Efficacy and Safety of HSK21542 for Pruritus Management in Hemodialysis Patients: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial

Mingming Pan¹Min Gao¹Li Zhou²Yan Xu³Li Yao⁴Chao-Qing Wu⁵Changlin Mei^6,7Zhanzheng Zhao⁸Dong Sun⁹Tianjun Guan¹⁰QINKAI CHEN¹¹Ming Shi¹²Hui Xu¹³Ya-Ming Li¹⁴Wan-Yun Zhao¹⁴Rui Yan¹⁵Bi-Cheng Liu^1*

• ¹Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, China
• ²Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, China
• ³Department of Nephrology, The Affiliated Hospital of Qingdao University, Qingdao, China
• ⁴Department of Nephrology, The First Hospital of China Medical University, Shenyang, China
• ⁵Department of Nephrology, The People’s Hospital of Guangxi Zhuang Autonomous Region,, Nanning, China
• ⁶Department of Nephrology, Changzheng Hospital, Second Military Medical University, Shanghai, China
• ⁷Department of Nephrology, Zhabei Central Hospital of JingAn District of Shanghai, Shanghai, China
• ⁸Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China
• ⁹Department of Nephrology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, China
• ¹⁰Department of Nephrology, Zhongshan Hospital, Xiamen University, Xiamen, China
• ¹¹Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang, China
• ¹²Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan, China
• ¹³Department of Nephrology, Xiangya Hospital of the Central South University, Changsha, China
• ¹⁴Haisco Pharmaceutical Group Co., Ltd., Chengdu, China
• ¹⁵Department of Nephrology, Affiliated Hospital of Guizhou Medical University, Guiyang, China

Background: Chronic 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. Methods: Adult 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.Results: A 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. Conclusion: The 0.3 μg/kg dose of HSK21542 demonstrated superior efficacy and safety in reducing pruritus and improving quality of life in hemodialysis patients.