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).

Study Overview

• Status: Not yet recruiting
• Conditions: Chronic Obstructive Pulmonary Disease (COPD)
• Intervention / Treatment: Other: XH-S004 20 mg, 40 mg or 60 mg; Other: Placebo

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).

• Study Type: Interventional
• Enrollment (Estimated): 81
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Bin Cao; Phone Number: +86 13911318339; Email: caobin_ben@163.com
• Study Contact Backup: Name: Yeming Wang; Phone Number: +86 18810663558; Email: wwyymm_love@163.c0m

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100000
      • China-Japan Friendship Hospital
      • Contact: Bin Cao; Phone Number: +86 13911318339; Email: caobin_ben@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm1: Participant Group; Up-titration design: prticipants received XH-S004 20 mg once daily (QD) from day 1 to day 28 in treatment period 1, XH-S004 40 mg once daily (QD) from day 29 to day 112 in treatment period 2, and XH-S004 60 mg once daily (QD) from day 113 to day 140 in treatment period 3. Pharmaceutical form: Tablets Route of administration: Oral	Other: XH-S004 20 mg, 40 mg or 60 mg; Administered once per day for 140 days.
Placebo Comparator: Participant Group; Participants received the matching placebo once daily (QD) from day 1 to day 140 in treatment period 1, treatment period 2 and treatment period 3. Pharmaceutical form: Tablets Route of administration: Oral	Other: Placebo; Administered once per day for 140 days.

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 pre-brondilator FEV1 after first drug administration.	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.	At baseline, day 28, day 112 and day 140
Change from baseline in post-brondilator FEV1 after first drug administration	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.	At baseline, day 28, day 112 and day 140

Collaborators and Investigators

• Sponsor: S-INFINITY Pharmaceuticals Co., Ltd

Study record dates

Study Major Dates

• Study Start (Estimated): July 15, 2025
• Primary Completion (Estimated): November 13, 2026
• Study Completion (Estimated): November 13, 2026

Study Registration Dates

• First Submitted: June 16, 2025
• First Submitted That Met QC Criteria: June 16, 2025
• First Posted (Estimated): June 25, 2025

Study Record Updates

• Last Update Posted (Estimated): June 25, 2025
• Last Update Submitted That Met QC Criteria: June 16, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: COPD; Active neutrophil elastase
• Additional Relevant MeSH Terms: Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: XH-S004-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No