Omalizumab for Lupus

Age at entry at least 18 years

Must give written informed consent prior to entry in the protocol. After preliminary screening visit under the Studies of the pathogenesis and natural history of systemic lupus erythematosus (SLE) protocol 94-AR-0066.

Must fulfill at least 4 of the criteria for SLE as defined by the American College of Rheumatology (Criteria published by EM Tan et al., Arthritis Rheum 25:1271, 1982, updated by MC Hochberg, Arthritis Rheum 40:1725, 1997).

Increased (>mean plus 2SD of healthy controls) autoantibody levels of any of the following IgE autoantibodies: anti-dsDNA, anti-Sm, anti-SSA.

Moderately active lupus defined by either of these (a or b) sets of criteria:

1. Chronic glomerulonephritis: Subjects who meet following conditions at 8 weeks after completion of adequate induction immunosuppressive therapy:

   -Subjects with lupus nephritis not achieving complete renal response

   defined as A) no active urinary sediment at the time of screening AND

   B) Urinary protein to creatinine ratio of \<1 mg/mg or 24 hours urinary protein of less than 1 gm at the time of screening.

   -Received at least 6 months of adequate induction immunosuppressive therapy (with pulse methylprednisolone, cyclophosphamide, azathioprine, cyclosporine, mycophenolate mofetil or high dose daily corticosteroids),

   AND all of the following as assessed at the time of screening:

   • less than 30 percent increase in creatinine compared to lowest level during treatment with induction immunosuppressive therapy,
   • proteinuria \< 1.5 times before starting treatment with induction immunosuppressive therapy,
   • \< 2 plus cellular casts in the urinary sediment (on a scale of 0-4), and

   • Extra-renal disease activity does not exceed 10 on the non-renal components of the SLEDAI 2K score.

     (b)Patients with no active lupus nephritis and moderately active extra-renal lupus defined as a SLEDAI 2K score in the range of 4-14, inclusive.

   Medications allowed at entry:

   • Prednisone less than or equal to 20 mg/day
   • Hydroxychloroquine up to 400 mg or 6.5 mg/kg/day (if > 400 mg)
   • Methotrexate up to 25 mg once a week
   • Azathioprine up to 2 mg/kg/day
   • Mycophenolate mofetil up to 3 grams/day
   • Cyclosporine up to 5 mg/kg/day

EXCLUSION CRITERIA:

Subjects will be excluded from the study if they meet any of the following criteria:

Pregnant or lactating women. Women of childbearing potential are required to have a negative pregnancy test at screening.

Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice two forms of birth control during and for a period of 3 months after the completion of the study. Acceptable forms of birth control include abstinence, barrier methods, implantable intrauterine devices and oral, transdermal patch or injectable contraceptives.

Weight > 105 kg

Total IgE level > 700 IU/mL

Active SLE requiring aggressive immunosuppressive therapy (ie CNS vasculitis, proliferative lupus nephritis requiring induction therapy, etc)

History of stroke, MI

Use of rituximab within 6 months or any other biologic within 5 half-life of the drug at the time the first administration of study medication.

Significant impairment of major organ function (lung, heart, liver, kidney)

Therapy with cyclophosphamide, pulse methylprednisolone or IVIG within 8 weeks at the time of first administration of study medication.

Initiation or a change in the dose of an ACE-inhibitor or ARB within 2 weeks of first study treatment.

Allergy to murine or human antibodies

History of anaphylaxis

Bronchial asthma treated within 12 months

Serum creatinine > 2.0 mg/dL

Previous history of ischemic heart disease or evidence of ischemic heart disease on ECG.

Congestive heart failure (New York Heart Association Class III and IV) or cardiomyopathy as per the assessment of clinician performing history and physical examination and to be confirmed by echocardiogram when clinically indicated.

History of thrombosis or recurrent 2nd trimester spontaneous abortions (3 or more) and elevated levels of anti-cardiolipin antibodies or lupus anticoagulant

History of malignancy with the exception of basal cell or squamous cell carcinoma of the skin or adequately treated in situ carcinoma of the cervix.

Active infection that requires the use of intravenous antibiotics and has not resolved at least 2 weeks prior to the administration of the first dose of study medication.

Active hepatitis B, hepatitis C or HIV infection

WBC \<2,500/microL or Hgb \<8.0 g/dL or platelets \<70,000/microL.

Alkaline phosphatase, ALT and/or AST > 2.0 times upper limit of normal (ULN)

Significant concurrent medical condition that, in the opinion of the Principal Investigator, could affect the patient's ability to tolerate or complete the study.

Live vaccines within 4 weeks of first injection.

Known or suspected Helminthic infection/infestation.

History of menorrhagia, GI Bleed or other clinically significant bleeding.

Subjects currently on anticoagulants or anti-platelet agents. Any subject who was on these agents in the past within the biologic half-life of these agents will also be excluded. Daily baby aspirin (81 mg) therapy for the prevention of cardiovascular disease (CVD) will be allowed.