Efficacy and Safety of Tozorakimab in Symptomatic Chronic Obstructive Pulmonary Disease With a History of Exacerbations

Inclusion Criteria:

1. Participant must be ≥ 40 years of age and capable of giving signed informed consent.

2. Documented diagnosis of COPD for at least one year prior to enrolment.

3. Post BD FEV1/FVC < 0.70 and post-BD FEV1 >20% of predicted normal value

4. Documented history of ≥ 2 moderate or ≥ 1 severe COPD exacerbations within 12 monthsprior to enrolment.

5. Documented optimised inhaled dual or triple therapy for at least 3 months prior toenrolment.

6. Smoking history of ≥ 10 pack-years.

7. CAT total score ≥ 10, with each of the phlegm (sputum) and cough items with a score ≥ 2

Exclusion Criteria:

1. Clinically important pulmonary disease other than COPD.

2. Radiological findings suggestive of a respiratory disease other than COPD that issignificantly contributing to the participant's respiratory symptoms. Radiologicalfindings of pulmonary nodules suspicious for lung cancer, as per applicableguidances, without appropriate follow up prior to randomisation. Radiologicalfindings suggestive of acute infection.

3. Current diagnosis of asthma, prior history of asthma, or asthma-COPD overlap.Childhood history of asthma is allowed and defined as asthma diagnosed and resolvedbefore the age of 18

4. Any unstable disorder, including, but not limited to, cardiovascular,gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious,endocrine, metabolic, haematological, psychiatric disorder, major physical and/orcognitive impairment that could affect safety, study findings or participantsability to complete the study.

5. COPD exacerbation, within 2 weeks prior to randomization, that was treated withsystemic corticosteroids and/or antibiotics, and/or led to hospitalization.

6. Active significant infection within the 4 weeks prior to randomization, pneumoniawithin 6 weeks prior to randomization, or medical condition that predisposes theparticipant to infection.

7. Suspicion of, or confirmed, ongoing SARS-CoV-2 infection.

8. Significant COVID-19 illness within the 6 months prior to enrolment.

9. Unstable cardiovascular disorder.

10. Diagnosis of cor pulmonale, pulmonary arterial hypertension and/or right ventricularfailure.

11. History of active severe inflammatory bowel disease or colitis within one year priorto enrolment, or unexplained diarrhoea within the 4 weeks prior to randomisation.

12. History of known immunodeficiency disorder, including a positive test for HIV-1 orHIV 2.

13. History of positive test or treatment for hepatitis B or hepatitis C (except forcured hepatitis C)

14. Evidence of active liver disease, including jaundice during screening.

15. Malignancy, current or within the past 5 years, except for adequately treatednon-invasive basal cell and squamous cell carcinoma of the skin and cervicalcarcinoma-in-situ treated with apparent success more than one year prior toenrolment. Suspected malignancy or undefined neoplasms.

16. Participants who have evidence of active TB.

17. History of partial or total lung resection.

18. Scheduled major surgical procedure during the course of the study.

19. Participants that have previously received tozorakimab.

20. Any clinically significant abnormal findings in physical examination, vital signs,ECG, or laboratory testing during the screening period, which in the opinion of theinvestigator may put the participant at risk because of their participation in thestudy, or may influence the results of the study, or the participant's ability tocomplete the entire duration of the study.