Omalizumab in Adult and Adolescent Patients With Severe Persistent Allergic Asthma

Study Overview
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Brief Summary
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Omalizumab will be given as add-on treatment to optimized asthma therapy in patients with severe persistent asthma, who demonstrate inadequate asthma symptom control. Response to omalizumab over time will be assessed by physicians and patients evaluating the overall improvement in control of their asthma. THIS STUDY IS NOT ENROLLING PATIENTS IN THE US.

Official Title
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A Randomized, Open Label, Parallel-group, International, Multicenter Study Evaluating Persistency of Response to Omalizumab During 32 Weeks Treatment Given as Add on to Optimized Asthma Therapy in Adult and Adolescent Patients With Severe Persistent Allergic Asthma, Who Remain Inadequately Controlled Despite GINA (2004) Step 4 Therapy

Conditions
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Asthma

Intervention / Treatment
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* Drug: Omalizumab
* Other: Optimized asthma therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who met the following criteria were included: Males or females of any race, who were 12-75 years of age A body weight ≥ 20 kg and ≤ 150 kg and with a total serum IgE level ≥ 30 to ≤ 700 IU/ml A diagnosis of allergic asthma ≥ 1 year duration according to American Thoracic Society (ATS) criteria and at screening a history consistent with GINA (2204) step 3 or 4 clinical features A positive prick skin test (diameter of wheal >= 3 mm) to at least one perennial allergen documented within the past 2 years or taken at visit 1 Increase in FEV1 ≥12% over baseline value within 30 minutes of taking 2 to 4 puffs (2-4x100µg) salbutamol (albuterol) or nebulized salbutamol up to 5mg An FEV1 ≥ 40 and ≤ 80% of the predicted normal value for the patient at randomization Receiving moderate to high dose inhaled corticosteroid ≥ 800 µg BDP or equivalent and a regular inhaled long acting B-2 agonists for at least 3 months prior to screening and > 1000 µg (BDP) and a LABA for at least 4 weeks during the run-in and at randomization Patients who have suffered multiple (i.e. at least two) independent documented severe asthma exacerbations while receiving high doses of ICS (≥ 800 µg BDP or equivalent) plus regular inhaled LABA Evidence of poor asthma control at screening (based on patient history) and for at least 4 weeks immediately prior to randomisation Exclusion Criteria: Patients who met the following criteria were excluded: Had received systemic corticosteroids for reasons other than asthma within 4 weeks of Visit 1 A smoking history >10 pack years An active lung disease other than allergic asthma Elevated serum IgE levels for reasons other than allergy Patients with significant underlying medical conditions

