Asthma
Conditions
Keywords
Asthma, GSK3511294 (Depemokimab), Mepolizumab, Benralizumab, Interventional, Eosinophilic phenotype
Brief summary
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.
Interventions
BIOLOGICALGSK3511294 (Depemokimab)
GSK3511294 (Depemokimab) 100 mg SC along with the placebo and SOC will be administered.
BIOLOGICALMepolizumab
Mepolizumab 100 mg SC will be administered in a single-use PFS.
BIOLOGICALBenralizumab
Benralizumab 30 mg will be administered in a single-use PFS.
BIOLOGICALPlacebo
Placebo will be a sterile liquid formulation.
DRUGStandard of care (SoC)
Non-biologic SoC will include inhaled corticosteroid (ICS) plus at least one other controller, long-acting beta-2-agonist (LABA), long-acting muscarinic antagonist (LAMA), with or without maintenance oral corticosteroids (OCS).
DEVICEPre-filled Syringes (PFS)
PFS will include glass barrel with pre-staked needle and plunger.
Sponsors
GlaxoSmithKline
IQVIA Pty Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This is a double-blind study.
Intervention model description
This is randomized, double-blind, parallel group, multi-center and non-inferiority study.
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion 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 \[for example (e.g.), LABA, LAMA, leukotriene receptor antagonist (LTRA), or theophylline\]. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Annualized Rate of Clinically Significant Exacerbations Over 52 Weeks | Up to Week 52 | Clinically significant exacerbations recorded were defined as worsening of asthma requiring the use of systemic corticosteroids (CS) \[such as intramuscular (IM), intravenous (IV) or oral\] and/or hospitalization and/or Emergency Department (ED) visit. For all participants, IV or oral steroids (e.g., prednisone) for at least 3 days or a single IM corticosteroid dose is required. For participants on maintenance systemic corticosteroids, at least double the existing maintenance dose for at least 3 days is required. Exacerbations recorded in the electronic case report form (eCRF) were considered as verified clinically significant exacerbations and included in the primary analysis. Exacerbations separated by less than 7 days was treated as a continuation of the same exacerbation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Weighted Mean (WM) Change From Baseline in St. George's Respiratory Questionnaire (SGRQ) Total Score | From Baseline (Day 1) up to Week 52 | SGRQ: validated, disease specific questionnaire comprising of 51 questions designed to measure health related quality of life in participants with disease of airway obstruction. It assesses how respiratory symptoms and limitations affect daily life. SGRQ 3 domains: Symptoms, Activity and, Impacts. Each item has an empirically derived weight, and domain scores are combined to produce a total score ranging: 0 to 100. Scores are expressed as a percentage of overall impairment between 100 (worst possible health status) and 0 (best possible health status). Higher scores indicating greater impairment of quality of life. Change from Baseline (CFB): value at indicated time point minus Baseline value. For each participant, WM CFB in SGRQ total score was calculated using linear trapezoidal rule to estimate area under the curve (AUC) from Baseline (Day 1) across Weeks 4, 12, 26, and 52 and presented as a single consolidated SGRQ total score on original scale (i.e., not expressed per unit time). |
| Weighted Mean Change From Baseline in Asthma Control Questionnaire-5 (ACQ-5) Score | From Baseline (Day 1) up to Week 52 | The ACQ 5 is a validated, 5-item patient reported tool assessing asthma symptoms over the past week. The 5 questions enquired to recall how their asthma had been during the previous week and to respond about the frequency and/or severity of symptoms (nocturnal awakening, waking in the morning, activity limitation, shortness of breath and wheezing). Each item is scored from 0 (no impairment) to 6 (maximum impairment), and the final ACQ 5 score is the average of all items, ranging from 0 to 6. Lower scores indicate better asthma control, while higher scores indicate poorer control. CFB was defined as value at the indicated time point minus Baseline value. For each participant, the WM CFB in ACQ-5 score was calculated using the linear trapezoidal rule to estimate the AUC from Baseline (Day 1) across Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48 and 52) and presented as a single consolidated ACQ-5 score on the original scale (i.e., not expressed per unit/time). |
| Weighted Mean Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in One Second (FEV1) | From Baseline (Day 1) up to Week 52 | Forced Expiratory Volume in One Second (FEV1) is defined as the volume of air that can be forced out in one second after taking a deep breath by a person and was measured by spirometry testing. Change from Baseline in clinic pre-bronchodilator FEV1 was determined. Change from Baseline was defined as value at the indicated time point minus Baseline value. For each participant, the WM change from baseline in FEV1 was calculated using the linear trapezoidal rule to estimate the AUC from Baseline (Day 1) across Weeks 12, 26, 40, and 52). WM change from baseline in FEV1 over 52-week period was presented as a single consolidated data. |
Countries
Australia, Austria, Canada, Finland, France, Germany, Ireland, Israel, Italy, Japan, Netherlands, Norway, Portugal, Puerto Rico, Slovenia, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORGSK Clinical Trials
GlaxoSmithKline
Participant flow
Recruitment details
A total of 1717 participants were randomized to the study out of which 1687 participants were included in Full Analysis Set (FAS). FAS population included all randomised participants who received at least one dose of study intervention excluding 27 participants from 4 sites with Good Clinical Practices (GCP) non-compliance/significant data integrity concerns and 3 were randomized in error but did not receive study intervention.
Pre-assignment details
A total of 1717 participants were randomized in the study.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 58.9 YEARS STANDARD_DEVIATION 13.24 |
| Race/Ethnicity, Customized AMERICAN INDIAN OR ALASKA NATIVE | 3 Participants |
| Race/Ethnicity, Customized ASIAN | 140 Participants |
| Race/Ethnicity, Customized BLACK OR AFRICAN AMERICAN | 35 Participants |
| Race/Ethnicity, Customized MIXED RACE | 10 Participants |
| Race/Ethnicity, Customized NATIVE HAWAIIAN OR OTHER PACIFIC ISLANDER | 6 Participants |
| Race/Ethnicity, Customized Other: Unspecified | 7 Participants |
| Race/Ethnicity, Customized WHITE | 1304 Participants |
| Sex: Female, Male Female | 1050 Participants |
| Sex: Female, Male Male | 637 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 859 | 1 / 855 |
| other Total, other adverse events | 587 / 859 | 554 / 855 |
| serious Total, serious adverse events | 81 / 859 | 76 / 855 |
Outcome results
None listed