Abstract
Background
Many patients with chronic obstructive pulmonary disease (COPD) remain symptomatic despite the use of available maintenance therapies. Ensifentrine is a novel, selective, dual inhibitor of phosphodiesterase (PDE)3 and PDE4 approved for use as a maintenance therapy in adult patients with COPD. This study evaluated the effect of ensifentrine added on to dual or triple therapy on symptoms and health status in symptomatic patients with COPD using the COPD Assessment Test™ (CAT).
Methods
In this single-center, Phase 3b, open-label study, patients aged 40 to 80 years with symptomatic (modified Medical Research Council Dyspnea Scale ≥2; CAT ≥10), moderate to severe COPD on stable dual bronchodilator or triple therapy received 3 mg twice-daily nebulized ensifentrine for 12 weeks. CAT scores were assessed at baseline, week 6, and week 12.
Results
Twenty eligible patients received ensifentrine. Patients with ≥1 postdose assessment (n=18) were analyzed. After 12 weeks, ensifentrine improved CAT scores by ≥2 units in 67.0% (95% CI, 38.0%, 100.0%) of patients. Mean change from baseline was –2.3 units (95% CI, –4.0, –0.6), exceeding the clinically important difference of –2 units. At week 6, 44.4% (95% CI, 22.0%, 89.5%) of patients were CAT responders; the mean change from baseline in CAT score was –1.5 units (95% CI, –4.0, 1.1). No adverse events were reported.
Conclusion
Ensifentrine provided clinically meaningful improvement in health status measured by CAT score in two-thirds of symptomatic patients with COPD taking dual bronchodilator or triple therapy in a real-world setting.
Clinical Trial Registration Number
Clinical trial registered on June 10, 2024, with Clinicaltrials.gov (Identifier: NCT06460493).
Keywords: chronic obstructive pulmonary disease, ensifentrine, quality of life, phosphodiesterase inhibitor, COPD Assessment Test
Introduction
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory condition characterized by chronic respiratory symptoms and persistent airflow limitation. COPD is a leading cause of morbidity and mortality, with a prevalence that continues to increase worldwide.1–3 The aim of COPD management is to reduce symptoms, reduce the frequency and severity of exacerbations, and improve health status.1 Current standard-of-care treatment regimens for patients with COPD include long-acting bronchodilators (long-acting muscarinic antagonists [LAMA] or long-acting β-agonists [LABA]), which can be used together (dual therapy) and combined with inhaled corticosteroids (ICS; triple therapy).4 Despite routine maintenance treatment with LAMA/LABA and LAMA/LABA/ICS therapy, many patients with COPD continue to experience persistent daily symptoms, particularly dyspnea (or shortness of breath) that can be disabling, cough, and impaired mucus clearance, resulting in reduced quality of life. Validated tools used to assess treatment effectiveness include patient-reported questionnaires such as the St. George’s Respiratory Questionnaire (SGRQ), Evaluating-Respiratory Symptoms (E-RS), Chronic Respiratory Questionnaire, and Clinical COPD Questionnaire to facilitate communication between the patient and physician. Although these tools are often used in clinical trials, they are not practical for use in routine clinical practice, given that they are complex, often time-consuming to complete, and may require additional specialized software.5–7
The COPD Assessment Test™ (CAT) is a validated, short, and simple patient-completed questionnaire developed for use in a clinical setting to assess COPD symptoms over time and their effect on a patient’s well-being.5 The CAT consists of 8 items selected to capture the wide range of COPD symptoms and impacts (ie, Cough, Mucus, Chest Tightness, Breathlessness, Limited Activities, Confidence, Sleep, and Energy), with each item presented on a 6-point scale from 0 (no impairment) to 5 (maximum impairment). Total CAT scores range from 0 to 40 and correlate closely with the SGRQ.1,8 The total score corresponds to the impact of COPD on daily life (mild, 0–9; moderate, 10–20; severe, 21–30; very severe, 31–40). The CAT is advantageous over other health status questionnaires because it takes 2 to 3 minutes to complete, its results can be viewed immediately and, by utilizing the score, improvement can be tracked to provide a holistic assessment of the patient’s health status.8
