A Comparison of PT027 vs PT007 Used as Needed in Participants With Asthma

Study Overview
=================
Brief Summary
-----------------
This is a US study comparing the efficacy and safety of BDA MDI [Budesonide/Albuterol Sulfate (BDA) metered dose inhaler (MDI)] with AS [Albuterol Sulfate] MDI, both are administered as needed for up to 12 months.

Detailed Description
-----------------
This is a phase IIIb, multicenter, randomized, double-blind, parallel-group, event-driven, variable-length, decentralized study. Participants from around 40 to 50 centers located in the US will be screened and randomized 1:1 to receive one of the following two treatments to be used as needed: BDA MDI (160/180 μg) and AS MDI (180 μg). Participants 12 years of age and older with asthma will be recruited with all visits conducted virtually. Eligible participants must be using as-needed SABA (Short -acting β2agonist) alone, or as-needed SABA on a background of either low-dose ICS (Inhaled corticosteroid) or a LTRA (Leukotriene receptor agonist), for the treatment of asthma. Participants will be stratified by pre-study asthma medication (SABA only, low-dose ICS + SABA and LTRA + SABA) and number of prior severe exacerbations (0, ≥1) in the 12 months prior to the Screening visit.

Official Title
-----------------
A Multicenter, Randomized, Double-blind, Parallel-group, Event-driven, Decentralized, Phase IIIb Study Comparing PT027 With PT007 Administered as Needed in Participants 12 Years of Age and Older With Asthma (BATURA)

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Drug: BDA MDI
* Drug: AS MDI


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participant must be ≥12 years of age, at the time of signing the electronic informed consent form (eICF). For participants from 12 years of age to age of majority, their parents/legal guardian must provide signed consent, as appropriate, and participants will sign an assent form. Diagnosis of asthma by a prescribing healthcare professional. Protocol-specified documentation of asthma diagnosis is required to confirm diagnosis of asthma. Participants actively using SABA alone or SABA on a background of either low-dose ICS or LTRA. Self-reported use of a SABA on ≥2 occasions, in response to symptoms (ie, not for exercise prophylaxis only), in the previous 2 weeks prior to enrollment. An Asthma Impairment and Risk Questionnaire (AIRQ) score of ≥2 at Screening (Visit1/re-screen) and Randomisation (Randomization (Visit2) where applicable. Note, where screening Visit1/re-screen and randomization occur on the same day, AIRQ will only be completed once. Females of child-bearing potential must have a negative pregnancy test prior to randomization and agree to use an acceptable method of contraception throughout the study. Male participants who are in heterosexual relationships must be surgically sterile or agree to use an effective method of contraception (condom) if the female partner does not use contraception from the date the eICF is signed until 2 weeks after their last dose. Exclusion Criteria: Any evidence of significant lung disease other than asthma, such as chronic obstructive pulmonary disease, emphysema, idiopathic pulmonary fibrosis, sarcoidosis etc or any other significant disease (like malignancies or severe chronic diseases) that by Investigator judgment would interfere with the participant being able to comply with study procedures or complete the study. Hospitalization due to asthma in the 3 months prior to enrollment or self-reported admission to the Intensive Care Unit with life-threatening asthma at any time in the past Self-reported use of inhaled Long-Acting Beta-Agonists (LABA), theophylline, inhaled anticholinergic agent, cromone or medium/high dose ICS daily, as regular maintenance asthma therapy in the 3 months prior to enrollment Self-reported use of systemic corticosteroids (SCS) for the treatment of asthma and any other condition in the 6 weeks prior to enrollment Participants with a home supply of oral corticosteroids (OCS) to be used in the case of an asthma exacerbation or any other condition that could require a course of OCS, who are not willing to commit to the treating physician to stop using this medication for the duration of the study. Receipt of any marketed (eg, omalizumab, mepolizumab, reslizumab, benralizumab, dupilumab, tezepelumab) or investigational biologic for the treatment of asthma at any time in the past Receipt of bronchothermoplasty Use of a SABA prophylactically primarily to prevent exercise induced bronchospasm (EIB) and not to treat symptoms Currently receiving systemic treatment with potent cytochrome P3A4 inhibitors (eg, ketoconazole, itraconazole, and ritonavir) Judgment by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements. Previous screening, enrollment or randomization in the present study. For females only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding. Participants without access to a smartphone or the internet.

Ages Eligible for Study
-----------------
Minimum Age: 12 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PT027<br>Participants will receive Budesonide and Albuterol Sulfate Pressurised Inhalation Suspension 160/180 μg up to a maximum of 12 inhalations to max dose. | Drug: BDA MDI<br>* Participants will receive Budesonide and Albuterol Sulfate MDI 80/90 μg per Actuation 1 to 6 doses (2 inhalations/dose) per day as needed via Oral inhalation route.<br>|
| Experimental: PT007<br>Participants will receive Albuterol Sulfate Pressurised Inhalation Suspension 180 μg up to a maximum of 12 inhalations to max dose. | Drug: AS MDI<br>* Participants will receive Albuterol Sulfate MDI 90 μg per Actuation 1 to 6 doses (2 inhalations/dose) per day as needed via Oral inhalation route.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first severe asthma exacerbation | The time to first severe asthma exacerbation will be analyzed under the While on Treatment estimand in the Full analysis set (FAS) and is defined as the length in days from start of the Investigational Medicinal Products (IMP) period until the first date when the event occurs, up to the end of the study. Patients will be censored at treatment discontinuation or a step-up in maintenance therapy. To evaluate the efficacy of as needed BDA MDI compared with as needed AS MDI on the risk of severe asthma exacerbations in adult and adolescent participants with asthma previously receiving SABA alone or SABA as needed on a background of low-dose ICS or a LTRA. | Up to Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to first severe asthma exacerbation | The time to first severe exacerbation will analyzed under the Treatment Policy estimand in which all observed data while participants are in the study, regardless of whether they remain on randomized study treatment or experience a step-up in maintenance therapy, will be included in the analyses. To evaluate the efficacy of BDA MDI as needed compared with AS MDI as needed on the risk of severe asthma exacerbations in adults and adolescents with asthma who are taking SABA as needed alone or with a stable low-dose ICS or LTRA. | Up to Week 52 | 
| Annualized rate of severe asthma exacerbations | The annualized rate of severe asthma exacerbations will be evaluated based While on the Treatment estimand, where all data collected from the start of the IMP period up to the end of study participation, regardless of the occurrence of intercurrent events, will be used. | Up to Week 52 | 
| Total amount (mg/year) per participant of systemic glucocorticoid exposure | The total systemic corticosteroid exposure will be expressed as the annualized total dose of systemic corticosteroid (SCS) (mg/year) (While on Treatment estimand). To evaluate the effect of BDA MDI as needed compared with AS MDI as needed on systemic glucocorticoid exposure associated with asthma management. | Up to Week 52 | 
| Total days of systemic glucocorticoid exposure | To evaluate the effect of BDA MDI as needed compared with AS MDI as needed on systemic glucocorticoid exposure (While on Treatment estimand), associated with asthma management. | Up to Week 52 | 
| Number of participants with Serious Adverse Events (SAEs) and Adverse Events (AEs) | To evaluate the safety of BDA MDI as needed compared to AS MDI as needed in participants 12 years of age and older with asthma | From screening (Day -28 to 0) to end of the study or early study discontinuation (Upto Week 52) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metered-dose inhaler (MDI), Leukotriene receptor agonist (LTRA), Inhaled corticosteroid (ICS), Short -acting β2agonist (SABA)