Severe Asthma MedDRA version: 20.0 Level: PT Classification code 10003553 Term: Asthma System Organ Class: 10038738 - Respiratory, thoracic and mediastinal disorders
Conditions
Sponsors
AstraZeneca AB
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Subject must be 18 to 80 years of age inclusive at the time of signing the informed consent form 2)Subjects must have received a physician-prescribed medium- or highdose ICS as per GINA guideline for at least 12 months 3)Subjects must have received physician prescribed LABA and high dose ICS (total daily dose >500µg fluticasone propionate dry powder formulation equivalent) for at least 3 months prior to visit 1. The ICS and LABA can be parts of a combination product, or given by separate inhalers. 4)Additional maintenance asthma controller medications are allowed according to standard practice of care i.e., leukotriene receptor antagonists (LTRAs), theophylline, long-acting muscarinic antagonists (LAMAs), secondary ICS and cromones. The use of these medications must be documented for at least 3 months 5)Subjects must have received OCS for the treatment of asthma for at least 6 months prior to visit 1 and on a stable dose of between = 7.5 to = 30mg (prednisone or prednisolone equivalent) daily or daily equivalent for at least 1 month. The OCS dose may be administered every other day(or different doses every other day); Average dose over two days = The daily dose. 6)Morning pre-bronchodilator (BD) FEV1 must be =65 years) yes F.1.3.1 Number of subjects for this age range 23
Exclusion criteria
Exclusion criteria: 1)Any clinically important pulmonary disease other than asthma (e.g. active lung infection, Chronic Obstructive Pulmonary Disease (COPD), bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency, and primary ciliary dyskinesia) or ever diagnosed with pulmonary or systemic disease, other than asthma, that are associated with elevated peripheral eosinophil counts (e.g. allergic bronchopulmonary aspergillosis/mycosis, Churg-Strauss syndrome, hypereosinophilic syndrome). 2)Any disorder, including, but not limited to, cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physical impairment that is not stable in the opinion of the Investigator and could: Affect the safety of the subject throughout the study Influence the findings of the study or the interpretation Impede the subject's ability to complete the entire duration of study 3)History of cancer: Subjects who have had basal cell carcinoma, localized squamous cell carcinoma of the skin or in situ carcinoma of the cervix are eligible to participate in the study provided that curative therapy was completed at least 12 months prior to visit 1.Subjects who have had other malignancies are eligible provided that curative therapy was completed at least 5 years prior to visit 1 4)History of a clinically significant infection, including upper or lower respiratory tract infection (URTI and LRTI, respectively), requiring treatment with antibiotics or antiviral medications finalized 1 day during the conduct of the study. 11)Clinically significant asthma exacerbation, in the opinion of the Investigator, including those requiring use of systemic corticosteroids or increase in the maintenance dose of OCS within 30 days prior to to visit 1 12) During the optimization period, asthma control reached at an OCS dose of 30mg and/or 3 consecutive dose reductions after which asthma control was still obtained 13)Evidence of clinically significant infection or subject receiving treatment with antibiotics or antiviral meidcations
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of tezepelumab compared with placebo in reducing the prescribed OCS maintenance dose in patients with asthma requiring chronic treatment with maintenance OCS in addition to high dose ICS plus LABA;Secondary Objective: Key Secondary Objective: 1)To evaluate the effect of tezepelumab compared with placebo on asthma exacerbations Other Secondary Objectives: 1) To evaluate the effect of tezepelumab compared with placebo on the prescribed, OCS daily maintenance dose 2)To evaluate the effect of tezepelumab compared with placebo on Pre-BD lung function 3)To assess the effect of tezepelumab compared with placebo with regards to asthma symptoms and other asthma control metrics 4)To assess the effect of tezepelumab compared with placebo with regards to asthma related and general health-related quality of life 5)To evaluate the efficacy of tezepelumab compared with placebo on health resource utilization and productivity loss due to asthma 6)To assess the effect of tezepelumab on biomarkers 7)To evaluate the pharmacokinetics (PK) and immunogenicity of tezepelumab;Primary end point(s): Categorized percent reduction from baseline in the daily OCS dose at Week 48 while not losing asthma control The categories for percent change from baseline in daily OCS dose are defined as: 1. =90% to =100% reduction 2. =75% to 0% to <50% reduction 5. no change or any increase;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary Endpoint: Annualized asthma exacerbation rate (AAER) Other Secondary Endpoints: 1a)Proportion of subjects with 100% reduction from baseline in daily OCS dose at Week 48 1b)Proportion of subjects with daily OCS dose =5 mg at Week 48 1c)Proportion of subjects with =50% reduction from baseline in daily OCS dose at Week 48 2)Change from baseline in Pre-bronchodilator forced expiratory volume in 1 second (FEV1) 3a)Change from baseline in weekly mean daily Asthma Symptom Score as captured in the daily Asthma Symptom Diary (ASD 3b)Change from baseline in weekly mean rescue medication use 3c) Change from baseline in weekly mean home peak expiratory flow (morning and evening) 3d) Change from baseline in weekly mean number of night-time awakening due to asthma 3e) Change from baseline in Asthma Control Questionnaire 6 (ACQ-6) score 4a)Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) total score 4b)Change from baseline in European Quality of Life – 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score 5a) Number of asthma specific resource utilizations (e.g. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications) 5b) Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire (WPAI+CIQ) 6a)Change from baselin in FENO 6b)Change from baseline peripheral blood eosinophils and total IgE 7a) PK: Serum trough concentrations 7b)Immunogenicity: Incidence of anti-drug antibodies (ADA);Timepoint(s) of evaluation of this end point: Key Secondary Endpoint: Baseline to Week 48 Other Secondary Endpoints: 1)Week 48 2)Baseline, Week 48 3)Baseline, Week 48 4)Baseline, Week 48 5)Week 48 6)Baseline, Week 48 7)Baseline to Week 48 | — |
Countries
Argentina, Germany, Korea, Republic of, Poland, Turkey, Ukraine, United States
Outcome results
None listed