The minimum clinically important difference (MCID) is defined as the smallest change in an outcome score that an individual patient perceives as beneficial.8 The MCID is useful for interpretation of patient-reported outcome data over time and to determine whether a clinically meaningful improvement in symptoms occurs from one visit to the next, particularly in response to treatment or intervention.6,8 For CAT scores, a decrease from baseline of ≥2 units over 2 to 3 months suggests a meaningful improvement based on the determined reliable estimate of the MCID.8,9 The effect of COPD treatment regimens on CAT scores has been evaluated previously. Treatment with dual umeclidinium (UMEC)/vilanterol (VI; LAMA/LABA) over 12 weeks and triple therapy with fluticasone furoate/UMEC/VI (LAMA/LABA/ICS) have demonstrated clinically meaningful improvements in CAT scores.10–13 However, despite symptom improvements observed and multiple variations and combinations of dual and triple therapies used within these classes, many patients in routine clinical practice continue to report moderate to severe symptoms with a substantial effect on daily activities and emotional well-being.11,12,14–16 For example, Chen et al reported that 64% of patients taking dual or triple therapy for approximately 6 months reported a substantial burden of symptoms (CAT score >20) and that their COPD affected their work (55.9% of respondents) and leisure time (69.8% of respondents).14 Moreover, in a 2025 survey of approximately 2000 patients with COPD conducted during a visit with a healthcare provider, 64% reported that COPD had a moderate to great impact on their daily lives, with nearly half (50%) of patients reporting a moderate to great impact on their emotional well-being.17 Among patients who previously tried maintenance therapies, the majority (77%) indicated that they would be willing to try other therapies.16 The ongoing symptom burden in COPD patients despite dual or triple therapy highlights the need for additional treatment options that can provide benefit beyond commonly used therapies.
Ensifentrine is a novel, first-in-class, selective, dual inhibitor of phosphodiesterase (PDE)3 and PDE4 with demonstrated bronchodilatory and nonsteroidal anti-inflammatory effects that is approved for the maintenance treatment for COPD in adult patients.18–23 In two phase 3 clinical trials, ENHANCE-1 and ENHANCE-2, ensifentrine 3 mg demonstrated statistically significant improvements across all key forced expiratory volume in 1 second (FEV1) endpoints in patients with or without additional bronchodilator background therapy.20 In a pooled analysis of the ENHANCE trials, ensifentrine resulted in clinically meaningful improvements in dyspnea (assessed with the Transition Dyspnea Index [TDI]) and showed statistically significant improvements in COPD symptoms (assessed by E-RS daily diary) and quality of life (SGRQ) as early as 6 weeks, including when added on to LAMA or LABA + ICS treatment.4,20,24 Additionally, ensifentrine statistically significantly reduced the rate and risk of exacerbations in patients with moderate to severe COPD and in patients treated with LAMA (48% and 50%, respectively) and LABA + ICS (51% and 56%, respectively).4,20,24,25 Although the ENHANCE program demonstrated a statistically significant impact of ensifentrine on COPD symptoms and quality of life, the trials did not include patients on background dual (LAMA/LABA) or triple therapy (LAMA/LABA/ICS) regimens. Therefore, the objective of this study was to evaluate the effect of ensifentrine on health status when added on to routinely prescribed dual (LAMA/LABA) or triple (LAMA/LABA/ICS) therapy in patients with moderate to severe, symptomatic (baseline CAT score ≥10) COPD using the CAT questionnaire. This is a real-world, single-center, non-randomized and uncontrolled study to assess the effectiveness of ensifentrine in routine clinical practice.
Materials and Methods
Study Design
This study was a phase 3b, single-center, open-label study in 20 patients with symptomatic (baseline modified Medical Research Council [mMRC] Dyspnea Scale ≥2 and CAT ≥10), moderate-to-severe COPD receiving standard dual (LAMA/LABA) or triple (LAMA/LABA/ICS) therapy, intended to model the real-world experience of ensifentrine add-on therapy in a clinical practice (Figure S1). The CAT questionnaire was self-administered on paper at baseline, week 6, and week 12. Baseline CAT and mMRC Dyspnea Scale questionnaire scores were evaluated at visit 1. Enrolled patients received twice-daily ensifentrine 3 mg over 12 weeks via standard jet nebulizer. Medications permitted during study participation included continued use of prescribed inhaled short-acting muscarinic antagonists, short-acting β2-agonists (SABAs), or any form (except nebulized) of approved COPD doses of LABA/LAMA or LABA/LAMA/ICS and non-COPD medication not on the prohibited medications list (Table S1).
