Pan Ming-Ming, Gao Min, Zhou Li, Xu Yan, Yao Li, Wu Chao-Qing, Mei Chang-Lin, Zhao Zhan-Zheng, Sun Dong, Guan Tian-Jun, Chen Qin-Kai, Shi Ming, Xu Hui, Li Ya-Ming, Zhao Wan-Yun, Yan Rui, Liu Bi-Cheng
Institute of Nephrology, Zhong Da Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, China.
Department of Nephrology, Kidney Research Institute, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Front Pharmacol. 2025 Jun 24;16:1583515. doi: 10.3389/fphar.2025.1583515. eCollection 2025.
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.
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.
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.
The 0.3 μg/kg dose of HSK21542 demonstrated superior efficacy and safety in reducing pruritus and improving quality of life in hemodialysis patients.
慢性肾脏病相关性瘙痒（CKD-aP）是血液透析患者常见且令人苦恼的症状。这项II期试验评估了选择性κ阿片受体激动剂HSK21542治疗CKD-aP的疗效和安全性。
患有中度至重度瘙痒的成年血液透析患者按1:1:1随机分为安慰剂组，或每周透析后三次给予HSK21542（0.3μg/kg或0.6μg/kg），共12周。主要终点是第12周时每周最差瘙痒强度数字评定量表（WI-NRS）评分的基线变化。次要终点包括生活质量评估、安全性评估和药代动力学特性。
共纳入90例患者。在第12周时，安慰剂组WI-NRS评分相对于基线的平均变化为-2.94，0.3μg/kg HSK21542组为-3.40，0.6μg/kg HSK21542组为-2.21。WI-NRS评分降低3分或以上的患者百分比在安慰剂组为44.4%，0.3μg/kg HSK21542组为62.1%，0.6μg/kg HSK21542组为37.0%。与安慰剂相比，0.30μg/kg HSK21542组在Skindex-16评分方面有更显著改善。5-D瘙痒量表评分也呈现类似趋势。0.3μg/kg和0.6μg/kg剂量的HSK21542耐受性良好，无剂量依赖性不良反应。
0.3μg/kg剂量的HSK21542在减轻血液透析患者瘙痒和改善生活质量方面显示出卓越的疗效和安全性。
