A Study of HSK31858 in Participants with Non-Cystic Fibrosis Bronchiectasis

Phase 2 Randomized, Double-blind, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of HSK31858 in Participants with Non-cystic Fibrosis Bronchiectasis

This is a phase II, randomised, double-blind, placebo-controlled, multicenter study to assess the efficacy and safety of HSK31858 in non-cystic fibrosis bronchiectasis (NCFBE) participants.

Study Overview

• Status: Completed
• Conditions: Non-cystic Fibrosis Bronchiectasis (NCFBE)
• Intervention / Treatment: Drug: HSK31858; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China
      • The First Affiliated Hospital of Guangzhou Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1. Age ≥18 years and BMI≥18.0 kg/m^2 at the time of signing the ICF.

  2. Chest HRCT showed bronchiectasis affecting one or more lobes and was confirmed by a clinician as NCFBE(clinically characterized by chronic cough, expectoration and/or intermittent hemoptysis, with or without shortness of breath and respiratory failure). HRCT was considered effective if the patient had received HRCT in the same hospital within 12 months and screening HRCT is not necessary.

  3. Having daily expectoration(with sufficient sputum production at screening, if the subject is unable to produce sputum voluntarily, sample collection can be performed by induced expectoration).

  4. Have at least 2 pulmonary exacerbations in the past 12 months before Screening.

  5. If long-term treatment with bronchodilators (long-acting β-agonists and/or long-acting muscarinic antagonists) is required, the dose and regimen should remain stable for at least 3 months before the screening visit and throughout the study period.

  6. The estimated survival time ≥ 12 months.

  7. Women must be post-menopausal, surgically sterile, or using highly effective contraception methods from Day 1 to at least 30 days after the last dose.

  8. Males with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose.

  9. Give their signed study informed consent to participate.

Exclusion Criteria:

• 1. Have pulmonary hypertension or have a primary diagnosis of COPD or asthma as judged by the Investigator.

  2. A history of malignancy (excluding cured basal cell carcinoma of the skin, carcinoma in situ, and papillary carcinoma of the thyroid gland. The patients who had survived lung cancer surgery for at least 5 years without antitumor therapy can enroll in the study ) within 5 years prior to screening or a history of antitumor therapy.

  3. Have bronchiectasis due to CF (HRCT showed that the above lung diseases became predominant) as judged by the Investigator.

  4. Currently being treated Non-tuberculous Mycobacterial (NTM) pulmonary infections, allergic bronchopulmonary aspergillosis, or tuberculosis (TB), or active and currently symptomatic infections caused by COVID-19.

  5. Patients who had experienced any degree of acute exacerbation of bronchiectasis or were developing an acute exacerbation of bronchiectasis before 4 weeks of screening.

  6. Patients who had hemoptysis and required medical intervention within 4 weeks prior to screening(except for coughing up minorbloody streaks).

  7. Have an abnormal renal function test result (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m^2) at Screening.

  8. Subjects with a history of liver disease or current treatment for liver disease during the screening period, including but not limited to acute or chronic hepatitis, cirrhosis or liver failure, or aspartate aminotransferase (AST) > 2.0×ULN or alanine aminotransferase (ALT) > 2.0×ULN or total bilirubin (TBIL) > 1.5×ULN.

  9. Active hepatitis B virus infection (hepatitis B surface antigen positive with HBV-DNA load above the lower limit of detection), active hepatitis C virus infection (HCV antibody positive with HCV-RNA load above the lower limit of detection), or known HIV infection or syphilis infection.

  10. Any other unstable clinical condition, including but not limited to cardiovascular, gastrointestinal, hepatic, renal, neurological, musculoskeletal, infectious, endocrine, metabolic, hematologic, psychiatric, or major physiological dysfunction, that the investigator considers to be (a) likely to affect patient safety throughout the study; (b) Influence the results of the study and its interpretation; (c) impeding the patient's ability to complete the entire study.

