Participant must be at least 40 years of age at Screening Visit 1.
Participants with a peripheral blood eosinophil count of ≥ 300 cells/μL from the haematology sample collected at Screening Visit 0. Participants with a documented historical blood eosinophil count of ≥ 150 cells/μL in the 12 months prior to Screening Visit 0 that meet the following: it must have been measured between 12 months and 1 month prior to Screening Visit 0, and it must not have been measured within 14 days of a COPD exacerbation. Participants with no documented historical blood eosinophil count of ≥ 150 cells/µL must meet this threshold at the Screening Visit 1 assessment.
Participants with a clinically documented history of COPD for at least 1 year in accordance with the definition by the ATS or ERS.
Participants must present with a measured pre‐ and post‐salbutamol FEV₁/FVC ratio of < 0.70 at Screening Visit 1 to confirm the diagnosis of COPD and with a measured post‐salbutamol FEV₁ > 20% and ≤ 80% of predicted normal values calculated using NHANES III reference equations at Screening Visit 1.
Participants must have a well‐documented history (e.g. medical record verification) in the 12 months prior to Screening Visit 1 of 2 or more moderate COPD exacerbations that were treated with systemic corticosteroids (IM, IV, or oral) with or without antibiotics or at least 1 severe COPD exacerbation requiring hospitalisation.
Participants must have a well‐documented requirement for optimised standard of care background therapy that includes ICS plus 2 additional COPD medications (ICS‐based triple therapy) for the 12 months prior to Screening Visit 1 and meet the following criteria: immediately prior to Screening Visit 1, minimum of 3 months of use of 1) inhaled corticosteroid at a dose ≥ 500 μg per day fluticasone propionate dose equivalent plus 2) LABA and 3) LAMA unless documentation of safety or intolerance issues related to LABA or LAMA. For participants who are not continually maintained on ICS plus LABA plus LAMA for the entire 12 months prior to Visit 1, use of the following is allowed (but not in the 3 months immediately prior to Visit 1): inhaled corticosteroid at a dose ≥ 500 μg per day fluticasone propionate dose equivalent plus inhaled LABA or inhaled LAMA and PDE4 inhibitors, methylxanthines, or scheduled daily use of SABA and/or SAMA.
Current or former cigarette smokers with a history of cigarette smoking of ≥ 10 pack‐years at Screening (Visit 1) calculated as (number of pack years = (number of cigarettes per day/20) multiplied by number of years smoked (e.g. 20 cigarettes per day for 10 years or 10 cigarettes per day for 20 years)).
Contraceptive use for female participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
A female participant is eligible to participate if she is not pregnant or breastfeeding, and at least 1 of the following conditions applies: she is not a WOCBP, or she is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of < 1%, during the intervention period and for at least 16 weeks after the last dose of study intervention. The principal investigator should evaluate the effectiveness of the contraceptive method in relation to the first dose of study intervention.
A WOCBP must have a negative highly sensitive pregnancy urine test within 24 hours before the first dose of study intervention. If a urine test cannot be confirmed as negative (e.g. an ambiguous result), a serum pregnancy test is required. In such cases, the WOCBP must be excluded from participation if the serum pregnancy result is positive.
Participants capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form and in this protocol.
Participants with a past history or concurrent diagnosis of asthma are excluded regardless of whether they have active or inactive disease.
The Investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease. Participants with alpha₁‐antitrypsin deficiency as the underlying cause of COPD are excluded. Participants with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases, or other active pulmonary diseases are also excluded.
Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit 1.
Participants with lung volume reduction surgery within the 12 months prior to Screening Visit 1.
Participation in the acute phase of a pulmonary rehabilitation programme within 4 weeks prior to Screening Visit 1. Participants who are in the maintenance phase of a pulmonary rehabilitation programme are not excluded.
Participants receiving treatment with oxygen more than 2 L/min at rest over 24 hours. For participants receiving oxygen treatment, they should demonstrate an oxyhaemoglobin saturation ≥ 89% whilst breathing supplemental oxygen.
Participants with a QT interval, from the ECG conducted at Screening Visit 1, corrected with Fridericia's formula (QTcF) > 450 ms (or QTcF > 480 ms in participants with bundle branch block). Fridericia's formula must be used to determine eligibility and discontinuation for an individual participant. Participants are excluded if an abnormal ECG finding from the 12‐lead ECG conducted at Screening Visit 1 is considered to be clinically significant and would impact the individual's participation during the study, based on the evaluation of the Investigator.
Participants with any of the following are excluded: myocardial infarction or unstable angina in the 6 months prior to Screening Visit 1; unstable or life‐threatening cardiac arrhythmia requiring intervention in the 3 months prior to Screening Visit 1; NYHA Class IV heart failure.
Participants with historical or current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease), or haematological abnormalities that are uncontrolled. 'Significant' is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or which could affect the efficacy or safety analysis if the disease/condition exacerbated during the study.
Participants with other conditions that could lead to elevated eosinophils such as hypereosinophilic syndromes including eosinophilic granulomatosis with polyangiitis (also known as Churg‐Strauss syndrome) or eosinophilic oesophagitis.
Participants with a known, pre‐existing parasitic infestation within 6 months prior to Screening Visit 1.
A current malignancy or previous history of cancer in remission for less than 12 months prior to Screening Visit 1 (participants with localised carcinoma of the skin or cervix which was resected for cure are not excluded).
Participants with a known immunodeficiency (e.g. HIV) other than that explained by the use of corticosteroids taken for COPD.
Participants with cirrhosis or current unstable liver disease per investigator assessment defined as the presence of ascites, encephalopathy, coagulopathy, hypoalbuminaemia, oesophageal or gastric varices, or persistent jaundice. Stable non‐cirrhotic chronic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B or C (e.g. presence of HbsAg) or positive hepatitis C antibody test result) is acceptable if the participant otherwise meets entry criteria.
Participants who have received interventional product in previous mepolizumab studies are excluded.
Participants who have received any monoclonal antibody within 5 half‐lives of Screening Visit 1.
Participants who have received an investigational drug within 30 days of Visit 1, or within 5 drug half‐lives of the investigational drug, whichever is longer (this also includes investigational formulations of a marketed product).
Participants who have received short‐term oral corticosteroids treatment within 30 days of Visit 1.
Participants with a known allergy or sensitivity to any of the study interventions, or components thereof, or drug or other allergy that, in the opinion of the Investigator or Medical Monitor, contraindicates participation in the study, or intolerance to another monoclonal antibody or biologic including history of anaphylaxis to another biologic.
Participants at risk of non‐compliance, or unable to comply with the study procedures. Any infirmity, disability, or geographic location that would limit compliance for scheduled visits.
Participants with conditions that would limit the validity of informed consent to participate in the study, e.g. uncontrolled psychiatric disease or intellectual deficiency.
Participants with a known or suspected history of alcohol or drug abuse within 2 years prior to Visit 1.
