A Clinical Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Inhaled H057 in the Treatment of Acute Exacerbations of Bronchiectasis

A Multicenter, Randomized, Double-blind, Placebo-controlled Phase II Clinical Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Inhaled H057 in the Treatment of Acute Exacerbations of Bronchiectasis

This is a multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of inhaled H057 in the treatment of acute exacerbations of bronchiectasis.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute Exacerbations of Bronchiectasis
• Intervention / Treatment: Drug: Low-dose H057+standard-of-care; Drug: High-dose H057+standard-of-care; Drug: H057 placebo+standard-of-care

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhanyang Zhu; Phone Number: 86-021-64311017; Email: clinical_trial@hllife.com.cn

Study Locations

• China
  • Anhui
    • Fuyang, Anhui, China
      • Fuyang Hospital Of Anhui Medical University
      • Contact: Lei Zhao
      • Principal Investigator: Lei Zhao
    • Hefei, Anhui, China
      • Hefei First People's Hospital
      • Contact: Zhen Ding
      • Principal Investigator: Zhen Ding
  • Fujian
    • Fuzhou, Fujian, China
      • Fujian Medical University Union Hospital
      • Contact: Xiangqi Chen
      • Principal Investigator: Xiangqi Chen
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangzhou Medical University
      • Principal Investigator: Nanshan Zhong
      • Principal Investigator: Weijie Guan
      • Contact: Nanshan Zhong; Phone Number: 86-020-83062893; Email: nanshan@vip.163.com
      • Contact: Weijie Guan; Phone Number: 86-13826042052; Email: battery203@163.com
    • Shenzhen, Guangdong, China
      • Peking University Shenzhen Hospital
      • Contact: Ruilin Sun
      • Principal Investigator: Ruilin Sun
  • Guangxi Zhuang Autonomous Region
    • Baise, Guangxi Zhuang Autonomous Region, China
      • Affiliated Hospital of Youjiang Medical University for Nationalities
      • Contact: Yujie Jiang
      • Principal Investigator: Yujie Jiang
  • Hebei
    • Shijiazhuang, Hebei, China
      • Hebei General Hospital
      • Contact: Li Yan
      • Principal Investigator: Li Yan
  • Henan
    • Nanyang, Henan, China
      • Nanyang Second General Hospital
      • Contact: Fengling Ju
      • Principal Investigator: Fengling Ju
  • Hubei
    • Wuhan, Hubei, China
      • Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
      • Contact: Xiaorong Wang
      • Principal Investigator: Xiaorong Wang
    • Yichang, Hubei, China
      • Yichang Central People's Hospital
      • Contact: Xinyu Song
      • Principal Investigator: Xinyu Song
  • Hunan
    • Changsha, Hunan, China
      • The second Xiangya Hospital of Central South University
      • Principal Investigator: Hong Luo
      • Contact: Hong Luo
  • Jiangsu
    • Changzhou, Jiangsu, China
      • Changzhou First People's Hospital
      • Contact: Chong Li
      • Principal Investigator: Chong Li
  • Jiangxi
    • Jiujiang, Jiangxi, China
      • Jiujiang No.1 People's Hospital
      • Contact: Jun Li
      • Principal Investigator: Jun Li
  • Sichuan
    • Chengdu, Sichuan, China
      • Sichuan Provincial People's Hospital
      • Contact: Lingyun Gao
      • Principal Investigator: Lingyun Gao
    • Deyang, Sichuan, China
      • Deyang People's Hospital
      • Contact: Chunfang Zeng
      • Principal Investigator: Chunfang Zeng
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • Hangzhou First People's Hospital
      • Contact: Limin Wang
      • Principal Investigator: Limin Wang
    • Jinhua, Zhejiang, China
      • Jinhua Municipal Central Hospital
      • Principal Investigator: Dan Zhu
      • Contact: Dan Zhu
    • Ningbo, Zhejiang, China
      • Ningbo No.2 Hospital
      • Contact: Zhaoxing Dong
      • Principal Investigator: Zhaoxing Dong
    • Wenzhou, Zhejiang, China
      • The First Affiliated Hospital of Wenzhou Medical University
      • Contact: Xiaoying Huang
      • Principal Investigator: Xiaoying Huang

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

Subjects must meet all of the following criteria to be eligible for enrollment in this study:

