Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis
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|ClinicalTrials.gov Identifier: NCT02659150|
Recruitment Status : Enrolling by invitation
First Posted : January 20, 2016
Last Update Posted : January 1, 2019
|Condition or disease||Intervention/treatment||Phase|
|Rheumatoid Arthritis||Drug: tocilizumab||Phase 4|
This multi-center study will recruit 21 subjects to undergo an open-label tocilizumab treatment for 13-18 weeks in order to examine the efficacy of tocilizumab on plaque inflammation in RA patients. This multi-center study will employ PET/MR imaging of the carotid and coronary arteries and aorta to assess the effect of anti-IL-6 therapy on arterial inflammation in patients with RA who are synthetic dMARD inadequate responders and are naive to biologic therapy.
Secondary, exploratory evaluation will also examine correlations between atherosclerotic plaque inflammation and the inflammatory activity of the rheumatoid joint measured by PET-MR imaging, as well as how the changes in inflammation correlate with lipid and inflammatory biomarkers, and how stress levels are associated with inflammatory activity.
Adults between 50 and 75 years old diagnosed with RA will come in for an initial screening visit to assess for clinical eligibility criteria (visit 1). During the screening period, patient acceptability for the study will be assessed on the basis of medical history, concomitant medications, physical examination, and clinical laboratory test results. The study doctor will review the screening test results and procedures to determine the subject eligibility prior to imaging. Women able to become pregnant will be excluded due to teratogenic side effects.
A FDG-PET/MR imaging study will be performed at a second screening visit (visit 2) to assess for the presence of arterial, plaque and joint inflammation. A serum pregnancy test will be drawn and confirmed to be negative prior to imaging for female subjects of childbearing potential. Acceptability for study participants will be confirmed on the basis of a tissue-to-background ratio (TBR) of greater than or equal to 1.7 in qualifying vessel (calculated using the mean of the maximum SUV) as measured from FDG-PET/MR imaging. Participants who meet clinical and imaging eligibility criteria will be enrolled into the study (visit 3). Subjects will receive first dose of tocilizumab subcutaneously, on subsequent weeks, subjects will be instructed to self-administer tocilizumab at a dose of 162mg every week for a 12 week period. 4 weeks post-initiation, participants will return for a clinical safety follow-up (visit 4). Final evaluation will include physical exams, clinical assessments and carotid IMT test. A second FDG-PET/MR imaging session will take place 12 weeks post-administration (visit 5).
Effect of tocilizumab on arterial plaque inflammation will be examined by measuring the change in FDG uptake in the carotid arteries, coronary arteries and aorta between the baseline and 12 week FDG-PET/MRI.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||21 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Open-Label, Proof-of-Activity Study of the Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis|
|Actual Study Start Date :||May 18, 2016|
|Estimated Primary Completion Date :||June 30, 2019|
|Estimated Study Completion Date :||October 30, 2019|
tocilizumab will be given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
subjects will be treated with 162mg of weekly subcutaneous tocilizumab in an open-label manner, this will be done addition to MTX or monotherapy. On subsequent weeks after the first dose of tocilizumab, subjects will be instructed to inject the full amount of syringe according to the directions provided in the Instructions For Use (IFU).
Other Name: ACTEMRA
- Change in arterial FDG uptake (on FDG PET) from baseline to post-treatment [ Time Frame: 13-18 weeks ]carotid or aortic FDG uptake is measured on PET-MR imaging before and after 12 weeks of tocilizumab treatment.
- Change in arterial FDG uptake within atherosclerotic plaque in carotid/aortic arteries, from baseline to post-treatment [ Time Frame: 13-18 weeks ]Changes of inflammation occur within atherosclerotic plaque will be measured on MRI based on change in carotid or aortic plaque FDG uptake before and after 12 weeks treatment
- change in FDG uptake within joints [ Time Frame: 13-18 weeks ]FDG uptake within joints will be measured as an index of inflammation. We will measure changes in joint inflammation before and after treatment
- LDL [ Time Frame: 13-18 weeks ]measure of LDL changes before and after treatment
- fMRI signal in amygdala [ Time Frame: 13-18 weeks ]changes in activity (fMRI) in the amygdala before and after randomization
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02659150
|Principal Investigator:||Ahmed Tawakol, MD||Massachusetts General Hospital|