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
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)- interf...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1063106/full |
| _version_ | 1811188057665175552 |
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| author | Yan Liu Yan Liu Guanxing Zhai Weihui Fu Xiaoyan Zhang Xiaoyan Zhang Jianqing Xu Jianqing Xu |
| author_facet | Yan Liu Yan Liu Guanxing Zhai Weihui Fu Xiaoyan Zhang Xiaoyan Zhang Jianqing Xu Jianqing Xu |
| author_sort | Yan Liu |
| collection | DOAJ |
| description | 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]. |
| first_indexed | 2024-04-11T14:13:04Z |
| format | Article |
| id | doaj.art-f90200728a284e88a7cb709a858dda40 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-04-11T14:13:04Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Pharmacology |
| spelling | doaj.art-f90200728a284e88a7cb709a858dda402022-12-22T04:19:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-12-011310.3389/fphar.2022.10631061063106A randomized, double-blind, placebo-controlled phase I trial of inhalation treatment of recombinant TFF2-IFN protein: A multifunctional candidate for the treatment of COVID-19Yan Liu0Yan Liu1Guanxing Zhai2Weihui Fu3Xiaoyan Zhang4Xiaoyan Zhang5Jianqing Xu6Jianqing Xu7Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaNational Research Center for Translational Medicine at Shanghai, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaInstitutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, ChinaShanghai Public Health Clinical Center, Fudan University, Shanghai, ChinaBackground 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].https://www.frontiersin.org/articles/10.3389/fphar.2022.1063106/fullrespiratory viral infectionCOVID-19IFNTFF2safety |
| spellingShingle | Yan Liu Yan Liu Guanxing Zhai Weihui Fu Xiaoyan Zhang Xiaoyan Zhang Jianqing Xu Jianqing Xu 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 Frontiers in Pharmacology respiratory viral infection COVID-19 IFN TFF2 safety |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | respiratory viral infection COVID-19 IFN TFF2 safety |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1063106/full |
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