A Multicentre, Randomised, Double-blind, Parallel Group, Placebo-controlled, Time-to-first Asthma Exacerbation Phase III Efficacy and Safety Study of Benralizumab in Paediatric Patients With Severe Eosinophilic Asthma (DOMINICA)

Inclusion Criteria:

• Capable of giving assent (signing the assent form) to participate in the study. Thecaregiver of the patient must be capable of giving written informed consent for thepatient's participation in the study. Consent and assent forms must be completedprior to any study-specific procedures.

• Patient and the caregiver (where applicable) must be willing to and be able toanswer questionnaires that are part of the study procedures.

• Male or female patients aged ≥ 6 to < 18 years old.

• Patients with physician-diagnosed severe eosinophilic asthma for at least 12 monthsprior to Visit 1.

• Patients with a diagnosis of severe asthma confirmed, evaluated, and managed by theclinical site/site network for ≥ 6 months prior to Visit 1.

• Patients with an exacerbation history of asthma exacerbations (defined as arequirement for systemic corticosteroids and/or hospitalisation) within 12 monthsprior to Visit 1, OR,

1. 2 asthma exacerbations (defined as a requirement for systemic corticosteroidsand/or hospitalisation) per year within the 2 years prior to Visit 1 AND, oneor more of the following:

2. Currently on stable maintenance oral corticosteroids (OCS) used for at least 3months prior to Visit 1, OR,

3. At least one of the 2 exacerbations that occurred in the year prior to Visit 1resulted in hospitalisation.

• Patients on well-documented, stable treatment for asthma with high dose ICS and atleast one additional controller medication, such as long-acting β2 agonists (LABA),leukotriene receptor antagonists (LTRA), long-acting muscarinic antagonists (LAMA),or theophylline, since at least 6 months prior to Visit 1.

• Eosinophilic airway inflammation that is related to asthma characterised aseosinophilic in nature as indicated by peripheral blood eosinophil count of ≥ 300cells/μL during screening OR a blood eosinophil count of 150 to 299 cells/μL anddocumentation of elevated eosinophils in bronchoalveolar lavage (BAL), sputum, orbronchial biopsy within the 2 years prior to Visit 1.

• ≥ 70% compliance with maintenance asthma medication during the screening periodbased on the Paediatric Asthma Symptom - Observer reported (PASO) or Asthma DailyDiary.

• At least 70% daily PASO or Asthma Daily Diary completion during the entire screeningperiod, with at least 50% PASO or Asthma Daily Diary completion in the 14-day periodprior to randomisation.

• Pre-BD FEV1 ≤ 95% of the predicted normal value or pre-BD FEV1/FVC ratio < 0.85required at Visit 1. Patients with ≥ 25 % increase in pre-BD FEV1 value during thescreening period will be screen failed.

• ACQ-IA ≥ 1.5 with no meaningful improvement (ACQ-IA change ≤ -0.5) between screeningand Visit 2a.

• Body weight ≥ 15 kg.

• Females of childbearing potential (FOCBP) who are sexually active, as judged by theinvestigator, must commit to consistent and correct use of a highly effective methodof contraception.

Exclusion Criteria:

• Clinically important pulmonary disease other than asthma or patients who have everbeen diagnosed with pulmonary or systemic disease, other than asthma, that areassociated with elevated peripheral eosinophil counts.

• Life-threatening asthma.

• Asthma exacerbation requiring use of systemic corticosteroids or increase inmaintenance dose of OCS within 2 weeks prior to Visit 2a or acute upper/lowerrespiratory infection that requires antibiotics or antiviral medication within 2weeks prior to the first dose of the IP (Visit 2b).

• Any disorder that is not stable in the opinion of the investigator and could affectthe safety of the patient during the study, influence the findings of the studies ortheir interpretations or impede the patient's ability to complete the entireduration of the study.

• History of anaphylaxis to any biologic therapy.

• Current malignancy, or history of malignancy.

• A helminth parasitic infection.

• Use of immunosuppressive medication.

• Receipt of immunoglobulin or blood products within 30 days prior to Visit 1.

• Receipt of any marketed or investigational biologic within 5 half-lives prior toVisit 1.

• Previously received benralizumab (MEDI-563).

• Participation in another interventional clinical study.

• Patients with known hypersensitivity to benralizumab or any of the excipients of theproduct.

• Currently pregnant, breastfeeding, or lactating females.

• Previous randomisation in the present study.