Tocilizumab in Patients With Schnitzler's Syndrome (TOCISCH)
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|ClinicalTrials.gov Identifier: NCT03046381|
Recruitment Status : Recruiting
First Posted : February 8, 2017
Last Update Posted : January 31, 2019
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 very effective, well-tolerated and safe in other acquired autoinflammatory disorders, systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease that share many clinical features (rash, fever, joint involvement, lymphadenopathy, fatigue) and excessive cytokine production with SchS. The study consists of a run-in baseline period of 1-4 weeks followed by an open-label 20-week TCZ treatment phase with weekly s.c. injections (TCZ 162mg), followed by an optional study extension up to a total of 1 year with ongoing once weekly TCZ 162mg injections and a 4 week period of follow-up.
|Condition or disease||Intervention/treatment||Phase|
|Schnitzler's Syndrome||Drug: Tocilizumab||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||12 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Open-label Study to Assess the Efficacy and Safety of Tocilizumab in Patients With Active Schnitzler's Syndrome|
|Actual Study Start Date :||July 19, 2017|
|Estimated Primary Completion Date :||July 31, 2019|
|Estimated Study Completion Date :||July 31, 2019|
Tocilizumab 162mg 1x weekly as subcutaneous syringe
Tocilizumab 162mg 1x weekly s.c.
Other Name: RoActemra®
- 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
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03046381
|Contact: Karoline Krause, MD||+49 30 450 518 ext email@example.com|
|Contact: Marcus Maurer, MD||+49 30 450 518 ext firstname.lastname@example.org|
|Charité - Universitätsmedizin Berlin, Dpt. of Dermatology and Allergy||Recruiting|
|Berlin, Germay, Germany, 10117|
|Contact: Karoline Krause, MD +49 30 450 518 ext 336 email@example.com|
|Contact: Hanna Bonnekoh, MD +49 30 450 618 ext 077 firstname.lastname@example.org|
|Principal Investigator:||Karoline Krause, MD||Charite University, Berlin, Germany|