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.

Study Overview

• Status: Completed
• Conditions: Vulvovaginal Candidiasis
• Intervention / Treatment: Drug: Ibrexafungerp

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.

• Study Type: Interventional
• Enrollment (Actual): 150
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Precision Trials, AZ
  • California
    • San Diego, California, United States, 92111
      • Women's Healthcare Research
    • San Diego, California, United States, 92120
      • Wake Research (MCCR)
  • Florida
    • Miami, Florida, United States, 33186
      • New Age Medical Research
  • Georgia
    • Atlanta, Georgia, United States, 30328
      • Wake (Mount Vernon Clinical Research)
  • Idaho
    • Idaho Falls, Idaho, United States, 83404
      • Clinical Research Prime
    • Idaho Falls, Idaho, United States, 83404
      • Leavitt Women's Healthcare
  • Louisiana
    • New Orleans, Louisiana, United States, 70125
      • Women Under Study
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts's General
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Wayne State University
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Consultants in Women's Healthcare
  • Nevada
    • Las Vegas, Nevada, United States, 89123
      • Wake Research (CRCN)
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Capital Health Lawrence OBGYN
  • New York
    • Lake Success, New York, United States, 11042
      • Center for Colposcopy
  • North Carolina
    • Fayetteville, North Carolina, United States, 28303
      • Wake Research (Carolina Institute for Clinical Research)
    • Raleigh, North Carolina, United States, 27607
      • UWCR - Raleigh
    • Winston-Salem, North Carolina, United States, 27103
      • Lyndhurst Clinical Research
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson University
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Medical Research Center
  • Texas
    • Dallas, Texas, United States, 75230
      • Discovery Clinical Trials
    • Houston, Texas, United States, 77054
      • TMC Life Research, Inc
    • McAllen, Texas, United States, 78503
      • Discovery Clinical Trials
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Clinical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; Subjects without underlying medical conditions and have isolates other than C glabrata, C krusei, C auris. Single day dosing, 300mg Ibrexafungerp BID for a total of 600mg a day.	Drug: Ibrexafungerp; Each day dosing will consist of two 150mg tablets taken BID.
Experimental: Group B (3 Day dosing); Subjects with underlying medical conditions: DM, immunocompromised conditions (e.g. HIV), debilitation, immunosuppressive therapy (e.g. corticosteroids), recurrent VVC (≥3 episodes/year) and/or known to have C glabrata, C krusei or C auris isolates. Three day dosing, 300 mg Ibrexafungerp BID for a total of 600mg a day.	Drug: Ibrexafungerp; Each day dosing will consist of two 150mg tablets taken BID.
Experimental: Group B (7 Day dosing); Subjects with underlying medical conditions: DM, immunocompromised conditions (e.g. HIV), debilitation, immunosuppressive therapy (e.g. corticosteroids), recurrent VVC (≥3 episodes/year) and/or known to have C glabrata, C krusei or C auris isolates. Seven day dosing, 300mg Ibrexafungerp BID for a total of 600mg a day	Drug: Ibrexafungerp; Each day dosing will consist of two 150mg tablets taken BID.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Cure	Percentage of participants with complete resolution of signs and symptoms (total VSS score of 0) with no additional antifungal therapy required. The vulvovaginal signs and symptom (VSS) scale ranges from 0 to 18, with higher scores being worse.	14 days post-Baseline - Test-Of-Cure (TOC)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Improvement	Percentage of participants with a Total Composite Score of ≤1 on the VSS Scale and a Total Composite Score of ≤2 on the VSS scale. The vulvovaginal signs and symptom (VSS) scale ranges from 0 to 18, with higher scores being worse.	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
Clinical Success	Percentage of participants with at least 50% reduction from baseline in the total composite VSS score and no additional antifungal therapy required. The vulvovaginal signs and symptom (VSS) scale ranges from 0 to 18, with higher scores being worse.	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.
Mycological Response	Percentage of participants with negative culture growth for candida or participant was asymptomatic and a culture was not done	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.
Clinical Cure and Mycological Response	The number (percentage) of participants with Clinical Cure and Mycological Response at TOC and FU Visits	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
Clinical Cure at Follow-up	The number (percentage) of participants with a total composite score of 0 on the VSS scale and no additional antifungal therapy required. The vulvovaginal signs and symptom (VSS) scale ranges from 0 to 18, with higher scores being worse.	14 days post EOT, 30 days post-Baseline, 30 days post-EOT and 60 days post-EOT
Change in Total Composite Vulvovaginal Signs and Symptom Score From Baseline	The mean change in total composite vulvovaginal signs and symptom (VSS) score from Baseline to TOC and Follow-up Visits. The VSS score ranges from 0 (no signs and symptoms) to a maximum of 18, with higher scores being worse.	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
Clinical Improvement - 2	Percentage of subjects with a Total Composite Score of 2 on the VSS Scale or a composite score of 1 on the VSS scale. The vulvovaginal signs and symptom (VSS) scale ranges from 0 to 18, with higher scores being worse.	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

Collaborators and Investigators

• Sponsor: Scynexis, Inc.
• Investigators: Study Director: Lori Tierney, Scynexis, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2022
• Primary Completion (Actual): May 16, 2023
• Study Completion (Actual): August 2, 2023

Study Registration Dates

• First Submitted: May 23, 2022
• First Submitted That Met QC Criteria: May 26, 2022
• First Posted (Actual): June 1, 2022

Study Record Updates

• Last Update Posted (Actual): July 10, 2024
• Last Update Submitted That Met QC Criteria: July 9, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: candida; vulvovaginal candidiasis; Ibrexafungerp; yeast vaginitis; VVC; rVVC
• Additional Relevant MeSH Terms: Infections; Bacterial Infections and Mycoses; Mycoses; Vaginal Diseases; Vulvar Diseases; Vaginitis; Vulvitis; Vulvovaginitis; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Genital Diseases, Female; Candidiasis; Candidiasis, Vulvovaginal; Anti-Infective Agents; Antifungal Agents; Ibrexafungerp
• Other Study ID Numbers: SCY-078-307b

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No