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CompletedNCT04876677DARWiINUpdated Apr 9, 2026Results posted

Functional Respiratory Imaging Study (DARWiIN)

A Phase 3 interventional study of Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB) in Chronic Obstructive Pulmonary Disease, sponsored by Chiesi Farmaceutici S.p.A.. Completed at 8 sites in 2 countries. Open to participants aged 40 Years and older. Per ClinicalTrials.gov, last updated 2026-04-09.

Sponsored by Chiesi Farmaceutici S.p.A. · Phase 3, Interventional, and Treatment

Phase
Phase 3
Study type
Interventional
Enrollment
25
Allocation
Not applicable
Ages
40 Years and older
Sex
All
01

Study summary

The objective of this clinical study was to evaluate the tolerability, safety, and efficacy of stepping up from fluticasone propionate (FP)/salmeterol (SLM) dry-powder inhaler (DPI) (SERETIDE™ DISKUS™) to extrafine beclometasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) DPI (CHF5993) and to assess its effect on airway geometry and lung ventilation in subjects with advanced Chronic Obstructive Pulmonary Disease (COPD).

Primary Objectives:

  • Untrimmed siVaw for distal region at TLC - actual value for V2 pre-dose and V3 pre-dose
  • Trimmed siRaw for distal region at TLC - actual value for V2 pre-dose and V3 pre-dose

Secondary Objectives:

  • Untrimmed siVaw for distal region at TLC and FRC - actual value for V2 pre-dose, V2 post-dose, V3 pre-dose and V3 post-dose
  • Trimmed siRaw for distal region at TLC and FRC - actual value for V2 pre-dose, V2 post-dose, V3 pre-dose and V3 post-dose
  • Safety assessment through the evaluation of treatment-emergent adverse events (TEAEs).
Read the detailed description

The study was an open-label, single-arm, prospective study of a duration of approximately 14 weeks per patient, aimed at evaluating the effect of step-up from non-extra fine ICS/LABA DPI to extra fine triple therapy with CHF5993 DPI on airway geometry and lung ventilation using Functional Respiratory Imaging (FRI) in subjects with advanced COPD.

All parameters assessed in this trial were evaluated at the following visits:

  • Visit 1: Baseline Visit (Run-In Start): Screening and initiation of SERETIDE™ DISKUS™ DPI.
  • Visit 2 (Transition to CHF5993 DPI): End of the 6-week run-in period.
  • Visit 3 (End of Treatment): Completion of the 6-week CHF5993 DPI treatment phase.

The screening visit (V1) was followed by a 6-week run-in phase where participants were stabilized on SERETIDE™ DISKUS™ DPI 500/50μg, one inhalation twice daily (b.i.d.). This regimen provided a total daily dose of 1 mg of fluticasone propionate (FP) and 100 µg of salmeterol (SLM). At the screening visit (V1), patients received specific training on the proper use of the inhalation technique using In-Check Dial for both SERETIDE™ DISKUS™ and CHF5993 NEXThaler®. More precisely, to familiarize participants with the technique and ensure repeatable inhalations one assessment was set up for DISKUS™ resistance and the other for NEXThaler® resistance.

At the end of the run-in period (V2), patients transitioned to a 6-week treatment phase with CHF5993 DPI (until V3).

A follow-up call was conducted 2 weeks ± 2 days after V3 for males and women of non-childbearing potential, FRI, spirometry, and plethysmography were used to evaluate airway geometry, lung ventilation, and lung function.

02

Conditions studied

  • Chronic Obstructive Pulmonary Disease

Keywords

  • COPD
  • Functional Respiratory Imaging (FRI)
  • CHF5993 DPI
  • Seretide DISKUS
03

In context

Pulmonary Disease, Chronic Obstructive

4,131 studies on the registry are indexed under Pulmonary Disease, Chronic Obstructive; 697 are open to participants now.

This study's enrollment of 25 is below the median of 70 across 2,926 interventional studies indexed under Pulmonary Disease, Chronic Obstructive.

