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A Study of Tocilizumab (RoActemra) in Tocilizumab-Naive Participants With Rheumatoid Arthritis and Inadequate Response to Non-Biologic Disease-Modifying Antirheumatic Drugs (DMARDs) and/or Biologic Therapy (TOSCA)

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ClinicalTrials.gov Identifier: NCT02001987
Recruitment Status : Completed
First Posted : December 5, 2013
Results First Posted : November 2, 2018
Last Update Posted : November 2, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
This two part, multi-center, open-label, single-arm study will evaluate the efficacy and safety of tocilizumab as a monotherapy or in combination with methotrexate or other conventional synthetic disease modifying antirheumatic drugs (csDMARDs) in participants with moderate to severe active rheumatoid arthritis who have an inadequate response or are intolerant to non-biologic csDMARDs and/or biologic therapy.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Drug: Tocilizumab Drug: Methotrexate Drug: csDMARDs Phase 3

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 139 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multi-Center Open-Label Study to Evaluate the Efficacy, Safety and Tolerability of Subcutaneous Tocilizumab in Tocilizumab-Naive Patients With Active Rheumatoid Arthritis Who Have an Inadequate Response to Current Non-Biologic DMARD and/or Biologic Therapy
Study Start Date : January 2014
Actual Primary Completion Date : December 2015
Actual Study Completion Date : December 2015

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tocilizumab
Participants will receive tocilizumab at a dose of 162 milligrams (mg) as subcutaneous (SC) injection once a week administered as monotherapy or in combination with methotrexate or other csDMARDs (at investigator's discretion) for 24 weeks. Participants who complete the core study period will be allowed to enter a long-term-extension (LTE) period to continue study treatment for up to a maximum of another 52 weeks or until the commercial availability of SC tocilizumab, whichever occurs first.
Drug: Tocilizumab
Tocilizumab will be administered at a dose of 162 mg as SC injection once a week.
Other Names:
  • RoActemra
  • RO4877533

Drug: Methotrexate
Methotrexate will be administered at a stable dose that was initiated at least 4 weeks prior to Baseline, at investigator's discretion.

Drug: csDMARDs
csDMARDs (at investigator's discretion) will be administered at a stable dose that was initiated at least 4 weeks prior to Baseline, at investigator's discretion.




Primary Outcome Measures :
  1. Change From Baseline in Disease Activity Score Based on 28-joints Count and Erythrocyte Sedimentation Rate (DAS28-ESR) at Week 24 [ Time Frame: Baseline, Week 24 ]
    The DAS28-ESR was derived from assessments of erythrocyte sedimentation rate (ESR), tender joint count (TJC), swollen joint count (SJC), and Patient Global Assessment of disease activity (PGA) according to 100-millimeter (mm) Visual Analog Scale (VAS). DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in millimeters per hour (mm/h). DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to Week 24 was averaged among all participants, where negative changes indicated an improvement in disease activity.


Secondary Outcome Measures :
  1. Change From Baseline in DAS28-ESR at Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 ]
    The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-mm VAS. DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  2. Percentage of Participants With DAS28-ESR Low Disease Activity (LDA) and Remission at Week 24 [ Time Frame: Week 24 ]
    The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-mm VAS. DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. DAS28-ESR score less than or equal to (</=) 3.2 indicates LDA, DAS28-ESR score greater than (>) 3.2 indicates moderate to high disease activity, and DAS28-ESR less than (<) 2.6 indicates remission. Percentage of participants with DAS28-ESR LDA and remission at Week 24 is reported. 95 percent (%) confidence interval (CI) was determined using Clopper-Pearson method.

