A pilot open-label study to assess the efficacy and safety of tocilizumab (TCZ) in patients with active Schnitzler’s syndrome (SchS)

Phase 1

• Conditions: Schnitzler’s syndrome (SchS); MedDRA version: 19.1 Level: PT Classification code 10062908 Term: Schnitzler's syndrome System Organ Class: 10040785 - Skin and subcutaneous tissue disorders; Therapeutic area: Diseases [C] - Immune System Diseases [C20]

• Registration Number: EUCTR2016-003828-23-DE
• Lead Sponsor: Charité - Universitätsmedizin Berlin; Dpt. of Dermatology and Allergy

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2017-01-31
• Last Update Posted: 10 December 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: Not specified
• Target Recruitment: 12

Inclusion Criteria

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
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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 8
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

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)
o With Anakinra within 7 days prior to screening, with canakinumab within 100 days prior to screening
o with oral/parental corticosteriods greater than 10 mg/d within 2 weeks prior to screening
o with Cyclosporin A Methotrexate, Dapsone, Chloroquine, Hydroxychloroquine, Azathioprine, Cyclophosphamide within 4 weeks prior to screening
o other immunosuppressives within 4 weeks or 5 half lives prior to screening, whichever is longer
o 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.
o 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified