Trial Outcomes & Findings for Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk (NCT NCT02272946)
NCT ID: NCT02272946
Last Updated: 2023-04-20
Results Overview
Change in creatinine count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
43 participants
Primary outcome timeframe
weeks 4, 8, 12, 18, 24, and 36.
Results posted on
2023-04-20
Participant Flow
Participant milestones
| Measure |
Safety Arm
In Stage 1: all 10 participants received 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
In Stage II: 25 participants received150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Overall Study
STARTED
|
10
|
25
|
8
|
|
Overall Study
COMPLETED
|
10
|
25
|
8
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Effect of IL--1β Inhibition on Inflammation and Cardiovascular Risk
Baseline characteristics by cohort
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 22 subjects will receive 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: About 11 subjects will receive 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
Total
n=43 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
9 Participants
n=5 Participants
|
21 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
37 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
3 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
9 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
40 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
10 Participants
n=5 Participants
|
25 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
42 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Black or African American
|
2 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
7 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
8 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
35 Participants
n=4 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Hypertension
|
9 Participants
n=5 Participants
|
10 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
21 Participants
n=4 Participants
|
|
Cardiovascular Disease
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
6 Participants
n=4 Participants
|
|
Diabetes
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Dyslipidemia on Statin Therapy
|
8 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
29 Participants
n=4 Participants
|
PRIMARY outcome
Timeframe: weeks 4, 8, 12, 18, 24, and 36.Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
Change in CD4 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Change in CD4 Count From Baseline to Follow-up
Week 4
|
-0.085 log cells per mm^3
Interval -0.17 to 0.008
|
-0.024 log cells per mm^3
Interval -0.106 to 0.065
|
-0.020 log cells per mm^3
Interval -0.149 to 0.129
|
|
Change in CD4 Count From Baseline to Follow-up
Week 8
|
-0.090 log cells per mm^3
Interval -0.174 to 0.003
|
0.004 log cells per mm^3
Interval -0.084 to 0.1
|
-0.015 log cells per mm^3
Interval -0.145 to 0.134
|
|
Change in CD4 Count From Baseline to Follow-up
Week 12
|
-0.049 log cells per mm^3
Interval -0.139 to 0.05
|
-0.111 log cells per mm^3
Interval -0.186 to -0.029
|
-0.070 log cells per mm^3
Interval -0.192 to 0.072
|
|
Change in CD4 Count From Baseline to Follow-up
Week 18
|
—
|
-0.105 log cells per mm^3
Interval -0.182 to -0.02
|
-0.009 log cells per mm^3
Interval -0.14 to 0.142
|
|
Change in CD4 Count From Baseline to Follow-up
Week 24
|
—
|
-0.142 log cells per mm^3
Interval -0.22 to -0.057
|
-0.012 log cells per mm^3
Interval -0.147 to 0.145
|
|
