Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Inflammatory symptoms of Cryopyrin-Associated Periodic Syndrome (CAPS) are due to mutations in a the NLRP-3 gene (previously known as Cold Induced Autoinflammatory Syndrome-1 or CIAS1). These mutations result in the body's overproduction of interleukin-1 (IL-1), a protein that stimulates the inflammatory process. IL-1 Trap (rilonacept) was designed to bind to the interleukin-1 cytokine and prevent it from binding to its receptors in the body.
Primary Objective:
The primary objective of this study was to assess the effect of rilonacept on the clinical signs and symptoms of Cryopyrin-Associated Periodic Syndrome (CAPS) when used for chronic therapy as evaluated by the subjects themselves over time using a validated patient-reported outcomes tool.
Secondary Objective(s):
The secondary objectives were as follows:
This was a multi-center, two-part, double-blind, placebo-controlled study (Parts A and B) designed to assess the efficacy, safety, and tolerability of weekly subcutaneous (SC) doses of 160 mg of rilonacept in adult subjects with active CAPS. These phases were followed by extended open-label phases. After written informed consent was obtained, subjects who met the protocol eligibility criteria were enrolled at one of 27 study sites in the United States. The study consisted of a 3-week screening period preceding Part A, a 6-week long double-blind, randomized phase of the study. All subjects were then treated with single-blind rilonacept for 9-weeks, followed by a subsequent 9-week, double-blind, withdrawal phase during which subjects were re-randomized to either rilonacept or placebo. Subjects then continued treatment in a 24-week open-label extension phase (OLE) and a further 112-week long-term open-label extension (LTOLE), during which all subjects received rilonacept and a 6-week post-treatment follow-up period. Amendments 4 and 6 allowed eligible adult and pediatric subjects aged 7 and above to enroll directly into the open-label phases of the trial.
For reporting purposes, the 24-week OLE and the 112-week LTOLE was considered one Open Label Extension (OLE) phase. This occurred after the 24-week double blind (Parts A and B ) phase. In other words, OLE Week 1 corresponded to the week 25 in the study.
OLE Week 72 was the final timepoint where efficacy was measured. Safety continued after that timepoint until the end of the study.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Some subjects were treated with Placebo in the Study. This occurred (if subject randomized to Placebo) either during the first 6 weeks of the study or during the randomized withdrawal (weeks 15-24). |
|
| rilonacept 160 mg | Active Comparator | If randomized to rilonacept, subjects received this treatment during the first 6 weeks of the study or during the randomized withdrawal (weeks 15-24). All subjects received rilonacept 160 mg during weeks 6-14 (between Parts A and B). 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 rilonacept 160 mg | Other | After week 24 (the end of part B), all subjects went into weekly dosing of open label rilonacept 160 mg. During this phase of the study, adolescents aged 7 and above were entered into the study and rilonacept was dosed as 2.2 mg/kg injections, up to 160 mg, per week. Study drug is administered as a 2.0 mL subcutaneous injection once a week. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rilonacept 160 mg | Drug | Rilonacept was given by subcutaneous injection. It was administered weekly at the dose of 160mg. On Day 1, subjects received two injections of rilonacept (for a total of 320 mg). |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS) | 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. | Baseline (Days -21 to -1) and Week 6 (Days 21-42) |
| Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B) | 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. | Week 15 through Week 24 (randomized withdrawal) |
Not provided
| Measure | Description | Time Frame |
|---|---|---|
| Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient | 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. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Robert Evans, PharmD. | Regeneron Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Little Rock | Arkansas | 72204 | United States | |||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23031624 | Derived | Hoffman HM, Throne ML, Amar NJ, Cartwright RC, Kivitz AJ, Soo Y, Weinstein SP. Long-term efficacy and safety profile of rilonacept in the treatment of cryopryin-associated periodic syndromes: results of a 72-week open-label extension study. Clin Ther. 2012 Oct;34(10):2091-103. doi: 10.1016/j.clinthera.2012.09.009. Epub 2012 Sep 29. | |
| 18668535 |
| Label | URL |
|---|---|
| click here for more information on rilonacept | View source |
Not provided
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.
