Functional Respiratory Imaging Study

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the stepping-up effect from a double ICS/LABA DPI therapy to a triple DPI therapy on airway geometry and lung ventilation

Official Title
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Open Label, Prospective Study to Evaluate the Effect of Step-up From Non-extra Fine Inhaled Corticosteroids/Long Acting Beta2 Agonist (ICS/LABA) Dry Powder Inhaler (DPI) to Extra Fine Triple Therapy With CHF5993 DPI on Airway Geometry and Lung Ventilation Using Functional Respiratory Imaging (FRI) in Subjects With Advanced Chronic Obstructive Pulmonary Disease (COPD)

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject's signed Informed Consent Form; Male or female ≥ 40 years of age; Current smokers or ex-smokers of at least 10 pack-years, Established diagnosis of COPD Post-BD Forced Expiratory Volume in one second/Forced Vital Capacity (FEV1/FVC) < 0.7 and FEV1 ≤ 60% of predicted at V1 On a stable dose any non-extra fine ICS/LABA DPI twice daily regimen for at least 8 weeks before screening; Presence of lung hyperinflation Symptomatic subjects with COPD assessment test (CAT) score ≥ 10; Documented history of ≥ 1 moderate or severe COPD exacerbation in the previous 12 months Exclusion Criteria: Pregnant or lactating woman; Exacerbations defined as a sustained and acute deterioration of subject's symptoms and signs 30 days before screening; A current asthma diagnosis; Respiratory disorders other than COPD: Cardiovascular diseases; Evidence or history of other concurrent disease such as but not limited to hyperthyroidism, diabetes mellitus or other endocrine disease; Medical history or current diagnosis of narrow-angle glaucoma; History of lung transplant or lung reduction surgery; ECG criteria: any clinically significant abnormal 12-lead ECG that in the investigator's opinion would affect efficacy or safety evaluation or place the subjects at risk; Laboratory abnormalities; Alcohol/drug abuse; Contra-indications to Investigational medical products (IMPs), based on investigator judgement; Documented Covid-19 diagnosis or its complications which have not resolved within 14 days prior to screening; 15. Positive molecular Covid-19 test within the last 72 hours before the remaining of screening activities.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CHF5993<br>Beclometasone Dipropionate (BDP) 100 μg/inhalation + Formoterol Fumarate (FF) 6 μg/inhalation + Glycopyrronium Bromide (GB) 12.5 µg/inhalation | Drug: Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium<br>* Two inhalations bid: 4 inhalations; total daily dose of 400/24/50 μg BDP/FF/GB<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| specific airway volume (siVaw) upon inspiration | CT-based airway volumes | change from baseline at 6 weeks | 
| specific airway resistance (siRaw) upon inspiration | CT-based airway volumes | change from baseline at 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| siVaw upon expiration | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| siRaw upon expiration | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| ventilation mapping | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| perfusion mapping | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| airway wall thickness upon inspiration | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| imaged lobe and lung volumes at Total Lung Capacity (TLC) and Functional Residual Capacity (FRC) | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| air trapping | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| low attenuation score at TLC | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| Percentile 15th at TLC | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks | 
| regional lung deposition | calculated using Multidetector Computed Tomography | change from baseline at 6 weeks |