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
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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 a randomized control trial that will investigate whether time to clinical improvement in COVID 19 patients is improved following a 14 day course of IMU-838 + Oseltamivir versus Oseltamivir alone.
Methods
IONIC trial is an open label study in which participants will be randomised 1:1 in two parallel arms; the intervention arm (IMU-838 + Oseltamivir) and control arm (Oseltamivir only). The primary outcome is time-to-clinical improvement; defined as the time from randomisation to: a 2-point improvement on WHO ordinal scale; discharge from hospital, or death (whichever occurs first). The study is sponsored by UHCW NHS Trust and funded by LifeArc.
Discussion
The IONIC Protocol describes an overarching trial design to provide reliable evidence on the efficacy of IMU-838 (vidofludimus calcium) when delivered in combination with an antiviral therapy (Oseltamivir) [ IONIC Intervention ] for confirmed or suspected COVID-19 infection in adult patients receiving usual standard of care.
Trial Registration
The trial was registered with EudraCT (2020-001805-21) on 09.04.2020 and ISRCTN on 23.09.2020 ( ISRCTN53038326 ) and Clinicaltrials.gov on 17.08.2020 ( NCT04516915 )
Strengths and Limitations
This study is the first to recruit participants in the trial exploring the effectiveness of IMU-838 in COVID-19. In addition, we believe it is the only trial exploring the effectiveness of IMU-838 in combination with Oseltamivir (Tamiflu) in patients with moderate to severe COVID-19. However, to make the trial design flexible due to the on-going pandemic the trial is un-blinded.
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SciScore for 10.1101/2021.07.13.21258757: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Informed consent will be obtained from each patient before enrolment into the study. Sex as a biological variable Consent will then be obtained from the patient’s personal legal representative (or directly from the patient if they recover promptly) at the earliest opportunity. 2.3 Eligibility Criteria: Inclusion criteria will be any male or non-pregnant female who is 18 years or older with either: confirmed (positive result from a validated test) or suspected (has been in contact with a confirmed case of COVID 19 AND have mild to severe COVID 19 symptoms AND radiological evidence of pulmonary infiltrates) case of SARS-CoV-2. Randomization Trial Procedures: The IONIC trial is an … SciScore for 10.1101/2021.07.13.21258757: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Ethics Consent: Informed consent will be obtained from each patient before enrolment into the study. Sex as a biological variable Consent will then be obtained from the patient’s personal legal representative (or directly from the patient if they recover promptly) at the earliest opportunity. 2.3 Eligibility Criteria: Inclusion criteria will be any male or non-pregnant female who is 18 years or older with either: confirmed (positive result from a validated test) or suspected (has been in contact with a confirmed case of COVID 19 AND have mild to severe COVID 19 symptoms AND radiological evidence of pulmonary infiltrates) case of SARS-CoV-2. Randomization Trial Procedures: The IONIC trial is an interventional, randomised, parallel-group, open-label, Phase IIb trial to assess the efficacy and safety of an oral dose of IMU-838 (22.5 mg twice daily [45 mg/day]) plus Oseltamivir (75mg twice daily [150mg/day]) (IONIC Intervention) in comparison with Oseltamivir alone (75mg twice daily) for 14 days in hospitalised patients with COVID-19. Blinding not detected. Power Analysis not detected. Cell Line Authentication Authentication: Consent will then be obtained from the patient’s personal legal representative (or directly from the patient if they recover promptly) at the earliest opportunity. 2.3 Eligibility Criteria: Inclusion criteria will be any male or non-pregnant female who is 18 years or older with either: confirmed (positive result from a validated test) or suspected (has been in contact with a confirmed case of COVID 19 AND have mild to severe COVID 19 symptoms AND radiological evidence of pulmonary infiltrates) case of SARS-CoV-2. Table 2: Resources
No key resources detected.
Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: We found the following clinical trial numbers in your paper:
Identifier Status Title NCT04516915 Recruiting IMU-838 and Oseltamivir in the Treatment of COVID-19 ISRCTN53038326 NA NA Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
- Thank you for including a protocol registration statement.
Results from scite Reference Check: We found no unreliable references.
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