The Phase Ib Clinical Trial of the XH-S004 Tablet in Patients With Chronic Obstructive Pulmonary Disease (COPD) to Evaluate Its Safety, Tolerability, Pharmacokinetic Characteristics and Pharmacodynamic Characteristics After Multiple Administrations

The Phase Ib Clinical Trial of the XH-S004 Tablet in Patients With Chronic Obstructive Pulmonary Disease (COPD) to Evaluate Its Safety, Tolerability, Pharmacokinetic Characteristics and Pharmacodynamic Characteristics After Multiple Administrations

The objectives of the proposed study are to investigate safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and prliminary efficacy of XH-S004 in moderate to severe COPD patients with a stale standards of care (SOC).

This study is a multicenter, double-blind, placebo-controlled, up-titration study conducted in china, aimed at evaluating the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of XH-S004 administered once daily for 140 days in COPD patients.

This study plans to enroll 81 COPD patients. Patients who sign the informed consent form will be screened according to the enrollment criteria, and randomly divided into 2 groups in 2:1 ratio (XH-S004 group: 54 participants and placebo group: 27 participants). Participants in XH-S004 group will receive XH-S004 20 mg for 28 days in treatment period 1, then up-titrated to XH-S004 40 mg for 84 days in treatment period 2, finally continue with XH-S004 60 mg for 28 days in treamtment period 3. Participants in placebo group will receive matching placebo from day 1 to day 140 (140 days in total).

Inclusion Criteria:

1. Sign the informed consent form (ICF);
2. Male or Female participants ages 40-80 (inclusive);
3. BMI ≥ 18.5 kg/m2 and ≤ 26 kg/m2, with male weight ≥50 kg and female weight ≥45 kg (inclusive);
4. Patients diagnosed with COPD according to 2024 GOLD consensus had a medical record or relevant documentation proving a history of COPD for ≥12 months at screening visit;
5. Current or former smokers with a smoking history of ≥10 pack-years;
6. Post-bronchodilator FEV1/ forced vital capacity [FVC] ratio <0.70 and post-bronchodilator FEV1 % predicted >30% and ≤70%.
7. Sputum volume≥10ml/day at screening visit;
8. with a documented history: 1) Moderate-to-severe COPD patients with a stable SOC therapy prior to signing ICF, including LABA, LAMA, LABA/LAMA, LABA/LAMA/ICS (evaluated by investigator to confirm the treatment regimen complies with clinical practice); Continuous use with a stable dosage for ≥1 month prior to randomization; Medication compliance between 80% and 120% from signing ICF to randomization; 2) Acute exacerbation history of ≥2 moderate or ≥1 severe requiring hospitalization within 12 months prior to screening.
9. Medical Research Council (MRC) Dyspnea Scale grade ≥2.
10. COPD Assessment Test (CAT)≥10

Exclusion Criteria:

1. Have a primary diagnosis of asthma as determined by the investigator;
2. During screening period, WBC<the lower limit of normal range, or absolute neutrophil count<the lower limit of normal range;
3. During screening period, blood eosinophils ≥300 cells/microliter;
4. Pregnant and lactating females