Background
The rapid emergence of immune-evasive SARS-CoV-2 variants poses a significant challenge, as current therapies and vaccines struggle to keep pace. SNS812, an aerosolized broad-spectrum antiviral siRNA, targets a conserved region of the RNA-dependent RNA polymerase gene, unchanged since the 2003 SARS outbreak, offering potential efficacy against diverse variants. In a 2023 Phase I trial (NCT05677893) in the U.S., SNS812 showed excellent safety. Here we present the Phase II trial results which shows SNS812 is safe and effective in treating COVID-19.
Methods
This double-blind, randomized, placebo-controlled Phase II trial (NCT05941793) involved 135 symptomatic, PCR-confirmed COVID-19 patients, all vaccinated at least three months prior. Participants were randomly assigned to receive either 100mg SNS812, 200mg SNS812, or placebo. The primary endpoint was the incidence of treatment-emergent adverse events; efficacy endpoints included viral variant analysis, time to viral clearance, viral load reduction, and symptoms improvement.
Results
Baseline characteristics showed no significant differences between the groups. No drug-related adverse events were observed in the SNS812 treatment groups. All 135 participants had their viral sequence confirmed and identified which revealed that 90% of patients were infected with highly immune-evasive variants, with the majority being JN.1 (49.6%), LB.1 (17.1%), and KP.2 (11.1%). Viral load analysis showed that in the SNS812 treatment groups, viral load significantly decreased by 0.4 log within one day of SNS812 200mg administration (P=0.029). Additionally, the median time to viral clearance was reduced from 3.6 days (control group) to 2.9 days (200mg group)(P=0.007). For clinically meaningful symptoms, 12 out of 14 COVID-19 symptoms showed improvements, with key symptoms such as shortness of breath (P=0.007), loss of smell (P=0.028), and loss of taste (P=0.006) achieving statistical significance. Furthermore, a dose-dependent relationship was noted, with more significant improvement in 200mg group compared to the 100mg.
Conclusions
The Phase II study demonstrates that SNS812 is a safe and effective treatment for COVID-19, especially in the context of immune-evasive variants. Its ability to significantly reduce viral load within one day, accelerate viral clearance, and improve symptoms positions SNS812 as a promising pan-coronavirus therapeutic solution, capable of addressing ongoing viral mutations.
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