1. Age ≥18 years, regardless of gender;
2. Patients who are determined by the investigator to be in an acute exacerbation phase of bronchiectasis prior to enrollment: at least three out of the following six symptoms-cough, changes in sputum volume, purulent sputum, dyspnea or reduced exercise tolerance, fatigue or malaise, hemoptysis-have worsened for more than 48 hours, and the clinician deems that intervention is necessary;
3. Able to tolerate nebulized inhalation treatment;
4. After instruction, able to correctly use the nebulizer for treatment and accurately complete questionnaires;
5. Subjects must fully understand the purpose, nature, methods, and potential adverse events of the trial, voluntarily agree to participate, and sign the informed consent form, or have a legally authorized representative provide informed consent on their behalf.

Exclusion Criteria:

If a subject meets any of the following criteria, they are not eligible to participate in this study:

1. Patients with bronchiectasis caused by cystic fibrosis, as determined by the investigator;
2. Patients who have experienced an acute exacerbation of bronchiectasis for more than 7 days;
3. Patients with an acute exacerbation of bronchiectasis who have received intravenous antibiotic treatment for more than 72 hours prior to enrollment;
4. Patients with mild bronchiectasis caused by asthma;
5. Patients with comorbid allergic bronchopulmonary aspergillosis, active tuberculosis, or active non-tuberculous mycobacterial infection requiring standardized treatment;
6. Patients with moderate or massive hemoptysis during an acute exacerbation of bronchiectasis (moderate hemoptysis: 100-500 mL within 24 hours; massive hemoptysis: >500 mL within 24 hours or a single episode of 100-500 mL);
7. Patients with significant liver or kidney dysfunction (ALT, AST >2 times the upper limit of normal [ULN]; Cr >1.5 times ULN);
8. Patients with a history of malignancy or who have achieved clinical remission for less than 5 years;
9. Patients with any other unstable clinical conditions deemed significant by the investigator, including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematological, psychiatric, or major physiological dysfunction, and: a) Whose condition may affect the patient's safety during the study; b) That may impact the study results and their interpretation; c) That may hinder the patient's ability to complete the entire study;
10. Patients who are positive for hepatitis B surface antigen (HBsAg) with HBV-DNA >1000 copies/mL or 200 IU/mL, or positive for hepatitis C virus antibody (HCV-Ab), human immunodeficiency virus antibody (HIV-Ab), or anti-Treponema pallidum antibody;
11. Patients who are allergic to the active ingredients or excipients of the investigational product or who have a history of hypersensitivity or an allergic constitution;
12. Patients who have participated in other drug or medical device trials within the past 3 months or are currently participating in another clinical trial;
13. Pregnant women, lactating women, and women of childbearing potential;
14. Subjects whom the investigator considers unsuitable for participation in this study for any reason.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose H057+standard-of-care; Subjects are administered low-dose inhaled H057, combined with standard-of-care treatment, which included anti-infective therapy, expectorant therapy, hemostasis, oxygen therapy, and other supportive measures.	Drug: Low-dose H057+standard-of-care; Subjects are administered low-dose inhaled H057, combined with standard-of-care treatment, which included anti-infective therapy, expectorant therapy, hemostasis, oxygen therapy, and other supportive measures.
Experimental: High dose H057+standard-of-care; Subjects are administered high-dose inhaled H057, combined with standard-of-care treatment, which included anti-infective therapy, expectorant therapy, hemostasis, oxygen therapy, and other supportive measures.	Drug: High-dose H057+standard-of-care; Subjects are administered high-dose inhaled H057, combined with standard-of-care treatment, which included anti-infective therapy, expectorant therapy, hemostasis, oxygen therapy, and other supportive measures.
Placebo Comparator: H057 placebo+standard-of-care; Subjects are administered inhaled H057 placebo, combined with standard-of-care treatment, which included anti-infective therapy, expectorant therapy, hemostasis, oxygen therapy, and other supportive measures.	Drug: H057 placebo+standard-of-care; Subjects are administered inhaled H057 placebo, combined with standard-of-care treatment, which included anti-infective therapy, expectorant therapy, hemostasis, oxygen therapy, and other supportive measures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality-of-Life Bronchiectasis Respiratory Symptom Score	To evaluate change in Quality-of-Life Bronchiectasis Respiratory Symptom Score (QoL-B-RSS) from baseline. QoL-B-RSS, a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis (CF) bronchiectasis, contains 37 items on 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden). It scores ranging from 0 to 100, where lower scores indicated more severe symptoms.	baseline to day 15

