SARS-CoV-2 中和抗体 LY-CoV555 治疗门诊新冠患者的疗效。
SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19.
机构信息
From the Department of Medicine, Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles (P.C.), and Long Beach Clinical Trials, Long Beach (B.H.) - both in California; Eli Lilly, Indianapolis (A.N., A.C.A., J.V.N., K.L.C., L.S., M.D., G.O., A.E.S., J.S., D.R.P., P.K., D.M.S.), and Franciscan Health, Greenwood (I.S.) - both in Indiana; Baylor University Medical Center and Baylor Scott and White Research Institute, Dallas (R.L.G.); Vitalink Research, Union, SC (J.B.); Imperial Health, Lake Charles, LA (J.M.); Cook County Health (G.H.) and Northwestern University Feinberg School of Medicine (V.S.), Chicago; Indago Research and Health Center, Hialeah, FL (J.C.); and Las Vegas Medical Research Center, Las Vegas (B.M.).
出版信息
N Engl J Med. 2021 Jan 21;384(3):229-237. doi: 10.1056/NEJMoa2029849. Epub 2020 Oct 28.
BACKGROUND
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (Covid-19), which is most frequently mild yet can be severe and life-threatening. Virus-neutralizing monoclonal antibodies are predicted to reduce viral load, ameliorate symptoms, and prevent hospitalization.
METHODS
In this ongoing phase 2 trial involving outpatients with recently diagnosed mild or moderate Covid-19, we randomly assigned 452 patients to receive a single intravenous infusion of neutralizing antibody LY-CoV555 in one of three doses (700 mg, 2800 mg, or 7000 mg) or placebo and evaluated the quantitative virologic end points and clinical outcomes. The primary outcome was the change from baseline in the viral load at day 11. The results of a preplanned interim analysis as of September 5, 2020, are reported here.
RESULTS
At the time of the interim analysis, the observed mean decrease from baseline in the log viral load for the entire population was -3.81, for an elimination of more than 99.97% of viral RNA. For patients who received the 2800-mg dose of LY-CoV555, the difference from placebo in the decrease from baseline was -0.53 (95% confidence interval [CI], -0.98 to -0.08; P = 0.02), for a viral load that was lower by a factor of 3.4. Smaller differences from placebo in the change from baseline were observed among the patients who received the 700-mg dose (-0.20; 95% CI, -0.66 to 0.25; P = 0.38) or the 7000-mg dose (0.09; 95% CI, -0.37 to 0.55; P = 0.70). On days 2 to 6, the patients who received LY-CoV555 had a slightly lower severity of symptoms than those who received placebo. The percentage of patients who had a Covid-19-related hospitalization or visit to an emergency department was 1.6% in the LY-CoV555 group and 6.3% in the placebo group.
CONCLUSIONS
In this interim analysis of a phase 2 trial, one of three doses of neutralizing antibody LY-CoV555 appeared to accelerate the natural decline in viral load over time, whereas the other doses had not by day 11. (Funded by Eli Lilly; BLAZE-1 ClinicalTrials.gov number, NCT04427501.).
背景
严重急性呼吸系统综合症冠状病毒 2（SARS-CoV-2）导致 2019 年冠状病毒病（Covid-19），其通常为轻症，但也可能是重症并危及生命。病毒中和单克隆抗体被预测可以降低病毒载量、改善症状并预防住院。
方法
在这项涉及近期诊断为轻度或中度 Covid-19 的门诊患者的正在进行的 2 期试验中，我们将 452 名患者随机分配接受三种剂量之一（700mg、2800mg 或 7000mg）的中和抗体 LY-CoV555 或安慰剂的单次静脉输注，并评估定量病毒学终点和临床结局。主要结局是第 11 天从基线开始的病毒载量变化。这里报告截至 2020 年 9 月 5 日的预先计划的中期分析结果。
结果
在中期分析时，整个人群从基线开始的病毒载量的观察平均下降为-3.81，这意味着超过 99.97%的病毒 RNA 被消除。与安慰剂相比，接受 LY-CoV555 2800mg 剂量的患者的下降幅度为-0.53（95%置信区间[CI]，-0.98 至-0.08；P=0.02），病毒载量降低了 3.4 倍。接受 700mg 剂量的患者的从基线开始的变化中，与安慰剂相比，差异较小（-0.20；95%CI，-0.66 至 0.25；P=0.38），接受 7000mg 剂量的患者的变化（0.09；95%CI，-0.37 至 0.55；P=0.70）。在第 2 天至第 6 天，接受 LY-CoV555 的患者的症状严重程度略低于接受安慰剂的患者。在 LY-CoV555 组中，有 1.6%的患者因 Covid-19 住院或到急诊室就诊，而安慰剂组为 6.3%。
结论
在这项 2 期试验的中期分析中，三种剂量的中和抗体 LY-CoV555 之一似乎加速了病毒载量随时间的自然下降，而其他剂量在第 11 天没有。（由礼来公司资助；BLAZE-1 ClinicalTrials.gov 编号，NCT04427501）。
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