rilonacept for treatment of cryopyrin-associated periodic syndromes (caps)

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

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.

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 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.

Keywords: familial cold autoinflammatory syndrome (fcas) muckle-wells syndrome (mws) cias1 nlrp-3 pypaf1 cryopyrin caps interleukin-1