Trial Outcomes & Findings for Effect of Subcutaneous ACTEMRA on Inflamed Atherosclerotic Plaques in Patients With Rheumatoid Arthritis (NCT NCT02659150)
NCT ID: NCT02659150
Last Updated: 2021-02-23
Results Overview
The change in the target-to-background ratio of FDG uptake of the carotid, measured on PET-MR imaging before vs after 12 weeks of tocilizumab treatment. FDG uptake is calculated as Target to background values (TBR) . TBR, in turn, is calculated as the mean arterial standardized uptake value (SUV) divided by background blood pool SUV.
TERMINATED
PHASE4
16 participants
Baseline and 13-18 weeks follow-up
2021-02-23
Participant Flow
Participant milestones
| Measure |
Open-Label Tocilizumab
tocilizumab will be given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
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|---|---|
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Subject Enrollment
STARTED
|
16
|
|
Subject Enrollment
COMPLETED
|
11
|
|
Subject Enrollment
NOT COMPLETED
|
5
|
|
Baseline Imaging
STARTED
|
11
|
|
Baseline Imaging
COMPLETED
|
9
|
|
Baseline Imaging
NOT COMPLETED
|
2
|
|
Study Drug Dosing
STARTED
|
9
|
|
Study Drug Dosing
COMPLETED
|
8
|
|
Study Drug Dosing
NOT COMPLETED
|
1
|
|
Follow-up Imaging
STARTED
|
8
|
|
Follow-up Imaging
COMPLETED
|
8
|
|
Follow-up Imaging
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Open-Label Tocilizumab
tocilizumab will be given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
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|---|---|
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Subject Enrollment
Physician Decision
|
3
|
|
Subject Enrollment
Withdrawal by Subject
|
2
|
|
Baseline Imaging
Withdrawal by Subject
|
1
|
|
Baseline Imaging
Physician Decision
|
1
|
|
Study Drug Dosing
Adverse Event
|
1
|
Baseline Characteristics
8 of 16 subjects completed imaging
Baseline characteristics by cohort
| Measure |
Open-Label Tocilizumab
n=16 Participants
tocilizumab will be given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
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|---|---|
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Age, Continuous
|
62.1 years
STANDARD_DEVIATION 6.8 • n=16 Participants
|
|
Sex: Female, Male
Female
|
13 Participants
n=16 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=16 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=16 Participants
|
|
Race (NIH/OMB)
White
|
14 Participants
n=16 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=16 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=16 Participants
|
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Arterial Inflammation
|
2.17 Target to Background Ratio (TBR)
STANDARD_DEVIATION 0.56 • n=8 Participants • 8 of 16 subjects completed imaging
|
PRIMARY outcome
Timeframe: Baseline and 13-18 weeks follow-upPopulation: subjects completing both imaging visits
The change in the target-to-background ratio of FDG uptake of the carotid, measured on PET-MR imaging before vs after 12 weeks of tocilizumab treatment. FDG uptake is calculated as Target to background values (TBR) . TBR, in turn, is calculated as the mean arterial standardized uptake value (SUV) divided by background blood pool SUV.
Outcome measures
| Measure |
Open-Label Tocilizumab
n=8 Participants
tocilizumab was given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
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|---|---|
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Change in Arterial Inflammation in the Carotids
|
-0.10 Ratio
Standard Deviation 0.24
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SECONDARY outcome
Timeframe: Baseline and 13-18 weeks follow-upPopulation: participant who completed imaging
Change in FDG uptake in joints over the treatment period will be compared to the change in FDG uptake in arteries over the same period. FDG uptake is calculated as Target to background values (TBR)) . TBR, in turn, is calculated as the mean arterial standardized uptake value (SUV) divided by background blood pool SUV.