Browse Pulmonary Disease, Chronic Obstructive studies →

Lead sponsor

Chiesi Farmaceutici S.p.A. is the lead sponsor of 182 studies on the registry; 22 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 11 (65%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
40 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  1. Patient's signed ICF obtained prior to any study-related procedure;
  2. Male or female ≥40 years of age;
  3. Current smokers or ex-smokers of at least 10 pack-years, calculated as (number of cigarettes/day * number of years)/20 (e-cigarettes smoking could not be used to calculate pack-year history);
  4. Established diagnosis of COPD according to the 2020 GOLD Report, prior to the V1;
  5. Post-BD FEV1/forced vital capacity (FVC) \<0.7 and FEV1 ≤60% of predicted at V1 (Note: if the criterion was not met at screening, the measure could be repeated once before run-in Day 1);
  6. On a stable dose of any non-extrafine ICS/LABA DPI twice daily regimen for at least 8 weeks before screening;
  7. Presence of lung hyperinflation based on the increase of TLC exceeding either the ULN or 120% of predicted, and/or a plethysmographic FRC exceeding either ULN or 120% of predicted;
  8. Symptomatic patients with COPD Assessment Test (CAT) score ≥10 at V1 and V2;
  9. Documented history of ≥1 moderate or severe COPD exacerbation in the previous 12 months prior to V1;
  10. Had a cooperative attitude and the ability to be trained and use correctly the DPIs;
  11. Had a cooperative attitude and the ability to perform the required outcomes measurements (e.g., spirometry manoeuvres in sitting and supine position) and the ability to understand the risks involved;

  12. Women of childbearing potential (WOCBP) fulfilling one of the following criteria:

    1. WOCBP with fertile male partners: they and/or their partner had to be willing to use a highly effective birth control method from the signature of the informed consent and until the follow-up visit or
    2. WOCBP with non-fertile male partners (contraception was not required in this case).
  13. Female patients of non-childbearing potential defined as physiologically incapable of becoming pregnant (i.e., post-menopausal or permanently sterile; e.g., amenorrhea for ≥12 consecutive months without alternative medical cause). Permanent sterilisation methods included hysterectomy, bilateral salpingectomy, and bilateral oophorectomy. If indicated, as per Investigator's request, post-menopausal status could be confirmed by follicle-stimulating hormone (FSH) levels (according to local laboratory ranges).

Exclusion criteria

Exclusion Criteria:

  1. Pregnant or lactating woman;
  2. Exacerbations defined as a sustained and acute deterioration of patient's symptoms and signs (dyspnoea, cough and/or sputum production/purulence) that were either moderate, i.e., required treatment with systemic (oral/intravenous [IV]/intramuscular [IM]) corticosteroids and/or antibiotics, or severe, i.e., required hospitalisation, if their associated treatment/hospitalisation occurred within the 30 days before V1 (or 4 weeks in case the event was treated with just systemic corticosteroids) or if the event was recorded during the run-in period;
  3. A current asthma diagnosis;
  4. Respiratory disorders other than COPD: patients with known respiratory disorders other than COPD that in the Investigator's opinion could affect efficacy and safety evaluation or place the patient at risk. This could include but was not limited to known α1-anti-trypsine deficiency, active tuberculosis, bronchiectasis, sarcoidosis, lung fibrosis, pulmonary hypertension, and interstitial lung disease;
  5. Cardiovascular diseases: patients who had known clinically significant cardiovascular conditions such as but not limited to: unstable or acute ischaemic heart disease within one year prior to study entry, New York Heart Association (NYHA) class IV heart failure, history of atrial fibrillation, history of sustained, and non-sustained cardiac arrhythmias diagnosed within 6 months prior to study entry and not controlled with therapy according to the Investigator's opinion;
  6. Evidence or history of other concurrent disease such as but not limited to hyperthyroidism, diabetes mellitus, or other endocrine disease; haematological disease; autoimmune disorders (e.g,. rheumatoid arthritis); significant renal impairment; significant neurological disease or other disease or condition that might, in the judgement of the Investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study;
  7. Medical history or current diagnosis of narrow-angle glaucoma, clinically relevant prostatic hypertrophy, or bladder neck obstruction that in the opinion of the Investigator could have prevented use of anticholinergic agents;
  8. History of lung transplant or lung reduction surgery;
  9. Electrocardiogram (ECG) criteria: any clinically significant abnormal 12-lead ECG that in the Investigator's opinion could affect efficacy or safety evaluation or place the patients at risk. Male patients with a QTcF >450 ms and female patients with a QTcF >470 ms at V1 were not eligible;
  10. Laboratory abnormalities: patients with clinically significant laboratory abnormalities indicating a significant or unstable concomitant disease that could, in the judgement of the Investigator, place the patient at undue risk or potentially compromise the results or interpretation of the study;
  11. Alcohol/drug abuse: patients with a known or suspected history of alcohol and/or substance/drug abuse within 12 months prior to screening; or had a positive drug test at screening or V2;
  12. Participation in investigational study: patients who had received any investigational drug within the 30 days or a more appropriate time as determined by the Investigator (e.g., approximately five half-lives of the investigational drug, whatever was longer);
  13. Contra-indications to investigational medicinal products (IMPs), based on Investigator judgement;
  14. Hypersensitivity: history of hypersensitivity to any of the study medications components or a history of other allergy that in the opinion of the Investigator contraindicated the patient's participation;
  15. Patients mentally or legally incapacitated or patients accommodated in an establishment as a result of an official or judicial order;
  16. Documented Coronavirus disease 2019 (COVID-19) diagnosis or its complications which had not resolved within 14 days prior to screening;
  17. Positive molecular COVID-19 test within the last 72 h before the remaining of screening activities.
05

