Recurrent Vulvovaginal Candidiasis MedDRA version: 20.1 Level: PT Classification code 10047784 Term: Vulvovaginal candidiasis System Organ Class: 10021881 - Infections and infestations
Conditions
Sponsors
SCYNEXIS, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Subject is a postmenarchal female subject 18 years and older at Screening and is in good general health based on medical history, physical examination, vital sign measurements and safety laboratory tests performed at the Screening visit and prior to administration of the initial dose of study drug. 2. Subject has a diagnosis of symptomatic VVC that meets the following criteria at Screening: a. A total composite score of = 4 on the VSS Scale b. Positive microscopic examination with 10% KOH in a vaginal sample collected at Screening revealing yeast forms (hyphae/pseudohyphae) or budding yeasts c. Normal vaginal pH (= 4.5) d. A minimum of three episodes of VVC in the past 12 months, including the current episode, that required administration of antifungal medication. Besides the current episode, at least one of the previous episodes in the past 12 months is required to have been a physician-diagnosed episode of VVC, with at least one positive test confirming vaginal yeast infection (e.g., KOH, culture or fungal polymerase chain reaction) 3. Subject meets the following criteria at Baseline (Day 1): a. Significant resolution of signs and symptoms of Candida infection (total composite score = 2 on the VSS Scale) b. Culture positive for Candida spp. in a vaginal sample collected at Screening c. Normal vaginal pH (= 4.5) 4. Subject is able to take oral tablets and capsules. 5. Subject is not pregnant or lactating and is highly unlikely to become pregnant since she meets at least one of the following criteria: a. Subject is a female subject who is not of reproductive potential and is eligible without requiring the use of contraception. A female subject who is not of reproductive potential is defined as one who: (1) has reached natural menopause (defined as 6 months of spontaneous amenorrhea with serum follicle-stimulating hormone levels in the postmenopausal range as determined by the local laboratory, or 12 months of spontaneous amenorrhea); (2) has undergone bilateral oophorectomy and/or hysterectomy or (3) is 3 months post bilateral tubal ligation. Spontaneous amenorrhea does not include cases for which there is an underlying disease that causes amenorrhea (e.g. anorexia nervosa). b. Subject is a female subject who is of reproductive potential and is using an effective contraceptive method including intrauterine device, systemic hormonal contraceptives (i.e., implant, oral, injectable or patch) for at least 30 days before Baseline and agrees to continue using the contraceptive method through at least 10 days after the completion of study therapy. Subjects who are taking hormonal contraceptives must use a non-hormonal barrier method of contraception until 10 days after the last dose of study drug. Vasectomy in the male partner is also an acceptable contraceptive method as long as performed at least 3 months prior to Baseline. c. Subject is a female subject who is of reproductive potential and agrees to remain abstinent or use (or have her partner use) an acceptable barrier contraceptive method from the time of consent through 10 days after the completion of study therapy. Acceptable barrier methods of contraception for this study are: male condom, female condom and diaphragm. Note: Subjects must refrain from using any topical vaginal contraceptives such as spermicides or intra-vaginal hormonal contraceptive devices such as vaginal rings as these may interfere with the efficacy evaluations. Note: Women of childbearing potenti
Exclusion criteria
Exclusion criteria: 1. Subject has any vaginal condition other than RVVC that may interfere with the diagnosis or evaluation of response to therapy, such as suspected or confirmed 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 28 days prior to the Day -14 visit. 3. Subject is receiving or anticipates to require treatment with the prohibited medications (including prescription and over-the-counter medications, supplements, and herbal products) listed in Section 21.0 (Appendix A of the protocol), during the following timeframes: a. Systemic and topical vaginal antifungal treatment other than study drug and rescue medication (if needed), as specified in the protocol, anytime during the study. b. Select CYP3A4/5 inducers during the 14 days prior to enrollment and during study treatment. c. Select strong CYP3A4/5 inhibitors during 48 hours prior to enrollment and during study treatment. d. Select P-gp substrates during the 48 hours prior to enrollment or during study treatment with ibrexafungerp. e. Topical vaginal corticosteroids from 7 days prior to the Screening visit to the Week 24 (TOC) visit. 