  3. Change From Baseline in DAS28-ESR at Week 24 and at Last Assessment [ Time Frame: Baseline, Week 24, last assessment (up to Week 76) ]
    The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-millimeter (mm) VAS. DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  4. Percentage of Participants With DAS28-ESR LDA and Remission at Week 24 and at Last Assessment [ Time Frame: Week 24, last assessment (up to Week 76) ]
    The DAS28-ESR was derived from assessments of ESR, TJC, SJC, and PGA according to 100-mm VAS. DAS28-ESR scores were calculated as [0.56 × square root of TJC] + [0.28 × square root of SJC] + [0.70 × natural log (ESR)] + [0.014 × VAS]. TJC was defined as the number of painful joints and SJC was defined as the number of swollen joints, each assessed on 28 joints. ESR was measured in mm/h. DAS28-ESR scores could range from 0 to 10, where higher scores represented higher disease activity. DAS28-ESR score </=3.2 indicates LDA, DAS28-ESR score >3.2 indicates moderate to high disease activity, and DAS28-ESR <2.6 indicates remission. Percentage of participants with DAS28-ESR LDA and remission at Week 24 and at last assessment is reported.

  5. Percentage of Participants Achieving American College of Rheumatology 20% (ACR20), 50% (ACR50), and 70% (ACR70) Response at Week 24 [ Time Frame: Baseline, Week 24 ]
    The ACR 20, 50, and 70 responses at any time was defined as greater than or equal to (>/=) 20%, 50%, and 70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 20%, 50%, 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) PGA according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via a Health Assessment Questionnaire-Disability Index (HAQ-DI), and 5) Acute phase reactant (ESR in mm/h or C-Reactive Protein [CRP] in milligrams per liter [mg/L]). Percentage of participants with ACR 20, 50, and 70 responses at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

  6. Percentage of Participants Achieving ACR20, ACR50, and ACR70 Response at Week 24 and at Last Assessment [ Time Frame: Baseline, Week 24, last assessment (up to Week 76) ]
    The ACR 20, 50, and 70 responses at any time is defined as >/=20%, 50%, and 70% improvement compared to baseline in TJC (assessed on 68 joints) and SJC (assessed on 66 joints); and 20%, 50%, 70% improvement compared to baseline in 3 of the following 5 criteria, respectively: 1) PGA according to 100-mm VAS, 2) Physician's global assessment of disease activity according to 100-mm VAS, 3) participant's global assessment of pain according to 100-mm VAS, 4) Participant's assessment of functional ability via HAQ-DI, and 5) Acute phase reactant (ESR in mm/h or CRP in mg/L). Percentage of participants with ACR 20, 50, and 70 responses at Week 24 and at last assessment is reported.

  7. Percentage of Participants With European League Against Rheumatism (EULAR) Response Based on DAS28-ESR at Week 24 [ Time Frame: Baseline, Week 24 ]
    The DAS28-ESR-based EULAR response criteria were used to measure individual response as 'Good', 'Moderate', and 'No Response', depending upon DAS28-ESR absolute scores at Week 24 and the DAS28-ESR reduction from Baseline to Week 24. Good Response: change from baseline >1.2 with DAS28-ESR score </=3.2; Moderate Response: change from baseline >1.2 with DAS28-ESR score >3.2 to </=5.1 or change from baseline >0.6 to </=1.2 with DAS28-ESR score </=5.1; No Response: change from baseline </=0.6 or change from baseline >0.6 and </=1.2 with DAS28-ESR score >5.1. Percentage of participants with EULAR responses at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

  8. Percentage of Participants With EULAR Response Based on DAS28-ESR at Week 24 and at Last Assessment [ Time Frame: Baseline, Week 24, last assessment (up to Week 76) ]
    The DAS28-ESR-based EULAR response criteria were used to measure individual response as 'Good', 'Moderate', and 'No Response', depending upon DAS28-ESR absolute scores at Week 24 and the DAS28-ESR reduction from Baseline to Week 24. Good Response: change from baseline >1.2 with DAS28-ESR score </=3.2; Moderate Response: change from baseline >1.2 with DAS28-ESR score >3.2 to </=5.1 or change from baseline >0.6 to </=1.2 with DAS28-ESR score </=5.1; No Response: change from baseline </=0.6 or change from baseline >0.6 and </=1.2 with DAS28-ESR score >5.1. Percentage of participants with EULAR responses at Week 24 and at last assessment is reported.

