Efficacy and Safety of Canakinumab in Schnitzler Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01276522
Recruitment Status : Completed
First Posted : January 13, 2011
Last Update Posted : May 24, 2012
Information provided by (Responsible Party):
Radboud University

Brief Summary:

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.

Condition or disease Intervention/treatment Phase
Schnitzler Syndrome Drug: Canakinumab Phase 2

Detailed Description:

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Canakinumab in Schnitzler Syndrome
Study Start Date : January 2011
Actual Primary Completion Date : May 2011
Actual Study Completion Date : December 2011

Arm Intervention/treatment
Experimental: Canakinumab
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
Monthly subcutaneous injection with 150mg Canakinumab for 6 months
Other Name: Ilaris

Primary Outcome Measures :
  1. Complete or clinical remission at Day 14. [ Time Frame: Day 14 ]

Secondary Outcome Measures :
  1. Complete or clinical remission at Day 3 and Day 7 [ Time Frame: Day 3 and day 7 ]
  2. The prevention of disease relapse in patients who demonstrated complete remission at Day 14 [ Time Frame: Day 15 until end ]
  3. 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 [ Time Frame: Whole study ]
  4. Time to relapse after the last canakinumab dose [ Time Frame: Month 6 - 9 ]
  5. Safety and tolerability as well as PK/PD/IG properties of canakinumab in the treatment of patients with Schnitzler syndrome. [ Time Frame: Whole study ]
  6. Changes in patient quality of life by using: Medical Outcome Short Form (36) Health Survey (SF-36®). [ Time Frame: Whole study ]
  7. Optimal canakinumab dose and frequency in patients with Schnitzler syndrome [ Time Frame: Whole study ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01276522

Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Principal Investigator: Anna Simon, MD PhD Radboud University


Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Radboud University Identifier: NCT01276522     History of Changes
Other Study ID Numbers: 2010-SS-Canakinumab
First Posted: January 13, 2011    Key Record Dates
Last Update Posted: May 24, 2012
Last Verified: May 2012

Keywords provided by Radboud University:
Schnitzler syndrome
IL-1 beta

Additional relevant MeSH terms:
Schnitzler Syndrome
Pathologic Processes
Monoclonal Gammopathy of Undetermined Significance
Immunoproliferative Disorders
Immune System Diseases
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs