Study of Rezafungin Compared to Caspofungin in Subjects With Candidemia and/or Invasive Candidiasis

A Phase 3, Multicenter, Randomized, Double-blind Study of the Efficacy and Safety of Rezafungin for Injection vs. Intravenous Caspofungin Followed by Oral Fluconazole Step Down in the Treatment of Subjects With Candidemia and/or Invasive Candidiasis

The purpose of this pivotal study is to determine if intravenous Rezafungin is efficacious and safe in the treatment of candidemia and/or invasive candidiasis when compared to caspofungin (followed by optional oral fluconazole).

A Phase 3, multicenter, prospective, randomized, double-blind, efficacy and safety study of Rezafungin for Injection versus an active comparator regimen of caspofungin followed by optional oral fluconazole step-down therapy in subjects with candidemia and/or invasive candidiasis.

Inclusion Criteria:

1. Willing and able to provide written informed consent. If the subject is unable to consent for himself/herself, a legally acceptable representative must provide informed consent on his/her behalf.

2. Males or females ≥18 years of age.

3. Established mycological diagnosis of candidemia and/or invasive candidiasis from a sample taken ≤4 days (96 hours) before randomization defined as

   • ≥1 blood culture positive for yeast or Candida OR
   • Positive test for Candida from a Sponsor-approved rapid in vitro diagnostic (IVD) OR
   • Positive gram stain (or other method of direct microscopy) for yeast or positive culture for Candida spp. from a specimen obtained from a normally sterile site.

4. Presence of one or more systemic signs attributable to candidemia or invasive candidiasis appearing from ≤12 hours prior to the qualifying positive culture through time of randomization.

5. Willing to initiate or continue medical treatment to cure infections, including receipt of antibiotics and surgical procedures, if required.

6. Female subjects of childbearing potential (all female subjects between 18 years <2 years post-menopausal unless surgically sterile) must agree to and comply with using one barrier method (e.g., female condom with spermicide) plus one other highly effective method of birth control, or sexual abstinence while participating in this study. Male subjects must be vasectomized, abstain from sexual intercourse, or agree to use barrier contraception, and also agree not to donate sperm while participating in the study and for 90 days thereafter (and at least 120 days from the last dose of study drug).

7. For Candidemia only subjects, drawing of a set of blood cultures within 12 hours prior to randomization in the study. The result of these blood cultures is not required for inclusion in the study.

Exclusion Criteria:

1. Any of the following forms of invasive candidiasis at baseline:

   1. Septic arthritis in a prosthetic joint (septic arthritis in a native joint is allowed)
   2. Osteomyelitis
   3. Endocarditis or myocarditis
   4. Meningitis, endophthalmitis, chorioretinitis, or any central nervous system infection
   5. Chronic disseminated candidiasis
   6. Urinary tract candidiasis due to ascending Candida infection secondary to obstruction or surgical instrumentation of the urinary tract

2. Received systemic treatment with an antifungal agent at approved doses for treatment of candidemia for >48 hours (e.g., >2 doses of a once daily antifungal agent or >4 doses of a twice daily antifungal agent) ≤4 days (96 hours) before randomization

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

3. Alanine aminotransferase or aspartate aminotransferase levels >10-fold the upper limit of normal

4. Severe hepatic impairment in subjects with a history of chronic cirrhosis (Child-Pugh score >9)

5. Presence of an indwelling vascular catheter or device that cannot be removed or an abscess that cannot be drained and is likely to be the source of candidemia or invasive candidiasis

6. Known hypersensitivity to Rezafungin for Injection, caspofungin, any echinocandin, or to any of their excipients

7. Meets National Cancer Institute Common Terminology Criteria for Adverse Events, version 5, criteria for ataxia, tremor, motor neuropathy, or sensory neuropathy of Grade 2 or higher

8. History of severe ataxia, tremor, or neuropathy or a diagnosis of multiple sclerosis or a movement disorder (including Parkinson's Disease or Huntington's Disease)

9. Planned or ongoing therapy at Screening with a known neurotoxic medication

10. Previous participation in this or any previous rezafungin study

11. Current participation in another interventional treatment trial with an investigational agent

12. Recent use of an investigational medicinal product within 28 days of the first dose of study drug or presence of an investigational device at the time of screening.

13. Pregnant or lactating females

14. The Principal Investigator (PI) is of the opinion the subject should not participate in the study