National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.
Pirogov Russian National Research Medical University, Moscow, Russia.
Allergy. 2023 Jun;78(6):1639-1653. doi: 10.1111/all.15663. Epub 2023 Feb 14.
Severe acute respiratory syndrome corona virus (SARS-CoV-2) infection frequently causes severe and prolonged disease but only few specific treatments are available. We aimed to investigate safety and efficacy of a SARS-CoV-2-specific siRNA-peptide dendrimer formulation MIR 19® (siR-7-EM/KK-46) targeting a conserved sequence in known SARS-CoV-2 variants for treatment of COVID-19.
We conducted an open-label, randomized, controlled multicenter phase II trial (NCT05184127) evaluating safety and efficacy of inhaled siR-7-EM/KK-46 (3.7 mg and 11.1 mg/day: low and high dose, respectively) in comparison with standard etiotropic drug treatment (control group) in patients hospitalized with moderate COVID-19 (N = 52 for each group). The primary endpoint was the time to clinical improvement according to predefined criteria within 14 days of randomization.
Patients from the low-dose group achieved the primary endpoint defined by simultaneous achievement of relief of fever, normalization of respiratory rate, reduction of coughing, and oxygen saturation of >95% for 48 h significantly earlier (median 6 days; 95% confidence interval [CI]: 5-7, HR 1.75, p = .0005) than patients from the control group (8 days; 95% CI: 7-10). No significant clinical efficacy was observed for the high-dose group. Adverse events were reported in 26 (50.00%), 25 (48.08%), and 28 (53.85%) patients from the low-, high-dose and control group, respectively. None of them were associated with siR-7-EM/KK-46.
siR-7-EM/KK-46, a SARS-CoV-2-specific siRNA-peptide dendrimer formulation is safe, well tolerated and significantly reduces time to clinical improvement in patients hospitalized with moderate COVID-19 compared to standard therapy in a randomized controlled trial.
严重急性呼吸综合征冠状病毒 (SARS-CoV-2) 感染常导致严重和长期的疾病，但仅有少数特定的治疗方法。我们旨在研究一种针对已知 SARS-CoV-2 变体保守序列的 SARS-CoV-2 特异性 siRNA-肽树突状制剂 MIR 19®（siR-7-EM/KK-46）治疗 COVID-19 的安全性和疗效。
我们进行了一项开放标签、随机、对照的多中心 II 期试验（NCT05184127），评估吸入性 siR-7-EM/KK-46（低剂量和高剂量分别为 3.7 毫克和 11.1 毫克/天）与标准病因治疗（对照组）在中度 COVID-19 住院患者中的安全性和疗效（每组 52 例）。主要终点是随机分组后 14 天内根据预先定义的标准达到临床改善的时间。
低剂量组的患者同时达到退热、呼吸频率正常、咳嗽减少和氧饱和度>95%持续 48 小时的主要终点显著早于对照组（中位数 6 天；95%置信区间 [CI]：5-7，HR 1.75，p=0.0005）。高剂量组未观察到显著的临床疗效。低、高剂量组和对照组分别有 26（50.00%）、25（48.08%）和 28（53.85%）例患者报告不良事件。它们都与 siR-7-EM/KK-46 无关。
在一项随机对照试验中，SARS-CoV-2 特异性 siRNA-肽树突状制剂 MIR 19®（siR-7-EM/KK-46）是安全的，耐受性良好，与标准治疗相比，可显著缩短中度 COVID-19 住院患者达到临床改善的时间。
