The efficacy and safety of inhaled peptide YKYY017 for COVID-19 patients with mild illness: a phase 2 randomized controlled trial
Yeming Wang, Lianhan Shang, Lei Wu, Xia Wang, Banghan Ding, Ke Hu, Yingli He, Guangming Li, Jie Zhai, Junyan Hu, Yingping Tian, Jun Wang, Li Yan, Bin Liu, Gengshen Song, Yuxian He, Chen Wang, Bin Cao
doi:10.1038/s41467-025-62214-x
YKYY017 is a SARS-CoV-2 membrane fusion inhibitor. We report efficacy and safety of inhaled YKYY017 for COVID-19 patients with mild to moderate illness from a phase 2 trial (ChiCTR2300075467). 239 patients aged 18-75 years with mostly mild COVID-19 were randomly allocated to receive aerosol inhalation of 10 or 20 mg YKYY017 or placebo once daily. The primary endpoint is the change in SARS-CoV-2 viral load from baseline to Day 4. The mean (±SE) differences in viral load change from baseline were -0.48 ± 0.27 log 10 copies/mL (95% CI, -1.01 to 0.06) for the 20 mg group and -0.27 ± 0.27 log 10 copies/mL (95% CI, -0.79 to 0.26) for the 10 mg group, compared to the placebo group. Viral load changes at visits other than Day 4 did not differ significantly from placebo in either the 10 or 20 mg YKYY017 groups. The time to sustained symptom recovery was shorter in the 20 mg YKYY017 group (median 117.53, 95%CI 95.33 to 141.45 hours) than in the placebo group (median 143.00, 95%CI 139.17 to 186.87 hours; HR 1.552, 95%CI 1.089 to 2.214, p = 0.0151), whereas the 10 mg YKYY017 group showed a similar but not statistically significant trend compared to placebo (p = 0.0833). The time to sustained symptom alleviation was shorter in both the 20 and 10 mg YKYY017 groups than in the placebo group. The adverse events were mostly mild to moderate. The primary outcome was not met. Following a supplementary phase 1b trial, we are planning another phase 2/3 trial using a twice-daily 20 mg YKYY017 regimen to further assess efficacy and safety. Despite World Health Organization (WHO)'s declaration of ending the COVID-19 public health emergency in May 2023 1 , SARS-CoV-2 continues to cause several waves of infections annually across various geographic regions. The summer of 2024 witnessed a notable spike in COVID-19 cases, underscoring the persistent threat of COVID-19 and the need for effective treatment strategies 2 . While several small-molecule oral antivirals have gained regulatory approval, concerns about systemic adverse effects have driven the development of alternative drug delivery methods 3 . Moreover, some oral antivirals require co-administration with ritonavir, presenting clinical management challenges for patients with underlying health conditions 4 . Inhaled antiviral provides the potential for rapid and
Methods
Trial design This trial was a phase 2 randomized double-blind clinical trial to evaluate the efficacy and safety of YKYY017 aerosol inhalation in the treatment of patients with mild to moderate COVID-19 (Trial registration: ChiCTR2300075467). We enrolled patients aged 18 to 75 years with mild to moderate COVID-19. We conducted the trial in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. This trial was approved by the ethics committee in China-Japan Friendship Hospital (approval number: YM2023-043-02) and the ethics committee at each participating center. Written informed consent was obtained from all participants or their legal representatives.
Reporting summary Further information on research design is available in the Nature Portfolio Reporting Summary linked to this article.
Author contributions
Additional information Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41467-025-62214-x . Correspondence and requests for materials should be addressed to Gengshen Song, Yuxian He, Chen Wang or Bin Cao. Peer review information Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work. A peer review file is available. Reprints and permissions information is available at http://www.nature.com/reprints Publisher's note Springer Nature remains neutral with regard to..
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