Study design

Phase
Phase 3
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    CHF5993 DPI 100/6/12.5 μg

    All patients (25 subjects) received CHF5993 as follows: \- Treatment period (6 weeks): two inhalations b.i.d. of CHF5993 DPI 100/6/12.5 µg, giving a total daily dose of beclometasone dipropionate (BDP)/formoterol fumarate (FF)/glycopyrronium bromide (GB) 400/24/50 µg. After the screening visit (V1) that was to be performed 6 weeks ± 2 days before Visit 2 (V2), eligible patients were to undergo a 6-week run-in period with fluticasone dipropionate (FP)/salmeterol (SLM) DPI 500/50 µg (SERETIDE™ DISKUS™). At the end of the run-in period (V2), patients were to be switched to the treatment period with BDP/FF/GB DPI (CHF5993), as said for 6 weeks, until Visit 3 (V3).

    Drug: Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB)

Interventions

  • DrugBeclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB)

    Treatment period: two inhalations b.i.d. of CHF5993 DPI 100/6/12.5 µg, for a total daily dose of BDP/FF/GB 400/24/50 µg. All the eligible patients were treated

    Also known as: CHF5993

06

What researchers measure

Primary outcomes

  1. Untrimmed Airway Volume (siVaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose and V3 Pre-dose

    siVaw was measured using Functional Respiratory Imaging (FRI) at Total Lung Capacity (TLC). siVaw represents the 3D reconstruction and quantification of the volume of air within the segmented airway tree. Higher siVaw values indicate a reduction in airway obstruction and improved ventilation efficiency in the lungs. For patients with COPD, siVaw is typically reduced due to airway obstruction and structural changes in the lungs. The siVaw comparisons were made on 'untrimmed' airways SO that all visible generations in a given scan (from Visit 2 or 3 respectively) were used in order to capture all available volume information. The data were summarized by the descriptive statistics for actual values at each timepoint.

    Time frame: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days)

  2. Trimmed Airway Volume (siRaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose and V3 Pre-dose

    siRaw was measured using Functional Respiratory Imaging (FRI) at TLC. siRaw represents the 3D reconstruction and quantification of resistance to airflow within the segmented airway tree. Lower siRaw values indicate improved airway patency, reduced airflow resistance, and enhanced ventilation efficiency in the lungs. For patients with COPD, siRaw is elevated due to airway narrowing, obstruction, and other structural changes in the lungs. The siRaw was evaluated using 'trimmed' data, meaning that only airway generations visible in both scans (i.e., the same airways) were used. The use of trimmed data in Multidetector computed tomography (MDCT) ensures that differences between scans are solely due to changes in airway calibre, not variations in the number of airway generations included in Computational Fluid Dynamics (CFD) calculations. The data were summarized by the descriptive statistics for actual values at each timepoint.

