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

Обзор

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).

Подробное описание

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).

Вмешательства

• Другое XH-S004 20 mg, 40 mg or 60 mg
  Administered once per day for 140 days.
• Другое Placebo
  Administered once per day for 140 days.

Первичные конечные точки

• Percentage of Participants Who Experienced at Least One of Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs) [Срок оценки: From randomisation to study completion, up to 168 days]

Вторичные конечные точки (7)

• Time to reach maximum plasma concentration (Tmax) [Срок оценки: From randomisation to study completion, up to 168 days]
• Maximum measured concentration (Cmax) of XH-S004 [Срок оценки: From randomisation to study completion, up to 168 days]
• Maximum measured concentration of XH-S004 at steady state (Cmax,ss) [Срок оценки: From randomisation to study completion, up to 168 days]
• Area Under the Plasma Concentration-time Curve (AUC) of XH-S004 [Срок оценки: From randomisation to study completion, up to 168 days]
• Change From Baseline in Blood Concentration of Active Neutrophil Elastase (NE) [Срок оценки: From randomisation to study completion, up to 168 days]
• Change from baseline in pre-brondilator FEV1 after first drug administration. [Срок оценки: At baseline, day 28, day 112 and day 140]
• Change from baseline in post-brondilator FEV1 after first drug administration [Срок оценки: At baseline, day 28, day 112 and day 140]

Критерии участия

Критерии включения

• 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 ≥2.
• COPD Assessment Test (CAT)≥10

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• China-Japan Friendship Hospital — Пекин

Идентификаторы

NCT: NCT07035652 · XH-S004-102

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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