Schnitzler SyndromePhase 2NCT01276522
Efficacy and Safety of Canakinumab in Schnitzler Syndrome
A Phase 2 study testing Canakinumab in people with Schnitzler Syndrome, run by Radboud University Medical Center at 1 site in Netherlands.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Schnitzler Syndrome
- What is being tested?
- Canakinumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteNetherlands
- Study dates
- Jan 2011to Dec 2011
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 13Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Radboud University Nijmegen Medical Centre
Nijmegen, 6500 HB
About this study
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.
Read the 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.
- Conditions
- Schnitzler Syndrome
- Being tested
- Canakinumab
- Keywords
- Schnitzler syndrome, IL-1 beta, Canakinumab, Ilaris, Treatment, Efficacy, Safety
- Medical subject headings
- Schnitzler Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CanakinumabDrug
Also called Ilaris
Monthly subcutaneous injection with 150mg Canakinumab for 6 months
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Canakinumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Complete or clinical remission at Day 14.
Measured: Day 14
Secondary outcomes (7)
Complete or clinical remission at Day 3 and Day 7
Measured: Day 3 and day 7
The prevention of disease relapse in patients who demonstrated complete remission at Day 14
Measured: 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
Measured: Whole study
Time to relapse after the last canakinumab dose
Measured: Month 6 - 9
Safety and tolerability as well as PK/PD/IG properties of canakinumab in the treatment of patients with Schnitzler syndrome.
Measured: Whole study
Changes in patient quality of life by using: Medical Outcome Short Form (36) Health Survey (SF-36®).
Measured: Whole study
Optimal canakinumab dose and frequency in patients with Schnitzler syndrome
Measured: Whole study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2011 (estimated)
- Study startJan 2011
- Primary completionMay 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Schnitzler SyndromeStudies of the same condition, open and under way.
- More trials run by Radboud University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis
- Responsible party
- Sponsor
- Investigators
- Anna Simon, MD PhD, Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01276522
- Sponsor's protocol ID
- 2010-SS-Canakinumab
- Status last verified
- May 2012
- First submitted
- 12 Jan 2011
- Last updated
- 24 May 2012
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 17586002de 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.
PubMed 16096327Ryan 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.
PubMed 17936890Schuster 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.
PubMed 20064173Martinez-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.
PubMed 15986356Lipsker 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.
PubMed 11204501Lachmann 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.
PubMed 19494217Lachmann 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.
PubMed 19364880de 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.
PubMed 23087179
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Canakinumab in Schnitzler Syndrome
- ClinicalTrials.gov ID
- NCT01276522
- Acronym / sponsor ID
- 2010-SS-Canakinumab
- Conditions
- Schnitzler Syndrome
- Keywords
- Schnitzler syndrome, IL-1 beta, Canakinumab, Ilaris, Treatment, Efficacy, Safety
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Collaborators
- Novartis
- Study start
- Jan 2011
- Primary completion
- May 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 13 Jan 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Canakinumab | Experimental | Drug: CanakinumabA 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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).
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CanakinumabAlso: IlarisMonthly subcutaneous injection with 150mg Canakinumab for 6 months | Drug | Canakinumab |
Primary outcome
Complete or clinical remission at Day 14.
Time frame: Day 14
7 secondary outcomes
Complete or clinical remission at Day 3 and Day 7
Time frame: 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
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
Time to relapse after the last canakinumab dose
Time frame: 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
Changes in patient quality of life by using: Medical Outcome Short Form (36) Health Survey (SF-36®).
Time frame: Whole study
Optimal canakinumab dose and frequency in patients with Schnitzler syndrome
Time frame: Whole study
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2012.
- Background: PubMed 17586002de 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.
- Background: PubMed 16096327de 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.
- Background: PubMed 17936890Ryan 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.
- Background: PubMed 20064173Schuster 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.
- Background: PubMed 15986356Martinez-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.
- Background: PubMed 11204501Lipsker 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.
- Background: PubMed 19494217Lachmann 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.
- Background: PubMed 19364880Lachmann 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.
- Derived from this study: PubMed 23087179de 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.
Related trials for Schnitzler Syndrome
RecruitingObservational study
A Study to Assess the Effectiveness and Safety of Canakinumab in Clinical Use in Patients With Schnitzler's Syndrome
Schnitzler Syndrome
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AutoInflammatory Disease Alliance Registry (AIDA)
Hereditary Autoinflammatory Diseases, Schnitzler Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Anna Simon, MD PhD principal investigator
Radboud University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Canakinumab in people with Schnitzler Syndrome, run by Radboud University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Complete or clinical remission at Day 14. (time frame: Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01276522, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2012.