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

NCT05601778 | Completed Phase 2

• 1 other identifier: HSK31858-201
• Study Type: interventional
• Target: 226
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-cystic Fibrosis Bronchiectasis (NCFBE)

Keywords

HSK31858; NCFBE; phase II

Outcome Measures

Primary Outcomes (1)

• Frequency of pulmonary exacerbations

  Number of events per person-time over 24-weeks

  24-week treatment period

Secondary Outcomes (5)

• Time to first pulmonary exacerbation

  24-week treatment period

• Change from Baseline(Screening) in forced expiratory volume in 1 second (FEV1)

  24-week treatment period

• Change from Baseline(Screening) in 24-hour Sputum Weight and Sputum purulence score

  24-week treatment period

• Change from Baseline(Screening) in Frequency of Hemoptysis

  24-week treatment period

• Change from Baseline in the Respiratory Symptoms Domain Score of the Quality of Life (QOL) Bronchiectasis questionnaire

  24-week treatment period

Study Arms (3)

HSK31858 20mg

EXPERIMENTAL

multiple oral doses: 20mg/d for 24w

Drug: HSK31858

HSK31858 40mg

EXPERIMENTAL

multiple oral doses: 20mg/d for 24w

Drug: HSK31858

placebo

PLACEBO COMPARATOR

multiple oral doses for 24w

Drug: placebo

Interventions

HSK31858 DRUG

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

HSK31858 20mg; HSK31858 40mg

placebo DRUG

the placebo comparator of study

placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Age ≥18 years and BMI≥18.0 kg/m\^2 at the time of signing the ICF.
• \. 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.
• \. 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).
• \. Have at least 2 pulmonary exacerbations in the past 12 months before Screening.
• \. 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.
• \. The estimated survival time ≥ 12 months.
• \. 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.
• \. Males with female partners of childbearing potential must be using effective contraception from Day 1 to at least 90 days after the last dose.
• \. Give their signed study informed consent to participate.

You may not qualify if:

• \. Have pulmonary hypertension or have a primary diagnosis of COPD or asthma as judged by the Investigator.
• \. 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.
• \. Have bronchiectasis due to CF (HRCT showed that the above lung diseases became predominant) as judged by the Investigator.
• \. 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.
• \. Patients who had experienced any degree of acute exacerbation of bronchiectasis or were developing an acute exacerbation of bronchiectasis before 4 weeks of screening.
• \. Patients who had hemoptysis and required medical intervention within 4 weeks prior to screening(except for coughing up minorbloody streaks).
• \. Have an abnormal renal function test result (estimated glomerular filtration rate \[eGFR\] \< 60 mL/min/1.73m\^2) at Screening.
• \. 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.
• \. 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.
• \. 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.
• \. 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.
• \. Medications that may cause hyperkeratosis (e.g., tumor necrosis factor-α antagonists) within 4 weeks prior to screening.
• \. 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).
• \. Patients who had smoked an average of 10 cigarettes or more per day in the previous 1 year were screened.
• \. Pregnancy and lactation.

Sponsors & Collaborators

• Haisco Pharmaceutical Group Co., Ltd.: lead

Study Sites (1)

The First Affiliated Hospital of Guangzhou Medical University

Guangzhou, Guangdong, China

Location

Related Publications (3)

• Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available.

  PMID: 11986413 BACKGROUND

• 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.

  PMID: 29357265 BACKGROUND

• Zhong NS, Qiu R, Cao J, Huang YM, Zhou H, Xu XX, Xu JF, Ye H, Yang ZR, Gao LY, Shen Y, Xiao ZK, Xie SG, Lin DJ, Zhao L, Xiong H, Zhang XM, Li FQ, Guan WJ, Chalmers JD; SAVE-BE trial investigators. Effects of the DPP-1 inhibitor HSK31858 in adults with bronchiectasis in China (SAVE-BE): a phase 2, multicentre, double-blind, randomised, placebo-controlled trial. Lancet Respir Med. 2025 May;13(5):414-424. doi: 10.1016/S2213-2600(25)00019-0. Epub 2025 Mar 25.

  PMID: 40154523 DERIVED

Related Links

• Related Info
• Related Info

Study Officials

• Nanshan Zhong

  The First Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

• Weijie Guan

  The First Affiliated Hospital of Guangzhou Medical University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 27, 2022
• First Posted: November 1, 2022
• Study Start: December 6, 2022
• Primary Completion: March 29, 2024
• Study Completion: June 7, 2024
• Last Updated: September 26, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)