
Wang J, Bansal AT, Martin M, Germer S, Benayed R, Essioux L, Lee JS, Begovich A, Hemmings A, Kenwright A, Taylor KE, Upmanyu R, Cutler P, Harari O, Marchini J, Criswell LA, Platt A. Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. Pharmacogenomics J. 2013 Jun;13(3):235-41. doi: 10.1038/tpj.2012.8. Epub 2012 Apr 10.
Kremer JM, Blanco R, Brzosko M, Burgos-Vargas R, Halland AM, Vernon E, Ambs P, Fleischmann R. Tocilizumab inhibits structural joint damage in rheumatoid arthritis patients with inadequate responses to methotrexate: results from the double-blind treatment phase of a randomized placebo-controlled trial of tocilizumab safety and prevention of structural joint damage at one year. Arthritis Rheum. 2011 Mar;63(3):609-21. doi: 10.1002/art.30158.
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

For IPD and results data, please see https://clinicaltrials.gov/study/NCT00106535