Compassionate Use of Opaganib For Patients with Severe COVID-19

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Abstract

Background

Opaganib is a selective sphingosine-kinase (SK)-2 inhibitor with anti-inflammatory and anti-viral properties.

Methods

We provided opaganib on a compassionate-use basis to patients with severe COVID-19. Patients who required oxygen support via high-flow nasal cannula (HFNC) were offered the treatment. For comparison, we used a control group with same-sex, same-severity patients.

Results

Seven patients received at least one dose of opaganib since April 2, 2020. One patient, who received both hydroxychloroquine and azithromycin, developed diarrhea and all his medications were stopped. This was the only adverse effect possibly related to opaganib. A second patient was weaned of oxygen and discharged after receiving two doses of opaganib. Therefore, five patients were included in this analysis. Baseline characteristics were not significantly different between cases and controls. Patients treated with opaganib had significantly faster increase in lymphocyte count. All other clinical outcomes had a non-statistically significant trend in favor of the treatment group: median time to weaning from HFNC was 10 and 15 days in cases vs. controls (HR= 0.3, 95% CI: 0.07-1.7, p=0.2), time to ambient air was 13 vs.14.5 days (HR=0.4, 95% CI: 0.15-1.5), none of the cases required mechanical ventilation compared with 33% of controls.

Conclusion

In this small cohort of severe COVID-19 patients, opaganib was safe and well tolerated with improvement in both clinical and laboratory parameters in all treated patients. The efficacy of opaganib for COVID-19 infection should be further tested in randomized placebo-controlled trials.

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  1. SciScore for 10.1101/2020.06.20.20099010: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board StatementConsent: Patients who were intubated, those who could not provide informed consent, debilitated patients, pregnant or nursing women, patients on warfarin, apixaban, argatroban or rivaroxaban, and patients with New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG, were excluded.
    IRB: Ethical considerations: Individual approval was granted for each patient treated with opaganib by the SZMC institutional review board (IRB) and the Israeli Ministry of Health.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablePatients who were intubated, those who could not provide informed consent, debilitated patients, pregnant or nursing women, patients on warfarin, apixaban, argatroban or rivaroxaban, and patients with New York Heart Association Class III or IV cardiac disease, myocardial infarction within the past 6 months, unstable arrhythmia, or evidence of ischemia on ECG, were excluded.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    All analyses were conducted by one of the authors (M.B-M) with SPSS software, version 25.0 (IBM).
    SPSS
    suggested: (SPSS, RRID:SCR_002865)

    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:

    IdentifierStatusTitle
    NCT04207255RecruitingAddition of Opaganib to Androgen Antagonists in Patients Wit…
    NCT03377179RecruitingA Study of ABC294640 (Yeliva ®) Alone and in Combination Wit…
    NCT04435106CompletedCompassionate Use of Opaganib in Patients With Coronavirus D…


    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.


    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.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.