We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Rilonacept for Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00288704
Recruitment Status : Completed
First Posted : February 8, 2006
Results First Posted : November 13, 2009
Last Update Posted : December 6, 2011
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Familial Cold Autoinflammatory Syndrome (FCAS)
Familial Cold Urticaria
Muckle-Wells Syndrome (MWS)
Genetic Diseases, Inborn
Interventions Drug: rilonacept 160 mg
Drug: Placebo
Enrollment 104
Recruitment Details 47 subjects were randomized into Part A. 44 of these subjects continued into the open label extension (OLE). 57 subjects were enrolled directly into the OLE without completing parts A and B of the study. 104 total subjects were in the entire study. 101 were in the OLE.
Pre-assignment Details The study population included male or female adult subjects (Parts A and B), and adult and pediatric subjects (OLE phase), with confirmed NLRP-3 (Cold Induced Autoinflammatory Syndrome-1 or CIAS1) gene mutation. Only one person per household was enrolled into Parts A and B of the study. However, multiple family members went into the OLE.
Arm/Group Title Placebo Rilonacept 160 mg Open-Label Extension (OLE) Rilonacept 160 mg
Hide Arm/Group Description If assigned, subjects received Placebo during 1) the first 6 weeks of the study (Part A) or 2) during the randomized withdrawal period from weeks 15-24 (Part B). No subject received Placebo during the open-label extension (after week 24). The drug is administered subcutaneously on a weekly basis.

If assigned, subjects received rilonacept 160 mg during 1) the first 6 weeks of the study (Part A) or 2) during the randomized withdrawal period from weeks 15-24 (Part B). Note: Between weeks 6 and 15 (Parts A and B), all subjects received rilonacept 160 mg.

Study drug is administered as a 2.0 mL subcutaneous injection once a week. At baseline (week 0) subjects receive a loading dose of rilonacept 320 mg.

After week 24 of study, all subjects received weekly injections of rilonacept 160 mg until the end of the study. This was not part of the double blind (Part A) or randomized withdrawal (Part B) portion of the results. Pediatric subjects received rilonacept dosed 2.2 mg/kg weekly up to 160 mg.

Study drug is administered as a 2.0 mL subcutaneous injection once a week.
Period Title: Part A, Double Blind, Weeks 1-6
Started 24 23 0 [1]
Completed 24 22 0
Not Completed 0 1 0
Reason Not Completed
Pre-dose Condition             0             1             0
[1]
Subjects enrolled into the open-label phase do not complete this part of the study.
Period Title: Part B, Randomized Withdrawal, Wks 15-24
Started 23 [1] 22 0
Completed 23 21 0
Not Completed 0 1 0
Reason Not Completed
Adverse Event             0             1             0
[1]
1 subject discontinued during weeks 6-14 due to non-compliance with study drug dosing procedures.
Period Title: Open-Label Extension (OLE) Weeks 24-117
Started 0 [1] 0 101
Completed 0 0 81
Not Completed 0 0 20
Reason Not Completed
Adverse Event             0             0             1
Withdrawal by Subject             0             0             1
Death             0             0             2
Sponsor Decision             0             0             15
Pregnancy             0             0             1
[1]
After week 24, all subjects are treated with Open label rilonacept.
Arm/Group Title Placebo Rilonacept 160 mg Open-Label Rilonacept 160 mg Total
Hide Arm/Group Description [Not Specified] [Not Specified] 57 new subjects entered the study directly into the OLE. This was not part of the double blind or randomized withdrawal portion of the results. The 44 subjects who completed Parts A and B were not included in this category for baseline characteristics. Pediatric subjects , age 7 or older, received rilonacept dosed 2.2 mg/kg weekly up to 160 mg during the OLE. Total of all reporting groups
Overall Number of Baseline Participants 24 23 57 104
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 23 participants 57 participants 104 participants
<=18 years
0
   0.0%
0
   0.0%
8
  14.0%
8
   7.7%
Between 18 and 65 years
17
  70.8%
20
  87.0%
46
  80.7%
83
  79.8%
>=65 years
7
  29.2%
3
  13.0%
3
   5.3%
13
  12.5%
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 24 participants 23 participants 57 participants 104 participants
55.5  (14.7) 45.9  (16) 37.7  (17.2) 43.6  (17.8)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 23 participants 57 participants 104 participants
Female
16
  66.7%
15
  65.2%
37
  64.9%
68
  65.4%
Male
8
  33.3%
8
  34.8%
20
  35.1%
36
  34.6%
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 23 participants 57 participants 104 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
24
 100.0%
23
 100.0%
56
  98.2%
103
  99.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
   1.8%
1
   1.0%
[1]
Measure Description: Everyone in Part A and Part B of the study was non hispanic and white.
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 24 participants 23 participants 57 participants 104 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
24
 100.0%
23
 100.0%
57
 100.0%
104
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 24 participants 23 participants 57 participants 104 participants
24 23 57 104
1.Primary Outcome
Title Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)
Hide Description