    Time frame: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days)

Secondary outcomes

  1. Untrimmed Airway Volume (siVaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

    Airway volume (siVaw) was measured using Functional Respiratory Imaging (FRI) at TLC. siVaw quantifies the volume of air in the segmented airway tree. Higher siVaw values indicate reduced airway obstruction and improved ventilation. For this outcome, siVaw was assessed in distal lung regions, using 'untrimmed' data to include all visible airway generations. The data were summarized by the descriptive statistics for actual values at each timepoint.

    Time frame: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days) and V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)

  2. Untrimmed siVaw for Distal Region at Functional Residual Capacity (FRC) - Actual Value for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

    Airway volume (siVaw) was measured using Functional Respiratory Imaging (FRI) at FRC. siVaw quantifies the air volume in the segmented airway tree at the end of a normal exhalation, expressed in milliliters (mL). Higher siVaw values at FRC indicate reduced airway obstruction and improved residual ventilation. In this outcome, siVaw was assessed in central and distal lung regions using 'untrimmed' data, ensuring all visible airway generations were included. Percent change in siVaw was calculated to evaluate treatment effects at these time points: Baseline (V2 pre-dose) to post-dose at V3, reflecting long-term improvements. Pre-dose to post-dose at V2, assessing the acute effect of SERETIDE™ DISKUS™ DPI. Pre-dose to post-dose at V3, assessing the acute effect of CHF5993 DPI. Percentage change from time point t at time point t1 was defined as follows: 100\*((value at time point t - value at time point t1) / value at time point t1)

    Time frame: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days), V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)

  3. Trimmed siRaw Via Functional Respiratory Imaging (FRI) for Distal Region at Total Lung Capacity (TLC) - Actual Values for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

    Airway resistance (siRaw) was measured using FRI at TLC. siRaw quantifies airflow resistance within the segmented airway tree during inspiration. Lower siRaw values indicate reduced airway resistance, improved airway patency, and enhanced ventilation. For this outcome, siRaw was assessed in central and distal lung regions using 'untrimmed' data, ensuring all visible airway generations were included. The data were summarized by the descriptive statistics for actual values at each timepoint.

    Time frame: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days), V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)

  4. Trimmed siRaw for Distal Region Using Functional Respiratory Imaging (FRI) at Functional Residual Capacity (FRC) - Actual Values for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

    Airway resistance (siRaw) was measured using Functional Respiratory Imaging (FRI) at Functional Residual Capacity (FRC). siRaw quantifies airflow resistance within the segmented airway tree at the end of a normal exhalation, expressed in cmH₂O·s. Lower siRaw values at FRC indicate reduced airway obstruction and improved airflow efficiency. For this outcome, siRaw was assessed in central and distal lung regions using 'untrimmed' data to include all visible airway generations. The data were summarized by the descriptive statistics for actual values at each timepoint.

    Time frame: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days), V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)

07

Results

Posted Apr 9, 2026

Participant flow

In total, 45 patients were screened of whom 20 were screening failures. The other 25 patients were enrolled and received two inhalations b.i.d. of CHF5993 DPI 100/6/12.5 µg. All enrolled and treated patients completed the study, and 23 patients were included in the PP analysis set due to eligibility criteria violations.

Participant flow — Overall Study
MilestoneCHF5993 DPI 100/6/12.5 μg
Started25
Saf population25
Pp population23
Completed25
Not completed0

Outcome measures

PrimaryUntrimmed Airway Volume (siVaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose and V3 Pre-dose

siVaw was measured using Functional Respiratory Imaging (FRI) at Total Lung Capacity (TLC). siVaw represents the 3D reconstruction and quantification of the volume of air within the segmented airway tree. Higher siVaw values indicate a reduction in airway obstruction and improved ventilation efficiency in the lungs. For patients with COPD, siVaw is typically reduced due to airway obstruction and structural changes in the lungs. The siVaw comparisons were made on 'untrimmed' airways SO that all visible generations in a given scan (from Visit 2 or 3 respectively) were used in order to capture all available volume information. The data were summarized by the descriptive statistics for actual values at each timepoint.

