Ignite Creation Date:
2024-05-05 @ 11:04 PM
Last Modification Date:
2024-10-26 @ 10:28 AM
Study NCT ID:
NCT01245127
Status:
COMPLETED
Last Update Posted:
2019-07-05
First Post:
2010-11-19
Brief Title:
Ilaris Canakinumab in the Schnitzler Syndrome
Sponsor:
Universitaire Ziekenhuizen KU Leuven
Organization:
Universitaire Ziekenhuizen KU Leuven
Study Overview
Official Title:
Ilaris Canakinumab in the Schnitzler Syndrome A Case Series
Status:
COMPLETED
Status Verified Date:
2010-11
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:
Schnitzler syndrome
Schnitzler syndrome is a rare disabling autoinflammatory syndrome characterized by a chronic urticarial rash and monoclonal gammopathy accompanied by intermittent fever arthralgia or arthritis or bone pain Diagnostic criteria have been established The disease never remits spontaneously Although there is no standard of care there have been promising developments in therapeutic options especially anti-interleukin-1 therapy Anakinra a synthetic analogue of the endogenous interleukin-1 receptor antagonist has caused rapid clinical remission in 24 patients with Schnitzler syndrome However to sustain remission continuous daily administration 100 mg sc is required The level of monoclonal protein does not decrease Side effects of anakinra include painful injection site reactions and neutropenia
Interleukin-1 and the autoinflammatory diseases
As a key proinflammatory cytokine mediating local and systemic responses to infection and tissue injury interleukin-1 can induce a range of responses including fever pain sensitization bone and cartilage destruction and the acute-phase inflammatory response The so-called autoinflammatory diseases are mediated entirely by interleukin-1 reducing interleukin-1 activity brings about a rapid and sustained remission Autoinflammatory diseases include relatively uncommon disorders such as familial Mediterranean fever adult and juvenile Stills disease the hyper-IG D syndrome Behçets syndrome the cryoporin-associated periodic syndrome CAPS deficiency of the interleukin-1 receptor antagonist DIRA and Schnitzlers syndrome Some common conditions such as gout and type 2 diabetes are also likely to be autoinflammatory diseases
Canakinumab
Canakinumab Ilaris Novartis Pharma is a fully human anti-interleukin-1-bèta monoclonal antibody Treatment with subcutaneous canakinumab 150 mg once every 8 weeks was associated with a rapid remission of symptoms in the great majority of children and adults with CAPS Serum inflammatory markers quickly returned to normal In general the side effects seen in this small study 35 patients were not serious though suspected infections ware significantly more prevalent in patients receiving canakinumab than in those receiving placebo The prolonged duration of action of canakinumab and low incidence of injection-site reactions may confer certain advantages over other interleukin-1 inhibitors anakinra and rilonacept since both are frequently associated with injection-site reactions and both require more frequent administration daily for anakinra and weekly for rilonacept
Canakinumab was approved for the treatment of CAPS by the US Food and Drug Administration in June 2009 and by the European Medicines Agency in October 2009
Canakinumab is currently being evaluated for its potential in the treatment of systemic-onset juvenile idiopathic arthritis diabetes mellitus and difficult-to-treat gouty arthritis
Schnitzler syndrome is a rare disabling autoinflammatory syndrome characterized by a chronic urticarial rash and monoclonal gammopathy accompanied by intermittent fever arthralgia or arthritis or bone pain Diagnostic criteria have been established The disease never remits spontaneously Although there is no standard of care there have been promising developments in therapeutic options especially anti-interleukin-1 therapy Anakinra a synthetic analogue of the endogenous interleukin-1 receptor antagonist has caused rapid clinical remission in 24 patients with Schnitzler syndrome However to sustain remission continuous daily administration 100 mg sc is required The level of monoclonal protein does not decrease Side effects of anakinra include painful injection site reactions and neutropenia
Interleukin-1 and the autoinflammatory diseases
