Change in Patient-Reported Outcomes in Severe Eosinophilic Asthma Patients Treated With Benralizumab Under Real-life Conditions (imPROve)

imPROve-asthma - A Prospective, 24-month, Observational Study to Investigate the Change in Patient-Reported Outcomes in Severe Eosinophilic Asthma Patients Treated With Benralizumab Biologic Therapy Under Real-life Conditions in Germany

The main aim of this study is to investigate the change in asthma control after 6 months of therapy in patients treated with benralizumab biologic therapy for severe eosinophilic asthma under real-life conditions in a pulmonary care setting in Germany. The study also aims to investigate Quality-of-Life (QoL), the early treatment response, treatment effectiveness and the change in asthma control over time, following benralizumab therapy. This study will also describe the physician-chosen reasons for starting beralizumab therapy or switching to benralizumab therapy.

Study Overview

• Status: Completed
• Conditions: Asthma

• Study Type: Observational
• Enrollment (Actual): 246

Contacts and Locations

Study Locations

• Germany
  • Aschaffenburg, Germany
    • Research Site
  • Augsburg, Germany
    • Research Site
  • Bamberg, Germany
    • Research Site
  • Beelitz, Germany
    • Research Site
  • Berlin, Germany
    • Research Site
  • Biberach, Germany
    • Research Site
  • Bonn, Germany
    • Research Site
  • Bremen, Germany
    • Research Site
  • Cottbus, Germany
    • Research Site
  • Darmstadt, Germany
    • Research Site
  • Dresden, Germany
    • Research Site
  • Duesseldorf, Germany
    • Research Site
  • Dusseldorf, Germany
    • Research Site
  • Flensburg, Germany
    • Research Site
  • Frankfurt, Germany
    • Research Site
  • Fuerstenwalde, Germany
    • Research Site
  • Furstenwalde, Germany
    • Research Site
  • Gelsenkirchen, Germany
    • Research Site
  • Gerlingen, Germany
    • Research Site
  • Gotingen, Germany
    • Research Site
  • Halberstadt, Germany
    • Research Site
  • Halle, Germany
    • Research Site
  • Hamburg, Germany
    • Research Site
  • Hannover, Germany
    • Research Site
  • Heidelberg, Germany
    • Research Site
  • Hemer, Germany
    • Research Site
  • Hettstedt, Germany
    • Research Site
  • Ibbenbueren, Germany
    • Research Site
  • Immenhausen, Germany
    • Research Site
  • Konstanz, Germany
    • Research Site
  • Leipzig, Germany
    • Research Site
  • Magdeburg, Germany
    • Research Site
  • Marburg, Germany
    • Research Site
  • Markkleeberg, Germany
    • Research Site
  • Munchen, Germany
    • Research Site
  • Neu-Isenburg, Germany
    • Research Site
  • Peine, Germany
    • Research Site
  • Radebeul, Germany
    • Research Site
  • Regensburg, Germany
    • Research Site
  • Reinfeld, Germany
    • Research Site
  • Rheine, Germany
    • Research Site
  • Rostock, Germany
    • Research Site
  • Roth, Germany
    • Research Site
  • Saalfeld, Germany
    • Research Site
  • Schleswig, Germany
    • Research Site
  • Teuchern, Germany
    • Research Site
  • Treuenbrietzen, Germany
    • Research Site
  • Waren, Germany
    • Research Site
  • Warendorf, Germany
    • Research Site
  • Wedel, Germany
    • Research Site
  • Wiesbaden, Germany
    • Research Site
  • Witten, Germany
    • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

approximately 350 to 500 patients in 70 pulmonology sites (hospitals and outpatient practices) in Germany Primary study cohort: approximately 250 patients Secondary study cohort: approximately 100 to 250 patients

Description

Inclusion Criteria:

• Male or female patients aged 18 years or older with confirmed diagnosis of severe asthma according to the ATS/ERS and local German guidelines
• Decision was made by the investigator (regardless of this NIS) to start treating the patient with benralizumab according to severe eosinophilic asthma indication (NB: can include patients that are switched from another EU approved biologic treatment if required for a medical reason).
• Patients must be able and willing to read and comprehend written instructions, and comprehend and complete the questionnaires required by the protocol
• After full explanation, patients must have signed an informed consent document indicating that they understand the purpose of and the procedures required for the study and are willing to participate in the study.

