Candidemia, Fungal Infection, Invasive Candidiases, Mycoses
Conditions
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
Brief 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).
Detailed description
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.
Interventions
Intravenous antifungal therapy
DRUGCaspofungin
Intravenous antifungal therapy
DRUGFluconazole
Oral antifungal therapy
DRUGintravenous placebo
Normal saline
DRUGoral placebo
Microcrystalline cellulose
Sponsors
Cidara Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All-Cause Mortality (US FDA Only) | Day 30 (-2 days) | The number and percentage of subjects in each treatment group who are alive and deceased (or with missing data) in the mITT population. |
| Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) | Day 14 (±1 day) | The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure \[for qualifying invasive candidiasis subjects at baseline\], and mycological eradication, as confirmed by the Data Review Committee \[DRC\]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Comparison of Global Response (as Assessed by the DRC) by Visit | Day 5, Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose) and Follow-up (Days 52-59) | The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure \[for qualifying invasive candidiasis subjects at baseline\], and mycological eradication, as confirmed by the Data Review Committee \[DRC\]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol. |
| Comparison of Mycological Eradication by Visit | Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59) | The number and percentage of subjects in each treatment group who have a mycological response of eradication, failure, or indeterminate in the mITT population. A mycological response of eradication means clearance of objective evidence of infection and is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was eradication or failure. Definitions for the mycological responses of eradication, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 8 (Mycological Response) of the clinical protocol. Note: Eradication includes both documented and presumed eradication. |
| Comparison of Investigators' Assessment of Clinical Response by Visit | Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59) | The number and percentage of subjects in each treatment group for whom the Investigator determined a clinical response of cure, failure, or indeterminate in the mITT population. A clinical response of cure, as assessed by the Investigator, is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the clinical responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 9 (Investigator's Assessment of Clinical Response) of the clinical protocol. |
| Global Response as Assessed by Data Review Committee (US FDA Only) | Day 14 (±1 day) | The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure \[for qualifying invasive candidiasis subjects at baseline\], and mycological eradication, as confirmed by the Data Review Committee \[DRC\]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol. |
| Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | Day 1 through Follow-up Visit (Days 52-59) | The number and percentage of subjects in each treatment group that experienced at least one treatment-emergent adverse event (TEAE) based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and electrocardiogram (ECG) abnormalities. Notes: A subject with multiple adverse events (AEs) was counted only once. TEAE was defined as an AE that occurred during or after study drug administration and up through the Follow-up visit. The maximum severity and strongest relationship were counted for subjects with multiple events. |
| Evaluate Pharmacokinetics (Cmax) | Day 1, 10 minutes before the end of infusion | Evaluate the maximum plasma concentration (Cmax) of rezafungin for injection. |
| Evaluate Pharmacokinetics (Cmin) | Day 8, pre-dose, within 30 minutes prior to the start of infusion | Evaluate the minimum plasma concentration (Cmin) of rezafungin for injection. |
| Comparison of Radiological Response by Investigator by Visit | Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59) | The number and percentage of subjects with invasive candidiasis (documented by radiologic/imaging evidence at baseline) in each treatment group who have a radiological response (as assessed by the Investigator) of cure, failure, and indeterminate in the mITT population. A radiological response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the radiological responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 10 (Radiological Response) of the clinical protocol. |
| All-Cause Mortality (EU EMA Only) | Day 30 (-2 days) | The number and percentage of subjects in each treatment group who are alive and deceased (or with missing data) in the mITT population. |
Countries
Argentina, Australia, Belgium, Bulgaria, China, Colombia, France, Germany, Greece, Israel, Italy, Singapore, South Korea, Spain, Taiwan, Thailand, Turkey (Türkiye), United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Group 1: Rezafungin for Injection Subjects in Rezafungin treatment group will receive a 400 mg loading dose in Week 1, followed by 200 mg once weekly, for a total of 2 to 4 doses.
Daily intravenous placebo infusions, when not administered Rezafungin and a daily placebo for oral step-down therapy (first eligibility on Day 4 or later as advised by a site's national/regional/local guidelines) administered every day.
Rezafungin for Injection: Intravenous antifungal therapy
oral placebo: Microcrystalline cellulose | 100 |
| Group 2: Caspofungin Subjects in caspofungin arm will receive a total treatment of ≥14 days beginning with a single caspofungin 70 mg IV loading dose on Day 1 followed by 50 mg IV once daily up to 28 days. After ≥3 days of caspofungin treatment(or the minimum duration of IV therapy advised by the site's national/regional/local guidelines, whichever is greater), subjects may be switched to oral fluconazole if specific parameters are met.
If the subject qualifies, then oral step-down therapy of fluconazole (6 mg/kg to the nearest 200 mg) is administered. After switch to oral step down before Day 8, subjects in the caspofungin group will receive IV placebo on Day 8 to preserve the study blind.
Caspofungin: Intravenous antifungal therapy
Fluconazole: Oral antifungal therapy
intravenous placebo: Normal saline | 99 |
| Total | 199 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 3 |
| Overall Study | Death | 22 | 21 |
| Overall Study | Diagnosis of other types of invasive candidiasis | 1 | 1 |
| Overall Study | Lost to Follow-up | 4 | 5 |
| Overall Study | Per Medical Monitor, visits performed over the phone were to be considered as early discontinuation | 0 | 1 |
| Overall Study | Study visit missed or conducted over the phone due to Coronavirus disease 2019 (COVID-19) pandemic | 2 | 1 |
| Overall Study | Subject could not return for additional investigational product | 1 | 0 |
| Overall Study | Subject discharged to hospice care | 2 | 0 |
| Overall Study | Subject was dropped due to exclusion criterion number 9 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 7 | 8 |
| Overall Study | Withdrawal of consent by subject's legally authorized representative; subject placed in hospice | 1 | 0 |
Baseline characteristics
| Characteristic | Group 1: Rezafungin for Injection | Total | Group 2: Caspofungin |
|---|---|---|---|
| Absolute Neutrophil Count (ANC) (per microliter) at Baseline <500/μL | 9 Participants | 15 Participants | 6 Participants |
| Absolute Neutrophil Count (ANC) (per microliter) at Baseline ≥500/μL | 88 Participants | 181 Participants | 93 Participants |
| Absolute Neutrophil Count (ANC) (per microliter) at Baseline Missing | 3 Participants | 3 Participants | 0 Participants |
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 40 Participants | 81 Participants | 41 Participants |
| Age, Categorical Between 18 and 65 years | 60 Participants | 118 Participants | 58 Participants |
| Age, Continuous | 59.0 years | 61.0 years | 62.0 years STANDARD_DEVIATION 14.57 |
| Body Mass Index (BMI) | 25.43 kilograms/meter^2 STANDARD_DEVIATION 7.037 | 24.97 kilograms/meter^2 STANDARD_DEVIATION 6.763 | 24.07 kilograms/meter^2 |
| Child-Pugh Score Category <7 | 0 Participants | 0 Participants | 0 Participants |
| Child-Pugh Score Category 7-9 | 2 Participants | 8 Participants | 6 Participants |
| Child-Pugh Score Category No History of Liver Disease/Not Calculated | 98 Participants | 191 Participants | 93 Participants |
| Diagnosis Candidemia only | 70 Participants | 138 Participants | 68 Participants |
| Diagnosis Invasive candidiasis | 30 Participants | 61 Participants | 31 Participants |
| Estimated Creatinine Clearance | 93.73 milliliters (mL)/minute STANDARD_DEVIATION 109.485 | 87.98 milliliters (mL)/minute STANDARD_DEVIATION 89.788 | 64.93 milliliters (mL)/minute |
| Ethnicity (NIH/OMB) Hispanic or Latino | 7 Participants | 11 Participants | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 89 Participants | 183 Participants | 94 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 5 Participants | 1 Participants |
| Height | 169.51 centimeters STANDARD_DEVIATION 9.984 | 168.42 centimeters STANDARD_DEVIATION 10.727 | 168.00 centimeters |
| Modified Acute Physiology and Chronic Health Evaluation (APACHE) II Score | 12.5 units on a scale STANDARD_DEVIATION 8.01 | 12.8 units on a scale STANDARD_DEVIATION 7.56 | 12.0 units on a scale |
| Modified Acute Physiology and Chronic Health Evaluation (APACHE) II Score Category 0-9 | 41 Participants | 78 Participants | 37 Participants |
| Modified Acute Physiology and Chronic Health Evaluation (APACHE) II Score Category 10-19 | 43 Participants | 87 Participants | 44 Participants |
| Modified Acute Physiology and Chronic Health Evaluation (APACHE) II Score Category ≥20 | 15 Participants | 33 Participants | 18 Participants |
| Modified Acute Physiology and Chronic Health Evaluation (APACHE) II Score Category Missing | 1 Participants | 1 Participants | 0 Participants |
| Modified APACHE II Score/ANC APACHE II score <20 and ANC ≥500/μL | 75 Participants | 153 Participants | 78 Participants |
| Modified APACHE II Score/ANC APACHE II score ≥20 or ANC <500/μL | 22 Participants | 43 Participants | 21 Participants |
| Modified APACHE II Score/ANC Missing | 3 Participants | 3 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 27 Participants | 58 Participants | 31 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 9 Participants | 4 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 6 Participants | 9 Participants | 3 Participants |
| Race (NIH/OMB) White | 61 Participants | 121 Participants | 60 Participants |
| Randomization Strata Candidemia only, APACHE II score <20 and ANC ≥500/μL | 51 Participants | 104 Participants | 53 Participants |
| Randomization Strata Candidemia only, APACHE II score ≥20 or ANC <500/μL | 19 Participants | 36 Participants | 17 Participants |
| Randomization Strata Invasive candidiasis, APACHE II score <20 and ANC ≥500/μL | 25 Participants | 49 Participants | 24 Participants |
| Randomization Strata Invasive candidiasis, APACHE II score ≥20 or ANC <500/μL | 5 Participants | 10 Participants | 5 Participants |
| Region of Enrollment Australia | 8 participants | 13 participants | 5 participants |
| Region of Enrollment Belgium | 5 participants | 12 participants | 7 participants |
| Region of Enrollment Bulgaria | 6 participants | 10 participants | 4 participants |
| Region of Enrollment China | 6 participants | 11 participants | 5 participants |
| Region of Enrollment Colombia | 1 participants | 1 participants | 0 participants |
| Region of Enrollment France | 5 participants | 6 participants | 1 participants |
| Region of Enrollment Greece | 6 participants | 17 participants | 11 participants |
| Region of Enrollment Israel | 3 participants | 5 participants | 2 participants |
| Region of Enrollment Italy | 2 participants | 5 participants | 3 participants |
| Region of Enrollment Singapore | 3 participants | 3 participants | 0 participants |
| Region of Enrollment South Korea | 6 participants | 12 participants | 6 participants |
| Region of Enrollment Spain | 12 participants | 24 participants | 12 participants |
| Region of Enrollment Taiwan | 3 participants | 4 participants | 1 participants |
| Region of Enrollment Thailand | 8 participants | 25 participants | 17 participants |
| Region of Enrollment United States | 26 participants | 51 participants | 25 participants |
| Sex: Female, Male Female | 33 Participants | 76 Participants | 43 Participants |
| Sex: Female, Male Male | 67 Participants | 123 Participants | 56 Participants |
| Weight | 68.00 kilograms | 67.90 kilograms | 69.82 kilograms STANDARD_DEVIATION 22.602 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 29 / 98 | 25 / 98 |
| other Total, other adverse events | 90 / 98 | 66 / 98 |
| serious Total, serious adverse events | 55 / 98 | 52 / 98 |
Outcome results
Primary
All-Cause Mortality (US FDA Only)
The number and percentage of subjects in each treatment group who are alive and deceased (or with missing data) in the mITT population.
Time frame: Day 30 (-2 days)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Rezafungin for Injection | All-Cause Mortality (US FDA Only) | Deceased: Known Deceased (subjects who died on or before Day 30) | 19 Participants |
| Group 1: Rezafungin for Injection | All-Cause Mortality (US FDA Only) | Deceased: Unknown Survival Status | 3 Participants |
| Group 1: Rezafungin for Injection | All-Cause Mortality (US FDA Only) | Alive | 71 Participants |
| Group 2: Caspofungin | All-Cause Mortality (US FDA Only) | Alive | 74 Participants |
| Group 2: Caspofungin | All-Cause Mortality (US FDA Only) | Deceased: Known Deceased (subjects who died on or before Day 30) | 17 Participants |
| Group 2: Caspofungin | All-Cause Mortality (US FDA Only) | Deceased: Unknown Survival Status | 3 Participants |
Primary
Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only)
The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure \[for qualifying invasive candidiasis subjects at baseline\], and mycological eradication, as confirmed by the Data Review Committee \[DRC\]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol.
Time frame: Day 14 (±1 day)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Rezafungin for Injection | Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) | Cure | 55 Participants |
| Group 1: Rezafungin for Injection | Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) | Failure | 28 Participants |
| Group 1: Rezafungin for Injection | Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) | Indeterminate | 10 Participants |
| Group 2: Caspofungin | Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) | Cure | 57 Participants |
| Group 2: Caspofungin | Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) | Failure | 29 Participants |
| Group 2: Caspofungin | Global Response as Assessed by Data Review Committee (EU European Medicines Agency [EMA] Only) | Indeterminate | 8 Participants |
Secondary
All-Cause Mortality (EU EMA Only)
The number and percentage of subjects in each treatment group who are alive and deceased (or with missing data) in the mITT population.
Time frame: Day 30 (-2 days)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Rezafungin for Injection | All-Cause Mortality (EU EMA Only) | Alive | 71 Participants |
| Group 1: Rezafungin for Injection | All-Cause Mortality (EU EMA Only) | Deceased: Known Deceased (subjects who died on or before Day 30) | 19 Participants |
| Group 1: Rezafungin for Injection | All-Cause Mortality (EU EMA Only) | Deceased: Unknown Survival Status | 3 Participants |
| Group 2: Caspofungin | All-Cause Mortality (EU EMA Only) | Deceased: Unknown Survival Status | 3 Participants |
| Group 2: Caspofungin | All-Cause Mortality (EU EMA Only) | Deceased: Known Deceased (subjects who died on or before Day 30) | 17 Participants |
| Group 2: Caspofungin | All-Cause Mortality (EU EMA Only) | Alive | 74 Participants |
Secondary
Comparison of Global Response (as Assessed by the DRC) by Visit
The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure \[for qualifying invasive candidiasis subjects at baseline\], and mycological eradication, as confirmed by the Data Review Committee \[DRC\]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol.
Time frame: Day 5, Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose) and Follow-up (Days 52-59)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Follow-up (Days 52-59) | Indeterminate | 13 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | EOT (≤2 days of last dose) | Cure | 56 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | EOT (≤2 days of last dose) | Failure | 29 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | EOT (≤2 days of last dose) | Indeterminate | 8 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 5 | Cure | 52 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 5 | Failure | 32 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 30 (-2 days) | Cure | 46 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 30 (-2 days) | Failure | 31 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 5 | Indeterminate | 9 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Follow-up (Days 52-59) | Cure | 42 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Follow-up (Days 52-59) | Failure | 38 Participants |
| Group 1: Rezafungin for Injection | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 30 (-2 days) | Indeterminate | 16 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 30 (-2 days) | Failure | 36 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 30 (-2 days) | Indeterminate | 12 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Follow-up (Days 52-59) | Failure | 42 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | EOT (≤2 days of last dose) | Cure | 59 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Follow-up (Days 52-59) | Cure | 39 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | EOT (≤2 days of last dose) | Failure | 32 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 30 (-2 days) | Cure | 46 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 5 | Failure | 37 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Follow-up (Days 52-59) | Indeterminate | 13 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 5 | Indeterminate | 8 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | EOT (≤2 days of last dose) | Indeterminate | 3 Participants |
| Group 2: Caspofungin | Comparison of Global Response (as Assessed by the DRC) by Visit | Day 5 | Cure | 49 Participants |
Secondary
Comparison of Investigators' Assessment of Clinical Response by Visit
The number and percentage of subjects in each treatment group for whom the Investigator determined a clinical response of cure, failure, or indeterminate in the mITT population. A clinical response of cure, as assessed by the Investigator, is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the clinical responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 9 (Investigator's Assessment of Clinical Response) of the clinical protocol.
Time frame: Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 5 | Cure | 59 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 5 | Failure | 31 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 5 | Indeterminate | 3 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 14 (±1 day) | Cure | 62 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 14 (±1 day) | Failure | 26 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 14 (±1 day) | Indeterminate | 5 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 30 (-2 days) | Cure | 51 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 30 (-2 days) | Failure | 32 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 30 (-2 days) | Indeterminate | 10 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Follow-up (Days 52-59) | Indeterminate | 9 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Follow-up (Days 52-59) | Cure | 46 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | Follow-up (Days 52-59) | Failure | 38 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | EOT (≤2 days of last dose) | Cure | 65 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | EOT (≤2 days of last dose) | Failure | 22 Participants |
| Group 1: Rezafungin for Injection | Comparison of Investigators' Assessment of Clinical Response by Visit | EOT (≤2 days of last dose) | Indeterminate | 6 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 30 (-2 days) | Failure | 34 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 5 | Cure | 70 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Follow-up (Days 52-59) | Failure | 40 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 5 | Failure | 22 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 30 (-2 days) | Indeterminate | 8 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 5 | Indeterminate | 2 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Follow-up (Days 52-59) | Indeterminate | 10 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 14 (±1 day) | Cure | 63 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | EOT (≤2 days of last dose) | Indeterminate | 4 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 14 (±1 day) | Failure | 27 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | EOT (≤2 days of last dose) | Failure | 26 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 14 (±1 day) | Indeterminate | 4 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Follow-up (Days 52-59) | Cure | 44 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | Day 30 (-2 days) | Cure | 52 Participants |
| Group 2: Caspofungin | Comparison of Investigators' Assessment of Clinical Response by Visit | EOT (≤2 days of last dose) | Cure | 64 Participants |
Secondary
Comparison of Mycological Eradication by Visit
The number and percentage of subjects in each treatment group who have a mycological response of eradication, failure, or indeterminate in the mITT population. A mycological response of eradication means clearance of objective evidence of infection and is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was eradication or failure. Definitions for the mycological responses of eradication, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 8 (Mycological Response) of the clinical protocol. Note: Eradication includes both documented and presumed eradication.
Time frame: Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 5 | Indeterminate | 4 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 30 (-2 days) | Eradication | 56 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Follow-up (Days 52-59) | Failure | 41 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 30 (-2 days) | Indeterminate | 4 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 14 (±1 day) | Eradication | 63 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | EOT (≤2 days of last dose) | Eradication | 63 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 5 | Failure | 25 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | EOT (≤2 days of last dose) | Failure | 26 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 14 (±1 day) | Failure | 26 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 5 | Eradication | 64 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 30 (-2 days) | Failure | 33 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | EOT (≤2 days of last dose) | Indeterminate | 4 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Day 14 (±1 day) | Indeterminate | 4 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Follow-up (Days 52-59) | Eradication | 48 Participants |
| Group 1: Rezafungin for Injection | Comparison of Mycological Eradication by Visit | Follow-up (Days 52-59) | Indeterminate | 4 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Follow-up (Days 52-59) | Eradication | 49 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Follow-up (Days 52-59) | Failure | 43 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Follow-up (Days 52-59) | Indeterminate | 2 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 5 | Eradication | 58 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 5 | Failure | 27 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 5 | Indeterminate | 9 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 14 (±1 day) | Eradication | 62 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 14 (±1 day) | Failure | 28 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 14 (±1 day) | Indeterminate | 4 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 30 (-2 days) | Failure | 38 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 30 (-2 days) | Indeterminate | 3 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | EOT (≤2 days of last dose) | Eradication | 63 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | EOT (≤2 days of last dose) | Failure | 29 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | Day 30 (-2 days) | Eradication | 53 Participants |
| Group 2: Caspofungin | Comparison of Mycological Eradication by Visit | EOT (≤2 days of last dose) | Indeterminate | 2 Participants |
Secondary
Comparison of Radiological Response by Investigator by Visit
The number and percentage of subjects with invasive candidiasis (documented by radiologic/imaging evidence at baseline) in each treatment group who have a radiological response (as assessed by the Investigator) of cure, failure, and indeterminate in the mITT population. A radiological response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the radiological responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 10 (Radiological Response) of the clinical protocol.
Time frame: Day 5, Day 14 (±1 day), Day 30 (-2 days), End of Treatment (EOT) (≤2 days of last dose), and Follow-up (Days 52-59)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 30 (-2 days) | Cure | 10 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | EOT (≤2 days of last dose) | Failure | 2 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 5 | Failure | 2 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | EOT (≤2 days of last dose) | Indeterminate | 5 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 30 (-2 days) | Failure | 4 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Follow-up (Days 52-59) | Cure | 12 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 14 (±1 day) | Indeterminate | 4 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 14 (±1 day) | Failure | 2 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 30 (-2 days) | Indeterminate | 3 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 5 | Cure | 4 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Follow-up (Days 52-59) | Failure | 3 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | EOT (≤2 days of last dose) | Cure | 9 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Follow-up (Days 52-59) | Indeterminate | 2 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 5 | Indeterminate | 9 Participants |
| Group 1: Rezafungin for Injection | Comparison of Radiological Response by Investigator by Visit | Day 14 (±1 day) | Cure | 11 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 5 | Indeterminate | 9 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 5 | Cure | 6 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 5 | Failure | 2 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Follow-up (Days 52-59) | Indeterminate | 0 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 14 (±1 day) | Indeterminate | 1 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 30 (-2 days) | Cure | 11 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 30 (-2 days) | Failure | 6 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 30 (-2 days) | Indeterminate | 0 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | EOT (≤2 days of last dose) | Cure | 11 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | EOT (≤2 days of last dose) | Failure | 6 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | EOT (≤2 days of last dose) | Indeterminate | 0 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 14 (±1 day) | Cure | 10 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Day 14 (±1 day) | Failure | 6 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Follow-up (Days 52-59) | Cure | 10 Participants |
| Group 2: Caspofungin | Comparison of Radiological Response by Investigator by Visit | Follow-up (Days 52-59) | Failure | 7 Participants |
Secondary
Evaluate Pharmacokinetics (Cmax)
Evaluate the maximum plasma concentration (Cmax) of rezafungin for injection.
Time frame: Day 1, 10 minutes before the end of infusion
Population: The Pharmacokinetic (PK) Population includes all subjects who received any amount of study drug and had at least one blood sample with measurable concentrations.~Note: Although blood samples were collected from all subjects receiving study drug, only PK samples from subjects receiving rezafungin for injection were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Rezafungin for Injection | Evaluate Pharmacokinetics (Cmax) | 24.18 micrograms/milliliter | Standard Deviation 32.497 |
Secondary
Evaluate Pharmacokinetics (Cmin)
Evaluate the minimum plasma concentration (Cmin) of rezafungin for injection.
Time frame: Day 8, pre-dose, within 30 minutes prior to the start of infusion
Population: The Pharmacokinetic (PK) Population includes all subjects who received any amount of study drug and had at least one blood sample with measurable concentrations.~Note: Although blood samples were collected from all subjects receiving study drug, only PK samples from subjects receiving rezafungin for injection were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Rezafungin for Injection | Evaluate Pharmacokinetics (Cmin) | 2.94 micrograms/milliliter | Standard Deviation 2.656 |
Secondary
Evaluate Pharmacokinetics (Cmin)
Evaluate the minimum plasma concentration (Cmin) of rezafungin for injection.
Time frame: Day 15, pre-dose, within 30 minutes prior to the start of infusion
Population: The Pharmacokinetic (PK) Population includes all subjects who received any amount of study drug and had at least one blood sample with measurable concentrations.~Note: Although blood samples were collected from all subjects receiving study drug, only PK samples from subjects receiving rezafungin for injection were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Rezafungin for Injection | Evaluate Pharmacokinetics (Cmin) | 2.81 micrograms/milliliter | Standard Deviation 1.378 |
Secondary
Evaluate Pharmacokinetics (Cmin)
Evaluate the minimum plasma concentration (Cmin) of rezafungin for injection.
Time frame: Day 22, pre-dose, within 30 minutes prior to the start of infusion
Population: The Pharmacokinetic (PK) Population includes all subjects who received any amount of study drug and had at least one blood sample with measurable concentrations.~Note: Although blood samples were collected from all subjects receiving study drug, only PK samples from subjects receiving rezafungin for injection were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Group 1: Rezafungin for Injection | Evaluate Pharmacokinetics (Cmin) | 3.74 micrograms/milliliter | Standard Deviation 1.948 |
Secondary
Global Response as Assessed by Data Review Committee (US FDA Only)
The number and percentage of subjects in each treatment group who have a global response of cure (clinical cure as assessed by the Investigator, radiological cure \[for qualifying invasive candidiasis subjects at baseline\], and mycological eradication, as confirmed by the Data Review Committee \[DRC\]), failure and indeterminate in the mITT population. A global response of cure is indicative of an efficacious outcome and the desired result, whereas a response of failure is indicative of a non-efficacious outcome and the undesired response. Indeterminate responses indicate there was not enough data obtained to determine if the response was cure or failure. Definitions for the global responses of cure, failure, and indeterminate are complex. Detailed definitions for the possible responses to this outcome measure type are provided in Table 7 (Global Response) of the clinical protocol.
Time frame: Day 14 (±1 day)
Population: The modified Intent-to-Treat (mITT) Population includes all subjects who had a documented Candida infection based on central laboratory evaluation of a blood culture or a culture from a normally sterile site obtained ≤4 days (96 hours) before randomization and received ≥1 dose of study drug.
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Rezafungin for Injection | Global Response as Assessed by Data Review Committee (US FDA Only) | Cure | 55 Participants |
| Group 1: Rezafungin for Injection | Global Response as Assessed by Data Review Committee (US FDA Only) | Failure | 28 Participants |
| Group 1: Rezafungin for Injection | Global Response as Assessed by Data Review Committee (US FDA Only) | Indeterminate | 10 Participants |
| Group 2: Caspofungin | Global Response as Assessed by Data Review Committee (US FDA Only) | Cure | 57 Participants |
| Group 2: Caspofungin | Global Response as Assessed by Data Review Committee (US FDA Only) | Indeterminate | 8 Participants |
| Group 2: Caspofungin | Global Response as Assessed by Data Review Committee (US FDA Only) | Failure | 29 Participants |
Secondary
Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability]
The number and percentage of subjects in each treatment group that experienced at least one treatment-emergent adverse event (TEAE) based on clinical chemistry, hematology and urine analysis laboratory test, vital sign, physical exams and electrocardiogram (ECG) abnormalities. Notes: A subject with multiple adverse events (AEs) was counted only once. TEAE was defined as an AE that occurred during or after study drug administration and up through the Follow-up visit. The maximum severity and strongest relationship were counted for subjects with multiple events.
Time frame: Day 1 through Follow-up Visit (Days 52-59)
Population: The Safety Population includes all subjects who received any amount of the study drug. Safety analyses were performed on the Safety Population. Subjects who received the wrong study drug for their entire course of study drug were analyzed in the treatment group based on the drug received. Subjects who received the wrong study drug for part of their course of study drug were analyzed in the treatment group based on majority of (i.e., most frequent) doses received.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Group 1: Rezafungin for Injection | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE leading to study discontinuation | 20 Participants |
| Group 1: Rezafungin for Injection | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one grade 4/5 TEAE | 36 Participants |
| Group 1: Rezafungin for Injection | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one study drug-related TEAE | 16 Participants |
| Group 1: Rezafungin for Injection | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE | 89 Participants |
| Group 1: Rezafungin for Injection | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE leading to discontinuation of study drug | 13 Participants |
| Group 1: Rezafungin for Injection | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE up through Day 7 | 68 Participants |
| Group 1: Rezafungin for Injection | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE leading to interruption of study drug | 3 Participants |
| Group 2: Caspofungin | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE up through Day 7 | 61 Participants |
| Group 2: Caspofungin | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one grade 4/5 TEAE | 37 Participants |
| Group 2: Caspofungin | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE leading to interruption of study drug | 1 Participants |
| Group 2: Caspofungin | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE leading to discontinuation of study drug | 11 Participants |
| Group 2: Caspofungin | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE leading to study discontinuation | 17 Participants |
| Group 2: Caspofungin | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one TEAE | 83 Participants |
| Group 2: Caspofungin | Number of Subjects With Treatment-Emergent Adverse Events [Safety and Tolerability] | At least one study drug-related TEAE | 9 Participants |