Back to resultsDynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Etanercept
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Etanercept, Enbrel, DCE-MRI, RA
Eligibility Criteria
Inclusion Criteria: Fulfillment of the 1987 American College of Rheumatology (ACR) criteria for RA with a disease duration > 6 months Presence of active disease (defined as both tender and swollen joints) in at least one wrist Sub-optimal response to methotrexate (MTX) defined by the presence of the following criteria (based on 68/66 joint count): 8 or more swollen joints AND 8 or more tender joints (with involvement of the wrist, fingers and at least one region outside the hands) at screening Must be receiving MTX at a stable dose > 15 mg/week at least 12 weeks prior to baseline a lower dose is acceptable if otherwise not tolerated (toxicity documentation required). Exclusion Criteria: Patients who are currently receiving disease modifying anti-rheumatic drug (DMARD) therapy (other than MTX, hydroxychloroquine or sulfasalazine) including tumor necrosis factor (TNF) antagonists (etanercept, infliximab, and adalimumab), abatacept, rituximab, leflunomide, cyclosporine, and gold (oral and intramuscular injection) within 8 weeks or 5.5 half-lives, whichever is longer, of screening Co-existing condition requiring medications that alter vascular flow (e.g., nitrates, calcium channel blockers, ergot containing drugs) [Potential effects of antihypertensive and migraine medications will be discussed with the Sponsor] Comorbid autoimmune disorders including systemic lupus erythematosus Unable to undergo an MRI examination (e.g., presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip or pedicle screws allergic to contrast agent tattoos [in area of examination if contains metallic pigment]) or will likely require sedation for the procedure
Sites / Locations
- Research Site
- Research Site
- Research Site
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Etanercept
Arm Description
Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Outcomes
Primary Outcome Measures
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29
Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 29. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-57
Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 57. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-85
Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 85. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, increases in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Percent Change in Synovial Initial Area Under the (Contrast-time) Curve (IAUC) From Days 1-29
Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 29. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Percent Change in the Synovial Initial Area Under the Contrast-Tme Curve (IAUC) From Days 1-57
Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 57. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Percent Change in the Synovial Initial Area Under the Contrast-Time Curve (IAUC) From Days 1-85
Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 85. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Secondary Outcome Measures
Percent Change in Synovial Volume From Days 1-29
Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 29. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.
Percent Change in Synovial Volume From Days 1-57
Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 57. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.
Percent Change in Synovial Volume From Days 1-85
Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 85. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 29
Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 29 and from study day -28 to study day 1.
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 57
Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 57 and from study day -28 to study day 1.
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 85
Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 85 and from study day -28 to study day 1
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 29
Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 29 and from Day -28 to Day 1
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 57
Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 57 and from Day -28 to Day 1
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 85
Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 85 and from Day -28 to Day 1
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00361634
Brief Title
Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis
Official Title
DCE-MRI of the Wrist to Measure Short-Term Responses in Rheumatoid Arthritis Subjects Treated With Etanercept
Study Type
Interventional
2. Study Status
Record Verification Date
July 2013
Overall Recruitment Status
Completed
Study Start Date
September 2006 (undefined)
Primary Completion Date
August 2009 (Actual)
Study Completion Date
March 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Amgen
4. Oversight
5. Study Description
Brief Summary
The purpose of this study is to assess whether DCE-MRI can detect changes of active disease in rheumatoid arthritis (RA) patients after 4, 8 and 12 weeks of etanercept.
Detailed Description
The current literature shows the promise of magnetic resonance imaging (MRI) for assessing response to therapy in RA but the heterogeneity of the methodology and the semi-quantitative nature of the image analysis limits its applicability. To evaluate the ability of DCE-MRI to serve as a biomarker for treatment-induced changes in RA associated synovial inflammation, the reproducibility of the measurement and an effect size are required. Additional endpoints such as synovial volume, bone erosion progression and bone marrow edema-like changes may also prove useful for short-term assessment of a therapeutic intervention, but have not been explored in the context of a pharmacodynamic biomarker. It is therefore critical to conduct a carefully designed longitudinal study, focused on identifying the key parameters related to the instrumentation and data analysis, to fully evaluate the potential utility of MRI in an early clinical development setting. Importantly, this study will also demonstrate the feasibility of using DCE-MRI at multiple centers to acquire useful information that will drive program decisions.
