[Translation] An open-label phase I clinical trial comparing the pharmacokinetics and safety profiles of a single oral dose of HSK31858 tablets in participants with hepatic impairment and normal hepatic function.

主要研究目的：比较HSK31858片在肝功能正常参与者和不同程度肝功能不全参与者中的药代动力学特征；次要研究目的：评价HSK31858片在肝功能正常参与者和不同程度肝功能不全参与者中的安全性。

[Translation]

Primary study objective: To compare the pharmacokinetic characteristics of HSK31858 tablets in participants with normal liver function and participants with varying degrees of hepatic impairment; Secondary study objective: To evaluate the safety of HSK31858 tablets in participants with normal liver function and participants with varying degrees of hepatic impairment.

Start Date12 Mar 2026

Sponsor / Collaborator

Haisco Pharmaceutical Group Co., Ltd.

CTR20253262

/ RecruitingPhase 3

评价HSK31858片在非囊性纤维化支气管扩张患者中长期安全性的多中心、单臂、开放扩展研究

[Translation] A multicenter, single-arm, open-label extension study to evaluate the medium- and long-term safety of HSK31858 tablets in patients with non-cystic fibrosis bronchiectasis

在既往参与HSK31858-301研究的NCFBE患者中评估HSK31858片长期用药的安全性

[Translation]

To evaluate the safety of long-term use of HSK31858 tablets in NCFBE patients who previously participated in the HSK31858-301 study.

Start Date28 Sep 2025

Sponsor / Collaborator

Haisco Pharmaceutical Group Co., Ltd.

NCT07134465

/ Enrolling by invitationPhase 1

A Single-center, Open-label, Two-period, Fixed-sequence Clinical Study to Evaluate the Effect of Itraconazole on the Pharmacokinetics of HSK31858 in Healthy Subjects

This is a single-center, open-label, two-period, fixed-sequence clinical study to evaluate the effect of Itraconazole on the pharmacokinetics of HSK31858 in healthy subjects

Start Date11 Aug 2025

Sponsor / Collaborator

Haisco Pharmaceutical Group Co., Ltd.

100 Clinical Results associated with HSK-31858

100 Translational Medicine associated with HSK-31858

100 Patents (Medical) associated with HSK-31858

Literatures (Medical) associated with HSK-31858

01 Aug 2025·BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Safety, tolerability, pharmacokinetics and pharmacodynamics of HSK31858, a novel oral dipeptidyl peptidase‐1 inhibitor, in healthy volunteers: An integrated phase 1, randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending dose study

Article

Author: Jie Hou ; Yuhao Wang ; Chao Yu ; Mengyue Hu ; Meixia Chen ; Hanmo Liu ; Nan Wu ; Lu Wang

Abstract:

Aim:

Dipeptidyl peptidase‐1 (DPP‐1) inhibitors have been studied for the treatment of neutrophil‐mediated inflammatory diseases including bronchiectasis, bronchial asthma and cystic fibrosis. This study evaluated the pharmacokinetics, pharmacodynamics, safety and tolerability of DPP‐1 inhibitor HSK31858 in healthy Chinese volunteers.

Methods:

Volunteers in Part A randomly received single doses of HSK31858 (15, 40, 60 and 80 mg) or placebo in fasted states. The 40‐mg cohort also received HSK31858 40 mg or placebo in fed states. In Part B, volunteers randomly received HSK31858 10, 20 and 40 mg or placebo once daily for 28 days in fasted states. The primary endpoints were safety and tolerability of HSK31858.

Results:

Among 38 volunteers in Part A and 36 in Part B, HSK31858 was well tolerated; no deaths, serious adverse events, or discontinuations due to adverse events occurred. The median Tmax was 0.75 to 1.0 h and the mean terminal t1/2 was 16.5 to 21.0 h in the fasted state with single doses of HSK31858. Both Cmax and AUC0‐t exhibited a dose‐dependent rise. Food had no effect on AUC. Multiple doses of HSK31858 demonstrated a similar pharmacokinetics profile, with about 2‐fold accumulation in AUC. HSK31858 dose‐dependently inhibited neutrophil count‐normalized neutrophil elastase (NEnorm) activity. The maximal percentage decrease in NEnorm activity relative to baseline during 28 days of HSK31858 treatments was 13.6% and 76.4% with HSK31858 10 and 40 mg once‐daily, respectively.

Conclusion:

HSK31858 was safe and well tolerated. The pharmacokinetics and pharmacodynamics profile of HSK31858 supports further clinical development for the treatment of neutrophil‐mediated inflammatory diseases.

Trial Registration:

NCT05663593.

