Treatment of <scp>COVID</scp> ‐19 patients with a <scp>SARS‐CoV</scp> ‐2‐specific <scp>siRNA</scp> ‐peptide dendrimer formulation
Musa Khaitov, Alexandra Nikonova, И.А. Кофиади, I.P. Shilovskiy, Smirnov Vv, Olga Elisytina, Artem Maerle, Artem Shatilov, A.V. Shatilova, Sergey Andreev, I.V. Sergeev, D. Yu. Trofimov, Т. В. Латышева, Natalia Ilyna, Alexander Martynov, Sevastyan O. Rabdano, Ellina Ruzanova, Nikita Savelev, Iuliia Pletiukhina, Ariana Safi, В. А. Ратников, V. P. Gorelov, Viktor Kaschenko, Natalya Kucherenko, Irina Umarova, Svetlana Moskaleva, Sergei Fabrichnikov, Oleg Zuev, N. B. Pavlov, Daria Kruchko, Igor Berzin, D. V. Goryachev, В. А. Меркулов, German A. Shipulin, Sergey Udin, В. П. Трухин, Rudolf Valenta, В. В. Скворцова
Abstract
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.