- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01034397
A Study of Tocilizumab Plus Non-biological DMARD in Patients With Moderate to Severe Rheumatoid Arthritis and an Inadequate Response to Non-biological DMARDs
February 28, 2018 updated by: Hoffmann-La Roche
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
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
54
Phase
- Phase 4
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Almada, Portugal, 2801-951
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Coimbra, Portugal, 3000-075
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Coimbra, Portugal, 3041-801
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Lisboa, Portugal, 1649-035
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Lisboa, Portugal, 1050-34
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Lisboa, Portugal, 1349-019
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Lisboa, Portugal, 1069-639
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Ponte Do Lima, Portugal, 4990-041
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Porto, Portugal, 4200-319
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Porto, Portugal, 4099-001
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Vila Nova de Gaia, Portugal, 4400-129
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
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8mg/kg (minimal dose 480mg, maximum dose 800mg) iv infusion every 4 weeks for 24 weeks
stable dose at investigator's prescription
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Placebo Comparator: 2
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stable dose at investigator's prescription
iv every 4 weeks for 24 weeks
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
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.
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Week 12
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percent Change From Baseline to Week 12 in OMERACT RAMRIS Score
Time Frame: Week 12
|
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.
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Week 12
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Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Score
Time Frame: Week 12
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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.
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Week 12
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Percent Change From Baseline to Week 24 in OMERACT RAMRIS Score
Time Frame: Week 24
|
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.
|
Week 24
|
Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Score
Time Frame: Week 24
|
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.
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Week 24
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Absolute Change From Baseline to Week 12 in OMERACT-RAMRIS Synovitis Score
Time Frame: Week 12
|
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.
|
Week 12
|
Absolute Change From Baseline to Week 24 in OMERACT-RAMRIS Synovitis Score
Time Frame: Week 24
|
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.
|
Week 24
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Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score
Time Frame: Week 12
|
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.
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Week 12
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Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Erosion Score
Time Frame: Week 12
|
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.
|
Week 12
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Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score
Time Frame: Week 24
|
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.
|
Week 24
|
Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Erosion Score
Time Frame: Week 24
|
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.
|
Week 24
|
Percent Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score
Time Frame: Week 12
|
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.
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Week 12
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Absolute Change From Baseline to Week 12 in OMERACT RAMRIS Bone Edema Score
Time Frame: Week 12
|
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.
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Week 12
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Percent Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score
Time Frame: Week 24
|
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.
|
Week 24
|
Absolute Change From Baseline to Week 24 in OMERACT RAMRIS Bone Edema Score
Time Frame: Week 24
|
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.
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Week 24
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Percent Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score
Time Frame: Week 12
|
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.
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Week 12
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Absolute Change From Baseline to Week 12 in Dynamic Contrast Enhanced (DCE)-MRI Early Enhancement Rate (EER) Global Score
Time Frame: Week 12
|
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.
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Week 12
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Percent Change From Baseline to Week 24 in DCE-MRI EER Global Score
Time Frame: Week 24
|
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.
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Week 24
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Absolute Change From Baseline to Week 24 in DCE-MRI EER Global Score
Time Frame: Week 24
|
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.
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Week 24
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Percent Change From Baseline to Week 12 in DCE-MRI EER MCP Score
Time Frame: Week 12
|
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.
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Week 12
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Absolute Change From Baseline to Week 12 in DCE-MRI EER MCP Score
Time Frame: Week 12
|
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.
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Week 12
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Percent Change From Baseline to Week 24 in DCE-MRI EER MCP Score
Time Frame: Week 24
|
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.
|
Week 24
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Absolute Change From Baseline to Week 24 in DCE-MRI EER MCP Score
Time Frame: Week 24
|
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.
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Week 24
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Percent Change From Baseline to Week 12 in DCE-MRI EER Wrist Score
Time Frame: Week 12
|
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.
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Week 12
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Absolute Change From Baseline to Week 12 in DCE-MRI EER Wrist Score
Time Frame: Week 12
|
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.
|
Week 12
|
Percent Change From Baseline to Week 24 in DCE-MRI EER Wrist Score
Time Frame: Week 24
|
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.
|
Week 24
|
Absolute Change From Baseline to Week 24 in DCE-MRI EER Wrist Score
Time Frame: Week 24
|
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.
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Week 24
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Disease Activity Score Based on 28-Joint Count (DAS28)
Time Frame: Baseline, Weeks 12 and 24
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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.
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Baseline, Weeks 12 and 24
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Change From Baseline to Week 12 in DAS28 Global Score
Time Frame: Week 12
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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.
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Week 12
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Change From Baseline to Week 24 in DAS28 Global Score
Time Frame: Week 24
|
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.
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Week 24
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Tender and Swollen Joint Counts
Time Frame: Weeks 12 and 24
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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.
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Weeks 12 and 24
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Change From Baseline to Week 12 in TJC
Time Frame: Week 12
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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.
