Bencheqroun, HassanAhmed, YasirKoçak, MehmetVilla, EnriqueBarrera, CesarMohiuddin, MariyaFortunet, RaulIyoha, EmmanuelBates, DeborahOkpalor, ChineduAgbosasa, OlaMohammed, KarimPondell, StephenMohamed, AmrMohamed, Yehia I.Gök Yavuz, BetülKaseb, Mohamed O.Kasseb, Osama O.Gocio, Michelle YorkTu, Peter Tsu-ManLi, DanLu, JianmingSelim, AbdulhafezMa, QingKaseb, Ahmed O.2022-12-152022-12-152022Bencheqroun, H., Ahmed, Y., Koçak, M., Villa, E., Barrera, C., Mohiuddin, M. ... Kaseb, A. O. (2022). A randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety and efficacy of thymoquinone formula (TQF) for treating outpatient SARS-CoV-2. Pathogens, 11(5). https://doi.org/10.3390/pathogens110505512076-0817https://doi.org/10.3390/pathogens11050551https://hdl.handle.net/20.500.12511/10126There 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.enAttribution 4.0 Internationalinfo:eu-repo/semantics/openAccessCoronavirusCOVID-19PandemicSARS-CoV-2TQ FormulaArticle11510.3390/pathogens11050551Q20008016005000012-s2.0-8513020906035631072Q2