Omalizumab to Treat Hyper-IgE (Job's) Syndrome
Condition: Hyper-IgE Syndrome; Job's Syndrome
MeSH terms: Job Syndrome; Syndrome
Study type: Interventional
Phase: Phase 1

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Omalizumab (Xolair)
Intervention type(s): Drug
Intervention MeSH terms: Omalizumab
Primary purpose: Treatment
Keywords: Phenotype; Monoclonal; Immunoglobulin; Immunodeficiency; Dermatitis; Job's Syndrome; Hyper-IgE Syndrome; HIES