Invasive Mould Infection
Conditions
Keywords
Invasive Mould Infection, Mould infection, Prophylaxis for Invasive Mould Infection, Anti-fungal therapy, Invasive Mold Infection, Mold infection, Prophylaxis for Invasive Mold Infection, Early antifungal therapy
Brief summary
The purpose of this study is to determine if EL219 is safe and effective compared to liposomal amphotericin B (LAmB) or voricanozole for early treatment of invasive mould infections
Detailed description
A Phase 2, multicenter, randomized, double-blind Study of Safety and Efficacy of EL219 versus Comparator (LAmB or voriconazole) for early antifungal therapy of suspected or confirmed Invasive Mould Infections (IMI)
Interventions
DRUGEL219
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.
DRUGActive Comparator- IV Antifungal (LAmB or voriconazole)
LAmB has broad-spectrum activity but its use is limited by toxicity and once-daily IV administration. It is not administered outside of the monitored setting given risks for electrolyte disturbances and cardiac arrhythmias. Voriconazole is a first-line therapy for IA and the most common azole used in the US and globally but does not have activity against many non-Aspergillus moulds.
Sponsors
Elion Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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. 18 years and older, of any gender, race, or ethnicity 3. Are at risk for invasive fungal infections (IFIs), by virtue of acquired or inherited immunocompromising condition including but not limited to the following: 1. Receipt of a blood or marrow transplant (BMT) from an allogeneic donor 2. Active hematologic malignancy. 3. Recent neutropenia with absolute neutrophil count \<500 cells/mm3 \>10 days 4. Receipt of corticosteroids at mean minimum doses of 0.3 mg/kg/day prednisone equivalent for \>3 weeks. 5. 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. 6. Inherited severe immunodeficiency 4. Has suspected or confirmed mould infection (IMI) supported 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. Diagnostic tests must have regulatory approval in the region in which the diagnostic is performed and are inclusive of Platelia serum or bronchoalveolar lavage (BAL) galactomannan, serum or 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: 1. 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. 2. A female of non-childbearing potential must be surgically sterile (i.e., have undergone complete hysterectomy, bilateral oophorectomy, or tubal ligation/occlusion without reversal surgery) or in a menopausal state (at least 2 years without menses), or confirmation of menopause by follicle-stimulating hormone (FSH) levels (≥40 mIU/mL). 8. A WOCBP must have a negative pregnancy test (highly sensitive serum β-human chorionic gonadotropin or a urine test) during both the current hospitalization AND 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 (e.g. condom and spermicide) 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Primary Outcome/Measure All-Cause Mortality | From enrollment to Day 21 | All-cause mortality at Day 21 (plus or minus 3 days) in the Intent-to-Treat (ITT) analysis set. |
| Primary Outcome/Measure SAE TEAE | From enrollment to the end of treatment at Day 42 | During the blinded portion of the study, serious adverse events and treatment-emergent adverse events categorized in a tiered approach in the Safety analysis set. Tier 1 TEAEs include renal, electrolyte, hepatic, infusion-related reactions, photophobia and photosensitivity. Tier 2 includes all other TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome Measure-EAT Success | From enrollment through Day 21 | Early antifungal therapy (EAT) success at Day 21 (plus or minus 3 days) in the ITT analysis set defined by non-occurrence of the following: death, cessation of study antifungals for progression of IMI, and/or toxicity, missing data (classified as indeterminate but analyzed as a failure). |
| Secondary Outcome Measure-Overall Success | From enrollment through Day 42 | Overall success at Day 42 (plus or minus 7 days) confirmed by the Data Review Committee, in the population with proven or probable IA (modified Intent-to-Treat) |
| Secondary Outcome Measure-Participant is Alive | From enrollment through Day 42 | Participant is alive, favorable composite clinical, mycologic, and radiographic response (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 \[EORTC/MSG\] criteria) |
Countries
Belgium, Canada, France, Italy, Spain, United States
Contacts
CONTACTLaura A. Navalta
CONTACTGordana Schnider, MHA
STUDY_DIRECTORTaylor G. Sandison, MD
Sponsor: Elion Therapeutics, Chief Medical Officer
Outcome results
None listed