| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Inadequately Controlled Asthma |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Respiratory Tract Diseases [C08] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10003553 |
| E.1.2 | Term | Asthma |
| E.1.2 | System Organ Class | 10038738 - Respiratory, thoracic and mediastinal disorders |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To assess the effect of BFF MDI 320/9.6 μg relative to BD MDI (superiority) on lung function in participants with inadequately controlled asthma |
|
| E.2.2 | Secondary objectives of the trial |
1. To assess the effect of BFF MDI 320/9.6 μg relative to BD MDI 320 μg (superiority) on lung function.
2. To assess the effect of BFF MDI 320/9.6 μg relative to BD MDI 320 μg on symptoms and patient reported outcomes. |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. 12 to 80 years of age, male and female, BMI <40 kg/m2; females must be not of childbearing potential or using a form of highly effective birth control.
2. Participants who have a documented history of physician-diagnosed asthma ≥ 6 months prior to Visit 1, according to GINA guidelines [GINA 2020]. Healthcare records for one year prior to Visit 1 must be provided for adolescent participants (12 to < 18 years of age) to ensure consistent evaluation and follow-up of treatment in those participants.
3. Participants who have been regularly using a stable daily ICS or an ICS/LABA regimen (including a stable ICS dose), with the ICS doses, for at least 8 weeks prior to Visit 1.
4. ACQ-7 total score ≥ 1.5 at Visits 1 and 4.
5. Pre-bronchodilator/pre-dose FEV1 <90% predicted normal value at Visits 1, 2 and 3, and a pre-dose FEV1 of 50% to 90% at Visit 4 (pre-randomization).
6. Reversibility to albuterol, defined as a post-albuterol increase in FEV1 of ≥ 12% and ≥ 200 mL for participants ≥ 18 years of age OR a postalbuterol increase in FEV1 of ≥ 12% for participants 12 to < 18 years of age, either in the 12 months prior to Visit 1 or at Visit 2 or Visit 3.
7. A pre-bronchodilator/pre-dose FEV1 at Visits 2, 3, and 4 that have not changed 20% or more (increase or decrease) from the prebronchodilator/pre-dose FEV1 recorded at the previous visit.
8. Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment.
9. Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
10. Demonstrate acceptable MDI administration technique.
11. eDiary compliance ≥ 70% during screening, defined as completing the daily eDiary and answering "Yes" to taking 2 puffs of run-in BD MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization. |
|
| E.4 | Principal exclusion criteria |
1. Life-threatening asthma as defined as a history of significant asthma episode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma related syncopal episode(s).
2. Any respiratory infection or asthma exacerbation treated with systemic corticosteroids and/or additional ICS treatment in the 8 weeks prior to Visit 1 and throughout the Screening Period.
3. Hospitalization for asthma within 8 weeks of Visit 1.
4. Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, hematological, neurological, endocrine, gastrointestinal, or pulmonary (eg, active tuberculosis, bronchiectasis, pulmonary eosinophilic syndromes, and COPD). Significant is defined as any disease that, in the opinion of the Investigator, would put the safety of the participant at risk through participation, or that could affect the efficacy or safety
analysis.
5. Known history of drug or alcohol abuse within 12 months of Visit 1.
6. Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1.
7. Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer. Any other study intervention that is not identified in this protocol is prohibited for use during study duration.
8. Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).
9. Use of a nebulizer or a home nebulizer for receiving asthma medications.
10. Do not meet the stable dosing period prior to Visit 1 or unable to abstain from protocol-defined prohibited medications during Screening and Treatment Periods.
11. Receipt of COVID-19 vaccine (regardless of vaccine delivery platform, eg, vector, lipid nanoparticle) < 7 days prior to Visit 1 (from last vaccination or booster dose).
12. Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.
13. Any clinically relevant abnormal findings in physical examination, clinical chemistry, hematology, vital signs, or ECG, which in the opinion of the Investigator, may put the participant at risk because of his/her participation in the study.
14. Current smokers, former smokers with > 10 pack-years history, or former smokers who stopped smoking < 6 months prior to Visit 1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).
15. Planned hospitalization during the study.
16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
17. Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.
18. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.
19. For women only – currently pregnant (confirmed with positive highly sensitive urine pregnancy test), breast-feeding, or planned pregnancy during the study or not using acceptable contraception measures, as judged by the Investigator. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| 1. Europe (EU): Change from baseline in morning pre-dose trough FEV1 over 24 Weeks. |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
| Europe(EU) over 24 weeks. |
|
| E.5.2 | Secondary end point(s) |
1. EU (Key secondary): To assess the effect of BFF MDI 320/9.6 μg relative to BD MDI.
- Change from baseline in FEV1 AUC0-3 over 24 Weeks.
2. To assess the effect of BFF MDI 320/9.6 μg relative to BD MDI and Symbicort TBH on lung function, symptoms, and PROs.
- Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 24 Weeks.
- Percentage of responders in ACQ-7 (≥ 0.5 decrease equals response) over 24 Weeks.
- Percentage of responders in ACQ-5 (≥ 0.5 decrease equals response) over 24 Weeks.
- Percentage of responders in the AQLQ(s)+12 (≥ 0.5 increase equals response) over 24 Weeks.
- Percentage of responders in AQLQ(s)+12 (≥ 0.5 increase equals response) over 12 to 24 weeks.
- Onset of action on Day 1: Absolute change in FEV1 at 5 minutes postdose on Day 1. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| As listed for each endpoint. |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | Yes |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | Yes |
| E.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 14 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 32 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
| Canada |
| Japan |
| United States |
| Viet Nam |
| Germany |
| Italy |
| Spain |
|
| E.8.7 | Trial has a data monitoring committee | No |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The study will end when the last remaining participant completes his/her Week 24 Visit and subsequent 2-week follow-up phone call. If study intervention was discontinued prior to the Week 24 Visit, then study will end at the completion of the Week 24 Visit. |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | |
| E.8.9.1 | In the Member State concerned months | 27 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial months | 29 |
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