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A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01332994
First received: March 18, 2011
Last updated: August 5, 2015
Last verified: August 2015

March 18, 2011
August 5, 2015
March 2011
February 2014   (final data collection date for primary outcome measure)
Percentage of Participants Achieving Remission at Week 16 According to DAS28 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
The DAS28 was calculated as [0.28 times (x) the square root of number of swollen joints] plus (+) [0.56 x the square root of number of tender joints] + [0.7 x the natural log of erythrocyte sedimentation rate (ESR)] + [0.014 x Visual Analog Scale (VAS) patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
Early efficacy rate defined as Disease Activity Score (DAS28) remission <2.6 after 4 courses of TCZ treatment [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01332994 on ClinicalTrials.gov Archive Site
  • Percentage of Participants Achieving Remission According to DAS28 at Weeks 4, 8, and 12 [ Time Frame: Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
  • Percentage of Participants Achieving Remission According to DAS28 at Weeks 16, 20, 24, and 28 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Weeks 16, 20, 24, and 28 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
  • Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
  • Percentage of Participants Achieving Remission According to DAS28 at Week 32 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Remission was defined as a DAS28 score <2.6 at the assessment visit.
  • Percentage of Participants Achieving Low Disease Activity Score (LDAS) According to DAS28 [ Time Frame: Week 16 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x the patient global assessment of disease activity using a VAS]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score <3.2 at the assessment visit.
  • Percentage of Participants Achieving LDAS According to DAS28 Among Among Nonresponding Participants Treated With Rituximab [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x the patient global assessment of disease activity using a VAS]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. LDAS was defined as a DAS28 score <3.2 at the assessment visit.
  • Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from Baseline to the assessment visit were considered clinically relevant.
  • Percentage of Participants Achieving a Clinically Relevant Reduction From Baseline in DAS28 at Weeks 4, 8, and 12 [ Time Frame: Baseline and Weeks 4, 8, and 12 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from Baseline to the assessment visit were considered clinically relevant.
  • Percentage of Participants Achieving a Clinically Relevant Reduction in DAS28 From Week 16 to Week 32 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity. Reductions >1.2 points from the reference visit (Week 16) to the assessment visit were considered clinically relevant.
  • DAS28 Scores During and After Treatment [ Time Frame: Baseline and Weeks 4, 8, 12, 16 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
  • DAS28 Scores During and After Treatment Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 20, 24, 28, and 32 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
  • DAS28 Scores During and After Treatment Among Nonresponding Participants Treated With Rituximab [ Time Frame: Baseline and Weeks 4, 8, 12, 16, 24, and 32 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
  • DAS28 Scores During Safety Follow-Up Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 40, 48, 56, and 66 ] [ Designated as safety issue: No ]
    The DAS28 was calculated as [0.28 x the square root of number of swollen joints] + [0.56 x the square root of number of tender joints] + [0.7 x the natural log of ESR] + [0.014 x VAS patient global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' DAS28 scores ranged from 0 to 10, with higher scores indicating increased disease activity.
  • Percentage of Participants Achieving a Response According to European League Against Rheumatism (EULAR) Criteria at Weeks 4, 8, 12 and 16 [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
  • Percentage of Participants Achieving a Response According to EULAR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from the reference visit (Week 16). Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
  • Percentage of Participants Achieving a Response According to EULAR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ] [ Designated as safety issue: No ]
    Response was determined using EULAR criteria based upon DAS28 absolute scores at the assessment visit and the DAS28 reduction from Baseline. Participants with a score ≤3.2 and reduction of >1.2 points were assessed as having a 'good' response. Participants with a score >3.2 with reduction of >1.2 points, or a score ≤5.1 with reduction of >0.6 to ≤1.2 points, were assessed as having a 'moderate' response. Participants with a score >5.1 with reduction of >0.6 to ≤1.2 points, or any score with reduction ≤0.6 points, were assessed as nonresponders with response recorded as 'none.'
