Clinical trial NCT05399641
Conditions: Vulvovaginal Candidiasis
Keywords: vulvovaginal candidiasis candida VVC rVVC Ibrexafungerp yeast vaginitis
Sponsor: Scynexis, Inc.
Start date: 2022-05-01; Completion date: 2023-08-02
Enrollment: 150 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

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.

Arms: arm 1: 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. arm 2: 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. arm 3: 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
Interventions: intervention 1: Ibrexafungerp
Intervention descriptions: intervention 1: Each day dosing will consist of two 150mg tablets taken BID.

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
SCYNEXIS, Inc. 
Clinical Trial Protocol 
Oral Ibrexafungerp for the Treatment of Complicated Vulvovaginal 
Candidiasis (VVC) in Subjects who have failed Fluconazole Therapy 
Protocol Number SCY-078-307b 
NCT05399641 
SCYNEXIS, Inc. 
1 Evertrust Plaza, 13th Floor 
 Jersey City, NJ 07302 
Original Protocol Issue Date: 03 September 2021 (Version 1.0) 
Amendment 1: 12 October 2021 (Version 2.0) 
Amendment 2: 17 January 2022 (Version 3.0)  
STATEMENT OF CONFIDENTIALITY 
The information in this document contains trade secrets and commercial information that are 
privileged or confidential and may not be disclosed unless such disclosure is required by 
federal or state law or regulations. In any event, persons to whom the information is disclosed 
must be informed that the information is privileged or confidential and may not be further 
disclosed by them. These restrictions on disclosure will apply equally to all future 
information supplied to you which is indicated as privileged or confidential. 


SCYNEXIS, Inc. 
 
US IND Number 107,521 
Clinical Protocol Number SCY-078-307b 
 
Version 3.0 
 
 
17 January 2022 
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1. 
CONTACT INFORMATION 
 
 
 
 
 
Sponsor 
SCYNEXIS, Inc. 
1 Evertrust Plaza, 13th Floor 
Jersey City, NJ 07302 
 
 
 
 
 


SCYNEXIS, Inc. 
 
US IND Number 107,521 
Clinical Protocol Number SCY-078-307b 
 
Version 3.0 
 
 
17 January 2022 
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2. 
PROTOCOL APPROVALS 
PROTOCOL ID: SCY-078-307b 
Oral Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis (VVC) in 
Subjects who have failed Fluconazole Therapy  
SCYNEXIS, Inc. Approval: 
 
 
 
 
 
Date 
 
 


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Clinical Protocol Number SCY-078-307b 
 
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3. 
INVESTIGATOR AGREEMENT STATEMENT 
PROTOCOL ID: SCY-078-307b 
Oral Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis (VVC) in 
Subjects who have failed Fluconazole Therapy   
I understand that all documentation provided to me by SCYNEXIS, Inc. or its designated 
representative(s) concerning this study that has not been published previously will be kept in the 
strictest confidence. This documentation includes the study protocol, Investigator’s Brochure, 
electronic case report forms, and other scientific data. This study will not commence without the 
prior written approval of a properly constituted Institutional Review Board or Ethics Committee. 
No changes will be made to the study protocol without the prior written approval of SCYNEXIS, 
Inc. and the Institutional Review Board/Ethics Committee (IRB/EC), except where necessary to 
eliminate an immediate hazard to the subject. All subjects will provide a written informed consent 
prior to participation. 
I have read the protocol, including all appendices, and I agree that it contains all necessary details 
for me and my staff to conduct this study as described. I have read, understood, and agree to abide 
by all the conditions and instructions contained in this protocol, and in compliance with 
International Conference on Harmonization (ICH) guidelines, Good Clinical Practices (GCP), 
Safety Reporting obligations and any applicable local requirements. 
Principal Investigator’s Signature 
 
Date 
 
 
 
Principal Investigator’s Name  
 
 


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TABLE OF CONTENTS 
1. 
CONTACT INFORMATION ......................................................................................2 
2. 
PROTOCOL APPROVALS .........................................................................................3 
3. 
INVESTIGATOR AGREEMENT STATEMENT .......................................................4 
TABLE OF CONTENTS .................................................................................................................5 
LIST OF TABLES ...........................................................................................................................9 
LIST OF FIGURES .........................................................................................................................9 
4. 
ABBREVIATIONS ....................................................................................................10 
5. 
PROTOCOL SYNOPSIS............................................................................................12 
6. 
SCHEMATIC OF STUDY DESIGN .........................................................................19 
7. 
BACKGROUND INFORMATION AND SCIENTIFIC RATIONALE ...................20 
7.1. 
Background Information .............................................................................................20 
7.1.1. 
Vulvovaginal Candidiasis ...........................................................................................20 
7.1.2. 
The glucan synthesis inhibitor ibrexafungerp (formerly known as SCY-078) ...........20 
7.1.3. 
Antifungal activity ......................................................................................................21 
7.1.4. 
Clinical experience .....................................................................................................22 
7.2. 
Rationale for the Study ...............................................................................................24 
7.2.1. 
Rationale for Study Indication and Population ...........................................................24 
7.2.2. 
Rationale for Selected Dose Levels and Dosing Regimens ........................................24 
7.2.3. 
Rationale for Study Endpoints ....................................................................................24 
7.2.4. 
Rationale for Study Design .........................................................................................24 
8. 
STUDY OBJECTIVES ..............................................................................................24 
8.1. 
Primary Objectives .....................................................................................................24 
8.2. 
Secondary Objectives..................................................................................................24 
8.3. 
Exploratory Objective .................................................................................................25 
9. 
STUDY ENDPOINTS ................................................................................................25 
9.1. 
Primary Endpoints ......................................................................................................25 
9.2. 
Secondary Endpoints ..................................................................................................25 
10. 
STUDY DESIGN .......................................................................................................26 
10.1. 
Overall Description of the Study ................................................................................26 
10.1.1. 
Study Visits .................................................................................................................26 


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10.1.2. 
Study Assessments ......................................................................................................27 
10.2.  
Blinding, Randomization, and Stratification...............................................................28 
10.3.  
Study Duration ............................................................................................................28 
10.4.  
Number of Centers ......................................................................................................28 
11. 
STUDY POPULATION .............................................................................................28 
11.1. 
Inclusion Criteria ........................................................................................................28 
11.2. 
Exclusion Criteria .......................................................................................................29 
11.3.   
Discontinuation Criteria ..............................................................................................30 
11.4.  
Early Termination .......................................................................................................30 
11.5.  
Replacement of Dropouts ...........................................................................................31 
12. 
STUDY TREATMENTS ...........................................................................................31 
12.1. 
Study Treatment Groups .............................................................................................31 
12.2. 
Dietary Requirements .................................................................................................32 
12.3. 
Study Drugs ................................................................................................................32 
12.4. 
Ibrexafungerp Description ..........................................................................................32 
12.4.1. 
Formulation, Packaging and Labelling .......................................................................32 
12.4.2. 
Storage and Stability ...................................................................................................33 
12.5. 
Drug Accountability ....................................................................................................33 
12.6. 
Subject Compliance with Study Drug Dosing ............................................................33 
13. 
NON-STUDY TREATMENTS ..................................................................................33 
13.1. 
Prior and Concomitant Medications ...........................................................................33 
13.2. 
Prohibited Medications ...............................................................................................34 
13.2.1. 
Medications to be Administered with Caution and Monitored as Appropriate ..........34 
13.3. 
Study Restrictions .......................................................................................................34 
14. 
STUDY PROCEDURES ............................................................................................34 
14.1. 
Informed Consent........................................................................................................34 
14.2. 
Assignment of Subject Number ..................................................................................35 
14.3. 
Inclusion and Exclusion Criteria .................................................................................35 
14.4. 
Medical History and Demographics ...........................................................................35 
14.5. 
Abbreviated Physical Examination .............................................................................35 
14.6. 
Urine Pregnancy Test ..................................................................................................35 


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14.7. 
Safety Laboratory Tests ..............................................................................................35 
14.7.1. 
Hematology .................................................................................................................35 
14.7.2. 
Blood Chemistry .........................................................................................................36 
14.8. 
Rating of Vulvovaginal Symptoms by the Subject Using the VSS Scale ...................36 
14.9. 
Vulvovaginal Samples for Identification of Other Pathogens and Vaginal pH ..........36 
14.10. 
Vulvovaginal Samples for KOH and Fungal Culture .................................................37 
14.11. 
Rating of Vulvovaginal Signs by the Investigator Using the VSS Scale ....................37 
14.12. 
Quality of Life (QOL) Questionnaire .........................................................................38 
14.13. 
Randomization ............................................................................................................38 
14.14. 
Study Drug ..................................................................................................................38 
14.15. 
Study Drug Dosing .....................................................................................................38 
14.16. 
Study Drug Collection and Treatment Compliance Evaluation ..................................39 
14.17. 
Vital Signs ...................................................................................................................39 
14.18. 
Prior and Concomitant Medication Review ................................................................39 
14.19. 
Adverse Event Monitoring ..........................................................................................39 
15. 
STUDY SCHEDULE .................................................................................................40 
16. 
SAFETY ASSESSMENTS AND MONITORING.....................................................43 
16.1. 
Definition of an Adverse Event ..................................................................................43 
16.2. 
Definition of a Serious Adverse Event .......................................................................43 
16.3. 
Events of Clinical Interest ...........................................................................................44 
16.4. 
Overdose .....................................................................................................................44 
16.5. 
Pregnancy ...................................................................................................................44 
16.6. 
Unexpected Adverse Event .........................................................................................44 
16.7. 
Grading of Adverse Events .........................................................................................45 
16.7.1. 
Clarification of the difference in meaning between “severe” and “serious” ..............45 
16.8. 
Causality Assessment .................................................................................................45 
16.9. 
Adverse Event Collection Timeframe ........................................................................45 
16.10. 
Serious Adverse Event Reporting Requirements ........................................................46 
16.11. 
Adverse Event and Serious Adverse Event Follow-up ...............................................46 
16.12. 
Serious Adverse Event Reporting – Procedures for Investigators ..............................46 
17. 
DATA COLLECTION, STUDY MONITORING AND RECORD 
MANAGEMENT .......................................................................................................47 


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17.1. 
Data Collection and Reporting ....................................................................................47 
17.2. 
Study Monitoring ........................................................................................................47 
17.3. 
Investigator Study Files ..............................................................................................47 
17.4. 
Retention of Records ...................................................................................................48 
18. 
ANALYTICAL PLAN ...............................................................................................48 
18.1. 
Sample Size Determination .........................................................................................49 
18.2. 
Analysis Populations ...................................................................................................49 
18.3. 
Subject Disposition, Discontinuation, and Baseline Data ...........................................49 
18.4. 
Handling of Missing Data, Dose Adjustments, and Early Withdrawals ....................49 
18.5. 
Prior and Concomitant Medications ...........................................................................49 
18.6. 
Efficacy .......................................................................................................................50 
18.6.1. 
Efficacy Assessments..................................................................................................50 
18.6.2. 
Efficacy Analyses .......................................................................................................50 
18.7. 
Safety ..........................................................................................................................51 
18.7.1. 
Safety Assessments .....................................................................................................51 
18.7.2. 
Safety Analyses ..........................................................................................................51 
19. 
ETHICS AND PROTECTION OF HUMAN PATIENTS .........................................51 
19.1. 
Ethical Conduct of the Study ......................................................................................51 
19.2. 
Institutional Review Board/Ethics Committee Review ..............................................52 
19.3. 
Informed Consent........................................................................................................52 
19.4. 
Future Use of Samples ................................................................................................52 
19.5. 
Subject Privacy and Subject Confidentiality...............................................................52 
19.6. 
Study Termination ......................................................................................................52 
19.7. 
Financial Disclosure ....................................................................................................53 
20. 
REFERENCES ...........................................................................................................54 
21. 
APPENDICES ............................................................................................................55 
APPENDIX 1. PROHIBITED MEDICATIONS AND MEDICATIONS TO BE 
ADMINISTERED WITH CAUTION ........................................................................55 
APPENDIX 2. VULVOVAGINAL SIGNS AND SYMPTOMS SCALE .................................57 
APPENDIX 3. SERIOUS ADVERSE EVENT REPORTING ..................................................58 
APPENDIX 4. PROTOCOL REVISION HISTORY .................................................................59 
 


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LIST OF TABLES 
Table 1: 
Schedule of Visits and Procedures (Study SCY-078-307b) .......................................39 
 
 
 
LIST OF FIGURES 
Figure 1: 
Schematic of Study Design .........................................................................................19 
 


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4. 
ABBREVIATIONS 
ABBREVIATION 
DEFINITION 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
BID 
Twice daily 
CI 
Confidence interval(s) 
CPK 
Creatinine phosphokinase 
DDI 
Drug-drug interaction 
ECI 
Event of clinical interest 
EOT 
End of treatment 
eCRF 
Electronic case report form 
GCP 
Good clinical practices 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
GSI 
Glucan synthesis inhibitors 
Hct 
Hematocrit 
HgB 
Hemoglobin 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s brochure 
ICF 
Informed consent form 
ICH 
International conference on harmonization 
IRB/EC 
Institutional review board/Ethics committee 
ITT 
Intent-to-Treat 
IV 
Intravenous 
KOH 
Potassium hydroxide 
MedDRA 
Medical dictionary for regulatory activities 
MITT 
Modified Intent-to-Treat 


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ABBREVIATION 
DEFINITION 
mg 
Milligram 
mL 
Milliliter 
OATP1B1 and OATP1B3 
Transporters that are expressed on the sinusoidal membrane of hepatocytes; they 
accept a number of therapeutic reagents as their substrates. In vitro and in vivo 
studies have shown that some drugs inhibit these transporters and cause clinically 
relevant drug-drug interactions (DDIs). 
QOL 
Quality of Life 
PI 
Principal Investigator 
PP 
Per-Protocol 
RBC 
Red blood cell 
RVVC 
Recurrent Vulvovaginal Candidiasis 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
TEAE 
Treatment emergent adverse event 
WBC 
White blood cell 
VSS 
Vulvovaginal Signs and Symptoms 
VVC 
Vulvovaginal candidiasis 


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5. 
PROTOCOL SYNOPSIS 
TITLE: Oral Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis (VVC) in 
Subjects who have failed Fluconazole Therapy  
STUDY OBJECTIVES: 
Primary Objective: 
• 
To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on clinical cure. 
Secondary Objectives: 
• 
To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on mycological and clinical outcomes. 
• 
To evaluate the safety and tolerability of oral ibrexafungerp in subjects with complicated VVC who 
failed fluconazole therapy. 
Exploratory Objective 
• To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on Quality of Life (QOL) outcomes. 
STUDY ENDPOINTS: 
Primary Endpoint: 
• 
Efficacy as measured by the percentage of subjects with clinical cure (total composite score of 0 on 
the Vulvovaginal Signs and Symptoms [VSS] Scale with no additional antifungal therapy required 
based on investigator’s judgment) at the Test-of-Cure (TOC) visit 
Secondary Endpoints: 
Efficacy as measured by: 
• 
The percentage of subjects with clinical improvement  
− 
Total composite score of 2 on the VSS Scale at the TOC and Follow-up (FU) visits. 
− 
Total composite score of 1 on the VSS Scale at the TOC and FU visits. 
• 
The percentage of subjects with clinical success (at least 50% reduction from baseline in the total 
composite VSS score) at the TOC and FU visits. 
• 
The percentage of subjects with mycological response (defined as a negative culture for growth of 
Candida spp. or subject is asymptomatic therefore culture not done) at the TOC and FU visits. 
• 
The percentage of subjects with both clinical cure and mycological response at the TOC and FU 
visits. 
• 
The percentage of subjects with clinical cure at the FU visits. 
• 
The absolute change in total composite VSS score from baseline to the TOC and FU visits. 
 
 


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Exploratory Endpoints: 
• 
Absolute improvement in QOL outcomes at TOC and FU visits compared to baseline as measured 
by QOL survey. 
• 
Subjects whose signs and symptoms have resolved enough that additional antifungal treatment was 
not required based on clinical judgement. 
• 
Time to resolution of symptoms. 
Safety and tolerability as measured by: 
Adverse events (AEs), vital signs, treatment discontinuation, and safety laboratory tests. 
 
