Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis

Phase 3

Completed

• Conditions: Vulvovaginal Candidiasis
• Interventions: Drug: Ibrexafungerp

• Registration Number: NCT05399641
• Lead Sponsor: Scynexis, Inc.

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.

Study Timeline

• Study Start: 2022-05-01
• Study First Submitted: 2022-05-23
• Study First Submitted QC: 2022-05-26
• Study First Posted: 2022-06-01
• Primary Completion: 2023-05-16
• Study Completion: 2023-08-02
• Results First Submitted: 2024-06-05
• Status Verified: 2024-07
• Results First Submitted QC: 2024-07-09
• Last Update Submitted: 2024-07-09
• Results First Posted: 2024-07-10
• Last Update Posted: 2024-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 150

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group A	Ibrexafungerp	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.
Group B (3 Day dosing)	Ibrexafungerp	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.
Group B (7 Day dosing)	Ibrexafungerp	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

Primary Outcome Measures

Name	Time	Method
Clinical Cure	14 days post-Baseline - Test-Of-Cure (TOC)	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.

Secondary Outcome Measures

Name	Time	Method
Change in Total Composite Vulvovaginal Signs and Symptom Score From Baseline	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	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.
Clinical Improvement	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	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.
Clinical Success	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.	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.
Mycological Response	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.	Percentage of participants with negative culture growth for candida or participant was asymptomatic and a culture was not done
Clinical Cure at Follow-up	14 days post EOT, 30 days post-Baseline, 30 days post-EOT and 60 days post-EOT	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.
Clinical Improvement - 2	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	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.
Clinical Cure and Mycological Response	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	The number (percentage) of participants with Clinical Cure and Mycological Response at TOC and FU Visits

Trial Locations

Locations (24)

Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States

Wake (Mount Vernon Clinical Research); 🇺🇸 Atlanta, Georgia, United States

Women's Healthcare Research; 🇺🇸 San Diego, California, United States

Wake Research (CRCN); 🇺🇸 Las Vegas, Nevada, United States

New Age Medical Research; 🇺🇸 Miami, Florida, United States

Massachusetts's General; 🇺🇸 Boston, Massachusetts, United States

Wake Research (Carolina Institute for Clinical Research); 🇺🇸 Fayetteville, North Carolina, United States

Lyndhurst Clinical Research; 🇺🇸 Winston-Salem, North Carolina, United States

Clinical Research Prime; 🇺🇸 Idaho Falls, Idaho, United States

Leavitt Women's Healthcare; 🇺🇸 Idaho Falls, Idaho, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Center for Colposcopy; 🇺🇸 Lake Success, New York, United States

Discovery Clinical Trials; 🇺🇸 McAllen, Texas, United States

Consultants in Women's Healthcare; 🇺🇸 Saint Louis, Missouri, United States

TMC Life Research, Inc; 🇺🇸 Houston, Texas, United States

Seattle Clinical Research Center; 🇺🇸 Seattle, Washington, United States

Wake Research (MCCR); 🇺🇸 San Diego, California, United States

UWCR - Raleigh; 🇺🇸 Raleigh, North Carolina, United States

Capital Health Lawrence OBGYN; 🇺🇸 Lawrenceville, New Jersey, United States

Oregon Health and Science University; 🇺🇸 Portland, Oregon, United States

Precision Trials, AZ; 🇺🇸 Phoenix, Arizona, United States

Wayne State University; 🇺🇸 Detroit, Michigan, United States

Medical Research Center; 🇺🇸 Memphis, Tennessee, United States

Women Under Study; 🇺🇸 New Orleans, Louisiana, United States