Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trial
BackgroundChronic kidney disease-associated pruritus (CKD-aP) is a common and distressing symptom in hemodialysis patients. This Phase II trial evaluated the efficacy and safety of HSK21542, a selective kappa-opioid receptor agonist, in managing CKD-aP.MethodsAdult patients on hemodialysis with mode...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-06-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1583515/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849684766348017664 |
|---|---|
| author | Ming-Ming Pan Min Gao Li Zhou Yan Xu Li Yao Chao-Qing Wu Chang-Lin Mei Chang-Lin Mei Zhan-Zheng Zhao Dong Sun Tian-Jun Guan Qin-Kai Chen Ming Shi Hui Xu Ya-Ming Li Wan-Yun Zhao Rui Yan Bi-Cheng Liu |
| author_facet | Ming-Ming Pan Min Gao Li Zhou Yan Xu Li Yao Chao-Qing Wu Chang-Lin Mei Chang-Lin Mei Zhan-Zheng Zhao Dong Sun Tian-Jun Guan Qin-Kai Chen Ming Shi Hui Xu Ya-Ming Li Wan-Yun Zhao Rui Yan Bi-Cheng Liu |
| author_sort | Ming-Ming Pan |
| collection | DOAJ |
| description | BackgroundChronic kidney disease-associated pruritus (CKD-aP) is a common and distressing symptom in hemodialysis patients. This Phase II trial evaluated the efficacy and safety of HSK21542, a selective kappa-opioid receptor agonist, in managing CKD-aP.MethodsAdult patients on hemodialysis with moderate to severe pruritus, were randomized 1:1:1 to placebo, or HSK21542 (0.3 μg/kg or 0.6 μg/kg) administered thrice weekly post-dialysis for 12 weeks. The primary endpoint was the change from baseline in the weekly mean of the worst itching intensity Numerical Rating Scale (WI-NRS) score at week 12. Secondary endpoints included quality-of-life assessments, safety evaluations, and pharmacokinetic properties.ResultsA total of 90 patients were enrolled. At week 12, mean changes in WI-NRS scores from baseline were −2.94 for the placebo group, −3.40 for the 0.3 μg/kg HSK21542 group, and −2.21 for the 0.6 μg/kg HSK21542 group. The percentages of patients who had a reduction of 3 points or above in their WI - NRS scores were 44.4% in the placebo group, 62.1% in the 0.3 μg/kg HSK21542 group, and 37.0% in the 0.6 μg/kg HSK21542 group. The 0.30 μg/kg HSK21542 group demonstrated more significant improvements in Skindex - 16 scores compared to the placebo. The 5-D Itch Scale scores also presented similar trends. Both the 0.3 μg/kg and 0.6 μg/kg doses of HSK21542 were well - tolerated, with no dose-dependent adverse effects.ConclusionThe 0.3 μg/kg dose of HSK21542 demonstrated superior efficacy and safety in reducing pruritus and improving quality of life in hemodialysis patients. |
| format | Article |
| id | doaj-art-98707bffbf044fefaebf1c6d07befcfe |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-98707bffbf044fefaebf1c6d07befcfe2025-08-20T03:23:22ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-06-011610.3389/fphar.2025.15835151583515Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trialMing-Ming Pan0Min Gao1Li Zhou2Yan Xu3Li Yao4Chao-Qing Wu5Chang-Lin Mei6Chang-Lin Mei7Zhan-Zheng Zhao8Dong Sun9Tian-Jun Guan10Qin-Kai Chen11Ming Shi12Hui Xu13Ya-Ming Li14Wan-Yun Zhao15Rui Yan16Bi-Cheng Liu17Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, ChinaInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, ChinaDepartment of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, Sichuan, ChinaDepartment of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, ChinaDepartment of Nephrology, The First Hospital of China Medical University, Shenyang, Liaoning, ChinaDepartment of Nephrology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, ChinaDepartment of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, ChinaDepartment of Nephrology, Zhabei Central Hospital of JingAn District of Shanghai, Shanghai, ChinaDepartment of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, ChinaDepartment of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China0Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, China1Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China2Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, Hubei, China3Department of Nephrology, Xiangya Hospital of the Central South University, Changsha, Hunan, China4Haisco Pharmaceutical Group Co., Ltd., Chengdu, Sichuan, China4Haisco Pharmaceutical Group