SARS-CoV-2 Clearance in COVID-19 Patients with Novaferon Treatment: A Randomized, Open-label, Parallel Group Trial

Zheng, Fang; Zhou, Yanwen; Zhou, Zhiguo; Ye, Fei; Huang, Baoying; Huang, Yaxiong; Ma, Jing; Zuo, Qi; Tan, Xin; Xie, Jun; Niu, Peihua; Wang, Wenlong; Xu, Yun; Peng, Feng; Zhou, Ning; Cai, Chunlin; Tang, Wei; Xiao, Xinqiang; Li, Yi; Zhou, Zhiguang; Jiang, Yongfang; Xie, Yuanlin; Tan, Wenjie; Gong, Guozhong

BACKGROUND: The anti-viral effects of Novaferon, a potent antiviral protein drug on COVID-19 was evaluated in laboratory, and in a randomized, open-label, parallel group trial. METHODS: In laboratory, the inhibition of Novaferon on viral replication in cells infected with SARS-CoV-2, and on prevention of SARS-CoV-2 entry into healthy cells was determined. Antiviral effects of Novaferon in COVID-19 patients with treatment of Novaferon, Novaferon plus Lopinavir/Ritonavir, or Lopinavir/Ritonavir were evaluated. The primary endpoint was the SARS-CoV-2 clearance rates on day 6 of treatment, and the secondary endpoint was the time to SARS-CoV-2 clearance. RESULTS: Novaferon inhibited the viral replication (EC(50) = 1.02 ng/ml), and prevented viral infection (EC(50) = 0.10 ng/ml). Results from the 89 enrolled COVID-19 patients showed that both Novaferon and Novaferon plus Lopinavir/Ritonavir groups had significantly higher viral clearance rates on day 6than Lopinavir/Ritonavir group (50.0% vs.24.1%, p = 0.0400, and 60.0% vs.24.1%, p = 0.0053). Median time to viral clearance were 6 days, 6 days, and 9 days for three groups respectively, a 3-dayreductionin both Novaferon and Novaferon plus Lopinavir/Ritonavir groups compared with Lopinavir/Ritonavir group. CONCLUSIONS: Novaferon exhibited anti-SARS-CoV-2 effects in vitro and in COVID-19 patients. These data justified the further evaluation of Novaferon. TRIAL REGISTRATION NUMBER: number ChiCTR2000029496at the Chinese Clinical Trial Registry (http://www.chictr.org.cn/).