STUDY PHASE:  3b 
STUDY DESIGN: 
This study is a Phase 3b, open-label, multicenter study to evaluate the efficacy and safety of oral 
ibrexafungerp in the treatment of subjects with complicated VVC episodes in subjects: 
• 
not responsive to, or  
• 
have isolates anticipated not to respond to, or  
• 
who are refractory to or intolerant of fluconazole.  
The susceptibility of historical isolates will be collected if available. 
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.  
STUDY VISITS: 
The study will consist of a Screening visit on Day -2 (±1), Baseline visit on Day 1 (if applicable, the 
Screening and Baseline visits can both be done on Day 1), Phone contacts on Days 3, 5 and 7 (±1), a 
TOC visit 14 (±3) days after Baseline, FU visits at: 14 days (±3) days after End Of Treatment (EOT), 30 
(±4) after Baseline, 30 (±4) days after EOT and 60 (±4) days after EOT. 
Screening (Day -2 (±1)):  At Screening, subjects who are experiencing vulvovaginal symptoms will be 
evaluated by the investigator, who will obtain a vaginal sample for potassium hydroxide (KOH) testing 
and vaginal pH determination by the local laboratory. The vaginal samples will also be evaluated locally 
for findings indicative of bacterial vaginosis and Trichomonas vaginalis (WET Mount and/or DNA 
Probe). A vaginal sample for fungal culture and for species identification and susceptibility testing will 
be obtained and sent to a designated central laboratory. If the investigator suspects Herpes virus, 
Neisseria gonorrhoeae, or Chlamydia trachomatis infection, a vaginal sample will be collected and sent 
to the local laboratory. The investigators and the subjects will rate the signs and symptoms of infection, 
respectively, on the VSS Scale (see Appendix 2). Safety procedures, including an abbreviated physical 
exam, vaginal exam, vital signs, laboratory tests, and a pregnancy test will also be performed. 
The Screening and Baseline (Day 1) visits may occur on the same day. 
Baseline visit (Day 1):  Subjects who meet all criteria for this study will complete a QOL questionnaire.  
They will receive the first dose of study drug, oral ibrexafungerp 300 mg, at the study site and will self-
administer subsequent doses as applicable, at home. For some subjects, 300mg BID dosing will be 


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repeated daily for a total of 3 consecutive days (Days 1-3) or for 7 consecutive days (Days 1-7) based on 
Candida species and presence or absence of underlying medical conditions. 
Phone Contact (Days 3, 5 and 7 [±1]): During this phone contact, AEs, resolution of symptoms, and 
concomitant medications (including antifungals) will be assessed. 
TOC visit (14 days [±3] after Baseline): At this visit, treatment compliance will be reviewed and any 
AEs and/or concomitant medications evaluated. The investigators and the subjects will again rate the 
signs and symptoms of infection on the VSS Scale and the subjects will complete a QOL questionnaire 
Vulvovaginal samples for fungal culture, species identification, and antifungal susceptibility testing will 
be obtained and sent to a designated central laboratory. Additional vaginal samples will be obtained for 
a KOH testing and vaginal pH by the local laboratory if symptoms persist or have worsened. 
FU visit (14 days [±3] after EOT): At this visit, treatment compliance will be reviewed and any AEs 
and/or concomitant medications evaluated. The investigators and the subjects will again rate the signs 
and symptoms of infection on the VSS Scale and the subjects will complete a QOL questionnaire 
Vulvovaginal samples for fungal culture, species identification, and antifungal susceptibility testing will 
be obtained and sent to a designated central laboratory. Additional vaginal samples will be obtained for 
a KOH test and vaginal pH measurement by the local laboratory if symptoms persist or have worsened. 
FU visits 30 (±4) days after Baseline, 30 (±4) days after EOT and 60 (±4) days after EOT: At the 
FU visits, subjects will rate their symptoms of infection on the VSS Scale and will complete a QOL 
questionnaire. Only if VSS symptoms are present will the investigator perform a vulvovaginal 
examination to rate the subject’s signs of infection, and collect samples for pH determination, KOH 
testing, and fungal culture. 
A second treatment cycle (Cycle 2) will be allowed for subjects who did not achieve sufficient clinical 
improvement (e.g. VSS remains ≥3) on the randomized treatment (Cycle 1) as evaluated at the TOC visit 
or at the FU EOT+14 visits.  The same visit schedule will be followed, starting with the Baseline visit. 
TARGET POPULATION: The study population will include female subjects who are ≥18 years of age 
with complicated VVC who have failed fluconazole therapy. 
KEY INCLUSION CRITERIA: 
Subjects must fulfill all the following KEY criteria at Screening (Day -2 (±1)) to be eligible for study 
admission: 
1) Subject is a post menarchal female ≥18 years of age at the time of signing the informed consent 
form (ICF).  
2) Subject has a diagnosis of symptomatic VVC that meets the following criteria at the Screening 
visit: 
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 on the VVS 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). 
d) Has no other vaginal co-infections based on WET Mount microscopic examination and/or 
DNA probe. 
3) Subject should also have:  


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a) A VVC episode with persistence of 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 
b) A recurrent vulvovaginal candidiasis (RVVC) episode with breakthrough symptoms while 
receiving maintenance antifungal therapy.  
OR 
c) 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  
d) A VVC episode caused by a candida species with documented resistance to fluconazole based 
on MIC determination. 
OR 
e) A known history of azole allergy or intolerance.  
4) Subject is able to take oral tablets. 
KEY EXCLUSION CRITERIA: 
A subject will be excluded from participation in the study if she meets any of the following KEY 
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. 
STUDY DRUGS: 
The study drug will be provided by SCYNEXIS Inc. as oral ibrexafungerp 150-mg tablets. 
 
 


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Treatment Cycle 1:  ALL randomized subjects: 
All subjects will receive open-label, oral ibrexafungerp 300mg BID (total daily dose of 600mg), for 
either one, three or seven consecutive days per the table below.  
 
Ibrexafungerp Treatment Groups: 
Treatment 
Group 
Criteria 
*Ibrexafungerp Dose (300mg AM 
and 300mg PM) 
Randomization and Stratification  
Group A 
Subjects without underlying medical 
conditions AND known to have isolates 
other than C glabrata, C krusei, C auris  
1 Day dosing 
N=50 
Group B 
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 
3 Day OR 7 Days dosing  
Randomized 1:1  
N=50:50 
    *Days of treatment is per CDC Guidelines (https://www.cdc.gov/std/treatment-
guidelines/candidiasis.htm) 
Enrollment will continue until the target number in each cohort is reached.    
Treatment Cycle 2: A second treatment cycle will be allowed for subjects who did not achieve sufficient 
clinical improvement (e.g. VSS remains ≥3) on the randomized treatment (Cycle 1) as evaluated at the 
TOC visit or at the FU EOT+14 visits  A second treatment cycle will also be allowed for subjects with 
clinical cure/improvement/success who experience a recurrence before the last FU visit.  During Cycle 
2, subjects may receive additional treatment with ibrexafungerp for a period up to 14 days as 
recommended by the investigator and following discussion with the sponsor. 
It is recommended that study drug be administered with or immediately after a meal or snack. 
STUDY BLINDING, RANDOMIZATION, AND STRATIFICATION:  This is an open-label study. 
Subjects will be randomized to treatment, stratified by group based on the Candida species and presence 
or absence of underlying medical conditions.  
STUDY EVALUATIONS 
Efficacy Evaluations 
Clinical Evaluation: The signs (edema, erythema, and excoriation or fissures) and symptoms (itching, 
burning, and irritation) of infection will be assessed by the investigator and the subject, respectively, on 
the VSS Scale. The VSS Scale is a standardized, predefined scale where each sign and symptom will be 
given a numerical rating based on severity (absent = 0; mild = 1; moderate = 2; or severe = 3) to calculate 
a total composite score. 
Mycological Evaluations: Mycological tests will include direct WET Mount microscopic examination 
(performed locally) to visualize clue cells indicative of bacterial vaginosis or trichomonas, direct 
microscopic examination with 10% KOH (performed locally) to identify yeast, and fungal cultures 
(performed at the central lab) for species identification and antifungal susceptibility testing. 
Safety and Tolerability Assessments 
Safety Evaluations: Safety will be evaluated throughout the study, from consent through the TOC visit, 
including the following parameters: AEs, concomitant medications, vital signs, safety laboratory tests, 
and study treatment discontinuations. 


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STATISTICAL ANALYSES: 
All statistical tests will be two-sided and interpreted at a 5% significance level. The study is not powered 
for formal statistical comparisons. Descriptive statistics (i.e., mean, standard deviation, median, 
minimum, maximum, etc.) will be provided for all continuous variables; frequencies and percentages 
will be tabulated for incidence and categorical variables.  For parameters measured over time, observed 
values and changes from baseline will be described for each time point. All analyses will be presented 
by treatment group.  Unless otherwise stated, data will be analyzed as is with no imputation.  No 
adjustment for multiplicity will be employed.   
The primary efficacy endpoint, the percentage of subjects with clinical cure at TOC will be assessed on 
the MITT population and will present the clinical cure rate and the 95% confidence interval calculated 
using the method of Clopper and Pearson. In addition, the clinical cure rate and 95% CI will be calculated 
where subjects with missing values will be removed from the analysis. 
Sample Size Determination 
This is an exploratory study and no formal sample size calculation was performed.  Approximately 150 
subjects will be enrolled in allocation 50:50:50 in respect of 1, 3 and 7 days of treatment.  Subjects will 
be randomized to treatment, stratified by group based on the Candida species and presence or absence 
of underlying conditions. The sample size of 150 is estimated to be adequate to perform an initial 
assessment of efficacy.   
Analysis Populations 
The study populations to be used in the analyses are defined as follows: 
Intent-to-Treat (ITT) Population: All ibrexafungerp-treated subjects. 
Modified Intent-to-Treat (MITT) Population: All treated subjects who have a positive culture for 
Candida species at Screening. 
Per-Protocol (PP) Population: All MITT subjects who have completed the study drug treatment, who 
did not have major protocol deviations likely to affect study efficacy AND who have available data at 
the TOC evaluation. 
Safety Population: All enrolled subjects who received at least one dose of study drug. 
Efficacy Analysis 
Efficacy assessments will be based on clinical evaluations, QOL outcomes, mycological testing, and 
additional antifungal use at the TOC visit.  Analysis by species will be conducted.  
The following treatment outcome definitions will be used for the assessment of efficacy relative to 
Baseline: 
Clinical Outcomes: 
Clinical Cure: complete resolution of signs and symptoms with total composite score of 0 on the VSS 
Scale and with no additional antifungal therapy required based on investigator’s judgment. 
Clinical Improvement: partial resolution of signs and symptoms with total composite score of 1 or 2 on 
the VSS Scale and with no additional antifungal therapy required based on investigator’s judgement. 
Clinical Success: at least 50% reduction from Baseline in the total composite VSS score with no 
additional antifungal therapy required based on investigator’s judgment. 
Clinical Failure: Persistence and/or worsening of signs and symptoms or need for additional antifungal 
therapy. 
Mycological Outcomes 
Mycological Eradication: negative culture for growth of Candida species 
Presumed Eradication: Subject is asymptomatic, therefore cultures not done 


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Mycological Persistence: positive culture for growth of Candida species 
Safety Analysis 
Safety will be evaluated throughout the study, including the following parameters: AEs, treatment 
discontinuations, physical examination, vital signs, safety laboratory tests, and prior and concomitant 
medications. 
No formal statistical analysis is planned for the safety data. Safety analysis will be conducted using the 
Safety Population. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) Version 19.1 or 
higher. The incidence and severity of treatment-emergent AEs and SAEs and their relationship to 
treatment will be summarized by system organ class and preferred term. The percentage of subjects who 
discontinued study treatment and the reasons for discontinuation will be summarized. 
Safety laboratory evaluations and vital signs will be summarized as observed values and as changes from 
Baseline. In addition, shifts (with respect to the reference range) from Baseline will be presented for 
laboratory tests. 
 
 
 


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6. 
SCHEMATIC OF STUDY DESIGN 
Schematic of Study Design 
Figure 1: 
Schematic of Study Design
 
 
 
Days 1-3 
Ibrexafungerp 
300mg BID 
TOC Visit (14(+3) days after Baseline) – VSS assessment, 
cultures 
Baseline Day 1* 
Collect baseline cultures 
 
Screening (Day -2 +1)* 
 
FU Visit (30 (+4) days after Baseline) – VSS assessment, cultures if 
applicable, QOL 
Days 3, 5, and 7 (+1) Phone Contact – Resolution of 
symptoms 
*Screening visit can be done on the same day as Baseline visit if needed. 
Day 1 
 Ibrexafungerp 
300mg BID 
Days 1-7 
Ibrexafungerp 
300mg BID 
FU Visit (30 (+4) days after EOT) – VSS assessment, QOL 
FU Visit (60 (+4) days after EOT) – VSS assessment, QOL 
FU Visit (14 (+3) days after EOT) – VSS assessment, cultures 


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7. 
BACKGROUND INFORMATION AND SCIENTIFIC 
RATIONALE 
7.1. 
Background Information 
Ibrexafungerp has been approved by the FDA for treatment of post menarcheal women with VVC.  
7.1.1. 
Vulvovaginal Candidiasis 
Vulvovaginal candidiasis (VVC) is a common fungal infection caused by Candida spp. and is a 
significant morbid condition in women from all social classes. 
Information on the incidence of VVC is incomplete, since the disease is not a reportable entity and 
data collection is hampered by inaccuracies of diagnosis and the use of non-representative study 
populations.1 VVC affects 70%–75% of women at least once during their lives, most frequently 
young women of childbearing age. Approximately 40%–50% of women will experience a 
recurrence2 and 5% to 8% of adult women have a recurrent vulvovaginal candidiasis.3 
Current treatments for VVC include topical antifungals and the use of prescription oral antifungals 
such as single doses of fluconazole. In two vaginal candidiasis studies conducted with fluconazole, 
the therapeutic cure rate, defined as the resolution of signs and symptoms of vaginal candidiasis 
along with negative KOH examination and negative culture for Candida, was achieved by 55% of 
subjects receiving single doses of fluconazole 150 mg. The therapeutic cure rate is reduced to 40% 
in subjects with a history of recurrent vaginitis4,5. Although a single dose of fluconazole is able to 
provide an acceptable therapeutic outcome for more than half of the treated individuals, the 
emergence of fluconazole resistance among C. albicans isolates and the frequency of cases caused 
by C. glabrata, a strain naturally less susceptible to fluconazole, signals the need for new 
therapeutic approaches. 
Additionally, recurrence of VVC after fluconazole therapy is not uncommon and these 
exacerbations often involve the same microorganism identified in the initial episode, suggesting 
that a small number of C. albicans remain as a reservoir in the vagina after completion of azole 
therapy, becoming the source of subsequent exacerbations6. This may be explained by the fact that 
azoles are fungistatic, which means that they slow the growth of, but do not kill, the fungus and 
azoles are not active against certain species of Candida that cause VVC. 
New curative approaches are needed, particularly involving agents with fungicidal activity (i.e., 
that can kill the fungus) and activity against fluconazole-resistant strains, so that the causative 
yeasts can be eradicated. A new therapeutic approach with these characteristics would be expected 
to result in improved short-term and potentially long-term outcomes for this condition. 
This study aims to provide evidence of the efficacy and evaluate the safety of oral ibrexafungerp 
as a new class of antifungal agent with fungicidal activity against Candida spp. in the treatment of 
complicated VVC in subjects who have failed fluconazole therapy. 
7.1.2. 
The glucan synthesis inhibitor ibrexafungerp (formerly known as SCY-078) 
Ibrexafungerp is a member of a new class of antifungal agents and is an orally active, semi-
synthetic, triterpenoid derivative of the natural product enfumafungin. Ibrexafungerp is a 


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structurally distinct class of glucan synthesis inhibitor (GSI) that inhibits the synthesis of the 
fungal cell wall polymer β-(1,3)-D-glucan. Time-kill studies have demonstrated that 
ibrexafungerp has in vitro fungicidal activity against Candida spp. isolates similar to that observed 
with the echinocandins. 
Ibrexafungerp is being developed as the first oral and intravenous (IV) GSI for the treatment and 
prevention of fungal infections caused by Candida and Aspergillus species with the potential to 
provide the therapeutic advantages of both an IV and oral formulation. 
7.1.3. 
Antifungal activity 
The spectrum and potency of activity of ibrexafungerp has been evaluated by numerous independent 
laboratories against an extensive panel of clinically relevant yeast and mold isolates using the 
Clinical and Laboratory Standards Institute (M27-A3 guidelines)7 and European Committee on 
Antimicrobial Susceptibility Testing methods. Overall, the epidemiological studies have 
demonstrated that ibrexafungerp has potent, broad-spectrum activity against the majority of the 
clinical isolates tested. These studies have laid the foundation in support of the use of ibrexafungerp 
for the treatment of invasive fungal infections8,9,10. 
7.1.3.1. 
Activity against Candida spp. 
Ibrexafungerp has been evaluated against >2000 Candida isolates, including all clinically relevant 
species with more than 300 C. albicans, more than 600 C. glabrata and more than 250 C. auris 
isolates tested. These in vitro studies have demonstrated the broad spectrum of anti-Candida 
activity of ibrexafungerp. Additionally, ibrexafungerp demonstrated in vitro activity against pre-
formed biofilms, which is a relevant feature when addressing catheter-related Candida infections 
and, potentially, VVC. Studies conducted with azole- and echinocandin- resistant strains have 
shown that ibrexafungerp retains activity (i.e., no significant change in minimum inhibitory 
concentration [MIC] compared to wild type) against >90% of azole- resistant strains and >70% of 
Candida strains with FKS mutations commonly associated with echinocandin resistance. 
Interestingly, although ibrexafungerp and the echinocandins share a similar mechanism of action 
(β-[1,3]-D-glucan synthesis inhibition), their clearly different molecular structure provides them 
with some differentiating characteristics in terms of microbiological activity. 
Ibrexafungerp was evaluated in vitro against approximately 190 clinical isolates of echinocandin-
resistant strains of Candida spp. containing mutations in the FKS gene. Overall, ibrexafungerp was 
active against the majority of the echinocandin-resistant strains tested. Moreover, ibrexafungerp 
was significantly active against approximately 70% of the isolates containing the most commonly 
reported FKS mutation associated with echinocandin resistance in C. glabrata (S663P in FKS2 
and S645P in FKS1). Selection of ibrexafungerp resistance in vitro occurs at a low frequency. A 
deletion at position F659 in FKS2 of C. glabrata was the predominant mutation observed in these 
studies; notably, ibrexafungerp did not select for mutations at positions S663 or S645. These results 
suggest that ibrexafungerp inhibits glucan synthase in a manner different to echinocandins. 
The in vitro studies also included several multidrug-resistant isolates. Consistent with the data 
described above, ibrexafungerp was active against >70% of these isolates. Ibrexafungerp has also 
demonstrated a potent activity against life-threatening and multi-drug-resistant C. auris strains in 


