Study to Evaluate Tezepelumab on Airway Inflammation in Adults With Uncontrolled Asthma (CASCADE)

Principal Inclusion Criteria:

• Subject must be 18 to 75 years of age.
• Documented physician-diagnosed asthma for at least 12 months.
• Subjects who have received a physician- prescribed asthma controller medication with medium or high dose ICS for at least 12 months; must be stable for at least 3 months prior to screening visit.
• At least one additional maintenance asthma controller medication is required according to standard practice of care and must be documented for at least 3 months.
• At enrolment, the subject must have a predicted normal value for the morning pre-bronchodilator FEV1>50% and more than 1L.
• Evidence of asthma as documented by reversibility of FEV1 ≥12% and ≥200 mL in the previous 12 months prior to screening, or during the screening period prior to randomization.
• ACQ-6 score ≥ 1.5 during the screening period prior to randomization.

Principal Exclusion Criteria:

• Any clinically important pulmonary disease other than asthma.
• History of cancer.
• Hospitalization or required OCS for asthma exacerbation within 6 weeks of enrolment or >3 exacerbations requiring OCS or hospitalization in the year prior to visit 1 or who had been intubated or admitted to ICU for asthma exacerbation in the year prior to enrolment.
• History of a clinically significant infection, including upper (URTI) or lower respiratory tract infection (LRTI), requiring treatment with antibiotics or antiviral medications finalized <2 weeks before visit 1 or during the run-in period.
• Current smokers or subjects with smoking history ≥10 pack-yrs, including e-cigarettes. Former smokers with a smoking history of <10 pack-yrs must have stopped for at least 6 months prior to visit 1, including e-cigarette use.
• History of chronic alcohol or drug abuse within 12 months prior to visit 1.
• Tuberculosis requiring treatment within 12 months prior to visit 1.
• History of known immunodeficiency disorder including a positive HIV test at visit 1, or the subject is taking antiretroviral medications as determined by medical history and/or subject's verbal report.
• History of anaphylaxis or documented immune complex disease (type III hypersensitivity reactions) following any biologic therapy Subject randomized in a previous Tezepelumab study or in a current study with another investigational product.
• Pregnant, breastfeeding or lactating women.