A Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Safety and Efficacy of ThymoQuinone Formula (TQF) for Treating Outpatient SARS-CoV-2
Hassan Bencheqroun, Yasir Ahmed, Mehmet Kocak, Enrique Villa, Cesar Barrera, Mariya Mohiuddin, Raul Fortunet, Emmanuel Iyoha, Deborah Bates, Chinedu Okpalor, Ola Agbosasa, Karim Mohammed, Stephen Pondell, Amr Mohamed, Yehia I Mohamed, Betul Gok Yavuz, Mohamed O Kaseb, Osama O Kasseb, Michelle York Gocio, Peter Tsu-Man Tu, Dan Li, Jianming Lu, Abdulhafez Selim, Qing Ma, Ahmed O Kaseb
Pathogens, doi:10.3390/pathogens11050551
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.
method and compared between the two arms of the study by the log-rank test. Median time-to-SCR was estimated through the Kaplan-Meier product-limit method. In comparing viral load (VL) distribution between the two arms of the study crosssectionally, the Wilcoxon-Mann-Whitney test, a non-parametric alternative to the twosample t-test, was used, where any measurement provided as '>25,000' was conservatively considered as 25,000 and the VL measurements of SARS-CoV-2-negative samples were considered as zero. For longitudinal modeling of VL, a random coefficient modeling approach through the SAS MIXED procedure was used with individual specific intercepts and slope estimates. The same approach was used for longitudinal individual symptom burden assessments, where both linear and quadratic changes over time were added to the model. We added symptom scores to obtain a measure of total symptom burden from days 1-14; similarly, subdomain scores were obtained as unweighted additions of relevant symptom scores. In all these longitudinal models, the primary interest was to investigate whether there was a significant change in these markers over time and whether such change depended on the treatment arm. For the T lymphocytes subsets, compared on day 1, day 7, and day 14, the abovementioned non-parametric testing approach was also used. As the flow-cytometry analysis was exploratory in nature, no multiplicity correction was carried out. Consequently, the widths of the intervals have..
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'abstract': '<jats:p>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.</jats:p>',
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