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)