A Study to Compare the Efficacy, Safety and Tolerability of FF/UMEC/VI With FF/VI in 12-17-year-olds With Asthma

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the effects of Fluticasone Furoate (FF)/ Umeclidinium (UMEC)/ Vilanterol (VI) on lung function compared with FF/VI after 24 weeks of treatment.

Official Title
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A Phase 3, 24-week, Randomized, Double-blind, Parallel-group Bayesian Dynamic Borrowing Study Comparing the Efficacy, Safety, Tolerability and Pharmacokinetics of FF/UMEC/VI With FF/VI in 12-17-year-old Participants With Inadequately Controlled Asthma on Stable Maintenance Therapy With ICS/LABA

Conditions
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Asthma

Intervention / Treatment
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* Drug: FF/UMEC/VI
* Device: ELLIPTA
* Drug: FF/VI


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 12 to 17 years of age (inclusive), at the time of signing the informed consent/assent. Participants who have a diagnosis of asthma as defined by the National Institutes of Health [NIH, 2020] at least 1 year prior to Visit 0. Participants who have required daily Inhaled corticosteroids (ICS)/ Long-Acting Beta2-Agonist (LABA) treatment for at least 12 weeks prior to Visit 0 with no changes to maintenance asthma medications during the 6 weeks immediately prior to Visit 0 (including no changes to a stable total ICS dose of >250 to <=500 microgram (mcg)/day fluticasone propionate, or equivalent). In the 1 year prior to Visit 1: A documented healthcare contact for acute asthma symptoms; OR A documented temporary change in asthma therapy for acute asthma symptoms, according to a prespecified asthma action plan (or equivalent). Participants with inadequately controlled asthma (ACQ-6 score ≥1.5) at Visit 1, despite ICS/LABA maintenance therapy. A best pre-bronchodilator FEV1 >40% to <=90% of the predicted normal value and a ≥12% increase in FEV1 with albuterol/salbutamol at Visit 1. Predicted values will be based on the European Respiratory Society (ERS) Global Lung Function Initiative. Exclusion Criteria: Chest X-ray documented pneumonia in the 6 weeks prior to Visit 1. Any asthma exacerbation requiring a change in maintenance asthma therapy and/or the use of systemic corticosteroids for at least 3 days in the 6 weeks prior to Visit 1. (Participants requiring a temporary change in asthma therapy (e.g., oral corticosteroids or increased dose of ICS) to treat an exacerbation in the 6 weeks prior to Visit 1 are not explicitly excluded at Visit 1 provided that, at the Investigator's discretion, the participant's condition is stable after they have resumed their pre-exacerbation maintenance asthma therapy (without modification), returned to their baseline asthma status and they are considered appropriate for enrollment into this study of up to 6 months duration) History of Life-threatening Asthma Participants with current evidence of active pulmonary diseases or abnormalities other than asthma (e.g., pneumonia, active tuberculosis, significant bronchiectasis, etc.). Current smokers and users of other inhaled products for recreation with or without nicotine (defined as participants who use cigarettes, e-cigarettes, other/vaping-related devices, cigars or pipe tobacco]) within 12 months prior to Visit 1.

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants receiving FF/UMEC/VI<br> | Drug: FF/UMEC/VI<br>* FF/UMEC/VI will be administered.<br>Device: ELLIPTA<br>* FF/UMEC/VI and FF/VI will be administered via ELLIPTA inhaler<br>|
| Active Comparator: Participants receiving FF/VI<br> | Device: ELLIPTA<br>* FF/UMEC/VI and FF/VI will be administered via ELLIPTA inhaler<br>Drug: FF/VI<br>* FF/VI will be administered.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in trough forced expiratory volume in 1 second (FEV1) (Liters) at Week 24 | FEV1 will be measured using spirometry. | Baseline (Week 0) and Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Asthma Control Questionnaire (7 items) (ACQ-7) (Scores on a scale) | ACQ-7 consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation)), a question on rescue use and an additional item relating to lung function which is calculated based on FEV1. A score of less than or equal to (<=) 0.75 indicates well-controlled asthma and a score greater than or equal to (>=)1.5 indicates poorly controlled asthma. | Baseline (Week 0) and Week 24 | 
| Change from Baseline in Asthma Control Questionnaire (6 items) (ACQ-6) (Scores on a scale) | ACQ-6 consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation)) and a question on rescue bronchodilator use. A score of less than or equal to (<=) 0.75 indicates well-controlled asthma and a score greater than or equal to (>=)1.5 indicates poorly controlled asthma. | Baseline (Week 0) and Week 24 | 
| Change from Baseline in Asthma Control Questionnaire (5 items) (ACQ-5) (Scores on a scale) | ACQ-5 consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation). A score of less than or equal to (<=) 0.75 indicates well-controlled asthma and a score greater than or equal to (>=)1.5 indicates poorly controlled asthma. | Baseline (Week 0) and Week 24 | 
| Number of Participants with a clinically important change from baseline in ACQ-7 Score | ACQ-7 consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation)), a question on rescue use and an additional item relating to lung function which is calculated based on FEV1. A score of less than or equal to (<=) 0.75 indicates well-controlled asthma and a score greater than or equal to (>=)1.5 indicates poorly controlled asthma. A change of 0.5 in score suggests a clinically important change in score. | Week 24 | 
| Number of Participants with a clinically important change from baseline in ACQ-6 Score | ACQ-6 consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation)) and a question on rescue bronchodilator use. A score of less than or equal to (<=) 0.75 indicates well-controlled asthma and a score greater than or equal to (>=)1.5 indicates poorly controlled asthma. A change of 0.5 in score suggests a clinically important change in score. | Week 24 | 
| Number of Participants with a clinically important change from baseline in ACQ-5 Score | ACQ-5 consists of 5 symptom related questions (nocturnal awakening, symptoms on waking in the morning, activity limitation, shortness of breath and wheeze with response options ranging from zero (no impairment/limitation) to 6 (total impairment/ limitation). A score of less than or equal to (<=) 0.75 indicates well-controlled asthma and a score greater than or equal to (>=)1.5 indicates poorly controlled asthma. A change of 0.5 in score suggests a clinically important change in score. | Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GW685698, Fluticasone Furoate, Umeclidinium, GSK573719, Vilanterol, GW642444, Trelegy, Relvar, Breo