A Study of Tocilizumab Plus Non-biological DMARD in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to Non-biological DMARDs

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01034397
First received: December 16, 2009
Last updated: January 22, 2015
Last verified: January 2015
  Purpose

This randomized, double-blind, placebo-controlled study will use Magnetic Resonance Imaging (MRI) to assess the efficacy of tocilizumab plus non-biological DMARD in patients with moderate to severe rheumatoid arthritis who have had an inadequate response to non-biological DMARDS. Patients will be randomized to receive either intravenous tocilizumab at 8mg/kg (minimal dose 480mg, maximum dose 800mg) or placebo every 4 weeks, in addition to their stable dose of non-biological DMARD. Anticipated time on study treatment is 24 weeks, and target sample size is <100.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: tocilizumab [RoActemra/Actemra]
Drug: placebo
Drug: non-biological DMARDs
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind, Placebo-controlled Study to Assess Efficacy of Tocilizumab+Non-biological DMARD in Reducing Synovitis as Measured by MRI at 12 Weeks After Initiation of Treatment in Patients With Moderate to Severe Rheumatoid Arthritis With Inadequate Response to Non-biological DMARDs

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Percent Change From Baseline to Week 12 in Synovitis Measured by Outcome Measures in Rheumatoid Arthritis Clinical Trials (OMERACT) Rheumatoid Arthritis Magnetic Resonance Image Scoring System (RAMRIS) Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Three wrist regions (distal radioulnar joint, radiocarpal joint, the intercarpal and intermetacarpal joint) and the 2nd to 5th metacarpophalangeal (MCP) were assessed for synovitis via magnetic resonance imaging (MRI) and scored using a scale ranging from 0-3 where 0 is normal and scores 1-3 (mild, moderate, severe) are by thirds of the presumed volume of enhancing tissue in the synovial compartment. These values were then summed yielding scores of 0-9 in the wrist region, 0-12 for MCP joints, and 0-22 on the aggregate. A negative value in synovitis change from Baseline score indicates an improvement.


Secondary Outcome Measures:
  • Percent Change From Baseline to Week 12 in OMERACT RAMRIS Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score plus (+) Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.

  • Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score plus (+) Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.

  • Percent Change From Baseline to Week 24 in OMERACT RAMRIS Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score + Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.

  • Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    RAMRIS score is the sum of its core components: Synovitis Score, Edema Score, and Erosion Score. Synovitis scored from 0 (normal) to 9 (maximum distension of synovial cavity). Edema scored 0 (normal) to 69 (maximum articular bone involvement). Erosion scored from 0 (normal) to 230 (maximum erosion of articular bone). RAMRIS=Synovial Score + Edema Score + Erosion Score. Minimum RAMRIS score=0 (normal), maximum RAMRIS score=308 (severe structural damage). For Synovial Score, Edema Score, Erosion Score, and RAMRIS score, increasing number=increasing severity.

  • Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Three wrist regions (distal radioulnar joint, radiocarpal joint, the intercarpal and intermetacarpal joint) and the 2nd to 5th MCP were assessed for synovitis via MRI and scored using a scale ranging from 0-3 where 0 is normal and scores 1-3 (mild, moderate, severe) are by thirds of the presumed volume of enhancing tissue in the synovial compartment. These values were then summed yielding scores of 0-9 in the wrist region, 0-12 for MCP joints, and 0-22 on the aggregate. A negative value in synovitis change from Baseline score indicates an improvement.

  • Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Synovitis is defined as an area in the synovial compartment that shows above normal postgadolinium enhancement of a thickness greater than the width of the normal synovium. T1-weighted images were acquired before and after the administration of intravenous contrast agent containing gadolinium. Intravenous contrast was required to demonstrate enhancing synovitis. Three wrist regions (distal radioulnar joint, radiocarpal joint, the intercarpal and intermetacarpal joint) and the 2nd to 5th MCP were assessed for synovitis via MRI and scored using a scale ranging from 0-3 where 0 is normal and scores 1-3 (mild, moderate, severe) are by thirds of the presumed volume of enhancing tissue in the synovial compartment. These values were then summed yielding scores of 0-9 in the wrist region, 0-12 for MCP joints, and 0-22 on the aggregate. A negative value in synovitis change from Baseline score indicates an improvement.

  • Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 centimeter (cm) (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.

  • Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 centimeter (cm) (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.

  • Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 cm (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.

  • Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for erosion via MRI and scored separately based on the proportion of eroded bone compared to the 'assessed bone volume' judged from all available images. Scoring ranges from 0 (no erosion) to 10 (91-100%). For long bones, the 'assessed bone volume' is from the articular surface to a depth of 1 cm (if the articular surface is absent its best estimated position is used), and in carpal bones it is the whole bone. Results were summed, resulting in scores from 0 to 80 for the wrist region, 0 to 150 for the MCP joints, and 0 to 230 on aggregate. A negative value in change from Baseline score indicates an improvement.

  • Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.

  • Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.

  • Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.

  • Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Bones from the wrist regions (carpal bones, distal radius, distal ulna and metacarpal bases) and the MCP joints (metacarpal heads and phalangeal bases) were assessed for edema via MRI and scored separately based on the proportion of bone with edema. Scoring ranged from 0 to 3 as follows: 0: no edema; 1: 1-33% of bone edematous; 2: 34-66% of bone edematous; 3: 67-100%. Summing these values yielded a scale from 0-45 for the wrist region, 0-24 for the MCP joints, and 0-69 on aggregate.

  • Percent Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of initial rate of enhancement (IRE) and number of voxels (Nvox), which are extracted by examining individual signal intensity vs time curves derived from defined regions of interest (ROIs). A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. Maximum enhancement (ME)=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of signal intensity (SI) until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Absolute Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Percent Change From Baseline to Week 24 in DCE-MRI EER Global Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Absolute Change From Baseline to Week 24 in DCE-MRI EER Global Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from all the assessed ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Percent Change From Baseline to Week 12 in DCE-MRI EER MCP Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Absolute Change From Baseline to Week 12 in DCE-MRI EER MCP Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Percent Change From Baseline to Week 24 in DCE-MRI EER MCP Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Absolute Change From Baseline to Week 24 in DCE-MRI EER MCP Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the MCP ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Percent Change From Baseline to Week 12 in DCE-MRI EER Wrist Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Absolute Change From Baseline to Week 12 in DCE-MRI EER Wrist Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Percent Change From Baseline to Week 24 in DCE-MRI EER Wrist Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Absolute Change From Baseline to Week 24 in DCE-MRI EER Wrist Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Contrast enhancement was quantified in terms of IRE and Nvox, which are extracted by examining individual signal intensity vs time curves derived from defined ROIs. A volume ROI was manually drawn around wrist and MCP 2-5 joints at each visit representative of size/volume of enhancement and underlying inflammation. ME=mean of ME and Nplateau+Nwashout (Nvoxels) are number of voxels that have a plateau and washout, used to assess volume of enhancing voxels within drawn ROIs. IRE=percentage increase of SI until l ME is reached calculated as maximum increase in post-contrast SI divided by baseline SI; IRE=increase in SI in %/s from time of onset of enhancement to ME. EER reflects the IRE parameter and the output is the mean from the wrist ROIs (range=between 0 and 1; 0=no change/enhancement, 1=maximum change/enhancement. Negative change from Baseline score=improvement.

  • Disease Activity Score Based on 28-Joint Count (DAS28) [ Time Frame: Baseline, Weeks 12 and 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from the number of swollen joints and tender joints (SJC and TJC) using the 28-joint count, the erythrocyte sedimentation rate (ESR) (millimeters per hour [mm/hr]) and global health assessment (participant rated global assessment of disease activity using 10-mm visual analog scale [VAS]); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity.

  • Change From Baseline to Week 12 in DAS28 Global Score [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    DAS28 was calculated from the number of swollen joints and tender joints (SJC and TJC) using the 28-joint count, the ESR (mm/hr) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Change in DAS28 global score was determined as the difference in the scores at baseline and Week 12. A negative number indicated improvement.

