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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00288704
First received: February 6, 2006
Last updated: December 1, 2011
Last verified: December 2011
Results First Received: September 30, 2009  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Double Blind (Subject, Caregiver, 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

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
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.

Reporting Groups
  Description
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.


Participant Flow for 3 periods

Period 1:   Part A, Double Blind, Weeks 1-6
    Placebo     Rilonacept 160 mg     Open-Label Extension (OLE) Rilonacept 160 mg  
STARTED     24     23     0 [1]
COMPLETED     24     22     0  
NOT COMPLETED     0     1     0  
Pre-dose Condition                 0                 1                 0  
[1] Subjects enrolled into the open-label phase do not complete this part of the study.

Period 2:   Part B, Randomized Withdrawal, Wks 15-24
    Placebo     Rilonacept 160 mg     Open-Label Extension (OLE) Rilonacept 160 mg  
STARTED     23 [1]   22     0  
COMPLETED     23     21     0  
NOT COMPLETED     0     1     0  
Adverse Event                 0                 1                 0  
[1] 1 subject discontinued during weeks 6-14 due to non-compliance with study drug dosing procedures.

Period 3:   Open-Label Extension (OLE) Weeks 24-117
    Placebo     Rilonacept 160 mg     Open-Label Extension (OLE) Rilonacept 160 mg  
STARTED     0 [1]   0     101  
COMPLETED     0     0     81  
NOT COMPLETED     0     0     20  
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.



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Placebo No text entered.
Rilonacept 160 mg No text entered.
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.
Total Total of all reporting groups

Baseline Measures
    Placebo     Rilonacept 160 mg     Open-Label Rilonacept 160 mg     Total  
Number of Participants  
[units: participants]
  24     23     57     104  
Age  
[units: participants]
       
<=18 years     0     0     8     8  
Between 18 and 65 years     17     20     46     83  
>=65 years     7     3     3     13  
Age  
[units: years]
Mean ± Standard Deviation
  55.5  ± 14.7     45.9  ± 16     37.7  ± 17.2     43.6  ± 17.8  
Gender  
[units: participants]
       
Female     16     15     37     68  
Male     8     8     20     36  
Ethnicity (NIH/OMB) [1]
[units: Participants]
       
Hispanic or Latino     0     0     0     0  
Not Hispanic or Latino     24     23     56     103  
Unknown or Not Reported     0     0     1     1  
Race (NIH/OMB)  
[units: Participants]
       
American Indian or Alaska Native     0     0     0     0  
Asian     0     0     0     0  
Native Hawaiian or Other Pacific Islander     0     0     0     0  
Black or African American     0     0     0     0  
White     24     23     57     104  
More than one race     0     0     0     0  
Unknown or Not Reported     0     0     0     0  
Region of Enrollment  
[units: participants]
       
United States     24     23     57     104  
[1] Everyone in Part A and Part B of the study was non hispanic and white.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change From Baseline to Week-6 (Part A) Endpoint in Mean Key Symptom Score (KSS)   [ Time Frame: Baseline (Days -21 to -1) and Week 6 (Days 21-42) ]

2.  Primary:   Mean Change in Key Symptom Score (KSS) From Week 15 to Week 24 (During the Randomized Withdrawal Phase or Part B)   [ Time Frame: Week 15 through Week 24 (randomized withdrawal) ]

3.  Other Pre-specified:   Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient   [ Time Frame: Baseline to Week 6 (Part A) ]

4.  Other Pre-specified:   Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment   [ Time Frame: Baseline to Week 6 (Part A) ]

5.  Other Pre-specified:   Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment   [ Time Frame: Baseline to Week 6 (Part A) ]

6.  Other Pre-specified:   Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L)   [ Time Frame: Baseline to Endpoint of Part A ]

7.  Other Pre-specified:   Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L)   [ Time Frame: Baseline to Endpoint of Part A ]

8.  Other Pre-specified:   Number of Subjects With at Least 30% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)   [ Time Frame: Baseline to Endpoint (Week 6) ]

9.  Other Pre-specified:   Number of Subjects With at Least 50% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)   [ Time Frame: Baseline to Week 6 (Part A) ]

10.  Other Pre-specified:   Number of Subjects With at Least 75% Improvement in Key Symptoms Scores (KSS) From Baseline to Endpoint (Week 6)   [ Time Frame: Baseline to Week 6 (Part A) ]

11.  Other Pre-specified:   Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS   [ Time Frame: From Baseline (week 0) to OLE Week 72 ]

12.  Other Pre-specified:   Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment   [ Time Frame: From Baseline (Week 0) to OLE Week 72 ]

13.  Other Pre-specified:   Change From Baseline to Open-Label Extension Week 72 in Number of Disease Flare Days   [ Time Frame: From Baseline (Week 0) to OLE Week 72 ]


  Serious Adverse Events


  Other Adverse Events


  More Information
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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 agreement is:
unchecked The only disclosure restriction on the PI 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. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
Cryopyrin Associated Periodic Syndrome (CAPS) is a rare disease with only a few hundred cases in the US.  


Results Point of Contact:  
Name/Title: Doug Nadler, MS Statistics
Organization: Regeneron Pharmaceuticals
phone: 914 345 7905
e-mail: clinicaltrials@regeneron.com


No publications provided by Regeneron Pharmaceuticals

Publications automatically indexed to this study:

Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00288704     History of Changes
Other Study ID Numbers: IL1T-AI-0505
Study First Received: February 6, 2006
Results First Received: September 30, 2009
Last Updated: December 1, 2011
Health Authority: United States: Food and Drug Administration