Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation.
| Title: | Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation. |
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| Authors: | Khaitov M; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Pirogov Russian National Research Medical University, Moscow, Russia.; Nikonova A; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; RUDN University, Moscow, Russia.; Kofiadi I; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Pirogov Russian National Research Medical University, Moscow, Russia.; Shilovskiy I; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Smirnov V; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.; Elisytina O; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; RUDN University, Moscow, Russia.; Maerle A; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Shatilov A; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Shatilova A; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Andreev S; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Sergeev I; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Trofimov D; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Latysheva T; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Ilyna N; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Martynov A; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; Rabdano S; Federal State Unitary Enterprise 'The Saint Petersburg Scientific Research Institute of Vaccines and Serums and the Enterprise for the Production of Bacterial Preparations' of Federal Medical and Biologic Agency (FSUE SPbSRIVS FMBA of Russia), St. Petersburg, Russia.; Ruzanova E; Federal State Unitary Enterprise 'The Saint Petersburg Scientific Research Institute of Vaccines and Serums and the Enterprise for the Production of Bacterial Preparations' of Federal Medical and Biologic Agency (FSUE SPbSRIVS FMBA of Russia), St. Petersburg, Russia.; Savelev N; Federal State Unitary Enterprise 'The Saint Petersburg Scientific Research Institute of Vaccines and Serums and the Enterprise for the Production of Bacterial Preparations' of Federal Medical and Biologic Agency (FSUE SPbSRIVS FMBA of Russia), St. Petersburg, Russia.; Pletiukhina I; Federal State Unitary Enterprise 'The Saint Petersburg Scientific Research Institute of Vaccines and Serums and the Enterprise for the Production of Bacterial Preparations' of Federal Medical and Biologic Agency (FSUE SPbSRIVS FMBA of Russia), St. Petersburg, Russia.; Safi A; Federal State Unitary Enterprise 'The Saint Petersburg Scientific Research Institute of Vaccines and Serums and the Enterprise for the Production of Bacterial Preparations' of Federal Medical and Biologic Agency (FSUE SPbSRIVS FMBA of Russia), St. Petersburg, Russia.; Ratnikov V; North-West District Scientific and Clinical Center named after L.G. Sokolov Federal Medical and Biological Agency, St. Petersburg, Russia.; Gorelov V; North-West District Scientific and Clinical Center named after L.G. Sokolov Federal Medical and Biological Agency, St. Petersburg, Russia.; Kaschenko V; North-West District Scientific and Clinical Center named after L.G. Sokolov Federal Medical and Biological Agency, St. Petersburg, Russia.; Kucherenko N; North-West District Scientific and Clinical Center named after L.G. Sokolov Federal Medical and Biological Agency, St. Petersburg, Russia.; Umarova I; North-West District Scientific and Clinical Center named after L.G. Sokolov Federal Medical and Biological Agency, St. Petersburg, Russia.; Moskaleva S; North-West District Scientific and Clinical Center named after L.G. Sokolov Federal Medical and Biological Agency, St. Petersburg, Russia.; Fabrichnikov S; North-West District Scientific and Clinical Center named after L.G. Sokolov Federal Medical and Biological Agency, St. Petersburg, Russia.; Zuev O; Federal Clinical Center of High Medical Technologies of the Federal Medical and Biological Agency of Russia, Moscow, Russia.; Pavlov N; Federal Clinical Center of High Medical Technologies of the Federal Medical and Biological Agency of Russia, Moscow, Russia.; Kruchko D; Federal Medico-biological Agency of Russia (FMBA Russia), Moscow, Russia.; Berzin I; Federal Medico-biological Agency of Russia (FMBA Russia), Moscow, Russia.; Goryachev D; Centre for Evaluation and Control of Finished Pharmaceutical Products, Federal State Budgetary Institution 'Scientific Centre for Expert Evaluation of Medicinal Products' of the Ministry of Health of the Russian Federation, Moscow, Russia.; Merkulov V; I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.; Centre for Evaluation and Control of Finished Pharmaceutical Products, Federal State Budgetary Institution 'Scientific Centre for Expert Evaluation of Medicinal Products' of the Ministry of Health of the Russian Federation, Moscow, Russia.; Shipulin G; Centre for Strategic Planning of FMBA of Russia Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks' of the Federal Medical Biological Agency, Moscow, Russia.; Udin S; Centre for Strategic Planning of FMBA of Russia Federal State Budgetary Institution 'Centre for Strategic Planning and Management of Biomedical Health Risks' of the Federal Medical Biological Agency, Moscow, Russia.; Trukhin V; Federal State Unitary Enterprise 'The Saint Petersburg Scientific Research Institute of Vaccines and Serums and the Enterprise for the Production of Bacterial Preparations' of Federal Medical and Biologic Agency (FSUE SPbSRIVS FMBA of Russia), St. Petersburg, Russia.; Valenta R; National Research Center (NRC) Institute of Immunology Federal Medical-Biological Agency (FMBA) of Russia, Moscow, Russia.; I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia.; Medical University of Vienna, Vienna, Austria.; Karl Landsteiner University of Healthcare, Krems, Austria.; Skvortsova V; Federal Medico-biological Agency of Russia (FMBA Russia), Moscow, Russia. |
| Source: | Allergy [Allergy] 2023 Jun; Vol. 78 (6), pp. 1639-1653. Date of Electronic Publication: 2023 Feb 14. |
| Publication Type: | Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: Wiley-Blackwell Country of Publication: Denmark NLM ID: 7804028 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1398-9995 (Electronic) Linking ISSN: 01054538 NLM ISO Abbreviation: Allergy Subsets: MEDLINE |
| Imprint Name(s): | Publication: Copenhagen : Wiley-Blackwell; Original Publication: Copenhagen, Munksgaard. |
| MeSH Terms: | COVID-19* ; Dendrimers*; Peptides/therapeutic use ; Humans ; SARS-CoV-2 ; RNA, Small Interfering ; Treatment Outcome |
| 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.; (© 2023 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.) |
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| Contributed Indexing: | Keywords: SARS-CoV-2; clinical trial; efficacy; safety; siRNA |
| Molecular Sequence: | ClinicalTrials.gov NCT05184127 |
| Substance Nomenclature: | 0 (Dendrimers); 0 (RNA, Small Interfering); 0 (Peptides) |
| SCR Organism: | SARS-CoV-2 variants |
| Entry Date(s): | Date Created: 20230201 Date Completed: 20230602 Latest Revision: 20230622 |
| Update Code: | 20260130 |
| DOI: | 10.1111/all.15663 |
| PMID: | 36721963 |
| Database: | MEDLINE |
Randomized Controlled Trial; Multicenter Study; Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't