Efficacy and Safety of Canakinumab in Schnitzler Syndrome

Schnitzler Syndrome Clinical Trial

Official title:

Efficacy and Safety of Canakinumab in Schnitzler Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01276522
• Other study ID #: 2010-SS-Canakinumab
• Status: Completed
• Phase: Phase 2
• First received: January 12, 2011
• Last updated: May 23, 2012
• Start date: January 2011
• Est. completion date: December 2011

Study information

• Verified date: May 2012
• Source: Radboud University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8
• Est. completion date: December 2011
• Est. primary completion date: May 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Schnitzler Syndrome
• Syndrome

Intervention

Drug:
• Canakinumab
Monthly subcutaneous injection with 150mg Canakinumab for 6 months

Locations

Country	Name	City	State
Netherlands	Radboud University Nijmegen Medical Centre	Nijmegen

Sponsors (2)

Lead Sponsor	Collaborator
Radboud University	Novartis

Country where clinical trial is conducted

Netherlands, 

References & Publications (8)

de Koning HD, Bodar EJ, Simon A, van der Hilst JC, Netea MG, van der Meer JW. Beneficial response to anakinra and thalidomide in Schnitzler's syndrome. Ann Rheum Dis. 2006 Apr;65(4):542-4. Epub 2005 Aug 11. — View Citation

de Koning HD, Bodar EJ, van der Meer JW, Simon A; Schnitzler Syndrome Study Group. Schnitzler syndrome: beyond the case reports: review and follow-up of 94 patients with an emphasis on prognosis and treatment. Semin Arthritis Rheum. 2007 Dec;37(3):137-48. Epub 2007 Jun 21. Review. — View Citation

Lachmann HJ, Kone-Paut I, Kuemmerle-Deschner JB, Leslie KS, Hachulla E, Quartier P, Gitton X, Widmer A, Patel N, Hawkins PN; Canakinumab in CAPS Study Group. Use of canakinumab in the cryopyrin-associated periodic syndrome. N Engl J Med. 2009 Jun 4;360(23):2416-25. doi: 10.1056/NEJMoa0810787. — View Citation

Lachmann HJ, Lowe P, Felix SD, Rordorf C, Leslie K, Madhoo S, Wittkowski H, Bek S, Hartmann N, Bosset S, Hawkins PN, Jung T. In vivo regulation of interleukin 1beta in patients with cryopyrin-associated periodic syndromes. J Exp Med. 2009 May 11;206(5):1029-36. doi: 10.1084/jem.20082481. Epub 2009 Apr 13. — View Citation

Lipsker D, Veran Y, Grunenberger F, Cribier B, Heid E, Grosshans E. The Schnitzler syndrome. Four new cases and review of the literature. Medicine (Baltimore). 2001 Jan;80(1):37-44. Review. — View Citation

Martinez-Taboada VM, Fontalba A, Blanco R, Fernández-Luna JL. Successful treatment of refractory Schnitzler syndrome with anakinra: comment on the article by Hawkins et al. Arthritis Rheum. 2005 Jul;52(7):2226-7. — View Citation

Ryan JG, de Koning HD, Beck LA, Booty MG, Kastner DL, Simon A. IL-1 blockade in Schnitzler syndrome: ex vivo findings correlate with clinical remission. J Allergy Clin Immunol. 2008 Jan;121(1):260-2. Epub 2007 Oct 22. — View Citation

Schuster C, Kränke B, Aberer E, Arbab E, Sturm G, Aberer W. Schnitzler syndrome: response to anakinra in two cases and a review of the literature. Int J Dermatol. 2009 Nov;48(11):1190-4. doi: 10.1111/j.1365-4632.2009.04151.x. Review. — View Citation

Outcome

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