Efficacy and Safety of Low-Dose, Rapidly Infused Bamlanivimab and Etesevimab: Phase 3 BLAZE-1 Trial for Mild-to-Moderate COVID-19.

IF 4.7 3区医学 Q1 INFECTIOUS DISEASES Infectious Diseases and Therapy Pub Date : 2024-09-04 DOI:10.1007/s40121-024-01031-z

Dipak R Patel, Lisa Macpherson, Martin Bohm, Himanshu Upadhyaya, Carmen Deveau, Ajay Nirula, Paul Klekotka, Mark Williams, Matthew M Hufford

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Abstract

Introduction: The monoclonal antibody therapies bamlanivimab (BAM) + etesevimab (ETE) received emergency use authorization (EUA) from the US Food and Drug Administration (February 9, 2021) for treatment of mild-to-moderate COVID-19. The EUA of BAM + ETE was revoked (December 14, 2023) due to the high prevalence of BAM + ETE-resistant variants of SARS-CoV-2. Efficacy and safety of 700/1400 mg and 2800/2800 mg BAM + ETE are well established and published; however, efficacy and safety of 350/700 mg BAM + ETE have not been disclosed to date.

Methods: This portion of phase 3, BLAZE-1 trial (J2X-MC-PYAB) enrolled patients (between June 17, 2020 and April 9, 2021) with mild-to-moderate COVID-19 within 3 days of laboratory diagnosis of SARS-CoV-2 infection. In total, 354 patients with at least one risk factor for severe COVID-19 were enrolled, randomized (2:3), and infused with placebo (N = 141) or 350/700 mg BAM + ETE (N = 213), over ~ 8 min. Primary endpoint was to assess proportion of patients with persistently high SARS-CoV-2 viral load (PHVL) (log viral load > 5.27) 7 days after infusion.

Results: Patients were aged (mean) 53 years, 49.7% female, and 82.7% White. Seven days after drug infusion, 10.8% (95% confidence interval: 6.6, 15.0; p < 0.001) of BAM + ETE-treated patients and 34.8% (26.9, 42.6) of placebo-treated patients had PHVL, and the viral load change from baseline (least square mean [standard error]) was - 3.50 (0.15; p < 0.001) in BAM + ETE-treated patients versus - 2.51 (0.19) in placebo-treated patients. The majority of treatment-emergent adverse events were considered mild or moderate in severity (BAM + ETE: 6.6%; placebo: 14.2%). No deaths were reported.

Conclusions: Consistent with previous studies, patients treated with BAM + ETE (350/700 mg) had a significantly lower proportion of PHVL and greater reduction in viral load compared with placebo. The overall safety profile is consistent with higher doses of BAM + ETE. Infusions of over ~ 8 min did not result in meaningful increase in incidence of TEAEs compared to higher doses of BAM + ETE administered over 30-60 min.

Trial registration: Clinical trial.gov identifier, NCT04427501.

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小剂量、快速输注巴马单抗和依替西单抗的有效性和安全性：轻度至中度 COVID-19 的 3 期 BLAZE-1 试验。

简介：单克隆抗体疗法 bamlanivimab (BAM) + etesevimab (ETE) 获得了美国食品药品管理局的紧急使用授权（EUA）（2021 年 2 月 9 日），用于治疗轻度至中度 COVID-19。由于SARS-CoV-2的BAM+ETE耐药变异体的高流行率，BAM+ETE的EUA被撤销（2023年12月14日）。700/1400 毫克和 2800/2800 毫克 BAM + ETE 的疗效和安全性已得到证实并已公布；但 350/700 毫克 BAM + ETE 的疗效和安全性迄今尚未披露：这部分 3 期 BLAZE-1 试验（J2X-MC-PYAB）招募了（2020 年 6 月 17 日至 2021 年 4 月 9 日期间）在实验室诊断为 SARS-CoV-2 感染 3 天内患有轻度至中度 COVID-19 的患者。共招募了 354 名至少有一个重度 COVID-19 危险因素的患者，对其进行随机分组（2:3），并在约 8 分钟内输注安慰剂（141 人）或 350/700 毫克 BAM + ETE（213 人）。主要终点是评估输液 7 天后 SARS-CoV-2 病毒载量（PHVL）持续偏高（病毒载量对数值大于 5.27）的患者比例：患者年龄（平均）53 岁，49.7% 为女性，82.7% 为白人。输注药物 7 天后，10.8%（95% 置信区间：6.6，15.0；P 结论：与之前的研究一致，接受治疗的患者病毒载量对数大于 5.27：与之前的研究一致，与安慰剂相比，接受 BAM + ETE（350/700 毫克）治疗的患者 PHVL 比例明显降低，病毒载量降低幅度更大。总体安全性与较高剂量的 BAM + ETE 一致。与 30-60 分钟的高剂量 BAM + ETE 相比，8 分钟以上的输注不会导致 TEAEs 的发生率明显增加：试验注册：Clinical trial.gov identifier，NCT04427501。

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来源期刊

Infectious Diseases and Therapy Medicine-Microbiology (medical)

CiteScore

8.60

自引率

1.90%

发文量

136

审稿时长

6 weeks

期刊介绍： Infectious Diseases and Therapy is an international, open access, peer-reviewed, rapid publication journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of infectious disease therapies and interventions, including vaccines and devices. Studies relating to diagnostic products and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. Areas of focus include, but are not limited to, bacterial and fungal infections, viral infections (including HIV/AIDS and hepatitis), parasitological diseases, tuberculosis and other mycobacterial diseases, vaccinations and other interventions, and drug-resistance, chronic infections, epidemiology and tropical, emergent, pediatric, dermal and sexually-transmitted diseases.