Candida Vulvovaginitis
Conditions
Brief summary
This is a multicenter, randomized, double-blind, double-dummy, active-controlled, dose-finding study to compare the efficacy, safety and tolerability of oral SCY-078 versus oral fluconazole in adult female subjects 18 years and older with moderate to severe Acute Vulvovaginal Candidiasis (AVVC). Approximately 180 eligible subjects (30 subjects per treatment group) will be enrolled and randomized into the study.
Detailed description
This is a Phase 2, multicenter, randomized, double-blind, double-dummy, active-controlled, dose-ranging study of female subjects with moderate to severe Acute Vulvovaginal Candidiasis. Subjects will be randomized to either the investigational arm (SCY-078) with 5 different dose regiments ranging from 1 to 3 days of treatment or to the active-control arm (fluconazole) for 1 day of treatment. After randomization subjects may be seen on study Day 3 (on site visit for PK subjects) , Day 10 (±2,) and Day 25 (+4).
Interventions
DRUGFluconazole
Oral Antifungal comparator
DRUGSCY-078
Investigational Antifungal
Sponsors
Scynexis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
randomized, double-blind, double-dummy, active-controlled, dose-finding
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Subject is a female of at least 18 years of age 2. Subject has a diagnosis of symptomatic AVVC at baseline including a positive microscopic examination with 10% KOH in a vaginal sample revealing yeast forms (hyphae/pseudohyphae) or budding yeasts, and vaginal pH (≤4.5) Key
Exclusion criteria
1. Subject has any vaginal condition other than AVVC that may interfere with the diagnosis or evaluation of response to therapy, such as suspected or confirmed concurrent causes of vulvovaginitis and/or cervicitis (mixed infection) 2. Need for systemic and/or topical (vaginal) antifungal treatment, including prescription or over-the-counter products during the study and treatment for VVC 28 days prior to randomization 3. Subject is actively menstruating at the time of the Baseline visit. 4. Subject has uncontrolled diabetes mellitus. 5. Subject has a vaginal sample with pH \>4.5. 6. Subject has a history of or an active cervical/vaginal cancer.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Cure (Complete Resolution of Signs and Symptoms) | 8-12 days | Measured by the percentage of subjects with clinical cure (complete resolution of signs and symptoms) at the test-of-cure (TOC) visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Co-occurrence of Clinical and Mycological Cure | 29 days | The percentage of subjects with both clinical cure and mycological eradication (negative fungal culture) the Test-of cure. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment Emergent Adverse Events | up to 29 days | The number of subjects with treatment related adverse events |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ibrexafungerp 750-mg 750 mg QD for 1 day only | 32 |
| Ibrexafungerp 300-mg 300 mg BID for 1 day only | 30 |
| Ibrexafungerp 450-mg 450 mg BID for 1 day only | 28 |
| Ibrexafungerp 150-mg 150 mg BID for 3 days | 32 |
| Ibrexafungerp 300-mg (3 Days) 300 mg BID for 3 days | 32 |
| Fluconazole 150 mg QD for 1 day | 32 |
| Total | 186 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 2 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 2 | 1 | 2 | 1 |
| Overall Study | Lost to Follow-up | 0 | 0 | 1 | 1 | 0 | 1 |
| Overall Study | Other | 0 | 1 | 2 | 1 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 1 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 2 | 1 | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Ibrexafungerp 750-mg | Total | Fluconazole | Ibrexafungerp 300-mg (3 Days) | Ibrexafungerp 150-mg | Ibrexafungerp 450-mg | Ibrexafungerp 300-mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.6 years STANDARD_DEVIATION 12.3 | 33.7 years STANDARD_DEVIATION 10.4 | 33.8 years STANDARD_DEVIATION 10.1 | 32.0 years STANDARD_DEVIATION 8.5 | 33.3 years STANDARD_DEVIATION 10.5 | 34.5 years STANDARD_DEVIATION 9.8 | 34.4 years STANDARD_DEVIATION 11.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 56 Participants | 11 Participants | 7 Participants | 11 Participants | 8 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 22 Participants | 130 Participants | 21 Participants | 25 Participants | 21 Participants | 20 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 9 Participants | 72 Participants | 13 Participants | 15 Participants | 13 Participants | 12 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 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 | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 109 Participants | 19 Participants | 16 Participants | 18 Participants | 14 Participants | 20 Participants |
| Region of Enrollment United States | 32 participants | 186 participants | 32 participants | 32 participants | 32 participants | 28 participants | 30 participants |
| Sex: Female, Male Female | 32 Participants | 186 Participants | 32 Participants | 32 Participants | 32 Participants | 28 Participants | 30 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 30 | 0 / 28 | 0 / 31 | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 21 / 32 | 13 / 30 | 15 / 28 | 15 / 31 | 18 / 32 | 10 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 30 | 0 / 28 | 0 / 31 | 0 / 32 | 0 / 32 |
Outcome results
Primary
Clinical Cure (Complete Resolution of Signs and Symptoms)
Measured by the percentage of subjects with clinical cure (complete resolution of signs and symptoms) at the test-of-cure (TOC) visit
Time frame: 8-12 days
Population: mITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp 750-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 9 Participants |
| Ibrexafungerp 750-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 17 Participants |
| Ibrexafungerp 300-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 14 Participants |
| Ibrexafungerp 300-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 13 Participants |
| Ibrexafungerp 450-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 13 Participants |
| Ibrexafungerp 450-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 8 Participants |
| Ibrexafungerp 150-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 15 Participants |
| Ibrexafungerp 150-mg | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 14 Participants |
| Ibrexafungerp 300-mg D1 to D3 | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 15 Participants |
| Ibrexafungerp 300-mg D1 to D3 | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 11 Participants |
| Fluconazole | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 10 Participants |
| Fluconazole | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 14 Participants |
Secondary
Co-occurrence of Clinical and Mycological Cure
The percentage of subjects with both clinical cure and mycological eradication (negative fungal culture) the Test-of cure.
