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

Elion Therapeutics, Inc.

Status and phase: Enrolling; Phase 2

Conditions: Suspected Invasive Mould Infection

Treatments: Drug: Antifungal Comparator; Drug: EL219

Study type: Interventional

Funder types: Industry

Identifiers

NCT07215273

EL219.IV.2.04

Details and patient eligibility

About

The purpose of this study is to determine if EL219 is safe and effective compared to the standard of care for early treatment of suspected invasive mould infection.

Full description

A Phase 2, multicenter, randomized, double-blind Study of Safety and Efficacy of EL219 versus standard anti-fungal therapy for suspected Invasive Mould Infections.

Enrollment: 80 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Participants who meet ALL the following inclusion criteria will be eligible to participate in the study:

1. Willing and able to provide written informed consent.

2. Males or females 18 years and older,

3. Are at risk for invasive fungal infections (IFIs), with one of the following:

   1. Receipt of a bone marrow transplant (BMT) from an allogeneic donor, with blood, bone marrow, or cord blood as stem cell source.
   2. Receiving or have recently (within 1 month) received cytotoxic, biologic, or immune modulating therapy(ies) for hematological malignancy.
   3. Receipt of corticosteroids at mean minimum doses of 0.3 mg/kg/day prednisone equivalent for more than 3 weeks.
   4. Receipt of other recognized T-cell immunosuppressants, such as cyclosporin, tumor necrosis factor alpha (TNF-α) blockers, or specific monoclonal antibodies during the last 3 months.
   5. Inherited severe immunodeficiency

Has suspected invasive mould infection (IMI) as defined by one or both of the following:

1. Results of an assay having regulatory clearance in Europe or the United States (Conformité Européene [CE] mark or United States Food and Drug Administration [US FDA] 510k clearance), demonstrating positivity at validated cut-off that is suggestive of IMI, but does not meet microbiologic criteria for probable invasive aspergillosis (IA; as defined by European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group [EORTC/MSG]). Diagnostic tests must have regulatory approval in the region in which the diagnostic is performed and are inclusive of Platelia serum galactomannan, serum or bronchoalveolar lavage (BAL) polymerase chain reaction (PCR), serum or BAL Aspergillus antigen lateral flow assays (LFAs; IMMY, OLM Diagnostics, or TECO®), or urine MycoMEIA®-Aspergillus assay

2. Abnormal findings on chest computed tomography (CT) scan without alternative microbiologic diagnosis Note: If CT of the chest is used to establish eligibility it must be performed within 7 days prior to randomization.

   5. Must have IV access in place or to be placed prior to beginning IV study therapy.

   6. Must be willing to adhere to dosing, study visit schedule, and mandatory diagnostic procedures.

   7. Female participants must meet 1 of the following criteria: A woman of childbearing potential (WOCBP) must agree to use a highly effective, preferably user-independent method of contraception (failure rate of <1% per year when used consistently and correctly) for at least 30 days prior to screening and agree to remain on a highly effective method until 2 months after study drug administration.

   8. A WOCBP must have a negative highly sensitive serum pregnancy test (β-human chorionic gonadotropin) at screening and a negative urine pregnancy test on Day -1 before study drug administration.

   9. Females must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of at least 2 months after study drug administration.

   10. Male participants must be vasectomized or agree to abstain from intercourse or if engaging in sexual activity that has risk of pregnancy, must agree to use a double barrier method and agree not to donate sperm during the study and for at least 120 days after study drug administration.

Exclusion criteria

Participants must NOT meet any of the following exclusion criteria:

1. Diagnosis of proven or probable IMI within 1 month prior to randomization (including meeting the criteria for proven or probable IMI during the screening period), or relapsed/recurrent IMI which has not responded to other antifungal therapies.

2. Participant has received prior antifungal treatment (azole prophylaxis permitted) for >96 hours prior to randomization.

3. Systemic bacterial infection diagnosed within the 14 days prior to randomization.

4. 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:

1. Alanine aminotransferase (ALT) ≥5 × upper limit of normal (ULN).

2. Total serum bilirubin ≥5 × ULN (excluding Gilbert's Syndrome).

3. Serum creatinine ≥2 mg/dL or creatinine clearance (CrCL) ≤30 mL/minute. 5. Known cirrhosis of the liver, diagnosed according to country or Medical Society-specific guidelines and documented in the medical records prior to screening.

   6. Diagnosed symptomatic heart failure with left ventricular ejection fraction (LVEF) at rest ≤50%, or shortening fraction ≤26%.

   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.

   8. Receiving either hemodialysis or peritoneal dialysis. 9. 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 >480 msec in females).

   10. Current or projected use of the following medications or drug classes known to interact with voriconazole: terfenadine, astemizole, cisapride, pimozide, quinidine, sirlolimus, rifampin, phenytoin, carbamazepine, ritonavir or other protease inhibitors, efavirenz or other non-nucleoside reductase inhibitors, rifabutin, St. John's Wort, ergot alkaloids, or long-acting barbiturates.

   11. History of hereditary problems with galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

   12. Known hypersensitivity to EL219 Powder for Injection, LAmB®, voriconazole, other azole antifungal, or any of their excipients.

   13. 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.

   14. Previous participation in any study using an investigational drug within 28 days of study drug administration on Day 1 or 5 half-lives of the drug, whichever is longer, and throughout the study until the Day 56 Safety Follow-up visit is completed. 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, Sponsor Medical Monitor should be consulted prior to enrolling a potential participant.

   15. Prior recipient of orthotopic lung transplant. 16. Likely to transition to hospice care for underlying hematological malignancy, is under a Do Not Resuscitate (DNR) order, or is receiving best supportive care only.

   17. Female participants who are pregnant or lactating or planning to become pregnant within 2 months following study drug administration.

   18. The Principal Investigator (PI) determines the participant should not participate in the study.

   19. Considered unlikely to follow up for required days due to logistic concerns (i.e., home location relative to study site).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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80 participants in 2 patient groups

EL219

Experimental group

Description:

Participants randomized to EL219 will receive a single loading dose of EL219 at 2 mg/kg via IV infusion on Day 1, and 1.5 mg/kg IV infusions on Days 8, 15, 22, 29, and 36. To maintain the blind, placebo IV infusions will be administered on Days 2-7 and 9-14 corresponding to Liposomal Amphotericin B (LAmB) dosing; thereafter, twice daily oral or IV placebo will be administered corresponding to voriconazole dosing until Day 42/EOT.

Treatment:

Drug: EL219

Antifungal Comparator

Active Comparator group

Description:

Standard of Care- Participants will receive LAmB 3 mg/kg IV infusions for at least 14 days and up to 42 days.Voriconazole Daily Dosing- Loading 6 mg/kg via IV infusion every 12 hrs for the first 24 hrs. Post-loading: 4 mg/kg oral every 12 hrs (admin as 50 mg overencapsulated tabs) OR 4 mg/kg via IV infusion every 12 hrs Participants on oral therapy will be administered placebo IV infusions corresponding to EL219 on Days 15, 22, 29, and 36 to maintain the blind. Participants may switch from LAmB to voriconazole (oral or IV) at any time, if any of the following occur: * Dx. of proven or probable IA per EORTC/MSG criteria * Other proven or probable susceptible MI * Possible IMI that requires continued antifungal therapy * Toxicity: Acute renal injury, hypokalemia or hypomagnesemia uncontrolled with IV supplementation, Increase in ALT to 3× baseline and/or total serum bilirubin 3× baseline, Intractable IRR * Change to oral due to imminent hosp. discharge

Treatment:

Drug: Antifungal Comparator