Trial Outcomes & Findings for Rilonacept for Treatment of Familial Mediterranean Fever (FMF) (NCT NCT00582907)
NCT ID: NCT00582907
Last Updated: 2013-02-11
Results Overview
Difference in number of attacks per treatment month between rilonacept and placebo
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
14 participants
Primary outcome timeframe
attacks were assessed at the end of each 3 month treatment course (overall up to 6 month of rilonacept and 6 months of placebo, each)
Results posted on
2013-02-11
Participant Flow
Participants were recruited from October 2008 until February 2010. The study was conducted in 6 clinics in the United States in FMF clinics or clinics in regions where a higher prevalence of FMF is expected based on local population ethnicity.
Participants had an estimated mean ≥1 FMF attack/month for 3 months before screening, and ≥1 attack/month during screening/run-in period. There was a wash-out period of other biologic medications for those using them at screening. 2 subjects withdrew consent, one lacked mutations and one had insufficient attacks and were excluded before baseline.
Participant milestones
| Measure |
Rilonacept-Placebo-Rilonacept-Placebo
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Overall study was 12 months.
|
Rilonacept-Placebo-Placebo-Rilonacept
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Overall study was 12 months.
|
Placebo-Rilonacept-Placebo-Rilonacept
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
|
Placebo-Rilonacept-Rilonacept-Placebo
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
|
|---|---|---|---|---|
|
1st Course
STARTED
|
4
|
3
|
3
|
4
|
|
1st Course
COMPLETED
|
3
|
3
|
3
|
3
|
|
1st Course
NOT COMPLETED
|
1
|
0
|
0
|
1
|
|
2nd Course
STARTED
|
3
|
3
|
3
|
3
|
|
2nd Course
COMPLETED
|
2
|
3
|
3
|
3
|
|
2nd Course
NOT COMPLETED
|
1
|
0
|
0
|
0
|
|
3rd Course
STARTED
|
2
|
3
|
3
|
3
|
|
3rd Course
COMPLETED
|
2
|
3
|
3
|
3
|
|
3rd Course
NOT COMPLETED
|
0
|
0
|
0
|
0
|
|
4th Course
STARTED
|
2
|
3
|
3
|
3
|
|
4th Course
COMPLETED
|
2
|
3
|
3
|
3
|
|
4th Course
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Rilonacept-Placebo-Rilonacept-Placebo
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Overall study was 12 months.
|
Rilonacept-Placebo-Placebo-Rilonacept
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine. Overall study was 12 months.
|
Placebo-Rilonacept-Placebo-Rilonacept
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
|
Placebo-Rilonacept-Rilonacept-Placebo
Patients received in the randomized sequence above two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
|
|---|---|---|---|---|
|
1st Course
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
|
1st Course
Lost to Follow-up
|
0
|
0
|
0
|
1
|
|
2nd Course
Lack of Efficacy
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Rilonacept for Treatment of Familial Mediterranean Fever (FMF)
Baseline characteristics by cohort
| Measure |
All Patients Received Both Rilonacept and Placebo
n=14 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|
|
Age, Categorical
<=18 years
|
4 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
10 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age Continuous
|
24.4 years
STANDARD_DEVIATION 11.8 • n=5 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
14 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: attacks were assessed at the end of each 3 month treatment course (overall up to 6 month of rilonacept and 6 months of placebo, each)Population: Patients who received at least one complete treatment course and reported attacks were analyzed for the primary outcome measure.
Difference in number of attacks per treatment month between rilonacept and placebo
Outcome measures
| Measure |
Rilonacept
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Assess the Efficacy of Rilonacept in Decreasing the Number of Acute FMF Attacks.
|
0.77 number of attacks per month
Interval 0.18 to 1.2
|
2.00 number of attacks per month
Interval 0.9 to 2.4
|
PRIMARY outcome
Timeframe: 12 months of entire study lengthPopulation: Safety analysis included all participants who received at least one dose of medication.
