Trial Outcomes & Findings for Rilonacept for Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS) (NCT NCT00288704)
NCT ID: NCT00288704
Last Updated: 2011-12-06
Results Overview
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.
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
104 participants
Primary outcome timeframe
Baseline (Days -21 to -1) and Week 6 (Days 21-42)
Results posted on
2011-12-06
Participant Flow
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.
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.
Participant milestones
| Measure |
Placebo
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.
|
Rilonacept 160 mg
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.
|
Open-Label Extension (OLE) Rilonacept 160 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.
|
|---|---|---|---|
|
Part A, Double Blind, Weeks 1-6
STARTED
|
24
|
23
|
0
|
|
Part A, Double Blind, Weeks 1-6
COMPLETED
|
24
|
22
|
0
|
|
Part A, Double Blind, Weeks 1-6
NOT COMPLETED
|
0
|
1
|
0
|
|
Part B, Randomized Withdrawal, Wks 15-24
STARTED
|
23
|
22
|
0
|
|
Part B, Randomized Withdrawal, Wks 15-24
COMPLETED
|
23
|
21
|
0
|
|
Part B, Randomized Withdrawal, Wks 15-24
NOT COMPLETED
|
0
|
1
|
0
|
|
Open-Label Extension (OLE) Weeks 24-117
STARTED
|
0
|
0
|
101
|
|
Open-Label Extension (OLE) Weeks 24-117
COMPLETED
|
0
|
0
|
81
|
|
Open-Label Extension (OLE) Weeks 24-117
NOT COMPLETED
|
0
|
0
|
20
|
Reasons for withdrawal
| Measure |
Placebo
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.
|
Rilonacept 160 mg
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.
|
Open-Label Extension (OLE) Rilonacept 160 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.
|
|---|---|---|---|
|
Part A, Double Blind, Weeks 1-6
Pre-dose Condition
|
0
|
1
|
0
|
|
Part B, Randomized Withdrawal, Wks 15-24
Adverse Event
|
0
|
1
|
0
|
|
Open-Label Extension (OLE) Weeks 24-117
Adverse Event
|
0
|
0
|
1
|
|
Open-Label Extension (OLE) Weeks 24-117
Withdrawal by Subject
|
0
|
0
|
1
|
|
Open-Label Extension (OLE) Weeks 24-117
Death
|
0
|
0
|
2
|
|
Open-Label Extension (OLE) Weeks 24-117
Sponsor Decision
|
0
|
0
|
15
|
|
Open-Label Extension (OLE) Weeks 24-117
Pregnancy
|
0
|
0
|
1
|
Baseline Characteristics
Rilonacept for Treatment of Cryopyrin-Associated Periodic Syndromes (CAPS)
Baseline characteristics by cohort
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
Open-Label Rilonacept 160 mg
n=57 Participants
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
n=104 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
8 Participants
n=5 Participants
|
8 Participants
n=4 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
17 Participants
n=5 Participants
|
20 Participants
n=7 Participants
|
46 Participants
n=5 Participants
|
83 Participants
n=4 Participants
|
|
Age, Categorical
>=65 years
|
7 Participants
n=5 Participants
|
3 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
13 Participants
n=4 Participants
|
|
Age Continuous
|
55.5 years
STANDARD_DEVIATION 14.7 • n=5 Participants
|
45.9 years
STANDARD_DEVIATION 16 • n=7 Participants
|
37.7 years
STANDARD_DEVIATION 17.2 • n=5 Participants
|
43.6 years
STANDARD_DEVIATION 17.8 • n=4 Participants
|
|
Sex: Female, Male
Female
|
16 Participants
n=5 Participants
|
15 Participants
n=7 Participants
|
37 Participants
n=5 Participants
|
68 Participants
n=4 Participants
|
|
Sex: Female, Male
Male
|
8 Participants
n=5 Participants
|
8 Participants
n=7 Participants
|
20 Participants
n=5 Participants
|
36 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
24 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
56 Participants
n=5 Participants
|
103 Participants
n=4 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
1 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
|
0 Participants
n=5 Participants
|
0 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
0 Participants
n=4 Participants
|
|
Race (NIH/OMB)
White
|
24 Participants
n=5 Participants
|
23 Participants
n=7 Participants
|
57 Participants
n=5 Participants
|
104 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
|
|
Region of Enrollment
United States
|
24 participants
n=5 Participants
|
23 participants
n=7 Participants
|
57 participants
n=5 Participants
|
104 participants
n=4 Participants
|
PRIMARY outcome
Timeframe: Baseline (Days -21 to -1) and Week 6 (Days 21-42)Population: Cryopyrin Associated Autoinflammatory Syndrome (CAPS) is a rare, orphan, hereditary disease. There are several hundred CAPS cases in the United States.
