Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis

Oral Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis (VVC) in Subjects Who Have Failed Fluconazole Therapy

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

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.

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.