Exclusion Criteria:

• Concomitant treatment with any other biologic for any indication
• Patients already treated with benralizumab
• Clinically important pulmonary disease other than asthma including: chronic obstructive pulmonary disease (as main diagnosis), bronchiectasis, idiopathic pulmonary fibrosis, pulmonary hypertension, alpha-1-antitrypsin-deficiency, and malignancy of any kind (NB: the following conditions are permitted: nasal polyposis, allergic rhinitis, atopic dermatitis, non-idiopathic pulmonary fibrosis).
• An acute or chronic condition that, in the investigator's opinion, would limit the patient's ability to complete questionnaires or participate in this study or impact the interpretations of results.
• Concurrent biologics for asthma are not allowed except for stable allergen immunotherapy (defined as a stable dose and regimen at the time of enrolment). Acceptable wash-out periods for other asthma biologics: ≥30 days from last dose of previous biologic
• Pregnancy or lactation period
• Participation in an observational trial that might, in the investigator's opinion, influence the assessment for the current study, or participation in a randomized clinical trial in the last 3 months

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Primary Study Cohort - Anti-IL5/IL5R naïve patients; Severe eosinophilic asthma patients who have never received anti-Interleukin-5 / anti-Interleukin-5-receptor (anti-IL-5/anti-IL-5R) biologic treatment for severe eosinophilic asthma, for whom the investigator had decided to initiate benralizumab biologic treatment.
Secondary Study Cohort - Biologic experienced patients; Patients that previously received a biologic treatment for severe asthma (at least one dose).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change in asthma control after 6 months of treatment in anti-IL5/IL5R naïve patients initiated with benralizumab treatment	Change from baseline in (Asthma Control Test - questionnaire) ACT score after 6 months treatment in anti-IL5/IL5R naïve patients. ACT is a simple, validated, 5-item tool giving a total score from 5 (worst control) to 25 (best control). Scores of 20 to 25 denote well-controlled asthma, scores ≤19 identifies patients with poorly controlled asthma. The minimum clinically important difference (MCID) is reported to be 3 points.	Baseline and 6 months after baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The investigator reported treatment effectiveness after 6 months of treatment in anti-IL5/IL5R naïve patients initiated with benralizumab treatment	Investigator-reported treatment effectiveness using GETE (Global Evaluation of Treatment Effectiveness) after 6 months of treatment. GETE grades overall treatment effectiveness using the following criteria: excellent (complete control of asthma); good (marked improvement of asthma); moderate (discernible, but limited improvement in asthma); poor (no appreciable change in asthma); or worsening (of asthma).	6 months after first treatment
The change in health-related quality of life (HRQL) in anti-IL5/IL5R naïve patients initiated with benralizumab treatment	Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score and domain scores (symptoms, activity and impact score) after 6 months treatment in anti-IL5/IL5R naïve patients. SGRQ is a validated, 50-item questionnaire, giving scores ranging from 0 (best health status) to 100 (worst health status). The SGRQ yields a total score and 3 domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. A difference of four units in the SGRQ total score is considered the MCID.	Baseline and 6 months after first treatment
The early treatment response in anti-IL5/IL5R naïve patients initiated with benralizumab treatment, day 7, ACQ-6	Change from baseline in ACQ-6 (Asthma-Control-Questionnaire-6) score after 7 days of treatment in anti-IL5/IL5R naïve patients. ACQ-6 is a validated questionnaire based on 5 symptoms questions (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing), and daily rescue bronchodilator use. Each item is scored on a 7-point scale (0=no impairment; 6=maximum impairment), and the ACQ score is the mean of these items. The MCID is greater than or equal to 0.5.	Baseline and day 7 after first treatment
