A Randomized, Double-Blind, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis

• INCLUSION CRITERIA:

Volunteers must satify all of the following inclusion criteria to be eligible for this study.

Subject must be at least 18 years of age and no older than 70 years of age.

Diagnosis of idiopathic anaphylaxis, a diagnosis of exclusion, assigned after other causes of anaphylaxis and other diseases in the differential diagnoses have been considered.

Anaphylaxis episodes (mild-severe) at least 6 times within the past 1 year period, documented according to medical records physician report, or patient report and 1 episode within the last 4 months, and with at least 1 of the following:

1. Elevated serum tryptase above baseline within 2 hours of the event.

2. Emergency room visit with documented anaphylaxis without an etiology established by the acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) [Grade 1]* and at least 1 of the following:

   1. Respiratory compromise or gastrointestinal involvement (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia, nausea, vomiting, or abdominal pain [Grade 2]*).
   2. Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, or incontinence [Grade 3]*).

3. Hospitalization for anaphylaxis: hospital records with documented anaphylaxis without known cause established by the acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-tongue-uvula) [Grade 1]*) and at least one of the following:

   1. Respiratory compromise or gastrointestinal involvement (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced peak expiratory flow, hypoxemia, nausea, vomiting, or abdominal pain [Grade 2]*).
   2. Reduced blood pressure or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, or incontinence [Grade 3]*).
4. Letter of referral, with copies of pertinent medical history and laboratory tests, from prospective study participant's local physician.
5. Ability to give informed consent.

6. Women of childbearing potential must have a negative beta-HCG serum or urine pregnancy test prior to each injection, and must agree to practice abstinence or effective contraception from initiation of the protocol and for 3 months following the last infusion of the study drug (effective contraception methods include abstinence; surgical sterilization of either partner, barrier methods such as diaphragm, condom, cap, or sponge; or hormonal contraception).

   • Severity grading of anaphylaxis

EXCLUSION CRITERIA:

A volunteer who satisfies any of the following exclusion criteria will be ineligible to participate in this study.

1. Presence of conditions which, in the judgment of the investigator or the referring physician, may put the subject at undue risk for study participation or travel (such as an acute infection, severe thrombocytopenia, coronary artery disease, uncontrolled hypertension, congestive heart failure, chronic beta blocker therapy such as atenolol or metoprolol, or myeloproliferative disease).
2. History of malignancy
3. Known cause for anaphylaxis or flushing
4. Diagnosis of mastocytosis
5. Inability to provide informed consent
6. Inability or refusal to undergo a bone marrow biopsy and aspirate
7. HIV positive or other known immunodeficiency
8. Active or chronic hepatitis
9. Use of any other investigational agent within 30 days of the study
10. Current use of chronic-oral corticosteroids or other immunosuppressant medications
11. Pregnant or nursing women
12. Positive pregnancy urine test
13. IgE levels and subject's weight that cause dosing to be above dosing guidelines.