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Schnitzler's SyndromePhase 2TOCISCHNCT03046381

Tocilizumab in Patients With Schnitzler's Syndrome

A Phase 2 study testing Tocilizumab in people with Schnitzler's Syndrome, run by Karoline Krause at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Schnitzler's Syndrome (SchS) is a late-onset multifactorial autoinflammatory disease characterized by chronic urticarial skin lesions and a monoclonal gammopathy usually belonging to the immunoglobulin M (IgM) or IgG class. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Schnitzler's Syndrome
What is being tested?
Tocilizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteGermany
Study dates
19 Jul 2017to 10 Apr 2019
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

  • Adults (18 years or older)
  • SchS diagnosis based on Strasbourg clinical criteria
  • Active SchS, refractory to treatment with antihistamines, NSAIDS or colchicine, hydroxychloroquine or dapsone
  • Patients who have a symptom score (PGA) of at least 8 (0-20) at baseline
  • If necessary, concurrent/ongoing treatment with a stable dose of systemic corticosteroids not greater than 10mg/d for 14 days prior to screening
  • If necessary, concurrent/ongoing treatment with a stable dose of antihistamines and NSAIDs for 7 days prior to screening
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  • Able to read, understand and willing to sign the informed consent form and abide with study procedures
  • Willing, committed and able to return for all clinic visits and complete all study-related procedures, including willingness to have SC injections administered by a qualified person
  • In females of childbearing potential: Negative pregnancy test within 28 days of randomization; males and females willing to use highly effective contraception (Pearl-Index < 1) during study treatment and for a minimum of 3 months after last dose of TCZ. Pregnancies occurring up to 90 days after the completion of the study medication must be reported to the investigator. A woman will be considered not of childbearing potential if she is post-menopausal for greater than two years or surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy)
  • Subjects are considered eligible, if they meet the following tuberculosis (TB) screening criteria: no history of latent or active TB prior to screening, no signs or symptoms suggestive of active TB, no recent close contacts with a person with active TB, and negative QuantiFERON-TB test at screening (if QuantiFERON-TB test is positive, the patient can only be included if active TB is ruled out with appropriate measurements according to standard of care, e.g. the patient is pre-treated with isoniazide for 4 weeks).
  • No participation in other clinical trials 4 weeks before and after participation in this study

Who cannot join

  • Major surgery (including joint surgery) within 8 weeks prior to screening or planned major surgery within 6 months following randomization.
  • Concurrent/ongoing treatment with biologics or recent treatment (less than 5 half lives)
  • With Anakinra within 7 days prior to screening, with canakinumab within 100 days prior to screening
  • with oral/parental corticosteriods greater than 10 mg/d within 2 weeks prior to screening
  • with Cyclosporin A Methotrexate, Dapsone, Chloroquine, Hydroxychloroquine, Azathioprine, Cyclophosphamide within 4 weeks prior to screening
  • other immunosuppressives within 4 weeks or 5 half lives prior to screening, whichever is longer
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  • Previous treatment within six months of randomization with any cell-depleting therapies, including investigational agents or approved therapies, some examples include: CAMPATH, anti-CD4, anti-CD5, anti-CD3, anti-CD19 and anti-CD20.
  • Treatment with intravenous gamma globulin, plasmapheresis or Prosorba column within 6 months of baseline.
  • Treatment with a live (attenuated) virus vaccine within 4 weeks prior to Baseline visit
  • Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial
  • Any previous treatment with alkylating agents such as chlorambucil, or with total lymphoid irradiation.
  • History of severe allergic or anaphylactic reactions to human, humanized or murine monoclonal antibodies.
  • An abnormal chest radiograph consistent with clinical signs of prior or present tuberculosis infection whether or not previously treated with anti-tuberculosis agents
  • Significant concomitant illness such as, but not limited to, cardiac, renal, neurological, endocrinological, metabolic, or lymphatic disease that would adversely affect the subject's participation or evaluation in this study
  • Evidence of current HIV, Hepatitis B, or Hepatitis C infection by clinical or serological history
  • Presence of any of the following laboratory abnormalities at enrollment visit: serum creatinine > 1.6 mg/dL (141 µmol/L) in female patients and > 1.9 mg/dL (168 µmol/L) in male patients, WBC <3,000/µl; platelet count <100000/µl ; ALT or AST >2 x ULN or total bilirubin >ULN, Hemoglobin <8.0 g/dL, neutrophil count <2,000 cells/µl or lymphocyte count <500/ µl
  • Evidence of active, recurrent or latent systemic infection
  • Active systemic inflammatory condition other than SchS including, but not limited to, rheumatoid arthritis
  • History of malignancies within five years prior to screening other than a successfully treated non-metastatic cutaneous, basal, or squamous cell carcinoma and/or in situ cervical cancer
  • Lactating females or pregnant females
  • Enrollment in another investigational treatment or device study or use of an investigational agent, or less than 4 weeks or 5 half-lives, whichever is longer, since end of another investigational device or drug trial
  • Subjects for whom there is concern about compliance with the protocol procedures
  • Any medical condition which, in the opinion of the Investigator, would interfere with participation in the study or place the subject at risk
  • History of substance abuse (drug or alcohol) or any other factor (e.g., serious psychiatric condition) that could limit the subject's ability to comply with study procedures.
  • Patients with known hypersensitivity to tocilizumab