  • Change From Baseline to Week 24 in DAS28 Global Score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    DAS28 was calculated from the number of swollen joints and tender joints (SJC and TJC) using the 28-joint count, the ESR (mm/hr) and global health assessment (participant rated global assessment of disease activity using 10-mm VAS); DAS28 score ranged from 0 to 10, where higher scores correspond to greater disease activity. Change in DAS28 global score was determined as the difference in the scores at baseline and Week 24. A negative number indicated improvement.

  • Tender and Swollen Joint Counts [ Time Frame: Weeks 12 and 24 ] [ Designated as safety issue: No ]
    TJC and SJC were determined using the 28 joint counts. Joints were classified as tender/not tender and swollen/not swollen and counted. The scores ranged from 0 to 28. Higher scores indicated higher disease activity.

  • Change From Baseline to Week 12 in TJC [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in TJC was determined as the difference in the number of tender joints at baseline and the number at Week 12. A negative number indicated improvement.

  • Change From Baseline to Week 24 in TJC [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in TJC was determined as the difference in the number of tender joints at baseline and the number at Week 24. A negative number indicated improvement.

  • Change From Baseline to Week 12 in SJC [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in SJC was determined as the difference in the number of swollen joints at baseline and the number at Week 12. A negative number indicated improvement.

  • Change From Baseline to Week 24 in SJC [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in SJC was determined as the difference in the number of swollen joints at baseline and the number at Week 24. A negative number indicated improvement.

  • Change From Baseline to Week 12 in Patient Global Assessment of Disease Activity [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    General health was assessed using the Patient Global Assessment of Disease Activity, a 0 to 10 mm VAS, where 0 mm = very well and 10 mm = extremely bad. Participants were asked to answer the following question: "In general how would you rate your health over the last 2-3 weeks?". Participants responded by marking the line and the distance from the left edge was recorded.

  • Change From Baseline to Week 24 in Patient Global Assessment of Disease Activity [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    General health was assessed using the Patient Global Assessment of Disease Activity, a 0 to 10 mm VAS, where 0 mm = very well and 10 mm = extremely bad. Participants were asked to answer the following question: "In general how would you rate your health over the last 2-3 weeks?". Participants responded by marking the line and the distance from the left edge was recorded.

  • Patient Global Assessment of Pain [ Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24 ] [ Designated as safety issue: No ]
    Patient's Global Assessment of Pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded.

  • Change From Baseline to Week 12 in Patient Global Assessment of Pain [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Patient's Global Assessment of Pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded. Change in Patient Global Assessment of Pain was determined as the difference in the scores at baseline and Week 12. A negative number indicated improvement.

  • Change From Baseline to Week 24 in Patient Global Assessment of Pain [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Patient's Global Assessment of Pain was assessed using a 10-mm horizontal VAS (0 to 10 mm) where 0=pain absent and 10=intolerable pain. Participants responded by placing a mark on the line to indicate their current level of pain; the distance from the left edge to the mark was recorded. Change in Patient Global Assessment of Pain was determined as the difference in the scores at baseline and Week 24. A negative number indicated improvement.

  • Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores [ Time Frame: Baseline, Weeks 12 and 24 ] [ Designated as safety issue: No ]
    The HAQ-DI includes 20 questions concerning participant's activities of daily life, grouped in 8 scales of 2 to 3 questions for each activity. To respond to each question, a four-level response (score of 0 to 3 points), with higher scores showing larger functional limitations, was chosen. Scoring was as follows with respect to performance of participant's everyday activities: 0=without difficulties; 1=with some difficulties; 2=with great difficulties; and 3=unable to perform these actions at all. Minimum score was 0, maximum score was 3.

  • Change From Baseline to Week 12 in Erythrocyte Sedimentation Rate (ESR) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    ESR is an inflammatory marker and is used to assess disease activity in rheumatoid arthritis (RA). A reduction in ESR indicates improvement.

  • Change From Baseline to Week 24 in ESR [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    ESR is an inflammatory marker and is used to assess disease activity in RA. A reduction in ESR indicates improvement.

