Inflammation Clinical Trial
Official title:
Continuation of a Pilot Open-Label Study of IL 1 Trap in Adult Subjects With Autoinflammatory Diseases: A Therapeutic Approach to Study Pathogenesis
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.
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 MEFV encoding Pyrin.
NOMID, MWS and FCAS are associated with mutations in CIAS1-encoding cryopyrin.
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. Our result of the FCAS/MWS part of this study and a
multi center phase III study in patients with FCAS/MWS provided the basis for the FDA
approval of IL-Trap for the treatment of patients with the CAPS.
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.
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/MWS and Still's disease, however only patients with Still's
disease will be newly enrolled from this point on, enrollment for the FCAS/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. Those Adults Still's patients, who complete
the extension phase, and maintain improved clinical and laboratory parameters compared to
baseline values, may continue to receive study medication at their current dose. These
individuals will have their medication supplied by the manufacturing company, Regeneron,
until June 2010. At that time the subjects' health insurance companies will begin to pay for
their medication supply or the subjects will begin treatment with Anakinra, another IL-1
blocker. Our follow-up plans for all patients who discontinue IL-1 Trap usage will be to
monitor for any medication side effects or toxicities and collect adverse event data for 3
months post discontinuation. We will help our subjects to obtain insurance coverage for
IL-1Trap.
;
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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