Phase 2-3 Trial: Prevention of the Progression to Moderate and Severe COVID-19 in SARS-CoV-2-Infected Non-Hospitalized Adults With Inhaled siRNA-Based MIR 19.

Abstract

Background: COVID-19 continues to be a major global health challenge. Inhaled siRNA-based MIR 19 has been shown to reduce the time to clinical improvement in patients hospitalized with moderate COVID-19.

Methods: We conducted an open-label, randomized, controlled multicenter phase 2b-3 trial (NCT05783206) evaluating the safety and efficacy of inhaled siR-7-EM/KK-46 (MIR 19) (5.55 mg/day) in comparison with standard care (control group) in outpatients with mild COVID-19 (N = 492 for each group). The primary endpoint was the proportion of patients who developed moderate or severe COVID-19 by the 28th day of randomization.

Results: Moderate or severe course of the disease was detected in 14 (2.85%) and 34 (6.91%) patients in the siR-7-EM/KK-46 (5.55 mg) and standard therapy groups, respectively (the difference in proportions was -4.107% [95% CI: -7.28% to -1.03%] (p = 0.002)). Adverse events (AE) were reported in 77 (15.65%) patients from the siR-7-EM/KK-46 (5.55 mg) group, while in the standard therapy group AEs were registered in 100 (20.33%) patients. No severe, treatment-related AEs were observed in the siR-7-EM/KK-46 group.

Conclusions: siR-7-EM/KK-46, a SARS-CoV-2-specific RNAi-based drug, was well-tolerated and significantly decreased the progression to moderate/severe disease in outpatients with mild COVID-19.