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
  Purpose

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.


Condition Intervention Phase
Familial Cold Autoinflammatory Syndrome (FCAS)
Familial Cold Urticaria
Muckle-Wells Syndrome (MWS)
Genetic Diseases, Inborn
Drug: rilonacept 160 mg
Drug: Placebo
Phase 3

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
Official Title: IL1T-AI-0505: A Multi-center, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, & Efficacy of Rilonacept in Subjects With Cryopyrin-Associated Periodic Syndromes (CAPS) Using Parallel Group & Randomized Withdrawal Designs

Resource links provided by NLM:


Further study details as provided by Regeneron Pharmaceuticals:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]

    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.


  • 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) ] [ Designated as safety issue: No ]

    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.



Enrollment: 104
Study Start Date: December 2005
Study Completion Date: August 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
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).
Drug: Placebo
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.
Active Comparator: rilonacept 160 mg

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.

Drug: rilonacept 160 mg
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).
Other Name: Rilonacept
Open-Label rilonacept 160 mg

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.

Drug: rilonacept 160 mg
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.

Detailed Description:

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:

  • To determine the safety and tolerability of rilonacept in subjects with CAPS
  • To assess the effect of rilonacept on laboratory measures of inflammation such as acute phase reactants

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.

  Eligibility

Ages Eligible for Study:   7 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Double-blind phases: adults age 18 and above; Open-label extension: Adults and children aged 7 years and older.
  • Was diagnosed with Familial Cold Auto-inflammatory Syndrome (FCAS) or Muckle-Wells Syndrome (MWS) based upon clinical signs and symptoms
  • Had documented mutation in NLRP-3 (Cold Induced Autoinflammatory Syndrome-1 or CIAS1) in subject or relative, and willingness to have a confirmatory genetic (Deoxyribonucleic acid or DNA) test (cheek swab).
  • Was able to understand and comply with study procedures and was able to provide informed consent
  • If female, was not currently pregnant and was willing to use contraception during the study

Exclusion Criteria:

  • Had evidence of untreated tuberculosis or other conditions/therapies that made the subject inappropriate for this study.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00288704

  Hide Study Locations
Locations
United States, Arkansas
Little Rock, Arkansas, United States, 72204
United States, California
Palm Desert, California, United States, 92260
Upland, California, United States, 91786
United States, Florida
Jacksonville, Florida, United States, 32216
Stuart, Florida, United States, 34996
United States, Georgia
Atlanta, Georgia, United States, 30342
Columbus, Georgia, United States, 31904
United States, Illinois
Aurora, Illinois, United States, 60504
United States, Kentucky
Louisville, Kentucky, United States, 40215
United States, Louisiana
Shreveport, Louisiana, United States, 71105
United States, Michigan
Chesterfield, Michigan, United States, 48047
United States, Missouri
St. Louis, Missouri, United States, 63141
United States, New York
New York, New York, United States, 10023
United States, North Carolina
Raleigh, North Carolina, United States, 27609
United States, Ohio
Cincinnati, Ohio, United States, 45236
United States, Pennsylvania
Duncansville, Pennsylvania, United States, 16635
United States, South Carolina
Columbia, South Carolina, United States, 29201
Greer, South Carolina, United States, 29651
United States, Tennessee
Chattanooga, Tennessee, United States, 37403
United States, Texas
Dallas, Texas, United States, 75235
Waco, Texas, United States, 76712
United States, Utah
Cedar City, Utah, United States, 84720
United States, Virginia
Forest, Virginia, United States, 24551
United States, Washington
Lakewood, Washington, United States, 98499
Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
Study Director: Robert Evans, PharmD. Regeneron Pharmaceuticals
  More Information

Additional Information:
No publications provided by Regeneron Pharmaceuticals

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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

Keywords provided by Regeneron Pharmaceuticals:
Familial Cold Autoinflammatory Syndrome (FCAS)
Muckle-Wells Syndrome (MWS)
CIAS1
NLRP-3
PYPAF1
Cryopyrin
CAPS
Interleukin-1

Additional relevant MeSH terms:
Genetic Diseases, Inborn
Urticaria
Cryopyrin-Associated Periodic Syndromes
Cellulitis
Eosinophilia
Skin Diseases, Vascular
Skin Diseases
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Hereditary Autoinflammatory Diseases
Skin Diseases, Genetic
Skin Diseases, Infectious
Infection
Suppuration
Connective Tissue Diseases
Inflammation
Pathologic Processes
Leukocyte Disorders
Hematologic Diseases

ClinicalTrials.gov processed this record on July 23, 2014