Safety Study of Rituximab (Rituxan®) in Chronic Urticaria

Major Inclusion Criteria: Chronic urticaria defined as symptoms >50% of the days or 3 days per week for more than 12 weeks Previous requirement for sustained or recurrent use of corticosteroids OR requirement for immunomodulatory treatment for urticaria (eg hydroxychloroquine, sulfasalazine, dapsone, cyclosporine, IVIg, etc) OR ongoing symptoms for at least 6 months duration with failure to respond at least maximally approved dosages of 2 different antihistamine therapies Chronic therapy with stable doses of antihistamines for at least 4 weeks. Patients may be taking more than one antihistamine or be taking combinations of antihistamines and leukotriene receptor antagonists High baseline score for pruritis (at least 2 on a 3 point scale) No underlying etiology clearly defined for urticaria Evidence of underlying autoimmunity as evidenced by clinical and laboratory criteria Concomitant use of hydroxychloroquine, sulfasalazine, or dapsone permitted if doses stable for at least 12 weeks Negative serum pregnancy test (for women of child-bearing age) Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment. No planned elective surgical procedures for at least 6 months Major Exclusion Criteria: Concomitant use of corticosteroids Current use of immunosuppressive medication (cyclosporine, IVIg, methotrexate, cyclophosphamide). Any such medication will be discontinued for at least 6 weeks before screening. Treatment with any investigational agent within 4 weeks of screening or 5 half-lives of the investigational drug (whichever is longer) Receipt of a live vaccine within 4 weeks prior to randomization Previous treatment with Rituximab (MabThera® / Rituxan®) Prior antibody therapy History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies Known history of HIV seropositivity (testing will be performed at screening) History of Hepatitis B and/or Hepatitis C (Hep BsAg and Hep C Ab will be obtained at screening) History of recurrent significant infection or history of recurrent bacterial infections Known active bacterial, viral, fungal, mycobacterial, or other infection (including tuberculosis or atypical mycobacterial disease, but excluding fungal infections of nail beds) Any major episode of infection requiring hospitalization or treatment with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to screening Known immunodeficiency syndrome, hypogammaglobulinemia, etc. Systemic lupus erythematosus Pregnancy (a negative serum pregnancy test will be performed for all women of childbearing potential within 7 days of treatment) or lactation Malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix. Atopic dermatitis Clinically relevant medical conditions (cardiovascular including poorly controlled hypertension or coronary artery disease, pulmonary, metabolic, renal, hepatic, psychiatric) or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications Plans or need to receive live viral vaccination over course of the study (e.g. Flu-Mist TM)