Efficacy and Safety of Canakinumab in Schnitzler Syndrome

This study has been completed.
Sponsor:
Collaborator:
Novartis
Information provided by (Responsible Party):
Radboud University
ClinicalTrials.gov Identifier:
NCT01276522
First received: January 12, 2011
Last updated: May 23, 2012
Last verified: May 2012
  Purpose

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 Intervention Phase
Schnitzler Syndrome
Drug: Canakinumab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Efficacy and Safety of Canakinumab in Schnitzler Syndrome

Resource links provided by NLM:


Further study details as provided by Radboud University:

Primary Outcome Measures:
  • Complete or clinical remission at Day 14. [ Time Frame: Day 14 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Complete or clinical remission at Day 3 and Day 7 [ Time Frame: Day 3 and day 7 ] [ Designated as safety issue: No ]
  • The prevention of disease relapse in patients who demonstrated complete remission at Day 14 [ Time Frame: Day 15 until end ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]
  • Time to relapse after the last canakinumab dose [ Time Frame: Month 6 - 9 ] [ Designated as safety issue: No ]
  • Safety and tolerability as well as PK/PD/IG properties of canakinumab in the treatment of patients with Schnitzler syndrome. [ Time Frame: Whole study ] [ Designated as safety issue: Yes ]
  • Changes in patient quality of life by using: Medical Outcome Short Form (36) Health Survey (SF-36®). [ Time Frame: Whole study ] [ Designated as safety issue: No ]
  • Optimal canakinumab dose and frequency in patients with Schnitzler syndrome [ Time Frame: Whole study ] [ Designated as safety issue: No ]

Enrollment: 8
Study Start Date: January 2011
Study Completion Date: December 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 : 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01276522

Locations
Netherlands
Radboud University Nijmegen Medical Centre
Nijmegen, Netherlands, 6500 HB
Sponsors and Collaborators
Radboud University
Novartis
Investigators
Principal Investigator: Anna Simon, MD PhD Radboud University
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Radboud University
ClinicalTrials.gov Identifier: NCT01276522     History of Changes
Other Study ID Numbers: 2010-SS-Canakinumab
Study First Received: January 12, 2011
Last Updated: May 23, 2012
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Radboud University:
Schnitzler syndrome
IL-1 beta
Canakinumab
Ilaris
Treatment
Efficacy
Safety

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

ClinicalTrials.gov processed this record on October 23, 2014