Omalizumab to Treat Hyper-IgE (Job's) Syndrome
Omalizumab to Treat Hyper-IgE (Job's) Syndrome
This study will evaluate the safety and effectiveness of a laboratory-made antibody called
 omalizumab in patients with Job's syndrome, or hyper-IgE syndrome (HIES). Patients with HIES
 have very high levels of IgE antibody, a protein made by white blood cells. IgE plays an
 important role in starting allergic reactions in the body and may be related to some HIES
 symptoms, such as skin rashes and asthma. Patients also have frequent lung infections, easily
 broken bones and other symptoms. Omalizumab, which is approved to treat allergic asthma, is
 directed against IgE. This study will see if blocking IgE with omalizumab in HIES patients is
 safe and if it can reduce patients' IgE count. It will also look at how the body handles
 omalizumab and how it affects patients' symptoms.

 Patients 6 years of age or older with HIES may be eligible for this study. Each candidate is
 screened with a medical history, physical examination, skin examination and blood test.

 Participants receive an injection of omalizumab under the skin once every 2 weeks for 6
 doses. At the time of each injection, patients are examined by a doctor, answer questions
 about their symptoms and have a blood sample drawn. After the sixth dose, patients have a
 physical examination, blood tests, skin examination and lung function tests. At follow-up
 visits scheduled 2, 4 and 6 months after the last dose of omalizumab, patients have a
 physical examination, answer questions about their symptoms, and have a blood sample drawn.
 Patients who show a significant response to omalizumab stay off the drug for 3 months after
 the last dose and then discuss with their study doctor and referring doctor about continuing
 the medicine.
The hyper-IgE syndromes (HIES) are disorder characterized by markedly elevated serum IgE
 levels, eosinophilia, dermatitis, and recurrent skin and lung infections. The autosomal
 dominant form of HIES, Job's syndrome, is also characterized by skeletal abnormalities and
 lung cysts, and is caused primarily by a mutation in the STAT3 gene. The most common allergic
 or atopic symptoms seen in HIES include a characteristic rash and bronchial
 hyper-responsiveness. The rash tends to respond to systemic antimicrobials, topical
 antiseptics, mad steroids. It is unclear what the role, if any, IgE plays in the pathogenesis
 of these allergic (and perhaps non-allergic) phenotypes.

 Omalizumab is a humanized monoclonal antibody specific for the FcepsilonRI portion of IgE
 that does not cross-link IgE. It has been used for amelioration of severe asthma and food
 allergies, and is being studied in a number of other allergic diseases. This study aims to
 determine whether administration of omalizumab is safe in patients with HIES, effective in
 inducing FcepsilonRI downregulation, and in reducing some of the cutaneous and/or respiratory
 symptoms associated with HIES. It also aims to determine whether the present maximum
 indicated dose has any effect on patients with HIES who have greater than indicated IgE
 levels. Finally, it aims to assess the safety and pharmacodynamic profile of increased doses
 of omalizumab likely to be required in most patients with HIES.
-INCLUSION CRITERIA:

 1. All Subjects must be at least 6 years of age and no older than 76 years of age (as per
 original safety studies).

 2. All subjects must meet the established diagnostic criteria for HIES as determined by
 the NIH scoring system, with a score greater than 40, or have a mutation in the STAT3
 gene.

 3. Baseline values within the following laboratory ranges:

 -  White blood cell count greater than or equal to 3,300 cells/microliter.

 -  Absolute neutrophil count greater than or equal to 1,000 cells/microliter.

 -  Hemoglobin greater than or equal to 10 g/dL.

 -  Platelet count greater than or equal to 100,000 platelets/micoliter.

 4. Women of childbearing potential only: negative urine pregnancy test. Both men and
 women and their partners must agree to practice abstinence or effective contraception
 from initiation of the protocol and for 2 months following the last dose 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).

 5. Weight (Kg) times serum IgE (IU/mL) less than 3,000,000, then as above greater than
 63,000, less than 3,000,000.

 6. Patients in tier II must be 16 years or older.

 7. Preference will be given to patients with dermatitis.

 8. Subjects (guardians for younger patients) must be able to give informed consent (or
 assent as appropriate).

 9. Subjects must already be signed to other NIH studies on HIES.

 10. Subjects must be willing to maintain their current regimens for skin care,
 prophylactic antibiotics (if applicable), and any asthma related oral or inhaled
 medications. Albuterol rescue medications may be used as needed.

 11. Patients participating in protocols at the National Institutes of Health are expected
 to have a primary physician outside of the NIH.

 EXCLUSION CRITERIA:

 1. Pregnant or nursing women.

 2. HIV positive diagnosis.

 3. Use of any other investigational agent within 30 days of the study.

 4. Any condition that, in the investigator's opinion, places the patient at undue risk by
 participating in the study.

 5. Previous anaphylaxis to the study medication.