A Study to Assess the Efficacy and Safety of Co-administration of GSK3862995B with GSK5784283 in Adult Participants With Moderate to Severe Chronic Obstructive Pulmonary Disease (COPD)ALARMONY

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

• Basal Metabolic Rate (BMI) >= 16 kilogram per meter square (kg/m^2)
• Moderate to severe COPD with frequent exacerbations, defined as o a clinically documented history of COPD as defined by the American Thoracic Society/European Respiratory Society for at least 1 year prior to the screening visit; o a post-salbutamol FEV1/Forced vital capacity (FVC) ratio of less than (<) 0.70 and a post-salbutamol FEV1 greater than (>) 30 percent (%) and >= 80% predicted normal values calculated withGlobal Lung Function Initiative (GLI)

Global Race Neutral equations in line with the American Thoracic Society (ATS) recommendations at screening; o a well-documented history (e.g., medical record verification, including capturing of all prior biologic use) of at least 2 moderate or 1 severe exacerbations in the 12 months prior to screening despite the use of Inhaled Corticosteroids (ICS) containing maintenance COPD treatment; at least one qualifying exacerbation must have occurred while participant was on ICS plus long-acting muscarinic antagonist (LAMA) plus long-acting beta agonist (LABA); Moderate exacerbations must have been treated with systemic corticosteroids and/or antibiotics (subcutaneous [SCS]; Intramuscular [IM], Intravenous [IV], or oral); Severe exacerbations are those requiring hospitalization or observation >24 hours in the emergency department /urgent care facility

• Smoking status: Current or former cigarette smokers with a history of cigarette smoking of >=10 pack-years at Screening. Former smokers are defined as those who have stopped all cigarette smoking for at least 6 months prior to the Screening Visit
• An eosinophilic phenotype with elevated Blood eosinophil count (BEC) at screening
• CAT total score ≥ 10,
• Participants should be on standard of care COPD maintenance inhaler therapy, defined as ICS plus LAMA plus LABA either as multiple inhalers or a single combination inhaler for at least 6 months prior to the Screening Visit and on a stable dose for at least 3 months prior to the Screening Visit
• Participants on adjunctive COPD therapies such as chronic macrolide antibiotics, Phosphodiesterase (PDE)4 or PDE3-4 inhibitors, or chronic oral corticosteroids (up to 15 mg prednisone equivalent per day) may participate, provided they have been on these medications for 6 months, and on a stable dose for at least 3 months immediately prior to the Screening Visit
• A female participant is eligible to participate if she is not pregnant or breastfeeding
• Is a Participant of non-childbearing potential (PONCBP)
• Is a Participant of childbearing potential (POCBP) and using a contraceptive method that is highly effective, with a failure rate of <1%, at least 42 days prior to and during the study intervention period and for at least 60 weeks after the last dose of study intervention.
• Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the Informed Consent Form (ICF) and in this protocol