01 Jul 2025·Journal of Thoracic Disease

Dipeptidyl peptidase 1 inhibitors and neutrophilic inflammation in bronchiectasis: a narrative review

Review

Author: Tang, Rui-Di ; Guan, Wei-Jie ; Yue, Jun-Qing ; Chalmers, James D

Background and Objective:

Bronchiectasis is a chronic respiratory disease characterized by predominantly neutrophilic inflammation, recurrent infection and pathological dilatation of the airways. Current therapeutic strategies primarily target infections and improving mucus clearance. However, no current treatment can directly ameliorate neutrophilic inflammation. Recently, dipeptidyl peptidase 1 (DPP-1) inhibitors effectively abrogated neutrophilic inflammation in bronchiectasis. This narrative review aimed to analyze the structural characteristics and functional effects of DPP-1, explore the mechanism of DPP-1 inhibitors in bronchiectasis, and highlight major clinical trial findings.

Methods:

We performed an online electronic search for relevant English literature on PubMed and Web of Science databases, with the keywords of "dipeptidyl peptidase 1", "cathepsin C", "cathepsin C structure", "cathepsin C maturation", "cathepsin C loss-of-function", "neutrophil serine proteases and bronchiectasis", "neutrophil serine proteases and cathepsin C", "neutrophil serine proteases and DPP-1", "DPP-1 inhibitors", "cathepsin C inhibitors", "DPP-1 inhibitors and bronchiectasis", "cathepsin C inhibitors and bronchiectasis". Two authors (R.D.T. and J.Q.Y.) independently searched and reviewed the articles.

Key Content and Findings:

Excessive and uncontrolled release of neutrophil serine proteases (NSPs) can lead to airway inflammatory responses and structural damage in bronchiectasis. Elevated levels of neutrophil elastase (NE) and other neutrophil markers in the airway are associated with exacerbations and lung function decline. In light of the pivotal role of DPP-1 in eliciting neutrophilic inflammation, several DPP-1 inhibitors have been developed and entered clinical trials for safety and efficacy assessment in bronchiectasis. Of these, brensocatib markedly prolonged the time to the first exacerbation and decreased the exacerbation frequency via decreasing the activity of NSPs. The phase III ASPEN trial has been completed and confirms reduced exacerbations and slower lung function decline with DPP-1 inhibitor treatment. Treatment with BI 1291583 reduced the risk of bronchiectasis exacerbations in the phase II Airleaf^® trial. HSK31858 significantly decreased the exacerbation frequency and prolonged the time to the first exacerbation in the latest phase II trial among the Chinese population.

Conclusions:

DPP-1 inhibitors have exhibited promising effects in improving several major clinical outcomes in bronchiectasis via suppressing the activity of NSPs.

01 May 2025·Lancet Respiratory Medicine

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

Article

Author: Xu, Xing-xiang ; Huang, Zeng-yu ; Li, Fang-qiong ; Xie, Shi-guang ; Ye, Huan ; Xie, Shi-Guang ; Lin, Ying-xiang ; Xu, Xing-Xiang ; Wu, Xiao-fei ; Liu, Han-mo ; Zhong, Nan-shan ; Zhang, Xian-ming ; Zhong, Nan-Shan ; Zhang, Xiao-ju ; Lin, Dian-Jie ; Qiu, Rong ; Xiong, Hao ; Chalmers, James D ; Zhang, Xian-Ming ; Zheng, Yao ; Lin, Dian-jie ; Huang, Yan-ming ; Guan, Wei-jie ; Yang, Zhi-Ren ; Li, Fang-Qiong ; Xu, Jin-fu ; Huang, Yan-Ming ; Shen, Yao ; Xiao, Zu-ke ; Xu, Jin-Fu ; Guan, Wei-Jie ; Zhao, Li ; Zhang, Guo-jun ; Song, Yuan-lin ; Li, Yuan-yuan ; Gao, Ling-yun ; Gao, Ling-Yun ; Cao, Jie ; Li, Ya-ming ; Yang, Zhi-ren ; Zhou, Hua ; Wen, Fu-qiang ; Qu, Jie-ming ; Wang, Ling-wei ; Chalmers, James Duncan ; Xiao, Zu-Ke

BACKGROUND:

Airway neutrophil inflammation with excessive neutrophil serine proteases is implicated in frequent exacerbations of bronchiectasis. HSK31858 is a novel reversible inhibitor of DPP-1. We aimed to assess the efficacy and safety of HSK31858 in decreasing the frequency of bronchiectasis exacerbations among adults with bronchiectasis.

METHODS:

SAVE-BE was a phase 2, double-blind, randomised, placebo-controlled trial in 25 tertiary centres in China. Participants were aged 18 years or older with a physician diagnosis of bronchiectasis, according to chest high-resolution CT showing bronchial dilatation and compatible respiratory symptoms, and at least two exacerbations within 12 months before screening. Participants were randomly assigned (1:1:1) via a central interactive web-response system to receive 20 mg HSK31858, 40 mg HSK31858, or placebo, orally, once daily for 24 weeks. Randomisation was stratified by exacerbation frequency in the previous year (less than three vs three or more annually) and study investigators and participants were masked to group assignment for analysis of study outcomes. The primary endpoint was the annualised exacerbation frequency over 24 weeks, assessed in the full analysis set. Safety was monitored throughout the study. This trial is registered with ClinicalTrials.gov, NCT05601778.