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over 100 different C. auris isolates, at concentrations indicative of potential clinically relevant 
effects. C. auris has been recently highlighted as a clinical alert by the Centers for Disease Control 
and Prevention (CDC) because of the global emergence of this fungal infection with limited 
therapeutic options and high mortality. 
7.1.4. 
Clinical experience 
To date, more than 1500 healthy subjects and patients have been exposed to ibrexafungerp in 
completed and ongoing clinical trials. 
Ibrexafungerp was generally well tolerated following single oral doses of up to 1600 mg and 
multiple oral doses of up to 800 mg/day for 28 consecutive days in Phase 1 studies. Reported 
adverse events (AEs) after oral administration have been generally transient and primarily mild to 
moderate in intensity. The most frequently reported AEs have been mild gastrointestinal (GI) 
events (nausea, vomiting, diarrhea and abdominal pain). 
A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the 
Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs. Placebo in Subjects with Acute 
Vulvovaginal Candidiasis 
The primary objective of this study was to evaluate the efficacy of oral ibrexafungerp in female 
subjects 12 years and older with VVC by comparing the clinical outcomes of ibrexafungerp and 
placebo. The primary end point of the study was efficacy as measured by the percentage of subjects 
with clinical cure (complete resolution of signs and symptoms) at the test-of-cure (TOC) visit. 
Approximately 366 eligible subjects were enrolled and randomly assigned in a 2:1 ratio to receive 
ibrexafungerp (300-mg dose twice daily [BID]) or matching placebo administered BID for 1 day. 
Overall, the percentage of subjects with clinical cure at the TOC visit was statistically significantly 
higher for the ibrexafungerp group than the placebo group (50.5% versus 28.6%; P=0.001). 
Ibrexafungerp was generally well-tolerated by subjects with AVVC when administered as a 300- 
mg oral dose (two 150mg tablets) BID for 1 day. Overall, a total of 150 subjects (60.7%) of the 
247 subjects who received ibrexafungerp and 63 subjects (50.8%) of the 124 subjects who received 
placebo experienced at least 1 TEAE during the study. 
The most frequently reported adverse events were gastrointestinal disorders, which were reported 
at a higher frequency for the ibrexafungerp group than the placebo group. The most frequently 
reported GI disorders in the ibrexafungerp groups included diarrhea and nausea (in more than 10% 
of subjects). 
Three (3) subjects reported SAEs during the study: 2 SAEs were reported by 1 subject (0.4%) who 
received ibrexafungerp (pneumonia and bronchial hyperreactivity), and 2 SAEs were reported by 
2 subjects (1.6%) who received placebo (diabetes mellitus and hypokalemia); none were 
considered to be related to the study drug. 
A total of 5 subjects in the ibrexafungerp group experienced TEAEs that resulted in 
discontinuation. Of these, 2 subjects experienced TEAEs leading to withdrawal of the study drug 
and discontinuation from the study (vomiting and dizziness). In addition, 3 subjects experienced 


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TEAEs leading to discontinuation after completing study treatment (bacterial vaginosis and 
vulvovaginal itching; not related to study drug). There were no deaths reported during the study. 
Mean clinical laboratory results and vital sign measurements observed at the TOC visit were 
generally similar to those observed at baseline, with no notable differences between treatment 
groups. 
SCY-078-306, A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to 
Evaluate the Efficacy and Safety of Oral Ibrexafungerp (SCY-078) vs. Placebo in Subjects with 
Acute Vulvovaginal Candidiasis 
A total of 455 subjects were enrolled, and 449 subjects received at least 1 dose of randomized 
study drug, 298 subjects received ibrexafungerp and 151 subjects received placebo. 
The primary objective was to evaluate the efficacy of oral ibrexafungerp versus placebo in female 
subjects 12 years and older with VVC by comparing the clinical outcomes of ibrexafungerp and 
placebo. Efficacy was defined as the percentage of subjects with clinical cure (complete resolution 
of signs and symptoms) at the TOC visit. The primary analysis was conducted using the Modified 
Intent-to-Treat (mITT) set, which included 272 randomized subjects (188 subjects in the 
ibrexafungerp group and 84 subjects in the placebo group) who had a diagnosis of symptomatic 
AVVC and a positive culture for Candida species at baseline. The study achieved the primary 
endpoint reaching statistical significance. Overall, the percentage of subjects with clinical cure at 
the TOC visit in the mITT set was statistically significantly higher for the ibrexafungerp group 
than the placebo group (63.3% versus 44.0%; P=0.007). 
Ibrexafungerp was generally well-tolerated by subjects with AVVC when administered as a 300- 
mg oral tablet BID for 1 day. 
Overall, a total of 99 subjects (33.2%) of the 298 subjects who received ibrexafungerp and 44 
subjects (29.1%) of the 151 subjects who received placebo experienced at least 1 TEAE during the 
study. 
The most frequently reported adverse events were GI disorders. The percentage of subjects who 
experienced treatment-related TEAEs was higher for the ibrexafungerp group than the placebo 
group (14.8% versus 4.0%, respectively), however the majority of these were GI disorders and 
were considered mild in severity. 
A total of 2 subjects reported SAEs during the study: 1 subject from the ibrexafungerp group 
reported a gastrointestinal bacterial infection and 1 subject from the placebo group reported 
diabetic ketoacidosis. 
Three subjects experienced a TEAE leading to study discontinuation, all in the ibrexafungerp 
group (diabetes mellitus [1 subject] and bacterial vaginosis [2 subjects]). 
Mean clinical laboratory results and vital sign measurements observed at the TOC visit were 
generally similar to those observed at baseline, with no notable differences between treatment 
groups. 
For additional information on ibrexafungerp, please refer to the Investigator´s Brochure (IB). 


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7.2. 
Rationale for the Study 
This study is an exploratory, open-label study to evaluate the efficacy and safety of oral 
ibrexafungerp for the treatment of complicated VVC in subjects who have failed fluconazole 
therapy.   The study design follows the CDC, ACOG and IDSA guidelines on the treatment of 
patients with complicated VVC. 
7.2.1. 
Rationale for Study Indication and Population 
Considering the properties of ibrexafungerp as a potent antifungal compound, with fungicidal 
activity against Candida spp., it will represent an important non-azole alternative treatment for 
subjects suffering from VVC who are not responsive to fluconazole.  The Phase 3 VANISH 
program for treatment of VVC with ibrexafungerp excluded patients with treatment failure and 
patients who had immunocompromised underlying medical conditions that complicated VVC. 
These women with VVC infections excluded from the VANISH study are the intended population 
for this study that is designed to facilitate the identification of a clinically meaningful effect of 
ibrexafungerp. 
7.2.2. 
Rationale for Selected Dose Levels and Dosing Regimens 
The selected oral ibrexafungerp dose regimen for this study will be BID doses of 300 mg, given 
for 1, or for 3 or 7 consecutive days. Oral ibrexafungerp 300 mg BID is the current approved dose 
for VVC. The current CDC, ACOG and IDSA guidelines recommend 3-7 days of treatment for 
complicated VVC and 7-14 days of treatment for non-albicans VVC. These dose regimens are in 
the range of doses that have been well tolerated in Phase 1, Phase 2, and ongoing Phase 3 studies. 
7.2.3. 
Rationale for Study Endpoints 
Study endpoints were selected in line with prior efficacy and safety studies in patients with VVC 
episodes.  
7.2.4. 
Rationale for Study Design 
This trial is being conducted as a phase 3b, open-label, ibrexafungerp only treatment for VVC. The 
duration of treatment and the subsequent evaluations and endpoints are consistent with prior 
clinical trials in patients with VVC 
8. 
STUDY OBJECTIVES 
8.1. 
Primary Objectives 
• 
To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on clinical cure. 
8.2. 
Secondary Objectives 
• 
To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on mycological and clinical outcomes. 


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• 
To evaluate the safety and tolerability of oral ibrexafungerp in subjects with complicated VVC 
who failed fluconazole therapy. 
8.3. 
Exploratory Objective 
• 
To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on QOL outcomes. 
9. 
STUDY ENDPOINTS 
9.1. 
Primary Endpoints 
• 
Efficacy as measured by the percentage of subjects with clinical cure (total composite score of 0 on 
the VSS Scale with no additional antifungal therapy required based on investigator’s judgment) at the 
TOC visit. 
9.2. 
Secondary Endpoints 
Efficacy as measured by: 
• 
The percentage of subjects with clinical improvement: 
- Total composite score of 2 on the VSS scale at the TOC and FU visits 
- Total composite score of 1 on the VSS scale at the TOC and FU visits 
• 
The percentage of subjects with clinical success (at least 50% reduction from baseline in the total 
composite VSS score) with no additional antifungal therapy required based on investigator’s 
judgment) at the TOC and FU visits. 
• 
The percentage of subjects with mycological response (defined as a negative culture for growth of 
Candida spp. or subject is asymptomatic, therefore culture not done) at the TOC and FU visits. 
• 
The percentage of subjects with both clinical cure and mycological response at the TOC and FU visits. 
• 
The percentage of subjects with clinical cure at the FU visits. 
• 
The absolute change in total composite VSS score from baseline to the TOC and FU visits. 
Exploratory Endpoints: 
• 
Absolute improvement in QOL outcomes at TOC and FU visits compared to baseline as measured by 
QOL survey. 
• 
Subjects whose signs and symptoms have resolved enough that additional antifungal treatment was 
not required based on clinical judgement. 
• 
Time to resolution of symptoms. 
Safety and tolerability as measured by: 
Adverse events (AEs), vital signs, treatment discontinuation, and safety laboratory tests. 


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10. 
STUDY DESIGN 
10.1. 
Overall Description of the Study 
This study is Phase 3b, open-label, multicenter study to evaluate the efficacy and safety of oral 
ibrexafungerp in the treatment of subjects with VVC episodes in subjects: 
• not responsive to, or  
• have isolates anticipated not to respond to, or  
• who are refractory to or intolerant of fluconazole.  
The susceptibility of historical isolates will be collected where available. 
Approximately 150 eligible subjects will be enrolled. Subjects will be randomized to receive oral 
ibrexafungerp 300mg administered twice a day for either one, three, or seven consecutive days, stratified 
by group based on Candida species and presence or absence of underlying medical conditions. 
10.1.1. 
Study Visits 
The study will consist of a Screening visit on Day -2 (±1), Baseline visit on Day 1 (if applicable, 
the Screening and Baseline visits can both be done on Day 1), Phone contacts on Days 3, 5 and 7 
(±1), a TOC visit 14 (±3) days after Baseline, FU visits at: 14 (±3) days after EOT, 30 (±4) after 
Baseline, 30 (±4) after EOT and 60 (±4) days after EOT. 
10.1.1.1. Screening (Day -2) 
 
At Screening, subjects who are experiencing vulvovaginal symptoms will be evaluated by the 
investigator, who will obtain a vaginal sample for potassium hydroxide (KOH) testing and vaginal 
pH determination by the local laboratory prior to randomization and initiation of treatment. The 
vaginal samples will also be evaluated locally for findings indicative of bacterial vaginosis and 
Trichomonas vaginalis (WET Mount and/or DNA probe). If the investigator suspects Herpes 
virus, Neisseria gonorrhoeae or Chlamydia trachomatis infection, a vaginal sample will be 
collected and sent to a qualified local laboratory. A vaginal sample for fungal culture and for 
species identification and susceptibility testing will be obtained and sent to a designated central 
laboratory. The investigators and the subjects will rate the signs and symptoms of infection, 
respectively, on the VSS Scale (see Appendix 2). Safety procedures, including an abbreviated 
physical exam, vaginal exam, vital signs, laboratory tests and a pregnancy test will also be 
performed.  
 
To be eligible for inclusion, subjects must have a minimum composite score of vulvovaginal signs 
and symptoms ≥ 4 with at least 2 signs or symptoms having a score of 2 (moderate) or greater in 
the VSS Scale at Baseline, a positive KOH test, a normal vaginal pH (≤4.5) and confirmed absence 
of other vaginal co-infections. 
The Screening and Baseline (Day 1) visits may occur on the same day.  


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10.1.1.2. Baseline (Day 1) 
Subjects who meet all criteria for this study will complete a QOL questionnaire.  They will receive 
the first dose of study drug, oral ibrexafungerp 300 mg, at the study site and will self-administer 
subsequent doses as applicable at home. For some subjects, 300mg BID dosing will be repeated 
daily for a total of 3 or 7 consecutive dosing days based on Candida species and presence or 
absence of underlying medical conditions.  Doses will be self-administered at 12-hourly (±3 hours) 
intervals.   
10.1.1.3. Phone Contact (Days 3, 5 and 7[±1]) 
During this phone contact, AEs, resolution of symptoms (applicable section of the VSS scale), and 
concomitant medications (including antifungals) will be assessed. 
10.1.1.4. TOC visit (14 ±3 days after Baseline) 
At this visit, study drug container(s) will be returned, reviewed, and treatment compliance 
evaluated. The investigators and the subjects will again rate the signs and symptoms of infection 
on the VSS Scale and the subjects will complete a QOL questionnaire. 
Vulvovaginal samples for fungal culture, species identification, and antifungal susceptibility 
testing will be obtained and sent to a designated central laboratory. Additional vaginal samples 
will be obtained for a KOH test and pH measurements by the local laboratory if symptoms persist 
or have worsened. AEs and/or concomitant medications will be evaluated.   
10.1.1.5. FU visit (14 ±3 days after EOT) 
At this visit, study drug container(s) will be returned, reviewed, and treatment compliance 
evaluated. The investigators and the subjects will again rate the signs and symptoms of infection 
on the VSS Scale and the subjects will complete a QOL questionnaire. 
Vulvovaginal samples for fungal culture, species identification, and antifungal susceptibility 
testing will be obtained and sent to a designated central laboratory. Additional vaginal samples 
will be obtained for a KOH and vaginal pH testing by the local laboratory if symptoms persist or 
have worsened.  AEs and/or concomitant medications will be evaluated.   
10.1.1.6. FU visits 30 (±4) days after Baseline, 30 (±4) days after EOT and 60 (±4) days after 
EOT: 
At the FU visits, subjects will rate their symptoms of infection on the VSS Scale and will complete 
a QOL questionnaire. Only if VSS symptoms are present will the investigator perform a 
vulvovaginal examination to rate the subject’s signs of infection and collect samples for pH 
determination, KOH testing, and fungal culture. 
10.1.1.7. All Visits 
AEs and prior/concomitant medications will be assessed and documented at all visits. 
10.1.2. 
Study Assessments 
The study will include efficacy, safety, and tolerability assessments. 


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10.1.2.1. Efficacy Assessments 
Efficacy assessments will be based on VSS scores, clinical evaluations, QOL outcomes, 
mycological testing and additional antifungal use assessed at the TOC and FU visits. 
10.1.2.2. Safety Assessments 
Safety will be evaluated throughout the study, including the following parameters: AEs, treatment 
discontinuations, physical examination, vital signs, safety laboratory tests, and prior and 
concomitant medications. 
10.2.  
Blinding, Randomization, and Stratification 
This is an open label study. Subjects will be randomized to treatment, stratified by group based on 
the Candida species and presence or absence of underlying medical conditions.   
10.3.  
Study Duration 
Each subject is expected to complete the study in approximately 65 days and up to approximately 
130 days for subjects who require additional treatment and enter Treatment Cycle 2. 
10.4.  
Number of Centers 
Multiple centers will participate in subject enrollment and treatment. 
11. 
STUDY POPULATION 
The study population will include female subjects who are ≥18 years of age with complicated VVC 
who have failed fluconazole therapy. 
11.1. 
Inclusion Criteria 
Subjects must fulfill all of the following criteria to be eligible for study admission: 
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: 
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 on 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). 
d) Has no other vaginal co-infections based on WET Mount microscopic examination (and/or 
DNA probe). 
3) Subject should also have:  
a) 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. 


