PMID- 36578554
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230103
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 13
DP  - 2022
TI  - A randomized, double-blind, placebo-controlled phase I trial of inhalation 
      treatment of recombinant TFF2-IFN protein: A multifunctional candidate for the 
      treatment of COVID-19.
PG  - 1063106
LID - 10.3389/fphar.2022.1063106 [doi]
LID - 1063106
AB  - Background and Objectives: 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. Methods: 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. Results: 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. 
      Conclusion: 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. Systematic Review Registration: 
      [http://www.chictr.org.cn], identifier [ChiCTR2000035633].
CI  - Copyright (c) 2022 Liu, Zhai, Fu, Zhang and Xu.
FAU - Liu, Yan
AU  - Liu Y
AD  - Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - National Research Center for Translational Medicine at Shanghai, Ruijin Hospital 
      Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
FAU - Zhai, Guanxing
AU  - Zhai G
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Fu, Weihui
AU  - Fu W
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Zhang, Xiaoyan
AU  - Zhang X
AD  - Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
FAU - Xu, Jianqing
AU  - Xu J
AD  - Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, 
      Shanghai, China.
AD  - Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
LA  - eng
PT  - Journal Article
DEP - 20221212
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC9790930
OTO - NOTNLM
OT  - COVID-19
OT  - IFN
OT  - TFF2
OT  - respiratory viral infection
OT  - safety
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/12/30 06:00
MHDA- 2022/12/30 06:01
PMCR- 2022/12/12
CRDT- 2022/12/29 02:27
PHST- 2022/10/06 00:00 [received]
PHST- 2022/11/30 00:00 [accepted]
PHST- 2022/12/29 02:27 [entrez]
PHST- 2022/12/30 06:00 [pubmed]
PHST- 2022/12/30 06:01 [medline]
PHST- 2022/12/12 00:00 [pmc-release]
AID - 1063106 [pii]
AID - 10.3389/fphar.2022.1063106 [doi]
PST - epublish
SO  - Front Pharmacol. 2022 Dec 12;13:1063106. doi: 10.3389/fphar.2022.1063106. 
      eCollection 2022.