  9. Change From Baseline in Simplified Disease Activity Index (SDAI) at Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 ]
    SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg per deciliter (dL). Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI </=3.3 indicates disease remission, </=11 indicates LDA, </=26 indicates moderate disease activity, and >26 indicates high disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  10. Percentage of Participants With SDAI LDA and Remission at Week 24 [ Time Frame: Week 24 ]
    SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg/dL. Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI </=3.3 indicates disease remission, </=11 indicates LDA, </=26 indicates moderate disease activity, and >26 indicates high disease activity. Percentage of participants with SDAI LDA and remission at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

  11. Change From Baseline in SDAI at Week 24 and at Last Assessment [ Time Frame: Baseline, Week 24, last assessment (up to Week 76) ]
    SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg/dL. Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI </=3.3 indicates disease remission, </=11 indicates LDA, </=26 indicates moderate disease activity, and >26 indicates high disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  12. Percentage of Participants With SDAI LDA and Remission at Week 24 and at Last Assessment [ Time Frame: Week 24, last assessment (up to Week 76) ]
    SDAI is a numerical sum of 5 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS and CRP in mg/dL. Higher scores indicate greater affection due to disease activity. SDAI total score = 0-86. SDAI </=3.3 indicates disease remission, </=11 indicates LDA, </=26 indicates moderate disease activity, and >26 indicates high disease activity. Percentage of participants with SDAI LDA and remission at Week 24 and at last assessment is reported.

  13. Change From Baseline in Clinical Disease Activity Index (CDAI) at Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 ]
    CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS. Higher scores represent greater affection due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, </=10 indicates LDA, </=22 indicates moderate disease activity, and >22 indicates high disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  14. Percentage of Participants With CDAI LDA and Remission at Week 24 [ Time Frame: Week 24 ]
    CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS. Higher scores represent greater affection due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, </=10 indicates LDA, </=22 indicates moderate disease activity, and >22 indicates high disease activity. Percentage of participants with CDAI LDA and remission at Week 24 is reported. 95% CI was determined using Clopper-Pearson method.

  15. Change From Baseline in CDAI at Week 24 and at Last Assessment [ Time Frame: Baseline, Week 24, last assessment (up to Week 76) ]
    CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS. Higher scores represent greater affection due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, </=10 indicates LDA, </=22 indicates moderate disease activity, and >22 indicates high disease activity. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  16. Percentage of Participants With CDAI LDA and Remission at Week 24 and at Last Assessment [ Time Frame: Week 24, last assessment (up to Week 76) ]
    CDAI is a numerical sum of 4 outcome parameters: TJC and SJC based on a 28-joint assessment, PGA and Physician's global assessment of disease activity according to 100-mm VAS. Higher scores represent greater affection due to disease activity. CDAI total score = 0-76. CDAI score </=2.8 indicates disease remission, </=10 indicates LDA, </=22 indicates moderate disease activity, and >22 indicates high disease activity. Percentage of participants with CDAI LDA and remission at Week 24 and at last assessment is reported.

  17. Change From Baseline in SJC at Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 ]
    A total of 28 joints were assessed for swelling. The number of swollen joints at could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  18. Change From Baseline in SJC at Week 24 and at Last Assessment [ Time Frame: Baseline, Week 24, last assessment (up to Week 76) ]
    A total of 28 joints were assessed for swelling. The number of swollen joints at could range from 0 to 28, where higher values represented more swollen joints. The change from Baseline to any time point was averaged among all participants, where negative changes indicated an improvement in disease activity.

  19. Change From Baseline in TJC at Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 ]
    A total of 28 joints were assessed for tenderness. The number of tender joints at could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to any time points was averaged among all participants, where negative changes indicated an improvement in disease activity.