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OR 
b) A recurrent vulvovaginal candidiasis (RVVC) episode with breakthrough symptoms while 
receiving maintenance antifungal therapy.   
OR 
c) 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  
d) A VVC episode caused by candida species with documented resistance to fluconazole 
based on MIC determination. 
OR 
e) 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.  
11.2. 
Exclusion Criteria 
A subject will be excluded from participation in the study if she meets any of the following 
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. 


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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. 
11.3.   
Discontinuation Criteria 
A subject may be discontinued from the study or study drug for any of the following reasons: 
• 
Withdrawal of consent by the subject 
• 
Investigator or sponsor decision that withdrawal is in the subject’s best interest 
• 
Occurrence of an AE that, in the opinion of the investigator, warrants discontinuation of 
the subject from the study drug 
• 
Lost to follow up (every attempt should be made to contact the subject) 
The reason for a subject’s discontinuation of treatment or withdrawal from the study will be clearly 
documented in the source documents and on the electronic case report form (eCRF). All TOC 
procedures should be performed for subjects who discontinue from the study before the TOC visit. 
11.4.  
Early Termination 
If the subject experiences persistence or worsening or recurrence of symptoms that per the 
investigator’s assessment (e.g., symptoms ≥4) warrant the use of additional antifungal therapy, and 
the investigator does not consider continuing treatment with ibrexafungerp for a Second Treatment 
Cycle, a vaginal examination with investigator’s rating of signs should be completed. Additionally, 
vulvovaginal samples should be obtained for KOH testing and pH measurements by the local 
laboratory, fungal culture by the central laboratory and investigation of other pathogens such as 
bacterial vaginosis and Trichomonas vaginalis by the local laboratory. 


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If the KOH test is negative, the investigator should consider other causes for the persistence or 
worsening of the symptoms as additional antifungal medication may not be indicated. 
If the investigator’s rating of the vulvovaginal signs and vaginal sample collection is not possible 
prior to the initiation of the additional therapy, it should still be completed as soon as possible after 
additional therapy is initiated. 
In addition to the vaginal examination, the symptoms that led to the use of additional antifungal 
therapy should be documented in the eCRF and the following procedures should also be 
completed: 
• 
If additional antifungal therapy is administered prior to or at the TOC visit, all TOC visit 
procedures should be completed, and no additional visits will be needed. The subject will be 
considered as early termination due to lack of efficacy prior to or at TOC. 
• 
If additional antifungal therapy is administered after the TOC visit but prior to or at the FU 
visit, all FU visit procedures should be completed, and no additional visits will be needed. 
The subject will be considered as early termination due to lack of efficacy after TOC but 
prior to or at FU. 
11.5.  
Replacement of Dropouts 
Subjects who discontinue from the study may be replaced at the discretion of the investigator and 
Sponsor. 
12. 
STUDY TREATMENTS 
12.1. 
Study Treatment Groups 
Treatment Cycle 1 – ALL randomized subjects: 
Subjects who meet all the inclusion and none of the exclusion criteria will be randomized to 
treatment and stratified by group based on the Candida species and presence or absence of 
underlying conditions. Subjects will receive open-label oral ibrexafungerp 300 mg BID for one, 
three or seven consecutive days per the table below: 
 
Ibrexafungerp Treatment Groups: 
Treatme
nt Group 
Criteria 
*Ibrexafungerp Dose (300mg AM 
and 300mg PM) 
Randomization and Stratification  
Group A 
Subjects without underlying medical conditions AND 
known to have isolates other than C glabrata, C krusei, 
C auris  
1 Day dosing 
N=50 
Group B 
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 
3 Days OR 7 Days dosing  
Randomized 1:1  
N=50:50 


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*Days of treatment is per CDC Guidelines (https://www.cdc.gov/std/treatment-
guidelines/candidiasis.htm) 
Enrollment will continue until the target number in each cohort is reached.    
Treatment Cycle 2: A second treatment cycle will be allowed for subjects who did not achieve 
sufficient clinical improvement (e.g. VSS remains ≥3) on the randomized treatment (Cycle 1) as 
evaluated at the TOC and FU visits.  A second treatment cycle will also be allowed for subjects 
with clinical cure/improvement/success who experience a recurrence before the last FU visit.  
During Cycle 2, subjects may receive additional treatment with ibrexafungerp for a period up to 
14 days as recommended by the investigator and following discussion with the sponsor. 
12.2. 
Dietary Requirements 
There are no dietary requirements or restrictions for the administration of the study drug. It is 
recommended that study drug be administered preferably with or immediately after a meal or snack 
and with approximately 8 oz./240 mL of water. 
12.3. 
Study Drugs 
Study drug will consist of oral ibrexafungerp (150 mg tablets). 
12.4. 
Ibrexafungerp Description 
Study Drug Identifier:  ibrexafungerp 
12.4.1. 
Formulation, Packaging and Labelling 
Ibrexafungerp citrate drug product for oral administration will be supplied as a tablet containing 
150 mg of ibrexafungerp active ingredient on a free-base basis. In addition to the active ingredient, 
the tablet formulation also contains silicified microcrystalline cellulose, crospovidone, mannitol, 
colloidal silicon dioxide, magnesium stearate (non-bovine) and butylated hydroxyanisole. 
Oral tablets will be supplied in blister packs of four 150 mg tablets per blister.  Each blister 
constitutes one day’s dosing of 300 mg BID.  Labels on the blisters will contain study medication 
information and any other information required by applicable regulations and may include the 
following information: 
• Product Name 
• Sponsor Name 
• Study Protocol Number 
• Place to write the subject number 
• Number of tablets per blister pack 
• Dosing instructions 
• Storage conditions (e.g. room temperature 15°C – 25°C 
• Caution Statement: e.g. "Caution: New Drug – Limited by Federal (United States) 
Law to Investigational Use Only” 


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12.4.2. 
Storage and Stability 
The pharmacist or appropriate designee at each clinical research site will be responsible for the 
study drug. For long-term storage at the site, study drug supplies provided in blisters must be kept 
in a secure area (e.g., locked cabinet) and stored at room temperature. 
12.5. 
Drug Accountability 
The investigator or designee will inventory and acknowledge receipt of all shipments of the study 
drug. Drug accountability logs will be used to maintain accurate records of receipt, dispensing, 
administration to each subject and return of drug. A study monitor will periodically check the 
supplies of investigational products held by the site to verify accountability of all study drugs. At 
the conclusion of the study after final drug accountability has been completed by the monitor, all 
unused study drug and all empty/partially used blisters will be returned to the Sponsor or destroyed 
on site if the site has procedures in place for study drug destruction. 
Drug supplies will be maintained in a secure, limited-access storage area under the recommended 
storage conditions (see Section 12.4.2). 
The study drug supplied for this study is only for use in subjects properly consented and enrolled 
under this protocol. A study site designee (e.g. pharmacist, study nurse/coordinator) will: 
• Record the treatment in the appropriate drug accountability log 
• Report and document any study medication issues such as crushed or broken tablets 
− All product quality complaints should be reported to the Sponsor 
• Collect blister packs (containers) and count the number of tablets remaining at the TOC 
visit. 
• Record any unused or remaining drug in the drug accountability log and eCRF and note 
any discrepancies and reason for discrepancies 
12.6. 
Subject Compliance with Study Drug Dosing 
Subjects will be instructed to bring the assigned blister packs of study medication (including empty 
blister packs) with them to the TOC visit to assess treatment compliance. Compliance will be 
assessed based on remaining tablets as compared to what should have been taken. Details of 
treatment including any missing dose will be recorded on the eCRF. Sites are encouraged to contact 
the medical monitor or sponsor for concerns of compliance with the treatment regimen, especially 
for subjects who miss doses due to problems with tolerability. 
13. 
NON-STUDY TREATMENTS 
13.1. 
Prior and Concomitant Medications 
All medications (including prescription and over-the-counter medications, supplements, and 
herbal products) taken from 30 days before the Screening Visit (Day -2 [+ 1]) through the TOC 


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visit will be recorded in the eCRF. Only the use of antifungal medications, medications used to treat 
vaginal infections, vaginal (topical) medications, antibiotics for any reason or any other 
medications to treat a study-drug related AE will be recorded after the TOC visit through the last 
study visit (FU). Start and stop dates of concomitant medications will be recorded in the eCRF. 
Prior and concomitant medications will be reviewed and recorded at all scheduled and unscheduled 
study visits. 
13.2. 
Prohibited Medications 
Medications specifically not permitted in the exclusion criteria (Section 11.2) include the 
following: 
• Non-study systemic or topical antifungal therapy 
• Topical vaginal corticoids 
• Topical (vaginal) contraceptives 
• Other investigational drug(s) 
• Select strong CYP3A4/5 inhibitors, CYP3A4/5 inducers and select P-gp substrates.  
See Section 21 (Appendix 1) for the full list of prohibited medications. 
13.2.1. 
Medications to be Administered with Caution and Monitored as Appropriate 
The following medications must be administered with caution and must be monitored as 
appropriate: 
• CYP3A4 substrates, including but not limited to sirolimus, tacrolimus warfarin, 
cyclosporine and amiodarone 
• Organic anion-transporting polypeptide 1B3 (OATP1B3) substrates 
See Section 21 (Appendix 1) for the full list of medications to be administered with caution. 
13.3. 
Study Restrictions 
There are no study restrictions other than those described in Section 11.2 (Exclusion Criteria), 
Section 12.2 (Dietary Requirements) and Section 13.2 (Prohibited Medications). 
14. 
STUDY PROCEDURES 
The following sections provide a description of the individual study procedures to be performed 
during the conduct of the study. Detailed schedules of study assessments are provided in the 
Schedule of Visits and Procedures in Table 1. 
14.1. 
Informed Consent 
Every study subject must provide written informed consent at Screening, prior to participating in 
any Screening evaluations or any other study activities (see Section 19.3). 


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14.2. 
Assignment of Subject Number 
At Screening, all subjects who have signed an ICF will receive a unique subject identification (ID) 
number, which will consist of a site number followed by a 2-digit sequentially assigned subject 
number starting at 01, at each site. The subject numbers assigned to eligible subjects will be 
recorded in the eCRF. This number will be unique to each subject and will be used to identify the 
subject throughout the study.  
Subjects who are screen failures or who are not eligible for enrollment will be recorded as such in 
the eCRF. For subjects who sign an ICF (i.e., are assigned a subject number) but are NOT enrolled 
because they do not meet all of the inclusion/exclusion criteria, the applicable screening visit pages 
of the eCRF will be completed. The criteria that were not met for enrollment will be documented 
in the eCRF. 
14.3. 
Inclusion and Exclusion Criteria 
All inclusion and exclusion criteria will be reviewed at Screening (-2 +1) and at Baseline (Day 1) to 
ensure that the subject qualifies for the trial.  Screening and Baseline can be on the same day, if 
applicable. 
14.4. 
Medical History and Demographics 
During the Screening visit, a complete medical history for the prior year will be recorded for each 
subject. The medical history will include previous and current medical diagnoses and major 
surgical procedures. Subject demographics such as age, sex, race, and ethnicity will also be 
collected. 
14.5. 
Abbreviated Physical Examination 
An abbreviated physical examination, including general appearance and an overall examination of 
body systems, will be conducted at Screening, TOC visit, and at any unscheduled visit, if needed. 
14.6. 
Urine Pregnancy Test 
A urine pregnancy test based on the measurement of human chorionic gonadotropin with a 
sensitivity of at least 25 international units per liter will be performed at Screening and at 
unscheduled visits, if needed, by the local laboratory for all subjects of childbearing potential. The 
pregnancy test results will be reviewed at Baseline (Day 1) before administration of study drug. 
14.7. 
Safety Laboratory Tests 
Safety laboratory tests will be performed by a qualified local laboratory. Samples for safety 
laboratory tests will be collected at the Screening, TOC, and at any unscheduled visit, if needed. If 
indicated, these may be done more frequently as follow up to a laboratory abnormality. 
The following laboratory parameters will be determined: 
14.7.1. 
Hematology 
• White blood cell (WBC) count 
• Hemoglobin (HgB) 


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• Red blood cell (RBC) count 
• Hematocrit (Hct) 
• Platelet count 
 
• Differential WBC count will include percentages for lymphocytes, monocytes, 
eosinophils and basophils,  
• and absolute counts for neutrophils, lymphocytes, atypical lymphocytes, 
monocytes, eosinophils and basophils. 
14.7.2. 
Blood Chemistry 
• Glucose 
• Total creatine phosphokinase (CPK) 
• Albumin 
• Aspartate aminotransferase (AST/SGOT) 
• Sodium 
• Alanine aminotransferase (ALT/SGPT) 
• Potassium 
• Gamma glutamyl transferase (GGT) 
• Alkaline Phosphatase 
• Bilirubin (total, direct and indirect) 
• Creatinine 
• Total protein 
14.8. 
Rating of Vulvovaginal Symptoms by the Subject Using the VSS 
Scale 
Subjects will be asked to rate their vulvovaginal symptoms at Screening, Baseline (Day 1), during 
telephone interviews on Days 3, 5 and 7, at the TOC visit and at the FU visits. 
Subjects will also assess their symptoms at unscheduled visits, as needed. 
If the subject experiences persistence or worsening or recurrence of symptoms that per the 
investigator’s assessment (e.g. symptoms ≥4) warrant the use of rescue antifungal therapy, the 
rating of the symptoms that led to the use of rescue antifungal therapy must be documented in the 
eCRF and a vaginal examination with rating of signs by the investigator should be completed. If 
the investigator’s rating of the vulvovaginal signs and vaginal samples collection are not possible 
prior to the initiation of the rescue therapy, they should still be completed as soon as possible after 
rescue therapy is initiated. 
Subjects will rate their symptoms of infection using the VSS Scale, where each vulvovaginal 
symptom will be given a numerical rating based on severity, as follows: 
• Itching: absent = 0; mild = 1; moderate = 2; severe = 3 
• Burning: absent = 0; mild = 1; moderate = 2; severe = 3 
• Irritation: absent = 0; mild = 1; moderate = 2; severe = 3 
14.9. 
Vulvovaginal Samples for Identification of Other Pathogens and 
Vaginal pH 
A vulvovaginal specimen will be obtained at the Screening visit for local vaginal pH 
determination. This sample will also be tested by a local qualified laboratory to rule out bacterial 
vaginosis and Trichomonas vaginalis. Testing for Neisseria gonorrhoeae, Chlamydia trachomatis 
or Herpes virus will also be conducted by a qualified local laboratory if clinically indicated. 
Vaginal samples will be tested for bacterial vaginosis, T. vaginalis, N. gonorrhoeae, C. 


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trachomatis or Herpes virus at unscheduled visits, if needed. Samples should be collected prior to 
the initiation of rescue therapy, and if not possible, it should still be completed as soon as possible 
after rescue therapy is initiated. If there is persistence or recurrence of vulvovaginal symptoms, 
additional vulvovaginal specimens will be collected at the TOC and at the FU visits. 
Procedures for collecting and shipping vulvovaginal samples to the central laboratory will be 
described in the laboratory manual. 
14.10. 
Vulvovaginal Samples for KOH and Fungal Culture 
At Screening, a vulvovaginal specimen will be obtained for direct microscopic examination with 
10% KOH. Subjects must have a positive KOH test at screening to be enrolled. The screening 
KOH will be assessed at the site by the investigator or qualified designee. A vaginal sample will 
also be obtained at screening, at the TOC and at the first FU visit at 14 days after EOT for fungal 
culture and species identification by the central laboratory and for susceptibility testing against 
ibrexafungerp and additional antifungal agents (per CLSI M27-A3 guidelines). If there is 
persistence or recurrence of vulvovaginal symptoms, additional vulvovaginal specimens will be 
collected for KOH testing at the TOC and at the FU visits, and for fungal culture at the FU visits. 
Samples will also be obtained at any unscheduled visit, if needed. 
If the subject experiences persistence or worsening or recurrence of symptoms that per the 
investigator’s assessment (e.g. symptoms ≥4) warrant the use of rescue antifungal therapy, the 
subject may be enrolled into Treatment Cycle 2 and receive additional treatment with 
ibrexafungerp for a period up to 14 days as recommended by the investigator and following 
discussion with the sponsor.   
Whether or not a subject enters Treatment Cycle 2, or be prescribed rescue therapy, a vaginal 
examination with collection of samples for KOH (assess at the site) and culture should be 
completed prior to initiation of Treatment Cycle 2 or rescue therapy. If the KOH test is negative, 
the investigator should consider other causes for the persistence or worsening of the symptoms and 
antifungal rescue medication may not be indicated. If the collection of the vaginal culture is not 
possible prior to the initiation of the rescue therapy, it should still be collected as soon as possible 
after rescue therapy is given. 
14.11. 
Rating of Vulvovaginal Signs by the Investigator Using the VSS Scale 
The investigator (or qualified designee) will perform vulvovaginal examinations to rate the 
subject´s signs of infection at the Screening, TOC and first FU visits at 14 days after EOT. The 
vulvovaginal examination will be repeated at the rest of the FU visits only if the subject presents 
with symptoms. Otherwise, no additional vulvovaginal examination will be conducted, or signs 
rated. Vulvovaginal examinations may be conducted at unscheduled visits, if needed. 
If the subject experiences persistence or worsening or recurrence of symptoms that per the 
investigator’s assessment (e.g. symptoms ≥4) warrant the use of rescue antifungal therapy, the 
subject may be enrolled into Treatment Cycle 2 and receive additional treatment with 
ibrexafungerp for a period up to 14 days as recommended by the investigator and following 
discussion with the sponsor.   


