Division of Pulmonary, Allergy, and Critical Care, Department of Medicine, Duke Health, Durham, North Carolina.
Division of Infectious Diseases, Rhode Island Hospital and The Miriam Hospital, Alpert Medical School of Brown University, Providence, Rhode Island.
Ann Intern Med. 2022 Sep;175(9):1266-1274. doi: 10.7326/M22-1503. Epub 2022 Aug 9.
Ensovibep (MP0420) is a designed ankyrin repeat protein, a novel class of engineered proteins, under investigation as a treatment of SARS-CoV-2 infection.
To investigate if ensovibep, in addition to remdesivir and other standard care, improves clinical outcomes among patients hospitalized with COVID-19 compared with standard care alone.
Double-blind, randomized, placebo-controlled, clinical trial. (ClinicalTrials.gov: NCT04501978).
Multinational, multicenter trial.
Adults hospitalized with COVID-19.
Intravenous ensovibep, 600 mg, or placebo.
Ensovibep was assessed for early futility on the basis of pulmonary ordinal scores at day 5. The primary outcome was time to sustained recovery through day 90, defined as 14 consecutive days at home or place of usual residence after hospital discharge. A composite safety outcome that included death, serious adverse events, end-organ disease, and serious infections was assessed through day 90.
An independent data and safety monitoring board recommended that enrollment be halted for early futility after 485 patients were randomly assigned and received an infusion of ensovibep ( = 247) or placebo ( = 238). The odds ratio (OR) for a more favorable pulmonary outcome in the ensovibep (vs. placebo) group at day 5 was 0.93 (95% CI, 0.67 to 1.30; = 0.68; OR > 1 would favor ensovibep). The 90-day cumulative incidence of sustained recovery was 82% for ensovibep and 80% for placebo (subhazard ratio [sHR], 1.06 [CI, 0.88 to 1.28]; sHR > 1 would favor ensovibep). The primary composite safety outcome at day 90 occurred in 78 ensovibep participants (32%) and 70 placebo participants (29%) (HR, 1.07 [CI, 0.77 to 1.47]; HR < 1 would favor ensovibep).
The trial was prematurely stopped because of futility, limiting power for the primary outcome.
Compared with placebo, ensovibep did not improve clinical outcomes for hospitalized participants with COVID-19 receiving standard care, including remdesivir; no safety concerns were identified.
National Institutes of Health.
Ensvibep（MP0420）是一种设计的锚蛋白重复蛋白，是一种新型的工程蛋白，正在作为治疗 SARS-CoV-2 感染的药物进行研究。
研究 Ensvibep 是否与标准护理相比，除了瑞德西韦和其他标准护理外，还能改善因 COVID-19 住院的患者的临床结果。
双盲、随机、安慰剂对照临床试验。（ClinicalTrials.gov：NCT04501978）。
多国家、多中心试验。
因 COVID-19 住院的成年人。
静脉注射 Ensvibep，600mg，或安慰剂。
根据第 5 天的肺部ordinal 评分评估 Ensvibep 的早期无效性。主要结局是通过第 90 天的持续恢复时间，定义为出院后在家或常住地连续 14 天。通过第 90 天评估包括死亡、严重不良事件、终末器官疾病和严重感染的复合安全结局。
独立的数据和安全监测委员会建议在 485 名患者被随机分配并接受 Ensvibep 输注（n=247）或安慰剂（n=238）后，因早期无效而停止入组。第 5 天 Ensvibep（与安慰剂相比）组更有利的肺部结局的优势比（OR）为 0.93（95%CI，0.67 至 1.30；P=0.68；OR>1 会有利于 Ensvibep）。Ensvibep 的 90 天累积持续恢复发生率为 82%，安慰剂组为 80%（亚危险比[sHR]，1.06[CI，0.88 至 1.28]；sHR>1 会有利于 Ensvibep）。第 90 天的主要复合安全结局发生在 78 名 Ensvibep 参与者（32%）和 70 名安慰剂参与者（29%）（HR，1.07[CI，0.77 至 1.47]；HR<1 会有利于 Ensvibep）。
由于无效性，试验提前停止，限制了主要结局的效力。
与安慰剂相比，Ensvibep 并未改善接受标准治疗（包括瑞德西韦）的 COVID-19 住院患者的临床结局；未发现安全性问题。
美国国立卫生研究院。
