Opaganib, a Sphingosine Kinase-2 (SK2) Inhibitor in COVID-19 Pneumonia

Inclusion Criteria

• Adult male or female ≥18 to ≤80 years of age
• Proven COVID-19 infection per RT-PCR assay of a pharyngeal sample (nasopharyngeal or oropharyngeal) AND pneumonia defined as radiographic opacities on chest X-ray or CT scan. that diagnosed COVID-19 pneumonia. Pharyngeal samples collected either at screening or within 7-days prior to screening for the same ongoing COVID-19 pneumonia illness are acceptable
• The patient requires, at baseline, high flow supplemental oxygen or positive pressure ventilation or is receiving oxygen via face mask, such as a non-rebreather or reservoir mask, capable of delivering high concentrations of oxygen
• Patient agrees to use appropriate methods of contraception during the study and 3 months after the last dose of study drug
• The patient or legal representative has signed a written informed consent approved by the IRB/Ethics Committee

Exclusion Criteria

• Any co-morbidity that may add risk to the treatment in the judgment of the investigator, particularly patients with known cardiac conditions, and serious neuropsychiatric conditions such as psychosis or major depression
• Requiring intubation and mechanical ventilation at baseline
• Patient has a 'Do Not Intubate' and/or 'Do Not Resuscitate' order in place
• Oxygen saturation >95% on room air
• Any preexisting respiratory condition that requires intermittent or continuous ambulatory oxygen prior to hospitalization
• Patient is, in the investigator's clinical judgement, unlikely to survive >72 hours
• Pregnant (positive serum or urine test within 3 days prior to randomization) or nursing women .
• Unwillingness or inability to comply with procedures required in this protocol.
• Corrected QT (QTc) interval on electrocardiogram (ECG) >470 ms for females or >450 ms for males, calculated using Friedericia's formula (QTcF)
• AST (SGOT) or ALT (SGPT) > 2.0 x upper limit of normal (ULN)
• Total bilirubin >1.5x ULN (except where bilirubin increase is due to Gilbert's Syndrome)
• Serum creatinine >2.0 X ULN
• Absolute neutrophil count <1000 cells/mm3
• Platelet count <75,000/mm3
• Hemoglobin <8.0 g/dL
• Medications that are sensitive substrates, or substrates with a narrow therapeutic range, for CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19 CYP2D6 , CYP3A4, P-gP, BCRP and OATP1B1 should be avoided with opaganib
• Moderate or strong inhibitors of CYP1A2, CYP3A4, CYP2D6 or P-gP or moderate to strong inducers of CYP3A4 and CYP1A2 are prohibited
• Currently taking warfarin, apixaban, argatroban or rivaroxaban due to drug-drug interaction based on CYP450 metabolism
• Current drug or alcohol abuse
• Currently participating in a clinical study assessing pharmacological treatments, including anti-viral studies
• Treatment with any medication that causes QT prolongation within seven days, or 5 half-lives, whichever is longest, prior to initiation of study drug, or intention to use them throughout the study, including but not limited to: amiodarone, amitriptyline, citalopram dose greater than 20 mg/day, dihydroergotamine, disopyramide, dofetilide, dronedarone, ergotamine, ibutilde, ondansetron or other 5-HT3 receptor antagonists, pimozide, procainamide, quinidine, quinine, quinolone, ranolazine, risperidone, sotaloland tolteridine. Investigators are directed to the following up-to-date web site listing QT prolonging drugs: https://www.crediblemeds.org/index.php/drugsearch