A Study to Test if a Fixed-Dose Combination of Fluticasone Propionate/Albuterol Sulfate is Effective in Preventing Asthma Exacerbations

Study Overview
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Brief Summary
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The primary objective of the study is to demonstrate the efficacy of high dose and low dose fluticasone propionate (Fp)/albuterol sulfate (ABS) integrated electronic module multidose dry powder inhaler (eMDPI) compared to ABS eMDPI in decreasing severe clinical asthma exacerbation (CAEs). Secondary Objectives: To evaluate the efficacy of Fp/ABS compared to ABS and the effect on systemic corticosteroid (SCS) exposure To evaluate the safety and tolerability of Fp/A BS The duration for each participant will be a minimum of 28 weeks including 2 weeks of screening, 2-4 weeks of run-in period and a double blind treatment period of minimum 24 weeks, however due to the event-driven nature of this study, the duration may range up to approximately 35 months depending on the timing when the participant was enrolled to the study, and when the study reaches its completion criteria.

Official Title
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A Randomized, Double-Blind, Multicenter, Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Fluticasone Propionate/Albuterol Sulfate Fixed-Dose Combination on Severe Asthma Exacerbations in Patients With Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: TEV-56248
* Drug: Albuterol sulfate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participant has a diagnosis of asthma for at least 1 year according to the 2022 GINA guidelines. The participant has a documented history of at least 1 severe clinical asthma exacerbation (CAE) within the past 12 months before screening. The participant is using any prescribed inhaled asthma controller medication (at a stable dose for 1 month prior to the screening visit). If female, the participant is currently not pregnant, breastfeeding, or attempting to become pregnant (for at least 30 days before the screening visit and throughout the duration of the study), or is of nonchildbearing potential NOTE- Additional criteria apply, please contact the investigator for more information. Exclusion Criteria: The participant has life-threatening asthma defined as any history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s) within 5 years before screening. The participant has a suspected bacterial or viral infection (other than Coronavirus Disease [COVID-19]) of the upper or lower respiratory tract, sinus, or middle ear that has not resolved at least 2 weeks before the screening period. Participants with a confirmed infection with COVID-19 within 6 weeks prior to the screening visit, or with residual COVID-19 symptoms (long COVID-19). The participant has had a clinical asthma exacerbation (CAE) requiring systemic corticosteroids within 30 days before screening, or any hospitalization for asthma within 2 months before screening. The participant is a current tobacco smoker or has a smoking history of ≥10 pack-years, or the participant used tobacco within the past 6 months. The participant has significantly abused alcohol and/or prohibited drugs within the previous 24 months. The participant has participated as a randomized participant in any investigational drug study within 30 days. The participant has been hospitalized for psychiatric disorder or attempted suicide within 1 year of screening. NOTE- Additional criteria apply, please contact the investigator for more information

Ages Eligible for Study
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Minimum Age: 4 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TEV-56248 Low Dose<br>Inhalation powder via multidose dry powder inhaler with integrated electronic module (eMDPI) with a dosing frequency of 2 inhalations as needed to control asthma symptoms. | Drug: TEV-56248<br>* Fluticasone Propionate/Salbutamol Sulfate. Oral inhalation powder.<br>|
| Experimental: TEV-56248 High Dose<br>Inhalation powder via multidose dry powder inhaler with integrated electronic module (eMDPI) with a dosing frequency of 2 inhalations as needed to control asthma symptoms. | Drug: TEV-56248<br>* Fluticasone Propionate/Salbutamol Sulfate. Oral inhalation powder.<br>|
| Active Comparator: Albuterol sulfate<br>Inhalation powder via multidose dry powder inhaler with integrated electronic module (eMDPI) with a dosing frequency of 2 inhalations as needed to control asthma symptoms. | Drug: Albuterol sulfate<br>* Oral inhalation powder<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to First Severe Clinical Asthma Exacerbation (CAE) |  | Up to 35 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Annualized Severe CAE Rate | Annualized severe CAE rate is calculated for each participant as the sum of total number of CAE events divided by the duration of follow up time (years). | Up to 35 months | 
| Total Annualized SCS Exposure Over the Treatment Period | Total annualized SCS exposure will be calculated for each participant as the sum of the cumulative doses of SCS divided by the duration of time (years) the participant was in the treatment period, from randomization and up to end of treatment. | Up to 35 months | 
| Asthma Control Questionnaire-5 (ACQ-5) Response | Response is defined as achieving a decrease in score from baseline value of at least 0.5 (participants aged ≥6 years). The ACQ-5 is a shortened version of the validated asthma assessment tool (ie, ACQ) and includes 5 questions that are self-assessments (completed by the participant). Each item on the ACQ-5 has a possible score ranging from 0 to 6, and the total score is the mean of all responses. | Baseline, Week 24 | 
| Composite Responders Based on Asthma Quality of Life Questionnaire + 12 (AQLQ+12) or Pediatric AQLQ (PAQLQ) | Responders are defined as the composite of participants achieving an increase in score from baseline of at least 0.5 on the AQLQ+12 or PAQLQ (participants aged ≥7 years). The AQLQ + 12 is a modified version of the standardized AQLQ, which was developed to measure functional impairments experienced by adults ≥17 years of age. The AQLQ + 12 is valid for participants aged 12 to 70 years and includes 32 questions in 4 domains (symptoms, activity limitation, emotional function, and environmental stimuli). Responses are rated on a 7-point scale where 7 = no impairment and 1 = severe impairment. The PAQLQ Questionnaire includes 23 items in 3 domains (symptoms, activity limitation, emotional function) and a 7-point scale (7 = not bothered at all; 1 = extremely bothered). It is intended for participants ages 7-11. | Baseline, Week 24 | 
| Number of Participants with at Least One Adverse Event | Adverse events include clinically significant changes in clinical laboratory test results (serum chemistry, hematology, and urinalysis), vital signs measurements (blood pressure, pulse rate, body temperature, and respiratory rate), and 12-lead electrocardiogram (ECG) findings. | Up to 35 months | 
| Number of Participants with at Least One Serious Adverse Event |  | Up to 35 months | 
| Number of Participants Who Withdrew From the Trial Due to Treatment-Emergent Adverse Events |  | Up to 35 months |