Rejuveinix Reverses Severe Inflammatory Lung Damage in a Mouse Model of Fatal Sepsis

Uckun, Fatih M.; Ozercan, İbrahim Hanifi; Orhan, Cemal; Gitterle, Marcus; Şahin, Kazım

doi:10.1101/2020.12.31.424986

Cited by 2 publications

(4 citation statements)

References 3 publications

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“…Recently, we demonstrated that RJX prevents in the LPS-GalN mouse model of sepsis the marked increase of each of these cytokines in the serum as well as lungs and liver [26]. Furthermore, preliminary evidence suggested that it may also be effective in reversing sepsis if administered after the onset of sepsis [35].…”

Section: Discussionmentioning

confidence: 99%

“…RJX exhibited promising single-agent anti-inflammatory activity in a mouse model of fatal CRS and ARDS [26]. Preliminary evidence suggested that it may effectively reverse CRS and ARDS if administered after the onset of ALI in LPS-GalN challenged mice [35]. Further, RJX showed a very favorable clinical safety and pharmacokinetics (PK) profile in a recently completed randomized, double-blind, placebo-controlled Phase I ascending dose-escalation study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) [26].…”

Section: Introductionmentioning

confidence: 99%

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Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19

Uckun¹,

Saeed²,

Awili³

et al. 2022

Preprint

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Background. The identification of effective strategies capable of reducing the case mortality rate of high-risk COVID-19 is an urgent and unmet medical need. We recently reported the clinical safety profile of RJX, a well-defined intravenous GMP-grade pharmaceutical formulation of anti-oxidant and anti-inflammatory vitamins as active ingredients, in a Phase 1 study in healthy volunteers (ClinicalTrials.gov Identifier: NCT03680105) (Uckun et al., Front. Pharmacol. 11, 594321. 10.3389/fphar.2020.594321). Here we report data from a pilot clinical study (RPI-015) which examined the safety, tolerability, and feasibility of using RJX in combination with clinical standard of care (SOC) in hospitalized COVID-19 patients with pneumonia (ClinicalTrials.gov Identifier: NCT04708340). In addition to our early clinical proof of concept (POC) data, we also present non-clinical POC from a mouse model of CRS and ARDS that informed the design of the reported clinical study. Methods. 13 patients, who were hospitalized with COVID-19 pneumonia and abnormally elevated serum inflammatory biomarkers markers ≥3 months prior to the identification of the first confirmed U.S case of the Omicron variant, were treated with IV RJX (daily x 7 days) plus SOC. Non-clinical POC study examined the ability of RJX plus dexamethasone (DEX) to improve the survival outcome in the lipopolysaccharide (LPS)-Galactosamine (GalN) mouse model of fatal cytokine release syndrome (CRS), sepsis and acute respiratory distress syndrome (ARDS). Findings. In the Phase 1 clinical study, none of the 13 patients developed a treatment-related DLT, SAE, or Grade 3-5 AEs. Nine (9) of the 12 evaluable patients, including 3 patients with hypoxemic respiratory failure, showed rapid clinical recovery. In the non-clinical POC study in LPS-GalN challenged mice, the combination of RJX plus DEX was more effective than RJX alone or DEX alone, reversed the CRS as well as inflammatory tissue damage in the lungs and liver, and improved the survival outcome. Taken together, these findings provide the early clinical and non-clinical POC for the development of RJX as an adjunct to the SOC in the multi-modality management of high-risk COVID-19.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19

Uckun¹,

Saeed²,

Awili³

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recently, we demonstrated that RJX prevents in the LPS-GalN mouse model of sepsis the marked increase of each of these cytokines in the serum as well as lungs and liver [ 17 ]. Furthermore, preliminary evidence has suggested that it may also be effective in reversing sepsis if administered after the onset of sepsis [ 19 ]. Here we report on the activity of a combination of RJX plus DEX in therapeutic settings in a preclinical sepsis model.…”

Section: Discussionmentioning

confidence: 99%

“…Specifically, it decreased the inflammatory cytokine responses and improved survival when administered prophylactically in mice challenged with LPS-GalN. Furthermore, preliminary experiments have suggested that it may also be effective in reversing sepsis if administered after the onset of sepsis [ 17 , 19 ]. In addition, RJX showed a favorable clinical safety and pharmacokinetics profile in a recently completed randomized, double-blind, placebo-controlled phase I ascending dose-escalation study in healthy volunteers (Clinical Trial Registration: NCT03680105 [ClinicalTrials.gov]) [ 17 ].…”

mentioning

confidence: 99%

Evaluation of the Potential Of Rejuveinix Plus Dexamethasone Against Sepsis

Uckun¹,

Saeed

Awili

et al. 2022

Future Microbiol.

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Aim: Our main objectives were to compare the effects of Rejuveinix (RJX), dexamethasone (DEX) and their combination on the severity of sepsis and survival outcome in an animal model of fatal sepsis. Methods: We used the LPS plus D-galactosamine mouse model of sepsis to compare the anti-inflammatory activities of RJX, dexamethasone and a combination of RJX plus DEX. Additionally, we examined the clinical feasibility and tolerability of combining RJX with DEX in COVID-19 patients in a clinical phase I study. Data were analyzed using standard methods. Results & conclusion: RJX exhibited potent anti-inflammatory activity in the murine sepsis model. The combination of RJX plus DEX was more effective than either agent alone, decreased the inflammatory cytokine responses and associated organ damage, and improved the survival outcome in mice. In the phase I clinical study, RJX plus DEX was well tolerated by COVID-19 patients.

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Rejuveinix Reverses Severe Inflammatory Lung Damage in a Mouse Model of Fatal Sepsis

Cited by 2 publications

References 3 publications

Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19

Clinical and Non-clinical Proof of Concept Supporting the Development of RJX As an Adjunct to Standard of Care Against Severe COVID-19

Evaluation of the Potential Of Rejuveinix Plus Dexamethasone Against Sepsis

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