FINDINGS:

Between Dec 6, 2022, and March 31, 2024, 292 patients were screened, 226 of whom were enrolled and randomly assigned (75 to the 20 mg HSK31858 group, 76 to the 40 mg HSK31858 group, and 75 to the placebo group. 74 patients received 20 mg HSK31858, 75 received 40 mg HSK31858, and 75 received placebo and were included in the full analysis set. In the full analysis set, 136 (61%) participants were female and 88 (39%) were male. The mean annualised frequency of exacerbations was 1·00 per person-year (SD 1·44) in the 20 mg HSK31858 group, 0·75 per person-year (1·37) in the 40 mg HSK31858 group, and 1·88 per person-year (1·97) in the placebo group. The least-squares mean frequency of exacerbations was 1·05 per person-year (95% CI 0·73-1·51) in the 20 mg HSK31858 group, 0·83 per person-year (0·55-1·25) in the 40 mg HSK31858 group, and 2·01 per person-year (1·53-2·63) in the placebo group. The incidence rate ratio compared with placebo was 0·52 (95% CI 0·34-0·80; p=0·0031) for the 20 mg HSK31858 group and 0·41 (0·26-0·66; p=0·0002) for the 40 mg HSK31858 group. The incidence of adverse events was similar across the three groups. Neither HSK31858 dose was associated with an increased incidence of adverse events of special interest (eg, hyperkeratosis, gingivitis, or life-threatening infections).

INTERPRETATION:

Both HSK31858 doses improved clinical outcomes in adults with bronchiectasis, significantly reducing the exacerbation frequency compared with placebo. The development of new drugs targeted at amelioration of neutrophilic inflammation (eg, via suppression of DPP-1 activity) might lead to new options for hindering the progression of bronchiectasis.

FUNDING:

Haisco.

News (Medical) associated with HSK-31858

21 Nov 2023

·www.pharmaindustrial-india.com

Chiesi and Haisco Announce Licensing Agreement

Chiesi Farmaceutici and Haisco Pharmaceutical Group Co.Ltd have announced the execution of a Licensing Agreement to develop, manufacture, and commercialise outside China and adjacent territories (Hong Kong SAR, Macau SAR and Taiwan District) HSK31858, a novel, reversible dipeptidyl peptidase 1 (DPP1) inhibitor for respiratory diseases. HSK31858 is an oral, potent, and highly selective small molecule DPP1 inhibitor currently in Phase 2 trials in China with the potential to be an anti-inflammatory agent in bronchiectasis. With this agreement Chiesi will expand its product portfolio in its strategic respiratory field, aiming to further increase its impact in this area and contribute to developing treatments for severe respiratory diseases with high unmet medical needs. “This collaboration demonstrates our commitment to develop new medicines aimed at improving the lives of patients who suffer from severe respiratory diseases with limited treatment options,” commented Thomas Eichholtz, Head of Global Research and Development at Chiesi Group. “HSK31858 is an important addition to our pipeline, and it offers a great opportunity to combine the two partners’ strong experience in this field.” “This collaboration with Chiesi is an important milestone in our globalisation strategy, we are pleased that HSK31858 will benefit patients worldwide in the future” said Xiulian Fan, General Manager at Haisco Pharmaceutical. “We acknowledge and appreciate Chiesi’s significant commitment and expertise in the development of drugs in the respiratory field and believe that this partnership will help maximise the value of HSK31858”. Under the terms of the agreement, Chiesi will make an upfront payment and additional contingent milestone payments to Haisco, including royalties on product sales.

License out/inPhase 2

20 Nov 2023

·www.prnewswire.com

Chiesi Group signed a License Agreement with Haisco Pharmaceutical to develop, manufacture, and commercialise a novel, reversible dipeptidyl peptidase 1 inhibitor for bronchiectasis

Chiesi Group and Haisco Pharmaceutical will collaborate closely to develop HSK31858, a novel reversible dipeptidyl peptidase 1 (DPP1) inhibitor for respiratory diseases. This agreement expands Chiesi's comprehensive R&D program in bronchiectasis, a respiratory disease with high unmet medical needs, for which no approved treatment is available to date. Haisco Pharmaceutical will receive an upfront payment and future milestone payments, including royalties on product sales. PARMA, Italy and CHENGDU, China, Nov. 20, 2023 /PRNewswire/ -- Chiesi Farmaceutici S.p.A ("Chiesi Group"), an international, research-focused biopharmaceuticals and healthcare group, and Haisco Pharmaceutical Group Co.Ltd (Haisco Pharmaceutical) today announced the execution of a Licensing Agreement to develop, manufacture, and commercialise outside China and adjacent territories (Hong Kong SAR, Macau SAR and Taiwan District) HSK31858, a novel, reversible dipeptidyl peptidase 1 (DPP1) inhibitor for respiratory diseases. HSK31858 is an oral, potent, and highly selective small molecule DPP1 inhibitor currently in Phase 2 trials in China with the potential to be an anti-inflammatory agent in bronchiectasis. With this agreement Chiesi will expand its product portfolio in its strategic respiratory field, aiming to further increase its impact in this area and contribute to developing treatments for severe respiratory diseases with high unmet medical needs. "This collaboration demonstrates our commitment to develop new medicines aimed at improving the lives of patients who suffer from severe respiratory diseases with limited treatment options," commented Thomas Eichholtz, Head of Global Research and Development at Chiesi Group. "HSK31858 is an important addition to our pipeline, and it offers a great opportunity to combine the two partners' strong experience in this field." "This collaboration with Chiesi is an important milestone in our globalisation strategy, we are pleased that HSK31858 will benefit patients worldwide in the future" said Xiulian Fan, General Manager at Haisco Pharmaceutical. "We acknowledge and appreciate Chiesi's significant commitment and expertise in the development of drugs in the respiratory field and believe that this partnership will help maximise the value of HSK31858". Under the terms of the agreement, Chiesi will make an upfront payment and additional contingent milestone payments to Haisco, including royalties on product sales. SOURCE Chiesi

License out/inPhase 2Phase 1

100 Deals associated with HSK-31858

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Non-cystic fibrosis bronchiectasis	Phase 3	China	Haisco Pharmaceutical Group Co., Ltd.	26 Sep 2024
airway disease	Phase 2	China	Haisco Pharmaceutical Group Co., Ltd.	01 Dec 2024
Catarrhal bronchitis	Phase 2	China	Haisco Pharmaceutical Group Co., Ltd.	01 Dec 2024
Pulmonary Disease, Chronic Obstructive	Phase 2	China	Haisco Pharmaceutical Group Co., Ltd.	01 Dec 2024
Asthma	Phase 2	China	Haisco Pharmaceutical Group Co., Ltd.	22 Oct 2024
Acute Lung Injury	Phase 1	China	Haisco Pharmaceutical Group Co., Ltd.	28 Oct 2024
Respiratory Distress Syndrome, Acute	Phase 1	China	Haisco Pharmaceutical Group Co., Ltd.	28 Oct 2024

Clinical Result

Indication

Phase

Evaluation

View All Results

Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT05663593 (Pubmed \| Br J Clin Pharmacol)	Phase 1	-	-	HSK31858 15 mg	wdbvllqtdx(xhgklwnmyv) = ybvmskkyxh kxflcckysd (mmkzrrejnr ) View more	-	01 Aug 2025
				HSK31858 40 mg	yimfublhii(saiifzysiq) = ywycdqqaqz fdsrlbhiaj (yiugataisj ) View more
NCT05601778 (SAVE-BE, Pubmed \| Lancet Respir Med) Manual	Phase 2	Bronchiectasis	136	HSK31858 20 mg	cxtjiwgzrp(mdkpkfaofg) = xklmcmrwll fnkdzpfvas (psbpqqqmqf, 1.44)	Positive	25 Mar 2025
				HSK31858 40 mg	cxtjiwgzrp(mdkpkfaofg) = vhvwmolazt fnkdzpfvas (psbpqqqmqf, 1.37)
ERS2024	Phase 2	Bronchiectasis sputum purulence score	226	HSK31858 20mg	jtdlbfexdd(eflkpqcljf) = irayizbkvt iphmanngme (zshagvaswu ) View more	Positive	07 Sep 2024
				HSK31858 40mg	jtdlbfexdd(eflkpqcljf) = cugpfmidyu iphmanngme (zshagvaswu ) View more
NCT05663593 (ERS2023) Manual	Phase 1	Bronchiectasis	-	HSK31858	kneszzkata(lqqypmzkep) = HSK31858 was absorbed rapidly, with no significant accumulation of Cmax, while AUC accumulation was more pronounced. There was dose-dependent inhibitory effect in whole blood NE activity, with maximum inhibition of 13.6%, 44.1%,and 76.4% in the 10mg,20mg, and 40mg groups, repectively. yxjqtqilhq (vuaztldqyo )	Positive	09 Sep 2023
ERS2023	Phase 1	-	75	HSK31858	gltopgnefk(gvnbhsfblq) = HSK31858 was absorbed rapidly, with no significant accumulation of Cmax, while AUC accumulation was more pronounced. xjftofsjap (jjlorgtamm ) View more	Positive	09 Sep 2023
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