A Study of GSK3511294 in Participants With Severe Asthma With an Eosinophilic Phenotype
A Study of GSK3511294 in Participants With Severe Asthma With an Eosinophilic Phenotype
This study will assess the efficacy and safety of GSK3511294 as an adjunctive therapy in
 participants with severe uncontrolled asthma with an eosinophilic phenotype despite standard
 of care (SoC) treatment with medium to high dose inhaled corticosteroid (ICS) plus at least
 one additional controller.
Key inclusion criteria for study:

 -  Adults and adolescents >=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, 2007) or Global
 Initiative for Asthma (GINA) guidelines (GINA, 2020) and (a) Eosinophilic phenotype:
 participants who have, or with high likelihood of having, asthma with an eosinophilic
 phenotype as per randomization criteria, and (b) 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 <80 percent predicted National Health and
 Nutrition Examination Survey (NHANES III) recorded at Visit 1 (ii)For participants
 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 <90 percent 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 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 (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 percent and 200 milliliter [mL]) demonstrated at Visit 1 or
 Visit 2 using the Maximum Post Bronchodilator Procedure or (ii)Airway reversibility
 (FEV1>=12 percent and 200 mL) documented in the 12 months prior to Visit 2
 (randomization visit) or (iii) Airway hyperresponsiveness (methacholine: Provocative
 concentration causing a 20 percent fall in FEV1 [PC20] of <8 milligrams per milliliter
 (mg/mL), histamine: Provocative dose that decreases FEV1 by 20 percent [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 for study:

 -  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 who have known, pre-existing, clinically significant cardiac, endocrine,
 autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological
 or any other system abnormalities that are uncontrolled with standard treatment.

 -  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, reslizumab, or benralizumab within 12
 months prior to Visit 1 or who have a previous documented failure with
 Anti-Interleukin-5/ Anti-Interleukin-5 receptor (anti-IL-5/5R) therapy.

 -  Participants who have received omalizumab or dupilumab within 130 days prior to Visit
 1.

 -  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.

 -  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 = [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 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.

 -  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.