SCY-078-302 MARIO

Evaluation of the efficacy, safety and tolerability of oral ibrexafungerp compared to oral fluconazole step-down treatment following IV echinocandin in the treatment of adult subjects

Demonstration that treatment of Invasive Candidiasis/ Candidemia with IV echinocandin followed by oral ibrexafungerp is non-inferior to IV echinocandin followed by oral fluconazole based on 30-day all-cause mortality (ACM).

To demonstrate that treatment of Invasive Candidiasis/ Candidemia with intravenous (IV) echinocandin followed by oral ibrexafungerp is non-inferior to IV echinocandin followed by oral fluconazole based on Global Response (clinical, radiological and mycological response, as confirmed by the Data Review Committee [DRC]) at Day 14.

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 sign and/or symptom (e.g., fever [on one occasion > 38°C], hypotension, or local signs of inflammation)

1. Subject has any of the following forms of invasive candidiasis at Screening:

a. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed),

b. Osteomyelitis,

c. Endocarditis or myocarditis,

d. Meningitis, endophthalmitis, or any central nervous system infection,

e. Chronic disseminated candidiasis,

f. Urinary tract candidiasis due to ascending Candida infection secondary to unresolved obstruction or non-removeable device in the urinary tract,

g. 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,

h. Patients with concurrent invasive fungal infection other than Candida spp., e.g., cryptococcosis, mold infection or endemic fungal infection,

i. Patients who failed a previous antifungal therapy for the same infection,

j. 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.

 2. Subject has abnormal liver test parameters: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels > 10-fold the upper limit of normal (ULN).

3. Subject has severe hepatic impairment and a history of chronic cirrhosis (Child-Pugh score > 9).

4. 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. a. Exception: Receipt of antifungal therapy to which any Candida spp. isolated in qualifying culture is not susceptible.

5. Baseline QTcF ≥ 500 msec.