Cold Urticaria Treatment With Xolair (CUTEX)

Urticaria is a very frequent skin condition characterised by transient wheal and flare type skin reactions associated with severe pruritus. Cold contact urticaria (CCU) is a frequent form of physical urticaria that is characterized by the development of wheal and flare type skin reactions due to the release of histamine and other proinflammatory mast cell mediators following exposure of the skin to cold. Among all physical urticaria subtypes the frequency of CCU varies between 5.7% and 33.8% in different studies. Physical urticarias including CCU are known to severely impair the quality of life of affected patients.

The treatment of choice in CCU, as well as in other inducible forms and spontaneous urticaria, are non-sedating H1 antihistamines. Recent data have shown that updosing of H1 blockers is significantly more effective in reducing symptoms in cold urticaria than standard-dose treatment. Thus, patients who cannot be sufficiently controlled with standard-dose antihistamines should receive high-dose H1 blockers up to 4 times the standard dose as recommended by the new international guidelines for the management of urticaria.

Previous phase II studies in patients with chronic spontaneous urticaria have shown favorable results for the treatment with omalizumab (Xolair®). Proof-of-concept data from completed studies suggest that omalizumab improves urticaria in patients with chronic spontaneous urticaria who have failed treatment with H1 antihistamines as well as those who have failed treatment with a combination of H1 and H2 antihistamines and a leukotriene receptor antagonist. In addition, two case reports of patients with severe therapy refractory CCU treated with omalizumab reported a complete response with no urticarial symptoms after cold challenge. In summary, these data suggest that omalizumab may have a beneficial effect in the treatment of CCU.

• Drug: Omalizumab
  150mg, s.c., every 4 weeks
  Other Name: Xolair
• Drug: Omalizumab
  300mg, s.c., every 4 weeks
  Other Name: Xolair
• Drug: Placebo
  Placebo, s.c., every 4 weeks

• Experimental: Omalizumab 150mg
  Intervention: Drug: Omalizumab
• Experimental: Omalizumab 300mg
  Intervention: Drug: Omalizumab
• Placebo Comparator: Placebo
  Intervention: Drug: Placebo

Inclusion Criteria:

• Adults (18 years or older)
• Informed consent signed and dated
• Able to read, understand and willing to sign the informed consent form and abide with study procedures
• Diagnosis of CCU lasting for at least 6 months
• 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; females willing to use highly effective contraception (Pearl-Index < 1). 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)
• No participation in other clinical trials 4 weeks before and after participation in this study

Exclusion Criteria:

• Patients with acute urticaria
• Concurrent/ongoing treatment with immunosuppressives (e.g. systemic steroids, cyclosporine, methotrexate, dapsone or others) within 4 weeks or 5 half lives prior to day 0, whichever is longer
• Significant medical condition rendering the patient immunocompromised or not suitable for a clinical trial
• Significant concomitant illness that would adversely affect the subject's participation or evaluation in this study
• 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 cancer
• Presence of clinically significant laboratory abnormalities
• Lactating females or pregnant females
• 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) within the last 5 years that could limit the subject's ability to comply with study procedures
• Subjects who are detained officially or legally to an official institute
• Previous use of omalizumab within the last 6 months
• Intake of antihistamines or leukotriene antagonists within 7 days prior to visit 1
• Intake of oral corticosteroids within 14 days prior to visit 1
• Use of depot corticosteroids or chronic systemic corticosteroids within 21 days before beginning of the study
• Known hypersensitivity to any ingredients, including excipients (sucrose, histidine, polysorbate 20) of the study medication or drugs related to omalizumab (e.g.: monoclonal antibodies, polyclonal gammaglobulin)