Safety and antiviral activity of inhaled siRNA SNS812 for treatment of mild-to-moderate COVID-19: a phase 2 randomized trial
et al., Journal of Biomedical Science, doi:10.1186/s12929-026-01284-5 (results released 3/11/2025), NCT05941793, Mar 2025
RCT 135 patients with mild to moderate COVID-19 showing significant efficacy of inhaled SNS812 (siRNA targeting SARS-CoV-2 RdRP) for reducing viral load and accelerating symptom resolution. The trial randomized patients to 200mg, 100mg, or placebo arms, with treatment initiated within 3 days of symptom onset. The 200mg group demonstrated significantly faster viral clearance and greater viral load reduction starting from day 1. Symptom improvement showed dose-dependent effects with significant reduction in time to resolution for 6 of 14 symptoms, including shortness of breath and loss of taste/smell. The siRNA targets a highly conserved region of the viral RNA-dependent RNA polymerase gene and showed efficacy against multiple Omicron variants.
Targeted administration to the respiratory tract provides treatment directly
to the typical source of initial SARS-CoV-2 infection and replication, and
allows for rapid onset of action, higher local drug concentration, and reduced systemic side effects.
|
risk of no recovery, 51.7% lower, HR 0.48, p = 0.002, treatment 45, control 45, adjusted per study, inverted to make HR<1 favor treatment, 200mg, sustained resolution of nine target symptoms, day 28.
|
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risk of no recovery, 38.3% lower, HR 0.62, p = 0.04, treatment 43, control 45, adjusted per study, inverted to make HR<1 favor treatment, 100mg, sustained resolution of nine target symptoms, day 28.
|
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recovery time, 24.7% lower, relative time 0.75, p = 0.17, treatment 6.1 [4.25-7.17] n=45, control 8.1 [6.29-11.17] n=45, 200mg, median time to sustained resolution of nine target symptoms, Kaplan-Meier, day 28.
|
|
recovery time, 27.2% lower, relative time 0.73, p = 0.11, treatment 5.9 [4.88-6.75] n=43, control 8.1 [6.29-11.17] n=45, 100mg, median time to sustained resolution of nine target symptoms, Kaplan-Meier, day 28.
|
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risk of no improvement, 44.8% better, HR 0.55, p = 0.01, treatment 45, control 45, adjusted per study, inverted to make HR<1 favor treatment, 200mg, sustained alleviation of nine target symptoms, day 28.
|
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risk of no improvement, 34.2% better, HR 0.66, p = 0.08, treatment 43, control 45, adjusted per study, inverted to make HR<1 favor treatment, 100mg, sustained alleviation of nine target symptoms, day 28.
|
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time to improvement, 44.6% lower, relative time 0.55, p = 0.06, treatment 3.6 [2.63-5.88] n=45, control 6.5 [3.25-8.25] n=45, 200mg, median time to sustained alleviation of nine target symptoms, Kaplan-Meier, day 28.
|
|
time to improvement, 24.6% lower, relative time 0.75, p = 0.26, treatment 4.9 [3.88-5.96] n=43, control 6.5 [3.25-8.25] n=45, 100mg, median time to sustained alleviation of nine target symptoms, Kaplan-Meier, day 28.
|
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viral load, 13.6% lower, relative load 0.86, p = 0.04, treatment 45, control 44, adjusted per study, 200mg, viral load reduction rate, regression coefficient day 0-4, mixed model, multivariable.
|
|
viral load, 44.1% lower, relative load 0.56, p = 0.02, treatment mean 0.93 (±0.94) n=45, control mean 0.52 (±0.87) n=45, 200mg, magnitude of mean viral RNA reduction from baseline, day 1.
|
|
viral load, 21.9% lower, relative load 0.78, p = 0.16, treatment mean 1.6 (±1.21) n=45, control mean 1.25 (±1.14) n=45, 200mg, magnitude of mean viral RNA reduction from baseline, day 2.
|
|
viral load, 17.1% lower, relative load 0.83, p = 0.07, treatment mean 2.52 (±1.07) n=45, control mean 2.09 (±1.14) n=45, 200mg, magnitude of mean viral RNA reduction from baseline, day 3.
