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

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

Research output: Journal article (peer-reviewed)Journal article

10 Citations (Scopus)

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 ®) 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.

Original languageEnglish
Pages (from-to)1639-1653
Number of pages15
JournalAllergy: European Journal of Allergy and Clinical Immunology
Volume78
Issue number6
Early online date31 Jan 2023
DOIs
Publication statusPublished - Jun 2023

Keywords

  • SARS-CoV-2
  • clinical trial
  • efficacy
  • safety
  • siRNA

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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