Long-Term Safety and Efficacy of HSK39004 Dry Powder Inhaler in COPD

A Multicenter, Single-Arm, Open-Label Study to Evaluate the Long-Term Safety and Efficacy of HSK39004 Dry Powder Inhaler in Patients With Chronic Obstructive Pulmonary Disease (COPD)

This clinical trial evaluates the long-term safety and efficacy of 0.75 mg HSK39004 Dry Powder Inhaler administered twice daily for 52 weeks in subjects aged 40 to 80 years with moderate-to-severe stable chronic obstructive pulmonary disease (COPD), including both newly enrolled and those who have completed prior participation in the HSK39004-201, HSK39004-T1-201, or HSK39004-T1-202 studies as a long-term extension.

Key Inclusion Criteria:

1. Aged 40 to 80 years (inclusive) at the time of screening visit (Visit 1), male or female;

2. Subjects diagnosed with chronic obstructive pulmonary disease (COPD) in accordance with the GOLD 2026 diagnostic criteria prior to screening [GOLD 2026 criteria: presence of chronic respiratory symptoms such as dyspnea, chronic cough or sputum production, and/or a history of risk factor exposure, and the pulmonary function test results show: the forced expiratory volume in one second (FEV1) after using bronchodilators / forced vital capacity (FVC) <0.7];

3. At screening visit (Visit 1):

   • Post-bronchodilator FEV1/FVC < 0.7; and
   • Post-bronchodilator FEV1 ≥ 30% and < 80% of predicted value;

4. Modified Medical Research Council (mMRC) dyspnea scale score ≥ 2 at screening;

Key Exclusion Criteria:

1. Subjects with unresolved lower respiratory tract infection occurring within 6 weeks prior to screening (Visit 1) and/or before enrollment;
2. Severe or uncontrolled cardiovascular disease or history, including but not limited to: New York Heart Association (NYHA) functional class III/IV at screening; acute myocardial infarction, unstable angina, or acute coronary syndrome within 6 months prior to screening; clinically significant arrhythmia requiring intervention or marked QTcF prolongation (male >450 ms, female >470 ms) within 3 months prior to screening; or unstable or uncontrolled hypertension (systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg) at screening;
3. History of malignancy (except for carcinoma in situ, cutaneous squamous cell carcinoma, and basal cell carcinoma cured for more than 5 years), suspected malignancy, or undetermined neoplasm;
4. Concurrent severe, uncontrolled renal, neurological, endocrine, thyroid, urological, ophthalmic, immunological, psychiatric, gastrointestinal, hepatic, or hematological diseases/abnormalities that, in the investigator's judgment, may pose a safety risk to the subject or confound study outcome analysis;
5. Known hypersensitivity to HSK39004 inhalation powder, salbutamol, or any component of the drug delivery system;
6. Use of any protocol-prohibited medication prior to spirometry at screening (Visit 1);
7. History of lung lobectomy or lung volume reduction surgery within 12 months prior to screening;
8. Major surgery (requiring general anesthesia) within 6 weeks prior to screening with incomplete recovery, or planned surgery before study completion;
9. Subjects determined by the investigator to require oxygen therapy;
10. Clinically significant sleep apnea requiring continuous positive airway pressure (CPAP) or non-invasive positive pressure ventilation (NIPPV);