The early treatment response in anti-IL5/IL5R naïve patients initiated with benralizumab treatment, day 7, VAS-1	Change from baseline in patient satisfaction, measured on Visual Analogue Scale (VAS), after 7 days of treatment in anti-IL5/IL5R naïve patients. VAS Scores ranged from "extremly satisfied" (0 mm) to "not at all satisfied" (100 mm).	Baseline and day 7 after first treatment
The early treatment response in anti-IL5/IL5R naïve patients initiated with benralizumab treatment, day 7, VAS-2	Change from baseline in patient symptoms, measured on Visual Analogue Scale (VAS), after 7 days of treatment in anti-IL5/IL5R naïve patients. VAS Scores ranged from "not at all bothersome" (0 mm) to "extremly bothersome" (100 mm).	Baseline and day 7 after first treatment
The early treatment response in anti-IL5/IL5R naïve patients initiated with benralizumab treatment, day 14, ACQ-6	Change from baseline in ACQ-6 (Asthma-Control-Questionnaire-6) score after 14 days of treatment in anti-IL5/IL5R naïve patients. ACQ-6 is a validated questionnaire based on 5 symptoms questions (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing), and daily rescue bronchodilator use. Each item is scored on a 7-point scale (0=no impairment; 6=maximum impairment), and the ACQ score is the mean of these items. The MCID is greater than or equal to 0.5.	Baseline and day 14 after first treatment
The early treatment response in anti-IL5/IL5R naïve patients initiated with benralizumab treatment, day 14, VAS-1	Change from baseline in patient satisfaction, measured on Visual Analogue Scale (VAS), after 14 days of treatment in anti-IL5/IL5R naïve patients. VAS Scores ranged from "extremly satisfied" (0 mm) to "not at all satisfied" (100 mm).	Baseline and day 14 after first treatment
The early treatment response in anti-IL5/IL5R naïve patients initiated with benralizumab treatment, day 14, VAS-2	Change from baseline in patient symptoms, measured on Visual Analogue Scale (VAS), after 14 days of treatment in anti-IL5/IL5R naïve patients. VAS Scores ranged from "not at all bothersome" (0 mm) to "extremly bothersome" (100 mm).	Baseline and day 14 after first treatment
The change of asthma control over time and the maintained response after initiation of benralizumab treatment in anti-IL5/IL5R naïve patients initiated with benralizumab treatment using ACT	Change from baseline in asthma control at each visit during the study period, using ACT in anti-IL5/IL5R naïve patients. ACT is a simple, validated, 5- item tool giving a total score from 5 (worst control) to 25 (best control). Scores of 20 to 25 denote well-controlled asthma, scores ≤19 identifies patients with poorly controlled asthma. The minimum clinically important difference (MCID) is reported to be 3 points.	Date of enrollment until end of follow-up (approx. 24 months after enrollment)
The change of asthma control over time and the maintained response after initiation of benralizumab treatment in anti-IL5/IL5R naïve patients initiated with benralizumab treatment using ACQ-6	Change from baseline in asthma control at each visit during the study period, using ACQ-6 in anti-IL5/IL5R naïve patients. ACQ-6 is a validated questionnaire based on 5 symptoms questions (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing), and daily rescue bronchodilator use. Each item is scored on a 7-point scale (0=no impairment; 6=maximum impairment), and the ACQ score is the mean of these items. The MCID is greater than or equal to 0.5.	Date of enrollment until end of follow-up (approx. 24 months after enrollment)
The reasons for biologic treatment change	Investigator-chosen reasons for; Initiation of benralizumab / switching to benralizumab (treatment change from one biologic to another, regardless of the time since the last dose of the previous biologic) at enrolment; discontinuation of benralizumab during the treatment period.	Date of enrollment until end of follow-up (approx. 24 months after enrollment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The change of physical activity over time in anti-IL5/IL5R naïve patients	Change from baseline in steps per day over 24 months of treatment in anti-IL5/IL5R naïve patients.	Baseline until end of follow-up (approx. 24 months after enrollment)
The change in asthma control after 6, 12, 18 and 24 months of treatment in biologic experienced patients, using ACT	Change from baseline in (Asthma Control Test - questionnaire) ACT score at the end of 6, 12, 18 and 24 months of benralizumab treatment in biologic experienced patients. ACT is a simple, validated, 5-item tool giving a total score from 5 (worst control) to 25 (best control). Scores of 20 to 25 denote well-controlled asthma, scores ≤19 identifies patients with poorly controlled asthma. The minimum clinically important difference (MCID) is reported to be 3 points.	Baseline, 6, 12, 18 and 24 months after first treatment
