TY - JOUR
T1 - Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation
AU - Khaitov, Musa
AU - Nikonova, Alexandra
AU - Kofiadi, Ilya
AU - Shilovskiy, Igor
AU - Smirnov, Valeriy
AU - Elisytina, Olga
AU - Maerle, Artem
AU - Shatilov, Artem
AU - Shatilova, Anastasia
AU - Andreev, Sergey
AU - Sergeev, Ilya
AU - Trofimov, Dmitry
AU - Latysheva, Tatyana
AU - Ilyna, Natalia
AU - Martynov, Alexander
AU - Rabdano, Sevastyan
AU - Ruzanova, Ellina
AU - Savelev, Nikita
AU - Pletiukhina, Iuliia
AU - Safi, Ariana
AU - Ratnikov, Vyacheslav
AU - Gorelov, Viktor
AU - Kaschenko, Viktor
AU - Kucherenko, Natalya
AU - Umarova, Irina
AU - Moskaleva, Svetlana
AU - Fabrichnikov, Sergei
AU - Zuev, Oleg
AU - Pavlov, Nikolai
AU - Kruchko, Daria
AU - Berzin, Igor
AU - Goryachev, Dmitriy
AU - Merkulov, Vadim
AU - Shipulin, German
AU - Udin, Sergey
AU - Trukhin, Victor
AU - Valenta, Rudolf
AU - Skvortsova, Veronica
N1 - Funding Information:
The study was supported by the Federal Medico‐biological Agency of Russia (FMBA Russia). This paper is dedicated to the memory of Professor Rakhim Khaitov—mentor, colleague, friend, and father.
Publisher Copyright:
© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.
PY - 2023/6
Y1 - 2023/6
N2 - 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 ®) 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 MIR 19 ® (3.7mg 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 hours significantly earlier (median 6 days (95% confidence interval [CI]: 5-7, HR 1.75, P=0.0005) 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 MIR 19 ®.CONCLUSIONS: MIR 19 ®, 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.
AB - 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 ®) 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 MIR 19 ® (3.7mg 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 hours significantly earlier (median 6 days (95% confidence interval [CI]: 5-7, HR 1.75, P=0.0005) 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 MIR 19 ®.CONCLUSIONS: MIR 19 ®, 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.
KW - SARS-CoV-2
KW - clinical trial
KW - efficacy
KW - safety
KW - siRNA
UR - http://www.scopus.com/inward/record.url?scp=85148291938&partnerID=8YFLogxK
U2 - 10.1111/all.15663
DO - 10.1111/all.15663
M3 - Journal article
C2 - 36721963
SN - 0105-4538
VL - 78
SP - 1639
EP - 1653
JO - Allergy: European Journal of Allergy and Clinical Immunology
JF - Allergy: European Journal of Allergy and Clinical Immunology
IS - 6
ER -