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Whether or not a subject enters Treatment Cycle 2, or be prescribed rescue therapy, a vaginal 
examination with rating of signs by the investigator should be completed prior to initiation of rescue 
therapy. If the investigator’s rating of the vulvovaginal signs is not possible prior to the initiation 
of the rescue therapy, it should still be completed as soon as possible after rescue therapy is initiated. 
Investigators will assess the signs of infection using the VSS Scale provided in Section 21 
[Appendix 2]), a standardized, predefined scale where each sign of the vagina and/or vulva will be 
given a numerical rating based on severity, as follows: 
• Edema: absent = 0; mild = 1; moderate = 2; severe = 3 
• Erythema: absent = 0; mild = 1; moderate = 2; severe = 3 
• Excoriation or fissures: absent = 0; mild = 1; moderate = 2; severe = 3 
Other findings will be recorded using the most relevant medical term in the abbreviated physical 
examination page of the eCRF. 
14.12. 
Quality of Life (QOL) Questionnaire 
Subjects will complete a QOL questionnaire at Baseline, TOC and at the follow-up visits. 
14.13. 
Randomization 
This is an open label study.  Subjects will be randomized to treatment and stratified by group based 
on the Candida species and presence or absence of underlying conditions. 
14.14. 
Study Drug  
At Baseline (Day 1), eligible subjects will have their Day 1 dose administered in the clinical 
research unit and will be dispensed enough study medication for either single day BID dose, or for 
BID dosing for 3 or 7 consecutive days as explained in Section 12.1.  
14.15. 
Study Drug Dosing 
Treatment Cycle 1 applicable to all subjects: The first study drug dose (Day 1) will be administered 
at the clinical research center and the subsequent dose(s) will be self-administered by the subjects 
at approximately 12 ± 3-hour intervals at home.  
NOTE:  If administering the first dose at the study center would complicate the administration of 
the second dose 12 hours later (e.g. first dose at 3 p.m. will require second dose at 3 a.m.), the 
subject can self-administer both Day 1 doses at home to allow for a more convenient dosing 
schedule (e.g., 8 p.m. and 8 a.m.). Details of study treatment groups and dietary requirements for 
treatment administration are provided in Section 12.1 and Section 12.2, respectively. 
Treatment Cycle 2: A second treatment cycle will be allowed for subjects who did not achieve 
sufficient clinical improvement (e.g. VSS remains ≥3) on the randomized treatment (Cycle 1) as 
evaluated at the TOC and FU1 visits.  A second treatment cycle will also be allowed for subjects 
with clinical cure/improvement/success who experience a recurrence before the last FU visit.  


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During Cycle 2, subjects may receive additional treatment with ibrexafungerp for a period up to 
14 days as recommended by the investigator and following discussion with the sponsor. 
14.16. 
Study Drug Collection and Treatment Compliance Evaluation 
Treatment compliance will be reviewed by the investigator or designee at the TOC visit. Subjects 
will be instructed to bring all blister packs (including empty blister packs) of study medication 
with them to the visit to assess treatment compliance. Further details are available in Section 12.5. 
14.17. 
Vital Signs 
Vital signs, including blood pressure (systolic and diastolic), heart rate and body temperature will 
be measured at screening and at the TOC visit as well as at unscheduled study visits, if needed. 
14.18. 
Prior and Concomitant Medication Review 
All medications (including prescription and over-the-counter medications, supplements, and 
herbal products) taken from 30 days before Screening visit through the TOC visit will be recorded 
in the eCRF. Only the use of other antifungal medications, medications used to treat vaginal 
infections, vaginal (topical) medications and antibiotics for any reason or any other medications 
to treat a study-drug related AE will be recorded after the TOC visit through the last study visit. 
Start and stop dates of concomitant medications will be recorded in the eCRF. Prior and 
concomitant medications will be reviewed and recorded at all scheduled and unscheduled study 
visits. 
See Section 13.2 for prohibited medications, medications to be administered with caution and 
further details for non-study treatments. 
14.19. 
Adverse Event Monitoring 
AEs will be recorded and reviewed at all scheduled and unscheduled study visits from the time the 
ICF is signed through TOC visit.  New AEs starting after TOC will be recorded only if they led to 
the use of other antifungal medications or topical vaginal treatment, if they are a vaginal bacterial 
or parasitic infection, or if they are deemed related to the previously administered study drug. See 
Section 16 for further reference. 
 


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15. 
STUDY SCHEDULE 
Detailed schedules of all study visits and procedures are presented in Schedule of Visits and Procedures (Table 1). 
The actual visits will be dependent on the Dosing Group i.e there may be overlapping visits. 
Subjects entering Treatment Cycle 2, will follow the same Schedule of Visits and Procedures, starting with Baseline visit and may 
have visits that are Not Applicable during Treatment Cycle 1. 
Table 1: 
Schedule of Visits and Procedures (Study SCY-078-307b) 
Visit 
V1 
Screeninga 
V2 
Baselinea 
At 
Home 
V3 
TOC 
 
V4 FU 
 
V5 FU  
 
V6 FU  
 
V7 FU 
Unscheduled 
Visitsb 
Day (allowable window) 
Day -2(+1) 
Day 1 
Days 
2-7 
14 ±3 days 
post 
Baseline 
14 ±3 
days post 
EOT 
30±4 days 
post 
Baseline 
30 ±4 days 
post EOT 
60 ±4 
days post 
EOT 
Study Procedures 
 
 
 
Informed consent 
X 
 
 
 
 
 
 
 
 
Enrollment and assignment of 
Subject ID number 
X 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteriac 
X 
X 
 
 
 
 
 
 
 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
Abbreviated physical exam 
X 
 
 
X 
 
 
 
 
If needed 
Vital Signsk 
X 
X 
 
X 
 
 
 
 
If needed 
Urine pregnancy test
c
 
X 
 
 
X 
 
 
 
 
If needed 
Safety laboratory blood tests
d 
X 
 
 
X 
 
 
 
 
If needed 


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Visit 
V1 
Screeninga 
V2 
Baselinea 
At 
Home 
V3 
TOC 
 
V4 FU 
 
V5 FU  
 
V6 FU  
 
V7 FU 
Unscheduled 
Visitsb 
Day (allowable window) 
Day -2(+1) 
Day 1 
Days 
2-7 
14 ±3 days 
post 
Baseline 
14 ±3 
days post 
EOT 
30±4 days 
post 
Baseline 
30 ±4 days 
post EOT 
60 ±4 
days post 
EOT 
Rating of vulvovaginal 
symptoms by the Subject
e
 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
If needed 
Vaginal Examination and 
rating of vulvovaginal signs by 
the Investigatore 
X 
 
 
X 
 
 
X 
If 
symptoms 
If 
symptoms 
 
If 
symptoms 
If needed 
Vulvovaginal sample for other 
pathogense 
X 
 
 
If needed 
 
If needed 
if needed 
 
If needed 
 
If needed 
If needed 
Vulvovaginal sample for KOH 
and pH e 
X 
 
 
If symptoms 
If 
symptoms 
If 
symptoms 
If 
symptoms 
If 
symptoms 
If needed 
Vulvovaginal sample for fungal 
culturee 
X 
 
 
X 
 
X 
If 
symptoms 
 
If 
symptoms 
If 
Symptoms 
If needed 
Quality of Life Questionnaire 
 
X 
 
X 
 
X 
X 
 
X 
 
X 
 
Study drug dosing 
 
X 
X 
 
 
 
 
 
 
Study drug container(s) 
collection and subject data 
reviewed 
 
 
 
X 
 
 
 
 
 
Phone Contacth 
 
 
X 
 
 
 
 
 
 
Prior and concomitant 
medication reviewi 
X 
X 
X 
X 
 
X 
X 
X 
 
X 
X 
AE monitoringj 
X----------------------------------------------------X 
X 
X 
X 
X 
X 
Abbreviations: AE = adverse event; D = day; TOC = test of cure; V = visit; FU = follow up 


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a) 
Screening and Baseline may occur on the same day. 
b) 
Unscheduled visits can occur if the investigator determines there is a need for one outside of the scheduled per protocol visits. 
c) 
Results should be reviewed prior to enrollment at Baseline (Day 1). 
d) 
Hematology and blood chemistry. Safety laboratory tests will be performed by a qualified laboratory. 
e) 
A vaginal examination with rating of signs by the investigator will be completed at the TOC visit. If the subject experiences persistence or worsening 
or recurrence of symptoms, after the baseline visit (e.g. symptoms ≥4), that warrant the use of rescue antifungal therapy, the symptoms that led to the 
use of rescue antifungal therapy must be documented in the eCRF. Additionally, vulvovaginal samples should be obtained for KOH testing and pH 
measurement (both at the clinical research unit), fungal culture (central laboratory) and investigation of other pathogens such as bacterial vaginosis and 
Trichomonas vaginalis (at the local lab). If the investigator’s rating of the vulvovaginal signs and vaginal samples collection are not possible prior to 
the initiation of the rescue therapy, they should still be completed as soon as possible after rescue therapy is initiated. 
f) 
Vulvovaginal examinations will be repeated at the FU visits only if the subject presents symptoms. Otherwise, no additional vulvovaginal examination 
will be conducted or signs rated. 
g) 
The first study drug dose (Day 1) will be administered at the clinical research center and the subsequent dose(s) will be self-administered by the 
subjects at approximately 12 ± 3 hour intervals at home. 
h) 
The Day 3, 5, and 7 phone contacts will be used to evaluate symptom resolution, AEs, and concomitant medications. 
i) 
Only the use of antifungal medications, vaginal (topical) medications, antibiotics for any reason or any other medications to treat an AE will be 
recorded after the TOC visit through the last study visit (FU).   
j) 
New AEs starting after TOC will be recorded only if they led to the use of other antifungal medications or topical vaginal treatment, if they are a 
vaginal bacterial or parasitic infection, or if they are deemed related to the previously administered study drug 
k) 
Blood pressure (systolic and diastolic), heart rate and body temperature 
 
 


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16. 
SAFETY ASSESSMENTS AND MONITORING 
16.1. 
Definition of an Adverse Event 
An AE is any untoward medical occurrence associated with the use of a drug in humans, whether 
or not considered drug related. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal laboratory finding), symptom or disease temporally associated with the 
use of a study drug/study intervention, whether or not related to the study drug/study intervention. 
Any laboratory abnormality that is deemed to be clinically significant in the opinion of the 
investigator will be considered an AE and should be recorded in the eCRF, whether or not it is 
related to the study drug. 
Stable chronic conditions that are present prior to clinical trial enrollment and do not worsen are 
not considered AEs and will be accounted for in the subject’s medical history. 
The following can be considered AEs: 
• An exacerbation of a pre-existing illness 
• An increase in frequency or intensity of a pre-existing episodic event or condition 
• A condition detected or diagnosed after the initiation of treatment with study 
medication, even though it may have been present prior to the start of the study 
• Continuous persistent disease or symptoms present at baseline that worsen after signing 
the informed consent or following the initiation of treatment with study medication 
The following are not considered AEs: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction or 
transfusion); the condition that leads to the procedure is an AE 
• Pre-existing disease or conditions present or detected at the start of the study that do 
not worsen 
• Situations where an untoward medical occurrence has not occurred (e.g., 
hospitalizations for cosmetic surgery or elective surgery or social/convenience 
admissions) 
• The disease being studied, or signs or symptoms associated with the disease, unless 
more severe than expected for the subject’s condition or a worsening of the disease 
being studied 
16.2. 
Definition of a Serious Adverse Event 
A SAE is defined as an AE meeting one of the following outcomes: 
• Death 
• Life-threatening event 
• Inpatient hospitalization or prolongation of existing hospitalization 


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• Persistent or significant disability/incapacity or substantial disruption of the ability to 
conduct normal life functions 
• Congenital anomaly or birth defect 
Any other important medical event that may not result in one of the above outcomes may be 
considered a SAE when, based upon appropriate medical judgment, the event may jeopardize the 
participant and may require medical or surgical intervention to prevent one of the outcomes listed 
above. 
A life-threatening AE is any AE that places the subject, in the view of the investigator, at 
immediate risk of death from the AE as it occurred. It does not include an AE that, had it occurred 
in a more severe form, might have caused death. 
16.3. 
Events of Clinical Interest 
Not Applicable 
16.4. 
Overdose 
This refers to the administration of a quantity of a medicinal product given per administration or 
cumulatively, which is above the maximum recommended dose according to the authorized 
product information.  
An overdose can occur if a subject has taken, accidentally or intentionally, a drug administered in 
a dose exceeding the protocol-specified dose.  An overdose must be reported within 24 hours of 
the site becoming aware of the overdose if such overdose occurs with an associated SAE.  If an 
overdose occurs without an associated SAE, the overdose must be reported within 5 working days 
and documented in the subject’s medical record as well as in the dosing section of the eCRF.   
16.5. 
Pregnancy 
Female subjects who become pregnant should be immediately discontinued from the study and 
followed up to determine the outcome of the pregnancy. The pregnancy must be reported to the 
Sponsor within 24 hours of the site becoming aware of the pregnancy. If the pregnancy ends for 
any reason before the anticipated date, the investigator should notify the Sponsor. At the completion 
of the pregnancy, the investigator will document the outcome of the pregnancy. If the outcome of 
the pregnancy meets the criteria for immediate classification as an SAE (i.e., postpartum 
complication, spontaneous abortion, stillbirth, neonatal death or congenital anomaly), the 
investigator should follow the procedures for reporting an SAE. 
16.6. 
Unexpected Adverse Event 
An AE is considered “unexpected” if it is not listed in the IB or is of greater specificity or severity 
than those that have been observed with the particular study drug being tested. For example, under 
this definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the IB 
referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral thromboembolism and 
cerebral vasculitis would be unexpected (by virtue of greater specificity) if the IB listed only 
cerebral vascular accidents. "Unexpected," as used in this definition, also refers to AEs that are 


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mentioned in the IB as occurring with a class of drugs or as anticipated from the pharmacological 
properties of the drug but are not specifically mentioned as occurring with the particular drug under 
investigation. 
16.7. 
Grading of Adverse Events 
The severity (or intensity) of an AE refers to the extent to which it affects the subject’s daily 
activities and will be classified by the investigator as mild, moderate or severe using the following 
criteria: 
• Mild: Awareness of sign or symptom, but easily tolerated. Not likely to require medical 
attention. 
• Moderate: Discomfort enough to cause some interference with daily activity. May 
require medical intervention. 
• Severe: Intense enough to disrupt daily activities. Likely requires medical intervention. 
16.7.1. 
Clarification of the difference in meaning between “severe” and “serious” 
The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache). This is not the same as “serious”, which is based 
on the outcome or action criteria usually associated with events that pose a threat to life or 
functioning. Seriousness (not severity) serves as a guide for defining regulatory reporting 
obligations. 
16.8. 
Causality Assessment 
The investigator will assess causality (i.e., whether there is a reasonable possibility that the study 
drug caused the event) for all AEs and SAEs. The relationship will be characterized using the 
following classification: 
• Related: The temporal relationship of the AE with the study drug makes causality 
possible and as likely or more likely than due to another cause such as other drugs, a 
surgical intervention, or an underlying disease. 
• Not related: The temporal relationship of the AE with the study drug makes causality 
improbable and can be due to another cause such as other drugs, a surgical intervention, 
or an underlying disease. 
16.9. 
Adverse Event Collection Timeframe 
AEs will be recorded and reviewed at all scheduled and unscheduled study visits from the time the 
ICF is signed through TOC visit.  New AEs starting after TOC will be recorded only if they led to 
the use of other antifungal medications or topical vaginal treatment, if they are a vaginal bacterial 
or parasitic infection, or if they are deemed related to the previously administered study drug. 
All AEs reported by the subject or observed by members of the clinical staff will be evaluated by 
the principal investigator (PI) or qualified designee. The PI will attempt, if possible, to establish a 


