Study to Evaluate the Safety and Efficacy of the Coadministration of Ibrexafungerp (SCY-078) With Voriconazole in Patients With Invasive Pulmonary Aspergillosis

Study Overview
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Brief Summary
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Study to evaluate the safety and efficacy of coadminstration of SCY-078 with a mold-active azole (voriconazole) compared to voriconazole in patients with invasive pulmonary aspergillosis.

Detailed Description
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This is a multicenter, randomized, double-blind, two-arm study to evaluate the safety, tolerability, efficacy and PK of the coadministration of SCY-078 plus voriconazole compared to those of voriconazole in male and female subjects 18 years of age and older with a probable or proven invasive pulmonary aspergillosis.

Official Title
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A Multicenter, Randomized, Double-Blind Study to Evaluate the Safety and Efficacy of the Coadministration of SCY-078 With Voriconazole in Patients With Invasive Pulmonary Aspergillosis

Conditions
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Invasive Pulmonary Aspergillosis

Intervention / Treatment
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* Drug: SCY-078
* Drug: Voriconazole
* Other: Oral Placebo Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject is a male or female adult ≥18 years of age on the day the study informed consent form (ICF) is signed. Subject has a probable or proven IPA based on the protocol-specified criteria (Section 22.3) that requires antifungal treatment. Note: Subjects with possible IPA may enter the screening phase of the study but will only be randomized after meeting criteria for probable or proven IPA. Subject has a result of a serum GMI from a sample obtained within the 96 hours preceding enrollment into the study (Baseline/Treatment Day 1). Subject has a diagnosis of a hematological malignancy or a myelodysplastic syndrome or aplastic anemia or has undergone hematopoietic cell transplantation OR Subject who either recently resolved or ongoing neutropenia (neutropenia defined as absolute neutrophil count < 0.5 x 10⁹/L [< 500/mm³] for > 10 days), temporally related to the onset of fungal disease OR Subject who received treatment with other recognized T-cell immunosuppressants (such as cyclosporine, tacrolimus, monoclonal antibodies or nucleoside analogs) during the past 90 days including solid organ transplant patients OR Subject with inherited severe immunodeficiency (e.g. chronic granulomatous disease, severe combined immunodeficiency) Subject has not received more than 4 days (96 hours) of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study (Baseline/Treatment Day 1). However, subjects who have received more than 4 days but less than 7 days of prior mold-active antifungal therapy for the treatment of the IPA episode in the 7 days preceding enrollment into the study may be enrolled but will require approval from the study medical monitor, who will evaluate each subject on a case-by-case basis. Subject has an IPA episode that, in the investigator´s judgement, requires antifungal therapy and may be adequately treated with voriconazole (i.e., the IPA is not a breakthrough infection while receiving a mold-active azole antifungal [voriconazole, posaconazole, isavuconazole or itraconazole] that requires therapy with a non-azole antifungal agent). Exclusion Criteria: Subject has a fungal disease with central nervous system involvement suspected at Screening. Subject is receiving, has received or anticipates to be receiving concomitant medications that are listed in the prohibited medication list (Appendix A in full protocol) within the specified washout periods. Subject has a Karnofsky score <20. Subject is expected to die from a non-infectious cause within 30 days from the day the study ICF is signed. Subject is under mechanical ventilation. Subject has abnormal liver test parameters: AST or ALT >5 x ULN and/or total bilirubin >2.5 x ULN.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SCY-078 plus Voriconazole<br>Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral SCY-078 tablets (loading dose of 500 mg BID on Days 1 and 2 followed by maintenance dose of 500 mg QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks | Drug: SCY-078<br>* Oral tablets of SCY-078<br>* Other names: Ibrexafungerp;Drug: Voriconazole<br>* Voriconazole IV vials or oral tablets<br>|
| Placebo Comparator: Voriconazole mono-therapy<br>Either IV voriconazole (loading dose of 6 mg/kg BID on Day 1 followed by maintenance dose of 4 mg/kg BID from Day 2 onwards) OR oral voriconazole (loading dose of 400 mg BID on Day 1 followed by maintenance dose of 200 mg BID from Day 2 onwards). PLUS Oral Placebo Tablets matching SCY-078 tablets (loading dose of 2 tablets given BID on Days 1 and 2 followed by maintenance dose of 2 tablets given QD from Day 3 onwards). Treatment duration = minimum 6 weeks/Max 13 weeks | Drug: Voriconazole<br>* Voriconazole IV vials or oral tablets<br>Other: Oral Placebo Tablets<br>* Oral Placebo Tablets matching SCY-078<br>* Other names: SCY-078 matching Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events; discontinuation due to AE; death | Frequency of treatment-emergent adverse events (TEAEs), drug-related adverse events (AEs), discontinuations due to AEs and deaths. | through study completion, an average of 19 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite clinical, radiological and mycological response (global response) | Percentage of subjects with Complete Response or Partial Response | At end of treatment, day 42 and day 84 | 
| Death | Percentage of subjects who died (any cause) | At Day 42 and Day 84 | 
| Change in serum GMI | Absolute and percent change in serum GMI from Baseline | Weeks 1, 2, 4 and 6 | 
| Study drug and comparator plasma concentrations | SCY-078 and voriconazole plasma concentrations population PK analysis | Through the first 2 weeks of study | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aspergillosis, SCY-078, Ibrexafungerp, Coadministration