Placebo-controlled Efficacy and Safety Study of GSK3511294 in Participants With Severe Asthma With an Eosinophilic Phenotype
Placebo-controlled Efficacy and Safety Study of GSK3511294 in Participants With Severe Asthma With an Eosinophilic Phenotype
GSK3511294 is being developed as a long-acting (LA) injectable anti-interleukin-5 (anti-IL-5)
 therapy and is expected to deliver an efficacy and safety profile similar to current
 anti-IL-5 therapies with a reduced dosing frequency. This study is a multi-center,
 randomized, placebo-controlled, double-blind, parallel group design and aims to assess the
 efficacy and safety of GSK3511294 in participants with severe uncontrolled asthma with an
 eosinophilic phenotype despite standard of care (SoC) treatment with medium to high dose
 inhaled corticosteroids (ICS) plus at least one additional controller. All participants will
 receive study intervention as an adjunct therapy while remaining on their existing asthma
 therapy throughout the study. Assessments will include the annualized rate of clinically
 significant exacerbations and measures of lung function, asthma control, and safety.
 Approximately 375 participants will be enrolled in the study.
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 12 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 12 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 a mAb or biologic.

 Key radomization exclusion criteria:

 -  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 .

 -  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.