Patients
Eligible patients were aged 40 to 80 years with a confirmed diagnosis of moderate to severe COPD, defined as postbronchodilator FEV1/forced vital capacity (FVC) ratio of <0.7 and FEV1 of 30% to 75% of predicted normal. Patients were required to be symptomatic, with an mMRC Dyspnea Scale score ≥2, CAT score of ≥10, and smoking history of ≥10 pack-years. Stable use of background dual (LAMA/LABA) or triple (LABA/LAMA/ICS) maintenance therapy for ≥8 weeks prior to screening was also required. Prior to screening spirometry, patients were required to withhold twice-daily maintenance therapy for 24 hours, once-daily maintenance therapy for 48 hours, and SABA rescue medication for ≥4 hours. Patients with concomitant pulmonary diseases including asthma, lower respiratory tract infection, or major surgery within 6 weeks of screening; lung resection or reduction surgery within 1 year of screening; history of life-threatening COPD; recent hospitalizations due to COPD; pneumonia; or treatment requiring oral, intravenous, or intramuscular steroids within 3 months of screening were excluded. Full inclusion and exclusion criteria are described in Table S2.
Efficacy and Safety Evaluations
This study investigated the effect of nebulized ensifentrine over 12 weeks on symptoms and health status as assessed via CAT scores in patients with COPD. The primary endpoint evaluated proportion of CAT score responders, defined as an improvement from baseline of ≥2 units, at week 12. Secondary endpoints included the proportion of CAT score responders at week 6 and change from baseline in total and individual item CAT scores (Table S3). Safety assessments included the incidence of adverse events and change from baseline in vital signs (ie, blood pressure and pulse rate).
Statistical Analysis
Efficacy analyses were conducted using the full analysis set (FAS) population, which included all patients who received the study medication on day 1, had a baseline CAT, and had ≥1 post-treatment CAT assessment. Safety analyses were based on the safety analysis set (SAS) population, which included all patients who received the study medication on day 1. The proportion, standard error, and 95% CI for the percentage of CAT responders was estimated using Poisson regression, with a separate model fit to each assessment, and a term for background medication (linear contrast scaled to the proportion of subjects on dual therapy), and baseline CAT score as a covariate. A 2-sided unadjusted 95% CI for estimated proportions was used to determine study success, with the lower bound of the CI >0 indicating success. Change from baseline CAT scores (total and item-level) were analyzed using a mixed model for repeated measures model with terms for time, background medication (linear contrast scaled to the proportion of subjects on dual therapy), and baseline included as a covariate. Least-squares mean estimates, standard errors, and corresponding 95% CIs were generated for week 6 and week 12. Safety outcomes were analyzed descriptively as frequencies and percentages. Assuming 30% response rate in the study population, a sample size of 20 subjects provided the ability to demonstrate the responder proportion estimate and estimates of mean change from baseline did not extend to the clinically meaningful change limit of ≥2 units.
Oversight
The study was conducted in accordance with the Declaration of Helsinki, Council for International Organizations of Medical Sciences International Ethical Guidelines, International Council for Harmonisation, and Good Clinical Practice guidelines. All patients provided written informed consent prior to study participation.
Results
Patients
The study was conducted at a single center in the United States. In total, 23 patients provided consent and were screened for eligibility in the study; 20 eligible patients were administered nebulized ensifentrine and included in the SAS population. Of these, 18 (90.0%) patients had both a baseline CAT and ≥1 postbaseline CAT assessment and were included in the FAS population (Figure 1). All 18 patients in the FAS also completed 12 weeks of treatment. Treatment withdrawal occurred in 2 (10.0%) patients due to withdrawal of consent and not due to an adverse event.
Figure 1.
Patient enrollment and disposition. aCOPD severity screen failure due to pre- and postbronchodilator >75%; FEV1/FVC ratio ≥0.70.
Abbreviations: COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; FVC, forced vital capacity.