Differences in adverse events (AEs) between rilonacept and placebo per patient-month of treatment. We separately analyzed injection site reactions and infectious adverse events. Other adverse events were too small in number to analyze. The upper table (and first statistical analysis) regards injection site reactions and lower table (and second statistical analysis) regards infections.
Outcome measures
| Measure |
Rilonacept
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=14 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine if There is a Medically Important Difference Between the Safety Profiles of Rilonacept vs. Placebo.
Injection site reactions
|
1 AEs per patient-month of treatment
Interval 0.0 to 1.04
|
0 AEs per patient-month of treatment
Interval 0.0 to 0.36
|
|
To Determine if There is a Medically Important Difference Between the Safety Profiles of Rilonacept vs. Placebo.
Infections
|
0 AEs per patient-month of treatment
Interval 0.0 to 0.12
|
0.18 AEs per patient-month of treatment
Interval 0.0 to 0.29
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Participants who received any treatment and had recorded attacks
This outcome was the difference in days in the length of attacks between rilonacept and placebo.
Outcome measures
| Measure |
Rilonacept
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=14 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Difference in the Length of Attacks During Treatment With Rilonacept vs. Placebo.
|
2.8 Number of days
Interval 1.0 to 3.3
|
3.2 Number of days
Interval 2.7 to 4.0
|
SECONDARY outcome
Timeframe: Each treatment course of up to 3 monthsPopulation: Participants who at least one complete treatment course.
The percentage of rilonacept and placebo treatment courses without FMF attacks.
Outcome measures
| Measure |
Rilonacept
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
Percentage of Treatment Courses Without FMF Attacks in Rilonacept Courses as Compared to Placebo Courses.
|
29 Percentage of courses
|
0 Percentage of courses
|
SECONDARY outcome
Timeframe: Up to 3 months for each treatment coursePopulation: Participants who completed at least one complete treatment course.
Differences between rilonacept and placebo in the percentage of courses that attained at least a 50% decrease in FMF attacks when compared to attacks in the screening period.
Outcome measures
| Measure |
Rilonacept
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Proportion of Courses in Which Subjects Attained at Least a 50% Decrease in Acute FMF Attacks During Rilonacept Courses as Compared to Placebo Courses.
|
75 Percentage of courses
|
35 Percentage of courses
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: All participants who received an intervention and developed an attack were analyzed.
In a survival analysis we measured the difference (in days) until the development of the first and second attack within a treatment course of up to 3 months and examined differences in this parameter between rilonacept and placebo. Data regarding the development of the second attack are reported below. In regards to the first attack there were no significant differences between rilonacept and placebo (20 days (7.5,\>90)for rilonacept; 15 (8,32) for placebo, P=0.066).
Outcome measures
| Measure |
Rilonacept
n=13 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=14 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine Differences in the Time to the Development of Attacks Between the Treatment Arms (Rilonacept vs. Placebo).
|
90 days until second attack
Interval 25.0 to 90.0
|
36 days until second attack
Interval 15.0 to 68.0
|
SECONDARY outcome
Timeframe: 3 months (each treatment course, overall 12 months)Population: Participants who completed at least one treatment course of both rilonacept and placebo.
Erythrocyte sedimentation rate - ESR (mm/h)
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in the Erythrocyte Sedimentation Rate Between the Treatment Arms (Rilonacept vs. Placebo).
