A Study Evaluating the Efficacy of Budesonide, Glycopyrronium, and Formoterol Fumarate Metered-Dose Inhaler on Cardiopulmonary Outcomes in Chronic Obstructive Pulmonary Disease

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Astrazeneca AB

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

4 Jul 2024 → ongoing

Decision date (initial)

2024-06-17

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

AstraZeneca AB

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Evaluate the effect of combination triple therapy (BGF MDI 320/14.4/9.6 μg) compared with dual bronchodilator therapy (GFF MDI 14.4/9.6 μg) on severe cardiopulmonary outcomes.

Secondary objectives 1

1. Evaluate the effect of combination triple therapy (BGF MDI 320/14.4/9.6 μg) compared with dual bronchodilator therapy (GFF MDI 14.4/9.6 μg) on: -severe COPD exacerbations -severe cardiac events -cardiopulmonary deaths -moderate/severe COPD exacerbations -Myocardial Infarction hospitalization (or cardiac death) -Heart Failure acute healthcare visit/hospitalization (or cardiac death)

Conditions and MedDRA coding

Chronic Obstructive Pulmonary Disease (COPD)

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

Yes

IPD plan description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment https://vivli.org/. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1 Male or female participants must be 40 to 80 years of age inclusive, at the time of signing the ICF.
2. 10 A female is eligible to enter and participate in the study if the female is of: • Non-childbearing potential: either permanently sterilized or who are post-menopausal. • Childbearing potential: has a negative serum pregnancy test at V1 and must use one highly effective form of birth control.
3. 11 Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol.
4. 3 A diagnosis of COPD confirmed by a post-bronchodilator FEV1/FVC ratio < 70% predicted at V1.
5. 4 Current or former smokers with a history of at least 10 pack-years of cigarette smoking; defined as (number of cigarettes per day/20) x number of years smoked. Previous smokers are defined as those who have stopped smoking for at least 6 months prior to V1.
6. 5 A baseline peripheral blood eosinophil count of ≥ 100 cells/mm3 assessed at Visit 1 by the central laboratory
7. 6 A CAT score of ≥ 10 at Visit 1.
8. 7 Participant must fulfill at least 1 of the 4 CV disease/risk factor criteria below [(a), (b), (c), or (d)]. (a) Established CV (b) Combination of CV risk factors: • Hypertension • diabetes mellitus • chronic kidney disease• dyslipidemia • obesity (c) High risk of CV disease determined using an established CV risk assessment tool (d) CT coronary artery calcification
9. 8 Willing and, in the opinion of the investigator, able to adjust current COPD therapy, as required by the protocol.
10. 9 Willing to visit at the study site or participate in virtual visits as required per the protocol to complete all study assessments.
11. 2 Demonstrate acceptable MDI administration technique at Visit 1(V1) and Visit 2(V2) (randomization)

Exclusion criteria 16

1. 1 Active diagnosis of asthma within the past 5 years (previous diagnosis as a child or adolescent are eligible), asthma-COPD overlap, or any other chronic respiratory disease other than COPD such as alpha-1 antitrypsin deficiency, active tuberculosis, lung fibrosis, sarcoidosis, interstitial lung disease, and pulmonary hypertension.
2. 2 End-stage renal disease requiring renal replacement therapy.
3. 3 History of heart or lung transplant or actively listed for heart or lung transplant.
4. 4 Implanted left ventricular assist device or implant anticipated in < 3 months.
5. 5 History of lung cancer and/or treatment for lung cancer within the 5 years prior to Visit 1.
6. 6 Unstable or life-threatening cardiac disease – participants with any of the following at Visit 1 would be excluded: (a) An MI or unstable angina in the last 8 weeks (b) Unstable or life-threatening cardiac arrhythmia requiring intervention in the last 8 weeks. NOTE: Any participant who experiences unstable or life-threatening cardiac disease during the run-in period will be excluded but can be rescreened 8 weeks after the resolution of the event.
7. 7 Pneumonia and/or moderate or severe COPD exacerbation that has not resolved at least 8 weeks prior to Visit 1 (see Section 5.4 regarding rescreening or extension of run-in period).
8. 8 Any life-threatening condition, including malignancy, with a life expectancy < 5 years, other than CV disease or COPD, that might prevent the participant from completing the study.
9. 9 Use of maintenance ICS treatment within the past 12 months.
10. 10 Unable to abstain from protocol-defined prohibited medications
11. 11 Participation in another clinical study with a study intervention administered in the last 30 days or 5 half-lives, whichever is longer prior to Visit 1 (any other investigational product that is not identified in this protocol is prohibited for use during the duration of the study).
12. 12 Participants with a known hypersensitivity to LAMA, LABA or ICS or any component of the MDI.
13. 13 Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
14. 14 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.
15. 15 Previous randomization in the present study.
16. 16 For females only - currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Time to first severe cardiac or COPD event.

Secondary endpoints 1

1. -Time to first severe COPD exacerbation -Time to first severe cardiac event -Time to cardiopulmonary death -moderate/severe COPD exacerbation rate -Time to MI hospitalization (or cardiac death) -Time to HF acute healthcare visit/hospitalization (or cardiac death)

Investigational products

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

Test 1

Comparator 1

Auxiliary 1

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

16 EU/EEA countries · 262 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

Documents 193 files

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

Application history

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