Ignite Creation Date:
2024-05-05 @ 11:38 AM
Last Modification Date:
2024-10-26 @ 9:10 AM
Study NCT ID:
NCT00094900
Status:
COMPLETED
Last Update Posted:
2014-03-04
First Post:
2004-10-28
Brief Title:
Interleukin-1 Trap to Treat Autoinflammatory Diseases
Sponsor:
National Institute of Arthritis and Musculoskeletal and Skin Diseases NIAMS
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2014-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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 Stills 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 NOMIDMWSFCAS as shown by response to treatment with anakinra Kineret 2 the response to IL-1 blockade of subjects with Adult Stills disease and colchicine-resistant FMF once the efficacy of IL-1 Trap has been established in NOMIDMWSFCAS 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 75 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 Stills disease however only patients with Stills 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
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 NOMIDMWSFCAS as shown by response to treatment with anakinra Kineret 2 the response to IL-1 blockade of subjects with Adult Stills disease and colchicine-resistant FMF once the efficacy of IL-1 Trap has been established in NOMIDMWSFCAS 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 75 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 Stills disease however only patients with Stills 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
Detailed Description:
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 Stills 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 NOMIDMWSFCAS as shown by response to treatment with anakinra Kineret 2 the response to IL-1 blockade of subjects with Adult Stills disease and colchicine-resistant FMF once the efficacy of IL-1 Trap has been established in NOMIDMWSFCAS 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 75 days in humans Our result of the FCASMWS part of this study and a multi center phase III study in patients with FCASMWS 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 FCASMWS and Stills disease however only patients with Stills disease will be newly enrolled from this point on enrollment for the FCASMWS 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 Stills 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
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 NOMIDMWSFCAS as shown by response to treatment with anakinra Kineret 2 the response to IL-1 blockade of subjects with Adult Stills disease and colchicine-resistant FMF once the efficacy of IL-1 Trap has been established in NOMIDMWSFCAS 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 75 days in humans Our result of the FCASMWS part of this study and a multi center phase III study in patients with FCASMWS 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 FCASMWS and Stills disease however only patients with Stills disease will be newly enrolled from this point on enrollment for the FCASMWS 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 Stills 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 05-AR-0014 | None | None | None |