This study will investigate the efficacy and safety of Tezepelumab as add-on treatment to inhaled maintenance therapy in a COPD population with a history of exacerbations. This study will compare the safety and tolerability of Tezepelumab with placebo in participants with moderate to very severe COPD. On completion of all screening assessments and confirmation of eligibility, participants will be randomized in a ratio of 1:1:1 to receive Tezepelumab (420 mg Q4W or 210 mg Q4W) or placebo Q4W. Participants will receive Tezepelumab or matching placebo for a minimum of 52 weeks (with the last dose at Week 48) and a maximum of 76 weeks of treatment (with the last dose at Week 72).

This study will include eligible participants aged 40 to 80 years old with: 

1. Physician-diagnosed COPD for at least 12 months before Visit 1

2. COPD assessment test (CAT) score of > 15 at Visit 1

3. EOS ≥ 150 cells/μL during the screening period

4. Current or former smokers

5. History of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 months before Visit 1 of which at least 1 of the 2 moderate exacerbations must have required treatment with systemic corticosteroids.

Participants should be receiving regular inhaled maintenance therapy or dual therapy for at least 3 consecutive months prior to Visit 1.  

Participants should be encouraged to continue on the same regular COPD background therapy throughout the study.

Participants with other significant respiratory diseases, including asthma will be excluded.