Study of EL219 vs Standard of Care for Early Antifungal Therapy of Suspected Invasive Mould Infections

EL219 is specifically being developed for early antifungal therapy (EAT), when infection is suspected due to highly suggestive signs and symptoms of disease; in high-risk people, antifungals are recommended even before confirmation of the microbial cause of infection, because delayed therapy is associated with poor outcomes in those who lack adequate immune responses. EL219 may provide a once-weekly alternative to LAmB and other polyenes that could also reduce the toxicities that often limit the frequency and duration of administration for these highly efficacious antifungals.

Placebo IV infusions (inf.) on Days 2-7, 9-14 to match LAmB dosing. Thereafter, twice daily oral or IV placebo equal to voriconazole dosing until Day 42/EOT. Active Comparator/SoC will receive LAmB 3 mg/kg IV inf. for at least 14 days \& up to 42 days. Voriconazole daily dosing loading 6 mg/kg via IV inf. every 12hrs for first 24hrs. Post-load: 4 mg/kg oral every 12hrs (50 mg tablets) or 4 mg/kg via IV inf. every 12hrs. Oral therapy will be admin., placebo IV inf. to match EL219 on Days 15, 22, 29 \& 36. May switch from LAmB to voriconazole (oral or IV) if any of these occur: diagnosis of proven or probable IA per EORTC/MSG criteria, other proven or probable susceptible mould infection, possible IMI requiring continued antifungal therapy. Toxicity: acute renal injury, hypokalemia or hypomagnesemia not controlled by IV supplementation, increase ALT 3×baseline and/or total serum bilirubin 3×baseline, intractable IRR. Need to switch to oral therapy for imminent hospital discharge.