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

Phase 3

Active, not recruiting

Conditions: Moderate to Severe Chronic Obstructive Pulmonary Disease(COPD)

Registration Number: 2023-506565-57-00

Lead Sponsor: Astrazeneca AB

Brief Summary: 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

Detailed Description: This is a phase III, randomised, placebo-controlled, double-blind, multi-centre, 4-week, 3-way crossover pharmacodynamic study to assess the equivalence of BGF MDI HFO compared with BGF MDI HFA in participants with COPD. To demonstrate assay sensitivity, BGF MDI HFA will be compared to placebo MDI HFA for superiority in lung function, both pre- and post-dose.

Eligible participants are between 40 and 80 years of age, inclusive, who have an established clinical history of COPD as defined by the ATS/ERS. Participants are required to have an FEV1/FVC ratio of \< 0.70, have a post-bronchodilator FEV1 ≥ 40% and \< 80% predicted normal value, have a blood eosinophil count \< 300 cells/μL, and be current or former cigarette smokers with a history of at least 10 pack-years. Participants must not have had a COPD exacerbation treated with oral corticosteroids or antibiotics within 4 months prior to initiation of screening, and must not have had a COPD exacerbation that required hospitalisation within 12 months prior to initiation of screening. Eligible participants are those on treatment with LABA, LAMA, LAMA/LABA (open or fixed-dose combination), ICS/LABA (open or fixed-dose combination) inhaled maintenance therapies, or SABA, SAMA, or SAMA/SABA scheduled or as-needed inhaled therapies, or who are naïve to COPD therapy.

This study will be conducted at approximately 95 sites globally. After screening, participants will be randomised 1:1:1:1:1:1 to receive study interventions in one of 6 possible treatment sequences.

Recruitment & Eligibility

Status: Ongoing, recruitment ended

Sex: Not specified

Target Recruitment: 49

Inclusion Criteria

1 Participants must be 40 to 80 years inclusive at the time ofsigning the ICF.

5 At Visit 1: Participants with a pre-bronchodilator FEV1 of < 80%predicted normal.

6 At Visit 2: Participants with a post-bronchodilator FEV1/FVC ratioof < 0.70 and a postbronchodilator FEV1 of ≥ 40% to < 80% predicted normal.

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.

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).

9 Participants who are willing and, in the opinion of the Investigator, able to adjust current COPD therapy, as required by the protocol.

15 Participants who are willing to remain at the study centre as required per protocol to complete all visit assessments.

10 Females must not be of childbearing potential or must use aform of highly effective birth control.

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.

12 Participants with calculated eGFR > 30 mL/min/1.73 m2 usingthe CKD-EPI formula.

13 Participants who demonstrate acceptable MDI administrationand spirometry techniques.

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.

2 Participants who have a documented history of physician-diagnosed COPD as defined by the ATS/ERS (Celli et al 2004).

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.

4 At Visit 1: Participants with a blood eosinophil count < 300 cells/μL.

Exclusion Criteria

1.Confirmed diagnosis of asthma, in the opinion of the Investigator based on thorough review of medical history and medical records.

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.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.Symptomatic prostatic hypertrophy or bladder neck obstruction/urinary retention that, in the opinion of the Investigator, is clinically significant.

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.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.Participants with a known hypersensitivity to beta2-agonists, muscarinic antagonists, or corticosteroids, or any component of the MDI.

16.Known history of drug or alcohol abuse within 12 months of Visit 1 or known abuse at any time during the study.

17.History of QT prolongation associated with another medication that required discontinuation of that medication.

18.Unable to abstain from short-acting bronchodilators within 6hours prior to lung function testing at each study visit.

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]).

2.COPD due to α1-antitrypsin deficiency.

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.Trans-urethral resection of the prostate or full resection of the prostate within 6 months prior to Visit 1.

22.Unable to abstain from any protocol-defined prohibited medications during the Screening or Treatment Periods (see Section 6.9).

Participants with ECG QTcF interval > 480 milliseconds.

Participants with high-degree atrioventricular block II or III, or with sinus node dysfunction with clinically significant pauses who are not treated with pacemaker.

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.

Planned hospitalisation during the study.

3.A COPD exacerbation treated with systemic corticosteroids or antibiotics within 4 months prior to Visit 1 or during the Screening Period.

4.A COPD exacerbation that required hospitalisation within 12 months prior to Visit 1 or during the Screening Period.

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.Life-threatening COPD (eg, need for mechanical ventilation) at any time prior to Visit 1 or during the Screening Period.

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.Sleep apnoea that, in the opinion of the Investigator, is uncontrolled.

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
a)To assess the equivalence of BGF MDI HFO relative to BGF MDI HFA on change from baseline in FEV(1)AUC(0-4)		a)To assess the equivalence of BGF MDI HFO relative to BGF MDI HFA on change from baseline in FEV(1)AUC(0-4)
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)		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)
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)		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)
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		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 Outcome Measures

Name	Time	Method
Safety: a) AEs b) Vital signs (systolic and diastolic blood pressure, pulse rate)		Safety: a) AEs b) Vital signs (systolic and diastolic blood pressure, pulse rate)
Exploratory: a) Change from baseline in FEV(1) AUC(0-4) at TP 1		Exploratory: a) Change from baseline in FEV(1) AUC(0-4) at TP 1
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		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
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		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
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		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

Trial Locations

Locations (21): Erzsebet Gondozohaz Kft.
🇭🇺
Godollo, Hungary
Dr. Kenessey Albert Korhaz Rendelointezet
🇭🇺
Balassagyarmat, Hungary
Szalay Janos Rendelointezet
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Hajdunanas, Hungary
Da Vinci Spa Kft.
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Pecs, Hungary
Omnimodus Elixir Kft.
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Mosonmagyarovar, Hungary
Puspokladanyi Egeszsegugyi Szolgaltato Intezmeny
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Puspokladany, Hungary
PULMAG Grzegorz Gasior Marzena Kociolek S.C.
🇵🇱
Sosnowiec, Poland
Wojewodzki Szpital Specjalistyczny Im. Sw. Rafala W Czerwonej Gorze
🇵🇱
Checiny, Poland
Zanamed Medical Clinic Sp. z o.o.
🇵🇱
Lublin, Poland
Centrum Medycyny Oddechowej Mroz Sp. j.
🇵🇱
Bialystok, Poland
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Erzsebet Gondozohaz Kft.
🇭🇺Godollo, Hungary
Janos Mucsi
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