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diagnosis based on presenting signs and symptoms. The nature of the AE, time of onset relative to 
study drug administration, duration, severity, and relationship to treatment should be determined. 
Details of any corrective treatment must be recorded in the eCRF. The PI will determine whether 
any changes have occurred in baseline signs and symptoms. All AEs and SAEs will be collected 
in the eCRF. 
16.10. 
Serious Adverse Event Reporting Requirements 
All SAEs must be reported within 24 hours of the site becoming aware of the SAE (Appendix 3). 
Any event that is serious, study drug-related, and unexpected as assessed by the medical monitor or 
the Sponsor will be submitted to the regulatory authorities in accordance with national regulatory 
laws and regulations. The PI will be responsible for reporting all SAEs that require reporting to 
the local or central Institutional Review Board/Ethics Committee (IRB/EC) in accordance with its 
regulations and guidelines. 
16.11. 
Adverse Event and Serious Adverse Event Follow-up 
All AEs and SAEs will be followed up to resolution (the subject’s health has returned to her 
baseline status or all variables have returned to normal) or until an outcome is reached, stabilization 
occurs (the investigator does not expect any further improvement or worsening of the event) or the 
event is otherwise explained, regardless of whether the subject is still participating in the study. 
All appropriate therapeutic measures should be undertaken and recorded. Where appropriate, 
medical tests and examinations will be performed to document resolution of the event(s). 
16.12. 
Serious Adverse Event Reporting – Procedures for Investigators 
Initial Reports and Follow-Up SAE Reports: To report an SAE, the SAE eCRF form within the 
Electronic Data Capture (EDC) system must be completed. All SAEs, whether or not deemed drug-
related or expected, must be reported by the investigator or qualified designee within 24 hours of 
first becoming aware of the event (Appendix 3). The investigator/qualified designee will enter the 
required information regarding the SAE into the appropriate form, which will automatically result 
in distribution of the information to the appropriate sponsor contact. If the EDC system is 
temporarily unavailable (>24 hours), the event, including the investigator-determined causality to 
study drug, should be reported via a paper back-up SAE form to the Safety Surveillance team via 
(contact information, i.e., e-mail or fax will be available on the SAE form). 
Upon return of the availability of EDC system, the SAE information must be entered into the EDC 
system as soon as possible. The SAE form within the EDC system must be updated within 24 
hours of knowledge/receipt of SAE follow-up information. 


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17. 
DATA COLLECTION, STUDY MONITORING AND RECORD 
MANAGEMENT 
17.1. 
Data Collection and Reporting 
Data for this study will be collected using eCRFs. The investigator and study site staff will receive 
training regarding the completion of the eCRF. Visit-specific data should be entered into the eCRF 
and be ready for review as soon as possible, but no later than 5 days after each visit/time point. 
All protocol-required information collected during the study must be entered by the investigator 
or designated representative in the source documents and eCRF. All data entry, modification or 
deletion will be recorded indicating the individual subject, original value, the new value, the reason 
for change, who made the change, and when the change was made. All data changes will be clearly 
indicated with a means to locate prior values. The investigator will maintain a list of individuals 
who are authorized to enter or correct data on the eCRFs. 
The investigator or designated sub-investigator, following review of the data in the eCRF, will 
confirm the validity of each subject’s data by signing the eCRF. 
17.2. 
Study Monitoring 
Study progress will be monitored by the Sponsor or its representative as frequently as necessary 
to ensure adequate and accurate data collection, protocol compliance, and study conduct in 
accordance with accepted regulatory requirements. The PI must make all the subject data available 
to the monitor for review during the planned site monitoring visits. Arrangements for monitoring 
visits will be made in advance, except in emergency cases. 
17.3. 
Investigator Study Files 
The PI is responsible for maintaining all study-related documents in the study files. The Sponsor 
will notify the PI when retention of study files is no longer necessary. The following documents 
will be kept in the study files or be readily accessible: 
• original protocol and all amendments 
• signed agreement or protocol 
• signed and dated study staff roles and responsibilities log 
• copy of the current curriculum vitae of the PI and of all sub-investigators 
• IRB/EC membership list and all IRB/EC approvals for the protocol and amendments, 
informed consent documentation and all updates, advertisements, and written 
information provided to subjects; all IRB/EC correspondence; documentation that the 
IB and subsequent revisions have been submitted to the IRB/EC; documentation that 
all SAEs and any periodic safety reports have been submitted to the IRB/EC; and 
annual IRB/EC renewals (as required) 
• updated laboratory certification and the laboratory’s normal values (covering the entire 
time interval of the study for all laboratory tests conducted during the study) 


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• all confirmations of investigational drug receipt, drug accountability logs and drug 
return records 
• all correspondence to or from the Sponsor or its designees 
• blank informed consent form 
• Investigator’s Brochure 
• subject screening log 
• subject list (contains subject initials and/or protocol-specific subject number) 
• all subjects’ original signed informed consents 
• monitoring visit log 
17.4. 
Retention of Records 
Essential documents should be retained until at least 2 years after the last approval of a marketing 
application and until there are no pending or contemplated marketing applications, or at least 2 
years have elapsed since the formal discontinuation of the clinical development of the 
investigational product. These documents should be retained for a longer period, however, if 
required by the applicable regulatory requirements or by an agreement with the Sponsor. 
The Sponsor will inform the PI/institution in writing of the need for record retention and will notify 
the PI/institution in writing when the trial-related records are no longer needed. 
An investigator who withdraws from the responsibility of maintaining study records or wishes to 
move them to a new location has the obligation to place them in safekeeping and to inform the 
Sponsor of their location. 
18. 
ANALYTICAL PLAN 
All statistical processing will be performed using SAS® version 9.3 or later, unless otherwise 
stated. All statistical tests will be two-sided and interpreted at a 5% significance level. 
The study is not powered for formal statistical comparisons.  Descriptive statistics (i.e., mean, 
standard deviation, median, minimum, maximum, etc.) will be provided for all continuous 
variables; frequencies and percentages will be tabulated for incidence and categorical variables. For 
parameters measured over time, observed values and changes from baseline will be described for 
each time point. 
The clinical cure and mycological eradication rates will be described by baseline Candida species, 
when the number of isolates per species allows. 
All analyses will be presented by treatment group. Unless otherwise stated, data will be analyzed 
as is with no imputation. No adjustment for multiplicity will be employed. 
A Statistical Analysis Plan (SAP) describing all statistical analyses in detail will be provided as a 
separate document. The SAP will be finalized prior to database lock. 


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18.1. 
Sample Size Determination 
The primary efficacy endpoint of the study is the percentage of subjects with clinical cure 
(complete resolution of signs and symptoms with total composite score of 0 on the VSS Scale with 
no additional antifungal therapy required based on investigator’s judgment) at the TOC visit. This 
is an exploratory study, and no formal sample size calculation was performed.  Approximately 150 
subjects will be enrolled in allocation 50:50:50 in respect of 1, 3 or 7 days of treatment.  Subjects 
will be randomized to treatment, stratified by group based on the Candida species and presence or 
absence of underlying medical conditions. A sample size of 150 subjects is estimated to be 
adequate to perform an initial assessment of efficacy.   
18.2. 
Analysis Populations 
The study populations to be used in the analyses are defined as follows: 
Intent-to-Treat (ITT) Population: All ibrexafungerp-treated subjects. 
Modified Intent-to-Treat (MITT) Population: All treated subjects who have a positive culture 
for Candida species at Screening. 
Per-Protocol (PP) Population: All MITT subjects who have completed the study drug treatment, 
who did not have major protocol deviations likely to affect study efficacy AND who have a TOC 
evaluation. 
Safety Population: All enrolled subjects who received at least one dose of study drug. 
18.3. 
Subject Disposition, Discontinuation, and Baseline Data 
Subject disposition in terms of the number and percentage of subjects enrolled by site will be 
tabulated. The number of subjects enrolled, number completing the study, and reasons for 
discontinuation will be summarized by treatment group. Subject demographics and baseline 
characteristics such as age, race, ethnicity, sex, weight, height, body mass index, region (if 
applicable) and other relevant parameters will be tabulated by treatment group. 
Baseline is defined as the last non-missing assessment prior to the date (and time if appropriate) 
of the first dose of study drug. Change from baseline is defined as: post- baseline value – baseline 
value. 
18.4. 
Handling of Missing Data, Dose Adjustments, and Early 
Withdrawals 
For the efficacy analyses, subjects who do not have a TOC assessment will be assigned as treatment 
failures. For subjects who withdraw from the study early, every effort will be made to collect TOC 
visit information at the point of withdrawal. 
18.5. 
Prior and Concomitant Medications 
Prior and concomitant medications will be coded using the World Health Organization Drug 
Dictionary terminology. The number and percentage of subjects taking each medication before 
and after the first dose of study drug will be tabulated by treatment group. Medications taken and 
stopped prior to the first dose of study drug will be considered prior medications. Medications 


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started on or before the FU visit date with missing start dates or stop dates after the first dose of 
study drug will be considered concomitant medications. 
18.6. 
Efficacy 
18.6.1. 
Efficacy Assessments 
Efficacy assessments will be based on VSS scores, clinical evaluations, QOL outcomes, 
mycological testing, and additional antifungal use by the TOC visit and FU visits. 
18.6.1.1. The following treatment outcome definitions will be used for the assessment of 
efficacy relative to baseline: Clinical Outcome 
• Clinical Cure: Complete resolution of signs and symptoms with total composite score 
of 0 on the VSS Scale and with no additional antifungal therapy required based on 
investigator’s judgment 
• Clinical Improvement: partial resolution of signs and symptoms with total composite 
score of 1 or 2 on the VSS Scale and with no additional antifungal therapy required 
based on investigator’s judgement. 
• Clinical Success: at least 50% reduction from Baseline in the total composite VSS score 
with no additional antifungal therapy required based on investigator’s judgment 
• Clinical Failure: Persistence and/or worsening of signs and symptoms or need for 
additional antifungal therapy 
18.6.1.2. Mycological Outcome 
• Mycological Eradication: negative culture for growth of Candida species 
• Presumed Eradication: Subject is asymptomatic, therefore cultures not done 
• Mycological Persistence: positive culture for growth of Candida species 
18.6.2. 
Efficacy Analyses 
The efficacy analyses will be conducted using the MITT (primary analysis population), ITT and PP 
populations to evaluate ibrexafungerp. 
The primary efficacy endpoint, the percentage of subjects with Clinical Cure at TOC will be 
assessed on the MITT population and will present the Clinical Success rate and the 95% confidence 
interval calculated using the method of Clopper and Pearson. All other efficacy data will be 
summarized, but not subject to formal statistical analysis. 


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18.7. 
Safety 
18.7.1. 
Safety Assessments 
Safety will be evaluated throughout the study, including the following parameters: AEs, treatment 
discontinuations, physical examination, vital signs, safety laboratory tests, and prior and 
concomitant medications. 
AEs will be recorded and reviewed at all scheduled and unscheduled study visits from the time the 
Informed Consent Form is signed. An abbreviated physical examination, including general 
appearance and an overall examination of body systems, will be conducted at Screening, at the 
TOC visit and at the first FU (14 Days after EOT) visit. Vital signs, including blood pressure 
(systolic and diastolic), heart rate, respiratory rate and body temperature will be measured at the 
Screening and TOC visits and at unscheduled visits, if needed. Safety laboratory test (hematology 
and blood chemistry) will be measured at Screening, at the TOC visits and at unscheduled visits, 
if needed. All prior and concomitant medications taken before Screening through the TOC visit will 
be recorded. Only the use of antifungal medications, vaginal (topical) medications, antibiotics for 
any reason or any other medications to treat an AE will be recorded after the TOC visit through 
the last study visit. 
Study procedures are described in Section 14.0 and safety assessments and monitoring are 
described in Section 16.0. 
18.7.2. 
Safety Analyses 
Safety analyses will be conducted using the safety population. 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
Version 19.1 or higher. The incidence and severity of treatment-emergent AEs and SAEs and their 
relationship to treatment will be summarized by system organ class and preferred term. The 
percentage of subjects who discontinued study treatment and the reasons for discontinuation will 
be summarized by treatment group. 
Safety laboratory evaluations and vital signs will be summarized as observed values and as 
changes from Baseline. In addition, shifts (with respect to the reference range) from Baseline will 
be presented by treatment group for laboratory tests. 
19. 
ETHICS AND PROTECTION OF HUMAN PATIENTS 
19.1. 
Ethical Conduct of the Study 
The study will be conducted in accordance with the protocol, the ethical principles established by 
the Declaration of Helsinki (as amended in Fortaleza, Brazil, October 2013), the International 
Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guidelines, the US Code of 
Federal Regulations (CFR) sections that address clinical research studies, applicable European 
Union regulations and/or other national and local ethical and legal requirements, as applicable. 


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19.2. 
Institutional Review Board/Ethics Committee Review 
The PI or Sponsor/CRO must provide the IRB/EC with all appropriate materials, including a copy 
of the subject ICF. The study will not be initiated until the PI or CRO obtains written approval of 
the protocol and the subject ICF from the appropriate IRB/EC, and copies of these documents are 
received by the Sponsor. Appropriate reports on the progress of this study will be made by the PI 
to the IRB/EC, medical monitor, and Sponsor in accordance with applicable government 
regulations and in agreement with policy established by the Sponsor. 
19.3. 
Informed Consent 
The ICH issued guidelines to provide protection for human subjects in clinical investigations. The 
ICH Tripartite Guideline for Good Clinical Practice establishes the general requirements for 
informed consent. Each subject will be provided with oral and written information in a language 
they can understand that describes the nature and duration of the study. Before undergoing 
screening, each subject must consent in writing to study participation. The patient will sign and 
personally date the subject ICF. The person rendering consent will also sign and personally date 
the subject ICF as the person who obtained the consent of the subject. The original signed subject 
ICF will be retained with the study center’s records. Each subject will receive a copy of her signed 
subject ICF. In addition, the PI, or his or her designee, must document in the case history that 
informed consent was obtained before study participation. 
19.4. 
Future Use of Samples 
Biological samples collected during the study, including Candida spp. isolates (see Section 14.9 
and Section 14.10), may be maintained in repositories for potential future use. Future research of 
Candida isolates may include in vitro susceptibility testing of new or existing antifungals or 
analysis of mechanisms of resistance. All samples will be identified only by a coded number to 
maintain subject confidentiality. 
19.5. 
Subject Privacy and Subject Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records that leave the site will be 
identified only by a coded number to maintain subject privacy and confidentiality. All records will 
be kept in a locked file cabinet. All computer entry and networking programs will be performed 
with coded numbers only. Clinical information will not be released without written permission of 
the subject, except as necessary for monitoring by the medical monitor, IRB/EC, the Food and 
Drug Administration (FDA), the Sponsor or where required by law. All local privacy laws must 
be followed. 
19.6. 
Study Termination 
The PI, the sponsor, the FDA, and the IRB/EC each reserve the right to terminate the study in the 
interest of subjects’ safety and welfare. The sponsor reserves the right to terminate the study at any 
time for administrative reasons. The sponsor also reserves the right to discontinue study enrolment 
if a particular cohort is proving difficult to enroll. 
 


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19.7. 
Financial Disclosure 
The financial interests of all investigators from all participating clinical centers must be collected 
prior to study initiation and 1 year following the completion of the clinical trial. 


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20. 
REFERENCES 
1) Sobel JD. Vaginal candidosis. Lancet 2007;369:1961–71. 
2) Hurley R, De Louvois J. Candida vaginitis. Postgrad Med J 1979;55:645–47. 
3) Foxman B, Marsh JV, Gillespie B, Sobel JD. Frequency and response to vaginal symptoms 
among white and African American women: results of a random digit dialing survey. J 
Womens Health 1998;7:1167–74. 
4) Diflucan prescribing information. Pfizer. Revised November 2014. 
5) Sobel JD, Management of recurrent vulvovaginal candidiasis: unresolved issues. Curr Infect 
Dis Rep. 2006 Nov;8(6):481-6. 
6) Fidel PL, Sobel JD. Immunopathogenesis of recurrent vulvovaginal candidiasis. Clinical 
Microbiology Reviews 1996 July;9(3):335-348. 
7) CLSI. 2008a. Reference method for broth dilution antifungal susceptibility testing of yeasts; 
approved standard – third edition. CLSI document M27-A3. Clinical and Laboratory 
Standards Institute, Wayne, PA. 
8) Scorneaux B, Angulo D, Borroto-Esoda K, Ghannoum M, Peel M, Wring S. SCY-078 Is 
fungicidal against Candida species in Time-Kill studies. Antimicrobial Agents and 
Chemotherapy 2017 March;61(3):e01961-16. 
9) Arendrup MC, Jorgensen KM, Hare RK, Chowdhary A. In vitro activity of ibrexafungerp 
(SCY-078) against Candida auris isolates as determined by EUCAST methodology and 
comparison with activity against C. albicans and C glabrata and with the activities of six 
comparator agents. Antimicrobial Agents and Chemotherapy 2020 March;64(3):202136-19. 
10) Sobel JD, Borroto-Esoda K, Azie N, Angulo D. In vitro pH activity of ibrexafungerp against 
fluconazole-susceptible and -resistant Candida isolates from women with vulvovaginal 
candidiasis. Antimicrobial Agents Chemotherapy 2021 May doi:10.1128/AAC.00562-21. 
 
