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Completed

NCT Number: NCT00288704

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

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.

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Key information

Conditions

Familial Cold Autoinflammatory Syndrome (FCAS) Chronic Disease Chronic Inducible Urticaria Chronic Urticaria Cold Urticaria Congenital, Hereditary, and Neonatal Diseases and Abnormalities Cryopyrin-Associated Periodic Syndromes Disease Attributes Familial Cold Urticaria Genetic Diseases, Inborn Hereditary Autoinflammatory Diseases Hypersensitivity Hypersensitivity, Immediate Immune System Diseases Muckle-Wells Syndrome (MWS) Pathologic Processes Pathological Conditions, Signs and Symptoms Skin Diseases Skin Diseases, Genetic Skin Diseases, Vascular Skin and Connective Tissue Diseases Urticaria

Age range

7 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Little Rock, Arkansas, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

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).

Other names: Rilonacept

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.

Primary outcomes

  1. 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)

    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.

  2. 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)

    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.

Other outcomes

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

    Time frame: 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.

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

    Time frame: 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.

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

    Time frame: 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.

  4. Median Change From Baseline to Week 6 (Part A) Endpoint in C-Reactive Protein (mg/L)

    Time frame: Baseline to Endpoint of Part A

    An abnormal value for CRP was considered > 8.4 mg/L.

  5. Median Change From Baseline to Week 6 (Part A) Endpoint in Serum Amyloid A (mg/L)

    Time frame: Baseline to Endpoint of Part A

    An abnormal value for SAA was considered > 6.4 mg/L.

  6. 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)

    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).

  7. 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)

    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).

  8. 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)

    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).

  9. Summary of Mean Change From Baseline to Open-Label Extension Week 72 in KSS

    Time frame: From Baseline (week 0) to OLE Week 72

    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.

  10. Change From Baseline to Open-Label Extension Week 72 in Patient's Global Assessment

    Time frame: From Baseline (Week 0) to OLE Week 72

    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.

  11. 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

    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).

Sponsors and collaborators

Lead sponsor

Regeneron Pharmaceuticals

Industry

Registry information

Official study 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

Important dates

Study start
2005
Primary completion
2008
Study completion
2008
First posted
Feb 8, 2006
Registry last updated
Dec 6, 2011

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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