The Effect of Omalizumab on Airway Responsiveness to Adenosine in Patients With Poorly Controlled Asthma
Condition: Asthma
MeSH terms: Asthma
Study type: Interventional
Phase: Phase 4

Summary: 
      The purpose of this study is to determine whether the addition of omalizumab in patients with
      poorly controlled asthma (because of poor adherence) will decrease allergic airway
      inflammation and improve asthma control.
    

Detailed description: 
      Patients with moderate to severe allergic asthma who are poorly adherent to inhaled
      corticosteroids (ICS) have persistent airway inflammation that results in excessive morbidity
      and sometimes death. Omalizumab (OMB), an anti-IgE monoclonal antibody decreases the release
      of mediators from mast cells, reduces the frequency of exacerbations and allows a reduction
      in ICS dose. However, there are no data on the effects of OMB on airway inflammation.
      Bronchoprovocation with adenosine 5' monophosphate (AMP) is a robust and sensitive
      non-invasive measure of allergic airway inflammation, but the effect of OMB on this surrogate
      marker has not been previously reported. Based upon the mechanisms of actions of OMB and AMP
      and the fact that OMB will be administered at 2-4 week intervals in the clinic (i.e., direct
      observed therapy), it is our hypothesis that treatment with this new agent will reduce airway
      responsiveness to AMP and compensate for poor adherence to ICS.

      To test this hypothesis, we will select 16 patients (6-26 yrs) with a total IgE of 30-1300
      IU/ml, sensitivity to at least one allergen, an FEV1 ≥ 60% predicted, and documented poor
      adherence to ICS with inadequate asthma control. Subjects will be randomized to receive OMB
      (150-375 mg subcutaneously) or placebo every 2-4 weeks for four months each, in a
      double-blind, crossover manner with a 3 month washout period between treatments. Spirometry
      will be measured before each injection and at the end of each treatment period. The
      concentration of AMP that will provoke a 20% decrease in FEV1 (PC20 FEV1) and a free IgE
      serum concentration will be measured before and at the end of each treatment period. After
      randomization, a 5-day course of oral prednisone will be administered whenever
      bronchodilator-unresponsive symptoms persist or FEV1 is < 60% predicted. ANOVA for repeated
      measures will be used to evaluate differences between treatments in Δ PC20 (primary endpoint)
      and Δ FEV1, while the Friedman Statistic will be used to evaluate differences in the number
      of short courses of prednisone. The results of this study will provide new information on the
      extent to which OMB decreases airway responsiveness to AMP (i.e. allergic airway
      inflammation) and whether this new therapy will fill an unmet need for patients who have
      inadequately controlled asthma because of poor adherence to inhaled corticosteroids.
    

Intervention name(s): omalizumab
Intervention type(s): Drug
Intervention MeSH terms: Omalizumab
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double
Primary purpose: Treatment
Keywords: anti-IgE, omalizumab