RNA polymerase inhibitor enisamium for treatment of moderate COVID-19 patients: a randomized, placebo-controlled, multicenter, double-blind phase 3 clinical trial

Enisamium (trade name Amizon ® MAX) is an orally available therapeutic that inhibits influenza A virus and SARS-CoV-2 replication in vitro and improves influenza patient recovery. We evaluated the clinical efficacy of enisamium treatment combined with standard care compared to standard care plus treatment with a placebo control in adult, hospitalized patients with moderate COVID-19 requiring external oxygen. Hospitalized patients with laboratory-confirmed SARS-CoV-2 infection were randomly assigned to receive either enisamium (500 mg per dose, 4 times a day) or a placebo. All patients received standard of care as deemed necessary by the investigator and the health status of each patient. The primary outcome was an improvement of at least two points on an 8-point, modified WHO severity rating (SR) scale within 29 days of randomization. A total of 592 patients were enrolled and randomized between May 2020 and March 2021. Patients with a baseline SR of 4 were divided into two groups: 142 (49.8%) were assigned to the enisamium group and 143 (50.2%) to the placebo group. No differences were observed between the safety or patient tolerability profiles of the enisamium and placebo treatment. Analysis of the population showed that if patients were treated within 4 days of the onset of COVID-19 symptoms (n = 33), the median time to improvement was 8 days for the enisamium group and 13 days for the placebo group (p = 0.0051). For patients treated within 10 days of the onset of COVID-19 symptoms (n = 154), the median time to improvement was 10 days for the enisamium group and 12 days for the placebo group (p = 0.002). Comparison of groups using a stratified one-sided Logrank criterion (adjustment using stratification by age categories: “<40 years”, “40-<65 years” and “≥65 years”) showed statistically significant differences between the groups (p = 0.00945, one-sided). Our findings suggest that enisamium is safe to use in COVID-19 patients, and that enisamium treatment offers a clinical benefit when given to patients with moderate COVID-19 requiring supplementary oxygen, if enisamium is given within 10 days of the onset of symptoms. This trial was registered with ClinicalTrials.gov under NCT04682873 .