|
|
viral load, 17.1% lower, relative load 0.83, p = 0.01, treatment mean 2.98 (±1.14) n=45, control mean 2.47 (±1.14) n=45, 200mg, magnitude of mean viral RNA reduction from baseline, day 4.
|
|
viral load, 3.4% lower, relative load 0.97, p = 0.62, treatment mean 3.51 (±1.14) n=45, control mean 3.39 (±1.14) n=45, 200mg, magnitude of mean viral RNA reduction from baseline, day 6.
|
|
viral load, 0.5% lower, relative load 0.99, p = 0.93, treatment mean 3.69 (±1.07) n=45, control mean 3.67 (±0.94) n=45, 200mg, magnitude of mean viral RNA reduction from baseline, day 8.
|
|
time to viral-, 19.4% lower, relative time 0.81, p = 0.007, treatment 2.9 [2.54-3.08] n=45, control 3.6 [3.0-3.96] n=45, 200mg, median time to first of two consecutive negative antigen tests, Kaplan-Meier.
|
|
viral load, 8.8% lower, relative load 0.91, p = 0.81, treatment mean 0.57 (±1.05) n=43, control mean 0.52 (±0.87) n=45, 100mg, magnitude of mean viral RNA reduction from baseline, day 1.
|
|
viral load, 12.0% lower, relative load 0.88, p = 0.51, treatment mean 1.42 (±1.25) n=43, control mean 1.25 (±1.14) n=45, 100mg, magnitude of mean viral RNA reduction from baseline, day 2.
|
|
viral load, 4.6% lower, relative load 0.95, p = 0.71, treatment mean 2.19 (±1.38) n=43, control mean 2.09 (±1.14) n=45, 100mg, magnitude of mean viral RNA reduction from baseline, day 3.
|
|
viral load, 13.3% lower, relative load 0.87, p = 0.13, treatment mean 2.85 (±1.18) n=43, control mean 2.47 (±1.14) n=45, 100mg, magnitude of mean viral RNA reduction from baseline, day 4.
|
|
viral load, 0.6% higher, relative load 1.01, p = 0.93, treatment mean 3.37 (±1.11) n=43, control mean 3.39 (±1.14) n=45, 100mg, magnitude of mean viral RNA reduction from baseline, day 6.
|
|
viral load, 0.5% lower, relative load 0.99, p = 0.92, treatment mean 3.69 (±0.92) n=43, control mean 3.67 (±0.94) n=45, 100mg, magnitude of mean viral RNA reduction from baseline, day 8.
|
| Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates |
Chen et al., 11 Mar 2025, Double Blind Randomized Controlled Trial, placebo-controlled, Taiwan, peer-reviewed, 20 authors, study period 19 September, 2023 - 12 August, 2024, trial NCT05941793 (history).
Contact: pcyang@ntu.edu.tw.
Abstract: ## RESEARCH
Open Access
Safety and antiviral activity of inhaled siRNA SNS812 for treatment of mild-to-moderate COVID-19: a phase 2 randomized trial
Shey-Ying Chen 1† , Sui-Yuan Chang 2† , Yi-Chung Chang 3† , Ming-Che Liu 4,5,6,7 , Kuan-Yuan Chen 8 , Jer-Hwa Chang 9,10 , Wen-Pin Tseng 1 , Chien-Hao Lin 1 , Jhong-Lin Wu 1 , Pai-Chien Chou 11,12 , Tsong-Yih Ou 13 , Chin-Wang Hsu 14,15 , Feng-Yi Chou 6 , Hui-Ju Ho 3 , Jen-Fu Yang 3 , Chi-Fan Yang 16 , Yi-Fen Chen 3 , Kang-Yun Lee 17† , William Lu 3† and Pan-Chyr Yang 18*
Abstract
Background SARS-CoV-2 remains a global health threat because ongoing viral evolution and immune evasion reduce the effectiveness of existing therapies. SNS812 is an inhaled small interfering RNA targeting a highly conserved region of the viral RNA-dependent RNA polymerase gene, representing a strategy that may enable broader antiviral activity against emerging variants.