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality-of-Life Bronchiectasis Respiratory Symptom Score	To evaluate change in Quality-of-Life Bronchiectasis Respiratory Symptom Score (QoL-B-RSS) from baseline. QoL-B-RSS, a self-administered, patient-reported outcome measure assessing symptoms, functioning and health-related quality of life for patients with non-cystic fibrosis (CF) bronchiectasis, contains 37 items on 8 scales (Respiratory Symptoms, Physical, Role, Emotional and Social Functioning, Vitality, Health Perceptions and Treatment Burden). It scores ranging from 0 to 100, where lower scores indicated more severe symptoms.	baseline to day 29 or day 1 post-treatment
24-hour sputum volume	To evaluate change in 24-hour sputum volume from baseline	baseline to day 29 or day 1 post-treatment
FEV1%pred	To evaluate change in FEV1%pred from baseline	baseline to day 29 or day 1 post-treatment
the frequency of acute exacerbations in bronchiectasis		day 1 to day 180
safety of inhaled H057 in acute exacerbations of bronchiectasis	the incidence and severity of adverse events (AEs) and serious adverse events (SAEs), as well as changes in vital signs and laboratory test results, etc.	day 1 to day 180
pharmacokinetic characteristics--Cmax		day 1 to day 28
pharmacokinetic characteristics--Tmax		day 1 to day 28
pharmacokinetic characteristics--t1/2		day 1 to day 28
pharmacokinetic characteristics--AUC0-t		day 1 to day 28
pharmacokinetic characteristics--Rac		day 1 to day 28
pharmacodynamic characteristic	To evaluate change in neutrophil elastase levels from baseline	day 1 to day 28
treatment efficacy rate	Response to treatment is defined as the significant improvement or near resolution of acute exacerbation symptoms. Treatment failure is defined as the absence of significant improvement or progressive worsening of acute exacerbation symptoms, such as requiring hospitalization or the need for additional antibiotic therapy.	baseline to day 15
clinical pulmonary infection score	To evaluate change in clinical pulmonary infection score (CPIS) from baseline. The CPIS is calculated on the basis of points assigned for various signs and symptoms of pneumonia (eg, fever and extent of oxygenation impairment). It scores ranging from 0 to 12, where higher scores mean a worse outcome. Some studies suggest that a CPIS >6 may correlate with ventilator-associated pneumonia (VAP).	baseline to day 15
bronchiectasis exacerbation and symptom tool	To evaluate change in bronchiectasis exacerbation and symptom tool (BEST) from baseline. The BEST diary is to detect bronchiectasis exacerbations. It scores ranging from 0 to 26, where higher scores indicate more severe symptoms.The BEST symptom diary is responsive at onset and recovery from exacerbation and may be useful to capture and characterise exacerbations.	baseline to day 29 or day 1 post-treatment
Borg Scale	To evaluate change in Borg Scale from baseline. Borg Scale is one of commonly used measures to assess dyspnea in chronic lung disease.The scale was modified to form a 10-point scale including written indicators of severity. The scale has been used to quantify various "perceived symptoms" such as breathlessness and muscle fatigue during exercise. The higher Borg Scale means more severe breathlessness and muscle fatigue	baseline to day 29 or day 1 post-treatment
sputum purulence score	To evaluate change in sputum purulence score from baseline. It scores ranging from 0 to 8, where a higher score indicates greater severity of the condition.	baseline to day 29 or day 1 post-treatment

Collaborators and Investigators

• Sponsor: Shanghai Huilun Pharmaceutical Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027

Study Registration Dates

• First Submitted: April 16, 2025
• First Submitted That Met QC Criteria: May 5, 2025
• First Posted (Actual): May 6, 2025

Study Record Updates

• Last Update Posted (Actual): May 9, 2025
• Last Update Submitted That Met QC Criteria: May 6, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Bronchial Diseases; Bronchiectasis
• Other Study ID Numbers: PH-H057-II-03

Drug and device information, study documents

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