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

Study Overview
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Brief Summary
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This study will assess the efficacy and safety of GSK3511294 (Depemokimab) as an adjunctive therapy in participants with severe uncontrolled asthma with an eosinophilic phenotype.

Official Title
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A 52-week, Randomised, Double-blind, Placebo-controlled, Parallel-group, Multi-centre Study of the Efficacy and Safety of GSK3511294 Adjunctive Therapy in Adult and Adolescent Participants With Severe Uncontrolled Asthma With an Eosinophilic Phenotype

Conditions
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Asthma

Intervention / Treatment
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* Biological: GSK3511294 (Depemokimab)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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 (<)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% 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 (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 <8 milligrams per milliliter (mg/mL), histamine: Provocative dose that decreases FEV1 by 20% [PD20] of <7.8 micromoles, mannitol: decrease in FEV1 as per the labelled product instructions) documented in the 24 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 (Nucala), reslizumab (Cinqair/Cinqaero), or benralizumab (Fasenra) 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 (Xolair) or dupilumab (Dupixent) 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 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.

Ages Eligible for Study
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Minimum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized in a 2:1 ratio to receive either GSK3511294 (Depemokimab) or placebo as an adjunct therapy.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving GSK3511294 (Depemokimab)<br> | Biological: GSK3511294 (Depemokimab)<br>* GSK3511294 (Depemokimab) will be administered using a pre-filled syringe.<br>|
| Placebo Comparator: Participants receiving Placebo<br> | Biological: Placebo<br>* Placebo will be administered as normal saline using a pre-filled syringe.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized rate of clinically significant exacerbations over 52 weeks |  | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Saint (St.) George's Respiratory Questionnaire (SGRQ) total score at Week 52 | The SGRQ is a well-established instrument, comprising 50 items designed to measure Quality of Life in participants with diseases of airway obstruction. It consists of two parts: Part 1 produces the symptom score and Part 2 produces the activity and impact score. A Total score is also calculated which summarizes the impact of the disease on overall health status. Scores are expressed as a percentage of overall impairment where 100 represents worst possible health status and zero indicates best possible health status. Higher scores indicate worse quality of life. | Baseline (Day 1) and at Week 52 | 
| Change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score at Week 52 | The ACQ-5 is a five-item questionnaire, which has been developed as a measure of participants' asthma control that can be quickly and easily completed. The five questions enquire about the frequency and/or severity of symptoms (nocturnal awakening on waking in the morning, activity limitation, and shortness of breath, wheeze) over the previous week. The response options for all these questions consist of a zero (no impairment/limitation) to six (total impairment/ limitation) scale. Higher score indicates more limitations. | Baseline (Day 1) and at Week 52 | 
| Change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) at Week 52 | FEV1 will be measured using spirometry. | Baseline (Day 1) and at Week 52 | 
| Annualized rate of exacerbations requiring hospitalization and/or Emergency Department (ED) visit over 52 weeks |  | Up to Week 52 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Eosinophilic phenotype, Exacerbations, GSK3511294 (Depemokimab), Placebo