A study to investigate the effect on lung function of an approved COPD treatment (BGF, with HFA propellant) compared to BGF formulated with a new propellant (HFO) in participants 40 to 80 years of age with COPD

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

21 Jun 2024 → 12 Aug 2025

Decision date (initial)

2024-03-25

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

AstraZeneca AB

External identifiers

EU CT number

2023-506565-57-00

ClinicalTrials.gov

NCT06075095

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Pharmacodynamic

To assess the equivalence of BGF MDI HFO relative to BGF MDI HFA on lung function in participants with COPD
Second main objective is to demonstrate assay sensitivity viasuperiority of BGF MDI HFA relative to placebo MDI HFA on lung function in participants with COPD

Secondary objectives 1

1. Safety - To assess the safety and tolerability of BGF MDI HFO compared to BGF MDI HFA in participants with COPD (E.5.2 a, b). Exploratory: - To determine responsiveness to study intervention for TP 1 (E5.2.a); - To determine time to onset of action for each study intervention (E5.2 b); - To assess superiority of BGF MDI HFO relative to placebo MDI HFA on lung function, pre- and post-dose, in participants with COPD (E5.2 c, d).

Conditions and MedDRA coding

Moderate to Severe 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 15

1. 1 Participants must be 40 to 80 years inclusive at the time ofsigning the ICF.
2. 10 Females must not be of childbearing potential or must use aform of highly effective birth control.
3. 11 Capable of giving signed informed consent as described inAppendix A which includes compliance with the requirements and restrictions listed in the ICFand in this protocol.
4. 12 Participants with calculated eGFR > 30 mL/min/1.73 m2 usingthe CKD-EPI formula.
5. 13 Participants who demonstrate acceptable MDI administrationand spirometry techniques.
6. 14 Participants who remain compliant with placebo run-inadministrations, defined as ≥ 80% of planned doses over the last 7 days prior to Visit 3, based onePRO diary data.
7. 2 Participants who have a documented history of physician-diagnosed COPD as defined by the ATS/ERS (Celli et al 2004).
8. 3 Participants who have been receiving LABA, LAMA, LAMA/LABA, or ICS/LABA inhaled maintenance therapies for the management of their COPDfor at least 4 weeks prior to Visit 1, OR Participants who have been receiving SABA, SAMA, or SABA/SAMAeither scheduled or as needed for at least 4 weeks prior to Visit 1, OR Participants who are COPD treatment-naïve or have not received previously prescribed COPD treatment in the 4 weeks prior to Visit 1.
9. 4 At Visit 1: Participants with a blood eosinophil count < 300 cells/μL.
10. 5 At Visit 1: Participants with a pre-bronchodilator FEV1 of < 80%predicted normal.
11. 6 At Visit 2: Participants with a post-bronchodilator FEV1/FVC ratioof < 0.70 and a postbronchodilator FEV1 of ≥ 40% to < 80% predicted normal.
12. 7 At Visit 3 (TP 1 Day 1): Participants with a pre-dose FEV1 of <80% predicted normal that is within ± 20% or 200 mL of their Visit 2 pre-bronchodilatorFEV1 and an FEV1/FVC ratio of < 0.70.
13. 8 Current or former smokers with a history of at least 10 pack-years of tobacco smoking (1 pack-year = 20 cigarettes smoked per day for one year).
14. 9 Participants who are willing and, in the opinion of the Investigator, able to adjust current COPD therapy, as required by the protocol.
15. 15 Participants who are willing to remain at the study centre as required per protocol to complete all visit assessments.

