Wang Xinrui, Li Wanyu, Kong Fei, Guo Xiaolin, Jin Qinglong, Gao Runping, Hu Yulin, Cai Yanjun, Xin Guijie, Ji Huifan, Piao Hongxin, Fu Zhaoxu, Wang Yifei, Piao Zhiyong, Wang Siqi, Hua Rui, Wen Xiaoyu, Qi Yue, Jin Jinglan, Wang Chong, Wang Zhongfeng, Xu Fang, Zhou Qiang, Li Xu, Yu Ge, Wang Yang, Yang Tao, Xiang Wei, Pan Yu, Niu Junqi, Gao Yanhang
Department of Hepatology, Center of Infectious Diseases and Pathogen Biology, The First Hospital of Jilin University, Changchun, 130021, China.
Jilin Provincial Key Laboratory of Metabolic Liver Diseases, Jilin University, Changchun, 130021, China.
Hepatol Int. 2025 Jul 23. doi: 10.1007/s12072-025-10871-x.
Recombinant human serum albumin (rHA) is a promising alternative to human serum albumin (HSA) for managing ascites in cirrhotic patients. This phase Ib study aims to assess the safety, tolerability, and pharmacokinetics/pharmacodynamics (PK/PD) profiles of rHA in this population.
This randomized, open-label, phase Ib trial was conducted between December 2019 and September 2020 at 3 medical centers in China. Patients with cirrhotic ascites were randomly assigned to receive rHA or HSA at 10 g/day, 20 g/day, or 30 g/day. Each group had 12 participants (nine receiving rHA and three receiving HSA as positive control). Treatment lasted up to 14 days or until serum albumin levels reached 35 g/L, followed by a 28-day follow-up. Adverse events monitored assessed safety and tolerability, while PK/PD was evaluated by tracking serum albumin levels and plasma colloid osmotic pressure (PCOP) before and after each dose (ClinicalTrials.gov No. NCT04701697).
Thirty-six Chinese participants were enrolled, with 32 completing the study. The incidence of adverse events was similar between the rHA and HSA groups (44.4% vs. 44.4%, p > 0.05). Serum albumin concentration increases were comparable between groups during treatment and follow-up. While most participants experienced weight and abdominal circumference decreases, no significant dose effect was observed (p > 0.05). No anti-drug antibodies were detected.
In this study, rHA demonstrated similar safety and PK/PD to HSA in cirrhotic patients with ascites. rHA was well-tolerated, supporting the need to evaluate its safety and efficacy in a phase II clinical study.
重组人血清白蛋白（rHA）是用于治疗肝硬化患者腹水的一种有前景的人血清白蛋白（HSA）替代物。这项Ib期研究旨在评估rHA在该人群中的安全性、耐受性以及药代动力学/药效学（PK/PD）特征。
这项随机、开放标签的Ib期试验于2019年12月至2020年9月在中国的3个医学中心进行。肝硬化腹水患者被随机分配接受10g/天、20g/天或30g/天的rHA或HSA。每组有12名参与者（9名接受rHA，3名接受HSA作为阳性对照）。治疗持续长达14天或直至血清白蛋白水平达到35g/L，随后进行28天的随访。监测不良事件以评估安全性和耐受性，同时通过跟踪每次给药前后的血清白蛋白水平和血浆胶体渗透压（PCOP）来评估PK/PD（ClinicalTrials.gov编号：NCT04701697）。
36名中国参与者入组，32名完成研究。rHA组和HSA组不良事件的发生率相似（44.4%对44.4%，p>0.05）。治疗期间和随访期间各组血清白蛋白浓度升高相当。虽然大多数参与者体重和腹围下降，但未观察到显著的剂量效应（p>0.05）。未检测到抗药抗体。
在本研究中，rHA在肝硬化腹水患者中显示出与HSA相似的安全性和PK/PD。rHA耐受性良好，支持在II期临床研究中评估其安全性和有效性的必要性。