Change in CD4 Count From Baseline to Follow-up
Week 36
|
—
|
-0.109 log cells per mm^3
Interval -0.189 to -0.02
|
-0.164 log cells per mm^3
Interval -0.278 to -0.032
|
PRIMARY outcome
Timeframe: weeks 4, 8, 12, 18, 24, and 36.Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
Change in CD8 count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Change in CD8 Count From Baseline to Follow-up
Week 4
|
-0.101 log cells per mm^3
Interval -0.257 to 0.088
|
-0.039 log cells per mm^3
Interval -0.125 to 0.05
|
0.006 log cells per mm^3
Interval -0.133 to 0.168
|
|
Change in CD8 Count From Baseline to Follow-up
Week 8
|
-0.103 log cells per mm^3
Interval -0.259 to 0.086
|
-0.069 log cells per mm^3
Interval -0.154 to 0.03
|
-0.040 log cells per mm^3
Interval -0.173 to 0.115
|
|
Change in CD8 Count From Baseline to Follow-up
Week 12
|
-0.166 log cells per mm^3
Interval -0.313 to 0.014
|
-0.192 log cells per mm^3
Interval -0.264 to -0.11
|
-0.111 log cells per mm^3
Interval -0.234 to -0.032
|
|
Change in CD8 Count From Baseline to Follow-up
Week 18
|
—
|
-0.202 log cells per mm^3
Interval -0.274 to -0.12
|
-0.098 log cells per mm^3
Interval -0.223 to 0.047
|
|
Change in CD8 Count From Baseline to Follow-up
Week 24
|
—
|
-0.159 log cells per mm^3
Interval -0.239 to -0.07
|
-0.020 log cells per mm^3
Interval -0.16 to 0.145
|
|
Change in CD8 Count From Baseline to Follow-up
Week 36
|
—
|
-0.171 log cells per mm^3
Interval -0.25 to -0.08
|
-0.198 log cells per mm^3
Interval -0.313 to -0.063
|
PRIMARY outcome
Timeframe: weeks 4, 8, 12, 18, 24, and 36.Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
Change in absolute neutrophil count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Change in Absolute Neutrophil Count From Baseline to Follow-up
Week 4
|
-0.157 log unit (k) per uL
Interval -0.329 to 0.06
|
-0.149 log unit (k) per uL
Interval -0.244 to -0.04
|
-0.048 log unit (k) per uL
Interval -0.215 to 0.155
|
|
Change in Absolute Neutrophil Count From Baseline to Follow-up
Week 8
|
-0.137 log unit (k) per uL
Interval -0.314 to 0.084
|
-0.015 log unit (k) per uL
Interval -0.13 to 0.12
|
0.044 log unit (k) per uL
Interval -0.139 to 0.266
|
|
Change in Absolute Neutrophil Count From Baseline to Follow-up
Week 12
|
-0.065 log unit (k) per uL
Interval -0.262 to 0.184
|
-0.088 log unit (k) per uL
Interval -0.192 to 0.03
|
0.046 log unit (k) per uL
Interval -0.137 to 0.269
|
|
Change in Absolute Neutrophil Count From Baseline to Follow-up
Week 18
|
—
|
-0.110 log unit (k) per uL
Interval -0.213 to 0.01
|
0.053 log unit (k) per uL
Interval -0.131 to 0.278
|
|
Change in Absolute Neutrophil Count From Baseline to Follow-up
Week 24
|
—
|
-0.123 log unit (k) per uL
Interval -0.229 to 0.0
|
0.028 log unit (k) per uL
Interval -0.159 to 0.256
|
|
Change in Absolute Neutrophil Count From Baseline to Follow-up
Week 36
|
—
|
0.056 log unit (k) per uL
Interval -0.072 to 0.2
|
0.201 log unit (k) per uL
Interval -0.017 to 0.468
|
PRIMARY outcome
Timeframe: weeks 4, 8, 12, 18, 24, and 36.Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
Change in platelet count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Change in Platelet Count From Baseline to Follow-up
Week 18
|
—
|
0.015 log unit (k) per uL
Interval -0.044 to 0.08
|
0.028 log unit (k) per uL
Interval -0.065 to 0.129
|
|
Change in Platelet Count From Baseline to Follow-up
Week 24
|
—
|
0.016 log unit (k) per uL
Interval -0.046 to 0.08
|
0.054 log unit (k) per uL
Interval -0.044 to 0.162
