Functional Respiratory Imaging Study (DARWiIN)

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)

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

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Aalst, Belgium
    • OLV Hospital Aalst
  • Erpent, Belgium
    • Centre medical Erpent - Residence
  • Knokke, Belgium
    • AZ Zeno Knokke-Heist
  • Reet, Belgium
    • Heilige Familie AZ
  • Roeselare, Belgium
    • AZ Delta
• Hungary
  • Balassagyarmat, Hungary
    • Dr. Kenessey Albert Hospital
  • Budapest, Hungary
    • National Koranyi Institute for TB and Pulmonology
  • Miskolc, Hungary
    • CRU Hungary Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject's signed Informed Consent Form;
2. Male or female ≥ 40 years of age;
3. Current smokers or ex-smokers of at least 10 pack-years,
4. Established diagnosis of COPD
5. Post-BD Forced Expiratory Volume in one second/Forced Vital Capacity (FEV1/FVC) < 0.7 and FEV1 ≤ 60% of predicted at V1
6. On a stable dose any non-extra fine ICS/LABA DPI twice daily regimen for at least 8 weeks before screening;
7. Presence of lung hyperinflation
8. Symptomatic subjects with COPD assessment test (CAT) score ≥ 10;
9. Documented history of ≥ 1 moderate or severe COPD exacerbation in the previous 12 months

Exclusion Criteria:

1. Pregnant or lactating woman;
2. Exacerbations defined as a sustained and acute deterioration of subject's symptoms and signs 30 days before screening;
3. A current asthma diagnosis;
4. Respiratory disorders other than COPD:
5. Cardiovascular diseases;
6. Evidence or history of other concurrent disease such as but not limited to hyperthyroidism, diabetes mellitus or other endocrine disease;
7. Medical history or current diagnosis of narrow-angle glaucoma;
8. History of lung transplant or lung reduction surgery;
9. 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;
10. Laboratory abnormalities;
11. Alcohol/drug abuse;
12. Contra-indications to Investigational medical products (IMPs), based on investigator judgement;
13. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: CHF5993; 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; Two inhalations bid: 4 inhalations; total daily dose of 400/24/50 μg BDP/FF/GB

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Chiesi Farmaceutici S.p.A.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 25, 2021
• Primary Completion (ACTUAL): January 3, 2022
• Study Completion (ACTUAL): January 3, 2022

Study Registration Dates

• First Submitted: May 3, 2021
• First Submitted That Met QC Criteria: May 3, 2021
• First Posted (ACTUAL): May 6, 2021

Study Record Updates

• Last Update Posted (ACTUAL): January 25, 2022
• Last Update Submitted That Met QC Criteria: January 24, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Physiological Effects of Drugs; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Adjuvants, Anesthesia; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Beclomethasone; Glycopyrrolate; Formoterol Fumarate
• Other Study ID Numbers: CLI-05993BA1-08

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No