Time frame: 29 days
Population: mITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp 750-mg | Co-occurrence of Clinical and Mycological Cure | Clinical cure and Mycological Eradication | 4 Participants |
| Ibrexafungerp 750-mg | Co-occurrence of Clinical and Mycological Cure | Clinical failure and/or mycological persistence | 22 Participants |
| Ibrexafungerp 300-mg | Co-occurrence of Clinical and Mycological Cure | Clinical cure and Mycological Eradication | 10 Participants |
| Ibrexafungerp 300-mg | Co-occurrence of Clinical and Mycological Cure | Clinical failure and/or mycological persistence | 17 Participants |
| Ibrexafungerp 450-mg | Co-occurrence of Clinical and Mycological Cure | Clinical cure and Mycological Eradication | 11 Participants |
| Ibrexafungerp 450-mg | Co-occurrence of Clinical and Mycological Cure | Clinical failure and/or mycological persistence | 10 Participants |
| Ibrexafungerp 150-mg | Co-occurrence of Clinical and Mycological Cure | Clinical cure and Mycological Eradication | 8 Participants |
| Ibrexafungerp 150-mg | Co-occurrence of Clinical and Mycological Cure | Clinical failure and/or mycological persistence | 21 Participants |
| Ibrexafungerp 300-mg D1 to D3 | Co-occurrence of Clinical and Mycological Cure | Clinical cure and Mycological Eradication | 13 Participants |
| Ibrexafungerp 300-mg D1 to D3 | Co-occurrence of Clinical and Mycological Cure | Clinical failure and/or mycological persistence | 13 Participants |
| Fluconazole | Co-occurrence of Clinical and Mycological Cure | Clinical cure and Mycological Eradication | 10 Participants |
| Fluconazole | Co-occurrence of Clinical and Mycological Cure | Clinical failure and/or mycological persistence | 14 Participants |
Other Pre-specified
Incidence of Treatment Emergent Adverse Events
The number of subjects with treatment related adverse events
Time frame: up to 29 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp 750-mg | Incidence of Treatment Emergent Adverse Events | Treatment related Treatment-emergent adverse event | 20 Participants |
| Ibrexafungerp 750-mg | Incidence of Treatment Emergent Adverse Events | No Treatment related Treatment-emergent adverse event | 12 Participants |
| Ibrexafungerp 300-mg | Incidence of Treatment Emergent Adverse Events | Treatment related Treatment-emergent adverse event | 14 Participants |
| Ibrexafungerp 300-mg | Incidence of Treatment Emergent Adverse Events | No Treatment related Treatment-emergent adverse event | 16 Participants |
| Ibrexafungerp 450-mg | Incidence of Treatment Emergent Adverse Events | Treatment related Treatment-emergent adverse event | 16 Participants |
| Ibrexafungerp 450-mg | Incidence of Treatment Emergent Adverse Events | No Treatment related Treatment-emergent adverse event | 12 Participants |
| Ibrexafungerp 150-mg | Incidence of Treatment Emergent Adverse Events | Treatment related Treatment-emergent adverse event | 12 Participants |
| Ibrexafungerp 150-mg | Incidence of Treatment Emergent Adverse Events | No Treatment related Treatment-emergent adverse event | 19 Participants |
| Ibrexafungerp 300-mg D1 to D3 | Incidence of Treatment Emergent Adverse Events | Treatment related Treatment-emergent adverse event | 15 Participants |
| Ibrexafungerp 300-mg D1 to D3 | Incidence of Treatment Emergent Adverse Events | No Treatment related Treatment-emergent adverse event | 17 Participants |
| Fluconazole | Incidence of Treatment Emergent Adverse Events | Treatment related Treatment-emergent adverse event | 8 Participants |
| Fluconazole | Incidence of Treatment Emergent Adverse Events | No Treatment related Treatment-emergent adverse event | 24 Participants |