E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Acute Vulvovaginal Candidiasis |
|
E.1.1.1 | Medical condition in easily understood language |
|
E.1.1.2 | Therapeutic area | Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10047784 |
E.1.2 | Term | Vulvovaginal candidiasis |
E.1.2 | System Organ Class | 10021881 - Infections and infestations |
|
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the efficacy of oral ibrexafungerp versus placebo in subjects with acute vulvovaginal candidiasis (AVVC) by comparing the clinical outcomes of ibrexafungerp and placebo |
|
E.2.2 | Secondary objectives of the trial |
• To evaluate the efficacy of oral ibrexafungerp versus placebo in subjects with AVVC based on mycological and clinical outcomes
• To evaluate the safety and tolerability of oral ibrexafungerp versus placebo in subjects with AVVC |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Subject is a postmenarchal female subject 12 years and older 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/or prior to administration of the initial dose of study drug.
2. Subject has a diagnosis of symptomatic AVVC that meets the following criteria:
a. Minimum composite vulvovaginal signs and symptoms score of ≥4 with at least 2 signs or symptoms having a score of 2 (moderate) or greater in the VSS Scale at Baseline
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)
3. Subject is able to take oral tablet
4. 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, hormonal contraceptives (i.e., vaginal ring, 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. 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 methods 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.
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).
5. Subject is able to understand and sign a written informed consent form (ICF), which must be obtained prior to treatment and any study-related procedures. For subjects under the legal age of consent, the subject’s parent or legal representative must also be willing to sign the subject’s ICF.
Local regulations should be followed for consenting subjects under the age of consent.
6. Subject and/or parent /legal representative 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).
7. Subject and/or parent/legal representative is able to understand and follow all study-related procedures including study drug administration. |
|
E.4 | Principal exclusion criteria |
1. Subject has any vaginal condition other than AVVC 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 vaginalis, Herpesvirus, Neisseria gonorrhoeae, Chlamydia trachomatis, symptomatic human papillomavirus or other mixed infections.
2. Subject received systemic and/or topical (vaginal) antifung al treatment, including prescription or over-the-counter products, within 28 days of the Baseline visit.
3. Subject has active menstruation at the Baseline visit.
4. Subject has uncontrolled diabetes mellitus.
5. Subject has a history of or an active cervical/vaginal cancer.
6.Subject requires 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/or topical (vaginal) antifungal treatment, including prescription or over -the -counter products, within 28 days prior to enrollment if administered for the treatment of VVC and during the study for all cases
b. Select strong CYP3A4/5 inhibitors and CYP3A4/5 inducers during the 7 days prior to enrollment and during study treatment until the TOC visit
c. Select P-gp substrates during the 48 hours prior to enrollment or during study treatment with SCY-078
7. Subject has a known hypersensitivity to any of the components of the formulation.
8. Subject has a known human immunodeficiency virus infection and/or is receiving chemotherapy or has an illness that, in the judgment of the investigator, is serious enough to induce an immune deficiency.
9. Subject has had any major illness within 30 days before Screening.
10. 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.
11. Subject has received prior treatment with ibrexafungerp in a previous trial.
12. Subject has any other condition or laboratory abnormality 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.
13. Subject is an employee of SCYNEXIS, Inc., the investigator or the contract research organization (CRO) involved in the study, or is an immediate family member (partner, offspring, parent, sibling, or sibling’s offspring) of an employee involved in the study.
14. Subject is unlikely to comply with protocol requirements.
|
|
E.5 End points |
E.5.1 | Primary end point(s) |
Efficacy as measured by the percentage of subjects with clinical cure (complete resolution of signs and symptoms) at the test-of-cure (TOC) visit |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Secondary Endpoints:
Efficacy as measured by:
• The percentage of subjects with mycological eradication (negative culture for growth of Candida species) at the TOC visit
• The percentage of subjects with clinical cure and mycological eradication (responder outcome) at the TOC visit.
• The percentage of subjects with complete resolution of symptoms at the Follow-up (FU) visit.
• The percentage of subjects with clinical improvement (partial or complete resolution of signs and symptoms with total composite score no greater than 1) at the TOC visit.
• The absolute change in signs and symptoms score from Baseline to TOC and FU visits.
Safety and tolerability as measured by:
• Adverse events (AEs), vital signs, physical examination, treatment discontinuation and safety laboratory tests
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
Test-of-cure (TOC) visit and Follow-up (FU) visit |
|
E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 16 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Bulgaria |
Poland |
Russian Federation |
United States |
|
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 0 |
E.8.9.1 | In the Member State concerned months | 9 |
E.8.9.1 | In the Member State concerned days | 0 |
E.8.9.2 | In all countries concerned by the trial years | 0 |
E.8.9.2 | In all countries concerned by the trial months | 9 |
E.8.9.2 | In all countries concerned by the trial days | 0 |