  20. Change From Baseline in TJC at Week 24 and at Last Assessment [ Time Frame: Baseline, Week 24, last assessment (up to Week 76) ]
    A total of 28 joints were assessed for tenderness. The number of tender joints at could range from 0 to 28, where higher values represented more tender joints. The change from Baseline to any time points was averaged among all participants, where negative changes indicated an improvement in disease activity.

  21. Change From Baseline in Physician's Global Assessment of Disease Activity at Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, and 24 ]
    Physician-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the physician's evaluation of disease activity (0 mm=none; 100 mm=very severe). The change from Baseline to any time point was averaged among all participants, where negative change indicated a decrease in physician-assessed disease activity.

  22. Change From Baseline in PGA at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 ]
    Participant-assessed disease activity was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of disease activity (0 mm=none; 100 mm=very severe). The change from Baseline to any time point was averaged among all participants, where negative change indicated a decrease in participant-assessed disease activity.

  23. Change From Baseline in Pain VAS Score at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 ]
    Participant-assessed pain was scored on a 100-mm VAS, where the distance from 0 mm represented the participant's self evaluation of pain (0 mm=none; 100 mm=very severe). The change from Baseline to any time point was averaged among all participants, where negative change indicated a decrease in participant-assessed pain.

  24. Change From Baseline in Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-F) Score at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 ]
    FACIT-F is a 13-item questionnaire. Participants scored each item on a 5-point scale: 0 (not at all) to 4 (very much). Larger the participant's response to the questions (with the exception of 2 negatively stated questions), greater was the participant'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 participant'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). The changes from Baseline to any time point were averaged among all participants, where negative changes indicated an increase in fatigue.

  25. Percentage of Participants With Health Assessment Questionnaire-Disability Index (HAQ-DI) Remission at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 ]
    HAQ-DI assessed 20 items in 8 functional activity domains including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item was scored on a scale of 0 to 3, where 0 represented activities performed without difficulty and 3 represented inability to perform activities alone. The total score (range = 0-3) was calculated as an average of all item scores. Percentage of participants with HAQ-DI remission (HAQ-DI score <0.5) at each time point is reported.

  26. Percentage of Participants With HAQ-DI Clinically Meaningful Improvement at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48, 52, 56, 60, and 64 ]
    HAQ-DI assessed 20 items in 8 functional activity domains including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. Each item was scored on a scale of 0 to 3, where 0 represented activities performed without difficulty and 3 represented inability to perform activities alone. The total score (range = 0-3) was calculated as an average of all item scores. Percentage of participants with HAQ-DI clinically meaningful improvement (reduction in HAQ-DI score from baseline >/=0.22) at each time point is reported.

  27. Treatment Compliance From Baseline up to Week 24 [ Time Frame: Baseline up to Week 24 ]
    Treatment compliance from Baseline up to Week 24 was assessed using following formula: (number of actual injection received / number of theoretical injection which should be received at week 24) * 100.

  28. Change From Baseline in Rheumatoid Arthritis Impact of Disease (RAID) Score at Weeks 12, 24, 28, 40, 52, and 64 [ Time Frame: Baseline, Weeks 12, 24, 28, 40, 52, and 64 ]
    RAID assessed the impact of rheumatoid arthritis on participant's quality of life. It comprised 7 domains: pain, function, fatigue, physical and psychological well-being, sleep disturbance and coping. Each domain was a single question scored from 0 (best) to 10 (worst) on a continuous numerical rating scale (NRS). Each domain also had a specific weight assigned by a participant survey and RAID total score ranged from 0 (best) to 10 (worst). If only 1 domain was missing it was replaced by the mean of the others; otherwise, RAID score was not calculated. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better quality of life.

