Airway Dysfunction, Occlusions and Remodeling: COPD Patients and Mepolizumab

Inclusion Criteria: * Patient understands study procedures and is willing to participate in the study as indicated by the patient's signature. * Provision of written, informed consent prior to any study specific procedures. * Males and females 55-85 years of age. * An eosinophilic phenotype with elevated BEC with a documented measurement of ≥ 300 cells/µL at Baseline/screening Visit 1. * CT mucus-count ≥ 3 on baseline/screening CT OR on previous clinical CT acquired within last 12 weeks AND evaluable for mucus occlusions. * Moderate to severe COPD with frequent exacerbations, defined as: * A clinically documented history of COPD as defined by the American Thoracic Society/European Respiratory Society for at least 1 year. * A post-salbutamol FEV1/FVC ratio of \< 0.70 and a post-salbutamol FEV1 ≥ 30% and \< 80% predicted at screening. * A well-documented history (e.g., medical record verification) of at least 2 moderate or 1 severe exacerbation in the 12 months prior to screening: 1. At least one qualifying exacerbation must have occurred while participant is on ICS-LAMA-LABA. 2. Moderate exacerbations must have been treated with systemic corticosteroids. 3. Severe exacerbations are those requiring hospitalization (i.e., ≥ 24 hours) * Smoking status: Ex-cigarette smokers (quit ≥ 1 year) with a history of cigarette smoking of ≥ 10 pack-years at Baseline/screening Visit 1. * Participants should be on maintenance inhaler therapy, defined as ICS+LAMA+LABA, either as multiple inhalers or a single combination inhaler for at least 3 months prior to Baseline Visit 1. * Participants on adjunctive COPD therapies such as roflumilast, chronic macrolide antibiotics may participate, provided they have been on these medications for at least 6 months, and on a stable dose for at least 3 months immediately prior to Baseline Visit 1. These participants should remain on these therapies for the duration of the study. * Women of non-childbearing potential will be included. Such females will be: Permanently sterile due to one of the following procedures: 1. Documented hysterectomy. 2. Documented bilateral salpingectomy. 3. Documented bilateral oophorectomy. For permanently sterile individuals due to an alternate medical cause other than the above, (e.g., Mullerian agenesis, androgen insensitivity, gonadal dysgenesis), investigator discretion should be applied to determining study entry. If reproductive status is questionable, additional evaluation should be considered. Note: Documentation will stem from review of participant's medical records, medical examination, or medical history interview. Postmenopausal female. Females who are confirmed post-menopausal for ≥ 1year. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high FSH level in the postmenopausal range may be used to confirm a postmenopausal state in participants not using hormonal contraception or HRT. In the absence of 12 months of amenorrhea, confirmation with more than one FSH measurement is required. Females on HRT and whose menopausal status is in doubt must discontinue HRT to allow confirmation of postmenopausal status before study enrollment. Exclusion Criteria: * Patient has an implanted mechanically, electrically, or magnetically-activated device or any metal in their body which cannot be removed, including but not limited to pacemakers, neurostimulators, biostimulators, implanted insulin pumps, aneurysm clips, bioprosthesis, artificial limb, metallic fragment or foreign body, shunt, surgical staples (including clips or metallic sutures and/or ear implants) (at the discretion of the MRI Technologist). * In the Investigator's opinion, participant suffers from any physical, psychological, or other condition(s) that might prevent performance of the MRI or CT, such as severe claustrophobia. * Participant is unable to perform spirometry or plethysmography maneuvers. * Participant is unable to perform MRI and CT breath-hold maneuvers. * Participants with any diagnosis of asthma at any time are excluded. A diagnosis of asthma should be based on both a history of typical respiratory symptoms combined with evidence of variable expiratory airflow limitation at the time of diagnosis consistent with GINA 2023 or other accepted guidelines. * Participants with α1-antitrypsin deficiency as the underlying cause of COPD are excluded. Also excluded are participants with active tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, primary