Phase 2 Randomized Study of EL219 Versus Liposomal Amphotericin B and Voriconazole for Early Antifungal Therapy of Suspected Invasive Mould Infections

The primary objective is to evaluate the efficacy and safety of EL219 compared to the standard of care, consisting of liposomal amphotericin B followed by voriconazole, for early antifungal therapy in cases of suspected invasive mould infections.

Secondary objectives include:

• Assessment of the efficacy of EL219 in the treatment of invasive aspergillosis.
• Evaluation of the incidence of invasive fungal infections following 14 days of early antifungal therapy.
• Comparison of the duration of hospitalization and rehospitalization rates between EL219 and liposomal amphotericin B.

The study involves 26 participants consisting of both male and female individuals. The population includes adults, specifically those within the age ranges categorized as 3 and 4. Participants are characterized by a risk of invasive mould infection. Inclusion is contingent upon meeting specific clinical profiles, such as having undergone an allogeneic bone marrow transplant, receiving recent cytotoxic, biological, or immunomodulatory treatments for hematological malignancies, or undergoing prolonged corticosteroid therapy. Additionally, the use of immunosuppressants targeting T-lymphocytes, such as cyclosporine or tumor necrosis factor-alpha inhibitors, within the preceding three months is a relevant factor for study eligibility.

This Phase 2, multicenter, randomized, double-blind, controlled study is designed to evaluate the safety and efficacy of EL219 compared to the standard of care, consisting of liposomal amphotericin B followed by voriconazole, for the early antifungal therapy of suspected invasive mould infection. The trial methodology involves a comparison between the test product and a comparator regimen, utilizing placebo administrations to maintain blinding. The primary endpoints include all-cause mortality at Day 42 and the assessment of serious adverse events and treatment emergent adverse events. Secondary endpoints focus on overall success based on EORTC/MSG criteria, early antifungal therapy success, and the incidence of breakthrough infections. The study sequence includes a screening process to identify eligible participants at risk of fungal infections, followed by the administration of study drugs and subsequent monitoring through Day 42. The overall recruitment for the study is estimated to occur between March 2026 and December 2026.

EL219, consisting of N38-(1,3-dihydroxypropan-2-yl)-2'-epi-amphotericin B-38-amide, is administered as a solution for infusion via intravenous use at a dosage of 2 mg/kg.

Liposomal amphotericin B is utilized as a comparator and is administered via intravenous use at a dosage of 3 mg/kg. To maintain the double-blind nature of the study, Dextrose 5% is used as a placebo for the intravenous administration of EL219 and liposomal amphotericin B.

Voriconazole is administered as a comparator through two routes. The intravenous use of voriconazole is conducted at a dosage of 12 mg/kg. Additionally, oral voriconazole is provided in the form of a hard capsule for oral use at a dosage of 8 mg/kg. An oral voriconazole matching placebo is utilized to ensure blinding for the oral administration component.

The efficacy of EL219 in the treatment of suspected invasive mould infections is evaluated through several predefined endpoints. The primary efficacy endpoint is all-cause mortality at Day 42 within the intent-to-treat analysis set. Secondary efficacy assessments include overall success at Day 42 in the modified intent-to-treat population, which consists of participants with proven or probable aspergillosis. This success is confirmed by a data review committee and requires the participant to be alive and demonstrate a favorable composite clinical, mycologic, and radiographic response based on EORTC/MSG criteria.

Additional secondary parameters include early antifungal therapy success at Day 42, defined by the absence of death, missing data, or the requirement of non-study systemic antifungal therapy for more than 10 days due to disease progression or toxicity. The assessment also includes the occurrence of breakthrough invasive fungal infection established after 14 days of study drug administration. Furthermore, the duration of initial hospitalization and the motif and duration of rehospitalization following discharge are monitored within the intent-to-treat population.