Trial Outcomes & Findings for Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD) (NCT NCT01663103)
NCT ID: NCT01663103
Last Updated: 2016-09-12
Results Overview
Change in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.
Recruitment status
COMPLETED
Study phase
PHASE4
Target enrollment
42 participants
Primary outcome timeframe
3 months after start of treatment
Results posted on
2016-09-12
Participant Flow
Participant milestones
| Measure |
Rilonacept
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
|---|---|---|
|
Overall Study
STARTED
|
21
|
21
|
|
Overall Study
COMPLETED
|
18
|
19
|
|
Overall Study
NOT COMPLETED
|
3
|
2
|
Reasons for withdrawal
| Measure |
Rilonacept
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
2
|
|
Overall Study
Adverse Event
|
1
|
0
|
|
Overall Study
dog bite
|
1
|
0
|
Baseline Characteristics
Interleukin-1 Trap to Treat Vascular Dysfunction in Chronic Kidney Disease (CKD)
Baseline characteristics by cohort
| Measure |
Rilonacept
n=21 Participants
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
n=21 Participants
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
Total
n=42 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
61 years
STANDARD_DEVIATION 11 • n=5 Participants
|
65 years
STANDARD_DEVIATION 11 • n=7 Participants
|
63 years
STANDARD_DEVIATION 11 • n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
5 Participants
n=7 Participants
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
16 Participants
n=7 Participants
|
32 Participants
n=5 Participants
|
|
Race/Ethnicity, Customized
White
|
16 participants
n=5 Participants
|
16 participants
n=7 Participants
|
32 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
Hispanic
|
6 participants
n=5 Participants
|
6 participants
n=7 Participants
|
12 participants
n=5 Participants
|
|
Race/Ethnicity, Customized
African American
|
5 participants
n=5 Participants
|
5 participants
n=7 Participants
|
10 participants
n=5 Participants
|
|
Etiology of CKD
Hypertension
|
12 participants
n=5 Participants
|
10 participants
n=7 Participants
|
22 participants
n=5 Participants
|
|
Etiology of CKD
Type II Diabetes
|
10 participants
n=5 Participants
|
9 participants
n=7 Participants
|
19 participants
n=5 Participants
|
|
Etiology of CKD
Type I DIabetes
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Etiology of CKD
Autosomal Dominant Polycystic Kidney Disease
|
1 participants
n=5 Participants
|
2 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Etiology of CKD
Renal Cell Carcinoma
|
0 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
|
Etiology of CKD
Focal Segmental Glomerulosclerosis
|
1 participants
n=5 Participants
|
0 participants
n=7 Participants
|
1 participants
n=5 Participants
|
|
Estimated glomerular filtration rate
|
38 mL/min/1.73m^2
STANDARD_DEVIATION 14 • n=5 Participants
|
38 mL/min/1.73m^2
STANDARD_DEVIATION 12 • n=7 Participants
|
38 mL/min/1.73m^2
STANDARD_DEVIATION 13 • n=5 Participants
|
PRIMARY outcome
Timeframe: 3 months after start of treatmentChange in FMD after 3 months of treatment with rilonacept will be compared to change in the placebo group.
Outcome measures
| Measure |
Rilonacept
n=18 Participants
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
n=19 Participants
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo: Baseline
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
Placebo: End of Study
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
|---|---|---|---|---|
|
Change in Flow-mediated Dilation (FMD)
|
1.1 change in percent flow-mediated dilation
Standard Deviation 3.2
|
-0.9 change in percent flow-mediated dilation
Standard Deviation 2.2
|
—
|
—
|
SECONDARY outcome
Timeframe: 3 months after start of treatmentChange in aPWV after 3 months of treatment with rilonacept will be compared to change in the placebo group.
Outcome measures
| Measure |
Rilonacept
n=18 Participants
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
n=19 Participants
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo: Baseline
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
Placebo: End of Study
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
|---|---|---|---|---|
|
Change in Aortic Pulse-wave Velocity (aPWV)
|
12 change in pulse-wave velocity (cm/sec)
Standard Deviation 65
|
2 change in pulse-wave velocity (cm/sec)
Standard Deviation 71
|
—
|
—
|
SECONDARY outcome
Timeframe: 3 months after start of treatmentPopulation: sub-group from Denver site
FMD will be assessed following acute infusion of ascorbic acid compared to saline. The improvement in FMD with ascorbic acid reflects the degree of oxidative stress contributing to impairment in FMD.
Outcome measures
| Measure |
Rilonacept
n=10 Participants
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
n=7 Participants
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo: Baseline
n=13 Participants
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
Placebo: End of Study
n=10 Participants
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
|---|---|---|---|---|
|
Change in Contribution of Oxidative Stress to FMD
|
0.16 change in percent flow-mediated dilation
Standard Deviation 2.52
|
0.51 change in percent flow-mediated dilation
Standard Deviation 2.24
|
-0.04 change in percent flow-mediated dilation
Standard Deviation 1.96
|
0.69 change in percent flow-mediated dilation
Standard Deviation 1.73
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 months after start of treatmentChange in high-sensitivity C-reactive protein (hsCRP) after 3 months of rilonacept vs. placebo will be assessed as a circulating marker of inflammation.
Outcome measures
| Measure |
Rilonacept
n=16 Participants
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
n=19 Participants
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo: Baseline
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
Placebo: End of Study
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
|---|---|---|---|---|
|
Change in High-sensitivity C-reactive Protein (hsCRP)
|
-1.02 change in c-reactive protein (mg/L)
Interval -2.9 to 1.3
|
0.16 change in c-reactive protein (mg/L)
Interval -0.82 to 1.19
|
—
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 months after start of treatmentPopulation: sub-group from Denver site
Vascular endothelial cells will be collected and assessed for changes in protein expression of NADPH oxidase after 3 months of treatment with rilonacept vs. placebo. Protein expression is calculated as a ratio of intensity of staining in the patient cells relative to human umbilical vein endothelial cell (HUVEC) control cells. The absolute change in this ratio between baseline and week 12 is reported below.
Outcome measures
| Measure |
Rilonacept
n=6 Participants
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
n=5 Participants
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo: Baseline
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
Placebo: End of Study
Change in flow-mediated dilation following an acute infusion of ascorbic acid (as compared to saline) in the placebo group at baseline
|
|---|---|---|---|---|
|
Change in Vascular Endothelial NADPH Oxidase Expression
|
-0.02 absolute change in ratio
Standard Deviation 0.03
|
0.01 absolute change in ratio
Standard Deviation 0.03
|
—
|
—
|
Adverse Events
Rilonacept
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Rilonacept
n=21 participants at risk
12 weeks of treatment with rilonacept
Rilonacept: 12 weeks of treatment with rilonacept (subcutaneous injection with a loading dose of 320 mg, followed by 160 mg/wk)
|
Placebo
n=21 participants at risk
Twelve weeks of treatment with placebo
Placebo: Twelve weeks of treatment with placebo (subcutaneous injection of normal saline with a loading dose of 320 mg, followed by 160 mg/wk)
|
|---|---|---|
|
Skin and subcutaneous tissue disorders
Injection site reaction
|
4.8%
1/21
|
4.8%
1/21
|
|
Infections and infestations
Neck abscess/pyomyositis
|
4.8%
1/21
|
0.00%
0/21
|
|
Infections and infestations
upper respiratory infection
|
14.3%
3/21
|
9.5%
2/21
|
Additional Information
Dr. Kristen Nowak
University of Colorado Anschutz Medical Campus
Phone: 303-724-4842
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place