  29. Change From Baseline in Routine Assessment of Patient Index Data 3 (RAPID-3) at Weeks 2, 4, 12, 24, 28, 40, 52, and 64 [ Time Frame: Baseline, Weeks 2, 4, 12, 24, 28, 40, 52, and 64 ]
    RAPID-3 is a combined index derived from the Multidimensional Health Assessment Questionnaire that includes physical function score, pain VAS, and PGA VAS. The total RAPID-3 score ranges from 0 to 10 where higher scores represent worse outcomes. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

  30. Number of Participants With Patient Acceptable Symptom State (PASS) Score [ Time Frame: Baseline, Weeks 24, 52, and last assessment (up to Week 76) ]
    Participants were asked: "If you were to remain in the same condition for the next few months as you have been over the last 8 days, would this be 1) acceptable, 2) Inacceptable?" The number of participants who responded "acceptable" or "Inacceptable" at each time point is presented.

  31. Change From Baseline in Bristol Rheumatoid Arthritis Fatigue Multidimensional Questionnaire (BRAF-MDQ) Total Score at Weeks 24 and 52 [ Time Frame: Baseline, Weeks 24 and 52 ]
    BRAF-MDQ assessed the overall experience and impact of disease related fatigue, using four dimensions (physical fatigue [4 items], living with fatigue [7 items], cognitive fatigue [5 items], and emotional fatigue [4 items]). A total fatigue score (range 0 to 70) was obtained by summing the 20 item scores ranging from 0 to 3, except for item 1 (0-10), item 2 (0-7) and item 3 (0-2). Higher scores reflect greater fatigue. If only 1 domain was missing it was replaced by the mean of the others; otherwise, the total score was not calculated. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better quality of life.

  32. Change From Baseline in Bristol Rheumatoid Arthritis Fatigue (BRAF)-NRS Score at Weeks 24 and 52 [ Time Frame: Baseline, Weeks 24 and 52 ]
    BRAF-NRS are 3 standardized NRS (range = 0-10) for disease related fatigue domains (severity of fatigue, fatigue effect, and coping with fatigue). Higher values reflect greater problems for severity/level fatigue and effect fatigue NRS, but lower scores reflect greater problems for copped fatigue NRS.

  33. Change From Baseline in Medical Outcome Study (MOS) Sleep Questionnaire Score at Weeks 12, 24, 28, 40, 52, and 64 [ Time Frame: Baseline, Weeks 12, 24, 28, 40, 52, and 64 ]
    MOS sleep scale comprised of 6-item with each item score ranged from 0 to 100. The total score was the average of scores sum (range 0-100), with highest values reflecting biggest participant's sleeping problems. If more than 3 items were missing the index was not calculated. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

  34. Change From Baseline in Fluctuations of Disease Activity in Rheumatoid Arthritis (FLARE) Questionnaire Score at Weeks 2, 4, 8, 12, 16, 20, 24, 28, 40, 52, and 64 [ Time Frame: Baseline, Weeks 2, 4, 8, 12, 16, 20, 24, 28, 40, 52, and 64 ]
    FLARE is a 13-item questionnaire assessed disease flares between two medical consultations. Each item score ranged from 0 (completely untrue) to 10 (absolutely true) on a 6-step scale. The FLARE questionnaire global score (range = 0-10) is a mean score of 11 of the 13 items [items 6 ('doses of pain killers or anti-inflammatory medication') and 13 ('need for help') not taken into account], with the highest score corresponding to the highest disease activity. The global score was computed if at least the scores of 6 items were available. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

  35. Change From Baseline in BioSecure Questionnaire Score at Week 24 [ Time Frame: Baseline, Week 24 ]
    The BioSecure questionnaire comprised of 54-item aimed at evaluating the safety competences of participants (for example, participants' self-care safety skills and socio-demographic characteristics, type of information received, quality of life, and coping style data) treated by biologics for inflammatory arthritis and to determine the factors associated with a lower level of competences.

  36. Percentage of Participants With Discontinuations of Corticosteroid Dosage During Core Study Period [ Time Frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks) ]
    Percentage of participants with a discontinuation in corticosteroid dosage during core study period is reported. The discontinuations were categorized as either permanent or temporary. Participants with temporary discontinuation first followed by permanent discontinuation were counted in both categories. Participants who were receiving corticosteroids at Baseline were only included in the analysis.

