REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19.
REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19.
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DOI：
10.1056/nejmoa2035002
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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：
Trial Investigators
中科院分区：
文献类型：
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作者：
Weinreich DM;Sivapalasingam S;Norton T;Ali S;Gao H;Bhore R;Musser BJ;Soo Y;Rofail D;Im J;Perry C;Pan C;Hosain R;Mahmood A;Davis JD;Turner KC;Hooper AT;Hamilton JD;Baum A;Kyratsous CA;Kim Y;Cook A;Kampman W;Kohli A;Sachdeva Y;Graber X;Kowal B;DiCioccio T;Stahl N;Lipsich L;Braunstein N;Herman G;Yancopoulos GD;Trial Investigators
最近的数据表明，2019年冠状病毒病（Covid-19）的并发症和死亡可能与高病毒载量有关。在这项正在进行的双盲1-3期试验中，研究人员研究了两种针对严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）刺突蛋白的完全人类中和单克隆抗体，用于联合鸡尾酒（REGN-COV2）中，以降低出现耐药突变病毒的风险。患者被随机分配（1:1:1）接受安慰剂、2.4 g REGN-COV2或8.0 g REGN-COV2，并在基线时前瞻性地表征针对SARS-CoV-2的内源性免疫反应（血清抗体阳性或血清抗体阴性）。关键终点包括从基线（第1天）到第7天病毒载量的时间加权平均变化，以及到第29天至少有一次与covid -19相关的医疗就诊的患者的百分比。对所有患者进行安全性评估。报告了275名患者的数据。从第1天到第7天，在基线时血清抗体阴性的患者中，病毒载量时间加权平均变化的最小二乘平均差（REGN-COV2联合剂量组与安慰剂组）为- 0.56 log10拷贝/毫升（95%置信区间[CI]， - 1.02至- 0.11），在整个试验人群中为- 0.41 log10拷贝/毫升（95% CI, - 0.71至- 0.10）。在整个试验人群中，安慰剂组中6%的患者和REGN-COV2联合剂量组中3%的患者报告至少有一次就诊；在基线时血清抗体阴性的患者中，相应的百分比分别为15%和6%（差异为- 9个百分点；95% CI， - 29至11）。在REGN-COV2联合剂量组和安慰剂组中，超敏反应、输注相关反应和其他不良事件的患者百分比相似。在这项中期分析中，REGN-COV2抗体鸡尾酒降低了病毒载量，对尚未启动免疫反应或基线时病毒载量高的患者效果更大。REGN-COV2联合剂量组和安慰剂组的安全性结果相似。（由Regeneron制药公司和卫生与人类服务部生物医学和高级研究与发展管理局资助；ClinicalTrials.gov号码：NCT04425629。）
Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads. In this ongoing, double-blind, phase 1–3 trial involving nonhospitalized patients with Covid-19, we investigated two fully human, neutralizing monoclonal antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein, used in a combined cocktail (REGN-COV2) to reduce the risk of the emergence of treatment-resistant mutant virus. Patients were randomly assigned (1:1:1) to receive placebo, 2.4 g of REGN-COV2, or 8.0 g of REGN-COV2 and were prospectively characterized at baseline for endogenous immune response against SARS-CoV-2 (serum antibody–positive or serum antibody–negative). Key end points included the time-weighted average change in viral load from baseline (day 1) through day 7 and the percentage of patients with at least one Covid-19–related medically attended visit through day 29. Safety was assessed in all patients. Data from 275 patients are reported. The least-squares mean difference (combined REGN-COV2 dose groups vs. placebo group) in the time-weighted average change in viral load from day 1 through day 7 was −0.56 log10 copies per milliliter (95% confidence interval [CI], −1.02 to −0.11) among patients who were serum antibody–negative at baseline and −0.41 log10 copies per milliliter (95% CI, −0.71 to −0.10) in the overall trial population. In the overall trial population, 6% of the patients in the placebo group and 3% of the patients in the combined REGN-COV2 dose groups reported at least one medically attended visit; among patients who were serum antibody–negative at baseline, the corresponding percentages were 15% and 6% (difference, −9 percentage points; 95% CI, −29 to 11). The percentages of patients with hypersensitivity reactions, infusion-related reactions, and other adverse events were similar in the combined REGN-COV2 dose groups and the placebo group. In this interim analysis, the REGN-COV2 antibody cocktail reduced viral load, with a greater effect in patients whose immune response had not yet been initiated or who had a high viral load at baseline. Safety outcomes were similar in the combined REGN-COV2 dose groups and the placebo group. (Funded by Regeneron Pharmaceuticals and the Biomedical and Advanced Research and Development Authority of the Department of Health and Human Services; ClinicalTrials.gov number, NCT04425629.)