|
|
Change in Platelet Count From Baseline to Follow-up
Week 4
|
-0.098 log unit (k) per uL
Interval -0.168 to -0.022
|
-0.079 log unit (k) per uL
Interval -0.131 to -0.02
|
0.026 log unit (k) per uL
Interval -0.066 to 0.127
|
|
Change in Platelet Count From Baseline to Follow-up
Week 8
|
-0.029 log unit (k) per uL
Interval -0.104 to 0.053
|
-0.032 log unit (k) per uL
Interval -0.089 to 0.03
|
0.007 log unit (k) per uL
Interval -0.083 to 0.107
|
|
Change in Platelet Count From Baseline to Follow-up
Week 12
|
-0.014 log unit (k) per uL
Interval -0.093 to 0.072
|
-0.020 log unit (k) per uL
Interval -0.076 to 0.04
|
0.014 log unit (k) per uL
Interval -0.077 to 0.115
|
|
Change in Platelet Count From Baseline to Follow-up
Week 36
|
—
|
0.045 log unit (k) per uL
Interval -0.018 to 0.11
|
-0.016 log unit (k) per uL
Interval -0.107 to 0.085
|
PRIMARY outcome
Timeframe: weeks 4, 8, 12, 18, 24, and 36.Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
Change in creatinine count from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Change in Creatinine Count From Baseline to Follow-up
Week 4
|
-0.017 log mg/dL
Interval -0.047 to 0.013
|
0.032 log mg/dL
Interval -0.011 to 0.076
|
-0.011 log mg/dL
Interval -0.076 to 0.059
|
|
Change in Creatinine Count From Baseline to Follow-up
Week 8
|
-0.001 log mg/dL
Interval -0.03 to 0.03
|
0.014 log mg/dL
Interval -0.029 to 0.059
|
-0.012 log mg/dL
Interval -0.078 to 0.057
|
|
Change in Creatinine Count From Baseline to Follow-up
Week 12
|
-0.001 log mg/dL
Interval -0.032 to 0.031
|
-0.030 log mg/dL
Interval -0.07 to 0.013
|
-0.037 log mg/dL
Interval -0.103 to 0.034
|
|
Change in Creatinine Count From Baseline to Follow-up
Week 18
|
—
|
-0.017 log mg/dL
Interval -0.059 to 0.026
|
-0.068 log mg/dL
Interval -0.129 to -0.002
|
|
Change in Creatinine Count From Baseline to Follow-up
Week 24
|
—
|
-0.004 log mg/dL
Interval -0.048 to 0.043
|
-0.008 log mg/dL
Interval -0.076 to 0.065
|
|
Change in Creatinine Count From Baseline to Follow-up
Week 36
|
—
|
0.014 log mg/dL
Interval -0.032 to 0.061
|
-0.037 log mg/dL
Interval -0.103 to 0.034
|
PRIMARY outcome
Timeframe: weeks 4, 8, 12, 18, 24, and 36.Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
Change in AST from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Change in AST From Baseline to Follow-up
Week 4
|
0.032 log AST U/L
Interval -0.046 to 0.116
|
0.025 log AST U/L
Interval -0.078 to 0.138
|
-0.103 log AST U/L
Interval -0.122 to 0.235
|
|
Change in AST From Baseline to Follow-up
Week 8
|
-0.019 log AST U/L
Interval -0.093 to 0.061
|
0.001 log AST U/L
Interval -0.102 to 0.115
|
0.055 log AST U/L
Interval -0.11 to 0.25
|
|
Change in AST From Baseline to Follow-up
Week 12
|
0.019 log AST U/L
Interval -0.06 to 0.105
|
0.080 log AST U/L
Interval -0.029 to 0.202
|
0.070 log AST U/L
Interval -0.103 to 0.277
|
|
Change in AST From Baseline to Follow-up
Week 18
|
—
|
0.024 log AST U/L
Interval -0.081 to 0.141
|
0.069 log AST U/L
Interval -0.098 to 0.268
|
|
Change in AST From Baseline to Follow-up
Week 24
|
—
|
0.031 log AST U/L
Interval -0.08 to 0.155
|
-0.040 log AST U/L
Interval -0.196 to 0.146
|
|
Change in AST From Baseline to Follow-up
Week 36
|
—
|
0.008 log AST U/L
Interval -0.1 to 0.13
|
0.049 log AST U/L
Interval -0.121 to 0.251
|
PRIMARY outcome
Timeframe: weeks 4, 8, 12, 18, 24, and 36.Population: Safety only includes 10 individuals enrolled who received open label canakinumab and followed up to week 12.
Change in ALT from baseline (entry) to follow-up at weeks 4, 8, 12, 18, 24, and 36.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Change in ALT From Baseline to Follow-up
Week 4
|
0.100 log ALT U/L
Interval -0.134 to 0.398
|
0.079 log ALT U/L
Interval -0.034 to 0.206
|
-0.024 log ALT U/L
Interval -0.185 to 0.168
|
|
Change in ALT From Baseline to Follow-up
Week 8
|
-0.123 log ALT U/L
Interval -0.31 to 0.114
|
0.046 log ALT U/L
Interval -0.067 to 0.172
|
0.116 log ALT U/L
Interval -0.068 to 0.336
|
|
Change in ALT From Baseline to Follow-up
Week 12
|
0.098 log ALT U/L
Interval -0.142 to 0.406
|
0.111 log ALT U/L
Interval -0.007 to 0.243
|
0.087 log ALT U/L
Interval -0.098 to 0.311
|
|
Change in ALT From Baseline to Follow-up
Week 18
|
—
|
0.092 log ALT U/L
Interval -0.26 to 0.224
|
0.140 log ALT U/L
Interval -0.048 to 0.364
|
|
Change in ALT From Baseline to Follow-up
Week 24
|
—
|
0.038 log ALT U/L
Interval -0.08 to 0.17
|
0.052 log ALT U/L
Interval -0.127 to 0.268
|
|
Change in ALT From Baseline to Follow-up
Week 36
|
—
|
0.007 log ALT U/L
Interval -0.107 to 0.136
|
0.205 log ALT U/L
Interval 0.0 to 0.453
|
SECONDARY outcome
Timeframe: Baseline and Week 12Population: The safety arm is an open label study where brachial artery FMD was measured at baseline and week 8.
Brachial artery FMD is calculated as the percentage increase in brachial artery diameter with hyperemia (an increase in the quantity of blood flow to a body part) induced relative to the resting brachial artery diameter. Percentage of brachial artery diameter is measured as FMD diameter/basal diameter
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Flow-Mediated Dilation (FMD)
Baseline FMD at 45 Seconds
|
3 Percent change in artery diameter
Interval 2.0 to 5.0
|
3 Percent change in artery diameter
Interval 2.0 to 4.0
|
3 Percent change in artery diameter
Interval 3.0 to 5.0
|
|
Flow-Mediated Dilation (FMD)
Baseline FMD at 60 Seconds
|
4 Percent change in artery diameter
Interval 2.0 to 5.0
|
4 Percent change in artery diameter
Interval 2.0 to 6.0
|
4 Percent change in artery diameter
Interval 3.0 to 5.0
|
|
Flow-Mediated Dilation (FMD)
Baseline FMD at 75 Seconds
|
4 Percent change in artery diameter
Interval 2.0 to 5.0
|
3 Percent change in artery diameter
Interval 2.0 to 5.0
|
3 Percent change in artery diameter
Interval 3.0 to 4.0
|
|
Flow-Mediated Dilation (FMD)
Baseline FMD at 90 Seconds
|
2 Percent change in artery diameter
Interval 1.0 to 3.0
|
3 Percent change in artery diameter
Interval 2.0 to 4.0
|
2 Percent change in artery diameter
Interval 0.0 to 3.0
|
|
Flow-Mediated Dilation (FMD)
Week 12 FMD at 45 Seconds
|
—
|
3 Percent change in artery diameter
Interval 2.0 to 4.0
|
4 Percent change in artery diameter
Interval 2.0 to 5.0
|
|
Flow-Mediated Dilation (FMD)
Week 12 FMD at 60 Seconds
|
—
|
3 Percent change in artery diameter
