雾化聚乙二醇化干扰素α-2b在健康成年人中的安全性、耐受性、药代动力学和药效学：一项随机1期试验。

The safety, tolerability, pharmacokinetics, and pharmacodynamics of nebulized pegylated interferon α-2b in healthy adults: a randomized phase 1 trial.

作者信息

Huang Wenqi, Kang Yanneng, Zhao Yajun, Yang Jiao, Dai Changjuan, Wu Weibing, Xu Jinchao, Jin Wen, Wu Xiaolu, Zhou Qing

机构信息

Department of Hepatology, Xiamen Humanity Hospital Fujian Medical University, Xiamen, Fujian, 361000, China.

出版信息

BMC Pharmacol Toxicol. 2025 May 12;26(1):99. doi: 10.1186/s40360-025-00937-9.

DOI:10.1186/s40360-025-00937-9

PMID:40355915

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12070635/

Abstract

BACKGROUND

Interferons (IFNs) are proteins that combat viruses and regulate the immune system. Studies have demonstrated that aerosol inhalation of IFNα is both effective and safe for treating respiratory infections. However, IFNα has a short half-life and is rapidly cleared by lung defenses. Polyethylene glycol (PEG) ylation is a common strategy to extend the duration of drug action. PegIFNα-2b is a long-acting interferon formed by the covalent binding of 40 kDa Y-shaped branched PEG with recombinant human IFNα-2b. This study aimed to assess the safety, tolerability, pharmacokinetic, and pharmacodynamic characteristics of nebulized PegIFNα-2b in healthy adult subjects, providing guidance for further clinical investigations.

METHODS

This study employed a randomized, controlled clinical trial design with a total of 18 healthy adult subjects enrolled. Participants were randomly assigned in a 1:1:1 ratio to three groups. Treatment group 1 and group 2 received 90 µg and 180 µg of nebulized PegIFNα-2b, respectively, while the control group was administered a combination of 180 µg PegIFNα-2b and 15 mg inhalable Ambroxol Hydrochloride solution, all in a single dose. Safety, tolerability, and blood drug concentration were assessed, along with blood neopterin levels for pharmacokinetic and pharmacodynamic evaluation.

RESULTS

The incidence of adverse events (AEs) was 38.9% (7/18) with no significant difference among the groups (P > 0.05). AEs included anemia (N = 5) and leukopenia (N = 2), predominantly of grade 1 severity (6/7), with no severe events. Blood PegIFNα-2b concentrations were below detection limits in most subjects, except one in treatment group 2. Neopterin levels were generally low in treatment group 1 and the control group, with slightly higher observed in most subjects of treatment group 2, but differences were not significant (P > 0.05).

CONCLUSIONS

Nebulized PegIFNα-2b at doses of 90 µg and 180 µg showed acceptable safety and tolerability. Minimal systemic absorption was observed following inhalation. Further studies are needed to explore its potential, especially in patients with lower respiratory tract infections.

CLINICAL TRIAL REGISTRATION

ChiCTR2300074909, retrospectively registered in https://www.chictr.org.cn/ at 20 August 2023.

摘要

背景

干扰素（IFNs）是对抗病毒和调节免疫系统的蛋白质。研究表明，雾化吸入干扰素α治疗呼吸道感染既有效又安全。然而，干扰素α半衰期短，会被肺部防御系统迅速清除。聚乙二醇（PEG）化是延长药物作用持续时间的常用策略。聚乙二醇化干扰素α-2b是由40 kDa Y形支链PEG与重组人干扰素α-2b共价结合形成的长效干扰素。本研究旨在评估雾化聚乙二醇化干扰素α-2b在健康成年受试者中的安全性、耐受性、药代动力学和药效学特征，为进一步的临床研究提供指导。

方法

本研究采用随机对照临床试验设计，共纳入18名健康成年受试者。参与者按1:1:1的比例随机分为三组。治疗组1和治疗组2分别接受90 μg和180 μg的雾化聚乙二醇化干扰素α-2b，而对照组接受180 μg聚乙二醇化干扰素α-2b和15 mg可吸入盐酸氨溴索溶液的组合，均为单次给药。评估安全性、耐受性和血药浓度，以及血中新蝶呤水平进行药代动力学和药效学评估。

结果

不良事件（AEs）发生率为38.9%（7/18），各组间无显著差异（P>0.05）。不良事件包括贫血（N = 5）和白细胞减少（N = 2），主要为1级严重程度（6/7），无严重事件。除治疗组2中的1名受试者外，大多数受试者的血聚乙二醇化干扰素α-2b浓度低于检测限。治疗组1和对照组的新蝶呤水平普遍较低，治疗组2的大多数受试者中观察到略高，但差异不显著（P > 0.05）。