Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus-19 – The IONIC Trial Protocol

Sharma, Kavi; Berry, Lisa; Vryonis, Evangelos; Ali, Asad; Lara, Beatríz; Noufaily, Angela; Parsons, Nicholas R.; Bradley, Christopher; Haley, Becky; Tabuso, Maria; Arasaradnam, Ramesh P.

doi:10.1101/2021.07.13.21258757

2021

DOI: 10.1101/2021.07.13.21258757

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Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus-19 – The IONIC Trial Protocol

Kavi Sharma

Lisa Berry

Evangelos Vryonis

et al.

Abstract: Background: Globally there is a scarcity of effective treatments for SARS-CoV-2 infections (causing COVID 19). Repurposing existing medications may offer the best hope for treating COVID 19 patients to curb the pandemic. IMU-838 is a dihydroorotate dehydrogenase (DHODH) inhibitor, which is an effective mechanism for antiviral effects against respiratory viruses. When used synergistically with Oseltamivir, therapeutic effects have been observed against influenza and SARS-CoV-2 in rodents.(13) The IONIC trial is… Show more

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Cited by 2 publications

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A first in man study to evaluate the safety, pharmacokinetics and pharmacodynamics of RP7214, a dihydroorotate dehydrogenase inhibitor in healthy subjects

Nair

Barde

Routhu

et al. 2022

Brit J Clinical Pharma

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Dihydroorotate dehydrogenase (DHODH) is a mitochondrial enzyme that is essential for pyrimidine de novo synthesis. Rapidly growing cancer cells and replicating viruses are dependent on host cell nucleotides, the precursors of which are provided by DHODH. Hence, DHODH becomes an ideal target for pharmacological intervention. RP7214 is a potent and selective inhibitor of human DHODH and has shown antiviral and antileukaemic activity in preclinical studies. This paper describes the phase I study that evaluated the safety and pharmacokinetics of single and multiple ascending doses (SAD and MAD) and the food effect of RP7214 in healthy volunteers (HVs). The study was a randomized, double‐blind, placebo‐controlled trial of single dose (100, 200 and 400 mg QD), multiple doses (200 and 400 mg BID for 7 days) and a food effect study at a single dose of 200 mg. A total of 18, 12 and 12 HVs were enrolled in the SAD, MAD and food effect parts of the study, respectively. RP7214 was well tolerated at all dose levels. There were 20 treatment‐emergent adverse events (TEAEs) reported, out of which most were mild to moderate in severity while three TEAEs were grade ≥3. RP7214 showed accumulation on multiple dosing. Steady‐state concentrations were reached within about 3‐6 days. The mean plasma half‐life at steady‐state was 12.8 hours (9.9‐15.3). Food did not impact the absorption of RP7214. Inhibition of DHODH, as evidenced by increased dihydroorotate levels, was observed, confirming target engagement. The high systemic exposure with a favourable safety profile shows potential for the development of RP7214 in SARS‐CoV‐2 and acute myeloid leukaemia (NCT04680429).

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A first in man study to evaluate the safety, pharmacokinetics and pharmacodynamics of RP7214, a dihydroorotate dehydrogenase inhibitor in healthy subjects

Nair

Barde

Routhu

et al. 2022

Brit J Clinical Pharma

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Knowledge, Concept on severe Acute Respiratory Syndrome Coronavirus-2(SARS-CoV-2). A Review of the Literature and Future perspective

Kandula

Veerabhadrappa

Narayana

et al. 2023

RJPT

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Severe acute respiratory corona virus-2 (SARS-CoV-2) is a newly recognized pathogen and may cause severe respiratory illness among virus-infected people. The virus in the open market of Wuhan city, China was identified. The virus causative agent for the COVID-19 disease and became pandemic in December 2019 to now with no proper disease management protocols. So, the authors felt a need to bring awareness to the disease and its causative agent among worldwide.The current review article is trying to bringglance information on SARS-CoV-2 on various aspects of disease condition as Common characteristics, history, and mode of transmissions of the virus. The virus can be detected through investigations, Identified clinical manifestations for the virus, and available management used to treat the virus-infected patient. Here discussed possible preventive measures for SARS-CoV-2;to control the spread of the disease among the communities. This article information maybea help people to have an awareness of the disease.Health professional are trying hard for providing effective care to the virus affected people with minimal disease preventive protocols. People should understand the effectiveness of the vaccine and undergoing vaccination process which helps the spread of virus among the healthy people. Every individual should take initiation for the control of the disease spreads by following controlling measures.

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Prospective, Randomized, Parallel-Group, Open-Label Study to Evaluate the Efficacy and Safety of IMU-838, in Combination with Oseltamivir, in Adults with Coronavirus-19 – The IONIC Trial Protocol

Cited by 2 publications

References 15 publications

A first in man study to evaluate the safety, pharmacokinetics and pharmacodynamics of RP7214, a dihydroorotate dehydrogenase inhibitor in healthy subjects

A first in man study to evaluate the safety, pharmacokinetics and pharmacodynamics of RP7214, a dihydroorotate dehydrogenase inhibitor in healthy subjects

Knowledge, Concept on severe Acute Respiratory Syndrome Coronavirus-2(SARS-CoV-2). A Review of the Literature and Future perspective

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