Functional Respiratory Imaging Study (DARWiIN)

• ClinicalTrials.gov Identifier: NCT04876677
• Recruitment Status: Completed
• First Posted: May 6, 2021
• Last Update Posted: January 25, 2022
• Sponsor: Chiesi Farmaceutici S.p.A.
• Information provided by (Responsible Party): Chiesi Farmaceutici S.p.A.

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Chronic Obstructive Pulmonary Disease	Drug: Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 25 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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)
• Actual Study Start Date: May 25, 2021
• Actual Primary Completion Date: January 3, 2022
• Actual Study Completion Date: January 3, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. specific airway volume (siVaw) upon inspiration [ Time Frame: change from baseline at 6 weeks ]
   CT-based airway volumes
2. specific airway resistance (siRaw) upon inspiration [ Time Frame: change from baseline at 6 weeks ]
   CT-based airway volumes

Secondary Outcome Measures :

1. siVaw upon expiration [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
2. siRaw upon expiration [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
3. ventilation mapping [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
4. perfusion mapping [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
5. airway wall thickness upon inspiration [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
6. imaged lobe and lung volumes at Total Lung Capacity (TLC) and Functional Residual Capacity (FRC) [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
7. air trapping [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
8. low attenuation score at TLC [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
9. Percentile 15th at TLC [ Time Frame: change from baseline at 6 weeks ]
   calculated using Multidetector Computed Tomography
10. regional lung deposition [ Time Frame: change from baseline at 6 weeks ]
    calculated using Multidetector Computed Tomography

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Belgium

OLV Hospital Aalst

Aalst, Belgium

Centre medical Erpent - Residence

Erpent, Belgium

AZ Zeno Knokke-Heist

Knokke, Belgium

Heilige Familie AZ

Reet, Belgium

AZ Delta

Roeselare, Belgium

Hungary

Dr. Kenessey Albert Hospital

Balassagyarmat, Hungary

National Koranyi Institute for TB and Pulmonology

Budapest, Hungary

CRU Hungary Ltd

Miskolc, Hungary

Sponsors and Collaborators

Chiesi Farmaceutici S.p.A.

More Information

• Responsible Party: Chiesi Farmaceutici S.p.A.
• ClinicalTrials.gov Identifier: NCT04876677
• Other Study ID Numbers: CLI-05993BA1-08
• First Posted: May 6, 2021
• Last Update Posted: January 25, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Respiratory Tract Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Beclomethasone; Glycopyrrolate; Formoterol Fumarate; Bronchodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Asthmatic Agents; Respiratory System Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Adrenergic Agonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Adjuvants, Anesthesia; Muscarinic Antagonists; Cholinergic Antagonists; Cholinergic Agents