Candida Vulvovaginitis
Conditions
Brief summary
This is a Phase 3, randomized, multicenter, double-blind, placebo-controlled study to evaluate the efficacy and safety of oral Ibrexafungerp (SCY-078) compared to placebo in female subjects 12 years and older with AVVC.
Detailed description
Subjects who meet all of the inclusion and none of the exclusion criteria will be enrolled into the study and will be randomized in a 2:1 ratio to either oral ibrexafungerp or ibrexafungerp matching placebo, as follows: * Oral ibrexafungerp 300-mg dose BID for 1 day * Oral ibrexafungerp matching placebo BID for 1 day Subjects will receive their first dose of study drug at the site and will be dispensed the second dose for self-administration at home 12 hours after the first dose. Study Blinding, Randomization and Stratification: This is a randomized, double-blind study. All site and sponsor personnel will be blinded to treatment assignment. Approximately 366 eligible subjects will be enrolled and randomized in a 2:1 ratio to one of the two study treatment groups. For the purpose of maintaining treatment blinding, all subjects randomized to the placebo group will receive matching ibrexafungerp placebo tablets.
Interventions
DRUGIbrexafungerp
Ibrexafungerp 300 mg BID for 1 day
DRUGPlacebo
Matching placebo
Sponsors
Scynexis, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
randomized, placebo-controlled, double-blind study
Eligibility
Sex/Gender
FEMALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Subject is a postmenarchal female subject 12 years and older 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)
Exclusion criteria
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) 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 Subject is actively menstruating at the time of the Baseline visit. Subject has uncontrolled diabetes mellitus. Subject has a vaginal sample with pH \>4.5. 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) | Day 8-14 | 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 |
|---|---|---|
| Mycological Eradication (Negative Culture for Growth of Yeast) | Day 8-14 | percentage of subjects with mycological eradication (negative culture for growth of Candida species) at the TOC visit |
| Clinical Cure and Mycological Eradication (Responder Outcome) | Day 8-14 | percentage of subjects with clinical cure and mycological eradication (responder outcome) at the TOC visit |
| Complete Clinical Response at Follow-Up | Day 25 | percentage of subjects with complete resolution of signs and symptoms at the Follow-up (FU) visit |
| Overall Treatment-Emergent Adverse Events (Safety Set) | Up to 29 days | Number of subjects with treatment related adverse events |
Countries
United States
Participant flow
Recruitment details
Participants were recruited based on physician referral at 28 medical centers between 04Jan2019 and 04Sep2019.
Participants by arm
| Arm | Count |
|---|---|
| Ibrexafungerp (SCY-078) 300 mg orally every 12 hrs for 1 day (2 doses in 1 day)
Ibrexafungerp: Ibrexafungerp 300 mg BID for 1 day | 247 |
| Placebo Matching Placebo
Placebo: Matching placebo | 124 |
| Total | 371 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 4 | 0 |
| Overall Study | Lack of efficacy and or/use of antifungal therapy | 49 | 41 |
| Overall Study | Lost to Follow-up | 4 | 0 |
| Overall Study | Other | 2 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Pregnancy | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 3 |
Baseline characteristics
| Characteristic | Ibrexafungerp (SCY-078) | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical >=65 years | 3 Participants | 3 Participants | 6 Participants |
| Age, Categorical Between 18 and 65 years | 244 Participants | 120 Participants | 364 Participants |
| Age, Continuous | 34.5 years STANDARD_DEVIATION 11.22 | 35.8 years STANDARD_DEVIATION 12.47 | 34.9 years STANDARD_DEVIATION 11.63 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 64 Participants | 25 Participants | 89 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 183 Participants | 99 Participants | 282 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 0 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 101 Participants | 51 Participants | 152 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 | 8 Participants | 2 Participants | 10 Participants |
| Race (NIH/OMB) White | 132 Participants | 71 Participants | 203 Participants |
| Region of Enrollment United States | 247 participants | 124 participants | 371 participants |
| Sex: Female, Male Female | 247 Participants | 124 Participants | 371 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 247 | 0 / 124 |
| other Total, other adverse events | 117 / 247 | 34 / 124 |
| serious Total, serious adverse events | 1 / 247 | 2 / 124 |
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: Day 8-14
Population: mITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp (SCY-078) | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 95 Participants |
| Ibrexafungerp (SCY-078) | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 93 Participants |
| Placebo | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical cure | 28 Participants |
| Placebo | Clinical Cure (Complete Resolution of Signs and Symptoms) | Clinical failure | 70 Participants |
Secondary
Clinical Cure and Mycological Eradication (Responder Outcome)
percentage of subjects with clinical cure and mycological eradication (responder outcome) at the TOC visit
Time frame: Day 8-14
Population: mITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp (SCY-078) | Clinical Cure and Mycological Eradication (Responder Outcome) | Overall success | 64 Participants |
| Ibrexafungerp (SCY-078) | Clinical Cure and Mycological Eradication (Responder Outcome) | Overall failure | 114 Participants |
| Placebo | Clinical Cure and Mycological Eradication (Responder Outcome) | Overall success | 12 Participants |
| Placebo | Clinical Cure and Mycological Eradication (Responder Outcome) | Overall failure | 83 Participants |
Secondary
Complete Clinical Response at Follow-Up
percentage of subjects with complete resolution of signs and symptoms at the Follow-up (FU) visit
Time frame: Day 25
Population: mITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp (SCY-078) | Complete Clinical Response at Follow-Up | Clinical cure at Follow up | 113 Participants |
| Ibrexafungerp (SCY-078) | Complete Clinical Response at Follow-Up | Clinical failure at Follow up | 77 Participants |
| Placebo | Complete Clinical Response at Follow-Up | Clinical cure at Follow up | 44 Participants |
| Placebo | Complete Clinical Response at Follow-Up | Clinical failure at Follow up | 56 Participants |
Secondary
Mycological Eradication (Negative Culture for Growth of Yeast)
percentage of subjects with mycological eradication (negative culture for growth of Candida species) at the TOC visit
Time frame: Day 8-14
Population: mITT
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp (SCY-078) | Mycological Eradication (Negative Culture for Growth of Yeast) | Mycological eradication | 93 Participants |
| Ibrexafungerp (SCY-078) | Mycological Eradication (Negative Culture for Growth of Yeast) | Mycological persistence | 95 Participants |
| Placebo | Mycological Eradication (Negative Culture for Growth of Yeast) | Mycological eradication | 19 Participants |
| Placebo | Mycological Eradication (Negative Culture for Growth of Yeast) | Mycological persistence | 79 Participants |
Secondary
Overall Treatment-Emergent Adverse Events (Safety Set)
Number of subjects with treatment related adverse events
Time frame: Up to 29 days
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ibrexafungerp (SCY-078) | Overall Treatment-Emergent Adverse Events (Safety Set) | Any treatment-emergent, treatment-related adverse event | 98 Participants |
| Ibrexafungerp (SCY-078) | Overall Treatment-Emergent Adverse Events (Safety Set) | No treatment-emergent, treatment-related adverse events | 149 Participants |
| Placebo | Overall Treatment-Emergent Adverse Events (Safety Set) | Any treatment-emergent, treatment-related adverse event | 21 Participants |
| Placebo | Overall Treatment-Emergent Adverse Events (Safety Set) | No treatment-emergent, treatment-related adverse events | 103 Participants |