Interval 2.0 to 6.0
|
4 Percent change in artery diameter
Interval 3.0 to 5.0
|
|
Flow-Mediated Dilation (FMD)
Week 12 FMD at 75 Seconds
|
—
|
2 Percent change in artery diameter
Interval 2.0 to 6.0
|
4 Percent change in artery diameter
Interval 2.0 to 5.0
|
|
Flow-Mediated Dilation (FMD)
Week 12 FMD at 90 Seconds
|
—
|
2 Percent change in artery diameter
Interval 1.0 to 4.0
|
3 Percent change in artery diameter
Interval 2.0 to 5.0
|
|
Flow-Mediated Dilation (FMD)
Week 8 FMD at 45 Seconds
|
3 Percent change in artery diameter
Interval 2.0 to 3.0
|
—
|
—
|
|
Flow-Mediated Dilation (FMD)
Week 8 FMD at 60 Seconds
|
3 Percent change in artery diameter
Interval 2.0 to 4.0
|
—
|
—
|
|
Flow-Mediated Dilation (FMD)
Week 8 FMD at 75 Seconds
|
3 Percent change in artery diameter
Interval 2.0 to 4.0
|
—
|
—
|
|
Flow-Mediated Dilation (FMD)
Week 8 FMD at 90 Seconds
|
2 Percent change in artery diameter
Interval 1.0 to 4.0
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (entry) and Week 12Change From Baseline in Arterial Fluorodeoxyglucose (FDG) Uptake Assessed by FDG-PET/CT and reported as target-to-background (TBR) ratio to measure of vascular inflammation
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Arterial Inflammation Measured at Baseline and Follow-up at Week 12
Baseline (Entry)
|
3.27 target-to-background ratio
Standard Deviation 0.57
|
3.18 target-to-background ratio
Standard Deviation 0.58
|
3.85 target-to-background ratio
Standard Deviation 1.14
|
|
Arterial Inflammation Measured at Baseline and Follow-up at Week 12
Week 12
|
2.97 target-to-background ratio
Standard Deviation 0.64
|
3.21 target-to-background ratio
Standard Deviation 0.73
|
4.01 target-to-background ratio
Standard Deviation 0.78
|
SECONDARY outcome
Timeframe: Baseline, 4 weeks, 8 weeks, 12 weeks, and week 18Population: The safety arm is an open label study with D-Dimer markers evaluated at baseline, week 4, and week 8.
D-Dimer will be assessed from baseline to weeks 4, 8, 12, and 18.
Outcome measures
| Measure |
Safety Arm
n=10 Participants
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
D-Dimer
Baseline
|
548.3 ng/mL
Interval 429.5 to 1040.1
|
2121.89 ng/mL
Interval 1809.53 to 2970.82
|
1917.03 ng/mL
Interval 1692.92 to 2092.69
|
|
D-Dimer
Week 4
|
499.7 ng/mL
Interval 373.1 to 1226.0
|
2042.96 ng/mL
Interval 1905.96 to 3077.26
|
2080.01 ng/mL
Interval 1388.74 to 2676.91
|
|
D-Dimer
Week 8
|
562.4 ng/mL
Interval 445.5 to 844.4
|
—
|
—
|
|
D-Dimer
Week 12
|
—
|
2126.05 ng/mL
Interval 1766.84 to 2671.45
|
1894.52 ng/mL
Interval 1548.59 to 2341.66
|
|
D-Dimer
Week 18
|
—
|
1879.56 ng/mL
Interval 1336.44 to 2551.52
|
1669.79 ng/mL
Interval 1269.7 to 2402.89
|
SECONDARY outcome
Timeframe: Baseline, 4 weeks, 12 weeks, and week 18Population: The safety arm did not evaluate Human Serum Amyloid A
SAA will be assessed from baseline to weeks 4, 12, and 18.
