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
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Percentage of Participants Who Experienced at Least One of Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)
研究概览
简要总结
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).
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Sign the informed consent form (ICF);
- •Male or Female participants ages 40-80 (inclusive);
- •BMI ≥ 18.5 kg/m2 and ≤ 26 kg/m2, with male weight ≥50 kg and female weight ≥45 kg (inclusive);
- •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;
- •Current or former smokers with a smoking history of ≥10 pack-years;
- •Post-bronchodilator FEV1/ forced vital capacity [FVC] ratio <0.70 and post-bronchodilator FEV1 % predicted >30% and ≤70%.
- •Sputum volume≥10ml/day at screening visit;
- •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.
- •Medical Research Council (MRC) Dyspnea Scale grade ≥
- •COPD Assessment Test (CAT)≥10
排除标准
- •Have a primary diagnosis of asthma as determined by the investigator;
- •During screening period, WBC<the lower limit of normal range, or absolute neutrophil count<the lower limit of normal range;
- •During screening period, blood eosinophils ≥300 cells/microliter;
- •Pregnant and lactating females
结局指标
主要结局
Percentage of Participants Who Experienced at Least One of Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs)
时间窗: From randomisation to study completion, up to 168 days
次要结局
- Change from baseline in pre-brondilator FEV1 after first drug administration.(At baseline, day 28, day 112 and day 140)
- Time to reach maximum plasma concentration (Tmax)(From randomisation to study completion, up to 168 days)
- Maximum measured concentration (Cmax) of XH-S004(From randomisation to study completion, up to 168 days)
- Maximum measured concentration of XH-S004 at steady state (Cmax,ss)(From randomisation to study completion, up to 168 days)
- Area Under the Plasma Concentration-time Curve (AUC) of XH-S004(From randomisation to study completion, up to 168 days)
- Change From Baseline in Blood Concentration of Active Neutrophil Elastase (NE)(From randomisation to study completion, up to 168 days)
- Change from baseline in post-brondilator FEV1 after first drug administration(At baseline, day 28, day 112 and day 140)