Baseline demographics and characteristics in the FAS population are shown in Table 1. Briefly, the mean (SD) age of patients was 71.3 (7.1) years; 44.0% of patients were female and 100.0% of patients were White, with mean post-bronchodilator FEV1 percent predicted of 56.0%. The most common COPD diagnoses in patients were emphysema (94.0%) and chronic bronchitis (83.0%). At baseline, 56.0% and 44.0% of patients were receiving background dual LABA/LAMA or triple LABA/LAMA/ICS therapy, respectively. The mean (SD) time since COPD diagnosis was 13.7 (7.8) years. Patients were symptomatic despite receiving dual or triple maintenance therapies. The majority of patients (56.0%) had a baseline CAT score range of 10 to 20, 39.0% had a CAT score range of 21 to 20, and 6.0% had a CAT score of >30. Among these patients, 33.0%, 61.0%, and 6.0% of patients had a baseline mMRC Dyspnea Scale score of 2, 3, and 4, respectively. The most frequently reported concomitant illnesses were hypertension (72.0%), gastroesophageal reflux disease (33.0%), depression (28.0%), anxiety (22.0%), hypercholesterolemia (22.0%), osteoarthritis (22.0%), and seasonal allergies (22.0%).
Table 1.
Baseline Demographics and Clinical Characteristics, Full Analysis Set
| Demographics | Ensifentrine 3 mg (N=18) |
|---|---|
| Age, y, mean (SD) | 71.3 (7.1) |
| Sex, female, n (%) | 8.0 (44.0) |
| Race, White, n (%) | 18.0 (100.0) |
| Baseline disease characteristics, n (%) | |
| History of chronic bronchitisa | 15.0 (83.0) |
| Diagnosis of emphysema | 17.0 (94.0) |
| Mean postbronchodilator FEV1, L (SD)b % predicted |
1.6 (0.5) 56.0% |
| Mean time since diagnosis, y (SD) | 13.7 (7.8) |
| Exacerbation within 1 y before screening | 2.0 (11.0) |
| Current smoker | 11.0 (61.0) |
| Baselinec CAT score distribution, n (%) | |
| 10-20 | 10.0 (56.0) |
| 21-30 | 7.0 (39.0) |
| >30 | 1.0 (6.0) |
| Baselinec mMRC Dyspnea Scale score distribution, n (%) | |
| 2 | 6.0 (33.0) |
| 3 | 11.0 (61.0) |
| 4 | 1.0 (6.0) |
| Background medications, n (%) | |
| LABA/LAMA | 10.0 (56.0) |
| LABA/LAMA/ICS | 8.0 (44.0) |
| Duration of background medications, y (SD) | |
| LABA/LAMA | 4.6 (2.7) |
| LABA/LAMA/ICS | 4.3 (4.0) |
| Most frequently reported (≥20%) concomitant illnesses, n (%)d | |
| Hypertension | 13.0 (72.0) |
| Gastroesophageal reflux disease | 6.0 (33.0) |
| Depression | 5.0 (28.0) |
| Anxiety | 4.0 (22.0) |
| Hypercholesterolemia | 4.0 (22.0) |
| Osteoarthritis | 4.0 (22.0) |
| Seasonal allergy | 4.0 (22.0) |
Notes: Full analysis set (N=18). aChronic bronchitis was defined as regular production of sputum for ≥3 months in 2 consecutive years in the absence of other conditions that may explain it. bScreening spirometry was evaluated at visit 2 (day 1). cBaseline CAT and mMRC Dyspnea Scale scores were evaluated at visit 1. CAT score ranges are defined as medium impact on daily life (10–20); high impact on daily life (21–30); very high impact on daily life (>30). dConcomitant illness refers to events ongoing or beginning after screening test.
Abbreviations: CAT, COPD Assessment Test™; COPD, chronic obstructive pulmonary disease; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; LABA, long-acting β-agonist; LAMA, long-acting muscarinic antagonist; mMRC, Modified Medical Research Council.
Primary Endpoint
Ensifentrine added on to dual (LABA/LAMA) or triple (LABA/LAMA/ICS) therapy resulted in a ≥2-unit CAT score improvement in 67.0% (95% CI, 38.0%, 100.0%) of patients at week 12 (Table 2). Higher responder rates were observed in patients using dual therapy (80.0%) and triple therapy (50.0%) at week 12 (Figure 2). The 95% CI for the responder rate at week 12 excluded 0.
Table 2.
Mean CAT Score and Percent Responders Over 12 Weeks, Full Analysis Set
| Timepoint | CAT Score, Mean (SD) |
LSM Change from Baseline, Units (95% CI) |
% CAT Respondersa (95% CI) |
|---|---|---|---|
| Baseline | 18.3 (6.4) | – | – |
| Week 6 | 16.7 (7.6) | –1.5 (–4.0, 1.1) | 44.4% (22.0%, 89.5%) |
| Week 12 | 15.9 (7.3) | –2.3 (–4.0, –0.6) | 67.0% (38.0%, 100.0%) |
Notes: Full analysis set (N=18). aResponders were defined as patients with improvement of ≥2 units in CAT score compared with baseline.
