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

This is a multicentre, randomized, double-blind, placebo-controlled, parallel group study to
evaluate the effect of tezepelumab on airway inflammation in adults with inadequately
controlled moderate-to-severe asthma, taking inhaled corticosteroids and at least one
additional asthma controller. Approximately 110 subjects will be randomized globally.
Subjects will receive tezepelumab, or placebo, administered via subcutaneous injection at the
study site, over a 28-week treatment period. The study also includes a post-treatment
follow-up period of 12 weeks.

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. Former smokers with a
smoking history of <10 pack-yrs must have stopped for at least 6 months prior to visit
1

- 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 the current study or previous tezepelumab studies

- Pregnant, breastfeeding or lactating women