  • Percentage of Participants Achieving a Response According to American College of Rheumatology (ACR) Criteria at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate a swollen joint count (SJC) ranging from 0 to 66 swollen joints and a tender joint count (TJC) ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, Health Assessment Questionnaire Disability Index (HAQ-DI), or C-reactive protein (CRP); plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
  • Percentage of Participants Achieving a Response According to ACR Criteria at Week 32 Compared to Week 16 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from the reference visit (Week 16) of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
  • Percentage of Participants Achieving a Response According to ACR Criteria at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ] [ Designated as safety issue: No ]
    Response was determined using ACR criteria based upon assessment of 66 joints for swelling and 68 joints for tenderness; joints were classified dichotomously as swollen or not swollen and tender or not tender. Respectively, these assessments were used to generate an SJC ranging from 0 to 66 swollen joints and a TJC ranging from 0 to 68 tender joints. Response was defined as a reduction from Baseline of at least 20% for one of the following: VAS scores for patient-reported pain, patient global assessment of disease activity, or physician global assessment of disease activity, HAQ-DI, or CRP; plus a reduction in individual SJC and TJC of 20% (ACR20), 50% (ACR50), or 70% (ACR70). VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.'
  • Change From Baseline in Clinical Disease Activity Index (CDAI) and Simplified Disease Activity Index (SDAI) Scores at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
  • Change From Week 16 to 32 in CDAI and SDAI Scores Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
  • Change From Baseline in CDAI and SDAI Scores at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ] [ Designated as safety issue: No ]
    The CDAI was calculated as [SJC + TJC + VAS patient global assessment of disease activity + VAS physician global assessment of disease activity]. VAS assessments involved a 10-cm horizontal scale from 'no disease activity' to 'maximum disease activity.' CDAI scores ranged from 0 to 76, with higher scores indicating increased disease activity. The SDAI was determined by adding CRP level to the CDAI score. Scores ranged from 0 to 86, with higher scores also indicating increased disease activity. A reduction in either score at the assessment visit reflects improvement in disease.
  • Change From Baseline in Hemoglobin at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline] and expressed in grams per liter (g/L).
  • Change From Baseline in CRP at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean CRP at the assessment visit minus mean CRP at Baseline] and expressed in milligrams per deciliter (mg/dL).
  • Change From Baseline in ESR at Weeks 4, 8, 12, and 16 [ Time Frame: Baseline and Weeks 4, 8, 12, and 16 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean ESR at the assessment visit minus mean ESR at Baseline] and expressed in millimeters per hour (mm/h).
  • Change in Hemoglobin From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change was calculated as [mean hemoglobin at Week 32 minus mean hemoglobin at Week 16] and expressed in g/L.
  • Change in CRP From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change was calculated as [mean CRP at Week 32 minus mean CRP at Week 16] and expressed in mg/dL.
  • Change in ESR From Week 16 to 32 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change was calculated as [mean ESR at Week 32 minus mean ESR at Week 16] and expressed in mm/h.
  • Change From Baseline in Hemoglobin at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including hemoglobin level, were collected prior to each dose of study medication. The mean hemoglobin level was determined at Baseline and for assessment visits by averaging the observed hemoglobin level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean hemoglobin at the assessment visit minus mean hemoglobin at Baseline] and expressed in g/L.
  • Change From Baseline in CRP at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including CRP level, were collected prior to each dose of study medication. The mean CRP level was determined at Baseline and for assessment visits by averaging the observed CRP level among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean CRP at the assessment visit minus mean CRP at Baseline] and expressed in mg/dL.
  • Change From Baseline in ESR at Weeks 20, 24, 28, and 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 20, 24, 28, and 32 ] [ Designated as safety issue: No ]
    Blood samples for laboratory assessments, including ESR, were collected prior to each dose of study medication. The mean ESR was determined at Baseline and for assessment visits by averaging the observed ESR among all participants providing evaluable blood samples. Change from Baseline was calculated as [mean ESR at the assessment visit minus mean ESR at Baseline] and expressed in mm/h.
  • Percentage of Participants Withdrawing From the Study for Insufficient Therapeutic Response [ Time Frame: Baseline to Week 16 ] [ Designated as safety issue: No ]
    Study discontinuation was documented by reason for each participant prematurely withdrawing from the study. The percentage of participants was calculated as the number withdrawing for insufficient therapeutic response divided by the total number of participants who began treatment.
  • Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants With Early Remission [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
  • Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
  • Percentage of B-Cells at Baseline by B-Cell Subpopulation Among Nonresponding Participants Treated With Rituximab [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional (cluster of differentiation [CD] 19-positive, immunoglobulin (Ig) D-positive, CD38 medium, CD10-positive); naive (CD19-positive, IgD-positive, CD38 medium, CD27-negative); pre-switch memory (CD19-positive, CD27-positive, IgD-positive); post-switch memory (CD19-positive, CD27-positive, IgD-negative); IgG-positive class-switched (CD19-positive, IgG-positive); IgA-positive class-switched (CD19-positive, IgA-positive); double-negative memory (CD19-positive, IgD-negative, CD27-negative); and plasmablasts (CD19-positive, IgD-negative, CD38 high, CD27 high). Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined.
  • Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Week 16 Among Participants With Early Remission [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline to Week 16 in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
  • Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 24, and 32 Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Baseline and Weeks 16, 24, and 32 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
  • Spearman's Rank Correlation Coefficient Between Percentage of B-Cells at Baseline and Difference in DAS28 Scores Between Baseline and Weeks 16, 32, 40, 48, and 66 Among Nonresponding Participants Treated With Rituximab [ Time Frame: Baseline and Weeks 16, 32, 40, 48, and 66 ] [ Designated as safety issue: No ]
    Blood samples were collected to analyze total B-cell panel via immunophenotyping. Subpopulations were as follows: transitional, naïve, pre-switch memory, post-switch memory, IgG-positive class-switched, IgA-positive class-switched, double-negative memory, and plasmablasts. Naive B-cell compartment was defined as the sum of transitional and naive B-cells. The sum of memory B-cell subsets with or without double-negative B-cells was also determined. Extent of disease response, using change from Baseline in DAS28 score, was correlated to the percentage of B-cells within each subpopulation at Baseline. Correlation is indicated by a correlation coefficient (r) >0.2, with greater values indicating a stronger correlation.
  • Mean Number of Work Days Missed Per Week [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    Work days missed were documented by reason (either rheumatoid arthritis [RA] or other reasons) for each participant over the preceding 7-day period. The mean number of work days missed was calculated by averaging the number of days missed per week among all participants.
  • Quality of Life as Assessed Using Short Form 36 (SF-36) [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants.
  • Change From Baseline in Quality of Life as Assessed Using SF-36 at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 16 minus mean score at Baseline].
  • Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 32 minus mean score at Week 16].
  • Change From Week 16 to 32 in Quality of Life as Assessed Using SF-36 Scores Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The SF-36 evaluates participant-rated quality of life using 8 domains: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, and mental health. The score for each section is the average of the individual question scores, which are scaled from 0 to 100, with higher scores indicating better functioning. The mean score at each timepoint was determined by averaging the scores among all participants, and the change in each domain score was calculated as [mean score at Week 32 minus mean score at Week 16].
  • Quality of Life as Assessed Using HAQ-DI [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants.
  • Change From Baseline in Quality of Life as Assessed Using HAQ-DI at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 16 minus mean score at Baseline].
  • Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 32 minus the mean score at Week 16].
  • Change From Week 16 to 32 in Quality of Life as Assessed Using HAQ-DI Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. The mean index score at each timepoint was determined by averaging the scores among all participants, and the change in score was calculated as [mean score at Week 32 minus the mean score at Week 16].
  • Percentage of Participants Achieving a Response According to HAQ-DI Criteria [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The HAQ-DI evaluates participant-reported quality of life using 8 categories: dressing/grooming, arising, eating, walking, hygiene, reach, grip, and other common activities such as running errands and performing household chores. Each category contains multiple questions, which are answered using a 4-point scale from 0 to 3. The overall index score is taken as an average of the individual item responses and may range from 0 to 3, where higher scores indicate more difficulty in daily living activities. Response was defined as a change in index score >0.22 from Baseline to Week 16.
  • Quality of Life as Assessed Using Functional Assessment of Chronic Illness Therapy (FACIT) [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The FACIT-F evaluates quality of life using 5 categories: physical well-being (PWB), social/family well-being (SWB), emotional well-being (EWB), functional well-being (FWB), and fatigue (FS). Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-General (FACIT-G; range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-Fatigue (FACIT-F) trial outcome index (TOI; range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants.
  • Change From Baseline in Quality of Life as Assessed Using FACIT at Week 16 [ Time Frame: Baseline and Week 16 ] [ Designated as safety issue: No ]
    The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 16 minus mean score at Baseline].
  • Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Participants Treated With 8 Courses of Tocilizumab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 32 minus mean score at Week 16].