Expanded Access: Amgen provides expanded access for this clinical trial. Contact the Amgen Call Center (866-572-6436) for more information.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Etanercept, Enbrel, DCE-MRI, RA
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Etanercept
Arm Type
Experimental
Arm Description
Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Intervention Type
Drug
Intervention Name(s)
Etanercept
Other Intervention Name(s)
Enbrel®
Primary Outcome Measure Information:
Title
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29
Description
Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 29. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Time Frame
Day 1 to Day 29
Title
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-57
Description
Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 57. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Time Frame
Day 1 to Day 57
Title
Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-85
Description
Percent change in transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from study day 1 to study day 85. Ktrans reflects contrast delivery (capillary blood flow) and transport across the vascular endothelium (capillary permeability-surface area product), with the dominant factor depending on whether delivery is flow or permeability limited. A Ktrans value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, increases in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Time Frame
Day 1 to Day 85
Title
Percent Change in Synovial Initial Area Under the (Contrast-time) Curve (IAUC) From Days 1-29
Description
Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 29. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Time Frame
Day 1 to Day 29
Title
Percent Change in the Synovial Initial Area Under the Contrast-Tme Curve (IAUC) From Days 1-57
Description
Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 57. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Time Frame
Day 1 to Day 57
Title
Percent Change in the Synovial Initial Area Under the Contrast-Time Curve (IAUC) From Days 1-85
Description
Percent change in the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 85. IAUC reflects the contrast distribution volume (extravascular extracellular space) in addition to contrast delivery and transport across the vascular endothelium. An IAUC value of zero indicates the absence of disease (ie, no leakage of the contrast agent into the synovial volume); therefore, an increase in this parameter indicates worsening disease (ie, greater permeability of the synovial membrane).
Time Frame
Day 1 to Day 85
Secondary Outcome Measure Information:
Title
Percent Change in Synovial Volume From Days 1-29
Description
Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 29. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.
Time Frame
Day 1 to Day 29
Title
Percent Change in Synovial Volume From Days 1-57
Description
Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 57. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.
Time Frame
Day 1 to Day 57
Title
Percent Change in Synovial Volume From Days 1-85
Description
Percent change in the synovial volume for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of the wrist from Day 1 to Day 85. Synovial volume was evaluated by image subtraction from the T1-weighted images pre-and post-administration of the contrast agent.
Time Frame
Day 1 to Day 85
Title
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 29
Description
Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 29 and from study day -28 to study day 1.
Time Frame
Day -28 to Day 29
Title
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 57
Description
Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 57 and from study day -28 to study day 1.
Time Frame
Day -28 to Day 57
Title
Difference Between Percent Change in Ktrans From Days -28 to 1 and Days 1 to 85
Description
Difference in percent change between synovial transfer constant (Ktrans) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from study day 1 to study day 85 and from study day -28 to study day 1
Time Frame
Day -28 to Day 85
Title
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 29
Description
Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 29 and from Day -28 to Day 1
Time Frame
Day -28 to Day 29
Title
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 57
Description
Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 57 and from Day -28 to Day 1
Time Frame
Day -28 to Day 57
Title
Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 85
Description
Difference in percent change between the synovial initial area under the contrast-time curve (IAUC) for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) from Day 1 to Day 85 and from Day -28 to Day 1
Time Frame
Day -28 to Day 85
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Fulfillment of the 1987 American College of Rheumatology (ACR) criteria for RA with a disease duration > 6 months
Presence of active disease (defined as both tender and swollen joints) in at least one wrist
Sub-optimal response to methotrexate (MTX) defined by the presence of the following criteria (based on 68/66 joint count): 8 or more swollen joints AND 8 or more tender joints (with involvement of the wrist, fingers and at least one region outside the hands) at screening
Must be receiving MTX at a stable dose > 15 mg/week at least 12 weeks prior to baseline
a lower dose is acceptable if otherwise not tolerated (toxicity documentation required).
Exclusion Criteria:
Patients who are currently receiving disease modifying anti-rheumatic drug (DMARD) therapy (other than MTX, hydroxychloroquine or sulfasalazine) including tumor necrosis factor (TNF) antagonists (etanercept, infliximab, and adalimumab), abatacept, rituximab, leflunomide, cyclosporine, and gold (oral and intramuscular injection) within 8 weeks or 5.5 half-lives, whichever is longer, of screening
Co-existing condition requiring medications that alter vascular flow (e.g., nitrates, calcium channel blockers, ergot containing drugs) [Potential effects of antihypertensive and migraine medications will be discussed with the Sponsor]
Comorbid autoimmune disorders including systemic lupus erythematosus
Unable to undergo an MRI examination (e.g., presence of a pacemaker, defibrillator, or other implanted device such as anterior interbody cages, aneurysm clip or pedicle screws
allergic to contrast agent
tattoos [in area of examination if contains metallic pigment])
or will likely require sedation for the procedure
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MD
Organizational Affiliation
Amgen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Los Angeles
State/Province
California
Country
United States
Facility Name
Research Site
City
Seattle
State/Province
Washington
Country
United States
Facility Name
Research Site
City
London
Country
United Kingdom
12. IPD Sharing Statement
Links:
URL
http://www.amgentrials.com
Description
AmgenTrials clinical trials website
Learn more about this trial
Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis
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