Non-invasive Measures of Effects of Xolair in Asthma
Non-invasive Measures of Effects of Xolair in Asthma
The purpose of this study is to look at the effectiveness of Xolair® (omalizumab) in people
 with asthma taking Advair Diskus®. The study will look at the effects of Xolair® on lung
 function using high resolution computed tomography (HRCT) scans after asthma symptoms are
 induced with a special substance called methacholine. This study is only taking place at
 UCLA, where about 13 subjects will be enrolled. Participation requires 10-14 visits over
 about 26 weeks.

 Subjects will receive an albuterol inhaler to use as needed for immediate relief of symptoms
 and fluticasone 250 mcg/salmeterol 50 mcg or fluticasone 500 mcg/salmeterol 50 mcg (Advair
 Diskus® 250/50 or 500/50) to be taken twice daily. At certain visits, they will be given
 Xolair® injections followed by various assessments, including CT scans and lung function
 tests.
This is a prospective pilot study evaluating the effect of omalizumab on the small airways of
 moderate to severe asthmatic individuals who are not fully controlled on
 fluticasone/salmeterol 250/50 or 500/50 mcg 1 puff bid. After screening, all subjects will be
 placed on fluticasone/salmeterol 250/50 or 500/50 mcg 1 puff bid for a 6-week run-in.
 Subjects will then be evaluated for level of asthma control. Individuals with total control
 of their asthma (no daytime or nighttime symptoms, no rescue use of short-acting inhaled
 beta-agonist, normal PEF, no unscheduled office visits, no ER visits) will be excluded from
 the study. Subjects without total asthma control will then have baseline studies performed to
 include HRCT of the chest before and after a methacholine challenge test (MCT), spirometry,
 closing volume, inspiratory capacity, symptom scores, asthma questionnaires, exhaled NO
 (performed at different expiratory flow rates to estimate alveolar NO) and blood work for
 evaluation of eosinophils and ECP, and banked serum. Subjects who meet acceptable criteria
 for omalizumab dosing based on serum IgE levels and body weight and the presence of atopy (at
 least one positive skin test to a common environmental allergen) will then receive omalizumab
 in addition to fluticasone/salmeterol 250/50 or 500/50 mcg 1 puff bid for sixteen weeks.
 Subjects will be seen every 2-4 weeks during the sixteen-week treatment phase to receive
 injections as prescribed and every 4 weeks to measure spirometry, inspiratory capacity, and
 to evaluate the level of compliance. After the sixteen-week treatment phase subjects will
 again undergo HRCT of the chest before and after a MCT [in the case where the follow-up
 methacholine responsiveness is diminished (improved) a mid-scan will be performed at the
 prior (target) methacholine dose and the challenge then continued to a maximum dose of 16
 mg/ml and a third scan done], spirometry, closing volume, inspiratory capacity, exhaled NO at
 different expiratory flow rates (to estimate alveolar NO) and blood work for evaluation of
 eosinophils and ECP and banked serum.
Inclusion Criteria:

 -  Male or female aged 18 to 65 years, inclusive.

 -  History of moderate to severe asthma: Currently on a medium to high dose of an inhaled
 corticosteroid (ICS)and long-acting bronchodilator, and/or Criteria for medium dose of
 ICS as per GINA guidelines. ICS requirements are as follows: Beclomethasone HFA 80* -
 4 puffs/day; Budesonide DPI 180*- 4 puffs/day; Budesonide/Fomoterol MDI* - 4
 puffs/day; Ciclesonide 80* - 2 puffs/day; Ciclesonide 160* - 2 puffs/day; Flunisolide
 CFC 250* - 6 puffs/day; Fluticasone 110* - 3 puffs/day; Fluticasone 220* - 2
 puffs/day; Fluticasone/salmeterol DPI 250/50 - 2 puffs/day; Fluticasone/salmeterol MDI
 115/21 - 4 puffs/day; Fluticasone/salmeterol DPI 500/50 - 2 puffs/day;
 Fluticasone/salmeterol MDI 230/21 - 4 puffs/day; Triamcinolone* - 10 puffs/day;
 Mometasone 110* - 4 puffs/day; Mometasone 220* - 2 puffs/day

 * with a LABA (fometerol or salmeterol)

 -  FEV1 greater than/equal to 60% Hankinson predicted normal

 -  FEV1/FVC less than lower limit of normal Hankinson predicted

 -  Methacholine PC20 less than/equal to 8 mg/ml

 -  Be able to sign the Informed Consent Form.

 -  Positive skin test or a positive, in vitro response, to one relevant perennial
 aeroallergen (dog, cat, cockroaches, dermatophagoides farinae [dust mite], or
 dermatophagoides pteronyssinus) documented within the 12 months prior to screening or
 during the screening process (diameter of wheal greater than/equal to 3 mm vs.
 control).

 -  Meet the study drug-dosing table eligibility criteria (serum IgE level greater
 than/equal to 30 to less than/equal to 700 IU/mL and body weight greater than/equal 30
 to less than/equal to 150 kg

 Exclusion Criteria:

 -  The use of the following medications will exclude subjects from entering the study:
 Oral or parenteral steroids- 6 months; Omalizumab- less than 12 months; Short and
 long-acting anticholinergics- Stop at time of run-in; Antileukotrienes,
 beta-adrenergic blocking agents, inhaled cromolyn sodium or nedocromil, macrolide
 antibiotics- Stop at time of run-in

 -  Tobacco within 1 year or >5 pack years.

 -  Pregnant women, lactating women, or women of childbearing age not willing to take
 precautions to avoid becoming pregnant during the study.

 -  Subjects with upper respiratory infection or receiving an influenza vaccine within 6
 weeks before the study.

 -  Subjects with a history of allergy or adverse reaction to inhaled beta2-agonists,
 methacholine, salmeterol, fluticasone, epinephrine or omalizumab or related classes of
 drug(s).

 -  Subjects with clinically significant evidence of cardiovascular, central nervous
 system, endocrine, gastrointestinal, hematopoietic, hepatic, renal, psychiatric,
 respiratory (other than asthma) disease, or any other severe medical condition(s) that
 in the view of the investigator prohibits participation in the study

 -  Use of any other investigational agent in the last 30 days.

 -  Subjects with exacerbations during the run-in period that in the opinion of the
 investigator result in an unstable baseline

 -  Asthma totally controlled during the two weeks prior to omalizumab treatment. Total
 control is defined as: No days with symptom score > 1; No use of rescue albuterol; PEF
 > 80% predicted; No night-time awakening; No unscheduled physician or ED visits for
 asthma