Abbreviations: CAT, COPD Assessment Test™; COPD, chronic obstructive pulmonary disease; LSM, least squares mean.
Figure 2.
Percentage of CAT score responders by background medication over 12 weeks, FAS.
Abbreviations: CAT, COPD Assessment Test™; COPD, chronic obstructive pulmonary disease; FAS, full analysis set (N=18); LABA, long-acting β-agonist; LAMA, long-acting muscarinic antagonist; ICS, inhaled corticosteroid.
Secondary Endpoints
At week 6, the mean (SD) CAT score was 16.7 (7.6) with an estimated change from baseline of –1.5 (1.0, 95% CI [–4.0, 1.1]) units. At week 12, the mean (SD) CAT score was 15.9 (7.3) with an estimated change from baseline of –2.3 (0.8, 95% CI [–4.0, –0.6]) units, exceeding the MCID of –2 units, with the null result within the CI (Table 2). Ensifentrine treatment resulted in a ≥2-unit CAT score improvement in 44.4% (95% CI, 22.0%, 89.5%) of patients at week 6. The responder rates were 50.0% and 38.0% in patients using dual and triple therapies, respectively. The 95% CI for responder rate at week 6 excluded 0. Treatment with ensifentrine demonstrated progressive improvement in CAT scores from week 6 to week 12 (Table 2 and Figure 3). Among the individual CAT items, the largest magnitudes of improvement were observed at week 12 in the LS mean estimates for Mucus, Chest Tightness, and Breathlessness scores (Table S4).
Figure 3.
LSM change from baseline in CAT scores over 12 weeks, FAS.
Abbreviations: CAT, COPD Assessment Test™; COPD, chronic obstructive pulmonary disease; FAS, full analysis set (N=18); LSM, least squares mean; MCID, minimum clinically important difference.
Safety
Ensifentrine was well tolerated over 12 weeks, with no reports of adverse events, deaths, or other serious adverse events. Overall, no trends or clinically significant changes or abnormal values in systolic blood pressure, diastolic pressure, or pulse rate were observed during the study (Table S5).
Discussion
The intent of this study was to characterize symptomatic response in patients already receiving maximal dual or triple maintenance therapy. The strict inclusion and exclusion criteria of traditional randomized controlled trials inherently limit generalizability to all patient populations, or may not fully capture real-world treatment patterns and adherence. Therefore, this study was designed as an uncontrolled, single-center, real-world evaluation to reflect the use of ensifentrine in routine clinical practice. In this study, twice-daily nebulized ensifentrine added to dual and triple maintenance therapy demonstrated a clinically meaningful improvement in COPD symptoms assessed by the CAT. These findings reflect a real-world example of a single center’s experience of treating patients with moderate to severe COPD with ensifentrine among patients who remain symptomatic with what was considered maximal bronchodilator therapy. Importantly, this is the first study to evaluate the effect of ensifentrine on health status and COPD symptoms, assessed by the CAT, in patients receiving background dual (LABA/LAMA) and triple (LABA/LAMA/ICS) therapy. In this study population, enrolled patients were highly symptomatic, with a mean (SD) baseline CAT score of 18.3 (6.4) units and mean (SD) time since COPD diagnosis was 13.7 (7.8) years, despite stable treatment with maintenance therapies. These findings align with previous reports highlighting that patients with COPD continue to experience substantial symptom burden even with good adherence to dual and triple therapy, with CAT scores exceeding 20 units in >60% of patients.14
Treatment with ensifentrine demonstrated clinically meaningful improvements in CAT scores at week 12 in 67.0% of symptomatic patients. Among patients receiving dual (LABA/LAMA) and triple (LABA/LAMA/ICS) therapy, the week 12 CAT responder rate was 80.0% and 50.0%, respectively, and demonstrated a clinically meaningful improvement from baseline with ensifentrine added on to their existing therapy. Analysis of these data excluded 0 at both time points in the 95% CI, suggesting a statistical nonzero effect. The larger percentage improvement in the dual therapy group may be due to the anti-inflammatory effect of ensifentrine.19,26,27 Ensifentrine also produced progressive improvement in total CAT score reduction over the 12-week treatment period, suggesting incremental increases over time due to anti-inflammatory or other pharmacology beyond bronchodilation alone.19,26–31 These data support the use of ensifentrine as a complementary treatment to add on to LAMA and LABA combination therapies, providing a clinically meaningful improvement in two-thirds of patients who remain symptomatic on dual and triple maintenance therapy. By providing a clinically meaningful response in these patients who previously had limited options for additional therapy, ensifentrine helps meet an unmet need in moderate to severe COPD management. Treatment with ensifentrine also demonstrated the largest magnitude of improvement in Mucus, Chest Tightness, and Breathlessness scores, which are profound symptoms in COPD and have debilitating effects on patients’ daily lives. Furthermore, these improvements are consistent with mechanisms associated with ensifentrine, including additional bronchodilation, reduced airway inflammation, and enhanced mucociliary clearance.19,26–32 As a new treatment for COPD, its dual mechanism of action allows ensifentrine to be used as a monotherapy or added to current inhaled routinely prescribed bronchodilator and anti-inflammatory therapies, producing complementary effects in patients needing additional therapeutic options.
