Phase 2 EL219 Versus Liposomal Amphotericin B or Voriconazole for Early Antifungal Therapy

Exclusion Criteria22

• Participant has received prior antifungal treatment (azole or echinocandin prophylaxis permitted) for >96 hours prior to randomization.
• Active, microbiologically confirmed systemic bacterial infection with ongoing receipt of antibacterial therapy. Antibacterial prophylaxis and secondary therapy is allowed, providing that follow-up cultures have been without growth for >2 days.
• Participants with 1 or more of the following laboratory abnormalities as defined by the National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v5.0:
• Alanine aminotransferase (ALT) ≥5 × upper limit of normal (ULN).
• Total serum bilirubin ≥5 × ULN (excluding Gilbert's Syndrome).
• Serum creatinine ≥2 mg/dL or creatinine clearance (CrCL) ≤30 mL/minute.
• Known cirrhosis of the liver, diagnosed according to country or Medical Society-specific guidelines and documented in the medical records prior to screening.
• Known New York Heart Association (NYHA) Class III or Class IV heart failure.
• Diagnosed reduced lung function with either diffusion capacity (corrected for hemoglobin) or forced expiratory volume in 1 second (FEV1) ≤65% of predicted value, or oxygen (O2) saturation ≤82% on room air.
• Receiving either hemodialysis or peritoneal dialysis.
• Personal or family history of long QT interval on ECG (QT) syndrome or a prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF; >470 msec in males and >490 msec in females).
• If the Investigator chooses voriconazole as Comparator therapy, current or projected use of the following medications or drug classes known to interact with voriconazole: terfenadine, astemizole, cisapride, pimozide, quinidine, sirolimus, rifampin, phenytoin, carbamazepine, flucloxacillin, eplerenone, fineronone, voclosporin, ritonavir or other protease inhibitors, efavirenz, venetoclax or other non-nucleoside reductase inhibitors, rifabutin, naloxegol, tolvaptan, ivabradine, lurasidone, St. John's Wort, ergot alkaloids, or long-acting barbiturates.
• If the Investigator chooses voriconazole as Comparator therapy, history of hereditary problems with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.
• Known hypersensitivity to EL219 Powder for Injection, polyenes, or known hypersensitivity to voriconazole if the Investigator chooses voriconazole as Comparator therapy.
• History of severe allergic response to mRNA-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine and/or polyethylene glycol (PEG)-containing products.
• Previous participation in any study using an investigational drug within 5 half-lives of the drug, or intention to use investigational drug before completion of the Day 56 Safety Follow-Up. Concurrent participation in another trial may be allowed (e.g., interventional trial with a previously approved study drug\[s\] or observational trial). In such cases, the Medical Monitor should be consulted prior to enrolling a potential participant.
• Prior recipient of orthotopic lung transplant.
• Imminent transition to hospice or withdrawn care such as with refractory malignancy or multiorgan failure.
• Female participants who are pregnant or lactating or planning to become pregnant within 2 months following study drug administration.
• The Principal Investigator (PI) determines the participant should not participate in the study.
• Considered unlikely to follow up for required days due to logistic concerns (i.e., home location relative to study site).
• Persons committed to an institution by virtue of an order issued either by the judicial or the administrative authorities or are in a dependent relationship with the Sponsor or the Investigator.