Abstract:
:Background: New treatment platforms that can prevent acute respiratory distress syndrome (ARDS) or reduce its mortality rate in high-risk coronavirus disease 2019 (COVID-19) patients, such as those with an underlying cancer, are urgently needed. Rejuveinix (RJX) is an intravenous formulation of anti-oxidants and anti-inflammatory agents. Its active ingredients include ascorbic acid, cyanocobalamin, thiamine hydrochloride, riboflavin 5' phosphate, niacinamide, pyridoxine hydrochloride, and calcium D-pantothenate. RJX is being developed as an anti-inflammatory and anti-oxidant treatment platform for patients with sepsis, including COVID-19 patients with viral sepsis and ARDS. Here, we report its clinical safety profile in a phase 1 clinical study (ClinicalTrials.gov Identifier: NCT03680105) and its potent protective activity in the lipopolysaccharide galactosamine (LPS-GalN) mouse model of ARDS. Methods: A phase 1, double-blind, placebo-controlled, randomized, two-part, ascending dose-escalation study was performed in participating 76 healthy volunteer human subjects in compliance with the ICH (E6) good clinical practice guidelines to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of RJX (Protocol No. RPI003; ClinicalTrials.gov Identifier: NCT03680105). The ability of RJX to prevent fatal shock, ARDS, and multi-organ failure was examined in the well-established LPS-GalN mouse model of sepsis and ARDS. Standard methods were employed for the statistical analysis of data in both studies. Findings: In the phase 1 clinical study, no participant developed serious adverse events (SAEs) or Grade 3-Grade 4 adverse events (AEs) or prematurely discontinued participation in the study. In the non-clinical study, RJX exhibited potent and dose-dependent protective activity, decreased the inflammatory cytokine responses (interleukin-6, tumor necrosis factor alpha, transforming growth factor beta), and improved survival in the LPS-GalN mouse model of sepsis and ARDS. Histopathological examinations showed that RJX attenuated the LPS-GalN induced acute lung injury (ALI) and pulmonary edema as well as liver damage. Conclusion: RJX showed a very favorable safety profile and tolerability in human subjects. It shows potential to favorably affect the clinical course of high-risk COVID-19 by preventing ARDS and its complications.
journal_name
Front Pharmacoljournal_title
Frontiers in pharmacologyauthors
Uckun FM,Carlson J,Orhan C,Powell J,Pizzimenti NM,van Wyk H,Ozercan IH,Volk M,Sahin Kdoi
10.3389/fphar.2020.594321subject
Has Abstractpub_date
2020-11-10 00:00:00pages
594321issn
1663-9812pii
594321journal_volume
11pub_type
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章,评审
doi:10.3389/fphar.2018.00903
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pub_type: 杂志文章
doi:10.3389/fphar.2013.00005
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abstract::This study investigates the protein expression of C-MYC, BCL-2, and BCL-6 in diffuse large B-cell lymphoma (DLBCL) and their relationship with genetic abnormalities. A retrospective study of 42 cases on paraffin-embedded tissue specimens diagnosed with DLBCL was performed using immunohistochemistry (IHC) and fluoresce...
journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.01497
更新日期:2019-01-07 00:00:00
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2018.00215
更新日期:2018-03-15 00:00:00
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2013.00098
更新日期:2013-08-08 00:00:00
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pub_type: 杂志文章,评审
doi:10.3389/fphar.2019.00114
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2012.00140
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journal_title:Frontiers in pharmacology
pub_type: 杂志文章
doi:10.3389/fphar.2019.00275
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pub_type: 杂志文章
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