Clinical trial NCT05399641: Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis
Official title: Oral Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis (VVC) in Subjects Who Have Failed Fluconazole Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Vulvovaginal Candidiasis
Keywords: vulvovaginal candidiasis
candida
VVC
rVVC
Ibrexafungerp
yeast vaginitis
Lead sponsor: Scynexis, Inc.
Sponsor class: INDUSTRY
First posted: 2022-06-01
Enrollment: 150
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Open-label, 3 group, stratified
Primary purpose: TREATMENT

Brief summary: This study will treat subjects with complicated VVC who have failed prior fluconazole therapy with Ibrexafungerp for 1, 3 or 7 days of treatment.

Detailed description: This study will treat subjects with complicated VVC who have failed prior fluconazole therapy with Ibrexafungerp for 1, 3 or 7 days of treatment.

Approximately 150 eligible subjects will be enrolled. Subjects will be randomized to receive oral ibrexafungerp 300 mg administered twice a day (BID) for either one, three, or seven consecutive days, stratified by group based on Candida species and presence or absence of underlying medical conditions.

The primary endpoint for this study is the percentage of subjects with a clinical cure at the Test of Cure Visit. Test of Cure is defined as a score of zero on the Vulvovaginal Signs and Symptoms Scale and not requiring additional antifungal treatment.

Eligibility criteria: Inclusion Criteria:

1. Subject is a post menarchal female ≥18 years of age at the time of signing the ICF.
2. Subject has a diagnosis of symptomatic VVC that meets the following criteria at the

   Screening visit:
   1. Minimum composite vulvovaginal signs and symptoms score of ≥4 with at least 2 signs or symptoms having a score of 2 (moderate) or greater on the VSS scale at baseline.
   2. Positive microscopic examination with 10% KOH in a vaginal sample collected at Screening revealing yeast forms (hyphae/pseudohyphae) or budding yeasts
   3. Normal vaginal pH (≤ 4.5).
   4. Has no other vaginal co-infections based on wet mount microscopic examination (and/or DNA probe).
3. Subject should also have:

   1. A VVC with persistent symptoms despite fluconazole therapy (last dose of fluconazole must have been administered at least 7 days prior, but no longer than 28 days prior to screening. OR
   2. A recurrent vulvovaginal candidiasis (RVVC) episode with breakthrough symptoms while receiving maintenance antifungal therapy. OR
   3. A VVC episode caused by a non-albicans candida species known to have either intrinsic resistance to fluconazole e.g. C.krusei or suspected resistance to fluconazole, e.g. C.glabrata, C. auris but likely without MIC data in hand. OR
   4. A VVC episode caused by Candida species with documented resistance to fluconazole based on MIC determination. OR
   5. A known history of azole allergy or intolerance.
4. Subject is able to take oral tablets.
5. Subject is not pregnant or lactating and plans not to become pregnant. Women of childbearing potential \< 1 year post-menopausal must agree to and comply with using one barrier method (male condom, female condom, and diaphragm) plus one other highly effective method of birth control, or sexual abstinence, from the time of consent through 10 days after the completion of study therapy. Subjects must refrain from using any topical vaginal contraceptives as these may have an impact on the signs and symptoms of VVC. Note: Women of childbearing potential must have a negative urine pregnancy test prior to enrollment (performed by the site's local laboratory).
6. Subject is able to understand and sign a written ICF, which must be obtained prior to treatment and any study-related procedures.
7. Subject is able to understand and sign a consent or authorization form, which shall permit the use, disclosure and transfer of the subject's personal health information (e.g., in the US Health Information Portability and Accountability Act Authorization form).
8. Subject is able to understand and follow all study-related procedures including study drug administration.

Exclusion Criteria:

1. Subject has any vaginal condition other than VVC that may interfere with the diagnosis or evaluation of response to therapy, such as concurrent causes of vulvovaginitis and/or cervicitis including bacterial vaginosis, Trichomonas, Herpes virus, Neisseria gonorrhoeae, Chlamydia, symptomatic human papillomavirus infection, or other mixed infections.
2. Subject received systemic and/or topical vaginal antifungal treatment, including prescription or over-the-counter products, within 7 days prior to the Screening visit.