  37. Time to Permanent Discontinuation of Corticosteroid Dosage During Core Study Period [ Time Frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks) ]
    Time to permanent discontinuation in corticosteroid dosage during core study period is reported. Participants who permanently discontinued corticosteroids at any time during core study period were only included in the analysis.

  38. Time to First Temporary Discontinuation of Corticosteroid Dosage During Core Study Period [ Time Frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks) ]
    Time to first temporary discontinuation in corticosteroid dosage during core study period is reported. Participants who temporarily discontinued corticosteroids at any time during core study period were only included in the analysis.

  39. Percentage of Participants With Change in Corticosteroid Dosage During Core Study Period [ Time Frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks) ]
    Percentage of participants with a change in corticosteroid dosage during core study period compared to Baseline is reported. The change included either an initiation/ increase (>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (</=-5mg/day prednisone or equivalent) of corticosteroid dosage.

  40. Time to Change in Corticosteroid Dosage During Core Study Period [ Time Frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks) ]
    Time to first change in corticosteroid dosage during core study period compared to Baseline is reported. The change included either an initiation/ increase (>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (</=-5mg/day prednisone or equivalent) of corticosteroid dosage. Participants with a change in corticosteroid dosage during core study period were only included in the analysis.

  41. Number of Participants According to Reasons for Change in Corticosteroid Dosage During Core Study Period [ Time Frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks) ]
    Number of participants according to reasons for a change in corticosteroid dosage during core study period compared to Baseline is reported. The change included either an initiation/ increase (>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (</=-5mg/day prednisone or equivalent) of corticosteroid dosage. Participants with a change in corticosteroid dosage during core study period were only included in the analysis.

  42. Percentage of Participants With Discontinuations of Corticosteroid Dosage During Study [ Time Frame: Screening up to 8 weeks after last dose (overall up to 88 weeks) ]
    Percentage of participants with a discontinuation in corticosteroid dosage during study is reported. The discontinuations were categorized as either permanent or temporary. Participants with temporary discontinuation first followed by permanent discontinuation were counted in both categories. Participants who were receiving corticosteroids at Baseline were only included in the analysis.

  43. Time to Permanent Discontinuation of Corticosteroid Dosage During Study [ Time Frame: Screening up to 8 weeks after last dose (overall up to 88 weeks) ]
    Time to permanent discontinuation in corticosteroid dosage during study is reported. Participants who permanently discontinued corticosteroids at any time during entire study were only included in the analysis.

  44. Time to First Temporary Discontinuation of Corticosteroid Dosage During Study [ Time Frame: Screening up to 8 weeks after last dose (overall up to 88 weeks) ]
    Time to first temporary discontinuation in corticosteroid dosage during study is reported. Participants who temporarily discontinued corticosteroids at any time during entire study were only included in the analysis.

  45. Percentage of Participants With Change in Corticosteroid Dosage During Study [ Time Frame: Screening up to 8 weeks after last dose (overall up to 88 weeks) ]
    Percentage of participants with a change in corticosteroid dosage during study compared to Baseline is reported. The change included either an initiation/ increase (>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (</=-5mg/day prednisone or equivalent) of corticosteroid dosage.

  46. Time to Change in Corticosteroid Dosage During Study [ Time Frame: Screening up to 8 weeks after last dose (overall up to 88 weeks) ]
    Time to first change in corticosteroid dosage during study compared to Baseline is reported. The change included either an initiation/ increase (>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (</=-5mg/day prednisone or equivalent) of corticosteroid dosage. Participants with a change in corticosteroid dosage during entire study were only included in the analysis.

