Effect of Omalizumab in Patients With Severe Persistent Non-atopic Uncontrolled Asthma

Study Overview
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Brief Summary
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This study will assess the change in the expression of FcεRI receptors of blood basophils and dendritic cells after 16 weeks of treatment with omalizumab as compared with placebo, in adult patients with non-atopic severe persistent asthma, uncontrolled despite optimal therapy.

Official Title
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A 16-week Treatment, Multicenter, Randomized, Double Blind, Placebo-controlled, Parallel-group Study to Assess the Effect of Omalizumab on the Expression of FcεRI Receptors of Blood Basophils and Dendritic Cells in Patients With Severe Persistent Non-atopic Asthma, Uncontrolled Despite Optimal Therapy

Conditions
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Asthma

Intervention / Treatment
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* Drug: omalizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe persistent asthma with the following characteristics: Uncontrolled according to Global Initiative for Asthma (GINA) 2007 guidelines and at least 2 exacerbations having required systemic corticosteroid and/or at least 1 hospitalization or emergency room visit in the past year. Treated with high-dose inhaled corticosteroid (i.e. > 1,000 µg beclometasone dipropionate equivalent per day) plus inhaled long-acting β2 agonist (with or without maintenance oral corticosteroid). Non-atopic, i.e. negative blood multiallergic testing and negative Aspergillus-specific IgE-radio allergosorbent blood test and negative skin prick tests to a battery of common aeroallergens Exclusion Criteria: Current smokers or smoking history stopped for less than 3 years or > 10 pack years. Asthma exacerbation during the 4 weeks prior to randomization. Active lung disease other than non-atopic asthma. Patients with an active cancer, a suspicion of cancer or any history of cancer with less than 5 disease free years. Pregnant or nursing (lactating) women. Treatment with omalizumab. Other protocol-defined inclusion/exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Omalizumab<br>Participants received subcutaneous injections of omalizumab every 2 weeks or every 4 weeks; dosage dependent on IgE level and body weight. | Drug: omalizumab<br>* Omalizumab was supplied in 5mL vials with solution for subcutaneous injection.<br>|
| Placebo Comparator: Placebo<br>Participants received subcutaneous injections of placebo to omalizumab every 2 weeks or every 4 weeks. | Drug: Placebo<br>* Placebo was supplied in vials with solution for subcutaneous injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in the Expression of FcεRI Receptors of Blood Basophils | Venous blood samples were collected at screening and at Week 16. Flow cytometry analysis determined the FcεRI receptors expression of blood basophils (mean fluorescence intensity(MFI)). Relative change in mean fluorescence intensity at the end of study was expressed as a percentage of baseline value. | Baseline and 16 weeks | 
| Change From Baseline in the Expression of FcεRI Receptors of Dendritic Cells | Venous blood samples were collected at screening and at Week 16. Flow cytometry analysis determined the FcεRI receptors expression of dendritic cells (mean fluorescence intensity (MFI)). Relative change in mean fluorescence intensity at the end of study was expressed as a percentage of baseline value. | Baseline and 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fractional Exhaled Nitric Oxide (FeNO) | FeNO was measured at baseline, and after 4, 8, 12 and 16 weeks of treatment. Absolute change in FeNO was expressed at each time point versus baseline value. | Baseline and 4, 8, 12 and 16 weeks | 
| Change From Baseline in Induced Sputum Eosinophil Count | The induced sputum eosinophil count was measured in a subset of patients in selected centers. Sputum samples were collected at screening and Week 16. Sputum eosinophil count was expressed as a percentage of total nonsquamous cells. Absolute change in sputum eosinophil count was expressed versus baseline value. | Baseline and 16 weeks | 
| Change From Baseline in Score of the Shortened Version of the Asthma Control Questionnaire (Symptoms Plus Short-acting β2-agonist) | The shortened version of the asthma control questionnaire (symptoms plus β2-agonist) consists of 6 subscores (nighttime waking, symptoms on waking, activity limitation, shortness of breath, wheeze and rescue short-acting β2-agonist use) between 0 and 6 (0 = no impairment; 6 = maximum impairment) and a total score between 0 and 6 (subscores mean value). Absolute change in total score and subscores count was expressed versus baseline value. A decrease in score indicates improvement. | Baseline and 16 weeks | 
| Change From Baseline in Nasal Symptom Global Score and Individual Components | Nasal symptom score calculated from six scales assessing the nasal symptom severity (sneezing, runny nose, congestion, itchy nose, postnasal drip and nasal symptoms overall). These six scores were rated on a scale from 1 to 7, with 7 being the worst rating. Absolute changes in these six scores were expressed versus baseline values. A negative change indicates improvement. The range of the global score was from 1 to 7, since this is the mean value of all the subscores. | Baseline and 16 weeks | 
| Physician and Patient Global Evaluation of Treatment Effectiveness | The GETE is an assessment of asthma symptoms controlled in response to asthma treatment. The evaluation was performed independently by both investigator and patient using the same 5 point scale. The scale points are: excellent, good, moderate, poor and worsening. A good or excellent response is suggested as a means of defining a patient who has responded to treatment. | 16 weeks | 
| Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to 16 Weeks | Spirometry was conducted according to internationally accepted standards. At least three maneuvers were performed at each sampling timepoint. The FEV1 recorded was taken from the maneuver obtained from the single best test curve. The best test curve was defined as the spirogram that gave the largest FEV1. | Baseline and 16 weeks | 
| Number of Patients With at Least One Asthma-related Event Over 16 Weeks | Asthma-related events were: unscheduled medical visits, emergency room visits and hospitalizations. Details of exacerbations requiring oral or IV corticosteroids were recorded at each visit. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe asthma,, non-atopic,, omalizumab