Results of clinical trials phases I and II of MIR 19®
AbstractIntroduction. In connection with the threat of coronavirus infection, increased the need for the development of fundamentally new antiviral drugs with increased efficiency and availability. One of the promising directions in the development of such drugs is the use of inhibitors of viral reproduction based on small interfering RNA (siRNA).
Aim – to study the safety of MIR 19® (siCoV/KK46) in single and multiple doses, as well as to study the efficacy and choice of dosage of MIR 19® in the treatment of hospitalized patients with infection caused by SARS-CoV-2 (COVID-19) who do not require treatment in the intensive care unit.
Material and methods. Phase I clinical trial, the safety of MIR 19® was studied for single and multiple administration. As safety criteria, the incidence of any adverse events, the incidence of serious adverse events according to complaints, the results of a physical examination, the results of assessing heart rate and blood pressure, respiratory rate and body temperature, as well as laboratory monitoring data – indicators of clinical and biochemical blood tests, general urine analysis. Also, for the registration and monitoring of AEs, the instrumental research methods – ECG and spirography were used. An open-label, randomized, controlled, multicentre, phase II study (NCT05184127) was then conducted to evaluate the safety and efficacy of inhaled MIR 19® (3.7 and 11.1 mg/day: low and high dose, respectively) compared with standard treatment (group of comparison) in patients with coronavirus infection / COVID-19 who did not require mechanical ventilation at the time of inclusion in the study (n = 52 for each group).
Results. Based on the results of the phase I clinical trial, it can be concluded that the single and multiple administration of the MIR 19® preparation is safe in healthy volunteers. Phase II clinical trials showed that patients in the low-dose group achieved the primary endpoint of simultaneously achieving fever reduction, respiratory rate normalization, cough reduction, and blood oxygen saturation > 95 % within 48 h, significantly earlier (median 6 days) than patients in the group of comparison (median 8 days). In the high dose group, no greater clinical efficacy was observed in relation to the group of comparison. None of adverse events were associated with MIR 19®.
Conclusion. MIR 19®, an etiotropic drug specifically suppressing SARS-CoV-2 replication, is safe with single and multiple use, is well tolerated and significantly reduces the time to clinical improvement in patients hospitalized with moderate COVID-19, compared with standard therapy in a randomized controlled trial. MIR 19® is registered (registration certificate LP-007720), it is included in the Temporary Methodological Recommendations of the Ministry of Health of the Russian Federation «Prevention, diagnosis and treatment of new coronavirus infection (COVID-19)» and is actively used in clinical practice.
Keywords:SARS-CoV-2; COVID-19; miRNA; MIR 19®; siCoV/KK46; clinical research; safety; efficiency
For citation: Khaitov M.R., Nikonova A.A., Kofiadi I.A., Shilovsky I.P., Smirnov V.V., Elisyutina O.G., Gudima G.O., Maerle A.V., Shatilov A.A., Shatilova A.V., Andreev S.M., Sergeev I.V., Trofimov D.Yu., Latysheva T.V., Ilyina N.I., Martynov A.I., Rabdano S.O., Ruzanova E.A., Savelyev N.S., Pletyukhina Yu.V., Safi A.S., Ratnikov V.A., Gorelov V.P., Kashchenko V.A., Kucherenko N.G., Umarova I.A., Moskaleva S.S., Fabrichnikov S.V., Zuev O.V., Pavlov N.B., Kryuchko D.S., Berzin I.A., Goryachev D.V., Merkulov V.A., Shipulin G.A., Yudin S.M., Trukhin V.P., Valenta R., Skvortsova V.I. Results of clinical trials phases I and II of MIR 19®. Immunologiya. 2023; 44 (3): 291–316. DOI: https://doi.org/10.33029/1816-2134-2023-44-3-291-316 (in Russian)
Conflict of interests. The authors declare no conflict of interests.
Funding. The study was funded by Federal Medical-Biological Agency.
Authors’ contribution. Research concept and methodology – Khaitov M.R., Valenta R., Shilovsky I.I., Kofiadi I.A., Smirnov V.V., Martynov A.I., Berzin I.A., Trukhin V.P., Skvortsova V.I.; conducting the study – Elisyutina O.G., Maerle A.V., Shatilov A.A., Shatilova A.V., Andreev S.M., Sergeev I.V., Trofimov D.Yu., Latysheva T.V., Ilyina N.I., Rabdano S.O., Ruzanova E.A., Savelev N.S., Pletyukhina Yu.V., Safi A.S., Ratnikov V.A., Gorelov V.P., Kashchenko V.A., Kucherenko N.G., Umarova I.A., Moskaleva S.S., Fabrichnikov S.V., Zuev O.V., Pavlov N.B., Kryuchko D.S., Goryachev D.V., Merkulov V.A., Shipulin G.A., Yudin S.M. data processing – Nikonova A.A., Kofiadi I.A., Shilovsky I.P., Gudima G.O.; writing and editing the article – Khaitov M.R., Nikonova A.A., Kofiadi I.A., Smirnov V.V., Gudima G.O.
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