Recurrent Vulvovaginal Candidiasis
Conditions
Brief summary
Recurrent vulvovaginal candidiasis (RVVC), also known as recurrent yeast infections, is defined as at least 3 episodes of acute VVC in the past 12 months. Several properties of oteseconazole (VT-1161) suggest that it might be a safer and more effective treatment for RVVC than other oral antifungal medicines. This study will evaluate the effectiveness and safety of oteseconazole (VT-1161) for the treatment of RVVC and consists of 2 parts. The first part of the study is a 2-week period for the treatment of the patient's current VVC episode with 3 150mg doses of fluconazole. The 2nd part consists of 12 weeks, when the patient will take either oteseconazole (VT-1161) 150 mg or a placebo (according to a random assignment), and then a 36-week follow-up period. In addition, at participating sites, an amendment to the study allows US patients who complete the initial 48 weeks without experiencing a confirmed RVVC episode to continue in a 48-week observational extension period designed to evaluate the continued effectiveness of oteseconazole (VT-1161). This study is identical to VMT-VT-1161-CL-011.
Interventions
Oteseconazole (VT-1161) 150mg capsule
DRUGPlacebo
matching placebo capsule
Sponsors
Mycovia Pharmaceuticals Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * 3 or more episodes of acute VVC in the past 12 months * Positive KOH or Gram stain test * Total vulvovaginal signs and symptoms score of ≥3 at screening visit * Total vulvovaginal signs and symptoms score of \<3 at baseline visit * Must be able to swallow pills Key
Exclusion criteria
* Presence or a history of another vaginal or vulvar condition(s) * Evidence of major organ system disease * History of cervical cancer * Poorly controlled diabetes mellitus * Pregnant * Recent use of topical or systemic antifungal or antibacterial drugs * Recent use of immunosuppressive or systemic corticosteroid therapies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population. | Maintenance phase (Baseline through Week 48) | The primary efficacy outcome measure was the percentage of subjects with 1 or more culture-verified acute VVC episodes during the maintenance phase (post-randomization through Week 48) in the intent-to-treat population. An acute VVC episode during the maintenance phase (considered a recurrent episode) was defined as a positive fungal culture for Candida species and a clinical signs and symptoms score of ≥3. To calculate the signs and symptoms score, each vulvovaginal sign (erythema, edema, excoriation) and symptom (itching, burning, irritation) was scored using the following scale, with a higher score indicating a worse outcome. 0 = none (complete absence of any sign or symptom), 1 = mild (slight), 2 = moderate (definitely present), 3 = severe (marked, intense) |
Countries
United States
Participant flow
Pre-assignment details
A total of 425 subjects were enrolled in a 2-week Induction Phase after providing consent. During the Induction Phase, subjects received 3 sequential 150mg of fluconazole administered 72 hours apart. Subjects whose presenting acute VVC (vulvovaginal candidiasis) episode resolved during the Induction Phase (a total of 330) entered a 48-week Maintenance Phase comprised of a 12-week treatment period and a 36-week follow-up period.
Participants by arm
| Arm | Count |
|---|---|
| Oteseconazole (VT-1161) 1 oteseconazole 150mg capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | 218 |
| Placebo 1 placebo capsule once daily for 7 days starting at Day 1, then once weekly for 11 weeks | 108 |
| Total | 326 |
Baseline characteristics
| Characteristic | Oteseconazole (VT-1161) | Total | Placebo |
|---|---|---|---|
| Age, Continuous | 34 years STANDARD_DEVIATION 9.4 | 34 years STANDARD_DEVIATION 9.9 | 36 years STANDARD_DEVIATION 10.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 23 Participants | 31 Participants | 8 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 | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) White | 193 Participants | 289 Participants | 96 Participants |
| Region of Enrollment Belgium | 18 participants | 26 participants | 8 participants |
| Region of Enrollment Czechia | 51 participants | 73 participants | 22 participants |
| Region of Enrollment Hungary | 8 participants | 11 participants | 3 participants |
| Region of Enrollment Romania | 44 participants | 72 participants | 28 participants |
| Region of Enrollment Ukraine | 17 participants | 26 participants | 9 participants |
| Region of Enrollment United States | 80 participants | 118 participants | 38 participants |
| Sex: Female, Male Female | 218 Participants | 326 Participants | 108 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 / 217 | 0 / 110 |
| other Total, other adverse events | 112 / 217 | 63 / 110 |
| serious Total, serious adverse events | 7 / 217 | 5 / 110 |
Outcome results
Primary
Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population.
The primary efficacy outcome measure was the percentage of subjects with 1 or more culture-verified acute VVC episodes during the maintenance phase (post-randomization through Week 48) in the intent-to-treat population. An acute VVC episode during the maintenance phase (considered a recurrent episode) was defined as a positive fungal culture for Candida species and a clinical signs and symptoms score of ≥3. To calculate the signs and symptoms score, each vulvovaginal sign (erythema, edema, excoriation) and symptom (itching, burning, irritation) was scored using the following scale, with a higher score indicating a worse outcome. 0 = none (complete absence of any sign or symptom), 1 = mild (slight), 2 = moderate (definitely present), 3 = severe (marked, intense)
Time frame: Maintenance phase (post-randomization through Week 48)
Population: Analysis was performed on the ITT population which included all randomized subjects except the 4 excluded subjects. Missing values were imputed with multiple imputation using the following auxiliary information: region, treatment, baseline body mass index, baseline age, ethnicity, and visit.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Oteseconazole (VT-1161) | Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population. | 3.9 percentage of subjects |
| Placebo | Percentage of Subjects With 1 or More Culture-verified Acute VVC Episodes During the Maintenance Phase of the Study in the Intent-to-treat (ITT) Population. | 39.4 percentage of subjects |