The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue). KSS was averaged over two 21-day daily reporting periods (the 3 weeks prior to both baseline and week 6). In part A, a negative change in mean values indicated improvement under treatment with rilonacept in symptoms.

The DHAF was used because it is a validated instrument to collect subject's self-reported responses.
Time Frame Baseline (Days -21 to -1) and Week 6 (Days 21-42)
Hide Outcome Measure Data
Hide Analysis Population Description
Cryopyrin Associated Autoinflammatory Syndrome (CAPS) is a rare, orphan, hereditary disease. There are several hundred CAPS cases in the United States.
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Mean (Standard Deviation)
Unit of Measure: Units of a Scale
Baseline Part A 2.4  (1.5) 3.1  (1.9)
Endpoint Part A (Week 6) in KSS 2.1  (1.6) 0.5  (0.5)
Change to Week 6 in KSS -0.3  (0.7) -2.6  (1.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Comparison of p-value was a parametric ANCOVA main effects model with part A Baseline variable as covariate and treatment.
2.Primary Outcome
Title Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B)
Hide Description

The mean Key Symptom Score (KSS --from the validated, patient-administered DHAF) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue).

Subjects all received rilonacept 160 mg from week 6 through week 14. At week 15, subjects were re-randomized in a 1:1 ratio between Placebo and rilonacept 160 mg. Subjects baseline period was the 21-day period prior to week 15 randomization.

A positive score indicated a worsening of symptoms versus an active treatment rilonacept baseline period.
Time Frame Week 15 through Week 24 (randomized withdrawal)
Hide Outcome Measure Data
Hide Analysis Population Description
Subjects were re-randomized as part of the randomized withdrawal period (Part B). Subjects were not necessarily assigned the same treatment as in the first double-blind portion (Part A). Subjects were analyzed using last observation carried forward.
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 23 22
Mean (Standard Deviation)
Unit of Measure: Units of a Scale
Baseline Part B 0.2  (0.4) 0.3  (0.3)
Endpoint Part B (Week 24) in KSS 1.2  (1.0) 0.4  (0.5)
Change to Week 24 in KSS 0.9  (0.9) 0.1  (0.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments

Subjects received rilonacept 160 mg for 9 weeks (weeks 6-15), and then were re-randomized 1:1 into either Placebo or rilonacept 160 mg. The endpoint for the period was 9 weeks later (week 24).

The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.001
Comments [Not Specified]
Method ANCOVA
Comments Comparison of p-value was a parametric ANCOVA main effects model with part A Baseline variable as covariate and treatment.
3.Other Pre-specified Outcome
Title Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient
Hide Description

A Disease flare day was any day where the mean Key Symptom Score (KSS) was greater than 3. The KSS was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue). KSS was calculated for 21 Day Periods at baseline and at the endpoint (from Weeks 3 - 6). The difference in the number of flares between the two periods was averaged for all subjects.