|
5.8 mm/h
Interval 2.0 to 16.0
|
14 mm/h
Interval 7.0 to 19.0
|
SECONDARY outcome
Timeframe: 3 months (each treatment course, overall 12 months)Population: Patients who received at least one course each of rilonacept and placebo
Differences between the treatment courses in the C-Reactive Protein levels mg/L
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in C-Reactive Protein Between the Treatment Arms (Rilonacept vs. Placebo)
|
2 mg/L
Interval 2.0 to 4.0
|
4 mg/L
Interval 2.0 to 9.0
|
SECONDARY outcome
Timeframe: 3 months (each treatment course, overall 12 months)Population: The number of patients who received at least one course each of rilonacept and placebo
The difference between the treatment arms in the platelet count X 10 to the power of 9
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in the Platelet Count Between the Treatment Arms (Rilonacept vs. Placebo)
|
262 cell count X10 to the power of 9
Interval 246.0 to 318.0
|
334 cell count X10 to the power of 9
Interval 305.0 to 352.0
|
SECONDARY outcome
Timeframe: 3 months (each treatment course, overall 12 months)Population: Patients who received at least one course each of rilonacept and placebo
The differences between treatment arms in the fibrinogen level (micromol/L)
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in the Fibrinogen Levels Between the Treatment Arms (Rilonacept vs. Placebo)
|
6.56 micromol/L
Interval 6.41 to 9.7
|
9.56 micromol/L
Interval 9.26 to 10.17
|
SECONDARY outcome
Timeframe: 3 months (each treatment course, overall 12 months)Population: Patients who received at least one course each of rilonacept and placebo
The difference between the treatment arms in serum amyloid A levels (mg/L)
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in Serum Amyloid A Levels Between the Treatment Arms (Rilonacept vs. Placebo)
|
13 mg/L
Interval 0.0 to 40.0
|
15 mg/L
Interval 0.0 to 192.0
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Participants who received at least one treatment course of rilonacept and placebo.
Differences in the health-related quality of life (HRQOL) during treatment with rilonacept vs. placebo. HRQOl was measured by the Childhood Health Questionnaire which was adopted also for adults. There are 2 summary scores: 1. Physical summary score. 2. Psychosocial summary score. The data reported below in the upper table is the physical summary composite score and in the lower table the psychosocial summary composite score. Scores were from 0-100 (higher is better) with a score of 50 representing the mean of the normal population.
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in the Quality of Life Between the Treatment Arms (Rilonacept vs. Placebo).
Physical HRQOL summary composite score
|
33 Composite HRQOL summary score
Interval 25.8 to 38.1
|
20.3 Composite HRQOL summary score
Interval 10.5 to 32.7
|
|
To Determine the Differences in the Quality of Life Between the Treatment Arms (Rilonacept vs. Placebo).
Psychosocial HRQOL summary composite score
|
53.3 Composite HRQOL summary score
Interval 48.6 to 57.2
|
49.8 Composite HRQOL summary score
Interval 42.5 to 59.0
|
SECONDARY outcome
Timeframe: overall 12 monthsPopulation: Participants who received at least one course each of placebo and rilonacept.
Differences in the Armenian Evaluation Score between rilonacept and placebo courses. The Armenian Evaluation Score is a composite score of disease severity based on the frequency, duration and character of attacks (degree of fever and severity of serositis). It was adapted to calculate a score for a 3-month treatment course. The lowest (best) score is 0 and higher values are worse. In theory there is no upper limit to the scale. The total score is reported (there are no subscales).
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in the FMF Severity Score of the Subjects Between the Treatment Arms (Rilonacept vs. Placebo).
|
5.5 units on a scale
Interval 3.0 to 13.0
|
11 units on a scale
Interval 7.8 to 12.5
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Participants who received at least one treatment course of both rilonacept and placebo.
The proportion of time within the trial that participants received rilonacept as opposed to placebo. The reason for this outcome is that participants who had at least 2 attacks within an individual treatment course were able to "escape" in a blinded manner to the other treatment arm until the end of that treatment course and then resume the original randomization sequence. Thus participants may have been treated for a longer time with one treatment arm or the other.
