2. Academic Validation
  3. Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects

  • Acta Pharmacol Sin. 2022 Mar 16;1-9. doi: 10.1038/s41401-022-00895-6.
Hong-Jie Qian 1 2,  Yu Wang 3,  Meng-Qi Zhang 1 2,  Yuan-Chao Xie 3 4,  Qing-Qing Wu 1 2,  Li-Yu Liang 1 2,  Ye Cao 1 2,  Hua-Qing Duan 5,  Guang-Hui Tian 5,  Juan Ma 6,  Zhuo-Bing Zhang 6,  Ning Li 6,  Jing-Ying Jia 1 2,  Jing Zhang 7,  Haji Akber Aisa 8,  Jing-Shan Shen 2 3,  Chen Yu 1 2,  Hua-Liang Jiang 2 4 9,  Wen-Hong Zhang 10,  Zhen Wang 11 12 13,  Gang-Yi Liu 14 15
Affiliations

Affiliations

  • 1 Central Laboratory, Shanghai Xuhui Central Hospital/Xuhui Hospital, Fudan University, Shanghai, 200031, China.
  • 2 Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, 200031, China.
  • 3 CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 4 Lingang Laboratory, Shanghai, 201602, China.
  • 5 Clinical Department, Vigonvita Life Sciences Co., Ltd, Suzhou, 215123, China.
  • 6 Research and Development Department, Shanghai Junshi Biosciences Co., Ltd, Shanghai, 200126, China.
  • 7 Phase 1 Clinical Research Center, Huashan Hospital, Fudan University, Shanghai, 200040, China.
  • 8 State Key Laboratory Basis of Xinjiang Indigenous Medicinal Plants Resource Utilization, Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi, 830011, China.
  • 9 State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
  • 10 Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 200040, China. zhangwenhong@fudan.edu.cn.
  • 11 Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, 200031, China. wangzhen@lglab.ac.cn.
  • 12 CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. wangzhen@lglab.ac.cn.
  • 13 Lingang Laboratory, Shanghai, 201602, China. wangzhen@lglab.ac.cn.
  • 14 Central Laboratory, Shanghai Xuhui Central Hospital/Xuhui Hospital, Fudan University, Shanghai, 200031, China. gyliu@shxh-centerlab.com.
  • 15 Shanghai Engineering Research Center of Phase I Clinical Research and Quality Consistency Evaluation for Drugs, Shanghai, 200031, China. gyliu@shxh-centerlab.com.
PMID: 35296780 DOI: 10.1038/s41401-022-00895-6
Abstract

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.

Keywords

SARS-CoV-2; VV116; healthy subjects; nucleoside analog; pharmacokinetics; safety.

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