中和抗体鸡尾酒REGN-COV2治疗Covid-19可显著降低病毒载量
2020-12-31   阅读:536   来源:新英格兰医学杂志

美国再生元制药公司David M. Weinreich团队研究了中和抗体鸡尾酒REGN-COV2治疗Covid-19门诊患者的疗效。2020年12月17日,该研究发表在《新英格兰医学杂志》上。

最新数据表明,Covid-19引起的并发症和死亡可能与高病毒载量有关。在这项正在进行的涉及Covid-19非住院患者的双盲临床1-3期试验中,研究组研究了两种针对SARS-CoV-2刺突蛋白的全人源中和单克隆抗体鸡尾酒(REGN-COV2)疗法降低抗药性突变病毒出现的风险。

研究组招募了275例患者,将其按1:1:1随机分配,分别接受安慰剂、2.4g或8.0g REGN-COV2治疗,并前瞻性地确定了针对SARS-CoV-2的内源性免疫应答基线。主要终点包括从第1天到第7天病毒载量相对于基线的时间加权平均变化,以及到29天至少有一次Covid-19相关医疗就诊的患者百分比。

从第1天到第7天,基线时血清抗体阴性的患者病毒载量的时间加权平均变化的最小二乘均值差为-0.56 log10拷贝/毫升,在整个试验人群中为-0.41 log10拷贝/毫升。在整个试验人群中,安慰剂组中有6%患者至少接受过一次医疗就诊,两个REGN-COV2组中有3%。在基线血清抗体阴性的患者中,相应的百分比分别为15%和6%。在REGN-COV2两个剂量组和安慰剂组中,出现超敏反应、输注相关反应和其他不良事件的患者百分比相差不大。

总之,在此中期分析中,抗体鸡尾酒REGN-COV2降低了病毒载量,对尚未开始免疫应答或基线时病毒载量高的患者影响更大。REGN-COV2两种剂量组和安慰剂组的安全性结果相差不大。

附:英文原文

Title: REGN-COV2, a Neutralizing Antibody Cocktail, in Outpatients with Covid-19

Author: David M. Weinreich, M.D.,, Sumathi Sivapalasingam, M.D.,, Thomas Norton, M.D.,, Shazia Ali, Pharm.D.,, Haitao Gao, Ph.D.,, Rafia Bhore, Ph.D.,, Bret J. Musser, Ph.D.,, Yuhwen Soo, Ph.D.,, Diana Rofail, Ph.D.,, Joseph Im, B.S.,, Christina Perry, M.B.A.,, Cynthia Pan, B.Pharm.,, Romana Hosain, M.D., M.P.H.,, Adnan Mahmood, M.D.,, John D. Davis, Ph.D.,, Kenneth C. Turner, Ph.D.,, Andrea T. Hooper, Ph.D.,, Jennifer D. Hamilton, Ph.D.,, Alina Baum, Ph.D.,, Christos A. Kyratsous, Ph.D.,, Yunji Kim, Pharm.D.,, Amanda Cook, B.S., Dip.Reg.Aff.,, Wendy Kampman, M.D.,, Anita Kohli, M.D.,, Yessica Sachdeva, M.D.,, Ximena Graber, M.D.,, Bari Kowal, M.S.,, Thomas DiCioccio, Ph.D.,, Neil Stahl, Ph.D.,, Leah Lipsich, Ph.D.,, Ned Braunstein, M.D.,, Gary Herman, M.D.,, and George D. Yancopoulos, M.D., Ph.D.

Issue&Volume: 2020-12-17

Abstract:

Background

Recent data suggest that complications and death from coronavirus disease 2019 (Covid-19) may be related to high viral loads.

Methods

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 from baseline in viral load from 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.

Results

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.

Conclusions

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.

DOI: 10.1056/NEJMoa2035002

 

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