The DHAF was used because it is a validated instrument to collect subject's self-reported responses. It was the basis for the KSS and the flare day count.
Time Frame Baseline to Week 6 (Part A)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Mean (Standard Deviation)
Unit of Measure: Days
Baseline Part A 6.2  (6.0) 8.6  (7.2)
Endpoint Part A (Week 6) in Flare Days 5.0  (6.1) 0.1  (0.5)
Change to Week 6 in Flare Days -1.2  (3.6) -8.4  (7.1)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Comparison of p-value was a parametric ANCOVA main effects model with part A Baseline variable as covariate and treatment.
4.Other Pre-specified Outcome
Title Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment
Hide Description The Physician's Global Assessment was an evaluation at each visit on a scale of 0=no disease activity to 10=severe disease activity. A negative value in change in Physician's Global Assessment is indicative of an improvement.
Time Frame Baseline to Week 6 (Part A)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Mean (Standard Deviation)
Unit of Measure: Units of a Scale
Baseline Part A 4.7  (2.0) 5.6  (1.7)
Endpoint Part A in Physician's Global Assessment 5.0  (2.5) 1.5  (1.4)
Change to Week 6 in Physician's Global Assessment 0.2  (2.1) -4.2  (2.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Comparison P-Value was a parametric ANCOVA main effects model with Part A Baseline variable as covariate and treatment.
5.Other Pre-specified Outcome
Title Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment
Hide Description The Patient's Global Assessment was a question on the Daily Health Assessment Form "Considering all the ways that Familial Cold Autoinflmatory Syndrome (FCAS) /Muckle-Wells Syndrome (MWS) affects you, please rate how you are doing based on the following scale" 0=very well to 10=very poor. A negative value in change in Patient's Global Assessment is indicative of an improvement.
Time Frame Baseline to Week 6 (Part A)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Mean (Standard Deviation)
Unit of Measure: Visual Analog Scale
Baseline in Part A 3.1  (2.0) 3.6  (2.1)
Endpoint Part A in Patient's Global Assessment 2.7  (1.8) 0.9  (1.1)
Change to Week 6 in Patient's Global Assessment -0.4  (1.1) -2.7  (2.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments [Not Specified]
Method ANCOVA
Comments Comparison p-value is a parametric ANCOVA main effects model with Part A Baseline variable as covariate and treatment.
6.Other Pre-specified Outcome
Title Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L)
Hide Description An abnormal value for CRP was considered > 8.4 mg/L.
Time Frame Baseline to Endpoint of Part A
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Median (Standard Deviation)
Unit of Measure: Milligrams per Liter
Baseline Part A 25.2  (15.7) 20.1  (14.7)
Endpoint Part A in CRP 21.8  (23.9) 1.3  (2.2)
Change to Part A Endpoint in CRP -2.1  (15.5) -18.4  (14.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments

Please note that the changes are medians (not means).

The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method ANCOVA
Comments Comparison p-value was a parametric ANCOVA main effects model with Part A Baseline variable as covariate and treatment.
7.Other Pre-specified Outcome
Title Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L)
Hide Description An abnormal value for SAA was considered > 6.4 mg/L.
Time Frame Baseline to Endpoint of Part A
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Median (Standard Deviation)
Unit of Measure: Milligrams per Liter
Baseline Part A 63.5  (122.3) 49.5  (48.3)
Endpoint Part A in SAA 39.7  (153.7) 2.5  (4.0)
Change to Endpoint in SAA -2.8  (79.7) -48.5  (48.5)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments

Please note that the changes are medians (not means).

