A Phase 3, Randomized, Double-blind Study for Patients With Invasive Candidiasis Treated With IV Echinocandin Followed by Either Oral Ibrexafungerp or Oral Fluconazole

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind study of two treatment regimens for invasive candidiasis included candidemia. Subjects will receive intravenous echinocandin followed by oral ibrexafungerp (SCY-078) vs intravenous echinocandin followed by oral fluconazole.

Official Title
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A Phase 3, Multicenter, Prospective, Randomized, Double-blind Study of Two Treatment Regimens for Candidemia and/or Invasive Candidiasis: Intravenous Echinocandin Followed by Oral Ibrexafungerp Versus Intravenous Echinocandin Followed by Oral Fluconazole (MARIO)

Conditions
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Candidiasis, Invasive, Candidemia

Intervention / Treatment
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* Drug: SCY-078
* Drug: Fluconazole
* Drug: Echinocandin


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Subject is a male or female adult ≥ 18 years of age on the day the study informed consent is signed. Subject has a diagnosis of candidemia and/or invasive candidiasis, defined as evidence of Candida spp in either a bloodstream or tissue culture from a normally sterile site (excluding eye, cardiac tissue, bone tissue, central nervous system or prosthetic device) collected ≤ 4 days (within 96 hours) prior to initiation of IV echinocandin accompanied by any related clinical signs and/or symptoms (e.g., fever [on one occasion > 38°C], hypotension, or local signs of inflammation). Key Exclusion Criteria: Subject has any of the following forms of invasive candidiasis at Screening: Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed), Osteomyelitis, Endocarditis or myocarditis, Meningitis, endophthalmitis, or any central nervous system infection, Chronic disseminated candidiasis, Urinary tract candidiasis due to ascending Candida infection secondary to unresolved obstruction or non-removeable device in the urinary tract, Patients with a sole diagnosis of mucocutaneous candidiasis, i.e., oropharyngeal, esophageal, or genital candidiasis; or Candida lower urinary tract infection or Candida isolated solely from respiratory tract specimens, Patients with concurrent invasive fungal infection other than Candida spp., e.g., cryptococcosis, mold infection or endemic fungal infection, Patients who failed a previous antifungal therapy for the same infection, Subject has an inappropriately controlled fungal disease source (e.g., indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained) that is likely to be the source of the candidemia or invasive candidiasis. Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 10-fold the upper limit of normal (ULN). Subject has severe hepatic impairment and a history of chronic cirrhosis (Child-Pugh score > 9). Subject has received more than 48 hours of non-echinocandin antifungal therapy for the treatment of invasive candidiasis (including candidemia) within 96 hours preceding initiation of IV echinocandin. o Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible. Baseline QTcF ≥ 500 msec.

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: IV echinocandin followed by oral ibrexafungerp (SCY-078)<br> | Drug: SCY-078<br>* Oral ibrexafungerp (SCY-078) as step-down therapy.<br>* Other names: Ibrexafungerp;Drug: Echinocandin<br>* Intravenous echinocandin<br>* Other names: Anidulafungin;|
| Active Comparator: IV echinocandin followed by oral fluconazole<br> | Drug: Fluconazole<br>* Oral fluconazole (SCY-078) as step-down therapy.<br>* Other names: Diflucan;Drug: Echinocandin<br>* Intravenous echinocandin<br>* Other names: Anidulafungin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| All-cause mortality (US FDA Only) | The number and percentage of subjects in each treatment group who are alive and deceased in the ITT population. | Day 30 | 
| Global Response at End of Treatment (EU European Medicines Agency [EMA] Only) | The percentage of subjects with Successful Global Response, as determined by the Data Review Committee | Up to 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Global Response at Day 14 | The percentage of subjects with Successful Global Response, as determined by the Data Review Committee | Day 14 |