The purpose of this study is to find out if XH-S004 can reduce pulmanary exacerbation over a 24-week treatment duration in participants with non-cystic fibrosis bronchiectasis.

This study is a multicenter, double-blind, placebo-controlled, parallel-group study conducted in china, aimed at evaluating the efficacy, safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of XH-S004 administered once daily for 24 weeks in participants with non-cystic fibrosis bronchiectasis (NCFBE).

This study plans to enroll 231 patients with bronchiectasis. Patients who sign the informed consent form will be screened according to the enrollment criteria, and randomly divided into 3 groups. Participants in groups 1 and 2 will receive different doses of XH-S004. Participants in group 3 will receive placebo.

Inclusion Criteria:

1. Understand the procedures and methods of this trial and sign a written informed consent form;
2. Male or female paticipants aged 18-85 years (inclusive) ;
3. Chest HRCT shows bronchiectasis affecting one or more lobes, and the condition is clinically diagnosed as non-cystic fibrosis bronchiectasis (clinical manifestations include chronic cough, significant productive cough, and/or intermittent hemoptysis, with or without varying degrees of polypnoea and other symptoms);
4. Based on medical history and the determination of the investigator , participants have at least 2 documented pulmonary exacerbations in the past 12 months before Screening;
5. Are current sputum producers with a history of chronic expectoration and able to provide a spontaneous sputum sample at screening visit (as described by the patient) ;
6. The body mass index (BMI) is ≥18 kg/m2 at screening;
7. Participants must ensure and agree that from 28 days prior to signing the informed consent form to 28 days after the final administration, women of childbearing potential, male participants, and their partners will use effective contraception methods other than oral drugs (e.g., condoms or intra-uterine contraceptive devices) and will not donate sperm or eggs during this period

Exclusion Criteria:

1. Have a primary diagnosis of chronic obstructive pulmonary disease (COPD) or asthma
2. Have bronchiectasis due to cystic fibrosis (CF), hypogammaglobulinemia, common variable immunodeficiency, or alpha1-antitrypsin deficiency
3. Are currently being treated for a nontuberculous mycobacterial lung infection, allergic bronchopulmonary aspergillosis, or tuberculosis
4. Have any acute infections, (including respiratory infections)
5. Patients who have previously received therapy with DPP1 inhibitors of the same class

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)