The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method ANCOVA
Comments Comparison p-value was a parametric ANCOVA main effects model with Part A Baseline variable as covariate and treatment.
8.Other Pre-specified Outcome
Title Number of Subjects With at Least 30% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)
Hide Description The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue).
Time Frame Baseline to Endpoint (Week 6)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Measure Type: Number
Unit of Measure: Participants
7 22
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
9.Other Pre-specified Outcome
Title Number of Subjects With at Least 50% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)
Hide Description The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue).
Time Frame Baseline to Week 6 (Part A)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Measure Type: Number
Unit of Measure: Participants
2 20
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
10.Other Pre-specified Outcome
Title Number of Subjects With at Least 75% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)
Hide Description The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue).
Time Frame Baseline to Week 6 (Part A)
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Placebo Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 24 23
Measure Type: Number
Unit of Measure: Participants
0 16
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Placebo, Rilonacept 160 mg
Comments The sample size calculations at the time suggested 50 subjects would be enrolled at baseline. The Full Analysis Set (FAS) was used. The FAS included subjects who received at least one dose of rilonacept. Last observation carried forward was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Fisher Exact
Comments [Not Specified]
11.Other Pre-specified Outcome
Title Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS
Hide Description

OLE Week 72 was the last timepoint at which efficacy was measured in the study. 56 of the 101 OLE subjects were included in the analysis.

The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue).

A negative change in mean values indicated improvement in symptoms.
Time Frame From Baseline (week 0) to OLE Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE.
Arm/Group Title Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 56
Mean (Standard Deviation)
Unit of Measure: Units of a scale
Baseline 2.6  (1.6)
Endpoint (OLE Week 72) in KSS 0.4  (0.5)
Change to Endpoint (OLE Week 72) in KSS -2.3  (1.6)
12.Other Pre-specified Outcome
Title Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment
Hide Description

The Patient's Global Assessment was a question on the Daily Health Assessment Form "Considering all the ways that FCAS/MWS affects you, please rate how you are doing based on the following scale" 0=very well to 10=very poor. A negative value in change in Patient's Global Assessment is indicative of an improvement.

OLE Week 72 was the last timepoint at which efficacy was measured in the study. 56 of the 101 OLE subjects were included in the analysis.
Time Frame From Baseline (Week 0) to OLE Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE.
Arm/Group Title Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 56
Mean (Standard Deviation)
Unit of Measure: Units of a Scale
Baseline 3.4  (1.9)
OLE Week 72 in Patient's Global Assessment 0.4  (0.6)
Change to OLE Wk 72 in Patient's Global Assessment -3.0  (2.0)
13.Other Pre-specified Outcome
Title Change From Baseline to Open-Label Extension Week 72 in Number of Disease Flare Days
Hide Description

OLE Week 72 was the last timepoint at which efficacy was measured in the study. 56 of the 101 OLE subjects were included in the analysis.

A Disease flare day was any day where the mean Key Symptom Score (KSS) was greater than 3. The mean Key Symptom Score (KSS --from the validated, patient-administered Daily Health Assessment Form(DHAF)) was the average on a 0-10 scale (0=None, 10=Very Severe) of 5 separate scales -- rash, feeling of fever/chills, joint pain, eye redness/pain, and fatigue).
Time Frame From Baseline (Week 0) to OLE Week 72
Hide Outcome Measure Data
Hide Analysis Population Description
44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE.
Arm/Group Title Rilonacept 160 mg
Hide Arm/Group Description:
[Not Specified]
Overall Number of Participants Analyzed 56
Mean (Standard Deviation)
Unit of Measure: Number of Days
Baseline 7.3  (6.4)
Endpoint in OLE Week 72 Disease Flare Days 0.6  (3.0)
Change to OLE Week 72 in Disease Flare Days -6.7  (6.9)
Time Frame Serious adverse events (SAEs) were reported for all phases (double blind, randomized withdrawal, and OLE) of the study. There were no SAEs for subjects on placebo during Parts A or B. Other adverse events were shown for the six week double-blind period.
Adverse Event Reporting Description All serious adverse events were considered not related to receiving rilonacept by the physician at the site. Other adverse events were shown if a minimum of 2 subjects (approximately 4 percent of the Part A subjects) had the event during the 6-week, double-blind period.
 