Time frame:
V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days)
Reported as:
Mean · liters
Untrimmed Airway Volume (siVaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose and V3 Pre-dose
litersCHF5993 DPI 100/6/12.5 μg - PP Population
Baseline / V2 pre-dose, TLC1.4088 ± 0.6647
V3 pre-dose, TLC1.3550 ± 0.6014
Statistical analysis
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = = 0.4521 (The model included the log of baseline (V2 pre-dose, but not for trimmed parameters) at TLC and visit (V2 post-dose, V3 pre-dose, V3 post-dose) as covariates, and the interaction between visit and logarithm of baseline (for untrimmed parameters).) · Adjusted mean change: -3.81 · 95% CI -13.44 to 6.89Model parameters were estimated using restricted maximum likelihood with an unstructured variance-covariance matrix and Kenward-Roger approximation.
PrimaryTrimmed Airway Volume (siRaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose and V3 Pre-dose

siRaw was measured using Functional Respiratory Imaging (FRI) at TLC. siRaw represents the 3D reconstruction and quantification of resistance to airflow within the segmented airway tree. Lower siRaw values indicate improved airway patency, reduced airflow resistance, and enhanced ventilation efficiency in the lungs. For patients with COPD, siRaw is elevated due to airway narrowing, obstruction, and other structural changes in the lungs. The siRaw was evaluated using 'trimmed' data, meaning that only airway generations visible in both scans (i.e., the same airways) were used. The use of trimmed data in Multidetector computed tomography (MDCT) ensures that differences between scans are solely due to changes in airway calibre, not variations in the number of airway generations included in Computational Fluid Dynamics (CFD) calculations. The data were summarized by the descriptive statistics for actual values at each timepoint.

Time frame:
V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days)
Reported as:
Mean · cmH₂O·s
Trimmed Airway Volume (siRaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose and V3 Pre-dose
cmH₂O·sCHF5993 DPI 100/6/12.5 μg - PP Population
Baseline / V2 pre-dose, TLC0.7160 ± 0.4034
V3 pre-dose, TLC0.8492 ± 0.5947
Statistical analysis
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = = 0.4871 (Model included the logarithm of baseline (V2 pre-dose, but not for trimmed parameters) at TLC and visit (V2 post-dose, V3 pre-dose, V3 post-dose) as covariates, and the interaction between visit and logarithm of baseline (for untrimmed parameters).) · Adjusted mean change: 11.95 · 95% CI -19.67 to 56.02Model parameters were estimated using restricted maximum likelihood with an unstructured variance-covariance matrix and Kenward-Roger approximation.
SecondaryUntrimmed Airway Volume (siVaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

Airway volume (siVaw) was measured using Functional Respiratory Imaging (FRI) at TLC. siVaw quantifies the volume of air in the segmented airway tree. Higher siVaw values indicate reduced airway obstruction and improved ventilation. For this outcome, siVaw was assessed in distal lung regions, using 'untrimmed' data to include all visible airway generations. The data were summarized by the descriptive statistics for actual values at each timepoint.

Time frame:
V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days) and V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)
Reported as:
Mean · liters
Untrimmed Airway Volume (siVaw) for Distal Region at Total Lung Capacity (TLC) - Actual Value for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose
litersCHF5993 DPI 100/6/12.5 μg - PP Population
Baseline / V2 pre-dose, TLC1.4088 ± 0.6647
V2 post-dose, TLC1.8706 ± 0.4954
V3 pre-dose, TLC1.3550 ± 0.6014
V3 post-dose, TLC1.9805 ± 0.6390
Statistical analysis
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = <0.0001 · Adjusted mean change: 39.76 · 95% CI 28.9 to 51.53
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = <0.0001 · Adjusted mean change: 62.63 · 95% CI 41.78 to 86.56
SecondaryUntrimmed siVaw for Distal Region at Functional Residual Capacity (FRC) - Actual Value for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

Airway volume (siVaw) was measured using Functional Respiratory Imaging (FRI) at FRC. siVaw quantifies the air volume in the segmented airway tree at the end of a normal exhalation, expressed in milliliters (mL). Higher siVaw values at FRC indicate reduced airway obstruction and improved residual ventilation. In this outcome, siVaw was assessed in central and distal lung regions using 'untrimmed' data, ensuring all visible airway generations were included. Percent change in siVaw was calculated to evaluate treatment effects at these time points: Baseline (V2 pre-dose) to post-dose at V3, reflecting long-term improvements. Pre-dose to post-dose at V2, assessing the acute effect of SERETIDE™ DISKUS™ DPI. Pre-dose to post-dose at V3, assessing the acute effect of CHF5993 DPI. Percentage change from time point t at time point t1 was defined as follows: 100\*((value at time point t - value at time point t1) / value at time point t1)