  • Change From Baseline to Week 12 in C-Reactive Protein (CRP) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement. CRP was measured in milligrams per deciliter (mg/dL).

  • Change From Baseline to Week 24 in CRP [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    The test for CRP is a laboratory measurement for evaluation of an acute phase reactant of inflammation through the use of an ultrasensitive assay. A decrease in the level of CRP indicates reduction in inflammation and therefore improvement.

  • Change From Baseline to Week 12 in Serum Cortisol [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in serum cortisol was determined as the difference in the scores at Baseline and Week 12.

  • Change From Baseline to Week 24 in Serum Cortisol [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in serum cortisol was determined as the difference in the scores at Baseline and Week 24.

  • Change From Baseline to Week 12 in Plasma Adrenocorticotrophic Hormone (ACTH) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in Plasma ACTH was determined as the difference in the scores at Baseline and Week 12.

  • Change From Baseline to Week 24 in Plasma ACTH [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in plasma ACTH was determined as the difference in the scores at baseline and Week 24.

  • Change From Baseline to Week 12 in Serum Androstenedione [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 12.

  • Change From Baseline to Week 12 in 17 Hydroxy Progesterone (17OHP) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in 17OHP was determined as the difference in the scores at Baseline and Week 12.

  • Change From Baseline to Week 24 in Serum Androstenedione [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 24.

  • Change From Baseline to Week 24 in 17OHP [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in 17OHP was determined as the difference in the scores at Baseline and Week 24.

  • Change From Baseline to Week 12 in Serum Dehydroepiandrosterone (DHEA) [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in DHEA was determined as the difference in the scores at Baseline and Week 12.

  • Change From Baseline to Week 24 in Serum DHEA [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in DHEA was determined as the difference in the scores at Baseline and Week 24.

  • Change From Baseline to Week 12 in Neuropeptide Y [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
    Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 12.

  • Change From Baseline to Week 24 in Neuropeptide Y [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
    Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 24.


Enrollment: 54
Study Start Date: March 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: tocilizumab [RoActemra/Actemra]
8mg/kg (minimal dose 480mg, maximum dose 800mg) iv infusion every 4 weeks for 24 weeks
Drug: non-biological DMARDs
stable dose at investigator's prescription
Placebo Comparator: 2 Drug: placebo
iv every 4 weeks for 24 weeks
Drug: non-biological DMARDs
stable dose at investigator's prescription

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • adult patients, >/=18 years of age
  • moderate to severe rheumatoid arthritis of >/=6 months duration
  • synovitis (swollen and tender joint) in the wrist of the dominant hand
  • non-biologic DMARDs at stable dose for >/=12 weeks prior to baseline
  • oral corticosteroids at stable dose for at least 25 out of 28 days prior to baseline

Exclusion Criteria:

  • rheumatic autoimmune disease other than RA
  • history of or current inflammatory joint disease other than RA
  • functional class IV (ACR classification)
  • intraarticular or parenteral corticosteroids within 6 weeks prior to baseline
  • previous treatment with a biologic agent for RA
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01034397

Locations
Portugal
Almada, Portugal, 2801-951
Coimbra, Portugal, 3000-075
Coimbra, Portugal, 3041-801
Lisboa, Portugal, 1349-019
Lisboa, Portugal, 1069-639
Lisboa, Portugal, 1649-035
Lisboa, Portugal, 1050-34
Ponte do Lima, Portugal, 4990-041
Porto, Portugal, 4099-001
Porto, Portugal, 4200-319
Vila Nova de Gaia, Portugal, 4400-129
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01034397     History of Changes
Other Study ID Numbers: ML22648, 2009-012218-30
Study First Received: December 16, 2009
Results First Received: July 9, 2014
Last Updated: January 22, 2015
Health Authority: Portugal: National Pharmacy and Medicines Institute

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Autoimmune Diseases
Connective Tissue Diseases
Immune System Diseases
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases

ClinicalTrials.gov processed this record on August 31, 2015