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

NCT00288704 | Completed Phase 3 Results DMC

• 1 other identifier: IL1T-AI-0505
• Study Type: interventional
• Target: 104
• Locations: 1 country
• Sites: 24

Brief Summary

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.

Conditions

Familial Cold Autoinflammatory Syndrome (FCAS); Familial Cold Urticaria; Muckle-Wells Syndrome (MWS); Genetic Diseases, Inborn

Keywords

Familial Cold Autoinflammatory Syndrome (FCAS); Muckle-Wells Syndrome (MWS); CIAS1; NLRP-3; PYPAF1; Cryopyrin; CAPS; Interleukin-1

Outcome Measures

Primary Outcomes (2)

• 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)

Other Outcomes (11)

• Mean Change From Baseline to Endpoint (Week 6) in Number of Disease Flare Days Per Patient

  Baseline to Week 6 (Part A)

• Change From Baseline to Endpoint (Week 6) in Physician's Global Assessment

  Baseline to Week 6 (Part A)

• Mean Change From Baseline to Endpoint (Week 6) in Patient's Global Assessment

  Baseline to Week 6 (Part A)

Study Arms (3)

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).

Drug: Placebo

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.

Drug: rilonacept 160 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.

Drug: rilonacept 160 mg

Interventions

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).

Also known as: Rilonacept

rilonacept 160 mg

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.

Placebo

Eligibility Criteria

• Age: 7 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• Had evidence of untreated tuberculosis or other conditions/therapies that made the subject inappropriate for this study.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: lead

Study Sites (24)

Unknown Facility

Little Rock, Arkansas, 72204, United States

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Palm Desert, California, 92260, United States

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Upland, California, 91786, United States

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Jacksonville, Florida, 32216, United States

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Stuart, Florida, 34996, United States

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Atlanta, Georgia, 30342, United States

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Columbus, Georgia, 31904, United States

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Aurora, Illinois, 60504, United States

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Louisville, Kentucky, 40215, United States

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Shreveport, Louisiana, 71105, United States

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Chesterfield, Michigan, 48047, United States

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St Louis, Missouri, 63141, United States

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New York, New York, 10023, United States

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Raleigh, North Carolina, 27609, United States

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Cincinnati, Ohio, 45236, United States

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Duncansville, Pennsylvania, 16635, United States

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Columbia, South Carolina, 29201, United States

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Greer, South Carolina, 29651, United States

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Chattanooga, Tennessee, 37403, United States

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Dallas, Texas, 75235, United States

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Waco, Texas, 76712, United States

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Cedar City, Utah, 84720, United States

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Forest, Virginia, 24551, United States

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Lakewood, Washington, 98499, United States

Location

Related Publications (2)

• 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.

  PMID: 23031624 DERIVED

• 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.

  PMID: 18668535 DERIVED

Related Links

• click here for more information on rilonacept

MeSH Terms

Conditions

Cryopyrin-Associated Periodic Syndromes; Genetic Diseases, Inborn

Interventions

rilonacept

Condition Hierarchy (Ancestors)

Hereditary Autoinflammatory Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin Diseases, Genetic; Skin Diseases; Skin and Connective Tissue Diseases; Chronic Inducible Urticaria; Chronic Urticaria; Urticaria; Skin Diseases, Vascular; Cold Urticaria; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

Cryopyrin Associated Periodic Syndrome (CAPS) is a rare disease with only a few hundred cases in the US.

Results Point of Contact

• Title: Doug Nadler, MS Statistics
• Organization: Regeneron Pharmaceuticals

clinicaltrials@regeneron.com

914 345 7905

Study Officials

• Robert Evans, PharmD.

  Regeneron Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2006
• First Posted: February 8, 2006
• Study Start: December 1, 2005
• Primary Completion: June 1, 2008
• Study Completion: August 1, 2008
• Last Updated: December 6, 2011
• Results First Posted: November 13, 2009

Record last verified: 2011-12

Locations

US (24)