Liu Yan, Zhai Guanxing, Fu Weihui, Zhang Xiaoyan, Xu Jianqing
Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
National Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Pharmacol. 2022 Dec 12;13:1063106. doi: 10.3389/fphar.2022.1063106. eCollection 2022.
Coronavirus disease 2019 (COVID-19) has caused global pandemics in the last 3 years, and the development of new therapeutics is urgently needed. This study aimed to assess the safety, tolerated, and prolonged retention of recombinant protein trefoil factor 2 (TFF2)- interferon (IFN) in the respiratory tract of healthy volunteers. We conducted a randomized, double-blind, placebo-controlled, single-dose, dose-escalation phase I study to evaluate safety, tolerability, pharmacokinetics (PK), and cytokine responses after administration of recombinant TFF2-IFN proteins. Healthy volunteers were informed, enrolled, and randomized into four groups with a dose escalation of 0.2, 1, 2, and 4 mg and then inhaled the investigation product or placebo. Thirty-two eligible participants were finally enrolled; eight were assigned to the placebo group and 24 to the TFF2-IFN group, with six participants per group. Data were collected from 19 November 2021, to 4 January 2022. All 32 participants completed the study. Of the participants who received the recombinant TFF2-IFN protein, 41.7% (10/24) reported 11 adverse events (AEs) during treatment and 62.5% (5/8) of those who received a placebo reported six AEs. Sixteen of the 17 AEs were grade 1. Only one grade 3 AE occurred in the placebo group and no worse event occurred as a serious adverse event. The pharmacokinetics was analyzed for times and concentrations of the investigation products in 0.2, 1, 2, and 4 mg groups in 24 recipients of TFF2-IFN, and the results showed that TFF2-IFN was retained in the lung for at least 6-8 h. Only the highest dose group (4 mg) had a transient detectable concentration in serum, while all other dose groups had a level below the lower limit of quantification. In this study, the recombinant TFF2-IFN protein was a well-tolerated and safe therapeutic when administered by nebulization, characterized by prolonged retention in the respiratory tract, which would be greatly beneficial in combating respiratory viral infection. : [http://www.chictr.org.cn], identifier [ChiCTR2000035633].
2019年冠状病毒病（COVID-19）在过去3年中引发了全球大流行，因此迫切需要开发新的治疗方法。本研究旨在评估重组蛋白三叶因子2（TFF2）-干扰素（IFN）在健康志愿者呼吸道中的安全性、耐受性和延长滞留情况。我们进行了一项随机、双盲、安慰剂对照、单剂量、剂量递增的I期研究，以评估重组TFF2-IFN蛋白给药后的安全性、耐受性、药代动力学（PK）和细胞因子反应。健康志愿者被告知相关信息后入组，并随机分为四组，剂量分别递增为0.2、1、2和4毫克，然后吸入研究产品或安慰剂。最终招募了32名符合条件的参与者；8人被分配到安慰剂组，24人被分配到TFF2-IFN组，每组6名参与者。数据收集时间为2021年11月19日至2022年1月4日。所有32名参与者均完成了研究。在接受重组TFF2-IFN蛋白的参与者中，41.7%（10/24）在治疗期间报告了11起不良事件（AE），而接受安慰剂的参与者中有62.5%（5/8）报告了6起AE。17起AE中有16起为1级。安慰剂组仅发生1起3级AE，未发生更严重的不良事件。对24名接受TFF2-IFN的参与者中0.2、1、2和4毫克组的研究产品的时间和浓度进行了药代动力学分析，结果表明TFF2-IFN在肺中至少保留6-8小时。只有最高剂量组（4毫克）在血清中有短暂的可检测浓度，而所有其他剂量组的水平均低于定量下限。在本研究中，重组TFF2-IFN蛋白通过雾化给药时耐受性良好且安全，其特点是在呼吸道中滞留时间延长，这将对对抗呼吸道病毒感染非常有益。注册号：[http://www.chictr.org.cn]，标识符[ChiCTR2000035633]
