Non-invasive Measures of Effects of Xolair in Asthma
Information source: University of California, Los Angeles
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Asthma
Intervention: Xolair injections (Drug)
Phase: Phase 4
Status: Terminated
Sponsored by: University of California, Los Angeles Official(s) and/or principal investigator(s): Eric C Kleerup, MD, Principal Investigator, Affiliation: University of California, Los Angeles
Summary
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.
Clinical Details
Official title: Non-Invasive Measures of Distal Lung Disease in Asthmatics Before and After Treatment With Omalizumab
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in methacholine shift at baseline compared with the shift after treatment phase. 6 (out of a possible 18) anatomic segment dorsal-peripheral zones demonstrating the greatest decrease in attenuation with methacholine will be selected for analysis.Baseline to post-treatment change in pre-methacholine lung attenuation, using the baseline lung attenuation curve as a covariate. Done for all anatomic segment dorsal-peripheral zones. Results averaged for each subject and averages mean across subjects
Secondary outcome: Physiologic markers (isovolume FEF25-75%, closing volume, the alveolar portion of FENO, and serum markers of inflammation)Ordinal data from questionnaires and diaries
Detailed description:
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 65 Years.
Gender(s): Female.
Criteria:
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
Locations and Contacts
UCLA, Los Angeles, California 90095, United States
Additional Information
Starting date: February 2009
Last updated: March 8, 2011
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