A Study to Evaluate the Efficacy and Safety of RSS0343 Tablets in Patients With Chronic Obstructive Pulmonary Disease

Inclusion criteria

• Voluntarily sign a written informed consent form.
• Aged 40 to 80 years, male or female.
• Body mass index (BMI) ≥18 kg/m².
• Diagnosed with chronic obstructive pulmonary disease (COPD) as defined by the Chinese Guidelines for the Diagnosis and Management of COPD (2021 Revised Edition), with a documented COPD history of ≥12 months prior to screening.
• Post-bronchodilator FEV₁/FVC <0.7 at the screening period; and post-bronchodilator FEV₁/FVC <0.7 with FEV₁% predicted ≥20% at baseline.
• Documented history of at least ≥1 moderate or severe acute exacerbation of COPD (AECOPD) within 12 months prior to screening.
• On stable doses of triple therapy or dual therapy for COPD maintenance treatment for ≥3 months prior to screening.
• COPD Assessment Test (CAT) score ≥10 at screening and randomization.
• Current or former smoking history of ≥10 pack-years at screening.
• Male and female subjects of childbearing potential and their partners must have no plans for conception or sperm/ova donation for 6 months (female subjects) or 3 months (male subjects) after the last dose and must voluntarily use effective contraception. Female subjects of childbearing potential must have a negative pregnancy test during screening and prior to the first dose and must not be lactating.

Exclusion criteria

• Subjects with systemic immunosuppressants, biologic agents, or Th2 cytokine inhibitors within 12 weeks prior to randomization or within 5 half-lives of the drug, whichever is longer.
• Subjects with medications known to potentially cause skin hyperkeratosis within 4 weeks prior to screening.
• Subjects with the followings within 4 weeks prior to randomization: systemic corticosteroids, phosphodiesterase inhibitors, xanthine derivatives, leukotriene receptor antagonists, bacterial lysates, antitussive/expectorant medications, infusion of blood products or immunoglobulins.
• Subjects with strong CYP3A inducers or inhibitors within 14 days or 5 half-lives (whichever is longer) prior to randomization.
• Administration of live, attenuated live, or viral vector vaccines within 4 weeks prior to randomization.
• Participation in another clinical trial involving an investigational product with active ingredients within 3 months prior to screening, or still within 5 half-lives of the investigational product at screening.
• Prior treatment with RSS0343 tablets or treatment with products targeting the same mechanism of action within 3 months prior to screening.
• Lung surgery or lung volume reduction surgery within 1 year prior to screening; or interventional procedures for chronic bronchitis within 1 year prior to screening.
• Requirement for supplemental oxygen therapy for ≥15 hours per day or mechanical ventilation; or clinically significant sleep apnea requiring the use of a continuous positive airway pressure (CPAP) device or non-invasive positive pressure ventilation (NIPPV) device.
• Presence of a moderate or severe acute exacerbation of COPD (AECOPD) from 4 weeks prior to screening up to randomization.
• Coexisting other respiratory or respiratory-related diseases.
• Occurrence of pulmonary or other infections requiring systemic anti-infective therapy from 4 weeks prior to screening up to randomization.
• Presence of autoimmune diseases mediated by eosinophils at screening.
• Diagnosis of hypothyroidism, myxedema, chronic lymphedema, acromegaly, or livedo reticularis.
• Diagnosis of psoriasis or lichen planus; Reiter's disease/keratoderma blennorrhagicum, keratoderma hemorrhagicum, or reactive arthritis; systemic lupus erythematosus, atopic dermatitis, chronic hand dermatitis, chronic contact dermatitis, or chronic psoriasis; chloracne, extensive verruca vulgaris, or keratotic dermatitis.
• Known other severe medical conditions.
• Laboratory tests, electrocardiogram (ECG), or other auxiliary examinations during the screening or baseline periods meeting the protocol-defined exclusion criteria.
• Suspected or known hypersensitivity to the investigational product or any of its excipients.
• Blood donation or blood loss ≥200 mL within 1 month prior to randomization, or ≥400 mL within 3 months prior to the first dose; or receipt of a blood transfusion within 8 weeks prior to the first dose; or difficulty with venipuncture, or physical condition unsuitable for intensive blood sampling.
• Female subjects who are lactating, have a positive pregnancy test result, or plan to become pregnant during the study period.
• History of drug abuse or substance abuse within 1 year prior to screening.
• Any other medical or social reason deemed by the investigator to make the subject unsuitable for participation in the trial.