Clinical Trials List
Protocol Number206785
NCT Number(ClinicalTrials.gov Identfier)NCT04718389
2021-01-04 - 2023-12-31
Phase III
Recruiting1
Terminated5
A 52-week, randomised, double-blind, double-dummy, parallel group, multi-centre, non-inferiority study assessing exacerbation rate, additional measures of asthma control and safety in adult and adolescent severe asthmatic participants with an eosinophilic phenotype treated with GSK3511294 compared with mepolizumab or benralizumab
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Trial Applicant
IQVIA RDS Taiwan Ltd.
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Sponsor
GlaxoSmithKline Research & Development Limited
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- Ming -Cheng Chan Division of Thoracic Medicine
- 王俊隆 Division of Thoracic Medicine
- 覃俊士 Division of Thoracic Medicine
- Wei- Chang Huang Division of Thoracic Medicine
- Pin-Kuei Fu Division of Thoracic Medicine
- 趙文震 Division of Thoracic Medicine
- 王振宇 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 林聖皓 Division of General Internal Medicine
- 紀炳銓 Division of General Internal Medicine
- 黃國揚 Division of General Internal Medicine
- 陳正雄 Division of General Internal Medicine
- 張竣期 Division of General Internal Medicine
- 詹博強 Division of General Internal Medicine
- 葉金水 Division of General Internal Medicine
- 蔡偉宏 Division of General Internal Medicine
- 蔡偉宏 Division of General Internal Medicine
- 施穎銘 Division of General Internal Medicine
- 林俊維 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 張晟瑜 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 黃建達 Division of General Internal Medicine
- 莊立邦 Division of General Internal Medicine
- 林錞語 Division of General Internal Medicine
- 羅友倫 Division of General Internal Medicine
- 羅君禹 Division of General Internal Medicine
- Chih-Hsi Kuo Division of General Internal Medicine
- Chun-Hua Wang Division of General Internal Medicine
- 謝孟亨 Division of General Internal Medicine
- 李忠恕 Division of General Internal Medicine
- Horng-Chyuan Lin Division of General Internal Medicine
- 張博瑞 Division of General Internal Medicine
- 林定佑 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Terminated
Co-Principal Investigator
- 廖偉志 Division of Thoracic Medicine
- Wen-Chien Cheng Division of Thoracic Medicine
- Bing-Ru Wu Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
severe asthmatic participants with an eosinophilic phenotype
Objectives
This study will assess whether switching participants who have benefitted from mepolizumab or benralizumab to GSK3511294 (Depemokimab) 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.
Test Drug
GSK3511294
Active Ingredient
GSK3511294
Dosage Form
prefilled safety syringe
Dosage
100mg/mL
Endpoints
Primary Outcome Measures :
Annualized rate of clinically significant exacerbations over 52 weeks [ Time Frame: Up to Week 52 ]
Clinically significant exacerbations of asthma are defined by worsening of asthma which requires use of systemic corticosteroids and/or hospitalization and/or Emergency Department (ED) visit. Annualized rate of exacerbations will be calculated as number of exacerbations experienced by the participant divided by the length of time the participant is measured on.
Secondary Outcome Measures :
Weighted mean change from Baseline in St. George's Respiratory Questionnaire (SGRQ) total score [ Time Frame: Baseline (Day 1) and up to Week 52 ]
The SGRQ is a well-established instrument, comprising 51 questions designed to measure Quality of Life in participants with diseases of airway obstruction. Higher score indicates worse quality of life.
Weighted mean change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score [ Time Frame: Baseline (Day 1) and up to 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.
Weighted mean change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
FEV1 is a measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 will be measured using spirometry.
Annualized rate of clinically significant exacerbations over 52 weeks [ Time Frame: Up to Week 52 ]
Clinically significant exacerbations of asthma are defined by worsening of asthma which requires use of systemic corticosteroids and/or hospitalization and/or Emergency Department (ED) visit. Annualized rate of exacerbations will be calculated as number of exacerbations experienced by the participant divided by the length of time the participant is measured on.
Secondary Outcome Measures :
Weighted mean change from Baseline in St. George's Respiratory Questionnaire (SGRQ) total score [ Time Frame: Baseline (Day 1) and up to Week 52 ]
The SGRQ is a well-established instrument, comprising 51 questions designed to measure Quality of Life in participants with diseases of airway obstruction. Higher score indicates worse quality of life.
Weighted mean change from Baseline in Asthma Control Questionnaire-5 (ACQ-5) score [ Time Frame: Baseline (Day 1) and up to 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.
Weighted mean change from Baseline in pre-bronchodilator forced expiratory volume in one second (FEV1) [ Time Frame: Baseline (Day 1) and up to Week 52 ]
FEV1 is a measure of pulmonary function and is the maximum amount of air that can be forced out in one second after taking a deep breath. FEV1 will be measured using spirometry.
Inclution Criteria
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].
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].
Exclusion Criteria
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.
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.
The Estimated Number of Participants
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Taiwan
48 participants
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Global
1700 participants
