Placebo-controlled Efficacy and Safety Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype

Key inclusion Criteria: * Adults and adolescents greater than or equal to (\>=)12 years of age, at the time of signing the informed consent/assent. * Participants must have a documented physician diagnosis of asthma for \>=2 years that meets the National Heart, Lung, and Blood Institute (NHLBI) guidelines or Global Initiative for Asthma (GINA) guidelines and 1. Have, or with high likelihood of having, asthma with an eosinophilic phenotype 2. Have previously confirmed history of \>=2 exacerbations requiring treatment with systemic corticosteroid (CS) (intramuscular \[IM\], intravenous \[IV\], or oral), in the 12 months prior to Visit 1, despite the use of medium to high-dose ICS. For participants receiving maintenance CS, the CS treatment for the exacerbations must have been a two-fold dose increase or greater. * Persistent airflow obstruction as indicated by: 1. For participants \>=18 years of age at Visit 1, a pre-bronchodilator FEV1 less than (\<)80% predicted (The Third National Health and Nutrition Examination Survey \[NHANES III\]) recorded at Visit 1 2. For participants 12-17 years of age at Visit 1: * A pre-bronchodilator FEV1 \<90% predicted (NHANES III) recorded at Visit 1 OR * FEV1:Forced Vital Capacity (FVC) ratio \<0.8 recorded at Visit 1. * A well-documented requirement for regular treatment with medium to high dose ICS (in the 12 months prior to Visit 1 with or without maintenance OCS). The maintenance ICS dose must be \>=440 micrograms (mcg) Fluticasone propionate (FP) Hydrofluoroalkane (HFA) product daily, or clinically comparable (GINA). Participants who are treated with medium dose ICS will also need to be treated with LABA to qualify for inclusion. * Current treatment with at least one additional controller medication, besides ICS, for at least 3 months (for example \[e.g.\], LABA, LAMA, leukotriene receptor antagonist \[LTRA\], or theophylline). Key randomization inclusion criteria: * For blood eosinophilic count: 1. An elevated peripheral blood eosinophil count of \>=300 cells/microliter (mcL) demonstrated in the past 12 months prior to Visit 1 that is related to asthma OR 2. An elevated peripheral blood eosinophil count of \>=150 cells/mcL at Screening Visit 1 that is related to asthma. * Evidence of airway reversibility or responsiveness as documented by either: 1. Airway reversibility (FEV1\>=12% and 200 milliliters \[mL\]) demonstrated at Visit 1 or Visit 2 using the Maximum Post Bronchodilator Procedure OR 2. Airway reversibility (FEV1\>=12% and 200 mL) documented in the 24 months prior to Visit 2 (randomization visit) OR 3. Airway hyperresponsiveness (methacholine: Provocative concentration causing a 20% fall in FEV1 \[PC20\] of \<8 milligrams (mg)/mL, histamine: PD20 of \<7.8 micromoles, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 months prior to Visit 2 (randomization visit). Key exclusion Criteria: * Presence of a known pre-existing, clinically important lung condition other than asthma. This includes (but is not limited to) current infection, bronchiectasis, pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a history of lung cancer. * Participants with other conditions that could lead to elevated eosinophils such as hyper-eosinophilic syndromes including (but not limited to) Eosinophilic Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or Eosinophilic Esophagitis. * A current malignancy or previous history of cancer in remission for less than 12 months prior to screening (Participants that had localized carcinoma of the skin which was resected for cure will not be excluded). * 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. * 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. * Participants who have received mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or benralizumab (Fasenra) within 12 months prior to Visit 1 or who have a previous documented failure with anti-IL-5/5 receptor (R) therapy. * Participants who have received omalizumab (Xolair) or dupilumab (Dupixent) within 130 days prior to Visit. * Participants who have received any monoclonal antibody (mAb) within 5 half-lives of Visit 1. * Previously participated in any study with mepolizumab, reslizumab, or benralizumab and received study intervention (including placebo) within 12 months prior to Visit 1. * The QT interval corrected using Fridericia's formula (QTcF) \>=450 milliseconds (msec) or QTcF \>=480 msec for participants with Bundle Branch Block at screening Visit 1. * Current smokers or former smokers with a smoking history of \>=10 pack years (number of pack years = \[number of cigarettes per day/20\] times number of years smoked). A former smoker is defined as a participant who quit smoking at least 6 months prior to Visit 1. * Participants with allergy/intolerance to the excipients of GSK3511294 or a any mAb or biologic. Key radomization exclusion criteria: * QTcF \>=450 msec or QTcF \>=480 msec for participants with Bundle Branch Block, at randomization Visit 2 are excluded. 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 participant's participation during the study, based on the evaluation of the Investigator. * Participants with a clinically significant asthma exacerbation in the 7 days prior to randomization should have their randomization visit delayed until the investigator considers the participant's asthma to be stable . * Any changes in the dose or regimen of Baseline ICS and/or additional controller medication (except for treatment of an exacerbation) during the run-in period.