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Week 12
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Change From Baseline to Week 24 in TJC
Time Frame: Week 24
|
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.
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Week 24
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Change From Baseline to Week 12 in SJC
Time Frame: Week 12
|
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.
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Week 12
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Change From Baseline to Week 24 in SJC
Time Frame: Week 24
|
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.
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Week 24
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Change From Baseline to Week 12 in Patient Global Assessment of Disease Activity
Time Frame: Week 12
|
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.
|
Week 12
|
Change From Baseline to Week 24 in Patient Global Assessment of Disease Activity
Time Frame: Week 24
|
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.
|
Week 24
|
Patient Global Assessment of Pain
Time Frame: Baseline, Weeks 4, 8, 12, 16, 20, and 24
|
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.
|
Baseline, Weeks 4, 8, 12, 16, 20, and 24
|
Change From Baseline to Week 12 in Patient Global Assessment of Pain
Time Frame: Week 12
|
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.
|
Week 12
|
Change From Baseline to Week 24 in Patient Global Assessment of Pain
Time Frame: Week 24
|
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.
|
Week 24
|
Health Assessment Questionnaire - Disease Index (HAQ-DI) Scores
Time Frame: Baseline, Weeks 12 and 24
|
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.
|
Baseline, Weeks 12 and 24
|
Change From Baseline to Week 12 in Erythrocyte Sedimentation Rate (ESR)
Time Frame: Week 12
|
ESR is an inflammatory marker and is used to assess disease activity in rheumatoid arthritis (RA).
A reduction in ESR indicates improvement.
|
Week 12
|
Change From Baseline to Week 24 in ESR
Time Frame: Week 24
|
ESR is an inflammatory marker and is used to assess disease activity in RA.
A reduction in ESR indicates improvement.
|
Week 24
|
Change From Baseline to Week 12 in C-Reactive Protein (CRP)
Time Frame: Week 12
|
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).
|
Week 12
|
Change From Baseline to Week 24 in CRP
Time Frame: Week 24
|
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.
|
Week 24
|
Change From Baseline to Week 12 in Serum Cortisol
Time Frame: Week 12
|
Change in serum cortisol was determined as the difference in the scores at Baseline and Week 12.
|
Week 12
|
Change From Baseline to Week 24 in Serum Cortisol
Time Frame: Week 24
|
Change in serum cortisol was determined as the difference in the scores at Baseline and Week 24.
|
Week 24
|
Change From Baseline to Week 12 in Plasma Adrenocorticotrophic Hormone (ACTH)
Time Frame: Week 12
|
Change in Plasma ACTH was determined as the difference in the scores at Baseline and Week 12.
|
Week 12
|
Change From Baseline to Week 24 in Plasma ACTH
Time Frame: Week 24
|
Change in plasma ACTH was determined as the difference in the scores at baseline and Week 24.
|
Week 24
|
Change From Baseline to Week 12 in Serum Androstenedione
Time Frame: Week 12
|
Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 12.
|
Week 12
|
Change From Baseline to Week 12 in 17 Hydroxy Progesterone (17OHP)
Time Frame: Week 12
|
Change in 17OHP was determined as the difference in the scores at Baseline and Week 12.
|
Week 12
|
Change From Baseline to Week 24 in Serum Androstenedione
Time Frame: Week 24
|
Change in serum androstenedione was determined as the difference in the scores at Baseline and Week 24.
|
Week 24
|
Change From Baseline to Week 24 in 17OHP
Time Frame: Week 24
|
Change in 17OHP was determined as the difference in the scores at Baseline and Week 24.
|
Week 24
|
Change From Baseline to Week 12 in Serum Dehydroepiandrosterone (DHEA)
Time Frame: Week 12
|
Change in DHEA was determined as the difference in the scores at Baseline and Week 12.
|
Week 12
|
Change From Baseline to Week 24 in Serum DHEA
Time Frame: Week 24
|
Change in DHEA was determined as the difference in the scores at Baseline and Week 24.
|
Week 24
|
Change From Baseline to Week 12 in Neuropeptide Y
Time Frame: Week 12
|
Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 12.
|
Week 12
|
Change From Baseline to Week 24 in Neuropeptide Y
Time Frame: Week 24
|
Change in Neuropeptide Y was determined as the difference in the scores at Baseline and Week 24.
|
Week 24
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
March 1, 2010
Primary Completion (Actual)
September 1, 2011
Study Completion (Actual)
September 1, 2011
Study Registration Dates
First Submitted
December 16, 2009
First Submitted That Met QC Criteria
December 16, 2009
First Posted (Estimate)
December 17, 2009
Study Record Updates
Last Update Posted (Actual)
March 29, 2018
Last Update Submitted That Met QC Criteria
February 28, 2018
Last Verified
February 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- ML22648
- 2009-012218-30
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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