Shapiro Adrienne E, Sarkis Elias, Acloque Jude, Free Almena, Gonzalez-Rojas Yaneicy, Hussain Rubaba, Juarez Erick, Moya Jaynier, Parikh Naval, Inman David, Cebrik Deborah, Nader Ahmed, Noormohamed Nadia, Wang Qianwen, Skingsley Andrew, Austin Daren, Peppercorn Amanda, Agostini Maria L, Parra Sergio, Chow Sophia, Mogalian Erik, Pang Phillip S, Hong David K, Sager Jennifer E, Yeh Wendy W, Alexander Elizabeth L, Gaffney Leah A, Kohli Anita
Departments of Global Health and Medicine, University of Washington, Seattle, Washington, USA.
Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Open Forum Infect Dis. 2023 Jul 14;10(8):ofad354. doi: 10.1093/ofid/ofad354. eCollection 2023 Aug.
Convenient administration of coronavirus disease 2019 (COVID-19) treatment in community settings is desirable. Sotrovimab is a pan-sarbecovirus dual-action monoclonal antibody formulated for intravenous (IV) or intramuscular (IM) administration for early treatment of mild/moderate COVID-19.
This multicenter phase 3 study based on a randomized open-label design tested the noninferiority of IM to IV administration according to an absolute noninferiority margin of 3.5%. From June to August 2021, patients aged ≥12 years with COVID-19, who were neither hospitalized nor receiving supplemental oxygen but were at high risk for progression, were randomized 1:1:1 to receive sotrovimab as a single 500-mg IV infusion or a 500- or 250-mg IM injection. The primary composite endpoint was progression to (1) all-cause hospitalization for >24 hours for acute management of illness or (2) all-cause death through day 29.
Sotrovimab 500 mg IM was noninferior to 500 mg IV: 10 (2.7%) of 376 participants vs 5 (1.3%) of 378 met the primary endpoint, respectively (absolute adjusted risk difference, 1.06%; 95% CI, -1.15% to 3.26%). The 95% CI upper limit was lower than the prespecified noninferiority margin of 3.5%. The 250-mg IM group was discontinued early because of the greater proportion of hospitalizations vs the 500-mg groups. Serious adverse events occurred in <1% to 2% of participants across groups. Four participants experienced serious disease-related events and died (500 mg IM, 2/393, <1%; 250 mg IM, 2/195, 1%).
Sotrovimab 500-mg IM injection was well tolerated and noninferior to IV administration. IM administration could expand outpatient treatment access for COVID-19.
ClinicalTrials.gov: NCT04913675.
在社区环境中方便地进行新型冠状病毒肺炎（COVID-19）治疗是可取的。索托维单抗是一种泛沙贝科病毒双作用单克隆抗体，可通过静脉注射（IV）或肌肉注射（IM）给药，用于早期治疗轻/中度COVID-19。
这项基于随机开放标签设计的多中心3期研究，根据3.5%的绝对非劣效性界值，测试了肌肉注射与静脉注射的非劣效性。2021年6月至8月，年龄≥12岁的COVID-19患者，既未住院也未接受补充氧气，但有病情进展的高风险，被随机分为1:1:1，接受索托维单抗作为单次500毫克静脉输注或500毫克或250毫克肌肉注射。主要复合终点为进展至（1）因疾病急性处理而全因住院超过24小时，或（2）至第29天全因死亡。
500毫克索托维单抗肌肉注射不劣于500毫克静脉注射：376名参与者中有10名（2.7%），378名参与者中有5名（1.3%）分别达到主要终点（绝对调整风险差异为1.06%；95%CI，-1.15%至3.26%）。95%CI上限低于预先设定的3.5%非劣效性界值。25毫克肌肉注射组因住院比例高于500毫克组而提前终止。各组中<1%至2%的参与者发生严重不良事件。4名参与者经历了严重的疾病相关事件并死亡（500毫克肌肉注射组，2/393，<1%；250毫克肌肉注射组，2/195，1%）。
500毫克索托维单抗肌肉注射耐受性良好，不劣于静脉注射。肌肉注射给药可扩大COVID-19的门诊治疗途径。
ClinicalTrials.gov：NCT04913675。