Ensifentrine was well tolerated, with no adverse events reported after the addition of ensifentrine to dual and triple therapy. Overall, these findings confirm and extend the results of the ENHANCE program which demonstrated important improvements in symptoms and quality of life in patients,4,20,24 but did not include patients on dual and triple therapy. These results demonstrate that ensifentrine provides additional improvement in symptoms despite patients receiving maximal bronchodilator therapy.
As a small, single-center study with limited sample size and patient diversity, these findings may not be generalizable to broader or more diverse patient populations, including frequent exacerbators or those treated in different clinical settings.
Conclusions
COPD is a debilitating chronic disease due to profound daily breathlessness, cough and impaired mucus clearance. Ensifentrine provided clinically meaningful improvement in symptom burden, measured by the CAT, in symptomatic patients with COPD taking dual (LAMA/LABA) or triple (LAMA/LABA/ICS) maintenance therapy over 12 weeks, with the greatest magnitude of improvement in Mucus, Chest Tightness, and Breathlessness scores. Thus, nebulized ensifentrine provided additional clinically important benefits to patients with COPD who remain symptomatic despite receiving maximum treatment with current routinely prescribed COPD maintenance therapies.
Acknowledgments
Medical writing support was provided by Hala Addassi, PhD, from Citrus Health Group, Inc. (Chicago, Illinois), which was in accordance with Good Publication Practice 2022 guidelines.
Funding Statement
This study was funded by Verona Pharma, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey) which contributed to its design. Medical writing assistance was also funded by Verona Pharma, a subsidiary of Merck & Co., Inc. (Rahway, New Jersey).
Abbreviations
COPD, chronic obstructive pulmonary disease; LAMA, long-acting muscarinic antagonist; LABA, long-acting β-agonist; ICS, inhaled corticosteroid; SGRQ, St. George’s Respiratory Questionnaire; E-RS, Evaluating-Respiratory Symptoms; CAT, COPD Assessment Test™; MCID, minimum clinically important difference; UMEC, umeclidinium; VI, vilanterol; PDE, phosphodiesterase; FEV1, forced expiratory volume in 1 second; TDI, Transition Dyspnea Index; mMRC, modified Medical Research Council; SABA, short-acting β2-agonist; FVC, forced vital capacity; SAMA, short-acting muscarinic antagonist; FAS, full analysis set; SAS, safety analysis set.
Data Sharing Statement
Aggregate data that support the findings of this study are available from the corresponding author (TS) upon reasonable request.
Ethics Approval and Consent to Participate
The study was conducted in accordance with the Declaration of Helsinki, Council for International Organizations of Medical Sciences International Ethical Guidelines, International Council for Harmonisation, and Good Clinical Practice guidelines. The study protocol, all study protocol amendments, written study informed consent form, Verona Pharma ensifentrine Clinical Investigators Brochure, and any other relevant documents were reviewed and approved by WCG Institutional Review Board (IRB: 20241980). All patients provided written informed consent prior to study participation.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
TS received grants or contracts from Verona Pharma, GSK, Chiesi, Sanofi, Genentech, DevPro, Amgen, Compleware, Amphastar, AstraZeneca, and Areteia. TR, DR, MM-B, and KR are employees of Verona Pharma. JD is an employee of Stat One, which provides consultant statistical services to Verona Pharma. The authors report no other conflicts of interest in this work.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
Aggregate data that support the findings of this study are available from the corresponding author (TS) upon reasonable request.