Efficacy and Safety of Canakinumab in Schnitzler Syndrome

Brief Title

Efficacy and Safety of Canakinumab in Schnitzler Syndrome

Official Title

Efficacy and Safety of Canakinumab in Schnitzler Syndrome

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.
    

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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Complete or clinical remission at Day 14.

Secondary Outcome

 Complete or clinical remission at Day 3 and Day 7

Condition

Schnitzler Syndrome

Intervention

Canakinumab

Study Arms / Comparison Groups

 Canakinumab
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

8

Start Date

January 2011

Completion Date

December 2011

Primary Completion Date

May 2011

Eligibility Criteria

        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 :
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               -  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
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Anna Simon, MD PhD, , 

Location Countries

Netherlands

Location Countries

Netherlands

Administrative Informations


NCT ID

NCT01276522

Organization ID

2010-SS-Canakinumab


Responsible Party

Sponsor

Study Sponsor

Radboud University

Collaborators

 Novartis

Study Sponsor

Anna Simon, MD PhD, Principal Investigator, Radboud University


Verification Date

May 2012