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.
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)
Baseline Part A
|
2.4 Units of a Scale
Standard Deviation 1.5
|
3.1 Units of a Scale
Standard Deviation 1.9
|
|
Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)
Endpoint Part A (Week 6) in KSS
|
2.1 Units of a Scale
Standard Deviation 1.6
|
0.5 Units of a Scale
Standard Deviation 0.5
|
|
Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)
Change to Week 6 in KSS
|
-0.3 Units of a Scale
Standard Deviation 0.7
|
-2.6 Units of a Scale
Standard Deviation 1.9
|
PRIMARY outcome
Timeframe: Week 15 through Week 24 (randomized withdrawal)Population: 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.
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.
Outcome measures
| Measure |
Placebo
n=23 Participants
|
Rilonacept 160 mg
n=22 Participants
|
|---|---|---|
|
Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B)
Baseline Part B
|
0.2 Units of a Scale
Standard Deviation 0.4
|
0.3 Units of a Scale
Standard Deviation 0.3
|
|
Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B)
Endpoint Part B (Week 24) in KSS
|
1.2 Units of a Scale
Standard Deviation 1.0
|
0.4 Units of a Scale
Standard Deviation 0.5
|
|
Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B)
Change to Week 24 in KSS
|
0.9 Units of a Scale
Standard Deviation 0.9
|
0.1 Units of a Scale
Standard Deviation 0.4
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 6 (Part A)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.
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient
Baseline Part A
|
6.2 Days
Standard Deviation 6.0
|
8.6 Days
Standard Deviation 7.2
|
|
Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient
Endpoint Part A (Week 6) in Flare Days
|
5.0 Days
Standard Deviation 6.1
|
0.1 Days
Standard Deviation 0.5
|
|
Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient
Change to Week 6 in Flare Days
|
-1.2 Days
Standard Deviation 3.6
|
-8.4 Days
Standard Deviation 7.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 6 (Part A)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.
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment
Baseline Part A
|
4.7 Units of a Scale
Standard Deviation 2.0
|
5.6 Units of a Scale
Standard Deviation 1.7
|
|
Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment
Endpoint Part A in Physician's Global Assessment
|
5.0 Units of a Scale
Standard Deviation 2.5
|
1.5 Units of a Scale
Standard Deviation 1.4
|
|
Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment
Change to Week 6 in Physician's Global Assessment
|
0.2 Units of a Scale
Standard Deviation 2.1
|
-4.2 Units of a Scale
Standard Deviation 2.4
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 6 (Part A)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.
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment
Endpoint Part A in Patient's Global Assessment
|
2.7 Visual Analog Scale
Standard Deviation 1.8
|
0.9 Visual Analog Scale
Standard Deviation 1.1
|
|
Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment
Change to Week 6 in Patient's Global Assessment
|
-0.4 Visual Analog Scale
Standard Deviation 1.1
|
-2.7 Visual Analog Scale
Standard Deviation 2.2
|
|
Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment
Baseline in Part A
|
3.1 Visual Analog Scale
Standard Deviation 2.0
|
3.6 Visual Analog Scale
Standard Deviation 2.1
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Endpoint of Part AAn abnormal value for CRP was considered \> 8.4 mg/L.
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L)
Baseline Part A
|
25.2 Milligrams per Liter
Standard Deviation 15.7
|
20.1 Milligrams per Liter
Standard Deviation 14.7
|
|
Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L)
Endpoint Part A in CRP
|
21.8 Milligrams per Liter
Standard Deviation 23.9
|
1.3 Milligrams per Liter
Standard Deviation 2.2
|
|
Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L)
Change to Part A Endpoint in CRP
|
-2.1 Milligrams per Liter
Standard Deviation 15.5
|
-18.4 Milligrams per Liter
Standard Deviation 14.3
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Endpoint of Part AAn abnormal value for SAA was considered \> 6.4 mg/L.
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L)
Baseline Part A
|
63.5 Milligrams per Liter
Standard Deviation 122.3
|
49.5 Milligrams per Liter
Standard Deviation 48.3
|
|
Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L)
Endpoint Part A in SAA
|
39.7 Milligrams per Liter
Standard Deviation 153.7
|
2.5 Milligrams per Liter
Standard Deviation 4.0
|
|
Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L)
Change to Endpoint in SAA
|
-2.8 Milligrams per Liter
Standard Deviation 79.7
|
-48.5 Milligrams per Liter
Standard Deviation 48.5
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Endpoint (Week 6)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).
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Number of Subjects With at Least 30% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)
|
7 Participants
|
22 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 6 (Part A)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).