 
 
 
 
 
 
 
 
 
 
 


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21. 
APPENDICES 
APPENDIX 1. PROHIBITED MEDICATIONS AND MEDICATIONS TO 
BE ADMINISTERED WITH CAUTION 
Prohibited Medications 
The use of any topical vaginal corticoids and topical vaginal contraceptives is prohibited during 
the study. No systemic or topical vaginal antifungal treatment other than the study drug is allowed 
during the study unless used as rescue medication after the subject has been documented as not 
responding to study drug. No investigational drugs other than the study drug are allowed within 30 
days before Screening and for the entire duration of the study. In addition, the medications listed 
below are also prohibited. 
Strong CYP3A4/5 inhibitors and CYP3A4/5 inducers 
 
CYP 
Strong Inhibitorsa 
Inducersa 
3A4/5 
Ketoconazole 
Itraconazole 
 
bosentan 
carbamazepine 
phenytoin 
rifampin 
St. John’s wort 
long-lasting 
barbiturates 
efavirenz 
etravirine 
a. The CYP3A4/5 inhibitors and CYP3A4/5 inducers listed in this table are not permitted during the 7 days prior 
to enrollment and during study treatment until TOC. 
 


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Medications to be administered with Caution and Monitored as Appropriate 
CYP3A4 substrates 
 
CYP 
Substrates 
3A4 
In vitro, ibrexafungerp (SCY-078) was an inhibitor of CYP3A mediated metabolism of 
midazolam, but was only a weak inhibitor of metabolism of testosterone. The clinical 
significance of this inhibition is unknown; caution should be exercised when 
administering ibrexafungerp (SCY-078) with drugs known to be CYP3A sensitive 
substrates with narrow therapeutic index, such as midazolam and cyclosporine. 
Subjects receiving sirolimus, tacrolimus, warfarin, cyclosporine or amiodarone are 
permitted for enrollment in the study and these medications may be administered 
concomitantly with ibrexafungerp (SCY-078) with close monitoring. Dosing 
adjustments and subsequent monitoring of sirolimus and warfarin should be undertaken 
in accordance with product prescribing information for the respective agents. 
 
OATP1B3 substrates 
OATP 
Substrate 
1B3 
In vitro, ibrexafungerp (SCY-078) is an inhibitor of the OATP1B3 liver uptake 
transporter. The clinical significance of this inhibition is unknown; however, there is a 
potential risk for increased exposure of the concomitant medications (arising from 
lowered hepatic clearance) when administering ibrexafungerp (SCY-078) with drugs 
known to be OATP1B3 selective substrates. Therefore, caution should be exercised 
when administering ibrexafungerp (SCY-078) with drugs known to be OATP1B3 
selective substrates such as telmisartan, including monitoring the subject for signs of 
overexposure associated with the concomitant medications as described in the product 
prescribing information. 
 
 
Sources: 
• FDA Draft Guidance for Industry. Drug Interaction Studies – Study Design, Data 
Analysis, and Implications for Dosing and Labeling. 2012. 
• Drug interactions in infectious disease by Stephen C. Piscitelli, Keith Rodvold (2007) 
• UCSF-FDA Transportal 
P-gp Drug Substrates  
digoxin, colchicine, dabigatran 


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APPENDIX 2. VULVOVAGINAL SIGNS AND SYMPTOMS SCALE 
SIGNS: 
To be rated by the investigator during the vulvovaginal examination 
Sign 
Absent 
 0 
Mild  
1 
Moderate  
2 
Severe  
3 
Edema 
 
 
 
 
Erythema 
 
 
 
 
Excoriation or fissures 
 
 
 
 
• Definitions: Absent: none  Mild: slight 
• Moderate: definitely noticeable  Severe: marked, intense 
SYMPTOMS: 
To be rated by the subject 
Symptom 
Absent  
0 
Mild  
1 
Moderate  
2 
Severe  
3 
Burning 
 
 
 
 
Itching 
 
 
 
 
Irritation 
 
 
 
 
Definitions: 
• Absent: I have no discomfort (i.e., burning, itching, irritation) 
• Mild: I have some discomfort (i.e., burning, itching, irritation), but it does not bother 
me much 
• Moderate: I have discomfort (i.e., burning, itching, irritation), which is annoying, but 
not enough to affect what I am doing 
• Severe: I have discomfort (i.e., burning, itching, irritation), which is annoying enough 
to affect what I am doing 


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APPENDIX 3. SERIOUS ADVERSE EVENT REPORTING  
SAEs, as defined in Section16 Safety Assessments and Monitoring will be reported in accordance 
with ICH E2A Clinical Safety Data Management: Definitions and Standards for Expedited 
Reporting. 
Site Responsibilities 
All SAEs that occur during the course of the study must be reported to SCYNEXIS within 24 hours 
of the knowledge of the occurrence. 
The Investigator will fill out the SAE form and provide as complete information as are available. 
At a minimum, subject number, the dates and times of the study drug administered, a narrative 
description of the event must be provided. An assessment by the Investigator as to the severity of 
the event and relatedness to study drug should also be provided, if possible. Investigator will report 
all SAEs to: 
SCYNEXIS Inc. 
1 Evertrust Plaza, 13th Floor 
Jersey City, NJ 07302 
SAE@SCYNEXIS.com 
and 
safety.scynexis@awinsals.com Telephone: +1.760.372.7230 Fax: +1.844.769.3213 
The investigator will report SAE and any follow up information to the Research Ethics Board 
(REB) per REB procedures and requirements. 
The investigator will provide SAE follow-up information as soon as information is available to 
SCYNEXIS. 
SCYNEXIS Responsibilities 
If the SAE is considered a Suspected, Unexpected Serious Adverse Reaction (SUSAR) 
SCYNEXIS or designee will create a CIOMS or a Medwatch 3500A Report for submission to the 
relevant regulatory authority within 15-days after SCYNEXIS has learned of the SAE. If the 
SUSAR is a fatal or life-threatening event, the reports will be sent within 7 days after SCYNEXIS 
has learned of the event. 
Follow-up reports will be provided to regulatory agencies as soon as information is available 
according to the same reporting periods. 
 
 
 
 
 
 


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APPENDIX 4. 
PROTOCOL REVISION HISTORY 
Revisions to Protocol dated 12 October 2021 (Protocol Version 2.0) 
Current Version and Date: Protocol Amendment 2 (Protocol Version 3.0) dated 17 January 2022 
 
Amended to delete the strikethrough text and include the bolded text 
 
Protocol Section 
Change and Rationale 
 
 
 
 
 
Synopsis: Study 
Endpoints 
 
Synopsis: Statistical 
Analysis 
 
Section 9.1: Primary 
Endpoint 
 
Section 9.2: Secondary 
Endpoints 
 
Section 18.6.1.: 
Efficacy Assessments 
 
- Definition of “Clinical Cure” changed from a total composite score on the VSS 
Scale of “≤ 2” to “0”.  In response to FDA comments 
- Addition of “Clinical Improvement” as another Clinical Outcome and 
Secondary Endpoint.  Follow-on to above change 
 
Clinical Outcomes: 
Clinical Cure: partial or Complete resolution of signs and symptoms with total composite 
score of ≤ 2 0 on the VSS Scale and with no additional antifungal therapy required based 
on investigator’s judgment. 
Clinical Improvement: partial resolution of signs and symptoms with total 
composite score of 1 or 2 on the VSS Scale and with no additional antifungal 
therapy required based on investigator’s judgement. 
 
Efficacy as measured by: 
The percentage of subjects with clinical improvement  
− Total composite score of 2 on the VSS Scale at the TOC and Follow-up (FU) visits. 
− Total composite score of 1 on the VSS Scale at the TOC and FU visits. 
 
 
 
 
 
 
 
Synopsis: Study Visits 
 
Section 6: Schematic of 
Study Design 
 
Section 10.1.1: Study 
Visits 
 
Section 14: Study 
Procedures 
 
Section 15: Study 
Schedule 
 
Changes to Study Visits:   In response to FDA comments 
- TOC visit was changed from 14 days after EOT to 14 days after Baseline 
- FU Visit 14 (±3) days after EOT was added 
- FU visit 30 (±3) days after Baseline was added 
 
STUDY VISITS: 
The study will consist of a Screening visit on Day -2 (±1), Baseline visit on Day 1 (if 
applicable, the Screening and Baseline visits can both be done on Day 1), Phone contacts 
on Days 3, 5 and 7 (±1), a TOC visit 14 (±3) days after EOT Baseline and FU visits at: 
14 days (±3) days after End Of Treatment (EOT), 30 (±4) after Baseline, 30 (±4) 
days after EOT and 60 (±4) days after EOT. 
 
TOC visit (14 days [±3] after EOT Baseline): At this visit….  
FU visit (14 days [±3] after EOT): At this visit, treatment compliance will be 
reviewed and any AEs and/or concomitant medications evaluated. The 
investigators and the subjects will again rate the signs and symptoms of infection 
on the VSS Scale and the subjects will complete a QOL questionnaire. Vulvovaginal 
samples for fungal culture, species identification, and antifungal susceptibility 
testing will be obtained and sent to a designated central laboratory. Additional 
vaginal samples will be obtained for a KOH test and vaginal pH measurement by 
the local laboratory if symptoms persist or have worsened. 
FU visits: 30 (±4) days after Baseline, 30 (±4) days after EOT and 60 (±4) days after 
EOT: At the FU visits….  
 


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Synopsis 
Section 10.1. Overall 
Description of the 
Study 
Section 10.2 Blinding, 
Randomization and 
Stratification 
Section 14.13 
Randomization 
 
Study design changed from non-randomized without stratification, to randomized 
with stratification.  In response to FDA comments 
 
STUDY BLINDING, RANDOMIZATION, AND STRATIFICATION:  This is an 
open-label study. There will be no blinding, randomization, or stratification.  Subjects 
will be randomized to treatment, stratified by group based on the Candida species 
and presence or absence of underlying medical conditions. 
 
Approximately 100 150 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. 
 
 
Synopsis 
 
Section 18.1: Sample 
size Determination 
Sample size increased from 100 to 150 subjects to be enrolled. Impact of response 
to FDA comments 
Sample Size Determination: 
The primary efficacy endpoint of the study is the percentage of subjects with clinical 
cure (partial or complete resolution of signs and symptoms with total composite score 
≤2 of 0 on the VSS Scale with no additional antifungal therapy required based on 
investigator’s judgment) at the TOC visit. As this is a single arm, a statement 
regardingCI) will be produced. It is estimated that 100 eligible subjects will be 
enrolled.   
This is an exploratory study, and no formal sample size calculation was 
performed.  Approximately 150 subjects will be enrolled in allocation 50:50:50 in 
respect of 1, 3 or 7 days of treatment.  Subjects will be randomized to treatment, 
stratified by group based on the Candida species and presence or absence of 
underlying medical conditions. A sample size of 150 subjects is estimated to be 
adequate to perform an initial assessment of efficacy.   
 
 
Synopsis 
 
Section 10.3: Study 
Duration 
 
Section 12.1: Study 
Treatment Groups 
 
Section 12.4.: 
Ibrexafungerp 
Description 
 
Section 12.5.: Drug 
accountability 
 
Section 14: Study 
Procedures  
 
- Treatment Groups changed from 3 groups to 2 groups (Treatment Cycle 1).  To 
simplify  
- Added potential for additional Treatment Cycle 2 treatment.  To provide 
additional treatment option to patients with inadequate response 
- Study duration increased to potentially 130 days.   As a result of the addition of 
Treatment Cycle 2 
- IP will be provided in blister packs. Changed from bottles.  Company logistics 
 
Ibrexafungerp Treatment Groups: 
Treatment 
Group 
Criteria 
*Ibrexafungerp Dose (300mg AM 
and 300mg PM) 
Randomization and Stratification  
Group A 
Subjects who do not fit criteria for Groups B 
and C 
Subjects without underlying medical 
conditions AND known to have isolates 
other than C glabrata, C krusei, C auris  
1 Day dosing 
N=50 
Group B 
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 
3 Day OR 7 Days dosing  
Randomized 1:1  
N=50:50 
Group C 
Subjects known to have C glabrata, C krusei 
or C auris isolates 
7 Day dosing 
 


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*Days of treatment is per CDC Guidelines (https://www.cdc.gov/std/treatment-
guidelines/candidiasis.htm) 
Enrollment will continue until the target number in each cohort is reached.    
Treatment Cycle 2: A second treatment cycle will be allowed for subjects who did 
not achieve sufficient clinical improvement (e.g. VSS remains ≥3) on the 
randomized treatment (Cycle 1) as evaluated at the TOC visit or at the FU EOT+14 
visits. A second treatment cycle will also be allowed for subjects with clinical 
cure/improvement/success who experience a recurrence before the last FU visit.  
During Cycle 2, subjects may receive additional treatment with ibrexafungerp for 
a period up to 14 days as recommended by the investigator and following discussion 
with the sponsor. 
Study Duration: Each subject is expected to complete the study in approximately 65 
days and up to approximately 130 days for subjects who require additional 
treatment and enter Treatment Cycle 2. 
Oral tablets will be supplied in blister packs of four 150 mg tablets per blister.  
Each blister constitutes one day’s dosing of 300 mg BID.   
 
 
 
Section 16.3: Events of 
Clinical Interest 
Events of Clinical Interest – Removed.  No longer required since Ibrexafungerp 
safety profile is well established 
 
16.3. Events of Clinical Interest - Not Applicable 
The following are considered events of clinical interest (ECIs) if they occur after 
dosing, and must be reported by the site when it becomes aware of the ECI: 
• ALT or AST > 8 x the upper limit of normal (ULN), confirmed by repeat testing 
• ALT or AST > 5 x ULN for more than 2 weeks if new compared to Baseline, 
confirmed by repeat testing 
• ALT or AST > 3 x ULN and total bilirubin >2 x ULN if new compared to Baseline, 
confirmed by repeat testing 
• ALT or AST > 3 x ULN, confirmed by repeat test, with the appearance of fatigue, 
nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or 
eosinophilia (> 5%) 
 
 
 


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Clinical Protocol Number SCY-078-307b 
 
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17 January 2022 
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Revisions to Protocol dated 03 September 2021 (Protocol Version 1.0) 
Current Version and Date: Protocol Amendment 1 (Protocol Version 2.0) dated 12 October 2021. 
Protocol Section 
Change and Rationale 
Section 4. Revision History 
This section is added to track revisions to the protocol.  Numbering of 
sections changed throughout. 
Section 6 Protocol Synopsis 
Section 7 Schematic of Study Design 
Section 9 Study Objectives 
Section 10 Study Endpoints 
Section 11.1 Study Visits 
Section 11.2 Study Assessments 
Section 15.12 Quality of Life 
Questionnaire 
Section 19.6.1 Efficacy Analysis 
 
 
Add text that the Quality of Life Questionnaire will be completed at 
Baseline, TOC and Follow-up visits to sections where it was previously 
omitted. 
 
Section 12.2 Inclusion Criteria 
Add text to clarify the pregnancy prevention requirements as part of 
Inclusion Criteria 
“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.” 
 

SAP_001.pdf: 
SCYNEXIS, Inc.  
 
