Efficacy and Safety of Canakinumab in Schnitzler Syndrome

May 23, 2012 updated by: Radboud University Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Enrollment (Actual)

8

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Nijmegen, Netherlands, 6500 HB
        • Radboud University Nijmegen Medical Centre

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Ilaris

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Complete or clinical remission at Day 14.
Time Frame: Day 14
Day 14

Secondary Outcome Measures

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Radboud University Medical Center

Collaborators

Novartis

Investigators

  • Principal Investigator: Anna Simon, MD PhD, Radboud university medical center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2011

Primary Completion (Actual)

May 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

January 12, 2011

First Submitted That Met QC Criteria

January 12, 2011

First Posted (Estimate)

January 13, 2011

Study Record Updates

Last Update Posted (Estimate)

May 24, 2012

Last Update Submitted That Met QC Criteria

May 23, 2012

Last Verified

May 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2010-SS-Canakinumab

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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