A Study of GSK3511294 (Depemokimab) in Participants With Severe Asthma With an Eosinophilic Phenotype

Key inclusion criteria for study:

• 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 guidelines (NHLBI) or Global Initiative for Asthma (GINA) guidelines and
• Eosinophilic phenotype: participants who have, or with high likelihood of having, asthma with an eosinophilic phenotype as per randomization criteria, and
• Exacerbation history: participants who 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 (i) For participants >=18 years of age at Visit 1, a pre-bronchodilator FEV1 less than ( =440 micrograms fluticasone propionate (FP) hydrofluoroalkane product (HFA) daily, or clinically comparable (GINA, 2020). 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 inclusion criteria for randomization:

• An elevated peripheral blood eosinophil count of >=300 cells per microliter demonstrated in the past 12 months prior to Visit 1 that is related to asthma or an elevated peripheral blood eosinophil count of >=150 cells per microliter at Screening Visit 1 that is related to asthma.
• Evidence of airway reversibility or responsiveness as documented by either:

(i) Airway reversibility (FEV1>=12% and 200 milliliter [mL]) demonstrated at Visit 1 or Visit 2 using the Maximum Post Bronchodilator Procedure or (ii) Airway reversibility (FEV1>=12% and 200 mL) documented in the 24 months prior to Visit 2 (randomization visit) or (iii) Airway hyper-responsiveness (methacholine: Provocative concentration causing a 20% fall in FEV1 [PC20] of =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] multiplied by 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 any mAb or biologic.

Key exclusion criteria for randomization:

• 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 Electrocardiogram (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.