Outcome measures
| Measure |
Open-Label Tocilizumab
n=8 Participants
tocilizumab was given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
|
|---|---|
|
Association Between Change in Arterial Inflammation and Change in Articular Inflammation
|
0.76 Correlation coefficient
|
SECONDARY outcome
Timeframe: Baseline and 13-18 weeks follow-upChanges of Target to Background Ratio within the most diseased segment of the carotid arteries( a plaque-based analysis) before vs. after 12 weeks treatment
Outcome measures
| Measure |
Open-Label Tocilizumab
n=8 Participants
tocilizumab was given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
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|---|---|
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Change in Target to Background Ratio Within Carotid Artery Plaques
|
-0.58 Ratio
Standard Deviation 0.32
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SECONDARY outcome
Timeframe: Baseline and 13-18 weeks follow-upPopulation: participant who completed imaging
Change in LDL over the treatment period will be compared to the change in FDG uptake in arteries over the same period. FDG uptake is calculated as Target to background values (TBR)) . TBR, in turn, is calculated as the mean arterial standardized uptake value (SUV) divided by background blood pool SUV.
Outcome measures
| Measure |
Open-Label Tocilizumab
n=8 Participants
tocilizumab was given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
|
|---|---|
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Association Between Change in Arterial Inflammation and Change in LDL
|
-0.66 Correlation coefficient
|
SECONDARY outcome
Timeframe: Baseline and 13-18 weeks follow-upPopulation: participant who completed imaging
Change in CRP (C-reactive protein) over the treatment period will be compared to the change in FDG uptake in arteries over the same period. FDG uptake is calculated as Target to background values (TBR)) . TBR, in turn, is calculated as the mean arterial standardized uptake value (SUV) divided by background blood pool SUV.
Outcome measures
| Measure |
Open-Label Tocilizumab
n=8 Participants
tocilizumab was given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
|
|---|---|
|
Association Between Change in Arterial Inflammation and Change in CRP
|
0.67 Correlation coefficient
|
SECONDARY outcome
Timeframe: Baseline to 13-18 weeks follow-upPopulation: Correlation coefficients cannot be calculated. The BOLD imaging was optional. Only one subject produced measurable BOLD imaging at baseline and follow-up. Thus while the data are analyzed, correlation coefficients cannot be calculated.
Correlation coefficients cannot be calculated. The BOLD imaging was optional. Only one subject produced measurable BOLD imaging at baseline and follow-up. Thus while the data are analyzed, correlation coefficients cannot be calculated.
Outcome measures
| Measure |
Open-Label Tocilizumab
n=1 Participants
tocilizumab was given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
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|---|---|
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Correlation Between Change in BOLD Signals in the Amygdala and Anterior Cingulate Cortex With Atherosclerotic Plaque FDG Uptake
|
NA participants
Correlation coefficients cannot be calculated. The BOLD imaging was optional. Only one subject produced measurable BOLD imaging at baseline and follow-up. Thus while the data are analyzed, correlation coefficients cannot be calculated for a single subject.
|
Adverse Events
Open-Label Tocilizumab
Serious adverse events
| Measure |
Open-Label Tocilizumab
n=16 participants at risk
tocilizumab will be given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
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|---|---|
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Respiratory, thoracic and mediastinal disorders
pneumonia
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
Other adverse events
| Measure |
Open-Label Tocilizumab
n=16 participants at risk
tocilizumab will be given to rheumatoid arthritis patients at a dose of 162 mg subcutaneously a week
tocilizumab: 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).
|
|---|---|
|
Hepatobiliary disorders
elevated hepatic enzymes
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Blood and lymphatic system disorders
Leukopenia
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Blood and lymphatic system disorders
Leukopenia and Throbocytopenia
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Musculoskeletal and connective tissue disorders
traumatic fracture
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Skin and subcutaneous tissue disorders
squamous cell carcinoma
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Hepatobiliary disorders
Adenomiomatosys of the fundus of the gallbladder
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Respiratory, thoracic and mediastinal disorders
sinusitis
|
18.8%
3/16 • Number of events 3 • 13-18 weeks
|
|
Renal and urinary disorders
cyst in the right kidney
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Cardiac disorders
pericardial cyst
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
|
Vascular disorders
vertebral hemangioma
|
6.2%
1/16 • Number of events 1 • 13-18 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place