From the Department of Infectious Diseases, Shanghai Institute of Virology (Z. Cao, H.G., W.W., Q.X.), the Department of Emergency Medicine, Shanghai Innovation Center for Digital Medicine (W.G.), the Clinical Research Center, Shanghai National Center for Translational Medicine, State Key Laboratory of Medical Genomics (P.C., Y.X.), the Departments of General Surgery (Y.J., Z.S., Y.S., R.Z.) and Gastroenterology (J.S.), the Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases (Y.Z., G.N.), and Shanghai National Clinical Research Center for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission of the People's Republic of China, Shanghai Key Laboratory for Endocrine Tumors (Y.Z., G.N.), Ruijin Hospital, the Department of Critical Care Medicine, Renji Hospital (S.M., Yuan Gao), the Department of Respiratory Medicine, Xinhua Hospital (Z. Cui), and the Department of Good Clinical Practice Office and Phase I Unit, Tongren Hospital (Q.Z.), Shanghai Jiao Tong University School of Medicine, the Department of Respiratory and Critical Medicine, Shanghai Pudong Hospital, Fudan University Pudong Medical Center (H.B.), the Departments of Pain Rehabilitation (H.F.) and Pharmacology (X.M.), Shanghai Public Health Clinical Center, Fudan University, and the Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine (Yueqiu Gao) - all in Shanghai, China.
N Engl J Med. 2023 Feb 2;388(5):406-417. doi: 10.1056/NEJMoa2208822. Epub 2022 Dec 28.
Nirmatrelvir-ritonavir has been authorized for emergency use by many countries for the treatment of coronavirus disease 2019 (Covid-19). However, the supply falls short of the global demand, which creates a need for more options. VV116 is an oral antiviral agent with potent activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
We conducted a phase 3, noninferiority, observer-blinded, randomized trial during the outbreak caused by the B.1.1.529 (omicron) variant of SARS-CoV-2. Symptomatic adults with mild-to-moderate Covid-19 with a high risk of progression were assigned to receive a 5-day course of either VV116 or nirmatrelvir-ritonavir. The primary end point was the time to sustained clinical recovery through day 28. Sustained clinical recovery was defined as the alleviation of all Covid-19-related target symptoms to a total score of 0 or 1 for the sum of each symptom (on a scale from 0 to 3, with higher scores indicating greater severity; total scores on the 11-item scale range from 0 to 33) for 2 consecutive days. A lower boundary of the two-sided 95% confidence interval for the hazard ratio of more than 0.8 was considered to indicate noninferiority (with a hazard ratio of >1 indicating a shorter time to sustained clinical recovery with VV116 than with nirmatrelvir-ritonavir).
A total of 822 participants underwent randomization, and 771 received VV116 (384 participants) or nirmatrelvir-ritonavir (387 participants). The noninferiority of VV116 to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery was established in the primary analysis (hazard ratio, 1.17; 95% confidence interval [CI], 1.01 to 1.35) and was maintained in the final analysis (median, 4 days with VV116 and 5 days with nirmatrelvir-ritonavir; hazard ratio, 1.17; 95% CI, 1.02 to 1.36). In the final analysis, the time to sustained symptom resolution (score of 0 for each of the 11 Covid-19-related target symptoms for 2 consecutive days) and to a first negative SARS-CoV-2 test did not differ substantially between the two groups. No participants in either group had died or had had progression to severe Covid-19 by day 28. The incidence of adverse events was lower in the VV116 group than in the nirmatrelvir-ritonavir group (67.4% vs. 77.3%).
Among adults with mild-to-moderate Covid-19 who were at risk for progression, VV116 was noninferior to nirmatrelvir-ritonavir with respect to the time to sustained clinical recovery, with fewer safety concerns. (Funded by Vigonvita Life Sciences and others; ClinicalTrials.gov number, NCT05341609; Chinese Clinical Trial Registry number, ChiCTR2200057856.).
奈玛特韦-利托那韦已在许多国家获得紧急使用授权，用于治疗 2019 年冠状病毒病（COVID-19）。然而，供应跟不上全球需求，这就需要更多的选择。VV116 是一种具有抗严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）活性的口服抗病毒药物。
我们在由 SARS-CoV-2 的 B.1.1.529（奥密克戎）变体引起的疫情期间进行了一项 3 期、非劣效性、观察者设盲、随机试验。有轻度至中度 COVID-19 且有进展为重症风险的症状性成年人被分配接受为期 5 天的 VV116 或奈玛特韦-利托那韦治疗。主要终点是通过第 28 天持续临床康复的时间。持续临床康复定义为所有 COVID-19 相关目标症状缓解，每个症状的总分（总分范围为 0 至 3，分数越高表示症状越严重；11 项症状量表的总分范围为 0 至 33）连续 2 天降至 0 或 1。双侧 95%置信区间下限大于 0.8 的风险比被认为是非劣效性（风险比>1 表示 VV116 比奈玛特韦-利托那韦更快达到持续临床康复）。
共有 822 名参与者接受了随机分组，其中 771 名接受了 VV116（384 名参与者）或奈玛特韦-利托那韦（387 名参与者）。在主要分析中，VV116 在持续临床康复时间方面不劣于奈玛特韦-利托那韦（风险比，1.17；95%置信区间[CI]，1.01 至 1.35），在最终分析中也得到了维持（中位数，VV116 为 4 天，奈玛特韦-利托那韦为 5 天；风险比，1.17；95%CI，1.02 至 1.36）。在最终分析中，两组之间持续症状缓解（11 项 COVID-19 相关目标症状中每个症状的评分连续 2 天均为 0）和首次 SARS-CoV-2 检测转阴的时间没有显著差异。两组均无参与者在第 28 天死亡或进展为重症 COVID-19。VV116 组的不良事件发生率低于奈玛特韦-利托那韦组（67.4%比 77.3%）。
在有进展为重症风险的轻度至中度 COVID-19 成年人中，VV116 在持续临床康复时间方面不劣于奈玛特韦-利托那韦，且安全性顾虑更少。（由 Vigonvita 生命科学等资助；临床试验.gov 编号，NCT05341609；中国临床试验注册中心编号，ChiCTR2200057856。）
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