  • Change From Week 16 to 32 in Quality of Life as Assessed Using FACIT Among Nonresponding Participants Treated With Rituximab [ Time Frame: Weeks 16 and 32 ] [ Designated as safety issue: No ]
    The FACIT-F evaluates quality of life using 5 categories: PWB, SWB, EWB, FWB, and FS. Participants answer each item on a 5-point scale from 0 to 4. The total score is the sum of individual responses across all 5 categories and may range from 0 to 160. The FACIT-G (range 0 to 108) is the sum of scores for PWB, SWB, EWB, and FWB; the FACIT-F TOI (range 0 to 108) is the sum of scores for PWB, FWB, and FS; and the FACIT-F fatigue (range 0 to 52) is the sum of scores for the FS only. For derivations of the FACIT-F reported here, higher scores indicate better quality of life. The mean score at each timepoint was determined by averaging scores among all participants, and the change in score was calculated as [mean score at Week 32 minus mean score at Week 16].
  • Rate of Disease Activity Score (DAS28) remission <2.6 at Week 32 [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
  • Response rate according to European League Against Rheumatism (EULAR) criteria [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
  • Response rate according to American College of Rheumatology (ACR) criteria [ Time Frame: Week 32 ] [ Designated as safety issue: No ]
  • Quality of life: Short Form (36) Health Survey [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
  • Quality of life: Health Assessment Questionnaire - Disability Index (HAQ-DI) [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
  • Quality of life: Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) scale [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
  • Safety: Incidence of adverse events [ Time Frame: 32 weeks ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
A Study of RoActemra/Actemra and, if Initially Inadequately Responded to RoActemra/Actemra, Followed by MabThera/Rituxan in Patients With Rheumatoid Arthritis
Efficacy and Safety Study of a Sequential Therapy of Tocilizumab (TCZ) and, if Initially Inadequately Responded to Tocilizumab (TCZ), Followed by Rituximab (RTX) in DMARD-IR Patients With Rheumatoid Arthritis (MIRAI)
This open-label, multi-center, two-arm, uncontrolled and non-randomized study will evaluate the efficacy and safety of RoActemra/Actemra (tocilizumab) in patients with rheumatoid arthritis. Patients will receive 8 mg/kg RoActemra/Actemra intravenously every 4 weeks for 12 weeks and - if adequately responded - for further 12 weeks. Patients, who show an inadequate clinical response after the first 12 weeks to RoActemra/Actemra, will receive 1 g MabThera/Rituxan (rituximab) intravenously at Week 16 and 18. The anticipated time of study treatment is 32 weeks.
Not Provided
Interventional
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Rheumatoid Arthritis
  • Drug: rituximab [MabThera/Rituxan]
    1 g intravenously at Week 16 and 18
  • Drug: tocilizumab [RoActemra/Actemra]
    8 mg/kg intravenously every 4 weeks for 12 weeks.
  • Drug: tocilizumab [RoActemra/Actemra]
    8 mg/kg intravenously every 4 weeks from Week 16 to Week 28
  • Experimental: 1
    Interventions:
    • Drug: tocilizumab [RoActemra/Actemra]
    • Drug: tocilizumab [RoActemra/Actemra]
  • Experimental: 2
    Interventions:
    • Drug: rituximab [MabThera/Rituxan]
    • Drug: tocilizumab [RoActemra/Actemra]
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
519
February 2014
February 2014   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Adult patients >/=18 years of age
  • Body weight < /=130kg
  • Active rheumatoid arthritis of at least 6 months duration, diagnosed according to the American College of Rheumatology (ACR) criteria of 1987
  • Disease Activity Score (DAS28) of >3.2
  • Inadequate clinical response to a stable dose of traditional Disease-Modifying Anti-Rheumatic Drugs (DMARD)
  • Have received permitted DMARDs, one or more; current DMARD therapy must have been at stable dose for at least 4 weeks prior to baseline

Exclusion Criteria:

  • Prior treatment with TNF-inhibitors or other biologic DMARD
  • Major surgery (including joint surgery) within eight weeks prior to baseline or planned major surgery within the study duration
  • Functional class IV (American College of Rheumatology classification)
  • Rheumatic autoimmune disease other than rheumatoid arthritis
  • History of or current inflammatory joint disease other than rheumatoid arthritis
Both
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
Germany
 
NCT01332994
ML22985
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
August 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP