A Variable Length Study to Evaluate the Efficacy and Safety of Budesonide/Glycopyrronium/Formoterol inhaler in Adults and Adolescents with Severe Asthma Inadequately Controlled with Standard of Care.

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

25 Apr 2021 → 20 Mar 2025

Decision date (initial)

2024-03-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB, Sweden

External identifiers

EU CT number

2023-505786-88-00

EudraCT number

2020-001521-31

ClinicalTrials.gov

NCT04609904

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

Main Objective of D5982C00008
1. To assess the effect of Budesonide, Glycopyrronium, and Formoterol Fumarate Metered Dose Inhaler (BGF MDI) relative to Budesonide and Formoterol Fumarate (BFF) MDI or Symbicort Pressurized MDI on lung function in participants with inadequately controlled asthma.
Main Objective of Pooled Studies D5982C00007 and D5982C00008
1. To assess the effect of BGF MDI relative to BFF MDI or Symbicort pMDI on asthma exacerbations in participants with inadequately controlled asthma.

Secondary objectives 1

1. Secondary Objectives of D5982C00008 1. To assess the effect of BGF MDI relative to BFF MDI or Symbicort pMDI on lung function in participants with inadequately controlled asthma. 2. To assess the effect of BGF MDI relative to BFF MDI or Symbicort pMDI on lung function, PROs, and symptoms in participants with inadequately controlled asthma. Secondary Objectives of Pooled Studies D5982C00007 and D5982C00008 1. To assess the effect of BGF MDI relative to BFF MDI or Symbicort pMDI on asthma exacerbations in participants with inadequately controlled asthma.

Conditions and MedDRA coding

Severe and inadequately controlled asthma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

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. Documented history of physician-diagnosed asthma > and/or = 1 year prior to V1.
3. Regularly using a stable daily ICS/LABA regimen (including a stable ICS dose) with medium-to-high ICS doses for at least 4 weeks prior to V1.
4. ACQ-7 total score ≥1.5 at Visits 1, 3, and 5 (pre-randomization).
5. FEV1 % (assessed as an average of the 60 and 30 minute pre-dose assessments) predicted normal at V1, 2, 3, 4, and 5 (pre-randomization) • Participants > and/or = 18 years of age: < 80% • Participants 12 to <18 years of age: < 90%
6. FEV1 post-albuterol at V2 or V3 (if repeat needed). • Participants > and/or = 18 years of age: Increase > and/or = 12% and > and/or = 200 mL. • Participants 12 to <18 years of age: Increase =12% either in the 12 months prior to Visit 1 or at Visit 2, or at Visit 3. • Note: Even if there is documented history of reversibility, all participants must be assessed for reversibility at Visit 2 (and Visit 3, if reversibility is not demonstrated at Visit 2) to provide reversibility baseline data for characterization.
7. Willing and, in the opinion of the Investigator, able to adjust current asthma therapy, as required by the protocol.
8. Demonstrate acceptable MDI/pMDI administration technique.
9. Received no asthma medication other than run-in BFF MDI BID and albuterol as needed during screening (except for allowed medications as defined in Table 9 and systemic corticosteroid or ICS for the treatment of an asthma exacerbation).
10. eDiary 14-day compliance ≥70% during screening (defined as completing the daily eDiary for any 10 mornings and any 10 evenings and answering "Yes" to taking 2 puffs of run-in BFF MDI for any 10 mornings and 10 evenings in the last 14 days prior to randomization).
11. No respiratory infection in the 4 weeks prior to randomization, or asthma exacerbation treated with systemic corticosteroid and/or additional ICS treatment in the 4 weeks prior to randomization.

Exclusion criteria 19

1. Completed treatment for respiratory infection or asthma exacerbation with systemic corticosteroids within 4 weeks of V1.
2. Narrow angle glaucoma not adequately treated and/or change in vision that may be relevant, in the opinion of the Investigator, within 3 months of Visit 1.
3. Life-threatening asthma defined as a history of significant asthmaepisode(s) requiring intubation associated with hypercapnia, respiratory arrest, hypoxic seizures, or asthma-related syncopal episode(s).
4. Participants where, in the opinion of the Investigator, treatment with biological therapy for asthma would be appropriate.
5. Any marketed or investigational biologics within 3 months or 5 halflives of V1, whichever is longer and must not be used during study duration.
6. Current smokers, former smokers with >10 pack-years history, or former smokers who stopped smoking <6 months prior to V1 (including all forms of tobacco, e-cigarettes or other vaping devices, and marijuana).
7. Current evidence of COPD.
8. Oral and IV corticosteroid use (any dose) within 4 weeks of V1. Use of systemic corticosteroids for any other reason except for the acute treatment of severe asthma exacerbation is prohibited for the duration of the study. Depot corticosteroid use for any reason within 3 months of V1.
9. Use of LAMA, either alone or as part of an inhaled combination therapy, in the 12 weeks prior to V1.
10. Use of oral beta2-agonist within 3 months of V1.
11. Use of any immunomodulators or immunosuppressive medication within 3 months or 5 half-lives, whichever is longer, and must not be used during the study duration.
12. Hospitalization for asthma within 2 months of Visit 1.
13. Known history of drug or alcohol abuse within 12 months of Visit 1.
14. Regular use of a nebulizer or a home nebulizer for receiving asthma medications.
15. Using any herbal products by inhalation or nebulizer within 4 weeks of Visit 1 and does not agree to stop during the study duration.
16. 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 the protocol is prohibited for use during study duration.
17. Participants with a known hypersensitivity to beta2-agonists, corticosteroids, anticholinergics, or any component of the MDI or pMDI.
18. Study Investigators, sub-Investigators, coordinators, and their employees or immediate family members.
19. For women only – currently pregnant (confirmed with positive highly sensitive 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. Europe (EU): Change from baseline in morning pre-dose trough FEV1 over 24 Weeks. Primary end point(s) of Pooled Studies D5982C00007 and D5982C00008. 1. Rate of severe asthma exacerbations.

Secondary endpoints 12

1. Onset of action on Day 1: Absolute change in FEV1 at 5 minutes on Day 1.
2. Change from baseline in FEV1 AUC0-3 over 24 Weeks
3. Percentage of responders in ACQ-7 (≥0.5 decrease equals response) over 24 weeks.
4. Percentage of responders in ACQ-5 (≥0.5 decrease equals response) over 24 weeks.
5. Percentage of responders in the Asthma Quality of Life Questionnaire for 12 years and older (AQLQ(s)+12) (≥0.5 increase equals response) over 24 weeks.
6. Percentage of responders in the St. George's Respiratory Questionnaire (SGRQ) (≥4.0 unit decrease equals response) at Week 24.
7. Rate of severe asthma exacerbations over the Treatment Period
8. Secondary end point of Pooled Studies D5982C00007 and D5982C00008: Time to first severe asthma exacerbation.
9. Secondary end point of Pooled Studies D5982C00007 and D5982C00008: Rate of moderate/severe asthma exacerbations.
10. Secondary end point of Pooled Studies D5982C00007 and D5982C00008: Time to first moderate/severe asthma exacerbation.
11. Secondary end point of Pooled Studies D5982C00007 and D5982C00008: Rate of severe asthma exacerbations for participants with percent predicted FEV1 ≤ 55% at baseline.
12. Secondary end point of Pooled Studies D5982C00007 and D5982C00008: Rate of severe asthma exacerbations for participants with ≥ 1 severe exacerbation in the 12 months prior to Visit 1.

Investigational products

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

Test 3

Comparator 1

Placebo 2

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Astrazeneca AB

Sponsor organisation

Astrazeneca AB

Address

Astraallen Gartuna, Karlebyhus Byggnad 674 Karlebyhus Byggnad 674

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

5 EU/EEA countries · 68 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Serious breaches 1 · Art. 52 CTR

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 42 files

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

Application history

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