Romark announced initial results from a phase 3 trial evaluating NT-300 (nitazoxanide extended-release tablets, 300 mg) versus placebo as a treatment for mild or moderate COVID-19. Nt-300 significantly reduced progression to severe disease compared to placebo. Based on the findings, Romark is working with the U.S. Food and Drug Administration (FDA) and plans to seek Emergency Use Authorization (EUA).
The multicenter, randomized, double-blind trial studied 1,092 subjects ages 12 and older with respiratory symptoms consistent with COVID-19. The subjects were enrolled at outpatient centers across the United States within 72 hours of symptom onset and treated either with two NT-300 tablets or placebo twice daily for five days. Efficacy analyses was based on 379 patients who had laboratory-confirmed SARS-CoV-2 infection at baseline.
For the primary endpoint, median time to sustained response (a measure of recovery time) was similar for subjects treated with NT-300 compared with placebo (approximately 13 days). In the pre-defined subgroup of patients with mild disease, median time to sustained response was reduced by 3.1 days with NT-300 (10.3 days, n=116) versus placebo (13.4 days, n=129).
For the key secondary endpoint, treatment with NT-300 was associated with an 85% (0.5% of NT-300-treated patients vs. 3.6% of patients treated with placebo) reduction in the progression to severe illness (shortness of breath). In the pre-defined subgroup at high risk of severe illness according to CDC criteria, 7/126 (5.6%) of placebo-treated subjects experienced severe illness compared to 1/112 (0.9%) of NT-300-treated subjects.
NT-300 was well tolerated. The only adverse event occurring in more than 2% of subjects was diarrhea (3.4% in the NT-300 group vs. 2.2% in the placebo group). There were no significant differences in adverse events between the two treatment groups.
Full findings from the study will be submitted for publication in a peer-reviewed journal.
NT-300 (nitazoxanide extended-release tablets) is an investigational broad-spectrum antiviral drug. Nitazoxanide, the active ingredient of NT-300, was originally developed for treating intestinal protozoan infections caused by Cryptosporidium parvum and Giardia lamblia. Laboratory studies demonstrating broad-spectrum antiviral activity led to the development of nitazoxanide as a broad-spectrum, host-directed antiviral drug.
In cell cultures nitazoxanide inhibits maturation of the SARS-CoV-2 spike protein, which in turn blocks SARS-CoV-2 syncytia formation. Nitazoxanide has also been shown to inhibit replication of SARS, MERS and other coronaviruses as well as influenza viruses, rhinoviruses, parainfluenza viruses, RSV and other respiratory viruses in cell culture studies. The broad-spectrum antiviral activity of nitazoxanide is attributed to its interference with human cellular pathways that the virus exploits to replicate, rather than to a virus-targeted mechanism.