Clinical Trial: Ilaris (Canakinumab) in the Schnitzler Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Ilaris (Canakinumab) in the Schnitzler Syndrome. A Case Series.

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 Still's disease, the hyper-IG D syndrome, Behçet's syndrome, the cryoporin-associated periodic syndrome (CAPS), deficiency of the interleukin-1 receptor antagonist (DIRA) and Schnitzler's syndrome. Some common conditions such as gout and type 2 diabetes, are also likely to be autoinflammatory diseases.

Canakinumab:

Detailed Summary:

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.

Sponsor: Universitaire Ziekenhuizen Leuven

Current Primary Outcome: Efficacy [ Time Frame: 28 weeks ]

Original Primary Outcome: Same as current

Current Secondary Outcome: Tolerability [ Time Frame: 28 weeks ]

Original Secondary Outcome: Same as current

Information By: Universitaire Ziekenhuizen Leuven

Dates:
Date Received: November 19, 2010
Date Started: May 2011
Date Completion:
Last Updated: June 14, 2012
Last Verified: November 2010