Efficacy and Safety of Canakinumab in Schnitzler Syndrome

Study Overview
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Brief Summary
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Schnitzler syndrome is a disabling inflammatory disease, characterized by chronic urticaria, fever, arthralgia, bone pain and gammopathy, which can so far only be effectively treated with anakinra, an interleukin-1 receptor antagonist. However, this drug is not registered for use in Schnitzler syndrome, and it needs to be injected daily, which is uncomfortable and unpractical. Therefore other treatments targeting IL-1 are needed. Canakinumab is a long-acting monoclonal antibody against IL-1β that has been registered for bimonthly use in the rare autoinflammatory disease Cryopyrin-associated periodic syndrome (CAPS). We hypothesize that it will be effective in Schnitzler syndrome too in view of clinical similarities to CAPS and the targeting of IL-1B, which is also blocked by anakinra (which blocks both IL-1B and IL-1A). This is a 6-month open-label, single treatment arm study of canakinumab 150 or 300 mg (in case of insufficient response to 150 mg) subcutaneous injection once per month in patients with active Schnitzler syndrome, in which efficacy and safety will be assessed.

Detailed Description
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More on Canakinumab: Canakinumab is a high-affinity human monoclonal anti-human interleukin-1β (IL-1β)antibody of the IgG1/k isotype), developed for the treatment of IL-1β driven inflammatory diseases. Canakinumab binds human IL-1β and functionally neutralizes the bioactivity of this pro-inflammatory cytokine. IL-1β is produced mainly by mononuclear phagocytes in response to injury and infection and plays a dominant role in the pathobiology of autoinflammatory syndromes (e.g. Cryopyrin associated periodic syndrome, CAPS), systemic Juvenile Idiopathic Arthritis and gout. Canakinumab is expected to treat the signs and symptoms of inflammation and the underlying structural damage of disease. Canakinumab has been administered in clinical trials as an intravenous (i.v.) infusion or as a subcutaneous (sc) injection and has been approved under the trade name ILARIS® in the US for patients ≥ 4 years of age with CAPS and in the European Union and Switzerland for CAPS patients ≥ 4 years of age.

Official Title
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Efficacy and Safety of Canakinumab in Schnitzler Syndrome

Conditions
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Schnitzler Syndrome

Intervention / Treatment
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* Drug: Canakinumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with a diagnosis of Schnitzler syndrome as per criteria (ref 1). Patients that have been / are treated with Anakinra must have demonstrated a partial or complete clinical response with an associated normalization of their biomarkers of inflammation (CRP). Male and female patients at least 18 years of age at the time of the screening visit. Patient's informed consent. Negative QuantiFERON test or negative Purified Protein Derivative (PPD) test (< 5 mm induration) at screening or within 1 month prior to the screening visit, according to the national guidelines. Patients with a positive PPD test (≥ 5 mm induration) at screening may be enrolled only if they have either a negative chest x-ray or a negative QuantiFERON test (QFT-TB G In-Tube). Adequate contraception in premenopausal females Exclusion Criteria: Pregnant or nursing (lactating) women History of being immunocompromised, including a positive HIV at screening (ELISA and Western blot). Serologic evidence of hepatitis B or C infection Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose History of significant medical conditions, which in the Investigator's opinion would exclude the patient from participating in this trial History of recurrent and/or evidence of active bacterial, fungal, or viral infection(s) Use of the following therapies: Anakinra within 24 hours prior to Baseline visit XML File Identifier : tl8ybe8lI1o6DeawQocCBa8TF/w= Corticosteroids (oral prednisone (or equivalent)) > 1.0 mg/kg/day (or greater than the maximum of 60 mg/day for children over 60 kg) within 3 days prior to the Baseline visit Intra-articular, peri-articular or intramuscular corticosteroid injections within 4 weeks prior to the Baseline visit Any other investigational biologics within 8 weeks prior to the Baseline visit Any other investigational drugs, other than investigational biologic treatment, within 30 days (or 3 months for investigational monoclonal antibodies) or 5 half-lives prior to the Baseline visit, whichever is longer History of hypersensitivity to any of the study drugs or to drugs of similar chemical classes

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Canakinumab<br>A 6-month open-label, single treatment arm study of canakinumab 150 or 300 mg (in case of insufficient response to 150 mg) subcutaneous injection once per month. | Drug: Canakinumab<br>* Monthly subcutaneous injection with 150mg Canakinumab for 6 months<br>* Other names: Ilaris;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete or clinical remission at Day 14. |  | Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete or clinical remission at Day 3 and Day 7 |  | Day 3 and day 7 | 
| The prevention of disease relapse in patients who demonstrated complete remission at Day 14 |  | Day 15 until end | 
| The change in biomarkers (CRP and SAA) and clinical parameters (physician and patient global assessment of disease activity) during the treatment and follow-up periods |  | Whole study | 
| Time to relapse after the last canakinumab dose |  | Month 6 - 9 | 
| Safety and tolerability as well as PK/PD/IG properties of canakinumab in the treatment of patients with Schnitzler syndrome. |  | Whole study | 
| Changes in patient quality of life by using: Medical Outcome Short Form (36) Health Survey (SF-36®). |  | Whole study | 
| Optimal canakinumab dose and frequency in patients with Schnitzler syndrome |  | Whole study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety, Efficacy, Schnitzler syndrome, IL-1 beta, Canakinumab, Ilaris, Treatment