Severe uncontrolled 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) Provision of signed and dated informed consent prior to any mandatory study specific procedures, sampling and analyses. 2) Subjects must be 12 to 80 years of age inclusive at the time of signing the informed consent form. 3) Documented physician-diagnosed asthma for at least 12 months. 4) Subjects who have received a physician-prescribed asthma controller medication with medium or high dose ICS for at least 12 months. 5) Documented treatment with a total daily dose of either medium or high dose ICS (= 500 ug fluticasone proprionate dry powder formulation equivalent total daily dose) for at least 3 months. 6) At least one additional maintenance asthma controller medication is require according to standard practice of care, eg. LABA, LTRA, theophylline, LAMA, cromones etc. Use of additional asthma controller medications must be document for at least 3 months. 7) Morning pre-BD FEV1 =65 years) yes F.1.3.1 Number of subjects for this age range 135
Exclusion criteria
Exclusion criteria: 1) Any clinically important pulmonary disease other than asthma. 2) History of cancer. 3) History of clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalized =10 pack-years. Former smokers with a smoking history of <10 pack years must have stopped for at least 6 months prior to Visit 1. 5) History or chronic alcohol or drug abuse within 12 months prior to Visit 1. 6) Tuberculosis requiring treatment within 12 months prior to Visit 1. 7) History of known immunodeficiency disorder including a positive human immunodeficiency virus (HIV) test at Visit 1, or the subject taking antiretroviral medications as determined by medical history and/or subject's verbal report. 8) History of anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) following any biological therapy. 9) Subject randomized in the current study or previous tezepelumab studies. 10) Treatment with the following medications within the last 12 weeks prior to randomization: Systemic immunosuppressive/immunomodulating drugs (e.g. methotrexate, cyclosporine, etc) except stable OCS.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the effect of tezepelumab SC Q4W on asthma exacerbations in adult and adolescent subjects with severe uncontrolled asthma compared with placebo.;Secondary Objective: 1) To assess the effect of tezepelumab SC Q4W on: a) pulmonary function compared with placebo. b) health status/health related quality of life compared with placebo. c) asthma control compared with placebo. d) asthma symptoms compared with placebo. Other Secondary objectives: 1) To assess the effect of tezepelumab SC Q4W on: a) other endpoints associated with asthma exacerbations. b) biomarkers. c) other asthma control metrics. d) general health-related quality of life. e) patient (PGI-C and PGI-S) and clinician impression of overall asthma severity (CGI-C). 2) To evaluate the effect of tezepelumab SC Q4W compared with placebo on health resource utilization and productivity loss due to asthma. 3) To evaluate the pharmacokinetics (PK) and immunogenicity of tezepelumab.;Primary end point(s): Primary endpoint: Annualized asthma exacerbation rate (AAER).;Timepoint(s) of evaluation of this end point: Baseline to Week 52. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key Secondary endpoints: 1) Change from baseline in the pre-dose/pre-bronchodilator (pre-BD) forced expiratory volume in 1 second (FEV1). 2) Change from baseline in Standardized Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(S)+12) total score. 3) Change from baseline in Asthma Control Questionnaire-6 (ACQ-6) score. 4) Change from baseline in weekly mean daily Asthma Symptom Diary score. Other Secondary endpoints: 1a) Time to first asthma exacerbation. b) Proportion of subjects with =1 asthma exacerbation. c)Annualized rate of exacerbations associated with emergency room visit, urgent care visit, or hospitalization. 2) Change from baseline in fractional exhaled in nitric oxide FENO (ppb), peripheral blood eosinophils and total serum IgE. 3) Change from baseline in weekly mean rescue medication use, weekly mean morning and evening peak expiratory flow (PEF), and weekly mean number of night time awakenings. 4) Asthma specific resource utilization (eg. unscheduled physician visits, unscheduled phone calls to physicians, use of other asthma medications). Work Productivity and Activity Impairment Questionnaire and Classroom Impairment Questionnaire (WPAI+CIQ) score. 5) PK: Serum trough concentrations; Immunogenicity: Incidence of anti-drug antibodies and neutralizing antibodies. 6) European Quality of Life - 5 Dimensions 5 Levels Questionnaire (EQ-5D-5L) score. 7) Patient Global Impression of Change/Severity (PGI-C, PGI-S) and Clinician Global Impression of Change (CGI-C).;Timepoint(s) of evaluation of this end point: Key Secondary endpoints: 1) Baseline, Week 52 2) Baseline, Week 52 3) Baseline, Week 52 4) Baseline, Week 52 Other Secondary endpoints: 1) Baseline to Week 52 2) Baseline, Week 52 3) Baseline, Week 52 4) Week 52 5) Baseline to Week 52 6) Week 52 7) Week 52 | — |
Countries
Argentina, Australia, Austria, Brazil, Canada, China, France, Germany, Israel, Japan, Korea, Republic of, Russian Federation, Saudi Arabia, South Africa, Taiwan, Ukraine, United Kingdom, United States, Vietnam
Contacts
Public ContactInformation Centre
AstraZeneca AB
Outcome results
None listed