Study to Evaluate Tezepelumab on Airway Inflammation in Adults With Uncontrolled Asthma (CASCADE)
Condition: Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases
MeSH terms: Asthma; Lung Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Bronchial Diseases; Respiratory Hypersensitivity; Hypersensitivity; Immune System Diseases; Hypersensitivity, Immediate; Inflammation
Intervention: Tezepelumab; Placebo
Intervention description: Tezepelumab subcutaneous injection; Placebo subcutaneous injection
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized in a 1:1 ratio to either tezepelumab or matching placebo both administered subcutaneously.
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Double-blind
Enrollment: 116.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Asthma; Uncontrolled asthma; Severe uncontrolled asthma

Summary:

      A phase 2, multicentre, randomized, double-blind, placebo-controlled, parallel group study to
      evaluate the effect of tezepelumab on airway inflammation in adults with inadequately
      controlled asthma.
    

Eligibility criteria:

        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.