As a key proinflammatory cytokine mediating local and systemic responses to infection and tissue injury interleukin-1 can induce a range of responses including fever pain sensitization bone and cartilage destruction and the acute-phase inflammatory response The so-called autoinflammatory diseases are mediated entirely by interleukin-1 reducing interleukin-1 activity brings about a rapid and sustained remission Autoinflammatory diseases include relatively uncommon disorders such as familial Mediterranean fever adult and juvenile Stills disease the hyper-IG D syndrome Behçets syndrome the cryoporin-associated periodic syndrome CAPS deficiency of the interleukin-1 receptor antagonist DIRA and Schnitzlers syndrome Some common conditions such as gout and type 2 diabetes are also likely to be autoinflammatory diseases
Canakinumab
Canakinumab Ilaris Novartis Pharma is a fully human anti-interleukin-1-bèta monoclonal antibody Treatment with subcutaneous canakinumab 150 mg once every 8 weeks was associated with a rapid remission of symptoms in the great majority of children and adults with CAPS Serum inflammatory markers quickly returned to normal In general the side effects seen in this small study 35 patients were not serious though suspected infections ware significantly more prevalent in patients receiving canakinumab than in those receiving placebo The prolonged duration of action of canakinumab and low incidence of injection-site reactions may confer certain advantages over other interleukin-1 inhibitors anakinra and rilonacept since both are frequently associated with injection-site reactions and both require more frequent administration daily for anakinra and weekly for rilonacept
Canakinumab was approved for the treatment of CAPS by the US Food and Drug Administration in June 2009 and by the European Medicines Agency in October 2009
Canakinumab is currently being evaluated for its potential in the treatment of systemic-onset juvenile idiopathic arthritis diabetes mellitus and difficult-to-treat gouty arthritis
Detailed Description:
Description of the study
Objectives
Primary objective To evaluate if canakinumab 150mg every 8 weeks can induce and maintain clinical remission in patients with the Schnitzler syndrome
Secondary objectives
To test if canakinumab 150mg can induce a complete clinical response at Day 7
To assess if addition canakinumab 150mg given at Day 7 for patients demonstrating only a partial response can induce a complete clinical response at Day 14
To evaluate if canakinumab 300mg every 8 weeks can maintain clinical remission in those patients who required canakinumab 150 mg additional dose on Day 7 and achieved clinical remission at Day 14
To evaluate the safety of canakinumab treatment in patients with the Schnitzler syndrome
To assess the changes in C-reactive protein CRP levels during the treatment period
Study rationale
Although no standard therapy has been established for the Schnitzler syndrome given the rarity of this auto-inflammatory syndrome reports on the use of Anakinra a synthetic analog of the endogenous interleukin-1 receptor antagonist have been encouraging However side effects including local infusion site reactions and neutropenia and the need for daily sc administration have hampered its use The anti-interleukin-1-inhibitor canakinumab may constitute an effective and more convenient alternative
Objectives
Primary objective To evaluate if canakinumab 150mg every 8 weeks can induce and maintain clinical remission in patients with the Schnitzler syndrome
Secondary objectives
To test if canakinumab 150mg can induce a complete clinical response at Day 7
To assess if addition canakinumab 150mg given at Day 7 for patients demonstrating only a partial response can induce a complete clinical response at Day 14
To evaluate if canakinumab 300mg every 8 weeks can maintain clinical remission in those patients who required canakinumab 150 mg additional dose on Day 7 and achieved clinical remission at Day 14
To evaluate the safety of canakinumab treatment in patients with the Schnitzler syndrome
To assess the changes in C-reactive protein CRP levels during the treatment period
Study rationale
Although no standard therapy has been established for the Schnitzler syndrome given the rarity of this auto-inflammatory syndrome reports on the use of Anakinra a synthetic analog of the endogenous interleukin-1 receptor antagonist have been encouraging However side effects including local infusion site reactions and neutropenia and the need for daily sc administration have hampered its use The anti-interleukin-1-inhibitor canakinumab may constitute an effective and more convenient alternative
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