Inclusion Criteria:
Participants are eligible to be included in the study only if all of the following criteria apply:
Age
1 Adult participants 40 to 80 years of age at the time of signing the informed consent.
Type of Participant and Disease Characteristics
2 Documented physician-diagnosed COPD for at least 12 months before Visit 1.
3 A post-BD FEV1/FVC normal value during screening.
4 Documented regular dose of triple (ICS+LABA+LAMA) or dual (LABA+LAMA,
ICS+LABA, ICS+LAMA) inhaled therapy for at least 3 consecutive months before
Visit 1
5 Documented history ≥ 2 moderate1 or ≥ 1 severe2 COPD exacerbations within 12 months
before Visit 1. At least 1 of the 2 moderate exacerbations must have been treated with
SCS.
6 EOS ≥ 150 cells/μL during the screening period.
7 CAT total score ≥ 15 at Visit 1.
8 Current or former smokers (with smoking cessation ≥ 6 months before Visit 1) have a
history of at least 10 pack-years of tobacco smoking (1 pack year = 20 cigarettes smoked
per day for 1 year).
Weight
9 Body weight ≥ 40 kg at Visit 1.
Sex and Contraceptive/Barrier Requirements
10 Participants not of childbearing potential are defined as participants who are either
permanently sterilised (hysterectomy, bilateral oophorectomy, or bilateral
salpingectomy), or who are postmenopausal. Women will be considered postmenopausal
if they have been amenorrhoeic for 12 months prior to the planned date of randomisation
without an alternative medical cause. The following age-specific requirements apply:
− Women amenorrhoeic for 12 months or more following cessation of exogenous hormonal
treatment and FSH levels in the postmenopausal range.
− Women ≥ 50 years old would be considered postmenopausal if they have been
amenorrhoeic for 12 months or more following cessation of all exogenous hormonal
treatment.

Exclusion Criteria:
Participants are excluded from the study if any of the following criteria apply:
Medical Conditions
1 Clinically important pulmonary disease other than COPD (eg, active lung infection,
clinically significant bronchiectasis, pulmonary fibrosis, cystic fibrosis, hypoventilation
syndrome associated with obesity, lung cancer, alpha 1 anti-trypsin deficiency and
primary ciliary dyskinesia) or another diagnosed pulmonary or systemic disease that is
associated with elevated peripheral EOS (eg, allergic bronchopulmonary
aspergillosis/mycosis, eosinophilic granulomatosis with polyangiitis, hypereosinophilic
syndrome).
2 Radiological findings suggestive of a respiratory disease other than COPD that is
significantly contributing to the participant’s respiratory symptoms. Radiological findings
of pulmonary nodules suspicious for lung cancer, as per applicable guidance, (eg, ACR
Lung-RADS v2022, (Christensen et al 2024)) without appropriate follow up before Visit
3 Radiological findings suggestive of acute infection.
4 Current physician diagnosed asthma according to the Global Initiative for Asthma (GINA
2024 and onwards versions) guidelines or other accepted guidelines, past physician
diagnosed asthma including paediatric asthma, or asthma-COPD overlap syndrome.
5 Any unstable disorder, including, but not limited to, cardiovascular, gastrointestinal,
hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic,
haematological, immune, psychiatric, or major physical/or cognitive impairment that is
not stable in the opinion of the investigator or the sponsor and/or could:
− Affect the safety of the participant throughout the study
− Influence the findings of the study or their interpretation
− Impede the participant’s ability to complete the entire duration of the study and/or
comply with the study visit schedule and procedures.
6 Unstable cardiovascular disorder (including but not limited to ischemic heart disease,
arrhythmia, cardiomyopathy, severe right and/or left heart failure (NYHA class IV)),
renal failure, uncontrolled hypertension, as defined by the Investigator, or any other
relevant cardiovascular disorder or ECG abnormality that in the Investigator’s judgment
may put the participant at risk or negatively affect the outcome of the study.
7 Acute upper or lower respiratory infection requiring antibiotics or systemic antiviral
medication within 2 weeks before Visit 1 (based on the last day of antibiotic/antiviral
treatment, whichever occurred later). Lower respiratory infection requiring hospitalisation
less than 4 weeks before Visit 1 (based on the date of discharge from hospital).
8 COPD exacerbation treated with SCS and/or antibiotics within 2 weeks before Visit 1
(based on the last dose of corticosteroids or antibiotics, whichever occurred later), or/and
requiring hospitalisation for COPD within 4 weeks before Visit 1 (based on the date of
discharge from hospital).
9 A helminth parasitic infection within 6 months before Visit 1 that has not been treated
with, or has failed to respond to, the SoC therapy, or diagnosed during the screening
period.
10 Immunodeficiency disorder including a positive HIV test before Visit 1 or during the
screening period.
11 Tuberculosis requiring treatment within the 12 months before Visit 2.
12 Anaphylaxis or documented immune complex disease (Type III hypersensitivity
reactions) following any biologic therapy.
13 Chronic alcohol or drug abuse within 12 months before Visit 1 or during screening, which
may compromise the interpretation of the study data as judged by investigator.
14 Major surgery within 8 weeks before Visit 1 or planned surgical procedures requiring
general anaesthesia or hospitalisation for > 1 day during the study.
15 Malignancy, current or past (within 5 years before Visit 1), except for basal cell
carcinoma, localised squamous cell carcinoma of the skin, or in situ carcinoma of the
cervix provided when a curative therapy was completed at least 12 months before Visit 1.
Prior/Concomitant Therapy
16 Past or planned partial or total lung volume reduction (single lobe or segmentectomy is
acceptable). Surgical or endoscopic (eg, valves) lung volume reduction within 6 months
before Visit 1 or a planned procedure.
17 Treatment with systemic immunosuppressive/immunomodulating medications including
maintenance use of SCS within the last 12 weeks or 5 half-lives before Visit 1 or during
the screening for other reasons than COPD exacerbation. Expected need for chronic use
during the study for any reason.
18 LTOT with signs and/or symptoms of cor pulmonale and/or right ventricular failure, or
LTOT > 4.0 litres/minute (L/min) at rest or an oxyhaemoglobin saturation LTOT.
19 Use, or need for chronic use, of any non-invasive positive pressure ventilation device.
Stable use of non-invasive ventilation for the treatment of Obstructive Sleep Apnoea is
permitted.
20 Treatment with maintenance allergen-specific immunotherapy initiated Visit 1.
21 Maintenance treatment with macrolides or other antibiotics for COPD if the duration of
the treatment is 22 Treatment with any marketed respiratory biologic or investigational biologic within
4 months or 5 half-lives before randomisation, whichever is longer.
Note: Treatment with marketed ocular biologics is allowed. Other marketed biologics that
are not likely to interfere with the safety assessment and/or efficacy of tezepelumab might
be allowed upon a prior AZ study physician/delegate approval.