A Phase 3 Trial to Evaluate the Safety and Efficacy of Ensifentrine in Patients With COPD

Inclusion Criteria

Informed Consent

• Capable of giving informed consent indicating that they understand the purpose of the study and study procedures and agree to comply with the requirements and restrictions listed in the informed consent form (ICF).

Age and Sex

• Age: Patient must be 40 to 80 years of age inclusive, at the time of Screening.
• Sex:
• Males are eligible to participate if they agree to use contraception as described in the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.
• Females are eligible to participate if they are not pregnant, not breastfeeding, and at least one of the following conditions apply:
• Not a woman of childbearing potential (WOCBP). Or
• A WOCBP who agrees to follow the contraceptive guidance from Screening and throughout the study and for at least 30 days after the last dose of blinded study medication.

Smoking History

• Smoking History: Current or former cigarette smokers with a history of cigarette smoking ≥10 pack years at Screening (Visit 0) [number of pack years = (number of cigarettes per day / 20) × number of years smoked (eg, 20 cigarettes per day for 10 years, or 10 cigarettes per day for 20 years)]. Pipe and/or cigar use cannot be used to calculate pack-year history. Former smokers are defined as those who have stopped smoking for at least 6 months prior to Visit 0. Smoking cessation programs are permitted during the study.

COPD Diagnosis, Symptoms, Severity and Maintenance Therapy

• COPD Diagnosis: Patients with an established clinical history of COPD as defined by the American Thoracic Society (ATS)/European Respiratory Society (ERS) guidelines (Celli BR, 2004) with symptoms compatible with COPD.
• COPD Symptoms: A score of ≥2 on the Modified Medical Research Council (mMRC) Dyspnea Scale.
• COPD Severity:
• Pre- and Post-albuterol/salbutamol FEV1/FVC ratio of 1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• Hepatitis B antibody:
• Positive findings for both Hepatitis B surface antigen (HBsAg) and Hepatitis B core antibody (anti-HBc) are excluded, as this indicates acute or chronic infection.
• Negative findings for HBsAg and Hepatitis B surface antibody (anti-HBs) but positive findings for anti-HBc are excluded as this may indicate current or resolving infection.
• Positive findings for anti-HBc and anti-HBs but negative findings for HBsAg are not excluded, as this indicates immunity due to natural infection.
• Positive findings for anti-HBs but negative findings for HBsAg and anti-HBc are not excluded, as this indicates immunity due to hepatitis B vaccination.
• Hepatitis C antibody positive.
• Any other abnormal hematology, biochemistry, or viral serology deemed by an investigator to be clinically significantly abnormal. Abnormal chemistry and/or hematology may be repeated during Screening.
• Chest X-ray (CXR; posterior-anterior) at Screening, or in the 12 months prior to Screening with clinically significant abnormalities not attributable to COPD. If a CXR within the past 12 months is not available but a computerized tomography (CT) scan within the same time period is available, the CT scan may be reviewed in place of a CXR. For subjects in Germany, if a CXR or CT scan is not available in the 12 months prior to Screening, the subject is not eligible for the study.
• Electrocardiogram (ECG) finding that is significantly abnormal on the 12-lead ECG obtained at Screening.

Other Exclusions

• Use of an experimental drug within 30 days or 5 half-lives of Screening, whichever is longer, and/or participation in a study treatment-free follow-up phase of a clinical trial within 30 days prior to Screening.
• Use of an experimental medical device or participation in a follow-up phase of an experimental medical device clinical trial within 30 days prior to Screening.
• Intolerance or hypersensitivity