The purpose of this study is to find out if XH-S004 can reduce pulmanary exacerbation over a 24-week treatment duration in participants with non-cystic fibrosis bronchiectasis.
This study is a multicenter, double-blind, placebo-controlled, parallel-group study conducted in china, aimed at evaluating the efficacy, safety and tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of XH-S004 administered once daily for 24 weeks in participants with non-cystic fibrosis bronchiectasis (NCFBE). This study plans to enroll 231 patients with bronchiectasis. Patients who sign the informed consent form will be screened according to the enrollment criteria, and randomly divided into 3 groups. Participants in groups 1 and 2 will receive different doses of XH-S004. Participants in group 3 will receive placebo.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
231
Administered once per day for 24 weeks.
Administered once per day for 24 weeks.
Administered once per day for 24 weeks.
Huadong Hospital Affiliated to fudan univercity
Shanghai, Shanghai Municipality, China
Time to the First Pulmonary Exacerbation Over 24-Week Treatment Period
Time to first pulmonary exacerbation was calculated as the number of days from the date of randomization to the date of first documentation of an exacerbation. Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics (EMBARC guideline) : 1. Increased cough 2. Increased sputum volume 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis.
Time frame: Baseline (Day 1) to Week 24
Incidence of pulmonary exacerbation as defined by EMBARC over 24-week treatment period.
Time to first pulmonary exacerbation was calculated as the number of days from the date of randomization to the date of first documentation of an exacerbation. Pulmonary exacerbation was defined as having 3 or more of the following symptoms for at least 48 hours resulting in a physician's decision to prescribe antibiotics (EMBARC guideline) : 1. Increased cough 2. Increased sputum volume 3. Increased sputum purulence 4. Increased breathlessness and/or decreased exercise tolerance 5. Fatigue and/or malaise 6. Hemoptysis.
Time frame: Baseline (Day 1) to Week 24
Incidence of Pulmonary exacerbation as defined by investigators over 24-week treatment period.
The definition of pulmonary exacerbation determined by investigator was defined as: Compared with previous symptoms, patient's current symptoms have worsened but not meet the EMBARC guideline-defined criteria for pulmonary exacerbation . However, the invetigator will have determined that oral/IV antibiotic therapy is required.
Time frame: Baseline (Day 1) to Week 24
Change from baseline in forced expiratory volume in 1 second (FEV1) in pulmonary function test at week 24 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.
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Time frame: At baseline and at week 24
Change from baseline in Quality of Life Questionnaire - Bronchiectasis (QOLB) respiratory symptoms domain score at week 24 after first drug administration;
The QOL-B is a validated, self-administered patient reported outcome (PRO) that assesses symptoms, functioning, and health-related (HR) QOL for participants with non-cystic fibrosis
Time frame: At baseline and at week 24
Change From Baseline in Concentration of Active Neutrophil Elastase (NE) in Sputum
The concentration of active NE in sputum, was measured by the difference between the pre-treatment concentration, on-treatment concentration and post-treatment concentration. In bronchiectasis, activation of neutrophils in the airway leads to release of NE which leads to damaged airway walls, mucus hypersecretion, exacerbated inflammation, which in turn affects neutrophil and macrophage functions, increasing the risk of infection. Negative change from Baseline indicates improvement.
Time frame: Baseline (Day 1) to Week 24