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.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Part A, Double Blind, Weeks 1-6 |
|
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
| Placebo | Drug | Subcutaneous injection of Placebo occurred during first 6 weeks of the study or during randomized withdrawal (weeks 15-24). On Day 1, subjects received two placebo injections. |
|
| rilonacept 160 mg | Drug | Rilonacept was given by subcutaneous injection. It was administered weekly at the dose of 160mg. No loading dose was given for subjects who entered directly into the open-label. |
|
| Baseline to Week 6 (Part A) |
| Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment | 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. | Baseline to Week 6 (Part A) |
| Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment | 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. | Baseline to Week 6 (Part A) |
| Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L) | An abnormal value for CRP was considered > 8.4 mg/L. | Baseline to Endpoint of Part A |
| Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L) | An abnormal value for SAA was considered > 6.4 mg/L. | Baseline to Endpoint of Part A |
| Number of Subjects With at Least 30% Improvement in Key Symptoms Scores (KSS) From 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). | Baseline to Endpoint (Week 6) |
| Number of Subjects With at Least 50% Improvement in Key Symptoms Scores (KSS) From 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). | Baseline to Week 6 (Part A) |
| Number of Subjects With at Least 75% Improvement in Key Symptoms Scores (KSS) From 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). | Baseline to Week 6 (Part A) |
| Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS | 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. | From Baseline (week 0) to OLE Week 72 |
| Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment | 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. | From Baseline (Week 0) to OLE Week 72 |
| Change From Baseline to Open-Label Extension Week 72 in Number of Disease Flare Days | 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). | From Baseline (Week 0) to OLE Week 72 |
| Palm Desert |
| California |
| 92260 |
| United States |
| Upland | California | 91786 | United States |
| Jacksonville | Florida | 32216 | United States |
| Stuart | Florida | 34996 | United States |
| Atlanta | Georgia | 30342 | United States |
| Columbus | Georgia | 31904 | United States |
| Aurora | Illinois | 60504 | United States |
| Louisville | Kentucky | 40215 | United States |
| Shreveport | Louisiana | 71105 | United States |
| Chesterfield | Michigan | 48047 | United States |
| St Louis | Missouri | 63141 | United States |
| New York | New York | 10023 | United States |
| Raleigh | North Carolina | 27609 | United States |
| Cincinnati | Ohio | 45236 | United States |
| Duncansville | Pennsylvania | 16635 | United States |
| Columbia | South Carolina | 29201 | United States |
| Greer | South Carolina | 29651 | United States |
| Chattanooga | Tennessee | 37403 | United States |
| Dallas | Texas | 75235 | United States |
| Waco | Texas | 76712 | United States |
| Cedar City | Utah | 84720 | United States |
| Forest | Virginia | 24551 | United States |
| Lakewood | Washington | 98499 | United States |
| Hoffman HM, Throne ML, Amar NJ, Sebai M, Kivitz AJ, Kavanaugh A, Weinstein SP, Belomestnov P, Yancopoulos GD, Stahl N, Mellis SJ. Efficacy and safety of rilonacept (interleukin-1 Trap) in patients with cryopyrin-associated periodic syndromes: results from two sequential placebo-controlled studies. Arthritis Rheum. 2008 Aug;58(8):2443-52. doi: 10.1002/art.23687. |
| 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. |
| FG002 | 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Part B, Randomized Withdrawal, Wks 15-24 |
|
|
| Open-Label Extension (OLE) Weeks 24-117 |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Placebo | |
| BG001 | Rilonacept 160 mg | |
| BG002 | Open-Label Rilonacept 160 mg | 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. |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||
| Age Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Ethnicity (NIH/OMB) | Everyone in Part A and Part B of the study was non hispanic and white. | Count of Participants | Participants |
| |||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS) | 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. | Cryopyrin Associated Autoinflammatory Syndrome (CAPS) is a rare, orphan, hereditary disease. There are several hundred CAPS cases in the United States. | Posted | Sep 2009 | Mean | Standard Deviation | Units of a Scale | Baseline (Days -21 to -1) and Week 6 (Days 21-42) |
|
