Depemokimab is being developed as a treatment for individuals with moderate to severe COPD. The aim of this study is to assess the efficacy and safety of depemokimab compared as an add-on medicine in participants with uncontrolled moderate to severe COPD with type 2 inflammation.

Inclusion Criteria:

• Participants must be greater than or equal to (>=) 40 to less than or equal to (<=) 80 years of age, at the time of signing the Informed consent

• Elevated Blood Eosinophil Count (BEC)

• 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-bronchodilator forced expiratory volume in one second (FEV1)/ forced vital capacity (FVC) ratio of < 0.70 and a post-bronchodilator FEV1 >30 percent (%) and <= 80% predicted normal values
  • A well-documented history of at least 2 moderate or 1 severe exacerbation in the 12 months prior to screening

• COPD assessment test (CAT) score >=10 at Visit 1

• Smoking status: Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years.

• Participants should be on optimized inhaler therapy, defined as inhaled corticosteroid (ICS) plus Long-acting muscarinic receptor antagonist (LAMA) plus Long-acting beta2-adrenergic receptor agonist (LABA) either as multiple inhalers or a single combination inhaler for at least 6 months prior to Screening Visit 1

• Body mass index (BMI) >=16 kilogram per square meter (kg/m^2)

• Male and eligible female participants

Exclusion Criteria:

The following subjects are excluded:

• Participants with a current or prior physician diagnosis of asthma
• Other clinically significant lung disease: The Investigator must judge that COPD is the primary diagnosis accounting for the clinical manifestations of the lung disease
• Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening Visit 1
• Lung resection: Participants with a history of or plan for lung volume reduction surgery / endobronchial valve procedure.
• Pulmonary rehabilitation: Participants in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to Screening Visit 1
• Continuous oxygen: Participants requiring oxygen supplementation for more than 12 hours per day
• Cor pulmonale - resulting in right heart failure, severe pulmonary hypertension
• Chronic hypercapnia requiring Non-invasive positive pressure ventilation (NIPPV) use (including Bi-Level Positive Airway Pressure [BiPAP] or Continuous Positive Airway Pressure [CPAP])
• Unstable cardiovascular disease or arrhythmia
• Parasitic Infection: Participants with a known, pre-existing parasitic infection within 6 months of Screening (Visit 1)

Study Sponsor will assess requests from qualified researchers for anonymized individual patient-level data and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf

Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or asset(s) with development terminated across all indications.

Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension may be granted, when justified, for up to 6 months.

This is a double-blind study neither the participants the caregivers the researchers nor the people assessing the outcomes know which treatment is being given to whom.