Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation

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.

Авторы
Khaitov M.R. 1, 2 , Nikonova Alexandra 1, 3 , Kofiadi I.A.1, 2 , Shilovskiy Igor1 , Smirnov Valeriy1, 4 , Elisytina Olga 1, 3 , Maerle Artem1 , Shatilov A.A.1 , Shatilova A.V.1 , Andreev S.M.1 , Sergeev Ilya1 , Trofimov Dmitry 1 , Latysheva T.V.1 , Ilyna Natalia1 , Martynov Alexander1 , Rabdano S.O.5 , Ruzanova Ellina5 , Savelev Nikita5 , Pletiukhina Iuliia5 , Safi Ariana5 , Ratnikov V.A.6 , Gorelov Viktor6 , Kaschenko Viktor6 , Kucherenko Natalya6 , Umarova Irina6 , Moskaleva Svetlana6 , Fabrichnikov S.V.6 , Zuev Oleg7 , Pavlov Nikolai7 , Kruchko Daria8 , Berzin I.A.8 , Goryachev D.V.9 , Merkulov V.A. 4, 9 , Shipulin G.A. 10 , Udin Sergey10 , Trukhin V.P.5 , Valenta R.1, 4, 11, 12 , Skvortsova V.I.8
Журнал
Издательство
Munksgaard International Publishers
Номер выпуска
6
Язык
Английский
Страницы
1639-1653
Статус
Опубликовано
Том
78
Год
2023
Организации
  • 1 National Research Center- Institute of Immunology Federal Medical-Biological Agency of Russia
  • 2 The Russian National Research Medical University named after N.I. Pirogov
  • 3 Peoples' Friendship University of Russia
  • 4 The State Education Institution of Higher Professional Training The First Sechenov Moscow State Medical University under Ministry of Health of the Russian Federation
  • 5 The federal state unitary enterprise "The Saint - Petersburg scientific reseach institute of vaccines and serums and the enterprise for the production of bacterial preparations" of Federal medical and biologic agency
  • 6 The Federal State Budgetary Institution "North-Western district scientific and clinical center named after L. G. Sokolov Federal Medical and Biological Agency
  • 7 Federal Clinical Center of High Medical Technologies of the Federal Medical and Biological Agency of Russia,
  • 8 Federal Medical-Biological Agency
  • 9 Federal State Budgetary Institution Scientific Centre for Expert Evaluation of Medicinal Products of the Ministry of Health of the Russian Federation
  • 10 Federal State Budgetary Institution «Centre for Strategic Planning and Management of Biomedical Health Risks» of the Federal Medical Agency
  • 11 Medical University of Vienna
  • 12 Karl Landsteiner University of Healthcare
Ключевые слова
clinical trial; efficacy; safety; SARS-CoV-2; siRNA
Дата создания
28.12.2023
Дата изменения
28.12.2023
Постоянная ссылка
https://repository.rudn.ru/ru/records/article/record/102482/
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Другие записи

Полькин В.В., Исаев П.А., Плугарь А.К., Ильин А.А., Рожнов В.А., Спирин П.И., Панасейкин Ю.А., Иванов С.А., Каприн А.Д.
Радиация и риск (Бюллетень Национального радиационно-эпидемиологического регистра). Том 32. 2023. С. 142-156