DCE-MRI Study (Dynamic Contrast-Enhanced Magnetic Resonance Imaging)

Condition(s) targeted: Rheumatoid Arthritis

Intervention: Etanercept (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: Amgen

Official(s) and/or principal investigator(s):
MD, Study Director, Affiliation: Amgen

Overall contact:
Amgen Call Center, Phone: 866-572-6436

The purpose of this study is to assess whether DCE-MRI can detect changes of active disease in RA subjects after 4, 8 and 12 weeks of etanercept.

Official title: DCE-MRI of the Wrist to Measure Short-Term Responses in Rheumatoid Arthritis Subjects Treated With Etanercept

Study design: Treatment, Non-Randomized, Open Label, Single Group Assignment, Pharmacodynamics Study

Primary outcome: To assess the sensitivity of DCE-MRI to detect changes in the wrist of RA subjects with active disease after 4, 8 and 12 weeks of etanercept treatment.

Secondary outcome:

To assess whether DCE-MRI can detect an etanercept effect after 4, 8, and 12 weeks of etanercept treatment when compared to 4 week etanercept-free period.

To assess the test-retest variability of DCE-MRI endpoints by comparing baseline data from Days -30 and -28.

To assess the sensitivity of non-dynamic MRI endpoints.

Detailed description: The current literature shows the promise of 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.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Fulfillment of the 1987 American College of Rheumatology (ACR) criteria for RA

(Appendix F) 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

- Subjects 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:

- Subjects who are currently receiving DMARD therapy (other than MTX,

hydroxychloroquine or sulfasalazine) including 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

Amgen Call Center, Phone: 866-572-6436

Research Site, London, United Kingdom; Recruiting

Research Site, Los Angeles, California, United States; Recruiting

Research Site, Seattle, Washington, United States; Recruiting

AmgenTrials clinical trials website

Starting date: September 2006
Ending date: December 2008
Last updated: July 16, 2009