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Adults and adolescents greater than or equal to (>=)12 years of age, at the time of signing the informed consent/assent |
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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 |
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Eosinophilic phenotype: participants who have, or with high likelihood of having, asthma with an eosinophilic phenotype as per randomization criteria, and |
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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 |
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Persistent airflow obstruction as indicated by (i) For participants >=18 years of age |
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Key inclusion criteria for randomization |
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at Visit 1, a pre-bronchodilator FEV1 less than (<)80 percent (%) predicted |
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National Health and Nutrition Examination Survey (NHANES III) recorded at |
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Visit 1 |
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(ii) For participants 12-17 years of age at Visit 1: A pre-bronchodilator FEV1 <90% |
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predicted (NHANES III) recorded at Visit 1 or FEV1: Forced Vital Capacity (FVC) ratio <0.8 |
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recorded at Visit 1 |
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A well-documented requirement for regular treatment with medium to high dose ICS (in |
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Evidence of airway reversibility or responsiveness as documented by either |
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the 12 months prior to Visit 1 with or without maintenance OCS). The maintenance ICS |
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dose must be >=440 micrograms fluticasone propionate (FP) hydrofluoroalkane product |
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(HFA) daily, or clinically comparable (GINA, 2020). Participants who are treated with |
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medium dose ICS will also need to be treated with LABA to qualify for inclusion |
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Current treatment with at least one additional controller medication, besides ICS, for |
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at least 3 months (for example [e.g.], LABA, LAMA, leukotriene receptor antagonist |
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[LTRA], or theophylline) |
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An elevated peripheral blood eosinophil count of >=300 cells per microliter |
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demonstrated in the past 12 months prior to Visit 1 that is related to asthma or an |
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elevated peripheral blood eosinophil count of >=150 cells per microliter at Screening |
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Visit 1 that is related to asthma |
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(i) Airway reversibility (FEV1>=12% and 200 milliliter [mL]) demonstrated at Visit 1 |
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or Visit 2 using the Maximum Post Bronchodilator Procedure or (ii) Airway |
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reversibility (FEV1>=12% and 200 mL) documented in the 24 months prior to Visit 2 |
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(randomization visit) or (iii) Airway hyper-responsiveness (methacholine: Provocative |
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concentration causing a 20% fall in FEV1 [PC20] of <8 milligrams per milliliter |
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(mg/mL), histamine: Provocative dose that decreases FEV1 by 20% [PD20] of <7.8 |
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micromoles, mannitol: decrease in FEV1 as per the labelled product instructions) |
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documented in the 24 months prior to Visit 2 (randomization visit) |
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Key exclusion criteria for randomization
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Presence of a known pre-existing, clinically important lung condition other than
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asthma. This includes (but is not limited to) current infection, bronchiectasis
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pulmonary fibrosis, bronchopulmonary aspergillosis, or diagnoses of emphysema or
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chronic bronchitis (chronic obstructive pulmonary disease other than asthma) or a
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history of lung cancer
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Participants with other conditions that could lead to elevated eosinophils such as
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hyper-eosinophilic syndromes including (but not limited to) Eosinophilic
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Granulomatosis with Polyangiitis (EGPA, formerly known as Churg-Strauss Syndrome) or
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Eosinophilic Esophagitis
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A current malignancy or previous history of cancer in remission for less than 12
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months prior to screening (Participants that had localized carcinoma of the skin which
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was resected for cure will not be excluded)
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Cirrhosis or current unstable liver or biliary disease per investigator assessment
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defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia
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esophageal or gastric varices, persistent jaundice
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Participants who have known, pre-existing, clinically significant cardiac, endocrine
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autoimmune, metabolic, neurological, renal, gastrointestinal, hepatic, hematological
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or any other system abnormalities that are uncontrolled with standard treatment
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Participants with current diagnosis of vasculitis. Participants with high clinical
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suspicion of vasculitis at screening will be evaluated and current vasculitis must be
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excluded prior to enrolment
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Participants who have received mepolizumab (Nucala), reslizumab (Cinqair/Cinqaero), or
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benralizumab (Fasenra) within 12 months prior to Visit 1 or who have a previous
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documented failure with Anti-Interleukin-5/Anti-Interleukin-5 receptor (anti-IL-5/5R)
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therapy
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Participants who have received omalizumab (Xolair) or dupilumab (Dupixent) within 130
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days prior to Visit 1
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Participants who have received any monoclonal antibody (mAb) within 5 half-lives of
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Visit 1
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Previously participated in any study with mepolizumab, reslizumab, or benralizumab and
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received study intervention (including placebo) within 12 months prior to Visit 1
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Corrected QT interval using Fridericia's formula (QTcF) >=450 milliseconds (msec) or
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QTcF >=480 msec for participants with Bundle Branch Block at screening Visit 1
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Current smokers or former smokers with a smoking history of >=10 pack years (number of
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pack years = [number of cigarettes per day/ 20] multiplied by number of years smoked)
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A former smoker is defined as a participant who quit smoking at least 6 months prior
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to Visit 1
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Participants with allergy/intolerance to the excipients of GSK3511294 or any mAb or
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biologic
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QTcF >= 450 msec or QTcF >=480 msec for participants with Bundle Branch Block, at
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randomization Visit 2 are excluded. Participants are excluded if an abnormal
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Electrocardiogram (ECG) finding from the 12-lead ECG conducted at Screening Visit 1 is
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considered to be clinically significant and would impact the participant's
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participation during the study, based on the evaluation of the Investigator
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Participants with a clinically significant asthma exacerbation in the 7 days prior to
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randomization should have their randomization visit delayed until the investigator
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considers the participant's asthma to be stable
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Any changes in the dose or regimen of Baseline ICS and/or additional controller
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medication (except for treatment of an exacerbation) during the run-in period
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