Efficacy and Safety of Canakinumab in Schnitzler Syndrome

NCT01276522 | Completed Phase 2

• 1 other identifier: 2010-SS-Canakinumab
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Schnitzler Syndrome

Keywords

Schnitzler syndrome; IL-1 beta; Canakinumab; Ilaris; Treatment; Efficacy; Safety

Outcome Measures

Primary Outcomes (1)

• Complete or clinical remission at Day 14.

  Day 14

Secondary Outcomes (7)

• Complete or clinical remission at Day 3 and Day 7

  Day 3 and day 7

• The prevention of disease relapse in patients who demonstrated complete remission at Day 14

  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

  Whole study

• Time to relapse after the last canakinumab dose

  Month 6 - 9

• Safety and tolerability as well as PK/PD/IG properties of canakinumab in the treatment of patients with Schnitzler syndrome.

  Whole study

Study Arms (1)

Canakinumab

EXPERIMENTAL

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

Interventions

Canakinumab DRUG

Monthly subcutaneous injection with 150mg Canakinumab for 6 months

Also known as: Ilaris

Canakinumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Radboud University Medical Center: lead
• Novartis: collaborator

Study Sites (1)

Radboud University Nijmegen Medical Centre

Nijmegen, 6500 HB, Netherlands

Location

Related Publications (9)

• 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. doi: 10.1016/j.semarthrit.2007.04.001. Epub 2007 Jun 21.

  PMID: 17586002 BACKGROUND

• 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. doi: 10.1136/ard.2005.045245. Epub 2005 Aug 11.

  PMID: 16096327 BACKGROUND

• 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. doi: 10.1016/j.jaci.2007.09.021. Epub 2007 Oct 22. No abstract available.

  PMID: 17936890 BACKGROUND

• Schuster C, Kranke 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.

  PMID: 20064173 BACKGROUND

• Martinez-Taboada VM, Fontalba A, Blanco R, Fernandez-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. doi: 10.1002/art.21101. No abstract available.

  PMID: 15986356 BACKGROUND

• 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. doi: 10.1097/00005792-200101000-00004.

  PMID: 11204501 BACKGROUND

• 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.

  PMID: 19494217 BACKGROUND

• 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.

  PMID: 19364880 BACKGROUND

• de Koning HD, Schalkwijk J, van der Ven-Jongekrijg J, Stoffels M, van der Meer JW, Simon A. Sustained efficacy of the monoclonal anti-interleukin-1 beta antibody canakinumab in a 9-month trial in Schnitzler's syndrome. Ann Rheum Dis. 2013 Oct;72(10):1634-8. doi: 10.1136/annrheumdis-2012-202192. Epub 2012 Oct 19.

  PMID: 23087179 DERIVED

MeSH Terms

Conditions

Schnitzler Syndrome

Interventions

canakinumab

Condition Hierarchy (Ancestors)

Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Anna Simon, MD PhD

  Radboud University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2011
• First Posted: January 13, 2011
• Study Start: January 1, 2011
• Primary Completion: May 1, 2011
• Study Completion: December 1, 2011
• Last Updated: May 24, 2012

Record last verified: 2012-05

Locations

NL (1)