  47. Number of Participants According to Reasons for Change in Corticosteroid Dosage During Study [ Time Frame: Screening up to 8 weeks after last dose (overall up to 88 weeks) ]
    Number of participants according to reasons for a change in corticosteroid dosage during study compared to Baseline is reported. The change included either an initiation/ increase (>+5mg/day prednisone or equivalent) of corticosteroid dosage or a decrease (</=-5mg/day prednisone or equivalent) of corticosteroid dosage. Participants with a change in corticosteroid dosage during entire study were only included in the analysis.

  48. Number of Participants According to Reasons for Changes in csDMARDs Treatment During Core Study Period [ Time Frame: Screening up to 8 weeks after last dose in core study period (overall up to 36 weeks) ]
    Number of participants according to reasons for changes in csDMARDs treatment during core study period is reported. The changes included Increase of dose (the dose increase had to be greater than the highest dose received within the 4 weeks on or before baseline); Addition of another csDMARD (without suppression of the first one); Switch (add and suppression) of a csDMARD for another reason than intolerance to the csDMARD suppressed; Modification of the administration route of MTX (with increase or maintenance of the dose): per oral route to intravenous (IV)/ intramuscular (IM)/ SC. Participants with a change in csDMARDs treatment during core study period were only included in the analysis.

  49. Number of Participants According to Reasons for Changes in csDMARDs Treatment During Study [ Time Frame: Screening up to 8 weeks after last dose (overall up to 88 weeks) ]
    Number of participants according to reasons for changes in csDMARDs treatment during study is reported. The changes included Increase of dose (the dose increase had to be greater than the highest dose received within the 4 weeks on or before baseline); Addition of another csDMARD (without suppression of the first one); Switch (add and suppression) of a csDMARD for another reason than intolerance to the csDMARD suppressed; Modification of the administration route of MTX (with increase or maintenance of the dose): per oral route to IV/IM/SC. Participants with a change in csDMARDs treatment during entire study were only included in the analysis.

  50. Change From Baseline in Synovitis Ultrasound B-Mode Score at Week 24 [ Time Frame: Baseline, Weeks 24 ]
    Synovitis was assessed by ultrasonographic evaluation (B-mode ultrasound) and scored from "0" to "3" for each 7 paired joints (wrists on both sides, 2nd and 3rd metacarpo-phalangeal [MCP 2/3] on both sides, 2nd and 3rd proximal inter-phalangeal [PIP 2/3] on both sides, 2nd and 5th metatarsophalangeal [MTP 2/5] on both sides). Synovitis total score was calculated by adding the sum of scores for each joint for a total score ranging from 0 to 42. A score of 0 indicated no damage and a score of 42 indicated most severe damage. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

  51. Change From Baseline in Synovitis Ultrasound Power-Doppler Mode Score at Week 24 [ Time Frame: Baseline, Weeks 24 ]
    Synovitis was assessed by ultrasonographic evaluation (Power-Doppler-mode ultrasound) and scored from "0" to "3" for each 7 paired joints (wrists on both sides, 2nd and 3rd metacarpo-phalangeal [MCP 2/3] on both sides, 2nd and 3rd proximal inter-phalangeal [PIP 2/3] on both sides, 2nd and 5th metatarsophalangeal [MTP 2/5] on both sides). Synovitis total score was calculated by adding the sum of scores for each joint for a total score ranging from 0 to 42. A score of 0 indicated no damage and a score of 42 indicated most severe damage. The changes from Baseline to any time point were averaged among all participants, where negative changes indicated better outcome.

