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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: A Randomized Double-Blinded, Placebo-Controlled Study of Omalizumab for Idiopathic Anaphylaxis

Brief Summary:

Background:

• Omalizumab is an approved drug for the treatment of asthma by the Food and Drug Administration.
• Researchers are now studying this drug in a double-blind placebo-controlled manner to assess efficacy in patients with idiopathic anaphylaxis (recurrent hypersensitive allergic episodes for which a cause is not identified).
• The study will improve understanding of the mechanisms involved in anaphylactic reactions as a response to the downregulation (a decrease in the number of receptors on the surface of cells) in mast cell (a resident cell with several types of tissues) activation, and lead to the development of strategies to better prevent or treat anaphylaxis.

Objectives:

• To determine whether treatment with omalizumab will reduce or prevent episodes of unprovoked anaphylaxis (an acute allergic reaction) in subjects with a history of idiopathic anaphylaxis.
• To assess pharmacodynamics (physiological effects of a drug) and identify patients with undiagnosed mastocytosis (rare disorders caused by too many mast cells).
• To investigate cellular and molecular mechanisms of signaling and the effect of omalizumab on mast cells or basophils (a cell in the leukocyte family that releases histamine, which affects allergic response) and explore other regulatory pathways that may be involved with modulation of mast cell degranulation.

Eligibility:

• Patients between 18 and 70 years of age who have been diagnosed with idiopathic anaphylaxis,
  

  Detailed Summary:

  Anaphylaxis is a severe systemic reaction caused by release of mediators from mast cells and basophils. Manifestations include cutaneous, respiratory, cardiovascular, or gastrointestinal signs and symptoms. Although anaphylaxis is frequently attributed to exposure to specific foods, drugs, and insect venoms in sensitive individuals, a causative factor is not identified in 30% to 50% of patients with recurrent anaphylactic episodes (idiopathic anaphylaxis).

  Currently, therapeutic options for the treatment of idiopathic anaphylaxis are limited with variable efficacy. This pilot study will examine the hypothesis that omalizumab (Xolair ) will decrease episodes of unexplained anaphylaxis in patients with idiopathic anaphylaxis. Omalizumab is approved for use in asthma. We will examine the safety profile and efficacy of omalizumab in patients with anaphylaxis. In addition, the study will investigate whether patients with anaphylaxis have unique molecular and cellular defects in mast cells that result in these cells being more susceptible to degranulation.

  The study will enroll patients with idiopathic anaphylaxis. Patients will undergo a clinical evaluation, blood tests, and a bone marrow biopsy and aspirate. Patients will be randomized to either drug or placebo and will receive, in a double-blind placebo-controlled approach, 2 doses of omalizumab or a matched placebo while hospitalized, followed by continued outpatient therapy, every 2 to 4 weeks, for up to 6 months. Patients will remain on the assigned regimen if they have experienced anaphylactic events (post 24-hr window) determined to be unrelated to study drug or have been followed for 6 months, whichever comes first. These unrelated events would be determined by the PI not to jeopardize patient safety or restrict the use of additional therapy such as corticosteroids to c
  Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
  

  Current Primary Outcome: The primary objective of this study is to determine if treatment with omalizumab over 6 months will produce a reduction in the number and timing of anaphylactic events in subjects with a history of frequent idiopathic anaphylaxis.
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome: Assess the pharmacodynamics of omalizumab in subjects with anaphylaxis. Examine the effects of omalizumab in the immunopathogenesis of anaphylaxis. Identify subjects with the D816V mutation.
  
  

  Original Secondary Outcome: Same as current
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: April 28, 2009
  Date Started: April 26, 2009
  Date Completion: May 13, 2018
  Last Updated: May 19, 2017
  Last Verified: July 12, 2016