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: OAT + Omalizumab<br>During the 8-week Run-in phase, asthma therapy was evaluated and optimized according to Global Initiative for Asthma (GINA) guidelines. During the treatment phase, participants continued to receive optimized asthma therapy (OAT), plus omalizumab add on therapy for 32 weeks, administered by subcutaneous injection once every 4 weeks. The dosage received was individualized based on body weight and serum IgE level. | Drug: Omalizumab<br>* Omalizumab administered by subcutaneous injection. The dosage received was individualized based on body weight and serum IgE level.<br>* Other names: Xolair;Other: Optimized asthma therapy<br>* Optimized asthma therapy (OAT) according to Global Initiative for Asthma (GINA) 2004 guidelines during the first 4 weeks of the run-in period of the study.<br>|
| Active Comparator: Optimized Asthma Treatment (OAT)<br>During the 8-week Run-in phase, asthma therapy was evaluated and optimized according to Global Initiative for Asthma (GINA) guidelines. In the treatment phase, participants continued to receive optimized asthma therapy (OAT) established during the run-in period of the study for 32 weeks. | Other: Optimized asthma therapy<br>* Optimized asthma therapy (OAT) according to Global Initiative for Asthma (GINA) 2004 guidelines during the first 4 weeks of the run-in period of the study.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistency of Response and Non-response as Based on Investigator's Global Evaluation of Treatment Effectiveness (GETE) | Persistency of response, based on GETE, was dichotomized into responders (excellent or good) and non-responders (moderate, poor or worsening). Persistent responders were patients who were responders at 16 weeks and still at 32 weeks. Persistent non-responders were patients who were non-responders at 16 weeks and still at 32 weeks. Patients were assessed for persistency of response if they were responders at Week 16 and had a second GETE obtained ≥ 4 weeks after the Week 16 assessment or discontinued prematurely for unsatisfactory therapeutic effect ≥ 4 weeks after the Week 16 assessment. | Weeks 16 and 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants by Investigator's Global Evaluation of Treatment Effectiveness (GETE) Category at Week 16 and Week 32 | Number of participants with persistent response, based on the investigator's GETE, dichotomized to responders (excellent or good) and non-responders (moderate, poor or worsening) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32. Persistency was defined as the proportion of responders at 16 weeks who were still responders at 32 weeks. GETE categories are excellent, good, moderate, poor, worsening, and missing as determined by the investigator. | Weeks 16 and 32 | 
| Percentage of Participants Who Were Responders at Both Week 16 and Week 32 Based on Investigator's GETE | Responders were defined as excellent or good based on the investigator's Global Evaluation of Treatment Effectiveness (GETE) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32. | Weeks 16 and 32 | 
| Number of Participants by Patient's Global Evaluation of Treatment Effectiveness (GETE) Category at Week 16 and 32 | Number of participants with persistent response, based on the patient's GETE, dichotomized to responders (excellent or good) and non-responders (moderate, poor or worsening) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32. Persistency was defined as the proportion of responders at 16 weeks who were still responders at 32 weeks. This is based on the patient's evaluation. | Weeks 16 and 32 | 
| Percentage of Participants Who Were Responders at Both Week 16 and Week 32 Based on Patient's GETE | Responders were defined as excellent or good based on the patient's Global Evaluation of Treatment Effectiveness (GETE) for patients receiving omalizumab as add on to optimal asthma therapy, assessed at week 16 and week 32. | Weeks 16 and 32 | 
| Lung Function Assessed by Forced Expiratory Volume for 1 Second (FEV1) | Predicted FEV1 was calculated using the Crapo formula for data at Visit 6 (time of randomization), (MALES: Predicted FEV1 (L) = 0.0414*height - 0.0244*age -2.190 and Females: Predicted FEV1 (L) = 0.0342*height - 0.0255*age - 1.578, where height is in cm). | Weeks 16 and 32 | 
| Change From Baseline in Asthma Control Questionnaire (ACQ) Overall Score at Weeks 16 and 32 | Asthma symptoms were evaluated by the Asthma Control Questionnaire (ACQ). The ACQ has six questions to be answered by the patient, each with a 7 point scale (0-good control, 6-poor control), and one question where the actual pre-bronchodilator FEV1 value expressed in % of predicted FEV1 was classified to scores from 0 (> 95% of predicted) to 6 (< 50% of predicted). The overall score is the average of the 7 questions; a minimum overall score of 0 = good control of asthma whereas a maximum overall score of 6 = poor control of asthma. A negative change in score indicates improvement in symptoms. | Baseline, Week 16, Week 32 | 
| Number Participants With Clinically Significant Asthma Exacerbations by Category During the 32 Week Treatment Period | A clinically significant exacerbation episode was defined as a worsening of asthma requiring treatment with rescue systemic (oral or IV) corticosteroids. The initiation of the rescue systemic corticosteroids marked the start of a clinically significant asthma exacerbation episode and cessation of the rescue systemic corticosteroids regimen marked the end of a clinically significant exacerbation episode. If an exacerbation episode was duplicated, overlapped by at least one day with another episode, or nested within another exacerbation episode, only one exacerbation was counted. | 32 Weeks | 
| Medical Resource Utilization: Number of Participants With Combined Hospital Admissions, Emergency Room Visits, and Other Outpatient Clinical Visits Due to an Asthma Exacerbation During the 32 Week Treatment Period | A combined total of unscheduled visits due to asthma exacerbations was calculated for each patient as the total number of hospital admissions, ER visits and unscheduled outpatient clinical visits due to asthma exacerbation. Where more than one type of visit was required on a single day for an asthma exacerbation only the most serious type was included. Where there was more than one visit for a single asthma exacerbation but the visits occurred on different dates, then all were counted. | 32 Weeks | 
| Percent Change in Dose of Maintenance Systemic Steroids at Weeks 16 and 32 | For the subgroup of patients requiring maintenance oral (systemic) corticosteroids throughout the screening period the dose of oral steroid (expressed as prednisolone equivalent dose) at baseline, Week 16 and Week 32 was presented by treatment group, as well as the absolute and percent change from baseline to Weeks 16 and 32. It should be noted that the dose of oral steroid at Weeks 16 and 32 was the dose the patient was maintained on and not the dose to treat an exacerbation if one occurred at that time. | Weeks 16 and 32 | 
| Number of Participants by Type of Dose Change of Maintenance Systemic Steroids at Weeks 16 and 32 | The type of change for the dose of maintenance systemic steroids could be presented as removal (no more maintenance systemic steroids used), decreased, or maintained. | Weeks 16 and 32 | 
| Change From Baseline in Asthma Quality of Life Questionnaire (AQLQ) Overall Score by Visit | There are 32 questions in the AQLQ and they are in 4 domains (symptoms, activity limitation, emotional function and environmental exposure). Each question was answered on a 7 point scale (1-totally limited/problems all the time, 7-not at all limited/no problems). The overall AQLQ score is the mean of all 32 responses, and the individual domain scores are the means of the items in those domains (a minimum domain / overall score of 1 = Severely impaired whereas a maximum domain / overall score of 7 = not impaired at all). A positive change from baseline score indicates improvement. | Baseline, Week 15, Week 31 | 
| Change From Baseline in EuroQual 5-Dimension Health Status Questionnaire (EQ-5D) Index Score and Health State Assessment on Scale From 0 to 100 at Weeks 15 and 31 | The utility-based EQ-5D questionnaire is in two parts and provides a generic measure of health for clinical and economic appraisal. The first health state classification part has 5 questions each with 3 categories (no problem, moderate problem, severe problems). The second visual analogue scale was measured from 0 (worst imaginable health state) to 100 (best imaginable health state). | Baseline, Week 15, Week 31 | 
| Changes From Baseline to Week 31 in the Percent Overall Work Impairment Due to Asthma Problems | The Work Productivity and Activity Impairment-Allergic Asthma (WPAI-AA) questionnaire measures time missed from work, impairment of work and regular activities within the last 7 days. Questionnaires were administered via phone 1 week prior to the study visit. Outcomes are expressed as impairment percentages, with higher numbers indicating greater impairment and less productivity. Overall work impairment due to asthma problems is derived from the proportion of hours missed from work due to asthma and the degree to which asthma problems affected productivity while working. | Baseline and Week 31 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, omalizumab, Severe persistent allergic asthma