The change in asthma control and the maintained response after initiation of benralizumab treatment in biologic experienced patients using ACQ-6	Change from baseline in ACQ-6 (Asthma-Control-Questionnaire-6) score at the end of 6, 12, 18 and 24 months of benralizumab treatment in biologic experienced patients. ACQ-6 is a validated questionnaire based on 5 symptoms questions (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing), and daily rescue bronchodilator use. Each item is scored on a 7-point scale (0=no impairment; 6=maximum impairment), and the ACQ score is the mean of these items. The MCID is greater than or equal to 0.5.	Baseline, 6, 12, 18 and 24 months after first treatment
The change in HRQL after 6, 12, 18 and 24 months of treatment in biologic experienced patients	Change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score and domain scores (symptoms, activity and impact score) after 6, 12, 18 and 24 months treatment in biologic experienced patients. SGRQ is a validated, 50-item questionnaire, giving scores ranging from 0 (best health status) to 100 (worst health status). The SGRQ yields a total score and 3 domain scores (symptoms, activity, and impacts). The total score indicates the impact of disease on overall health status. A difference of four units in the SGRQ total score is considered the MCID.	Baseline, 6, 12, 18 and 24 months after first treatment
The early treatment response in biologic experienced patients initiated with benralizumab treatment, ACQ-6	Change from baseline in ACQ-6 (Asthma-Control-Questionnaire-6) score after 7 and 14 days of treatment in biologic experienced patients. ACQ-6 is a validated questionnaire based on 5 symptoms questions (night-time waking, symptoms on waking, activity limitation, shortness of breath, wheezing), and daily rescue bronchodilator use. Each item is scored on a 7-point scale (0=no impairment; 6=maximum impairment), and the ACQ score is the mean of these items. The MCID is greater than or equal to 0.5.	Baseline, day 7 and day 14 after first treatment
The early treatment response in biologic experienced patients initiated with benralizumab treatment, patient satisfaction, VAS-1	Change from baseline in patient satisfaction, measured on Visual Analogue Scale (VAS), after 7 and 14 days of treatment in biologic experienced patients. VAS Scores ranged from "extremly satisfied" (0 mm) to "not at all satisfied" (100 mm).	Baseline, day 7 and day 14 after first treatment
The early treatment response in biologic experienced patients initiated with benralizumab treatment, patient symptoms, VAS-2	Change from baseline in patient symptoms, measured on Visual Analogue Scale (VAS), after 7 and 14 days of treatment in biologic experienced patients. VAS Scores ranged from "not at all bothersome" (0 mm) to "extremly bothersome" (100 mm).	Baseline, day 7 and day 14 after first treatment
The investigator reported treatment effectiveness after 6 months of treatment in biologic experienced patients initiated with benralizumab treatment	Investigator-reported treatment effectiveness using GETE (Global Evaluation of Treatment Effectiveness) after 6 months of treatment. GETE grades overall treatment effectiveness using the following criteria: excellent (complete control of asthma); good (marked improvement of asthma); moderate (discernible, but limited improvement in asthma); poor (no appreciable change in asthma); or worsening (of asthma).	6 months after first treatment

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2019
• Primary Completion (Actual): December 19, 2023
• Study Completion (Actual): December 19, 2023

Study Registration Dates

• First Submitted: October 13, 2019
• First Submitted That Met QC Criteria: November 29, 2019
• First Posted (Actual): December 3, 2019

Study Record Updates

• Last Update Posted (Actual): January 26, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: benralizumab
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Hematologic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Leukocyte Disorders; Eosinophilia; Hypereosinophilic Syndrome; Asthma; Pulmonary Eosinophilia
• Other Study ID Numbers: D3250R00053