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A Randomized, Double-Blind, Placebo-Controlled Phase I Trial of Inhalation Treatment of Recombinant TFF2/IFN Protein: A Multifunctional Candidate for Treatment of COVID-19

23 Pages Posted: 26 Aug 2022

See all articles by Yan Liu

Yan Liu

Fudan University - Institutes of Biomedical Sciences

Guanxing Zhai

Fudan University - Shanghai Public Health Clinical Center

Weihui Fu

Fudan University - Shanghai Public Health Clinical Center

Xiaoyan Zhang

Fudan University - Institutes of Biomedical Sciences

Jianqing Xu

Fudan University - Institutes of Biomedical Sciences

More...

Abstract

Background: Coronavirus disease 2019 (COVID-19) caused global pandemics during last three years, the development of new therapeutics is urgently needed.

Methods: We conducted a randomized, double-blind, placebo-controlled, single-dose, dose-escalation Phase Ⅰ study to evaluate the safety, tolerability, pharmacokinetics (PK) and cytokine responses after the administration of the recombinant TFF2-IFN proteins. Healthy volunteers were informed, enrolled and randomized into 4 groups with a dose escalation of 0.2, 1, 2, 4 mg/per dose, and then inhaled with the investigation product (IP) or placebo. 32 eligible participants were finally enrolled, 8 were assigned to placebo group and 24 to TFF2-IFN groups with 6 participants per group.

Findings: All 32 participants completed the study. 41.7% (10/24) of participants who received recombinant TFF2-IFN protein reported 11 AEs during treatment, and 62.5% (5/8) of participants who received placebo reported 6 AEs. 16 out of total 17 AEs were Grade 1 in severity. Only one Grade 3 AE was occurred in placebo group, and no worse event happened as SAE. The PK were analyzed for the times and concentrations of investigation product in 0.2, 1, 2, 4mg groups in 24 TFF2-IFN recipients, the results showed that TFF2-IFN retains in the lung for at least 6-8 hours, only the highest dose group (4mg/per) has a transient detectable concentration in sera, whereas all other dose groups had a level below the lower limit of quantification (LLOQ). In addition, only IFN-gamma was detectable and none of inflammatory cytokines appeared in sera.

Interpretation: In summary, the recombinant TFF2-IFN protein was a well-tolerated and safe therapeutics when administrated through nebulization, featured with prolonged retention in respiratory tract which will be greatly beneficial to combat against respiratory viral infection.

Trial Registration Details: The study was registered with Chinese Clinical Trial Register (Website: http://www.chictr.org.cn), ChiCTR2000035633.

Funding Information: We would like to thank Tree-year Action Plan for Shenkang Clinical Research from Shanghai Municipal Health Commission (SHDC2020CR3011A), the National Natural Science Foundation of China (82071788), Shanghai Jinshan Medical Health Science and Technology Innovation Fund Project (No. 2021-3-503), Shanghai Public Health Clinical Center, Fudan University, Shanghai, People's Republic of China Fund Project (No. KY-GW-2021-06), and the Special Medical Innovation Research Project of “Scientific and Technological Innovation Action Plan” of Shanghai Municipal Commission of Science and Technology in 2020 (20Y11900500) to support this study.

Declaration of Interests: No potential conflict of interest was reported by the author.

Ethics Approval Statement: The study was conducted at the Shanghai Public Health Clinical Center. The protocol and Informed consent were reviewed and approved by the ethic committee.

Keywords: Respiratory viral infection, COVID-19, Interferon, TFF2, Safety

Suggested Citation

Liu, Yan and Zhai, Guanxing and Fu, Weihui and Zhang, Xiaoyan and Xu, Jianqing, A Randomized, Double-Blind, Placebo-Controlled Phase I Trial of Inhalation Treatment of Recombinant TFF2/IFN Protein: A Multifunctional Candidate for Treatment of COVID-19. Available at SSRN: https://ssrn.com/abstract=4201398 or http://dx.doi.org/10.2139/ssrn.4201398

Yan Liu

Fudan University - Institutes of Biomedical Sciences ( email )

Guanxing Zhai

Fudan University - Shanghai Public Health Clinical Center ( email )

Weihui Fu

Fudan University - Shanghai Public Health Clinical Center ( email )

Xiaoyan Zhang (Contact Author)

Fudan University - Institutes of Biomedical Sciences ( email )

Jianqing Xu

Fudan University - Institutes of Biomedical Sciences ( email )