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

NCT ID: NCT00288704

Last Updated: 2011-12-06

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

104 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-12-31

Study Completion Date

2008-08-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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

Keywords

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

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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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).

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type 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

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.

Group Type ACTIVE_COMPARATOR

rilonacept 160 mg

Intervention Type 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).

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.

Group Type OTHER

rilonacept 160 mg

Intervention Type 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.

Interventions

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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).

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

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Rilonacept

Eligibility Criteria

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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.
Minimum Eligible Age

7 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Regeneron Pharmaceuticals

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Robert Evans, PharmD.

Role: STUDY_DIRECTOR

Regeneron Pharmaceuticals

Locations

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Little Rock, Arkansas, United States

Site Status

Palm Desert, California, United States

Site Status

Upland, California, United States

Site Status

Jacksonville, Florida, United States

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Stuart, Florida, United States

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Atlanta, Georgia, United States

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Columbus, Georgia, United States

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Aurora, Illinois, United States

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Louisville, Kentucky, United States

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Shreveport, Louisiana, United States

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Chesterfield, Michigan, United States

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St Louis, Missouri, United States

Site Status

New York, New York, United States

Site Status

Raleigh, North Carolina, United States

Site Status

Cincinnati, Ohio, United States

Site Status

Duncansville, Pennsylvania, United States

Site Status

Columbia, South Carolina, United States

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Greer, South Carolina, United States

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Chattanooga, Tennessee, United States

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Dallas, Texas, United States

Site Status

Waco, Texas, United States

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Cedar City, Utah, United States

Site Status

Forest, Virginia, United States

Site Status

Lakewood, Washington, United States

Site Status

Countries

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United States

References

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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.

Reference Type DERIVED
PMID: 23031624 (View on PubMed)

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.

Reference Type DERIVED
PMID: 18668535 (View on PubMed)

Related Links

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Other Identifiers

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IL1T-AI-0505

Identifier Type: -

Identifier Source: org_study_id