Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) to Measure Response to Etanercept in Rheumatoid Arthritis

Amgen14 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Rheumatoid Arthritis

Interventions

EtanerceptDRUG

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (3)

Research Site

Los Angeles, California, United States

Research Site

Seattle, Washington, United States

Research Site

London, United Kingdom

Outcomes

Primary Outcomes

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).

Time frame: Day 1 to Day 29

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).

Time frame: Day 1 to Day 57

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).

Time frame: Day 1 to Day 85

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: Day 1 to Day 29

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.

Time frame: Day 1 to Day 57

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.

Time frame: Day 1 to Day 85

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.

Time frame: Day -28 to Day 29

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.

Time frame: Day -28 to Day 57

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

Time frame: Day -28 to Day 85

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

Time frame: Day -28 to Day 29

Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 57

Time frame: Day -28 to Day 57

Difference Between Percent Change in IAUC From Days -28 to 1 and Days 1 to 85

Time frame: Day -28 to Day 85