Hcor Research Institute, São Paulo (SP), Brazil.
Brazilian Research in Intensive Care Network (BRICNet), São Paulo (SP), Brazil.
PLoS One. 2024 Feb 23;19(2):e0299197. doi: 10.1371/journal.pone.0299197. eCollection 2024.
Halofuginone (PJS-539) is an oral prolyl-tRNA synthetase inhibitor that has a potent in vitro activity against SARS-CoV-2 virus. The safety and efficacy of halofuginone in Covid-19 patients has not been studied.
We conducted a phase II, randomized, double-blind, placebo-controlled, dose ranging, safety and tolerability trial of halofuginone in symptomatic (≤ 7 days), mostly vaccinated, non-hospitalized adults with mild to moderate Covid-19. Patients were randomized in a 1:1:1 ratio to receive halofuginone 0.5mg, 1mg or placebo orally once daily for 10 days. The primary outcome was the decay rate of the SARS-CoV-2 viral load logarithmic curve within 10 days after randomization.
From September 25, 2021, to February 3, 2022, 153 patients were randomized. The mean decay rate in SARS-CoV-2 viral load log10 within 10 days was -3.75 (95% CI, -4.11; -3.19) in the placebo group, -3.83 (95% CI, -4.40; -2.27) in the halofuginone 0.5mg group and -4.13 (95% CI, -4.69; -3.57) in the halofuginone 1mg group, with no statistically significant difference in between placebo vs. halofuginone 0.5mg (mean difference -0.08; 95% CI -0.82 to 0.66, p = 0.96) and between placebo vs. halofuginone 1mg (mean difference -0.38; 95% CI, -1.11; 0.36, p = 0.41). There was no difference on bleeding episodes or serious adverse events at 28 days.
Among non-hospitalized adults with mild to moderate Covid-19 halofuginone treatment was safe and well tolerated but did not decrease SARS-CoV-2 viral load decay rate within 10 days.
哈洛芬酮（PJS-539）是一种口服脯氨酰-tRNA 合成酶抑制剂，对 SARS-CoV-2 病毒具有很强的体外活性。哈洛芬酮在 COVID-19 患者中的安全性和疗效尚未得到研究。
我们进行了一项 II 期、随机、双盲、安慰剂对照、剂量范围、安全性和耐受性试验，评估哈洛芬酮在症状（≤7 天）、主要接种疫苗、非住院的 COVID-19 轻症至中度成人患者中的应用。患者以 1:1:1 的比例随机接受哈洛芬酮 0.5mg、1mg 或安慰剂口服，每日 1 次，共 10 天。主要终点是随机分组后 10 天内 SARS-CoV-2 病毒载量对数曲线的衰减率。
从 2021 年 9 月 25 日至 2022 年 2 月 3 日，共有 153 名患者被随机分组。安慰剂组 10 天内 SARS-CoV-2 病毒载量对数的平均衰减率为 -3.75（95%CI，-4.11；-3.19），哈洛芬酮 0.5mg 组为 -3.83（95%CI，-4.40；-2.27），哈洛芬酮 1mg 组为 -4.13（95%CI，-4.69；-3.57），安慰剂与哈洛芬酮 0.5mg 组之间、安慰剂与哈洛芬酮 1mg 组之间的差异均无统计学意义（平均差异 -0.08；95%CI，-0.82 至 0.66，p=0.96）。28 天内出血事件或严重不良事件无差异。
在非住院的 COVID-19 轻症至中度成人患者中，哈洛芬酮治疗安全且耐受良好，但未能在 10 天内降低 SARS-CoV-2 病毒载量的衰减率。
