SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19.
SARS-CoV-2 Neutralizing Antibody LY-CoV555 in Outpatients with Covid-19.
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DOI：
10.1056/nejmoa2029849
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发表时间：
2021-01-21
期刊：
影响因子：
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通讯作者：
BLAZE-1 Investigators
中科院分区：
文献类型：
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作者：
Chen P;Nirula A;Heller B;Gottlieb RL;Boscia J;Morris J;Huhn G;Cardona J;Mocherla B;Stosor V;Shawa I;Adams AC;Van Naarden J;Custer KL;Shen L;Durante M;Oakley G;Schade AE;Sabo J;Patel DR;Klekotka P;Skovronsky DM;BLAZE-1 Investigators
严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起2019冠状病毒病（Covid-19），这种疾病通常是轻度的，但可能是严重的并危及生命。预计病毒中和单克隆抗体可降低病毒载量，改善症状，并防止住院治疗。在这项正在进行的II期试验中，我们将452名患者随机分配接受单次静脉输注中和抗体LY-CoV 555（三种剂量（700 mg，2800 mg或7000 mg）或安慰剂），并评估了定量病毒学终点和临床结局。主要结局是第11天病毒载量较基线的变化。本文报告了截至2020年9月5日的预先计划中期分析结果。在中期分析时，观察到整个人群的病毒载量对数较基线平均降低为−3.81，消除了99.97%以上的病毒RNA。对于接受2800 mg剂量LY-CoV 555的患者，与安慰剂相比，病毒载量较基线降低的差异为-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。在接受700 mg剂量（−0.20; 95% CI，−0.66至0.25; P=0.38）或7000 mg剂量（0.09; 95% CI，−0.37至0.55; P=0.70）的患者中，观察到与安慰剂相比基线变化的差异较小。在第2 - 6天，接受LY-CoV 555的患者的症状严重程度略低于接受安慰剂的患者。LY-CoV 555组中，发生与COVID-19相关的住院或急诊就诊的患者比例为1.6%，安慰剂组为6.3%。在这项2期试验的中期分析中，中和抗体LY-CoV 555的三种剂量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，NCT 04427501。）
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. 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. 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. 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.)