中和抗體雞尾酒REGN-COV2治療Covid-19可顯著降低病毒載量
作者：
小柯機器人發布時間：2020/12/22 21:51:45
美國再生元製藥公司David M. Weinreich團隊研究了中和抗體雞尾酒REGN-COV2治療Covid-19門診患者的療效。2020年12月17日，該研究發表在《新英格蘭醫學雜誌》上。
最新數據表明，Covid-19引起的併發症和死亡可能與高病毒載量有關。在這項正在進行的涉及Covid-19非住院患者的雙盲臨床1-3期試驗中，研究組研究了兩種針對SARS-CoV-2刺突蛋白的全人源中和單克隆抗體雞尾酒（REGN-COV2）療法降低抗藥性突變病毒出現的風險。
研究組招募了275例患者，將其按1：1：1隨機分配，分別接受安慰劑、2.4g或8.0g REGN-COV2治療，並前瞻性地確定了針對SARS-CoV-2的內源性免疫應答基線。主要終點包括從第1天到第7天病毒載量相對於基線的時間加權平均變化，以及到29天至少有一次Covid-19相關醫療就診的患者百分比。
從第1天到第7天，基線時血清抗體陰性的患者病毒載量的時間加權平均變化的最小二乘均值差為-0.56 log10拷貝/毫升，在整個試驗人群中為-0.41 log10拷貝/毫升。在整個試驗人群中，安慰劑組中有6％患者至少接受過一次醫療就診，兩個REGN-COV2組中有3％。在基線血清抗體陰性的患者中，相應的百分比分別為15％和6％。在REGN-COV2兩個劑量組和安慰劑組中，出現超敏反應、輸注相關反應和其他不良事件的患者百分比相差不大。
總之，在此中期分析中，抗體雞尾酒REGN-COV2降低了病毒載量，對尚未開始免疫應答或基線時病毒載量高的患者影響更大。REGN-COV2兩種劑量組和安慰劑組的安全性結果相差不大。
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
Source: https://www.nejm.org/doi/full/10.1056/NEJMoa2035002