Clinical Trial: Tocilizumab in Patients With Schnitzler's Syndrome

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Pilot Open-label Study to Assess the Efficacy and Safety of Tocilizumab in Patients With Active Schnitzler's Syndrome

Brief Summary:

Schnitzler's Syndrome (SchS) is a late-onset multifactorial autoinflammatory disease characterized by chronic urticarial skin lesions and a monoclonal gammopathy usually belonging to the immunoglobulin M (IgM) or IgG class. Symptoms associated with SchS are recurrent fever attacks, bone and muscle pain, arthralgia or arthritis, fatigue and lymphadenopathy. SchS is a rare disease with approximately 300 cases reported in the literature. The nature of SchS is chronic without known reports about spontaneous remissions. Disease onset occurs around the age of 50. About 15% of patients eventually develop a lymphoproliferative disorder, most often Waldenström's macroglobulinemia. The pathogenesis of SchS is still not well defined. Functional ex vivo studies showed excessive cytokine production (IL-1ß, IL-6 and IL-18) of peripheral blood monocytes (PBMCs) in SchS as compared to healthy controls. In addition to excessive IL-6 secretion from PBMCs IL-6 has repeatedly been reported to be elevated in the serum of SchS patients too. As IL-6 plays a major role in the development of multiple myeloma, IL-6 may also be associated with the formation of lymphoproliferative disorders in SchS.

Until now, there is no approved standard therapy available for the treatment of SchS. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other immunosuppressive agents have been reported to provide variable relief from symptoms of bone pain and arthralgia. Case reports and small studies about successful treatment of SchS with anti-IL-1 blockers (anakinra, rilonacept and canakinumab) accumulate. However, there have been complete and partial treatment failures to anti-IL-1 blockade in SchS. In these patients, anti-IL-6 treatment (tocilizumab [TCZ]) demonstrated to be very effective in reducing the clinical symptoms and inflammation markers in SchS. TCZ treatment has proved to be

Detailed Summary:
Sponsor: Karoline Krause

Current Primary Outcome: Physician global assessment [ Time Frame: Baseline vs. week 20 ]

Change in the investigator's assessment of total disease activity (physician global assessment [PGA]) between baseline and TCZ Treatment


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Complete responders [ Time Frame: Week 20 ]
    Proportion of patients with complete response (based on PGA with no or minimal overall autoinflammatory disease activity and CRP </= 10 mg/l)
  • Schnitzler Activity Score [ Time Frame: 60 weeks ]
    Change in the patient based Schnitzler Activity Score (SchAS) during the treatment period (The SchAS combines the key symptoms of SchS).
  • Inflammation marker CRP [ Time Frame: 60 weeks ]
    Change in CRP levels during the treatment period
  • Inflammation marker SAA [ Time Frame: 60 weeks ]
    Change in SAA levels during the treatment period
  • Inflammation marker S100 A8/9 [ Time Frame: 60 weeks ]
    Change in S100 A8/9 levels during the treatment period
  • Overall quality of life [ Time Frame: 60 weeks ]
    Change in the patient's quality of life (assessed by the SF-36)
  • Dermatology-specific quality of life [ Time Frame: 60 weeks ]
    Change in the patient's quality of life (assessed by the Dermatology Life Quality Index)
  • Safety and tolerability assessed by adverse event reporting over the whole study period [ Time Frame: 60 weeks ]
    Adverse event reporting over the whole study period


Original Secondary Outcome: Same as current

Information By: Charite University, Berlin, Germany

Dates:
Date Received: January 5, 2017
Date Started: May 1, 2017
Date Completion: July 31, 2019
Last Updated: February 9, 2017
Last Verified: February 2017