A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2

Abstract

There is an urgent need for an oral drug for the treatment of mild to moderate outpatient SARS-CoV-2. Our preclinical and clinical study’s aim was to determine the safety and preliminary efficacy of oral TQ Formula (TQF), in the treatment of outpatient SARS-CoV-2. In a double-blind, placebo-controlled phase 2 trial, we randomly assigned (1:1 ratio) non-hospitalized, adult (>18 years), symptomatic SARS-CoV-2 patients to receive oral TQF or placebo. The primary endpoints were safety and the median time-to-sustained-clinical-response (SCR). SCR was 6 days in the TQF arm vs. 8 days in the placebo arm (p = 0.77), and 5 days in the TQF arm vs. 7.5 days in the placebo arm in the high-risk cohort, HR 1.55 (95% CI: 0.70, 3.43, p = 0.25). No significant difference was found in the rate of AEs (p = 0.16). TQF led to a significantly faster decline in the total symptom burden (TSB) (p < 0.001), and a significant increase in cytotoxic CD8+ (p = 0.042) and helper CD4+ (p = 0.042) central memory T lymphocytes. TQF exhibited an in vitro inhibitory effect on the entry of five SARS-CoV-2 variants. TQF was well-tolerated. While the median time-to-SCR did not reach statistical significance; it was shorter in the TQF arm and preclinical/clinical signals of TQF activity across multiple endpoints were significant. Therefore, a confirmatory study is planned.

Keywords: COVID-19; SARS-CoV-2; TQ Formula; coronavirus; pandemic.

Figure 1

Consort diagram.

Figure 2

(A) Time-to-sustained-clinical-response (SCR) distribution by Kaplan–Meier curve. Shown are Kaplan–Meier estimates of SCR for TQF (blue) and placebo (red) arms. Stratified hazard ratios for SCR are reported, along with p values. CI denotes confidence interval. (B) Time-to-SCR distribution by Kaplan–Meier curve for high-risk patients. Shown are Kaplan–Meier estimates of SCR for TQF (blue) and placebo (red) arms. Stratified hazard ratios for SCR are reported, along with p values. (C) Viral load distribution over time by treatment arm. Shown are the viral load distribution from day 0 to day 14 for TQF (blue) and placebo (red) arms. (D) Model-based change of total symptom burden (TSB) change by study arm. Shown are the model-based change of TSB, defined as the duration and severity of symptoms over time, for TQF (blue) and placebo (red) arms. (E) Comparison of T cells between the treatment arms. Shown are comparison of percentage of CD45RA⁺CCR7⁺ in CD4 and CD8 T cells on day 14 between TQF (blue) and placebo (red) arms. (F) Potential mechanism of action of TQ Formula. TQ Formula may be effective treating COVID-19 via inhibiting viral entry through ACE2 blockage, reducing cytokine storm and promoting T cell recovery.