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 fluconazole or any of the components of the fluconazole or ibrexafungerp formulations. 7. Subject has a known human immunodeficiency virus infection and/or is receiving chemotherapy, has recently received immunosuppressive or systemic corticosteroid therapies, or has an illness that, in the judgment of the investigator, is serious enough to induce an immune deficiency. 8. Subject has had any major illness within 30 days before Screening. 9. Subject has participated in any other investigational study within at least 30 days (or 5.5 half-lives of the investigational product, whichever is longer) before signing the ICF. 10. Subject has received prior treatment with the study drug in a previous trial. 11. Subject has any other condition or laboratory abnormality evidencing a major organ system disease 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy of oral ibrexafungerp versus placebo in preventing recurrences of Vulvovaginal Candidiasis (VVC) in subjects with recurrent VVC (RVVC) based on clinical success;Secondary Objective: • To evaluate the efficacy of oral ibrexafungerp versus placebo in preventing recurrences of VVC in subjects with RVVC based on Mycologically Proven Recurrences at test of cure (TOC) • To evaluate the efficacy of oral ibrexafungerp versus placebo in preventing recurrences (Mycologically Proven, Presumed or Suspected) of VVC in subjects with RVVC. • To evaluate the efficacy of oral ibrexafungerp versus placebo in preventing recurrences of VVC in subjects with RVVC based on the number of Recurrences (Mycologically Proven, Presumed or Suspected) of VVC. • To evaluate the efficacy of oral ibrexafungerp versus placebo in subjects with RVVC based on Quality-of-Life (QOL) outcomes. • To evaluate the safety and tolerability of oral ibrexafungerp in subjects with RVVC. ;Primary end point(s): Efficacy as measured by the percentage of subjects with documented Clinical Success (defined as subjects having a TOC evaluation and no Mycologically Proven, Presumed or Suspected Recurrence of VVC) up to TOC (Week 24).;Timepoint(s) of evaluation of this end point: Test-of-cure (TOC) visit | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Efficacy as measured by the percentage of subjects with no Mycologically Proven Recurrence (defined as an episode of VVC with a total composite score = 3 on the VSS Scale and a culture positive for Candida spp. that required antifungal treatment) at TOC (Week 24). Efficacy as measured by: • The percentage of subjects with no Mycologically Proven Recurrence at Week 4, Week 8, Week 12 and Week 36 (end of follow-up [EOFU]). • The time to the first Recurrence (Mycologically Proven, Presumed or Suspected) of VVC through EOFU. • The percentage of subjects with Mycological Eradication (negative fungal culture) at Week 12, Week 24 (TOC) and Week 36 (EOFU). • The percentage of subjects with no Mycologically Proven, Presumed or Suspected Recurrences at Week 4, Week 8, Week 12 and Week 36 (EOFU). • The percentage of subjects with no Mycologically Proven or Presumed Recurrences at Week 4, Week 8, Week 12, TOC (Week 24) and Week 36 (EOFU). • The proportion of subjects in three ordered categories related to the number of Recurrences (Mycologically Proven, Presumed or Suspected) of VVC from Baseline (Day 1) to TOC (Week 24) and Week 36 (EOFU). The three categories of recurrence are defined as (i) 0 to 1 episodes, (ii) 2 to 3 episodes, and (iii) = 4 episodes. • The absolute number of Mycologically Proven, Presumed or Suspected Recurrences from Baseline (Day 1) to TOC (Week 24) and Week 36 (EOFU). • Absolute improvement in QOL outcomes at Week 12, Week 24 (TOC) and Week 36 (EOFU) as measured by EQ-5D, SF-36 and FSDS). Safety and tolerability as measured by: • AEs, vital signs, treatment discontinuation and safety laboratory tests at TOC (Week 24).;Timepoint(s) of evaluation of this end point: Test-of-cure (TOC) visit and Follow-up (FU) visit | — |
Countries
Bulgaria, Poland, Russian Federation, United States
Contacts
Public ContactVANISH Study Team
SCYNEXIS, Inc.
Outcome results
None listed