Evaluation whether canakinumab leads to improvement of urticaria

Single center prospective placebo-controlled cross-over phase II study.

• To assess if canakinumab can induce clinical improvement and/or complete clinical remission of chronic idiopathic urticaria at week 4 as compared to placebo
• To compare canakinumab and placebo treated patients in the percentage who achieve complete clinical remission at week 1, 2, 4, and 8.
• To compare the percentage with clinical improvement as measured by UAS7 score at week 1, 2, 4, and 8 in canakinumab and placebo treated patients
• To compare the percentage of canakinumab and placebo treated patients with 75% and 100% improvement of their baseline (Run-in-period) UAS7 score at week 1,2,4,and 8
• To compare the daily wheal score for Days 1 to 7 in canakinumab and placebo treated patients

Inclusion criteria

• Diagnosis of chronic idiopathic urticaria for more than 6 weeks as confirmed by clinical and, if necessary, histological examination

• CIU of moderate to severe severity defined by all of the following

  • Physician severity score of 2 or 3 (on a scale from 0 - 3)
  • Run-in period of the diary-based UAS7 score of > 21 (on a scale from 0 - 42)
  • Symptomatic despite use of non-sedating antihistamine with or without concomitant leukotriene antagonist/corticosteroids

• Use of maintenance non-sedating antihistamine at a stable dose for at least 1 week prior to entering run-in period

• Maintenance corticosteroids at a dose of <20 mg/day or <0.4 mg/kg stable for at least the week prior to study entry for treatment of the patient's CIU will be allowed.

• Age: > 18 years.

• Signed informed consent

• Negative or unreactive QuantiFERON test (QFT-TB G In-Tube) or history of adequate treatment of active or latent tuberculosis.

Exclusion criteria:

• Age < 18 or > 70 years

• History of cancer except for treated basal cell carcinoma of the skin

• With active or recurrent bacterial, fungal or viral infection at the time of enrollment, including patients with evidence of Human Immunodeficiency Virus (HIV) infection, Hepatitis B and Hepatitis C infection, active or untreated latent tuberculosis.

• Patients currently treated with systemic immunosuppressive agents or following treatments in the specified period before the baseline visit:

  • corticosteroids =20 mg/day or >0.4 mg/kg for 1 week prior to study entry;
  • leukotriene antagonists for 1 week prior to study entry
  • colchicine, dapsone or mycophenolate mofetil for 3 weeks;
  • etanercept, leflunomide (documentation of a completion of a full cholestyramine elimination treatment after most recent leflunomide use will be required), thalidomide or ciclosporin for 4 weeks;
  • adalimumab or intravenous immunoglobulin for 8 weeks;
  • infliximab, 6-mercaptopurine, azathioprine, cyclophosphamide or chlorambucil for 12 weeks

• Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose

• Contraindications to the class of drugs under study, e.g. known hypersensitivity or allergy to class of drugs or the investigational product,

• Pregnant or lactating women, patients (men or women) planning a pregnancy during the duration of the study, lack of safe contraception.

• Safe contraception is defined as follows:

• Double-barrier contraception such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices together with condom use.

• Both men and women must use safe contraception (double-barrier as defined above) during the duration of the study and until 6 months after the study.

• Please note that female subjects who are surgically sterilized/hysterectomized or post-menopausal for longer than 2 years are not considered as being of child bearing potential.

• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the subject.

• Participation in another study with investigational drug within the 30 days preceding and during the present study.

• Previous enrolment into the current study.

• Enrolment of the investigator, his/her family members, employees and other dependent persons.