  52. Percentage of Participants With Anti-Therapeutic Antibodies to Tocilizumab [ Time Frame: Baseline up to 8 weeks after last study drug administration (up to Week 84) ]
    Percentage of participants with a positive response to anti-therapeutic antibodies against tocilizumab by confirmatory assays at any time during the study is reported.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants with a diagnosis of active rheumatoid arthritis according to the revised (1987) ACR criteria or EULAR/ACR (2010) criteria and receiving outpatient treatment
  • Oral corticosteroids (</= 10 mg/day prednisone or equivalent), nonsteroidal anti-inflammatory drugs (NSAIDs), and permitted csDMARDs are allowed at a stable dose for at least 4 weeks prior to Baseline
  • At Screening either CRP >/=10 mg/L or ESR >/=20 mm/h and SJC >/=3 (based on 44 joints)
  • Inadequate response (IR) to tumor necrosis factor, abatacept and/or non-biological DMARDs

Exclusion Criteria:

  • Major surgery (including joint surgery) within 8 weeks prior to Screening or planned major surgery within 6 months following Baseline
  • Rheumatic autoimmune disease other than rheumatoid arthritis; Secondary Sjögren's syndrome with rheumatoid arthritis is permitted
  • Functional Class IV as defined by the ACR Classification of Functional Status in Rheumatoid Arthritis
  • Diagnosis of juvenile idiopathic arthritis or juvenile rheumatoid arthritis and/or rheumatoid arthritis before the age of 16
  • Prior history of or current inflammatory joint disease other than rheumatoid arthritis
  • Exposure to tocilizumab at any time prior to Baseline
  • Treatment with any investigational agent within 4 weeks (or five half-lives of the investigational drug, whichever was longer) of Screening
  • Previous treatment with any cell-depleting therapies, including investigational agents or approved therapies or any alkylating agents such as chlorambucil, or with total lymphoid irradiation
  • Treatment with IV gamma globulin, plasmapheresis within 6 months of Baseline
  • Intraarticular or parenteral corticosteroids within 4 weeks prior to Baseline
  • Immunization with a live/attenuated vaccine within 4 weeks prior to Baseline
  • History of severe allergic or anaphylactic reactions to human, humanized, or murine monoclonal antibodies
  • Serious uncontrolled concomitant disease or other significant condition
  • History of diverticulitis, diverticulosis requiring antibiotic treatment, or chronic ulcerative lower gastrointestinal disease
  • Current or history of recurrent bacterial, viral, fungal, mycobacterial, or other infections
  • Any infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of Screening or oral antibiotics within 2 weeks of Screening
  • Active tuberculosis requiring treatment within the previous 3 years
  • Positive for hepatitis B or C
  • Primary or secondary immunodeficiency disorder
  • Active cancer, or cancer diagnosed within the previous 10 years (except basal and squamous cell carcinoma of the skin or carcinoma in situ of the cervix uteri that has been excised or cured), or breast cancer diagnosed within the previous 20 years
  • History of alcohol, drug, or chemical abuse within 1 year prior to Screening
  • Neuropathies or other conditions that might interfere with pain evaluation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02001987


Locations
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France
Amiens, France, 80054
Bordeaux, France, 33076
Brest, France, 29609
Caen, France, 14033
Cahors, France, 46005
Clermont-ferrand, France, 63003
Echirolles, France, 38434
La Source, France, 45100
Le Mans, France, 72037
Lille, France, 59037
Limoges, France, 87042
Lomme, France, 59462
Lyon cedex 3, France, 69437
Marseille, France, 13274
Marseille, France, 13285
Metz Tessy, France, 74370
Monaco, France, 98012
Montpellier, France, 34295
Mulhouse, France, 68070
Paris, France, 75475
Paris, France, 75571
Paris, France, 75651
Paris, France, 75679
Paris, France, 75877
Rennes, France, 35033
Rouen, France, 76031
St Mande, France, 94163
St Priest En Jarez, France, 42277
Strasbourg, France, 67098
Thonon Les Bains, France, 74203
Toulouse, France, 31059
Vandoeuvre-les-nancy, France, 54511
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT02001987    
Other Study ID Numbers: ML28693
2013-001718-14 ( EudraCT Number )
First Posted: December 5, 2013    Key Record Dates
Results First Posted: November 2, 2018
Last Update Posted: November 2, 2018
Last Verified: March 2018
Additional relevant MeSH terms:
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Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Methotrexate
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors