Efficacy and Safety of Budesonide and Formoterol Fumarate Metered Dose Inhaler in Patients with Inadequately Controlled Asthma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AstraZeneca AB

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

23 Mar 2022 → 26 Feb 2025

Decision date (initial)

2024-06-18

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513568-24-00

EudraCT number

2021-002026-24

ClinicalTrials.gov

NCT05202262

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Dose response, Safety, Therapy, Pharmacogenomic

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

Secondary objectives 2

1. 1.To assess the effect of BFF MDI 320/9.6 μg relative to BD MDI 320 μg (superiority) on lung function
2. 2.To assess the effect of BFF MDI 320/9.6 μg relative to BD MDI 320 μg on symptoms and patient reported outcomes

Conditions and MedDRA coding

Inadequately Controlled Asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 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. 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. 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. 4. ACQ-7 total score ≥ 1.5 at Visits 1 and 4.
5. 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. 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. 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. 8. Asthma stability during run-in based on Investigator discretion using the symptom worsening assessment.
9. 9. Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
10. 10. Demonstrate acceptable MDI administration technique.
11. 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.

Exclusion criteria 19

1. 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. 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. 3. Hospitalization for asthma within 8 weeks of Visit 1.
4. 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. 5. Known history of drug or alcohol abuse within 12 months of Visit 1.
6. 6. Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1.
7. 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. 8. Previous or current randomization into studies within the AEROSPHERE program including KALOS, LOGOS, VATHOS, LITHOS, or any glycopyrronium studies (PT001).
9. 9. Use of a nebulizer or a home nebulizer for receiving asthma medications.
10. 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. 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. 12. Participants with known hypersensitivity to beta2-agonists, corticosteroids, or any component of the MDI.
13. 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. 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. 15. Planned hospitalization during the study.
16. 16. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
17. 17. Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members
18. 18. Judgment by the Investigator that the participant is unlikely to comply with study procedures, restrictions, and requirements.
19. 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1. Change from baseline in morning pre-dose trough FEV1 over 24 weeks.

Secondary endpoints 7

1. 1.Change from baseline in FEV1 AUC0-3 over 24 Weeks.
2. 2.Change from baseline in the mean number of puffs of rescue medication use (puffs/day) over 24 Weeks.
3. 3.Percentage of responders in ACQ-7 (≥ 0.5 decrease equals response) over 24 Weeks.
4. 4.Percentage of responders in ACQ-5 (≥ 0.5 decrease equals response) over 24 Weeks.
5. 5.Percentage of responders in the AQLQ(s)+12 (≥ 0.5 increase equals response) over 24 Weeks.
6. 6.Percentage of responders in AQLQ(s)+12 (≥ 0.5 increase equals response) over 12 to 24 weeks.
7. 7.Onset of action on Day 1: Absolute change in FEV1 at 5 minutes post dose on Day 1.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 2

Placebo 1

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AstraZeneca AB

Sponsor organisation

AstraZeneca AB

Address

-

City

Sodertalje

Postcode

151 85

Country

Sweden

Scientific contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Public contact point

Organisation

AstraZeneca AB

Contact name

AstraZeneca Clinical Study Information Center

Locations

3 EU/EEA countries · 27 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 28 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications