Chronic Obstructive Pulmonary Disease (COPD)
Conditions
Keywords
COPD, Active neutrophil elastase
Brief summary
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).
Detailed description
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).
Interventions
OTHERXH-S004 20 mg, 40 mg or 60 mg
Administered once per day for 140 days.
OTHERPlacebo
Administered once per day for 140 days.
Sponsors
S-INFINITY Pharmaceuticals Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Intervention model description
Parallel Assignment
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percentage of Participants Who Experienced at Least One of Treatment-Related Adverse Events (AEs) or Serious Adverse Events (SAEs) | From randomisation to study completion, up to 168 days |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| Time to reach maximum plasma concentration (Tmax) | From randomisation to study completion, up to 168 days | — |
| Change from baseline in pre-brondilator FEV1 after first drug administration. | At baseline, day 28, day 112 and day 140 | FEV1 was used to assess lung function and is the maximum amount of air that can be forced out in one second after taking a deep breath. |
| Change from baseline in post-brondilator FEV1 after first drug administration | At baseline, day 28, day 112 and day 140 | FEV1 was used to assess lung function and is the maximum amount of air that can be forced out in one second after taking a deep breath. |
| Change From Baseline in Blood Concentration of Active Neutrophil Elastase (NE) | From randomisation to study completion, up to 168 days | — |
Countries
China
Contacts
Primary ContactBin Cao
Backup ContactYeming Wang
Outcome results
None listed