Participants with a current or prior physician diagnosis of asthma are excluded

• 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 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
• COPD stability: Participants with pneumonia, COPD exacerbation, or lower respiratory tract infection within the 4 weeks prior to Screening are excluded
• Lung resection: Participants with a history of, or plan for lung volume reduction surgery / endobronchial valve procedure are excluded
• Pulmonary rehabilitation: Participants in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to the Screening Visit are excluded. Participants who are in the maintenance phase of a pulmonary rehabilitation program may participate
• Continuous oxygen: Participants 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 Liters per minute (L/min) at the time of the screening visit and for the duration of the study. Participants on long term oxygen therapy (LTOT) should be ambulatory and able to attend clinic visits
• Cor pulmonale – resulting in right heart failure, severe pulmonary hypertension is excluded
• Chronic hypercapnia requiring Non-invasive Positive Pressure Ventilation (NIPPV) use (including Bilevel Positive Airway Pressure [BiPAP] or Continuous positive airway pressure [CPAP]) are excluded
• Participants with unstable cardiac disease; myocardial infarction or stroke within 12 months prior to screening; or New York Heart Association Class III or IV heart failure
• Participants with clinically significant abnormal Electrocardiogram (ECG) at screening which in the judgment of the Investigator, may affect participant safety or affect study endpoints
• Participants with a history of lymphoma, leukemia, or any malignancy within the past 5 years, except for basal cell or squamous epithelial carcinomas of the skin that have been resected for cure with no evidence of recurrence or metastatic disease for 1-year
• A known or suspected immunodeficiency that has led to opportunistic infections, recurrent invasive infections, or prolonged infections that suggest an underlying immunocompromised state by the judgement of the investigator. Positive HIV antibody test
• Active Nontuberculous mycobacterial (NTM) lung infection on treatment or meeting ATS/ Infectious Diseases Society of America (IDSA) criteria for active lung infection
• Active tuberculosis, untreated latent Tuberculosis (TB), invasive fungal lung infections or allergic bronchopulmonary aspergillosis needing treatment
• Participants should not have an active, invasive fungal infection as assessed by the investigator and should not be on chronic antifungal therapy. Participants who have completed antifungal therapy more than 4 weeks prior to screening and have been deemed clinically cured are eligible
• Vasculitis: Participants with current diagnosis of vasculitis. Participants with high clinical suspicion of vasculitis at screening will be evaluated and current vasculitis must be excluded prior to enrolment
• Eosinophilic 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
• Parasitic Infection: Participants with a known, pre-existing parasitic infection within 6 months of Screening, or infection detected at Screening
• History of an unresolved clinically significant infection within 30 days prior to the screening visit
• Immunodeficiency: A known immunodeficiency other than that explained by use of corticosteroids (e.g., HIV)
• Other concurrent medical conditions: 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. Clinically 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
• A positive human immunodeficiency virus (HIV) test at screening or subject taking antiretroviral medications, as determined by medical history and/or subject’s verbal report
• Presence of hepatitis B surface antigen (HBsAg) and/or hepatitis B virus (HBV) DNA at screening or within 3 months prior to first dose of study intervention. HBV DNA will only be tested if a participant is core antibody positive
• Positive hepatitis C antibody test result at screening or within 3 months prior to first dose of study intervention
• Alanine aminotransferase (ALT) >2*Upper Limit to Normal (ULN)
• Total bilirubin >1.5xULN; Participants with Gilbert’s syndrome can be included with total bilirubin >1.5xULN as long as direct bilirubin is <=1.5*ULN
• 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
• Previous documented treatment failure or non-response to anti-IL-33 or anti – Thymic Stromal Lymphopoietin (TSLP) therapy
• Short term oral corticosteroids: Participants who have received short term use of oral corticosteroids within 4 weeks of the Screening Visit
• Use of immunosuppressive medication (e.g., methotrexate, mycophenolate, cyclosporine, azathioprine, intramuscular long-acting depot corticosteroid, maintenance systemic (oral) corticosteroids for an indication other than COPD) within 3 months prior to screening and up until the end of the study treatment period (i.e., Week 24-72 depending on whether the participant is scheduled to receive 2-6 doses of the study intervention)
• Received any live attenuated vaccine within 30 days prior to screening or plans to receive such vaccines up until the end of the study
• Ongoing treatment with cyclic doses of systemic antibiotics
• Current enrollment or past participation in another investigational study in which an investigational intervention (e.g., drug, vaccine, invasive device) was administered within the following time period prior to the screening visit of the current study: 30 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer). This also includes investigational formulations of a marketed product
• Previously participated in any clinical study with biologic treatments for respiratory conditions (e.g., omalizumab, mepolizumab, dupilumab, reslizumab, benralizumab, tezepelumab or depemokimab) and received study intervention (including placebo) within 12 months prior to Screening
• Receipt of any investigational non-biologic agent within 1 month or 5 half-lives prior to screening, whichever is longer and up until the end of the follow-up period
• Experimental vaccines are not permitted within 30 days prior to randomization and up until the end of the follow-up period
• Previous randomization in the present study
• Known or suspected history of alcohol or drug abuse with 2 years prior to screening
• History of severe allergic reaction, anaphylaxis or documented immune complex disease (Type III hypersensitivity reactions) to any biologic therapy
• 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