  11. Had participated in a clinical trial of any other drug or medical device in the 3 months prior to the screening (a drug or medical device treated with a clinical trial) or the subject had not been more than 5 half-lives from the last clinical trial of the drug at the time of screening.

  12. Medications that may cause hyperkeratosis (e.g., tumor necrosis factor-α antagonists) within 4 weeks prior to screening.

  13. Patients who have used a strong inducer or suppressor of CYP3A within 14 days or 5 half-lives of the first investigational drug (whichever is longer).

  14. Patients who had smoked an average of 10 cigarettes or more per day in the previous 1 year were screened.

  15. Pregnancy and lactation.

  16. The subjects were unable to complete the questionnaires due to their limited educational level, or the subjects and their families failed to fill in the subjects' log cards.

  17. Had received live attenuated vaccine within 30 days before randomization. 18. The investigators judged that there were other conditions that were not suitable for participation in the study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSK31858 20mg; multiple oral doses: 20mg/d for 24w	Drug: HSK31858; HSK31858 is a novel inhibitor of DPP1 developed by Hisco Pharmaceutical and can reduce pulmonary exacerbations over a 24-week treatment period in patients with non-cystic fibrosis bronchiectasis
Experimental: HSK31858 40mg; multiple oral doses: 20mg/d for 24w	Drug: HSK31858; HSK31858 is a novel inhibitor of DPP1 developed by Hisco Pharmaceutical and can reduce pulmonary exacerbations over a 24-week treatment period in patients with non-cystic fibrosis bronchiectasis
Placebo Comparator: placebo; multiple oral doses for 24w	Drug: placebo; the placebo comparator of study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of pulmonary exacerbations	Number of events per person-time over 24-weeks	24-week treatment period

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to first pulmonary exacerbation	Exacerbation is defined by signs and symptoms plus intervention with systemic antibiotics	24-week treatment period
Change from Baseline(Screening) in forced expiratory volume in 1 second (FEV1)	Change from Baseline(Screening) in FEV1 at 24-weeks	24-week treatment period
Change from Baseline(Screening) in 24-hour Sputum Weight and Sputum purulence score	Change from Baseline(Screening) in 24h Sputum Weight and Purulence Score at 24-weeks	24-week treatment period
Change from Baseline(Screening) in Frequency of Hemoptysis	Change from Baseline(Screening) in Hemoptysis	24-week treatment period
Change from Baseline in the Respiratory Symptoms Domain Score of the Quality of Life (QOL) Bronchiectasis questionnaire	Change from Baseline Quality of Life (QOL) Bronchiectasis questionnairescore at 24-weeks	24-week treatment period

Collaborators and Investigators

• Sponsor: Haisco Pharmaceutical Group Co., Ltd.
• Investigators: Principal Investigator: Nanshan Zhong, The First Affiliated Hospital of Guangzhou Medical University; Principal Investigator: Weijie Guan, The First Affiliated Hospital of Guangzhou Medical University

Publications and helpful links

General Publications

• Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available.
• Chalmers JD, Aliberti S, Filonenko A, Shteinberg M, Goeminne PC, Hill AT, Fardon TC, Obradovic D, Gerlinger C, Sotgiu G, Operschall E, Rutherford RM, Dimakou K, Polverino E, De Soyza A, McDonnell MJ. Characterization of the "Frequent Exacerbator Phenotype" in Bronchiectasis. Am J Respir Crit Care Med. 2018 Jun 1;197(11):1410-1420. doi: 10.1164/rccm.201711-2202OC.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2022
• Primary Completion (Actual): March 29, 2024
• Study Completion (Actual): June 7, 2024

Study Registration Dates

• First Submitted: October 27, 2022
• First Submitted That Met QC Criteria: October 27, 2022
• First Posted (Actual): November 1, 2022

Study Record Updates

• Last Update Posted (Actual): September 26, 2024
• Last Update Submitted That Met QC Criteria: September 24, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: phase II; NCFBE; HSK31858
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Bronchial Diseases; Fibrosis; Bronchiectasis
• Other Study ID Numbers: HSK31858-201

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
• product manufactured in and exported from the U.S.: No