A Real World Study to Capture Clinical and Patient Centered Outcomes in Adults With Severe Eosinophilic Asthma Treated With Benralizumab.

Study Overview
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Brief Summary
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Severe eosinophilic asthma (SEA) is associated with poor disease control and compromised health-related quality of life (HRQoL), leading to a substantial psychosocial and economic disease burden. Benralizumab (Fasenra®), an interleukin (IL)-5-alpha receptor monoclonal antibody, is approved as an add-on maintenance treatment for SEA. This study aims at collecting real-world data that extend beyond the clinical effectiveness of benralizumab to the participant-reported impact of treatment on their HRQoL, sleep quality, depression, anxiety, work productivity and activity impairment, but also on treatment effectiveness. Recent technological advances in portable spirometers and wearable activity trackers (WAT) to increase physical activity for participants with asthma, even for older participants, allow this study to collect data on lung function parameters and physical activity from such devices for the first time at a country level in Greece. Using a multi-aspect approach, this study will generate real-world evidence on a broad range of both well-established clinical and novel patient-centered outcomes which are critical to the assessment of the therapeutic benefit both from the physician's and the participant's perspective. All main study outcomes will be examined at various timepoints throughout the course of the 48-week observation period, starting as early as 4 weeks after treatment initiation, thus enabling the identification of 'early' treatment responders with a closer focus on patients' physical and psychological well-being and HRQoL in addition to asthma control and lung function metrics.

Official Title
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A Real World Multicenter 48 Week Prospective Cohort Study to Capture Clinical and Patient Centered Outcomes in Adults With Severe Eosinophilic Asthma Treated With Benralizumab in Routine Care Settings in Greece

Conditions
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Severe Eosinophilic Asthma

Intervention / Treatment
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* Drug: Cohort


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female outpatients aged 18 to 75 years (inclusive) at the time of benralizumab prescription Patients with physician-diagnosed Severe Eosinophilic Asthma SEA inadequately controlled despite high-dose inhaled corticosteroids (ICS) plus long-acting β-agonists (LABA) Patients who have been prescribed but not yet initiated treatment with benralizumab according to the Summary of Product Characteristics (SmPC), prior to signed Informed Consent, and for whom the decision to prescribe this therapy is clearly separated from the physician's decision to include the patient in the current study For patients that are not Oral Corticosteroid (OCS)-dependent: Blood eosinophil count (BEC) ≥150 cells/μL in the 2 weeks before benralizumab initiation and a historical value of ≥300 cells/μL during the previous year For OCS-dependent patients: BEC ≥150 cells/μL in the 2 weeks before benralizumab initiation or a historical value of ≥300 cells/μL during the previous year History of ≥1 documented Clinically Significant Exacerbations (CSE) in the 48 weeks prior to benralizumab initiation, and of ≥2 CSEs in the previous 24 months Patients must be willing and able to read and complete the study specific questionnaires Patients must be willing and able to use the study-specific wearable/handheld devices. Note: This requirement applies only at the time of benralizumab (Fasenra®) prescription. If a patient stops using any or both of the aforementioned devices for any reason during his/her participation in the study, (s)he may continue participating in the study and this will not be considered as a reason for withdrawal. -Patients must provide a written Informed Consent prior to inclusion to the study Exclusion Criteria: Patients that meet any of the contraindications to the administration of the benralizumab outlined in the SmPC Concomitant treatment with any other biologic agent for any indication Previous exposure to anti-IL5/ILR5 treatment Exposure to omalizumab in the past 6 months prior to benralizumab initiation Clinically important pulmonary disease other than asthma or ever been diagnosed with any disease, other than asthma, that is associated with elevated BEC Acute upper or lower respiratory infections within 8 weeks prior to the date of informed consent Heavy smokers with a >20 pack-year smoking history Currently pregnant (or intention to become pregnant within the study period), breastfeeding or lactating women Known evidence of lack of adherence to asthma controller medications Use of immunosuppressive medication (including but not limited to: OCS [for reasons other than asthma], methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroids [for reasons other than asthma] or any experimental anti-inflammatory therapy) within 3 months prior to the date of informed consent Patients who currently receive treatment with any investigational drug/device/intervention or who have received any investigational product within 30 days or 5 half-lives of the investigational agent (whichever is longer) before benralizumab initiation