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B) | 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. | 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. | Posted | Sep 2009 | Mean | Standard Deviation | Units of a Scale | Week 15 through Week 24 (randomized withdrawal) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient | 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. | Posted | Sep 2009 | Mean | Standard Deviation | Days | Baseline to Week 6 (Part A) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment | 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. | Posted | Sep 2009 | Mean | Standard Deviation | Units of a Scale | Baseline to Week 6 (Part A) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment | 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. | Posted | Sep 2009 | Mean | Standard Deviation | Visual Analog Scale | Baseline to Week 6 (Part A) |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L) | An abnormal value for CRP was considered > 8.4 mg/L. | Posted | Sep 2009 | Median | Standard Deviation | Milligrams per Liter | Baseline to Endpoint of Part A |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L) | An abnormal value for SAA was considered > 6.4 mg/L. | Posted | Sep 2009 | Median | Standard Deviation | Milligrams per Liter | Baseline to Endpoint of Part A |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Subjects With at Least 30% Improvement in Key Symptoms Scores (KSS) From 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). | Posted | Sep 2009 | Number | Participants | Baseline to Endpoint (Week 6) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Subjects With at Least 50% Improvement in Key Symptoms Scores (KSS) From 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). | Posted | Sep 2009 | Number | Participants | Baseline to Week 6 (Part A) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Number of Subjects With at Least 75% Improvement in Key Symptoms Scores (KSS) From 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). | Posted | Sep 2009 | Number | Participants | Baseline to Week 6 (Part A) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS | 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. | 44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE. | Posted | Sep 2009 | Mean | Standard Deviation | Units of a scale | From Baseline (week 0) to OLE Week 72 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment | 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. | 44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE. | Posted | Sep 2009 | Mean | Standard Deviation | Units of a Scale | From Baseline (Week 0) to OLE Week 72 |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Other Pre-specified | Change From Baseline to Open-Label Extension Week 72 in Number of Disease Flare Days | 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). | 44 subjects entered from part A of the study, and 12 subjects entered directly into the OLE. No placebo subjects were in the OLE. | Posted | Sep 2009 | Mean | Standard Deviation | Number of Days | From Baseline (Week 0) to OLE Week 72 |
|
|
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.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rilonacept 160 mg | 7 | 104 | 17 | 23 | |||
| EG001 | Placebo | 0 | 24 | 13 | 24 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Meningitis pneumococcal | Infections and infestations | MedDRA (11.0) | Non-systematic Assessment | 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. |
|
| Hyponatremia | Metabolism and nutrition disorders | MedDRA (11.0) | Non-systematic Assessment | Treatment Emergent Serious Adverse Events are reported for all phases of the study. |
|
| Hypokalemia | Metabolism and nutrition disorders | MedDra 11.0 | Non-systematic Assessment |
| |
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Sciatica | Nervous system disorders | MedDRA (11.0) | Non-systematic Assessment | 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. |
|
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Renal Colic | Renal and urinary disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Gastrooesophageal reflux disease | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Arteriosclerosis of the coronary artery | Cardiac disorders | MedDRA (11.0) | Non-systematic Assessment | 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. |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Injection Site Reaction | General disorders | MedDRA (11.0) | Non-systematic Assessment | 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. |
|
| Sinusitis | Infections and infestations | MedDRA (11.0) | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA (11.0) | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDra 11.0 | Non-systematic Assessment |
| |
| Diarrhea | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDra 11.0 | Non-systematic Assessment |
| |
| Abdominal pain, upper abdomen | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Hypoesthesia | Nervous system disorders | MedDRA (11.0) | Non-systematic Assessment |
| |
| Stomach Discomfort | Gastrointestinal disorders | MedDRA (11.0) | Non-systematic Assessment |
|
Cryopyrin Associated Periodic Syndrome (CAPS) is a rare disease with only a few hundred cases in the US.
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Doug Nadler, MS Statistics | Regeneron Pharmaceuticals | 914 345 7905 | clinicaltrials@regeneron.com |
| ID | Term |
|---|---|
| D056587 | Cryopyrin-Associated Periodic Syndromes |
| D030342 | Genetic Diseases, Inborn |
| ID | Term |
|---|---|
| D056660 | Hereditary Autoinflammatory Diseases |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D012873 | Skin Diseases, Genetic |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D000094482 | Chronic Inducible Urticaria |
| D000080223 | Chronic Urticaria |
| D014581 | Urticaria |
| D017445 | Skin Diseases, Vascular |
| D000096703 | Cold Urticaria |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
Not provided
Not provided
| ID | Term |
|---|---|
| C531377 | rilonacept |
Not provided
Not provided
Not provided
| Death |
|
| Sponsor Decision |
|
| Pregnancy |
|
| Between 18 and 65 years |
|
| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| Change to Week 6 in KSS |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|