Tolerability, pharmacokinetics and antiviral activity of rHSA/IFNα2a for the treatment of chronic hepatitis B infection
Tolerability, pharmacokinetics and antiviral activity of rHSA/IFNα2a for the treatment of chronic hepatitis B infection
复制标题
rHSA/IFN α 2a 治疗慢性乙型肝炎感染的耐受性、药代动力学和抗病毒活性
DOI：
10.1111/bcp.13184
复制
发表时间：
2017-05-01
影响因子：
3.4
通讯作者：
Niu, Junqi
中科院分区：
文献类型：
--
作者：
Ding, Yanhua;Lou, Jinfeng;Niu, Junqi
AIMSA重组人血清白蛋白-干扰素α 2a融合蛋白（rHSA/IFN α 2a）有望延长IFN α 2a的半衰期。本研究旨在评价rHSA/IFN α 2a的耐受性、安全性和有效性。一组32名未接受过治疗的非肝炎慢性B型肝炎患者被分为4个队列，每个队列接受600、750或900 μ g rHSA/IFN α 2 a或180 μ g PEG-IFN α 2 a治疗3个月。对耐受性、药代动力学和抗病毒反应进行了评估。32例入选患者中有31例完成了治疗研究。血细胞计数和更高的血清白蛋白水平证明，rHSA/IFN α 2a治疗比PEG-IFN α 2a 180 μ g治疗的耐受性更好。rHSA/IFN α 2a的半衰期（t（1/2））估计为120-140 h，可能适用于2周或更长的给药间隔。除t（1/2）外，rHSA/IFN α 2a 750 μ g和PEG-IFN α 2a 180 μ g之间末次给药的药代动力学相当，在两组中观察到相似的抑制HBV DNA复制的动力学。600、750和900 μ g rHSA/IFN α 2a组和PEG-IFN α 2a组治疗后血清HBV DNA水平的平均下降分别为-1.32、-2.13、-1.10和-2.48 log 10 IU/ml。在PEG-IFN α 2a和rHSA/IFN α 2a 750 μ g组中观察到相似的抑制HBV复制的功效。
AIMSA recombinant human serum albumin-interferon alpha2a fusion protein (rHSA/IFN alpha 2a) is expected to extend the half-life of IFNa2a. This study aims to evaluate the tolerability, safety and efficacy of rHSA/IFN alpha 2a.METHODSThis is an open, randomized, positive control, multiple-dose ascending Phase Ib study. A panel of 32 treatment naive and noncirrhotic chronic hepatitis B patients were divided into four cohorts, and each received 600, 750 or 900 mu g of rHSA/IFNa2a or 180 mu g of PEG-IFN alpha 2a for 3 months. Tolerability, pharmacokinetics and antiviral responses were assessed.RESULTSThirty-one of 32 enrolled patients completed the treatment study. The rHSA/IFN alpha 2a treatment was better tolerated than the PEG-IFN alpha 2a 180 mu g treatment, as evidenced by blood cell counts and higher serum albumin levels. Half-life (t(1/2)) of rHSA/IFN alpha 2a was estimated to be 120-140 h, and is potentially suitable for a dosing interval of 2 weeks or longer. Pharmacokinetics of the last dose between rHSA/IFN alpha 2a 750 mu g and PEG-IFN alpha 2a 180 mu g, with the exception of t(1/2), was comparable, and a similar kinetics of inhibiting HBV DNA replication was observed in both groups. Mean reductions in serum HBV DNA levels after treatment were -1.32, -2.13, -1.10 and -2.48 log10 IU/ml in the 600, 750 and 900 mu g rHSA/IFN alpha 2a groups and PEG-IFN alpha 2a group, respectively.CONCLUSIONSThe rHSA/IFN alpha 2a treatment was well tolerated and can be administered biweekly. Similar efficacy in inhibiting HBV replication was observed in both PEG-IFN alpha 2a and rHSA/IFN alpha 2a 750 mu g groups.