A Study of GSK3511294 Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype
A Study of GSK3511294 Compared With Mepolizumab or Benralizumab in Participants With Severe Asthma With an Eosinophilic Phenotype
This study will assess whether switching participants who have benefitted from mepolizumab or
 benralizumab to GSK3511294 is non-inferior to maintaining current treatment on the annualized
 rate of clinically significant exacerbations in participants with severe asthma with an
 eosinophilic phenotype. Throughout the study, all participants will continue their
 non-biologic Baseline standard of care (SoC) asthma treatment.
Key inclusion criteria for study:

 -  Adult and adolescent participants more than or equal to (>=)12 years of age, at the
 time of signing the informed consent/assent.

 -  Participants who 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.

 -  Participants receiving either mepolizumab 100 milligrams (mg) or benralizumab 30 mg
 for >=12 months prior to screening and have a documented benefit to therapy assessed
 by either:

 (i) >=50% reduction in exacerbation frequency since initiating treatment, or (ii)
 >=50% reduction in maintenance OCS use since initiating treatment, or (iii) No
 exacerbations in the past 6 months whilst receiving anti-IL-5/5R therapy and an Asthma
 Control Questionnaire (ACQ)-5 score of less than or equal to (<=)1.5 at screening.

 -  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. Participants who are treated with
 medium dose ICS will also need to be treated with a LABA to qualify for inclusion.

 -  Current treatment with at least one additional controller medication, besides ICS [for
 example (e.g.), LABA, LAMA, leukotriene receptor antagonist (LTRA), or theophylline].

 Key exclusion criteria for study:

 -  Participants with 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 excluded
 prior to enrolment.

 -  Participants who have received Omalizumab (Xolair), dupilumab (Dupixent) or reslizumab
 (Cinqair/Cinqaero) within 130 days prior to Visit 1.

 -  Participants who have received any Monoclonal antibody (mAb) within 5 half-lives of
 Visit 1.

 -  Corrected QT interval 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 equal to [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 a mAb or biologic.

 Key exclusion criteria for randomization:

 -  Evidence of a clinically significant abnormality in the 12-lead electrocardiogram
 (ECG) over-read conducted at Screening Visit 1, based on the evaluation of the
 investigator, or QTcF >=450 msec or QTcF >=480 msec for participants with Bundle
 Branch Block, at randomization Visit 2.

 -  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. If the 8-week screening period has
 elapsed, then the participant should be considered a run-in failure.

 -  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.