Article
作者: Shipulin, German ; Goryachev, Dmitriy ; Kucherenko, Natalya ; Valenta, Rudolf ; Sergeev, Ilya ; Umarova, Irina ; Safi, Ariana ; Trukhin, Victor ; Zuev, Oleg ; Smirnov, Valeriy ; Trofimov, Dmitry ; Kofiadi, Ilya ; Maerle, Artem ; Martynov, Alexander ; Kruchko, Daria ; Udin, Sergey ; Ratnikov, Vyacheslav ; Khaitov, Musa ; Pletiukhina, Iuliia ; Elisytina, Olga ; Nikonova, Alexandra ; Fabrichnikov, Sergei ; Merkulov, Vadim ; Shatilov, Artem ; Berzin, Igor ; Andreev, Sergey ; Pavlov, Nikolai ; Savelev, Nikita ; Kaschenko, Viktor ; Skvortsova, Veronica ; Rabdano, Sevastyan ; Ilyna, Natalia ; Ruzanova, Ellina ; Latysheva, Tatyana ; Gorelov, Viktor ; Shatilova, Anastasia ; Moskaleva, Svetlana ; Shilovskiy, Igor
Background: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.
Methods: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.
Results: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.
Conclusions: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.