A Study of Omalizumab (Xolair) in Subjects With Moderate to Severe Persistent Asthma (EXTRA)

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, placebo-controlled study of the efficacy, safety, and tolerability of subcutaneously administered Xolair as add-on therapy for the treatment of subjects aged 12-75 years old diagnosed with moderate to severe asthma who are inadequately controlled with high-dose inhaled corticosteroids (ICS)+ long-acting beta-agonists (LABA) with or without additional controller therapy.

Official Title
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A Phase IIIb Multicenter, Randomized, Double-Blind, Placebo-Controlled Study of Xolair in Subjects With Moderate to Severe Persistent Asthma Who Are Inadequately Controlled With High-Dose Inhaled Corticosteroids and Long-Acting Beta-Agonists

Conditions
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Asthma

Intervention / Treatment
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* Drug: omalizumab (Xolair)
* Drug: placebo
* Drug: corticosteroids
* Drug: long-acting beta-agonists


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form and an informed assent, if applicable Be between the ages of 12 to 75 years Have had a history of moderate to severe asthma for at least one year prior to screening Have had treatment with a stable regimen of of salmeterol 50 µg twice a day (BID) or formoterol 12 µg BID for at least 8 weeks prior to screening Have had treatment with a stable regimen of high-dose inhaled corticosteroids (ICS) for at least 8 weeks prior to screening Have inadequately controlled asthma Have had at least one asthma exacerbation requiring systemic corticosteroid rescue in the 12 months prior to the screening visit while receiving treatment with high-dose ICS Have less than 10 pack-years smoking history Have a positive skin test for or a positive, in vitro response to one relevant perennial aeroallergen documented within the 12 months prior to screening If a subject has not had a positive skin test or in vitro reactivity in the 12 months prior to screening, the subject must demonstrate a positive response to at least one relevant perennial aeroallergen in a skin or in vitro test prior to randomization Female subjects of childbearing potential must use an effective method of contraception from screening through their duration of participation in the study For the collection of additional blood samples for future research (optional), provide signed consent and an informed assent, if applicable. Exclusion Criteria: Have had an asthma exacerbation requiring intubation within 12 months prior to screening Have active lung disease other than asthma Have had an asthma exacerbation requiring treatment with the addition of systemic (oral or intravenous) corticosteroids or an increase in systemic corticosteroids within 30 days prior to screening Require chronic immunosuppressive therapy including cyclosporine, methotrexate, etc. Have significant medical illness other than asthma Have taken methotrexate, gold salts, cyclosporine, or macrolide antibiotics, within 3 months prior to screening Have taken other investigational drugs within 30 days prior to screening Have been treated with Xolair within the 12 months prior to screening Have a history of drug or alcohol abuse that, in the judgment of the investigator, may put the subject at risk for being unable to participate fully in the study for the duration of the study Have elevated serum IgE levels for reasons other than allergy Are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Xolair<br>The subcutaneous dose of Xolair administered in this study was either a minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study. | Drug: omalizumab (Xolair)<br>* Omalizumab (Xolair) was administered by subcutaneous (SC) injection every 2 or 4 weeks. Xolair was supplied as a sterile, white, preservative-free, lyophilized powder in single-use vials that were reconstituted with Sterile Water for Injection (SWFI), USP.<br>* Other names: Xolair;Drug: corticosteroids<br>* Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day.<br>Drug: long-acting beta-agonists<br>* 50 µg salmeterol twice daily or 12 µg formoterol twice daily.<br>|
| Placebo Comparator: placebo<br>The subcutaneous dose of placebo administered in this study was either a minimum of 0.008 mg/kg/IgE (IU/mL) every 2 weeks or a minimum of 0.016 mg/kg/IgE (IU/mL) every 4 weeks for 48 weeks. Participants maintained their high-dose inhaled corticosteroid (minimum of 500 µg of fluticasone dry powder inhaler twice a day or its ex-valve equivalent) and Long-Acting Beta-Agonist dose (either 50 µg salmeterol twice daily or 12 µg formoterol twice daily) throughout the study. Participants were permitted to use albuterol as rescue medicine throughout the study. | Drug: placebo<br>* Placebo was administered by subcutaneous (SC) injection every 2 or 4 weeks. Placebo contained the same ingredients as the lyophilized formulation of Xolair,excluding omalizumab.<br>Drug: corticosteroids<br>* Minimum dose of 500 µg of fluticasone dry-powder inhaler or its equivalent ex-valve dose twice a day.<br>Drug: long-acting beta-agonists<br>* 50 µg salmeterol twice daily or 12 µg formoterol twice daily.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Asthma Exacerbations Over the 48 Week Treatment Period | A protocol-defined asthma exacerbation was defined as worsening of asthma symptoms requiring treatment with systemic corticosteroids for 3 or more days; for patients receiving long-term oral corticosteroids, an exacerbation was a 20 mg or more increase in average daily dose of oral prednisone (or a similar dose of another systemic corticosteroid). The rate of protocol-defined asthma exacerbations, normalized by subject-time at risk and computed over the 48 week treatment period in each treatment group. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Total Asthma Symptom Scores | Change from baseline to week 48 in Total Asthma Symptom Score (TASS), which included a nocturnal asthma score (0 to 4 scale), morning asthma symptoms (yes or no), and a daytime asthma symptom score (0 to 4 scale, total score range 0 to 9, higher TASS scores represent worse symptoms; breathlessness, tightness in chest, wheezing and cough. Score achieved by week 48 minus baseline. | Baseline and Week 48 | 
| Change From Baseline in the Number of Puffs Per Day of Beta Agonist Rescue Medication | Change from baseline to week 48 in mean puffs per day of albuterol. Puffs per day was achieved by week 48 minus baseline. | Baseline and Week 48 | 
| Change From Baseline in Overall Asthma-related Quality of Life | Change from baseline to week 48 in overall asthma-specific health-related quality of life, as measured by the standardized version of the Asthma Quality of Life Questionnaire (AQLQ[S]) score. The AQLQ(S) consists of 4 domains (activity limitations, symptoms, emotional function, and environmental stimuli), with a total of 32 items; the overall score is the mean of these 32 items on a scale of 1 to 7 (1 = severe impairment, 7 = no impairment). Overall outcome achieved by mean visit minus baseline. | Baseline and Week 48 | 
| Number of Participants Assessed for Frequency and Severity of Treatment-emergent Adverse Events | This outcome is represented in the adverse event section of the database. | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Persistent Asthma, EXTRA, Xolair, Difficult Breathing