巴瑞替尼单抗单药治疗或与etesevimab或sotrovimab联合治疗对轻至中度新冠肺炎患者持续高病毒载量的影响：一项随机2期BLAZE-4试验。
Effect of Bamlanivimab as Monotherapy or in Combination with Etesevimab or Sotrovimab on Persistently High Viral Load in Patients with Mild-to-Moderate COVID-19: A Randomized, Phase 2 BLAZE-4 Trial.
作者信息
Nichols Russell M, Macpherson Lisa, Patel Dipak R, Yeh Wendy W, Peppercorn Amanda
机构信息
Eli Lilly and Company, Indianapolis, IN, USA.
Vir Biotechnology, Inc., San Francisco, CA, USA.
出版信息
Infect Dis Ther. 2024 Feb;13(2):401-411. doi: 10.1007/s40121-024-00918-1. Epub 2024 Jan 30.
INTRODUCTION
Treatment with monoclonal antibodies provides rapid, passive immunity and may stop COVID-19 disease progression. The study evaluated the effect of bamlanivimab (BAM) or BAM + etesevimab (ETE)/sotrovimab compared to placebo on SARS-CoV-2 viral load in patients with COVID-19.
METHODS
The phase 2, randomized, single-dose study included patients aged between ≥ 18 and < 65 years, not hospitalized at the time of randomization, and had ≥ 1 mild or moderate COVID-19 symptoms. Study included arms 1-6 (placebo, BAM 175 mg + ETE 350 mg, BAM 700 mg + ETE 1400 mg, BAM 2800 mg + ETE 2800 mg, BAM 700 mg alone, and BAM 350 mg + ETE 700 mg, respectively), BAM 700 mg + ETE 700 mg unintentional dosing; and arms 7 and 8 (BAM 700 mg + sotrovimab 500 mg and placebo, respectively). The primary endpoint was proportion of patients with SARS-CoV-2 log viral load > 5.27 on day 7 (persistently high viral load [PHVL]) who received BAM or BAM + (ETE or sotrovimab).
RESULTS
A total of 725 patients, mean age 39.6 years (range 18-75 years), 50.2% male were randomized and infused with study drug in arms 1-6; and a total 202 patients, mean age 38 years (range 18-63 years), 53.5% female were randomized and infused with study drug in arms 7 and 8. A significantly lower proportion of patients in arms 2-6 and arm 7 experienced PHVL on day 7 compared to placebo. On day 7, patients in arms 2, 3, and 6 consistently experienced significantly greater reduction in viral load than placebo. Significant improvement was observed in time to viral load clearance and time to symptom improvement by day 29 in some arms compared to placebo. No new safety concerns were observed with drug combinations.
CONCLUSION
The study demonstrated that a significantly lower proportion of patients with mild-to-moderate COVID-19 treated with BAM or BAM + (ETE or sotrovimab) experienced a PHVL at day 7.
TRIAL REGISTRATION
ClinicalTrials.gov identifier, NCT04634409.
引言
单克隆抗体治疗可提供快速的被动免疫，并可能阻止新冠病毒疾病进展。本研究评估了巴瑞替尼（BAM）或BAM+依替西单抗（ETE）/索托维单抗与安慰剂相比，对新冠病毒患者严重急性呼吸综合征冠状病毒2（SARS-CoV-2）病毒载量的影响。
方法
这项2期随机单剂量研究纳入了年龄在≥18至<65岁之间、随机分组时未住院且有≥1种轻度或中度新冠病毒疾病症状的患者。研究包括1-6组（分别为安慰剂、175毫克BAM+350毫克ETE、700毫克BAM+1400毫克ETE、2800毫克BAM+2800毫克ETE、单独使用700毫克BAM以及350毫克BAM+700毫克ETE）、700毫克BAM+700毫克ETE意外给药组；以及7组和8组（分别为700毫克BAM+500毫克索托维单抗和安慰剂）。主要终点是在第7天严重急性呼吸综合征冠状病毒2病毒载量对数>5.27（持续高病毒载量[PHVL]）的患者比例，这些患者接受了BAM或BAM+（ETE或索托维单抗）治疗。
结果
共有725例患者（平均年龄39.6岁，范围18 - 75岁，男性占50.2%）被随机分组并在1 - 6组接受研究药物输注；另有202例患者（平均年龄38岁，范围18 - 63岁，女性占53.5%）被随机分组并在7组和8组接受研究药物输注。与安慰剂相比，2 - 6组和7组中在第7天出现持续高病毒载量的患者比例显著更低。在第7天，2组、3组和6组的患者病毒载量持续下降幅度显著大于安慰剂组。与安慰剂相比，在第29天时，部分组在病毒载量清除时间和症状改善时间方面有显著改善。药物联合使用未观察到新的安全问题。
结论
该研究表明，接受BAM或BAM+（ETE或索托维单抗）治疗的轻度至中度新冠病毒疾病患者在第7天出现持续高病毒载量的比例显著更低。
试验注册
ClinicalTrials.gov标识符，NCT04634409。
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