Time frame:
V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days), V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)
Reported as:
Mean · percent change of lung volume
Untrimmed siVaw for Distal Region at Functional Residual Capacity (FRC) - Actual Value for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose
percent change of lung volumeCHF5993 DPI 100/6/12.5 μg - PP Population
Baseline / V2 pre-dose, FRC0.6321 ± 0.3164
V2 post-dose, FRC1.0204 ± 0.3404
V3 pre-dose, FRC0.6982 ± 0.3198
V3 post-dose, FRC1.0442 ± 0.3825
Statistical analysis
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = 0.0636 · Adjusted mean change: 16.26 · 95% CI -0.93 to 36.44
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = <0.0001 · Adjusted mean change: 77.87 · 95% CI 60.28 to 97.39
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = =0.0011 · Adjusted mean change: 39.49 · 95% CI 16.21 to 67.43
SecondaryTrimmed siRaw Via Functional Respiratory Imaging (FRI) for Distal Region at Total Lung Capacity (TLC) - Actual Values for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

Airway resistance (siRaw) was measured using FRI at TLC. siRaw quantifies airflow resistance within the segmented airway tree during inspiration. Lower siRaw values indicate reduced airway resistance, improved airway patency, and enhanced ventilation. For this outcome, siRaw was assessed in central and distal lung regions using 'untrimmed' data, ensuring all visible airway generations were included. The data were summarized by the descriptive statistics for actual values at each timepoint.

Time frame:
V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days), V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)
Reported as:
Mean · cmH₂O·s
Trimmed siRaw Via Functional Respiratory Imaging (FRI) for Distal Region at Total Lung Capacity (TLC) - Actual Values for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose
cmH₂O·sCHF5993 DPI 100/6/12.5 μg - PP Population
Baseline / V2 pre-dose, TLC0.7160 ± 0.4034
V2 post-dose, TLC0.3685 ± 0.1594
V3 pre-dose, TLC0.8492 ± 0.5947
V3 post-dose, TLC0.3121 ± 0.1416
Statistical analysis
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = =0.0002 · Adjusted mean change: -51.07 · 95% CI -64.56 to -32.44
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = =0.0009 · Adjusted mean change: -57.22 · 95% CI -72.88 to -32.52
SecondaryTrimmed siRaw for Distal Region Using Functional Respiratory Imaging (FRI) at Functional Residual Capacity (FRC) - Actual Values for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose

Airway resistance (siRaw) was measured using Functional Respiratory Imaging (FRI) at Functional Residual Capacity (FRC). siRaw quantifies airflow resistance within the segmented airway tree at the end of a normal exhalation, expressed in cmH₂O·s. Lower siRaw values at FRC indicate reduced airway obstruction and improved airflow efficiency. For this outcome, siRaw was assessed in central and distal lung regions using 'untrimmed' data to include all visible airway generations. The data were summarized by the descriptive statistics for actual values at each timepoint.

Time frame:
V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V2 within 60-120 min post-dose (assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days), V3 within 60-120 min post-dose (assessed at week 12 ± 2 days)
Reported as:
Mean · cmH₂O·s
Trimmed siRaw for Distal Region Using Functional Respiratory Imaging (FRI) at Functional Residual Capacity (FRC) - Actual Values for V2 Pre-dose, V2 Post-dose, V3 Pre-dose and V3 Post-dose
cmH₂O·sCHF5993 DPI 100/6/12.5 μg - PP Population
Baseline / V2 pre-dose, FRC0.4981 ± 0.3383
V2 post-dose, FRC0.2200 ± 0.1664
V3 pre-dose, FRC0.3625 ± 0.4733
V3 post-dose, FRC0.1889 ± 0.1453
Statistical analysis
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = 0.0261 · Adjusted mean change: -63.57 · 95% CI -84.85 to -12.42
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = =0.0006 · Adjusted mean change: -66.95 · 95% CI -81.4 to -41.27
  • CHF5993 DPI 100/6/12.5 μg - PP Population · Mixed Models Analysis · p = =0.3855 · Adjusted mean change: -29.28 · 95% CI -68.62 to 59.42

Adverse events

Collected over Throughout the study, from screening visit (Week 0, Visit 1), till follow up visit (Week 14 ± 2 days). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
CHF5993 DPI 100/6/12.5 μg - SAF Population0/25 (0%)0/25 (0%)11/25 (44%)
Most frequent other events
Most frequent other events
EventCHF5993 DPI 100/6/12.5 μg - SAF Population
HeadacheNervous system disorders3/25
Pleural calcificationRespiratory, thoracic and mediastinal disorders2/25
SciaticaNervous system disorders1/25
Hiatus herniaGastrointestinal disorders1/25
BronchiectasisRespiratory, thoracic and mediastinal disorders1/25
Pulmonary fibrosisRespiratory, thoracic and mediastinal disorders1/25
Hepatic steatosisHepatobiliary disorders1/25
ArthralgiaMusculoskeletal and connective tissue disorders1/25

Baseline characteristics

The Safety Analysis Population (SAF) included all 25 patients who received at least one dose of the investigational product (IMP), including SERETIDE™ DISKUS™ DPI in the run-in and CHF5993 DPI in the treatment phase. This population was used to assess safety, including treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). However, only 23 patients were included in the Per Protocol (PP) Population due to eligibility criteria violations.

Age, Continuous
Age, Continuous(years)CHF5993 DPI 100/6/12.5 μg
Mean65.0 ± 7.7
Sex: Female, Male
Sex: Female, Male(Participants)CHF5993 DPI 100/6/12.5 μg
Female9
Male16
Race (NIH/OMB)
Race (NIH/OMB)(Participants)CHF5993 DPI 100/6/12.5 μg
American Indian or Alaska Native0
Asian0
Native Hawaiian or Other Pacific Islander0
Black or African American0
White25
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)CHF5993 DPI 100/6/12.5 μg
Belgium8
Hungary17
BMI
BMI(kg/m²)CHF5993 DPI 100/6/12.5 μg
Mean27.71 ± 5.05
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Study locations

8 sites
  • OLV Hospital Aalst
    Aalst, Belgium
  • Pneumocare Scrl
    Erpent, Belgium
  • AZ Zeno Knokke-Heist
    Knokke, Belgium
  • Medlmprove BV
    Kontich, 2550, Belgium
  • AZ Delta
    Roeselare, Belgium
  • Dr. Kenessey Albert Hospital
    Balassagyarmat, Hungary
  • National Koranyi Institute for TB and Pulmonology
    Budapest, Hungary
  • CRU Hungary Ltd
    Miskolc, Hungary
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References and documents

Publications

  • Skloot GS, Guasconi A, Lavon BR, Georges G, De Backer W, Galkin D, Cortellini M, Panni I, Bates JHT. The effect of inhaled extrafine beclometasone dipropionate/formoterol fumarate/glycopyrronium bromide on distal and central airway indices, assessed using Functional Respiratory Imaging in COPD (DARWiIN). Respir Res. 2023 Oct 6;24(1):244. doi: 10.1186/s12931-023-02549-5. PubMed 37803368 ↗

Study documents

  • Study protocol · May 26, 2021
  • Statistical analysis plan · Mar 29, 2022

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — Chiesi commits to sharing with qualified scientific and medical Researchers, conducting legitimate research, Patient-level Data, Study-level Data, the Clinical Protocol and the full CSR, providing access to clinical trial information consistently with the principle of safeguarding commercially confidential information and patient privacy. Any shared Patient-level Data is anonymized to protect personally identifiable information.

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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Apr 9, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT04876677
Lead sponsor
Chiesi Farmaceutici S.p.A.
Responsible party
Sponsor
First posted
May 6, 2021
Start date
May 18, 2021
Primary completion
Jan 3, 2022
Completion
Jan 3, 2022
Results posted
Apr 9, 2026
Last update
Apr 9, 2026

Study contacts

Wilfried De Backer, MD, PhD
principal investigator · Medlmprove BV, Kontich, Belgium

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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