pulmonary hypertension, interstitial lung diseases or other active pulmonary diseases. * Participants with pneumonia, active COPD exacerbation at screening/baseline visit, or lower respiratory tract infection within the 4 weeks prior to Baseline Visit 1. * Participants with a history of, or plan for lung volume reduction surgery/endobronchial valve procedure. * Participants in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Baseline Visit 1 are excluded. Participants who are in the maintenance phase of a pulmonary rehabilitation program may participate. * Patients requiring oxygen supplementation for more than 12 hours per day are excluded. Non-continuous (i.e., 12 hours or less per day) oxygen is permitted up to 2 L/min at screening. * Participants with Cor-pulmonale resulting in right heart failure, severe pulmonary hypertension. * Participants with chronic hypercapnia requiring BiPAP. * Participants with unstable cardiovascular disease. * Participants with other conditions that could lead to elevated eosinophils such as Hypereosinophilic syndromes including Eosinophilic Granulomatosis with Polyangiitis (EGPA, also known as Churg-Strauss Syndrome), or Eosinophilic Esophagitis. * Participants with a known, pre-existing parasitic infection within 6 months of Baseline Visit 1. * Participants with a current malignancy or previous history of cancer in remission for less than 12 months prior to Baseline Visit 1 (localized carcinoma of the skin or cervix resected for cure not excluded). * Participants with a known immunodeficiency (e.g., human immunodeficiency virus-HIV). * Participants with cirrhosis or current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice. NOTE: stable non-cirrhotic liver disease (including Gilbert's syndrome, asymptomatic gallstones, and chronic stable hepatitis B (in whom Hepatitis D (HDV) has been excluded)) or C are acceptable if participant otherwise meets entry criteria. * Participants with (historical or) current evidence of clinically significant, neurological, psychiatric, renal, hepatic, immunological, endocrine (including uncontrolled diabetes or thyroid disease) or hematological 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. * Previous exposure to monoclonal antibodies targeting IL-5/5R, IL-4R/IL-13, IL-33, or TSLP within 6 months or 5 half-lives, prior to Baseline Visit 1. * Previous documented failure with anti-IL-5/5R or anti-IL-4R/IL-13 therapy. * Other monoclonal antibodies: participants who have received any monoclonal antibody within 5 half-lives of Screening Visit 1. * Participants who have received short term use of oral corticosteroids within 4 weeks of Visit 1. * Previous randomization in the present study. * Concurrent enrolment in another clinical trial. * 12-lead ECG at Baseline Visit 1: participants with QT interval corrected with Fridericia's formula (QTcF) \> 450 ms (or QTcF \> 480 ms in participants with bundle branch block). * QTcF is the QT interval corrected for heart rate according to Fridericia's formula that is selected for this study. It is either machine-read or manually over-read when not automatically machine read. This specific formula must be used to determine eligibility for an individual participant. * Participants are excluded if an abnormal ECG finding from the 12-lead ECG conducted at Baseline Visit 1 is considered to be clinically significant and would impact the participant's participation during the study, based on the evaluation of the Investigator. * Where a single ECG demonstrates a prolonged QTcF interval, obtain two more ECGs readings at a minimum of 2 minutes apart over a brief recording period (e.g., 5-10 minutes), The average of the triplicate QTcF measurements should be used to determine eligibility. * Participants with a known allergy or sensitivity to any of the study interventions or study treatment, 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 will limit the validity of informed consent to participate in the study, e.g., uncontrolled psychiatric disease or intellectual deficiency. * A known or suspected history of alcohol or drug abuse within 2 years prior to Baseline Visit 1. * For sputum induction, participants who have had previous bronchospasm or prior intolerance to a hypertonic saline solution, poorly controlled COPD on the day of sample collection, or oxygen saturation of less than 88% on room air will not take part in the induced sputum collection. * Female participants: Women of childbearing potential (after menarche) will NOT be enrolled.