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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Amgen
ClinicalTrials.gov Identifier:
NCT00361634
First received: August 4, 2006
Last updated: July 10, 2013
Last verified: July 2013
  Purpose

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.


Condition Intervention Phase
Rheumatoid Arthritis
Drug: Etanercept
Phase 1

Amgen has indicated that access to an investigational treatment associated with this study is available outside the clinical trial.  

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: DCE-MRI of the Wrist to Measure Short-Term Responses in Rheumatoid Arthritis Subjects Treated With Etanercept

Resource links provided by NLM:


Further study details as provided by Amgen:

Primary Outcome Measures:
  • Percent Change in Synovial Transfer Constant (Ktrans) From Days 1-29 [ Time Frame: Day 1 to Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 57 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 57 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 57 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to Day 85 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day -28 to Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day -28 to Day 57 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day -28 to Day 85 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day -28 to Day 29 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day -28 to Day 57 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day -28 to Day 85 ] [ Designated as safety issue: No ]
    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


Enrollment: 14
Study Start Date: September 2006
Study Completion Date: March 2010
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Etanercept
Etanercept 50 mg administered by subcutaneous injection once weekly for up to 12 weeks.
Drug: Etanercept
Other Name: Enbrel®

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  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: NCT00361634

Locations
United States, California
Research Site
Los Angeles, California, United States
United States, Washington
Research Site
Seattle, Washington, United States
United Kingdom
Research Site
London, United Kingdom
Sponsors and Collaborators
Amgen
Investigators
Study Director: MD Amgen
  More Information

Additional Information:
No publications provided

Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT00361634     History of Changes
Other Study ID Numbers: 20060118
Study First Received: August 4, 2006
Results First Received: August 13, 2010
Last Updated: July 10, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Amgen:
Etanercept
Enbrel
DCE-MRI
RA

Additional relevant MeSH terms:
Arthritis
Arthritis, Rheumatoid
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
TNFR-Fc fusion protein
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Inflammatory Agents
Therapeutic Uses
Antirheumatic Agents
Gastrointestinal Agents
Immunologic Factors
Immunosuppressive Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on August 27, 2014