Effect of Ensifentrine Treatment on CAT Score

A Study Assessing the Effect of Ensifentrine on CAT™ Scores Over 12 Weeks in Subjects With Moderate to Severe COPD

The purpose of this open-label, single center trial is to assess the effect of twice daily nebulized ensifentrine (3 mg) on COPD symptoms measured by the COPD Assessment Test (CAT™) scores over 12 weeks in subjects with symptomatic, moderate to severe COPD, taking maintenance LAMA/LABA or LAMA/LABA/ICS therapy. Subjects will continue the maintenance treatment during study participation.

Inclusion Criteria:

• Capable of giving informed consent.
• Current or former cigarette smokers with a history of cigarette smoking ≥ 10 pack years.
• Established clinical history of moderate to severe COPD.
• Pre- and post-albuterol FEV1/FVC ratio of < 0.70.
• Post-albuterol FEV1 ≥ 30 % and ≤ 75% of predicted normal.
• ≥2 on the modified Medical Research Council (mMRC) Dyspnea Scale.
• ≥10 on the COPD Assessment Test™.
• Taking stable dual (LAMA+LABA) or triple (LAMA+LABA+ICS) maintenance therapy for at least 8 weeks.
• Capable of using a standard jet nebulizer and performed spirometry assessment.

Exclusion Criteria:

1. Hospitalizations for COPD (or COPD exacerbation), pneumonia, or other serious infection or treatment with oral or parenteral (oral, intravenous, or intramuscular) glucocorticoids within the past 12 weeks.
2. Lower respiratory tract infection within the past 6 weeks or an active infection.
3. History of life-threatening COPD, including Intensive Care Unit admission and/or requiring intubation within 1-year.
4. Major surgery (requiring general anesthesia) within the past 6 weeks, lack of full recovery from surgery, or planned surgery through the end of the study.
5. Concomitant clinically significant pulmonary disease other than COPD (e.g., asthma, tuberculosis, lung cancer, bronchiectasis, sarcoidosis, lung fibrosis, interstitial lung diseases, sleep apnea (unless controlled with stable continuous positive airway pressure [CPAP] use), known alpha-1 antitrypsin deficiency, core pulmonale or other non-specific pulmonary disease).
6. Severe comorbidities including unstable cardiac, (e.g., myocardial infarction within 1 year prior to screening, unstable angina within 6 months, or unstable or life-threatening arrhythmia requiring intervention within 3 months) or any other clinically significant medical conditions including uncontrolled diseases (e.g., endocrine, neurological, hepatic, gastrointestinal, renal, hematological, urological, immunological, psychiatric or ophthalmic diseases) that would, in the opinion of the Investigator, preclude the subject from safely completing the required tests or the study, or is likely to result in disease progression that would require withdrawal of the subject.
7. HIV infection or other immunodeficiency.
8. Previous lung resection or lung reduction surgery within 1-year.
9. Long term oxygen use defined as oxygen therapy prescribed for greater than 12 hours per day.
10. Pulmonary rehabilitation unless such treatment has been stable for at least 4 weeks and remains stable during the study.
11. History of or current malignancy of any organ system, treated or untreated within the past 5 years, except for localized basal or squamous cell carcinoma of the skin.
12. Significant psychiatric disease that would likely result in the subject not being able to complete the study, in the opinion of the Investigator.
13. Findings on physical examination that an investigator considers to be clinically significant.
14. Known alanine aminotransferase (ALT) ≥ 2 × upper limit of normal (ULN), alkaline phosphatase and/or bilirubin > 1.5 × ULN (isolated bilirubin > 1.5 × ULN is acceptable if fractionated bilirubin < 35%).
15. Known diagnosis of severe chronic kidney disease.
16. Any other known abnormal clinical, cardiac or laboratory (hematology, biochemistry or viral) findings, deemed by an investigator to be clinically significantly abnormal.
17. Use of prohibited medications, including nebulized medication, within the time intervals.
18. Current or history of drug or alcohol abuse within the past 5 years.
19. Women who are breast feeding.
20. Use of an experimental drug within 30 days or 5 half-lives, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical study within 30 days.
21. Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical study within 30 days.
22. Affiliation with the investigator site, including an Investigator, Sub-Investigator, study coordinator, study nurse, other employee of participating investigator or study site or a family member of the aforementioned.
23. A disclosed history or one known to the Investigator of significant noncompliance in previous investigational studies or with prescribed medications.
24. Any other reason that the Investigator considers makes the subject unsuitable to participate.