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Cohort|Participants with Severe Eosinophilic Asthma|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in St. George's Respiratory Questionnaire (SGRQ) | Estimation of the proportion of patients achieving a minimum clinically important improvement in respiratory health status (≥ 4-point reduction from baseline in SGRQ total score) in SEA patients initiated on benralizumab | 16 weeks after the initiation of the treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in St. George's Respiratory Questionnaire (SGRQ) | Estimation of the proportion of patients achieving a moderately efficacious change in respiratory health status (≥ 8-point reduction from baseline in SGRQ total score) | 16 weeks after the initiation of the treatment | 
| Change in St. George's Respiratory Questionnaire (SGRQ) | Estimation of the proportion of patients achieving a minimum clinically important improvement (≥ 4-point reduction in baseline SGRQ total score) and of those achieving a moderately efficacious change in respiratory health status (≥ 8-point reduction in baseline SGRQ total score) | after 4, 8, 32 and 48 weeks of treatment | 
| Change in St. George's Respiratory Questionnaire (SGRQ) | Determination of predictors of early clinically important improvement in respiratory health status (measured by the SGRQ) at 4 weeks of treatment with benralizumab, and at 48 weeks post-benralizumab initiation among the 4-week SGRQ responders | after 4 and 48 weeks of treatment | 
| Change in ACQ-6 | Change in asthma control and the response rate as well as the response rate at 48 weeks post-benralizumab initiation among the 16-week ACQ-6 responders | after 4, 8, 16, 32, and 48 weeks of treatment | 
| Change in the annual rate of clinically significant exacerbations | Change in the annual rate of clinically significant exacerbations (CSE) and identification of factors influencing the CSE rate | between the 48-week periods pre- and post-benralizumab initiation | 
| change in asthma-related hospital-based health care resource utilization (HCRU) | Change in asthma-related hospital-based health care resource utilization (HCRU) | between the 48-week periods pre- and post-benralizumab initiation | 
| Change from baseline in clinic-measured spirometric lung function indices | Change from baseline in clinic-measured spirometric lung function indices and description of the FEV1 improvement rate at 48 weeks post-benralizumab initiation among patients who will achieve clinically meaningful improvement in FEV1 at 16 weeks post-benralizumab initiation | after 16 and 48 weeks of benralizumab treatment | 
| change from baseline in rescue medication use and in the proportion of nights with awakenings due to asthma requiring rescue medication use | Change from baseline in rescue medication use and in the proportion of nights with awakenings due to asthma requiring rescue medication use | after 4, 8, 16, 32 and 48 weeks of treatment | 
| change in cumulative oral corticosteroid (OCS) burden | Change in cumulative oral corticosteroid (OCS) burden | etween the 16-week periods pre- and post-benralizumab initiation and the 48-week periods pre- and post-benralizumab initiation | 
| change from baseline in anxiety and depression levels [assessed by the Hospital Anxiety and Depression Scale (HADS)] | Change from baseline in anxiety and depression levels [assessed by the Hospital Anxiety and Depression Scale (HADS)] | after 16 and 48 weeks of treatment | 
| change from baseline in patient-reported sleep quality [assessed by the Pittsburgh Sleep Quality Index (PSQI)] | Change from baseline in patient-reported sleep quality [assessed by the Pittsburgh Sleep Quality Index (PSQI)] | after 16 and 48 weeks of treatment | 
| change from baseline in work productivity and activity impairment [assessed by the Work Productivity and Activity Impairment:Respiratory Symptoms (WPAI:RS) questionnaire] | Change from baseline in work productivity and activity impairment [assessed by the Work Productivity and Activity Impairment:Respiratory Symptoms (WPAI:RS) questionnaire] | after 16 and 48 weeks of treatment | 
| clinician-assessed overall response to treatment using the Clinician Global Impression of Change (CGIC) | Clinician-assessed overall response to treatment using the Clinician Global Impression of Change (CGIC) | over the 48-week treatment period | 
| patient-perceived overall response to treatment using the Patient Global Impression of Change (PGIC) | Patient-perceived overall response to treatment using the Patient Global Impression of Change (PGIC) | after 48 weeks of treatment | 
| Percentage of patients remaining on treatment with benralizumab | Treatment persistence rate on therapy | at 48 weeks of treatment | 
| Percentage of patients having discontinued treatment with benralizumab | Percentage of patients having discontinued treatment with benralizumab | at 48 weeks of treatment | 
| description of reasons for treatment discontinuation | description of reasons for treatment discontinuation | at 48 weeks of treatment | 
| time to treatment discontinuation | time to treatment discontinuation | at 48 weeks of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Severe Asthma, Home Spirometry, Activity Tracker, Benralizumab