   Note: The screening visit may be rescheduled if required.
3. Subject is receiving or anticipates requiring treatment with the prohibited medications within the specified timeframes per Appendix I.
4. Subject has active menstruation at the Screening visit. Note: The Screening visit may be rescheduled if required.
5. Subject has a history of or an active cervical/vaginal cancer.
6. Subject has a known hypersensitivity to any of the components of the formulation.
7. Subject has participated in any other investigational study within at least 30 days (or 5.5 half- lives of the investigational product) before signing the ICF.
8. Subject has received prior treatment with ibrexafungerp.
9. Subject has any other condition or laboratory abnormality (such as severe hepatic impairment) that, in the judgment of the investigator, would put the subject at unacceptable risk for participation in the study or may interfere with the assessments included in the study.
10. Subject is unlikely to comply with protocol requirements.

Primary outcomes:
measure: Clinical Cure
timeFrame: 14 days post-Baseline - Test-Of-Cure (TOC)
Secondary outcomes:
measure: Clinical Improvement
timeFrame: 14 days post-Baseline Test-Of- Cure (TOC), 14 days post-End of Treatment (EOT), 30 days post-Baseline, 30 days post-End of Treatment and 60 days post-End of Treatment
measure: Clinical Success
timeFrame: 14 days post-Baseline Test-Of- Cure (TOC), 14 days post-End of Treatment (EOT), 30 days post-Baseline, 30 days post-End of Treatment and 60 days post-End of Treatment.
measure: Mycological Response
timeFrame: 14 days post-Baseline Test-Of- Cure (TOC), 14 days post-End of Treatment (EOT), 30 days post-Baseline, 30 days post-End of Treatment and 60 days post-End of Treatment.
measure: Clinical Cure and Mycological Response
timeFrame: 14 days post-Baseline Test-Of- Cure (TOC), 14 days post-End of Treatment (EOT), 30 days post-Baseline, 30 days post-End of Treatment and 60 days post-End of Treatment
measure: Clinical Cure at Follow-up
timeFrame: 14 days post EOT, 30 days post-Baseline, 30 days post-EOT and 60 days post-EOT
measure: Change in Total Composite Vulvovaginal Signs and Symptom Score From Baseline
timeFrame: From Baseline to 14 days post-Baseline (TOC), 14 days post-End of Treatment (EOT), 30 days post-Baseline, 30 days post-EOT and 60 days post-EOT
measure: Clinical Improvement - 2
timeFrame: 14 days post-Baseline Test-Of- Cure (TOC), 14 days post-End of Treatment, 30 days post-Baseline, 30 days post-End of Treatment and 60 days post- End of Treatment
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Precision Trials, AZ
state: Arizona
city: San Diego
country: United States
facility: Women's Healthcare Research
state: California
city: San Diego
country: United States
facility: Wake Research (MCCR)
state: California
city: Miami
country: United States
facility: New Age Medical Research
state: Florida
city: Atlanta
country: United States
facility: Wake (Mount Vernon Clinical Research)
state: Georgia
city: Idaho Falls
country: United States
facility: Clinical Research Prime
state: Idaho
city: Idaho Falls
country: United States
facility: Leavitt Women's Healthcare
state: Idaho
city: New Orleans
country: United States
facility: Women Under Study
state: Louisiana
city: Boston
country: United States
facility: Massachusetts's General
state: Massachusetts
city: Detroit
country: United States
facility: Wayne State University
state: Michigan
city: Saint Louis
country: United States
facility: Consultants in Women's Healthcare
state: Missouri
city: Las Vegas
country: United States
facility: Wake Research (CRCN)
state: Nevada
city: Lawrenceville
country: United States
facility: Capital Health Lawrence OBGYN
state: New Jersey
city: Lake Success
country: United States
facility: Center for Colposcopy
state: New York
city: Fayetteville
country: United States
facility: Wake Research (Carolina Institute for Clinical Research)
state: North Carolina
city: Raleigh
country: United States
facility: UWCR - Raleigh
state: North Carolina
city: Winston-Salem
country: United States
facility: Lyndhurst Clinical Research
state: North Carolina
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health and Science University
state: Oregon
city: Philadelphia
country: United States
facility: Jefferson University
state: Pennsylvania
city: Memphis
country: United States
facility: Medical Research Center
state: Tennessee
city: Dallas
country: United States
facility: Discovery Clinical Trials
state: Texas
city: Houston
country: United States
facility: TMC Life Research, Inc
state: Texas
city: McAllen
country: United States
facility: Discovery Clinical Trials
state: Texas
city: Seattle
country: United States
facility: Seattle Clinical Research Center
state: Washington
Study officials:
affiliation: Scynexis, Inc.
name: Lori Tierney
role: STUDY_DIRECTOR
References: