AZD7442（替沙格韦单抗/西加韦单抗）预防有症状新型冠状病毒肺炎的疗效、安全性及药代动力学：PROVENT和STORM CHASER试验的15个月最终分析
Efficacy, Safety, and Pharmacokinetics of AZD7442 (Tixagevimab/Cilgavimab) for Prevention of Symptomatic COVID-19: 15-Month Final Analysis of the PROVENT and STORM CHASER Trials.
作者信息
Levin Myron J, Ustianowski Andrew, De Wit Stephane, Beavon Rohini, Thissen Jesse, Seegobin Seth, Dey Kanika, Near Karen A, Streicher Katie, Kiazand Alexandre, Esser Mark T
机构信息
University of Colorado School of Medicine, Aurora, CO, USA.
North Manchester General Hospital, Manchester, UK.
出版信息
Infect Dis Ther. 2024 Jun;13(6):1253-1268. doi: 10.1007/s40121-024-00970-x. Epub 2024 May 4.
INTRODUCTION
The phase 3 PROVENT and STORM CHASER studies evaluated AZD7442 (tixagevimab/cilgavimab) for pre-exposure and post-exposure prophylaxis of symptomatic coronavirus disease 2019 (COVID-19). We report the final 15-month results of both studies.
METHODS
In PROVENT, participants were randomized 2:1 to receive 300 mg AZD7442 (n = 3460) or placebo (n = 1737). In STORM CHASER, participants were enrolled within 8 days of exposure to a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individual and randomized 2:1 to receive 300 mg AZD7442 (n = 749) or placebo (n = 372).
RESULTS
In PROVENT, the relative risk reduction (RRR) in symptomatic COVID-19 for AZD7442 versus placebo was 76.7% at primary analysis [95% confidence interval (CI) 46.1, 90.0; p < 0.001], 83.0% at day 183 (95% CI 67.3, 91.2; nominal p < 0.001), and 46.3% at day 366 (95% CI 23.1, 62.4; nominal p < 0.001). Severe/critical COVID-19 was reduced by 91.4% with AZD7442 versus placebo by day 366 (95% CI 61.3, 98.1; nominal p < 0.0001). Adverse events (AEs) occurred in 58.2% and 58.0% of participants administered AZD7442 or placebo, respectively; serious AEs (SAEs) occurred in 6.2% and 5.6%, respectively. In STORM CHASER, the RRR in symptomatic COVID-19 for AZD7442 versus placebo was 33.3% at primary analysis (95% CI - 25.9, 64.7; p = 0.212), 43.3% at day 183 (95% CI 1.4, 67.4; nominal p = 0.044) and 3.4% at day 366 (95% CI - 35.6, 31.2; nominal p = 0.842). Severe/critical COVID-19 did not occur in participants receiving AZD7442 versus 0.5% of participants receiving placebo by day 366. AEs occurred in 46.5% and 51.9% of participants administered AZD7442 or placebo, respectively; SAEs occurred in 2.7% and 4.3%, respectively. In both studies, serum concentration-time profiles over 457 days were similar for tixagevimab and cilgavimab and consistent with the extended half-life reported for AZD7442 (approximately 90 days).
CONCLUSION
This analysis provides proof of concept supporting long-term safety of intramuscularly administered AZD7442 for prevention of symptomatic/severe COVID-19. A graphical abstract is available with this article.
GOV IDENTIFIERS
PROVENT (NCT04625725) and STORM CHASER (NCT04625972).
简介
3期PROVENT和STORM CHASER研究评估了AZD7442（替沙格韦单抗/西加韦单抗）用于2019冠状病毒病（COVID-19）症状性疾病的暴露前和暴露后预防。我们报告了这两项研究的最终15个月结果。
方法
在PROVENT研究中，参与者按2:1随机分组，分别接受300mg AZD7442（n = 3460）或安慰剂（n = 1737）。在STORM CHASER研究中，参与者在接触严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染者后的8天内入组，并按2:1随机分组，分别接受300mg AZD7442（n = 749）或安慰剂（n = 372）。
结果
在PROVENT研究中，初步分析时AZD7442组与安慰剂组相比，有症状COVID-19的相对风险降低（RRR）为76.7%[95%置信区间（CI）46.1，90.0；p < 0.001]，在第183天时为83.0%（95%CI 67.3，91.2；名义p < 0.001），在第366天时为46.3%（95%CI 23.1，62.4；名义p < 0.001）。到第366天时，与安慰剂相比，AZD7442组的重症/危重症COVID-19减少了91.4%（95%CI 61.3，98.1；名义p < 0.0001）。接受AZD7442或安慰剂治疗的参与者中，不良事件（AE）发生率分别为58.2%和58.0%；严重不良事件（SAE）发生率分别为6.2%和5.6%。在STORM CHASER研究中，初步分析时AZD7442组与安慰剂组相比，有症状COVID-19的RRR为33.3%（95%CI -25.9，64.7；p = 0.212），在第183天时为43.3%（95%CI 1.4，67.4；名义p = 0.044），在第366天时为3.4%（95%CI -35.6，31.2；名义p = 0.842）。到第(此处原文有误，应该是366天)366天时，接受AZD7442治疗的参与者中未发生重症/危重症COVID-19，而接受安慰剂治疗的参与者中有0.5%发生。接受AZD7442或安慰剂治疗的参与者中，AE发生率分别为46.5%和51.9%；SAE发生率分别为2.7%和4.3%。在两项研究中，替沙格韦单抗和西加韦单抗在457天内的血清浓度-时间曲线相似，与报道的AZD7442延长半衰期（约90天）一致。
结论
该分析提供了概念验证，支持肌肉注射AZD7442预防有症状/重症COVID-19的长期安全性。本文提供了图形摘要。
政府标识符
PROVENT（NCT04625725）和STORM CHASER（NCT04625972）。
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