Chronic Obstructive Pulmonary DiseasePhase 3DARWiINNCT04876677
Functional Respiratory Imaging Study (DARWiIN)
A Phase 3 study testing Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB) in people with Chronic Obstructive Pulmonary Disease, run by Chiesi Farmaceutici S.p.A. at 8 sites in 2 countries.
Trial 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… Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 18 May 2021to 3 Jan 2022
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient's signed ICF obtained prior to any study-related procedure;
- Male or female ≥40 years of age;
- 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);
- Established diagnosis of COPD according to the 2020 GOLD Report, prior to the V1;
- 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);
- On a stable dose of any non-extrafine ICS/LABA DPI twice daily regimen for at least 8 weeks before screening;
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- 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;
- Symptomatic patients with COPD Assessment Test (CAT) score ≥10 at V1 and V2;
- Documented history of ≥1 moderate or severe COPD exacerbation in the previous 12 months prior to V1;
- Had a cooperative attitude and the ability to be trained and use correctly the DPIs;
- 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;
- Women of childbearing potential (WOCBP) fulfilling one of the following criteria:
- 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
- WOCBP with non-fertile male partners (contraception was not required in this case).
- 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).
Who cannot join
- Pregnant or lactating woman;
- 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;
- A current asthma diagnosis;
- 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;
- 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;
- 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;
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- 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;
- History of lung transplant or lung reduction surgery;
- 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;
- 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;
- 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;
- 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);
- Contra-indications to investigational medicinal products (IMPs), based on Investigator judgement;
- 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;
- Patients mentally or legally incapacitated or patients accommodated in an establishment as a result of an official or judicial order;
- Documented Coronavirus disease 2019 (COVID-19) diagnosis or its complications which had not resolved within 14 days prior to screening;
- Positive molecular COVID-19 test within the last 72 h before the remaining of screening activities.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
Belgium5 sites
OLV Hospital Aalst
Aalst
Pneumocare Scrl
Erpent
AZ Zeno Knokke-Heist
Knokke
Medlmprove BV
Kontich, 2550
AZ Delta
Roeselare
Hungary3 sites
Dr. Kenessey Albert Hospital
Balassagyarmat
National Koranyi Institute for TB and Pulmonology
Budapest
CRU Hungary Ltd
Miskolc
About this study
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)
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:
Read more
- 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB)
- Keywords
- COPD, Functional Respiratory Imaging (FRI), CHF5993 DPI, Seretide DISKUS
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB)Drug
Also called CHF5993
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
| Study group | Role | What they receive |
|---|---|---|
| CHF5993 DPI 100/6/12.5 μg | Experimental | 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). Receives: Drug: Beclomethasone dipropionate/Formoterol Fumarate/Glycopyrronium (BDP/FF/GB) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days)
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.
Measured: V2 pre-dose (i.e. baseline, assessed at week 6 ± 2 days), V3 pre-dose (assessed at week 12 ± 2 days)
Secondary outcomes (4)
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.
Measured: 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)
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)
Measured: 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)
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.
Measured: 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)
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.
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2021
- Study start18 May 2021
- Primary completion3 Jan 2022
- Study completion3 Jan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Chiesi Farmaceutici S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Chiesi Farmaceutici S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Wilfried De Backer, MD, PhD, Principal investigator, Medlmprove BV, Kontich, Belgium
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04876677
- Sponsor's protocol ID
- CLI-05993BA1-08
- Other IDs
- 2020-002356-20
- Acronym
- DARWiIN
- Status last verified
- Mar 2026
- First submitted
- 3 May 2021
- Last updated
- 9 Apr 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- 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.
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