Safety and Efficacy of Abatacept in Subjects With Chronic Urticaria Who Have Had an Inadequate Response to Anti-histamine Therapy

Inclusion Criteria

• Chronic active urticaria defined as symptoms > 50% of days or 3 days/week for more than 12 weeks
• 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) AND failure to respond to at least maximally approved dosages of 2 different antihistamine therapies
• One of the following 3 conditions:
• Previous or ongoing requirement for corticosteroids for symptom control OR
• Prior steroid treatment with steroid discontinuation due to unacceptable morbidity
• Previous or current use (without symptom control or with unacceptable morbidity: e.g., hypertension from cyclosporine, hemolysis from dapsone) of immunomodulatory treatment for urticaria (e.g., hydroxychloroquine, methotrexate, sulfasalazine, dapsone, cyclosporine, intravenous immunoglobulin (IVIg), mycophenolate, azathioprine, etc)
• High baseline score for pruritis (at least 2 on a 3 point scale)
• No underlying etiology clearly defined for urticaria
• Patients should exhibit evidence of underlying autoimmunity of at least one of the following:
• elevated erythrocyte sedimentation rate (ESR), C-Reactive Protein (CRP), anti-nuclear antibody (ANA)
• extractable nuclear antigens
• Thyroid antibodies
• other autoantibodies (e.g., intrinsic factor, parietal cell, ovarian), *elevated complement levels
• clinical characteristics suggestive of systemic autoimmune disease but without satisfying criteria for another diagnosis (e.g., arthralgias, myalgias, arthritis, low grade fever, significant fatigue associated with outbreaks)
• family history of autoimmune disease including thyroid autoimmunity
• a biopsy showing perivascular lymphocytic or mixed cellular infiltrate without vasculitis
• Concomitant use of hydroxychloroquine, methotrexate, or sulfasalazine will be permitted if dose stable for at least 8 weeks
• Concomitant use of steroids (≤ 15 mg/d Prednisone or equivalent) will be permitted if stable for 4 weeks and patient agrees to continue dose for the first 90 days
• Negative pregnancy test (for women of child-bearing age)
• Men and women of reproductive potential must agree to use an acceptable birth control during treatment and for 3 months after treatment
• No planned elective surgical procedures for at least 6 months from day#1

Exclusion Criteria

• Current use of other immunosuppressive medications (cyclosporine, tacrolimus, sirolimus, IVIg, cyclophosphamide, mycophenolate mofetil, azathioprine). Any such medication will be discontinued for at least 4 weeks before study drug start.
• Concomitant treatment with corticosteroids (≤ 15 mg/d), hydroxychloroquine, methotrexate, and sulfasalazine will be permitted if doses are stable at least 8 weeks
• Treatment with an 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 of randomization
• Prior treatment with Abatacept (Orencia®)
• Previous treatment with Rituximab (MabThera®/Rituxan®), unless 6 months after administration AND B cell reconstitution has occurred into normal range
• History of severe allergic or anaphylactic reactions to monoclonal antibodies or Fc fusion proteins
• History of significant laryngeal edema, tongue swelling, or airway compromise in the setting of urticarial/angioedema episode (isolated perioral, lip, and periorbital edema will not be exclusionary)
• Known history of Human Immunodeficiency Virus (HIV), Hepatitis B and/or Hepatitis C
• purified protein derivative (PPD) testing as part of screening that is positive*
• HIV, Hepatitis B surface antigen or Core Antibody positive, or anti Hepatitis C Antibody positive detected with screening
• History of recurrent significant infection, active bacterial, viral, fungal, mycobacterial, or other infection excluding fungal infections of nail beds, or major infection requiring hospit