STEP: Phase IIIb study of benralizumab to step-down maintenance therapy in patients with severe eosinophilic asthma - STEP

Exclusion Criteria

• -
• Medical Conditions:
• 1 Unable to commit to the scheduled visits as required by the protocol, or unable to commit to undergoing protocol guided reductions in asthma therapy, as directed by the Investigator.
• 2 Clinically important pulmonary disease other than asthma (e.g., active lung infection, chronic obstructive pulmonary disease [COPD], bronchiectasis, pulmonary fibrosis, cystic fibrosis), or ever been diagnosed with pulmonary or systemic disease, other than asthma, that is associated with elevated peripheral eosinophil counts (e.g., allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome).
• 3 Current smokers or former smokers with a smoking history ≥20 pack/years.
• 4 History of alcohol or drug abuse within 12 months prior to Visit 1(Week -1 to Week 0).
• 5 A helminth parasitic infection diagnosed within 24 weeks prior to Visit 1(Week -1 to Week 0) that has not been treated with, or has failed to respond to, standard of care therapy.
• 6 History of anaphylaxis to any biologic therapy.
• 7 Known history of allergy or reaction to any component of the study treatment formulation.
• 8 Respiratory exacerbation requiring use of Systemic corticosteroids (SCS) or acute upper/lower respiratory infection that required antibiotics or antiviral medication within 30 days prior to Visit 1(Week -1 to Week 0). An extension of the screening period up to 3 months is allowed to ensure that a patient recovering from any repiratory exacerbation or acute upper/lower respiratory infection can be included.
• 9 A history of known immunodeficiency disorder, including human immunodeficiency virus.
• 10 Current or history of malignancy within 5 years before the screening visit with the following exceptions:
• • In-situ carcinoma of the cervix where curative therapy has been completed and patients are in remission for at least 12 months prior to screening.
• • Basal cell or superficial squamous skin cancer.
• Patients who have had other malignancies are eligible provided that the patient is in remission and curative therapy was completed at least 5 years prior to the date informed consent was obtained.
• 11 Exclusion for any of the following:
• • Previous allogeneic bone marrow transplant.
• • Non-leucocyte depleted whole blood transfusion within 120 days of genetic sample collection.
• 12 Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, haematological, psychiatric, or major physical impairment that is not stable in the opinion of the investigator and could:
• (a) Affect the safety of the patient throughout the study,
• (b) Confound the study results or impact the scientific validity of the data outcome,
• or
• (c) Impede the patient’s ability to complete the entire duration of study.
• Prior/Concomitant Therapy:
• 13 Oral corticosteroid use during 4 weeks prior to Visit 1(Week -1 to Week 0).
• 14 Use of immunosuppressive medication (including but not limited to: methotrexate, troleandomycin, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, or any experimental anti-inflammatory therapy) within 3 months or 5 halflives (whichever is longer) prior to the date informed consent is obtained.
• 15 Receipt of any marketed or investigational biologic agent within 4 months or 5 half lives (whichever is longer) prior to Visit 1(Week -1 to Week 0) or receipt of any investigational non biologic agent within 30 days or 5 half-lives (whichever is longest) prior to Visit 1(Week -1 to Week 0). Exception:
• (a) For marketed non-respiratory biologics, it is allowed if the patient is stable on treatment for at least 3 months prior to Visit 1(Week -1 to Week 0) and throughout the study.
• (b) Covid-related prevention and treatment
• 16 Receipt of live attenuated vaccines 30 days prior to the date of first dose of benralizumab.
• 17 Intention to use any concomitant medication that is not permitted or failure to complete the required washout period for a particular prohibited medication.
• 18 Receipt of immunoglobulin or blood products within 30 days prior to the date informed consent is obtained.
• 19 Received bronchial thermoplasty (BT) as treatment of asthma within 12 months prior to Visit 1.
• Prior/Concurrent Clinical Study Experience:
• 20 Concurrent participation in another clinical study with an Investigational Product or a post-authorization safety study
• Diagnostic Assessments:
• 21 Any clinically significant abnormal findings in physical examination, medical history, vital signs, haematology, or clinical chemistry during the enrolment period, which in the opinion of the investigator, may put the patient at risk because of his/her participation in the study, or may influence the results of the study, or the patient’s ability to complete the entire duration of the study.
• Other Exclusions:
• 22 For females only - currently pregnant (confirmed with positive pregnancy test), breast feeding, or lactating.
• 23 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• 24 Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions, and requirements.
• 25 Previous enrolment in the present study.