Co., Ltd., Chengdu, Sichuan, China5Department of Nephrology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaInstitute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, ChinaBackgroundChronic kidney disease-associated pruritus (CKD-aP) is a common and distressing symptom in hemodialysis patients. This Phase II trial evaluated the efficacy and safety of HSK21542, a selective kappa-opioid receptor agonist, in managing CKD-aP.MethodsAdult patients on hemodialysis with moderate to severe pruritus, were randomized 1:1:1 to placebo, or HSK21542 (0.3 μg/kg or 0.6 μg/kg) administered thrice weekly post-dialysis for 12 weeks. The primary endpoint was the change from baseline in the weekly mean of the worst itching intensity Numerical Rating Scale (WI-NRS) score at week 12. Secondary endpoints included quality-of-life assessments, safety evaluations, and pharmacokinetic properties.ResultsA total of 90 patients were enrolled. At week 12, mean changes in WI-NRS scores from baseline were −2.94 for the placebo group, −3.40 for the 0.3 μg/kg HSK21542 group, and −2.21 for the 0.6 μg/kg HSK21542 group. The percentages of patients who had a reduction of 3 points or above in their WI - NRS scores were 44.4% in the placebo group, 62.1% in the 0.3 μg/kg HSK21542 group, and 37.0% in the 0.6 μg/kg HSK21542 group. The 0.30 μg/kg HSK21542 group demonstrated more significant improvements in Skindex - 16 scores compared to the placebo. The 5-D Itch Scale scores also presented similar trends. Both the 0.3 μg/kg and 0.6 μg/kg doses of HSK21542 were well - tolerated, with no dose-dependent adverse effects.ConclusionThe 0.3 μg/kg dose of HSK21542 demonstrated superior efficacy and safety in reducing pruritus and improving quality of life in hemodialysis patients.https://www.frontiersin.org/articles/10.3389/fphar.2025.1583515/fullCKD-aPHSK21542hemodialysisκ-opioid receptor agonisturemic pruritus |
| spellingShingle | Ming-Ming Pan Min Gao Li Zhou Yan Xu Li Yao Chao-Qing Wu Chang-Lin Mei Chang-Lin Mei Zhan-Zheng Zhao Dong Sun Tian-Jun Guan Qin-Kai Chen Ming Shi Hui Xu Ya-Ming Li Wan-Yun Zhao Rui Yan Bi-Cheng Liu Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trial Frontiers in Pharmacology CKD-aP HSK21542 hemodialysis κ-opioid receptor agonist uremic pruritus |
| title | Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trial |
| title_full | Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trial |
| title_fullStr | Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trial |
| title_full_unstemmed | Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trial |
| title_short | Efficacy and safety of HSK21542 for pruritus management in hemodialysis patients: a multicenter, randomized, double-blind, placebo-controlled trial |
| title_sort | efficacy and safety of hsk21542 for pruritus management in hemodialysis patients a multicenter randomized double blind placebo controlled trial |
| topic | CKD-aP HSK21542 hemodialysis κ-opioid receptor agonist uremic pruritus |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1583515/full |
| work_keys_str_mv | AT mingmingpan efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT mingao efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT lizhou efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT yanxu efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT liyao efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT chaoqingwu efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT changlinmei efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT changlinmei efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT zhanzhengzhao efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT dongsun efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT tianjunguan efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT qinkaichen efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT mingshi efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT huixu efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT yamingli efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT wanyunzhao efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT ruiyan efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial AT bichengliu efficacyandsafetyofhsk21542forpruritusmanagementinhemodialysispatientsamulticenterrandomizeddoubleblindplacebocontrolledtrial |