Arm/Group Title Rilonacept 160 mg Placebo
Hide Arm/Group Description [Not Specified] [Not Specified]
All-Cause Mortality
Rilonacept 160 mg Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Hide Serious Adverse Events
Rilonacept 160 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/104 (6.73%)      0/24 (0.00%)    
Cardiac disorders     
Arteriosclerosis of the coronary artery * 1 [1]  1/104 (0.96%)  1 0/24 (0.00%) 
Gastrointestinal disorders     
Gastrooesophageal reflux disease * 1  1/104 (0.96%)  1 0/24 (0.00%) 
Hepatobiliary disorders     
Cholelithiasis * 1  1/104 (0.96%)  1 0/24 (0.00%) 
Infections and infestations     
Meningitis pneumococcal * 1 [2]  1/104 (0.96%)  1 0/24 (0.00%) 
Metabolism and nutrition disorders     
Hyponatremia * 1 [3]  1/104 (0.96%)  1 0/24 (0.00%) 
Hypokalemia * 2  1/104 (0.96%)  1 0/24 (0.00%) 
Musculoskeletal and connective tissue disorders     
Arthritis * 1  1/104 (0.96%)  1 0/24 (0.00%) 
Nervous system disorders     
Sciatica * 1 [4]  1/104 (0.96%)  1 0/24 (0.00%) 
Renal and urinary disorders     
Renal Colic * 1  1/104 (0.96%)  1 0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Pulmonary Embolism * 1  1/104 (0.96%)  1 0/24 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
2
Term from vocabulary, MedDra 11.0
[1]
The arteriosclerosis of the coronary artery resulted in the subject's death. The investigator reported that this was deemed not to be drug-related but related to the patient's underlying history of CHD.
[2]
This SAE resulted in subject's death. The investigator reported that this was not drug-related. Interleukin-1 blockade may interfere with immune response to infections. Life-threatening infections have been reported in patients taking rilonacept.
[3]
Treatment Emergent Serious Adverse Events are reported for all phases of the study.
[4]
Sciatica was the only serious adverse event during the first 24 weeks of the study. It occurred during the single-blind period between Parts A and B when all subjects received rilonacept.
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 4%
Rilonacept 160 mg Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   17/23 (73.91%)      13/24 (54.17%)    
Gastrointestinal disorders     
Diarrhea * 1  1/23 (4.35%)  3/24 (12.50%) 
Nausea * 2  1/23 (4.35%)  3/24 (12.50%) 
Abdominal pain, upper abdomen * 1  0/23 (0.00%)  2/24 (8.33%) 
Stomach Discomfort * 1  1/23 (4.35%)  1/24 (4.17%) 
General disorders     
Injection Site Reaction * 1 [1]  11/23 (47.83%)  3/24 (12.50%) 
Infections and infestations     
Sinusitis * 1  2/23 (8.70%)  1/24 (4.17%) 
Urinary Tract Infection * 1  1/23 (4.35%)  1/24 (4.17%) 
Upper Respiratory Tract Infection * 2  6/23 (26.09%)  1/24 (4.17%) 
Nervous system disorders     
Hypoesthesia * 1  2/23 (8.70%)  0/24 (0.00%) 
Respiratory, thoracic and mediastinal disorders     
Cough * 1  2/23 (8.70%)  0/24 (0.00%) 
*
Indicates events were collected by non-systematic assessment
1
Term from vocabulary, MedDRA (11.0)
2
Term from vocabulary, MedDra 11.0
[1]
Included erythema, pruritis, swelling, bruising, inflammation, mass, or pain at the injection site. All injection site reactions in part a were mild or moderate in severity.
Cryopyrin Associated Periodic Syndrome (CAPS) is a rare disease with only a few hundred cases in the US.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI,after completion of a trial,is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review;provided that the sponsor can remove confidential or proprietary information from such communications. The sponsor cannot require other changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Doug Nadler, MS Statistics
Organization: Regeneron Pharmaceuticals
Phone: 914 345 7905
EMail: clinicaltrials@regeneron.com
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00288704    
Other Study ID Numbers: IL1T-AI-0505
First Submitted: February 6, 2006
First Posted: February 8, 2006
Results First Submitted: September 30, 2009
Results First Posted: November 13, 2009
Last Update Posted: December 6, 2011