Outcome measures
| Measure |
Rilonacept
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
Placebo
n=12 Participants
Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
Overall length of study for each participant is 12 months.
|
|---|---|---|
|
To Determine the Differences in the Proportion of Time Subjects Received Rilonacept vs Placebo
|
52.5 Percentage of time treated
Interval 50.5 to 70.5
|
47.5 Percentage of time treated
Interval 29.5 to 49.5
|
Adverse Events
Placebo
Serious events: 3 serious events
Other events: 12 other events
Deaths: 0 deaths
Rilonacept
Serious events: 3 serious events
Other events: 11 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Placebo
n=14 participants at risk
Adverse events during placebo treatment. Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
|
Rilonacept
n=13 participants at risk
Adverse events during rilonacept treatment. Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
|
|---|---|---|
|
Immune system disorders
Hospitalization for FMF attack
|
14.3%
2/14 • Number of events 3 • 1 year
|
15.4%
2/13 • Number of events 4 • 1 year
|
|
Infections and infestations
Pneumonia
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Infections and infestations
Respiratory Infection
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
Other adverse events
| Measure |
Placebo
n=14 participants at risk
Adverse events during placebo treatment. Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
|
Rilonacept
n=13 participants at risk
Adverse events during rilonacept treatment. Patients received in randomized sequences two 3-month courses of rilonacept (IL-1 Trap),2.2 mg/kg/wk (max 160 mg) by SC injection and two 3-month courses of equal volume placebo by weekly SC injection. This was in addition to the pre-study dose of colchicine.
Patients were randomized to 4 treatment sequences:
1\. rilonacept- placebo-rilonacept-placebo; 2. placebo-rilonacept-placebo-rilonacept 3. rilonacept- placebo-placebo-rilonacept and 4. placebo-rilonacept-rilonacept-placebo.
|
|---|---|---|
|
Injury, poisoning and procedural complications
Injection site reaction
|
35.7%
5/14 • Number of events 13 • 1 year
|
53.8%
7/13 • Number of events 53 • 1 year
|
|
Infections and infestations
Upper respiratory infection/Otitis
|
21.4%
3/14 • Number of events 3 • 1 year
|
0.00%
0/13 • 1 year
|
|
Infections and infestations
Sinusitis
|
7.1%
1/14 • Number of events 1 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Infections and infestations
Herpes labialis
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Infections and infestations
Herpes Zoster
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Infections and infestations
Epstein Barr virus
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
General disorders
Hypertension
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 2 • 1 year
|
|
Nervous system disorders
Headaches
|
7.1%
1/14 • Number of events 1 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Infections and infestations
Otitis
|
7.1%
1/14 • Number of events 1 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Infections and infestations
Bronchitis
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Infections and infestations
Influenza
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Musculoskeletal and connective tissue disorders
Arthralgia/bone pain
|
7.1%
1/14 • Number of events 1 • 1 year
|
15.4%
2/13 • Number of events 2 • 1 year
|
|
Gastrointestinal disorders
Loss of appetite
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 3 • 1 year
|
|
Respiratory, thoracic and mediastinal disorders
Asthma attack
|
7.1%
1/14 • Number of events 1 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Gastrointestinal disorders
Nausea, vomiting
|
7.1%
1/14 • Number of events 1 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
General disorders
Heat and cold sensitivity
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Nervous system disorders
Vertigo
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Injury, poisoning and procedural complications
Fracture - toe
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Eye disorders
Photophobia
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Skin and subcutaneous tissue disorders
Facial edema
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
General disorders
Fatigue
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Injury, poisoning and procedural complications
Abrasion
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Ear and labyrinth disorders
Sore throat
|
7.1%
1/14 • Number of events 1 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Investigations
Alanine aminotransferase (ALT) elevation
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Investigations
Creatine Kinase (CPK) elevation
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Renal and urinary disorders
Overactive bladder
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
|
Infections and infestations
Facial skin infection
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Ear and labyrinth disorders
Nose bleed
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Infections and infestations
Oral thrush
|
7.1%
1/14 • Number of events 1 • 1 year
|
0.00%
0/13 • 1 year
|
|
Infections and infestations
Conjunctivitis
|
0.00%
0/14 • 1 year
|
7.7%
1/13 • Number of events 1 • 1 year
|
Additional Information
Philip Hashkes, MD, MSc
Shaare Zedek Medical Center/Cleveland Clinic
Phone: 972-2-6555307
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place