Study of Rezafungin Compared to Caspofungin in Subjects With Candidemia and/or Invasive Candidiasis
Condition: Candidemia; Mycoses; Fungal Infection; Invasive Candidiases
MeSH terms: Mycoses; Candidiasis; Candidemia; Candidiasis, Invasive
Intervention: Rezafungin for Injection; Caspofungin; Fluconazole; intravenous placebo; oral placebo
Intervention description: Intravenous antifungal therapy; Intravenous antifungal therapy; Oral antifungal therapy; Normal saline; Microcrystalline cellulose
Intervention MeSH terms: Fluconazole; Caspofungin; Rezafungin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 199.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Mycoses; Candidiasis; Candidiasis, Invasive; Candidemia; Fungemia; Sepsis; Invasive Fungal Infections; Systemic Inflammatory Response Syndrome; Pathologic Processes; Fluconazole; Caspofungin; Echinocandins; Antifungal Agents; Anti-infective Agents; 14-alpha Demethylase Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Steroid Synthesis Inhibitors; Physiological Effects of Drugs; Cytochrome P-450 CYP2C9 Inhibitors; Cytochrome P-450 CYP2C19 Inhibitors

Summary:

      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).
    

Eligibility criteria:

        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