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • Charité - Universitätsmedizin Berlin, Dpt. of Dermatology and Allergy

    Berlin, Germay, 10117

Other trials in Germany

About this study

Official title: A Pilot Open-label Study to Assess the Efficacy and Safety of Tocilizumab in Patients With Active Schnitzler's Syndrome

Schnitzler's Syndrome (SchS) is a late-onset multifactorial autoinflammatory disease characterized by chronic urticarial skin lesions and a monoclonal gammopathy usually belonging to the immunoglobulin M (IgM) or IgG class. Symptoms associated with SchS are recurrent fever attacks, bone and muscle pain, arthralgia or arthritis, fatigue and lymphadenopathy. SchS is a rare disease with approximately 300 cases reported in the literature. The nature of SchS is chronic without known reports about spontaneous remissions. Disease onset occurs around the age of 50. About 15% of patients eventually develop a lymphoproliferative disorder, most often Waldenström's macroglobulinemia. The pathogenesis of SchS is still not well defined. Functional ex vivo studies showed excessive cytokine production (IL-1ß, IL-6 and IL-18) of peripheral blood monocytes (PBMCs) in SchS as compared to healthy controls. In addition to excessive IL-6 secretion from PBMCs IL-6 has repeatedly been reported to be elevated in the serum of SchS patients too. As IL-6 plays a major role in the development of multiple myeloma, IL-6 may also be associated with the formation of lymphoproliferative disorders in SchS.

Until now, there is no approved standard therapy available for the treatment of SchS. Non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and other immunosuppressive agents have been reported to provide variable relief from symptoms of bone pain and arthralgia. Case reports and small studies about successful treatment of SchS with anti-IL-1 blockers (anakinra, rilonacept and canakinumab) accumulate. However, there have been complete and partial treatment failures to anti-IL-1 blockade in SchS. In these patients, anti-IL-6 treatment (tocilizumab [TCZ]) demonstrated to be very effective in reducing the clinical symptoms and inflammation markers in SchS. TCZ treatment has proved to be very effective, well-tolerated and safe in other acquired autoinflammatory disorders, systemic juvenile idiopathic arthritis (sJIA) and adult-onset Still's disease that share many clinical features (rash, fever, joint involvement, lymphadenopathy, fatigue) and excessive cytokine production with SchS. The study consists of a run-in baseline period of 1-4 weeks followed by an open-label 20-week TCZ treatment phase with weekly s.c. injections (TCZ 162mg), followed by an optional study extension up to a total of 1 year with ongoing once weekly TCZ 162mg injections and a 4 week period of follow-up.

Being tested
Tocilizumab
Medical subject headings
Schnitzler Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TocilizumabDrug

    Also called RoActemra®

    Tocilizumab 162mg 1x weekly s.c.

Study groups in NCT03046381
Study groupRoleWhat they receive
TocilizumabOtherTocilizumab 162mg 1x weekly as subcutaneous syringe
Receives: Drug: Tocilizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Physician global assessment

    Change in the investigator's assessment of total disease activity (physician global assessment [PGA]) between baseline and TCZ Treatment

    Measured: Baseline vs. week 20

Secondary outcomes (8)

  1. Complete responders

    Proportion of patients with complete response (based on PGA with no or minimal overall autoinflammatory disease activity and CRP </= 10 mg/l)

    Measured: Week 20

  2. Schnitzler Activity Score

    Change in the patient based Schnitzler Activity Score (SchAS) during the treatment period (The SchAS combines the key symptoms of SchS).

    Measured: 60 weeks

  3. Inflammation marker CRP

    Change in CRP levels during the treatment period

    Measured: 60 weeks

  4. Inflammation marker SAA

    Change in SAA levels during the treatment period

    Measured: 60 weeks

  5. Inflammation marker S100 A8/9

    Change in S100 A8/9 levels during the treatment period

    Measured: 60 weeks

  6. Overall quality of life

    Change in the patient's quality of life (assessed by the SF-36)

    Measured: 60 weeks

  7. Dermatology-specific quality of life

    Change in the patient's quality of life (assessed by the Dermatology Life Quality Index)

    Measured: 60 weeks

  8. Safety and tolerability assessed by adverse event reporting over the whole study period

    Adverse event reporting over the whole study period

    Measured: 60 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Feb 2017 (estimated)
  2. Study start19 Jul 2017
  3. Primary completion11 Mar 2019
  4. Study completion10 Apr 2019

Resources

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)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03046381
Sponsor's protocol ID
TOCISCH
Acronym
TOCISCH
Status last verified
Feb 2020
First submitted
5 Jan 2017
Last updated
17 Feb 2020
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Bonnekoh H, Frischbutter S, Roll S, Maurer M, Krause K. Tocilizumab treatment in patients with Schnitzler syndrome: An open-label study. J Allergy Clin Immunol Pract. 2021 Jun;9(6):2486-2489.e4. doi: 10.1016/j.jaip.2021.01.024. Epub 2021 Feb 2. No abstract available.

    PubMed 33545397

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tocilizumab in people with Schnitzler's Syndrome, run by Karoline Krause at 1 site in Germany.

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 11 inclusion and 25 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 17 Feb 2020. 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 Germany. 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?

Physician global assessment (time frame: Baseline vs. week 20). 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 NCT03046381, which also lists 1 linked publication.

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 17 Feb 2020.

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