Outcome measures
| Measure |
Safety Arm
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Human Serum Amyloid A (SAA)
Baseline
|
—
|
479058.3 pg/mL
Interval 263456.0 to 44598329.0
|
513209.75 pg/mL
Interval 196985.0 to 842869.45
|
|
Human Serum Amyloid A (SAA)
Week 4
|
—
|
310588.7 pg/mL
Interval 240857.9 to 1323745.0
|
20045206 pg/mL
Interval 2841774.5 to 37070079.0
|
|
Human Serum Amyloid A (SAA)
Week 12
|
—
|
844889.8 pg/mL
Interval 139007.15 to 4572776.0
|
1968440.05 pg/mL
Interval 204694.55 to 36420571.5
|
|
Human Serum Amyloid A (SAA)
Week 18
|
—
|
8838641 pg/mL
Interval 2702749.0 to 19603171.0
|
615594.95 pg/mL
Interval 147562.15 to 8188797.0
|
SECONDARY outcome
Timeframe: Baseline, 4 weeks, 12 weeks, and week 18Population: The safety arm did not evaluate Tumor Necrosis Factor Alpha
TNFa will be assessed from baseline to weeks 4, 12, and 18.
Outcome measures
| Measure |
Safety Arm
In Stage 1: all 10 subjects will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 Participants
In Stage II: 25 participants received 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 Participants
In Stage II: 8 participants received 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Tumor Necrosis Factor Alpha (TNFa)
Week 18
|
—
|
1.16 pg/mL
Interval 1.06 to 1.5
|
1.41 pg/mL
Interval 1.01 to 1.63
|
|
Tumor Necrosis Factor Alpha (TNFa)
Baseline
|
—
|
1.69 pg/mL
Interval 1.3 to 2.04
|
1.24 pg/mL
Interval 1.16 to 1.9
|
|
Tumor Necrosis Factor Alpha (TNFa)
Week 4
|
—
|
1.47 pg/mL
Interval 0.96 to 1.88
|
1.34 pg/mL
Interval 1.13 to 2.19
|
|
Tumor Necrosis Factor Alpha (TNFa)
Week 12
|
—
|
1.18 pg/mL
Interval 0.9 to 1.44
|
1.4 pg/mL
Interval 0.86 to 1.98
|
Adverse Events
Safety Arm
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Canakinumab
Serious events: 2 serious events
Other events: 1 other events
Deaths: 1 deaths
Placebo
Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Safety Arm
n=10 participants at risk
In Stage 1: all 10 participants will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 participants at risk
In Stage II: 25 participants will receive 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 participants at risk
In Stage II: 8 participants will receive 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Kaposi Sarcoma
|
0.00%
0/10 • 36 weeks
|
4.0%
1/25 • 36 weeks
|
0.00%
0/8 • 36 weeks
|
|
Blood and lymphatic system disorders
Streptococcal Sepsis
|
0.00%
0/10 • 36 weeks
|
4.0%
1/25 • 36 weeks
|
0.00%
0/8 • 36 weeks
|
Other adverse events
| Measure |
Safety Arm
n=10 participants at risk
In Stage 1: all 10 participants will receive 150 mg Canakinumab subcutaneous injection. This will be a preliminary safety study (before Stage II).
Canakinumab: 150mg Canakinumab received subcutaneously
|
Canakinumab
n=25 participants at risk
In Stage II: 25 participants will receive 150mg Canakinumab subcutaneous injection.
Canakinumab: 150mg Canakinumab received subcutaneously
|
Placebo
n=8 participants at risk
In Stage II: 8 participants will receive 150mg placebo subcutaneous injection
Placebo: 150mg Placebo received subcutaneously
|
|---|---|---|---|
|
Skin and subcutaneous tissue disorders
Shingles
|
10.0%
1/10 • Number of events 1 • 36 weeks
|
4.0%
1/25 • Number of events 1 • 36 weeks
|
0.00%
0/8 • 36 weeks
|
|
Nervous system disorders
Syncope
|
0.00%
0/10 • 36 weeks
|
0.00%
0/25 • 36 weeks
|
12.5%
1/8 • Number of events 1 • 36 weeks
|
|
Skin and subcutaneous tissue disorders
Psoriasis
|
10.0%
1/10 • Number of events 1 • 36 weeks
|
0.00%
0/25 • 36 weeks
|
0.00%
0/8 • 36 weeks
|
Additional Information
Priscilla Hsue, MD
University of California, San Francisco
Phone: 628-206-5801
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place