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Number of Subjects With at Least 50% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)
|
2 Participants
|
20 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to Week 6 (Part A)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).
Outcome measures
| Measure |
Placebo
n=24 Participants
|
Rilonacept 160 mg
n=23 Participants
|
|---|---|---|
|
Number of Subjects With at Least 75% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)
|
0 Participants
|
16 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From Baseline (week 0) to OLE Week 72Population: 44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE.
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.
Outcome measures
| Measure |
Placebo
n=56 Participants
|
Rilonacept 160 mg
|
|---|---|---|
|
Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS
Baseline
|
2.6 Units of a scale
Standard Deviation 1.6
|
—
|
|
Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS
Endpoint (OLE Week 72) in KSS
|
0.4 Units of a scale
Standard Deviation 0.5
|
—
|
|
Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS
Change to Endpoint (OLE Week 72) in KSS
|
-2.3 Units of a scale
Standard Deviation 1.6
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From Baseline (Week 0) to OLE Week 72Population: 44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE.
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.
Outcome measures
| Measure |
Placebo
n=56 Participants
|
Rilonacept 160 mg
|
|---|---|---|
|
Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment
Baseline
|
3.4 Units of a Scale
Standard Deviation 1.9
|
—
|
|
Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment
OLE Week 72 in Patient's Global Assessment
|
0.4 Units of a Scale
Standard Deviation 0.6
|
—
|
|
Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment
Change to OLE Wk 72 in Patient's Global Assessment
|
-3.0 Units of a Scale
Standard Deviation 2.0
|
—
|
OTHER_PRE_SPECIFIED outcome
Timeframe: From Baseline (Week 0) to OLE Week 72Population: 44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE.
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).
Outcome measures
| Measure |
Placebo
n=56 Participants
|
Rilonacept 160 mg
|
|---|---|---|
|
Change From Baseline to Open-Label Extension Week 72 in Number of Disease Flare Days
Baseline
|
7.3 Number of Days
Standard Deviation 6.4
|
—
|
|
Change From Baseline to Open-Label Extension Week 72 in Number of Disease Flare Days
Endpoint in OLE Week 72 Disease Flare Days
|
0.6 Number of Days
Standard Deviation 3.0
|
—
|
|
Change From Baseline to Open-Label Extension Week 72 in Number of Disease Flare Days
Change to OLE Week 72 in Disease Flare Days
|
-6.7 Number of Days
Standard Deviation 6.9
|
—
|
Adverse Events
Rilonacept 160 mg
Serious events: 7 serious events
Other events: 17 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Rilonacept 160 mg
n=23 participants at risk；n=104 participants at risk
|
Placebo
n=24 participants at risk
|
|---|---|---|
|
Infections and infestations
Meningitis pneumococcal
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Metabolism and nutrition disorders
Hypokalemia
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary Embolism
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Nervous system disorders
Sciatica
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Hepatobiliary disorders
Cholelithiasis
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Renal and urinary disorders
Renal Colic
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Gastrointestinal disorders
Gastrooesophageal reflux disease
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Cardiac disorders
Arteriosclerosis of the coronary artery
|
0.96%
1/104 • Number of events 1 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
Other adverse events
| Measure |
Rilonacept 160 mg
n=23 participants at risk；n=104 participants at risk
|
Placebo
n=24 participants at risk
|
|---|---|---|
|
General disorders
Injection Site Reaction
|
47.8%
11/23 • 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.
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.
|
12.5%
3/24 • 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.
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.
|
|
Infections and infestations
Sinusitis
|
8.7%
2/23 • 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.
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.
|
4.2%
1/24 • 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.
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.
|
|
Infections and infestations
Urinary Tract Infection
|
4.3%
1/23 • 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.
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.
|
4.2%
1/24 • 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.
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.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
26.1%
6/23 • 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.
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.
|
4.2%
1/24 • 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.
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.
|
|
Gastrointestinal disorders
Diarrhea
|
4.3%
1/23 • 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.
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.
|
12.5%
3/24 • 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.
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.
|
|
Gastrointestinal disorders
Nausea
|
4.3%
1/23 • 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.
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.
|
12.5%
3/24 • 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.
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.
|
|
Gastrointestinal disorders
Abdominal pain, upper abdomen
|
0.00%
0/23 • 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.
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.
|
8.3%
2/24 • 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.
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.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
8.7%
2/23 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Nervous system disorders
Hypoesthesia
|
8.7%
2/23 • 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.
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.
|
0.00%
0/24 • 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.
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.
|
|
Gastrointestinal disorders
Stomach Discomfort
|
4.3%
1/23 • 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.
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.
|
4.2%
1/24 • 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.
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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER