Candidemia, Candidiasis, Invasive, Mycoses
Conditions
Keywords
Invasive Candidiasis, Invasive Candida infections, Candidemia, SCY-078, Micafungin, Fluconazole, Echinocandin
Brief summary
The purpose of this study is to compare the safety, pharmacokinetics, and efficacy of oral SCY-078 vs. standard-of-care following initial intravenous echinocandin therapy in the treatment of invasive candidiasis.
Detailed description
Patients will receive initial intravenous (IV) echinocandin therapy. Patients who are eligible for randomization will receive SCY-078 500-mg orally, SCY-078 750-mg orally, or standard-of-care.
Interventions
Sponsors
Scynexis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of invasive candidiasis defined as a positive culture of blood or from another normally sterile site for Candida. * Not of reproductive potential or if of reproductive potential, agrees to remain abstinent or use 2 methods of contraception.
Exclusion criteria
* Patient with Candida endocarditis, osteomyelitis, meningitis, or chronic disseminated candidiasis or evidence of endophthalmitis. * Patient has failed treatment with an echinocandin for this episode of invasive candidiasis. * Infection limited to the oropharynx, esophagus, urogenital system, or skin, or sputum/bronchoalveolar lavage culture. * Participation in a clinical study with other investigational drug(s) within 30 days prior to study entry or during this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | up to 10 weeks | All Related TEAEs by SOC and PT, by Treatment, Safety |
| Dose of SCY-078 That Achieves the Target Exposure (AUC) | 0 to 24 hours post-dose | Summary of PK Parameters on Day 1 by Treatment Arm, from non-compartmental analysis, PK |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Global Response | end of all antifungal therapy (administered for a maximum of 28 days) | Participant's clinical response (signs or symptoms) and microbiological response (presence of Candida culture) |
| Clinical Response | end of all antifungal therapy (administered for a maximum of 28 days) | Participant's persistence of signs or symptoms and administration of systemic non-study antifungal therapy |
| Microbiological Response | end of all antifungal therapy (administered for a maximum of 28 days) | Cultures or radiographs/imaging of blood or non-blood sites of infection showing evidence of Candida infection |
| Relapse | 2 weeks and 6 weeks after the end of all antifungal therapy, up to 10 weeks | If Invasive Candida infection recurs or if antifungal therapy for a proven or suspected Candida infection is administered |
Countries
El Salvador, Germany, Guatemala, Honduras, United States
Participant flow
Pre-assignment details
A total of 27 participants were enrolled, two of whom failed to meet all inclusion and exclusion criteria and were considered screen failures. Among the 25 enrolled participants who met all inclusion and exclusion criteria, three were not randomized. Thus, 22 patients were randomized to receive SCY-078 500 mg or SCY-078 750 mg or standard-of-care.
Participants by arm
| Arm | Count |
|---|---|
| Ibrexafungerp 500-mg A single loading dose of SCY-078 1000-mg orally on the first day, followed by SCY-078 500-mg orally once-daily on subsequent days. | 7 |
| Ibrexafungerp 750-mg A single loading dose of SCY-078 1250-mg orally on the first day, followed by SCY-078 750-mg orally once-daily on subsequent days. | 7 |
| Standard of Care (Fluconazole) Oral fluconazole 400 mg daily (with a loading dose of 800 mg on the first day | 7 |
| Standard of Care (Micafungin) IV micafungin 100 mg daily | 1 |
| Total | 22 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 1 | 0 |
| Overall Study | Did Not Complete Study for Reason Other: | 0 | 1 | 1 | 0 |
| Overall Study | Lost to Follow-up | 2 | 2 | 1 | 0 |
| Overall Study | Protocol Violation | 0 | 0 | 0 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Ibrexafungerp 500-mg | Ibrexafungerp 750-mg | Standard of Care (Fluconazole) | Standard of Care (Micafungin) | Total |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 6 Participants | 6 Participants | 1 Participants | 19 Participants |
| Age, Continuous | 56.4 years STANDARD_DEVIATION 7.81 | 48.9 years STANDARD_DEVIATION 15.46 | 49.6 years STANDARD_DEVIATION 15.66 | 63.0 years | 52.1 years STANDARD_DEVIATION 13.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 0 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 7 Participants | 6 Participants | 1 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 6 Participants | 1 Participants | 17 Participants |
| Region of Enrollment United States | 7 participants | 7 participants | 7 participants | 1 participants | 22 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 5 Participants | 0 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 2 Participants | 1 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 1 / 7 | 1 / 7 | 0 / 1 |
| other Total, other adverse events | 5 / 6 | 4 / 7 | 4 / 7 | 0 / 1 |
| serious Total, serious adverse events | 2 / 6 | 4 / 7 | 3 / 7 | 0 / 1 |
Outcome results
Primary
Dose of SCY-078 That Achieves the Target Exposure (AUC)
Summary of PK Parameters on Day 1 by Treatment Arm, from non-compartmental analysis, PK
Time frame: 0 to 24 hours post-dose
Population: Pharmacokinetic Population
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ibrexafungerp 500-mg | Dose of SCY-078 That Achieves the Target Exposure (AUC) | 3 Participants |
| Ibrexafungerp 750-mg | Dose of SCY-078 That Achieves the Target Exposure (AUC) | 4 Participants |
Primary
Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements
All Related TEAEs by SOC and PT, by Treatment, Safety
Time frame: up to 10 weeks
Population: ITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp 500-mg | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with at least One Drug-Related TEAE | 1 Participants |
| Ibrexafungerp 500-mg | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with no Drug- Related TEAE | 5 Participants |
| Ibrexafungerp 750-mg | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with at least One Drug-Related TEAE | 1 Participants |
| Ibrexafungerp 750-mg | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with no Drug- Related TEAE | 6 Participants |
| Standard of Care (Fluconazole) | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with at least One Drug-Related TEAE | 0 Participants |
| Standard of Care (Fluconazole) | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with no Drug- Related TEAE | 7 Participants |
| Standard of Care (Micafungin) | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with no Drug- Related TEAE | 1 Participants |
| Standard of Care (Micafungin) | Safety and Tolerability, Assessed by Adverse Events, Clinical Laboratory Results, Physical Examination Findings, ECG Results, and Vital Sign Measurements | Patients with at least One Drug-Related TEAE | 0 Participants |
Secondary
Clinical Response
Participant's persistence of signs or symptoms and administration of systemic non-study antifungal therapy
Time frame: end of all antifungal therapy (administered for a maximum of 28 days)
Population: ITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp 500-mg | Clinical Response | Unknown | 1 Participants |
| Ibrexafungerp 500-mg | Clinical Response | Unfavorable | 1 Participants |
| Ibrexafungerp 500-mg | Clinical Response | Favorable | 5 Participants |
| Ibrexafungerp 750-mg | Clinical Response | Unknown | 1 Participants |
| Ibrexafungerp 750-mg | Clinical Response | Favorable | 6 Participants |
| Ibrexafungerp 750-mg | Clinical Response | Unfavorable | 0 Participants |
| Standard of Care (Fluconazole) | Clinical Response | Favorable | 5 Participants |
| Standard of Care (Fluconazole) | Clinical Response | Unfavorable | 2 Participants |
| Standard of Care (Fluconazole) | Clinical Response | Unknown | 0 Participants |
| Standard of Care (Micafungin) | Clinical Response | Unknown | 0 Participants |
| Standard of Care (Micafungin) | Clinical Response | Unfavorable | 0 Participants |
| Standard of Care (Micafungin) | Clinical Response | Favorable | 1 Participants |
Secondary
Global Response
Participant's clinical response (signs or symptoms) and microbiological response (presence of Candida culture)
Time frame: end of all antifungal therapy (administered for a maximum of 28 days)
Population: ITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp 500-mg | Global Response | Favorable | 5 Participants |
| Ibrexafungerp 500-mg | Global Response | Unfavorable | 2 Participants |
| Ibrexafungerp 750-mg | Global Response | Unfavorable | 1 Participants |
| Ibrexafungerp 750-mg | Global Response | Favorable | 6 Participants |
| Standard of Care (Fluconazole) | Global Response | Unfavorable | 2 Participants |
| Standard of Care (Fluconazole) | Global Response | Favorable | 5 Participants |
| Standard of Care (Micafungin) | Global Response | Unfavorable | 0 Participants |
| Standard of Care (Micafungin) | Global Response | Favorable | 1 Participants |
Secondary
Microbiological Response
Cultures or radiographs/imaging of blood or non-blood sites of infection showing evidence of Candida infection
Time frame: end of all antifungal therapy (administered for a maximum of 28 days)
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp 500-mg | Microbiological Response | Favorable | 6 Participants |
| Ibrexafungerp 500-mg | Microbiological Response | Unknown | 1 Participants |
| Ibrexafungerp 500-mg | Microbiological Response | Unfavorable | 0 Participants |
| Ibrexafungerp 750-mg | Microbiological Response | Favorable | 6 Participants |
| Ibrexafungerp 750-mg | Microbiological Response | Unknown | 1 Participants |
| Ibrexafungerp 750-mg | Microbiological Response | Unfavorable | 0 Participants |
| Standard of Care (Fluconazole) | Microbiological Response | Unfavorable | 1 Participants |
| Standard of Care (Fluconazole) | Microbiological Response | Favorable | 6 Participants |
| Standard of Care (Fluconazole) | Microbiological Response | Unknown | 0 Participants |
| Standard of Care (Micafungin) | Microbiological Response | Favorable | 1 Participants |
| Standard of Care (Micafungin) | Microbiological Response | Unknown | 0 Participants |
| Standard of Care (Micafungin) | Microbiological Response | Unfavorable | 0 Participants |
Secondary
Relapse
If Invasive Candida infection recurs or if antifungal therapy for a proven or suspected Candida infection is administered
Time frame: 2 weeks and 6 weeks after the end of all antifungal therapy, up to 10 weeks
Population: Intent-To-Treat (ITT): All randomized participants~Overall number of participants includes all randomized participants, number analyzed includes participants analyzed at a particular time point.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Ibrexafungerp 500-mg | Relapse | Week 2 Post-Treatment | Did Not Relapse | 4 Participants |
| Ibrexafungerp 500-mg | Relapse | Week 6 Post-Treatment | Relapsed | 0 Participants |
| Ibrexafungerp 500-mg | Relapse | Week 2 Post-Treatment | Not Evaluable or Missing | 2 Participants |
| Ibrexafungerp 500-mg | Relapse | Week 6 Post-Treatment | Did Not Relapse | 4 Participants |
| Ibrexafungerp 500-mg | Relapse | Week 6 Post-Treatment | Not Evaluable or Missing | 3 Participants |
| Ibrexafungerp 500-mg | Relapse | Week 2 Post-Treatment | Relapsed | 1 Participants |
| Ibrexafungerp 750-mg | Relapse | Week 2 Post-Treatment | Relapsed | 0 Participants |
| Ibrexafungerp 750-mg | Relapse | Week 6 Post-Treatment | Relapsed | 0 Participants |
| Ibrexafungerp 750-mg | Relapse | Week 6 Post-Treatment | Not Evaluable or Missing | 5 Participants |
| Ibrexafungerp 750-mg | Relapse | Week 2 Post-Treatment | Did Not Relapse | 4 Participants |
| Ibrexafungerp 750-mg | Relapse | Week 2 Post-Treatment | Not Evaluable or Missing | 3 Participants |
| Ibrexafungerp 750-mg | Relapse | Week 6 Post-Treatment | Did Not Relapse | 2 Participants |
| Standard of Care (Fluconazole) | Relapse | Week 2 Post-Treatment | Not Evaluable or Missing | 2 Participants |
| Standard of Care (Fluconazole) | Relapse | Week 6 Post-Treatment | Did Not Relapse | 4 Participants |
| Standard of Care (Fluconazole) | Relapse | Week 2 Post-Treatment | Did Not Relapse | 5 Participants |
| Standard of Care (Fluconazole) | Relapse | Week 2 Post-Treatment | Relapsed | 0 Participants |
| Standard of Care (Fluconazole) | Relapse | Week 6 Post-Treatment | Relapsed | 0 Participants |
| Standard of Care (Fluconazole) | Relapse | Week 6 Post-Treatment | Not Evaluable or Missing | 3 Participants |
| Standard of Care (Micafungin) | Relapse | Week 6 Post-Treatment | Not Evaluable or Missing | 1 Participants |
| Standard of Care (Micafungin) | Relapse | Week 6 Post-Treatment | Relapsed | 0 Participants |
| Standard of Care (Micafungin) | Relapse | Week 6 Post-Treatment | Did Not Relapse | 0 Participants |
| Standard of Care (Micafungin) | Relapse | Week 2 Post-Treatment | Relapsed | 0 Participants |
| Standard of Care (Micafungin) | Relapse | Week 2 Post-Treatment | Did Not Relapse | 0 Participants |
| Standard of Care (Micafungin) | Relapse | Week 2 Post-Treatment | Not Evaluable or Missing | 1 Participants |