Interleukin-1 Trap to Treat Autoinflammatory Diseases
Status:
Completed
Trial end date:
2010-12-01
Target enrollment:
Participant gender:
Summary
Autoinflammatory diseases are illnesses characterized by episodes of inflammation that,
unlike autoimmune disorders, lack the production of high titer autoantibodies or
antigen-specific T cells. There is growing genetic and clinical evidence that Interleukin-1
(IL-1) plays a pathogenic role in several of these diseases. This exploratory study aims to
examine the utility of the experimental drug candidate, IL 1 Trap (Regeneron Pharmaceuticals,
Inc.) in the treatment of adult subjects with the autoinflammatory disorders Neonatal Onset
Multisystem Inflammatory Disease (NOMID), Muckle-Wells Syndrome (MWS), and Familial Cold
Autoinflammatory Syndrome (FCAS), Familial Mediterranean Fever (FMF), and adult Still's
disease. FMF is associated with mutations in pyrin encoding MEFV. NOMID, MWS and FCAS are
associated with mutations in cryopyrin-encoding CIAS1.
This pilot study is designed to address: 1) the utility of IL 1 Trap in the treatment of
subjects with diseases known to respond to IL-1 blockade (NOMID/MWS/FCAS) as shown by
response to treatment with anakinra [Kineret]; 2) the response to IL-1 blockade of subjects
with Adult Still's disease and colchicine-resistant FMF once the efficacy of IL-1 Trap has
been established in NOMID/MWS/FCAS subjects; and 3) the biochemistry and genetics of
autoinflammatory diseases and IL-1 related inflammation.
IL-1 Trap is a recombinant fusion protein with picomolar affinity for IL-1 and a half-life of
approximately 7.5 days in humans. This agent is currently in Phase 2 clinical studies for the
treatment of rheumatoid arthritis and initial studies have shown activity against clinical
and biochemical indicators of inflammation. Compared with anakinra, this agent may exhibit
improved dosing convenience, potential for fewer injection site reactions, and improved
efficacy due to the extremely high affinity of IL-1Trap for its target.
In this study, biochemical, genetic, and clinical correlates of autoinflammatory disease will
initially be measured at baseline following a withdrawal of any TNF or IL-1 inhibitor
medications where applicable. Subjects will receive a course of therapy with IL-1 Trap that
is predicted to provide an estimated 3-4 weeks of anti-inflammatory activity. Clinical,
biochemical, and genetic correlates of inflammation will be measured at appropriate intervals
to ascertain response and to further elucidate disease mechanisms. Subjects will be eligible,
based on clinical response, to enter a 1- year extension phase with IL-1 Trap. Those subjects
who complete the 1-year extension phase, and maintain improved clinical and laboratory
parameters compared to baseline values, may continue to receive study medication at their
current dose until the study drug is commercially available.
Investigator comment:
This protocol (from the NIH standpoint) is a continuation of the ongoing protocol 05-AR-0014,
with a new change in study sponsor, the NIH replacing Regeneron as sponsor. this protocol
therefore still contains background and procedural information that refer to patients with
FMF and FCAS and or MWS and Still's disease, however only patients with Still's disease will
be newly enrolled from this point on, enrollment for the FCAS and or MWS patients has already
been completed and it has been decided to not enroll any more FMF patients because the number
of subjects is too low to reach reasonable conclusions, in addition it has been difficult to
recruit patients that are eligible. The background section and study procedures have largely
been left as in the currently IRB approved protocol.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)