A randomized, double-blind, placebo-controlled trial of niclosamide nanohybrid for the treatment of patients with mild to moderate COVID-19

Abstract

Effective and reliable treatments for SARS-CoV-2 infections are a key part of global COVID-19 management. Based on vitro studies, niclosamide has been considered as a potential drug candidate for SARS-CoV-2, but its clinical development has been limited due to poor solubility and bioavailability. Here we report results from a randomized, double-blind, placebo-controlled clinical trial involving 300 patients (Clinical Trial Registration Number: KCT0007307) that assessed the efficacy and safety of the niclosamide nanohybrid CP-COV03 at two different doses. Oral CP-COV03 was well tolerated, with no serious adverse events reported in any treatment group. The primary endpoints demonstrated that CP-COV03 significantly alleviated all 12 FDA-recommended COVID-19 symptoms, with symptom improvement sustained for more than 48 h. Additionally, CP-COV03 reduced SARS-CoV-2 viral load by 56.7% within 16 h of the initial dose compared to baseline. Secondary endpoints, including time to sustained symptom resolution, time to return to usual health, and reduction in hospitalization risk, also showed favorable results in the CP-COV03 group compared to placebo. These findings indicate that CP-COV03 is a safe and effective therapeutic option for the treatment of mild to moderate COVID-19 and represents a promising advancement in the repurposing of niclosamide through nanohybrid engineering.

Fig. 1. CONSORT diagram for clinical trial.

Shown is the study flow chart for randomized, double-blind, placebo-controlled trial of multiple doses of CP-COV03 in mild or moderate COVID-19 (Created in BioRender. REJINOLD, S. (2025) https://BioRender.com/ wlivq3e).

Fig. 2. Viral load and pharmacokinetic analyses.

A The adjusted mean change in viral load from baseline of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) monitored starting from Day 0. Any data point that is more than 3 times the IQR above the third quartile or below the first quartile is an outlier (n = 77 for the placebo group, n = 70 for the low dose group, n = 80 for the high dose group). Error bars represent standard error (S.E.). B Pharmacokinetic profiles of niclosamide from clinical trial (n = 20 for the placebo group, n = 20 for the low dose group, n = 18 for the high dose group). Error bars represent standard error (S.E.).

Fig. 3. Correlation between CP-COV03 pharmacokinetic parameters and the viral load of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

A the low dose group; B the high dose group (n = 15 for the low dose, n = 11 for the high dose groups.