Methods In this phase 2, double-blind, randomised, placebo-controlled trial, adults with mild-to-moderate COVID19 within 3 days of symptom onset were randomly assigned (1:1:1) to receive placebo or inhaled SNS812 (100 mg or 200 mg) once daily for 7 days (ClinicalTrials.gov identifier: NCT05941793). Safety was the primary endpoint. Secondary endpoints included the time to sustained alleviation (TTSA) and resolution (TTSR) for prespecified composite target symptoms and individual symptoms. Virological outcomes were exploratory.
Results A total of 135 participants were enrolled, with more than 90% infected with immune-evasive SARS-CoV-2 variants. No treatment-related adverse events or serious adverse events were reported. In exploratory analyses, the 200 mg SNS812 group showed a shorter median time to SARS-CoV-2 antigen negativity (2.9 vs 3.6 days; p = 0.007) and a faster viral load reduction rate (- 0.755 vs - 0.652; p = 0.040), demonstrating dose-dependent virological effects. In the modified intention-to-treat population, exploratory symptom analyses showed shorter TTSA and TTSR for prespecified target symptoms with SNS812 200 mg compared with placebo (median TTSR 6.1 vs 8.1 days; adjusted hazard ratio 2.07, 95% CI 1.30-3.29; median TTSA 3.6 vs 6.5 days; adjusted hazard ratio 1.81, 95% CI 1.14-2.88).
Conclusion Inhaled SNS812 was safe and well tolerated and showed dose-dependent antiviral activity, with exploratory signals of symptomatic improvement in adults with mild-to-moderate COVID-19 infected with immune-evasive variants. These findings support further evaluation in larger, adequately powered trials, including older and higher-risk populations.
† Shey-Ying Chen, Sui-Yuan Chang and Yi-Chung Chang have contributed equally to this work.
† Kang-Yun Lee and William Lu are senior authorship.
*Correspondence:
Pan-Chyr Yang pcyang@ntu.edu.tw Full list of author information is available at the end of the article
© The Author(s) 2026. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your..
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"abstract": "<jats:title>Abstract</jats:title>\n <jats:sec>\n <jats:title>Background</jats:title>\n <jats:p>SARS-CoV-2 remains a global health threat because ongoing viral evolution and immune evasion reduce the effectiveness of existing therapies. SNS812 is an inhaled small interfering RNA targeting a highly conserved region of the viral RNA-dependent RNA polymerase gene, representing a strategy that may enable broader antiviral activity against emerging variants.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Methods</jats:title>\n <jats:p>In this phase 2, double-blind, randomised, placebo-controlled trial, adults with mild-to-moderate COVID-19 within 3 days of symptom onset were randomly assigned (1:1:1) to receive placebo or inhaled SNS812 (100 mg or 200 mg) once daily for 7 days (ClinicalTrials.gov identifier: NCT05941793). Safety was the primary endpoint. Secondary endpoints included the time to sustained alleviation (TTSA) and resolution (TTSR) for prespecified composite target symptoms and individual symptoms. Virological outcomes were exploratory.</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Results</jats:title>\n <jats:p>A total of 135 participants were enrolled, with more than 90% infected with immune-evasive SARS-CoV-2 variants. No treatment-related adverse events or serious adverse events were reported. In exploratory analyses, the 200 mg SNS812 group showed a shorter median time to SARS-CoV-2 antigen negativity (2.9 vs 3.6 days; p = 0.007) and a faster viral load reduction rate (− 0.755 vs − 0.652; p = 0.040), demonstrating dose-dependent virological effects. In the modified intention-to-treat population, exploratory symptom analyses showed shorter TTSA and TTSR for prespecified target symptoms with SNS812 200 mg compared with placebo (median TTSR 6.1 vs 8.1 days; adjusted hazard ratio 2.07, 95% CI 1.30–3.29; median TTSA 3.6 vs 6.5 days; adjusted hazard ratio 1.81, 95% CI 1.14–2.88).</jats:p>\n </jats:sec>\n <jats:sec>\n <jats:title>Conclusion</jats:title>\n <jats:p>Inhaled SNS812 was safe and well tolerated and showed dose-dependent antiviral activity, with exploratory signals of symptomatic improvement in adults with mild-to-moderate COVID-19 infected with immune-evasive variants. These findings support further evaluation in larger, adequately powered trials, including older and higher-risk populations.</jats:p>\n </jats:sec>",
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