Exclusion criteria 26

1. 1.Confirmed diagnosis of asthma, in the opinion of the Investigator based on thorough review of medical history and medical records.
2. 2.COPD due to α1-antitrypsin deficiency.
3. 3.A COPD exacerbation treated with systemic corticosteroids or antibiotics within 4 months prior to Visit 1 or during the Screening Period.
4. 4.A COPD exacerbation that required hospitalisation within 12 months prior to Visit 1 or during the Screening Period.
5. 5.A respiratory infection ending within 4 weeks prior to Visit 1 or beginning or ending during the Screening Period, per the Investigator’s judgement.
6. 6.Life-threatening COPD (eg, need for mechanical ventilation) at any time prior to Visit 1 or during the Screening Period.
7. 7.A SARS CoV 2 infection in the 8 weeks prior to Visit 1 or during the Screening Period, or that required hospitalisation at any time prior to Visit 1 or during the Screening Period.
8. 8.Sleep apnoea that, in the opinion of the Investigator, is uncontrolled.
9. 9.Other respiratory disorders including, but not limited to, known active tuberculosis, lung cancer, cystic fibrosis, significant bronchiectasis (high-resolution CT evidence of bronchiectasis that causes repeated acute exacerbations), severe neurological disorders affecting control of the upper airway, sarcoidosis, primary ciliary dyskinesia, idiopathic interstitial pulmonary fibrosis, primary pulmonary hypertension, or pulmonary thromboembolic disease.
10. 10.Significant or unstable ischaemic heart disease, arrhythmia, cardiomyopathy, heart failure, uncontrolled hypertension as defined by the Investigator, or any other relevant cardiovascular disorder as judged by the Investigator.
11. 11.Diagnosis of narrow-angle glaucoma that has not been adequately treated, or a change in vision that may be relevant, in the opinion of the Investigator. Note: All medications approved for control of intraocular pressures are allowed, including topical ophthalmic nonselective beta-blockers and prostaglandin analogues.
12. 12.Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant.
13. 13.Unresectable cancer that has not been in complete remission for at least 5 years prior to Visit 1. Note: Squamous cell and basal cell carcinomas of the skin are allowed.
14. 14.Historical or current evidence of a clinically significant disease including, but not limited to: cardiovascular, hepatic, renal, haematological, neurological, endocrine, gastrointestinal, or pulmonary. Immune deficiency disorders (ie, HIV infection) should be excluded even if controlled. 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 if the disease/condition is exacerbated during the study.
15. 15.Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the MDI.
16. 16.Known history of drug or alcohol abuse within 12 months of Visit 1 or known abuse at any time during the study.
17. 17.History of QT prolongation associated with another medication that required discontinuation of that medication.
18. 18.Unable to abstain from short-acting bronchodilators within 6hours prior to lung function testing at each study visit.
19. 19.Pulmonary resection or lung volume reduction surgery during the 6 months prior to Visit 1 (ie, lobectomy, bronchoscopic lung volume reduction [endobronchial blockers, airway bypass, endobronchial valves, thermal vapour ablation, biological sealants, and airway implants]).
20. 20.Long-term-oxygen therapy or nocturnal oxygen therapy required for greater than 15 hours per day. Note: As-needed oxygen use is allowed.
21. 21.Trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Visit 1.
22. 22.Unable to abstain from any protocol-defined prohibited medications during the Screening or Treatment Periods (see Section 6.9).
23. Participants with ECG QTcF interval > 480 milliseconds.
24. Participants with high-degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker.
25. Any clinically relevant abnormal findings in physical examination, clinical chemistry, haematology, urinalysis, vital signs, or ECG which, in the opinion of the Investigator, may put the participant at risk because of their participation in the study.
26. Planned hospitalisation during the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. a)To assess the equivalence of BGF MDI HFO relative to BGF MDI HFA on change from baseline in FEV(1)AUC(0-4)
2. b) To assess the equivalence of BGF MDI HFO relative to BGF MDI HFA on change from baseline in morning pre-dose trough FEV(1)
3. c) To demonstrate assay sensitivity via superiority of BGF MDI HFA relative to placebo MDI HFA on change from baseline in FEV(1) AUC(0-4)
4. d) To demonstrate assay sensitivity via superiority of BGF MDI HFA relative to placebo MDI HFA on change from baseline in morning pre-dose trough FEV(1

Secondary endpoints 5

1. Safety: a) AEs b) Vital signs (systolic and diastolic blood pressure, pulse rate)
2. Exploratory: a) Change from baseline in FEV(1) AUC(0-4) at TP 1
3. Exploratory: b) Time to onset defined as the first post-dose timepoint where the mean change from baseline in FEV1 exceeds 100 mL on TP 1
4. Exploratory: c) To demonstrate assay sensitivity via superiority of BGF MDI HFO relative to placebo MDI HFA on change from baseline in FEV(1)AUC(0-4) at Day 29
5. Exploratory: d) To demonstrate assay sensitivity via superiority of BGF MDIHFO relative to placebo MDI HFA on change from baseline in morning pre-dose trough FEV(1) at Day 29

Investigational products

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

Test 1

Comparator 1

Placebo 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

3 EU/EEA countries · 21 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 25 files

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

Application history

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