A Study of HSK31858 in Participants with Non-Cystic Fibrosis Bronchiectasis

Inclusion Criteria:

1. Age ≥18 years and BMI≥18.0 kg/m^2 at the time of signing the ICF.

2. Chest HRCT showed bronchiectasis affecting one or more lobes and was confirmedby a clinician as NCFBE(clinically characterized by chronic cough,expectoration and/or intermittent hemoptysis, with or without shortness ofbreath and respiratory failure). HRCT was considered effective if the patienthad received HRCT in the same hospital within 12 months and screening HRCT isnot necessary.

3. Having daily expectoration(with sufficient sputum production at screening, ifthe subject is unable to produce sputum voluntarily, sample collection can beperformed by induced expectoration).

4. Have at least 2 pulmonary exacerbations in the past 12 months before Screening.

5. If long-term treatment with bronchodilators (long-acting β-agonists and/orlong-acting muscarinic antagonists) is required, the dose and regimen shouldremain stable for at least 3 months before the screening visit and throughoutthe study period.

6. The estimated survival time ≥ 12 months.

7. Women must be post-menopausal, surgically sterile, or using highly effectivecontraception methods from Day 1 to at least 30 days after the last dose.

8. Males with female partners of childbearing potential must be using effectivecontraception from Day 1 to at least 90 days after the last dose.

9. Give their signed study informed consent to participate.

Exclusion Criteria:

1. Have pulmonary hypertension or have a primary diagnosis of COPD or asthma asjudged by the Investigator.

2. A history of malignancy (excluding cured basal cell carcinoma of the skin,carcinoma in situ, and papillary carcinoma of the thyroid gland. The patientswho had survived lung cancer surgery for at least 5 years without antitumortherapy can enroll in the study ) within 5 years prior to screening or ahistory of antitumor therapy.

3. Have bronchiectasis due to CF (HRCT showed that the above lung diseases becamepredominant) as judged by the Investigator.

4. Currently being treated Non-tuberculous Mycobacterial (NTM) pulmonaryinfections, allergic bronchopulmonary aspergillosis, or tuberculosis (TB), oractive and currently symptomatic infections caused by COVID-19.

5. Patients who had experienced any degree of acute exacerbation of bronchiectasisor were developing an acute exacerbation of bronchiectasis before 4 weeks ofscreening.

6. Patients who had hemoptysis and required medical intervention within 4 weeksprior to screening(except for coughing up minorbloody streaks).

7. Have an abnormal renal function test result (estimated glomerular filtrationrate [eGFR] < 60 mL/min/1.73m^2) at Screening.

8. Subjects with a history of liver disease or current treatment for liver diseaseduring the screening period, including but not limited to acute or chronichepatitis, cirrhosis or liver failure, or aspartate aminotransferase (AST) > 2.0×ULN or alanine aminotransferase (ALT) > 2.0×ULN or total bilirubin (TBIL) > 1.5×ULN.

9. Active hepatitis B virus infection (hepatitis B surface antigen positive withHBV-DNA load above the lower limit of detection), active hepatitis C virusinfection (HCV antibody positive with HCV-RNA load above the lower limit ofdetection), or known HIV infection or syphilis infection.

10. Any other unstable clinical condition, including but not limited tocardiovascular, gastrointestinal, hepatic, renal, neurological,musculoskeletal, infectious, endocrine, metabolic, hematologic, psychiatric, ormajor physiological dysfunction, that the investigator considers to be (a)likely to affect patient safety throughout the study; (b) Influence the resultsof the study and its interpretation; (c) impeding the patient's ability tocomplete the entire study.

11. Had participated in a clinical trial of any other drug or medical device in the 3 months prior to the screening (a drug or medical device treated with aclinical trial) or the subject had not been more than 5 half-lives from thelast clinical trial of the drug at the time of screening.

12. Medications that may cause hyperkeratosis (e.g., tumor necrosis factor-αantagonists) within 4 weeks prior to screening.

13. Patients who have used a strong inducer or suppressor of CYP3A within 14 daysor 5 half-lives of the first investigational drug (whichever is longer).

14. Patients who had smoked an average of 10 cigarettes or more per day in theprevious 1 year were screened.

15. Pregnancy and lactation.

16. The subjects were unable to complete the questionnaires due to their limitededucational level, or the subjects and their families failed to fill in thesubjects' log cards.

17. Had received live attenuated vaccine within 30 days before randomization. 18.The investigators judged that there were other conditions that were notsuitable for participation in the study.