Protocol No. SCY-078-307b 
Statistical Analysis Plan 
Confidential  
Page 1 of 23  
v 1.0: 11 SEP 2023 
 
 
Statistical Analysis Plan 
 
Study Protocol Number: SCY-078-307b 
Study Title: 
 Oral Ibrexafungerp for the Treatment of Complicated Vulvovaginal Candidiasis 
(VVC) in Subjects who have failed Fluconazole Therapy 
NCT05399641 
 
Study Sponsor: 
SCYNEXIS, Inc. 
1 Evertrust Plaza, 13th Floor 
Jersey City, NJ 07302, USA 
 
 
 
 
 
 
 
 
 
 
 
 


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v 1.0: 11 SEP 2023 
 
 
Table of Contents 
1. 
Signature Page ......................................................................................................................... 4 
2. 
Abbreviations........................................................................................................................... 4 
3. 
Introduction ............................................................................................................................. 6 
4. 
Objectives and Endpoints ........................................................................................................ 6 
4.1. 
Objectives ......................................................................................................................................... 6 
4.1.1. 
Primary Objectives .................................................................................................................... 6 
4.1.2. 
Secondary Objectives ................................................................................................................ 6 
4.1.3. 
Exploratory Objectives .............................................................................................................. 6 
4.2. 
Endpoints .......................................................................................................................................... 7 
4.2.1. 
Primary Endpoints ..................................................................................................................... 7 
4.2.2. 
Secondary Endpoints ................................................................................................................. 7 
5. 
Study Design............................................................................................................................ 8 
5.1. 
Study Design Overview .................................................................................................................... 8 
5.2. 
Study Schedule.................................................................................................................................. 8 
5.3. 
Randomization and Blinding ............................................................................................................ 8 
5.4. 
Sample Size ....................................................................................................................................... 8 
6. 
Statistical Analyses .................................................................................................................. 8 
6.1. 
General Considerations ..................................................................................................................... 8 
6.1.1. 
Baseline and Change from Baseline Definition ........................................................................ 9 
6.1.2. 
Missing Data Handling .............................................................................................................. 9 
6.2. 
Analysis Populations ....................................................................................................................... 10 
6.3. 
Demographics and Study Summary................................................................................................ 11 
6.3.1. 
Patient Disposition ................................................................................................................... 11 
6.3.2. 
Eligibility and Protocol Deviations ......................................................................................... 11 


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6.3.3. 
Demographics and Baseline Characteristics ............................................................................ 11 
6.3.4. 
Medical History ....................................................................................................................... 12 
6.3.5. 
Prior and Concomitant Medications ........................................................................................ 12 
6.3.6. 
Study Drug Administration ..................................................................................................... 12 
6.4. 
Efficacy Analyses Cycle 1 .............................................................................................................. 13 
6.4.1. 
Primary Efficacy Analysis ....................................................................................................... 13 
6.4.2. 
Secondary Efficacy Analyses .................................................................................................. 14 
6.4.3. 
Exploratory Efficacy Analyses ................................................................................................ 15 
6.5 Treatment Cycle 2 ............................................................................................................................... 16 
6.5.1. 
Efficacy Analysis (Treatment Cycle 2) ................................................................................... 16 
6.6. Safety Analyses .................................................................................................................................. 16 
6.6.1. 
Adverse Events ........................................................................................................................ 16 
6.6.2. 
Clinical Laboratory Assessments ............................................................................................ 17 
6.6.3. 
Physical Examinations and Clinical Assessment of Signs and Symptoms ............................. 18 
6.7. 
Patient Profile.................................................................................................................................. 18 
7. 
APPENDIX 1: VULVOVAGINAL SIGNS AND SYMPTOMS SCALE ........................... 19 
8. 
APPENDIX 2: QUALITY OF LIFE ..................................................................................... 20 
8.1. 
SECTION 1 ..................................................................................................................................... 20 
8.2. 
SECTION 2 ..................................................................................................................................... 23 
 
 
 


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1. Signature Page 
Authors 
The undersigned have reviewed and approved the statistical analysis plan and find the document to be 
consistent with the requirements of the Protocol. 
 
 
 
 
 
 
 
Date 
 
 
Approval 
The undersigned have reviewed and approved the statistical analysis plan and find the document to be 
consistent with the requirements of the Protocol. 
 
 
 
 
 
President & Chief Executive Officer 
SCYNEXIS, Inc. 
 
Date 
 
 
 
 
 
 
 
 
2. Abbreviations 
Abbreviation 
Definition 
AE 
Adverse event 
ATC 
Anatomical Therapeutic Class 


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Abbreviation 
Definition 
BID 
Twice a Day 
BMI 
Body Mass Index 
CRF 
Case report form 
EOT 
End of therapy 
FU 
Follow Up 
HIV 
Human immunodeficiency virus 
ITT 
Intent-to-Treat 
MedDRA 
Medical Dictionary for Regulatory Activities 
MITT 
Modified Intent-to-Treat 
PP 
Per-Protocol 
PT 
Preferred term 
QOL 
Quality of Life 
SAP 
Statistical analysis plan 
SAE 
Serious adverse event 
SD 
Standard deviation 
SOC 
System organ class 
TEAE 
Treatment-emergent adverse event 
TFLs 
Tables, figures, and listings 
TOC 
Test of Cure 
VVC 
VSS 
Complicated Vulvovaginal Candidiasis 
Vulvovaginal Signs and Symptoms Scale 
WHODrug 
World Health Organization Drug Enhanced Dictionary 
 
 
 
 
 
 


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3. Introduction 
The purpose of this statistical analysis plan (SAP) is to describe the procedures and statistical 
methodologies that will be used in the analysis and reporting of results for SCYNEXIS, Inc. Protocol SCY-
078-307b. 
This document is prepared based on the following documents: 
• the study protocol version 3.0 dated 17 January 2022. 
• the case report form (CRF) version 1.2 dated 9 September 2022. 
Readers are referred to the final study protocol, the CRF, and CRF completion guidelines for details of the 
study design, conduct and data collection. This SAP must be finalized prior to the locking of the clinical 
database for this study. The mock tables, figures, and patient data listings (TFLs) are provided in a separate 
document. 
4. Objectives and Endpoints 
4.1. Objectives 
4.1.1. 
Primary Objectives 
• To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on clinical cure.  
4.1.2. 
Secondary Objectives 
• To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on mycological and clinical outcomes.  
• To evaluate the safety and tolerability of oral ibrexafungerp in subjects with complicated VVC who 
failed fluconazole therapy.  
4.1.3. 
Exploratory Objectives 
• To evaluate the efficacy of oral ibrexafungerp in subjects with complicated VVC who failed 
fluconazole therapy, based on QOL outcomes.  


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4.2. Endpoints 
4.2.1. 
Primary Endpoints 
• Efficacy as measured by the percentage of subjects with clinical cure (total composite score of 0 on 
the VSS Scale (refer to Appendix 1) with no additional antifungal therapy required based on 
investigator’s judgment) at the TOC visit.  
4.2.2. 
Secondary Endpoints 
Efficacy as measured by:  
• The percentage of subjects with clinical improvement:  
o Total composite score of 2 on the VSS scale at the TOC and FU visits  
o Total composite score of 1 on the VSS scale at the TOC and FU visits.  
• The percentage of subjects with total composite score equal or less than 2 and equal or less than 1 
on the VSS scale at the TOC and FU visits. 
• The percentage of subjects with clinical success (at least 50% reduction from baseline in the total 
composite VSS score) with no additional antifungal therapy required based on investigator’s 
judgment) at the TOC and FU visits.  
• The percentage of subjects with mycological response (defined as a negative culture for growth of 
Candida spp. or subject is asymptomatic, therefore culture not done) at the TOC and FU visits.  
• The percentage of subjects with both clinical cure and mycological response at the TOC and FU 
visits.  
• The percentage of subjects with clinical cure at the FU visits.  
• The absolute change in total composite VSS score from baseline to the TOC and FU visits.  
Exploratory Endpoints:  
• Absolute improvement in QOL outcomes at TOC and FU visits compared to baseline as measured 
by QOL survey.  
• Subjects whose signs and symptoms have resolved enough that additional antifungal treatment was 
not required based on clinical judgement.  
• Time to resolution of symptoms.  
Safety and Tolerability as measured by:  
Adverse events (AEs), vital signs, treatment discontinuation, and safety laboratory tests. 


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5. Study Design 
5.1. Study Design Overview 
This study is a Phase 3b, open-label, multicenter study to evaluate the efficacy and safety of oral 
ibrexafungerp in the treatment of subjects with complicated VVC episodes in subjects: 
• not responsive to, or 
• have isolates anticipated not to respond to, or 
• who are refractory to or intolerant of fluconazole. 
The susceptibility of historical isolates will be collected if available. 
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. 
5.2. Study Schedule 
The scheduled assessments will be carried out as described in Section 15 of the study protocol. 
5.3. Randomization and Blinding 
This is an open-label study. Subjects will be randomized to treatment, stratified by group based on the 
Candida species and presence or absence of underlying medical conditions. 
5.4. Sample Size 
This is an exploratory study, and no formal sample size calculation was performed. Approximately 150 
subjects will be enrolled in allocation 50:50:50 in respect of 1, 3 and 7 days of treatment. Subjects will be 
randomized to treatment, stratified by group based on the Candida species and presence or absence of 
underlying conditions. The sample size of 150 is estimated to be adequate to perform an initial assessment 
of efficacy. 
6. Statistical Analyses 
6.1. General Considerations 
 


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Analytical Plan 
 
All statistical processing will be performed using SAS® version 9.3 or later, unless otherwise stated. All 
statistical tests will be two-sided and interpreted at a 5% significance level. 
The study is not powered for formal statistical comparisons. Descriptive statistics (i.e., mean, standard 
deviation, median, minimum, maximum, etc.) will be provided for all continuous variables; frequencies 
and percentages will be tabulated for incidence and categorical variables. For parameters measured over 
time, observed values and changes from baseline will be described for each time point. 
The clinical cure and mycological eradication rates will be described by baseline Candida species, when 
the number of isolates per species allows. 
All analyses will be presented by treatment group. Unless otherwise stated, data will be analyzed as it is 
with no imputation. No adjustment for multiplicity will be employed. 
This Statistical Analysis Plan (SAP) will describe all statistical analyses in detail. The SAP will be 
finalized prior to database lock. 
6.1.1. 
Baseline and Change from Baseline Definition 
Baseline is defined as the last assessment prior to the first dose of study drug. If time and date are 
available, then the baseline assessment could be on the same day as first dose so long as it's before the time 
of first dose. If time is not available, the date prior to first dose will need to be used. Change from baseline 
is defined as: non-missing post- baseline value – baseline value. Baseline values will be re-calculated in 
Cycle 2 for QOL scale, VVS composite score, physical examinations, lab results and vital signs. If above 
baseline value is not available in Cycle 2, then use the last available value in Cycle 1 as baseline for Cycle 
2. 
6.1.2. 
Missing Data Handling 
No imputation of missing data will be performed unless otherwise specified. 
The following rules will be used to impute partial dates for AE or concomitant medications: 
• Partial start dates:  
o If only the day of the month is missing:  
The onset date will be set to the first day of the month unless the month is the same as the 
first dose, where the onset date will be set to the date of the first dose date. However, if this 


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imputation leads to an onset date later than the end date of the event, the start date will still 
be set as the first day of the month. 
o If both the day and month are missing: 
The day and month will be assumed to be January 1 of the year, unless the event occurred in 
the same year as the first dose, where the start date will be set to the day of the first dose. 
However, if this imputation leads to an onset date later than the end date of the event, the 
start date will still be set as January 1 of the year. 
o If the start date is completely missing: 
The missing start date will be set to the date of the first dose. However, if this imputation 
leads to an onset date later than the end date of the event, the start date will be set to the first 
day of the month/year of the end date.  
• Partial end dates: 
o If only the day is missing: the end date will be set to the last day of the month or the last 
follow-up date whichever earlier. 
o If both the day and the month are missing: the end date will be set to December 31 or the 
last follow-up date whichever earlier. 
o If the end date is completely missing: no imputation will be implemented. 
6.2. Analysis Populations 
The study populations to be used in the analyses are defined as follows: 
Intent-to-Treat (ITT) Population: All ibrexafungerp-treated subjects. 
Modified Intent-to-Treat (MITT) Population: All treated subjects who have a positive culture for 
Candida species at Screening. 
Per-Protocol (PP) Population: All MITT subjects who have completed the study drug treatment, who did 
not have major protocol deviations likely to affect study efficacy AND who have a TOC evaluation. 
Safety Population: All enrolled subjects who received at least one dose of study drug. 


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6.3.  Demographics and Study Summary 
6.3.1. 
Patient Disposition 
The number of subjects enrolled, number completing the study, and reasons for discontinuation will be 
summarized by treatment group and by cycle.  
6.3.2. 
Eligibility and Protocol Deviations 
Eligibility status based upon meeting protocol entrance criteria (ex: resistant/intolerant/prophylaxis 
failures, etc.) and protocol deviations will be listed by subject. Protocol deviations recorded will be 
reviewed and major deviations will be identified prior to database lock. The PP population will be 
determined and subjects with major protocol violations, entry criteria violations or missing visits will be 
excluded. 
6.3.3. 
Demographics and Baseline Characteristics 
Demographic/baseline characteristics collected at the Screening/Day 1 visit will be summarized and 
presented for each treatment group. Descriptive statistics will be presented for the continuous variables.  
Frequency counts and percentages will be presented for the categorical variables for each category.  The 
following variables will be presented: 
• Demographic characteristics (Screening) 
• Age (years) 
• Sex (male, female) 
• Race  
• Ethnicity 
• Height (cm) 
• Weight (kg) 
• BMI (kg/m2) 
• Vulvovaginal Examination (Screening) 
• QOL questionnaire (Day 1) 
• Fertility Status 


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o Surgically Sterile / Infertile 
o Post-Menopausal  
o Potentially Able to Bear Children 
• Method of Birth Control 
o Oral Contraceptives  
o Depo Contraceptives (Implants / Injectables) 
6.3.4. 
Medical History 
Medical history terms will be coded using the Medical Dictionary for Regulatory Activities (MedDRA 
26.0) dictionary. All the medical history will be summarized by system organ class (SOC) term and 
preferred term for each cohort by treatment group. For subjects with the same SOC and preferred term 
occurring more than once, the first occurrence will be tabulated. Medical history events will be sorted 
alphabetically by SOC and within each SOC, the PT will be presented by decreasing order of total 
frequencies. 
Conditions will be listed, including the verbatim investigator description of the relevant medical condition, 
the coded terms (SOC, preferred term), start date, end date, and whether the condition is ongoing.   
6.3.5. 
Prior and Concomitant Medications 
Prior medications are defined as any medication started and discontinued prior to the first dose of study 
treatment. Concomitant medications are defined as any medication taken on or after the first dose of study 
treatment, including those who started prior to the date of the first dose of study treatment and continued 
past that date. See section 7.1.3 for handling of completely or partially missing dates for prior and 
concomitant medications. 
6.3.6. 
Study Drug Administration 
Treatment Cycle 1: All randomized subjects 
Subjects who meet all the inclusion and none of the exclusion criteria will be randomized to treatment and 
stratified into 2 groups based on the Candida species and presence or absence of underlying conditions. 
Subjects will receive open-label oral ibrexafungerp 300 mg BID for one, three or seven consecutive days 
per TABLE 1: 


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Table 1: Ibrexafungerp Treatment Groups 
Treatment 
Group 
Criteria 
Ibrexafungerp Dose  
Randomization and Stratification 
Group A 
Subjects without underlying 
medical conditions AND 
known to have isolates other 
than C glabrata, C krusei, C 
auris 
1 Day dosing (300mg AM and 300mg PM) 
N = 50 
Group B 
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 
3 Days or 7 Days dosing (300mg AM and 300mg PM) 
Randomized 1:1 N = 50:50 
6.4. Efficacy Analyses Cycle 1 
The efficacy analyses will be conducted using the MITT (primary analysis population), ITT and PP 
populations to evaluate ibrexafungerp. Efficacy outcomes will be presented by treatment group in Cycle 1.    
6.4.1. 
Primary Efficacy Analysis 
6.4.1.1. 
Definition of Primary Endpoint 
The primary efficacy endpoint is measured by the percentage of subjects with clinical cure (total composite 
score of 0 on the VSS Scale with no additional antifungal therapy required based on investigator’s 
judgment) at the TOC visit. 
6.4.1.2. 
Main Analysis Approach 
Clopper-Pearson method will be used to summarize 95% CI of proportion of clinical cure for group A and 
group B separately. Pairwise treatment comparison of subjects in group B 3 days vs. subjects in group B 7 
days will be performed to test primary efficacy endpoint (clinical cure at TOC visit) using a Fisher’s Exact 


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test; p-values and 95% confidence intervals for odds ratio will be presented. The primary endpoint will also 
be analyzed of subjects in group B 3 days vs. subjects in group B 7 days using a Cochran-Mantel-Haenszel 
row mean scores test stratified by site.  
VSS scores at Baseline, TOC, and FU will be summarized for each sign and symptom using frequency 
counts and percentages. 
Summary statistics will be provided for the total VSS composite score (observed value and change from 
baseline). Student’s t-test will be used for pairwise treatment comparison of subjects in group B 3 days vs. 
subjects in group B 7 days; p-values and 95% confidence intervals will be presented for the differences 
between treatment groups. 
6.4.2. 
Secondary Efficacy Analyses 
6.4.2.1. 
Definition of Secondary Endpoint 
The following treatment outcome definitions will be used for the assessment of efficacy relative to 
baseline: Clinical Outcome. 
• Clinical Cure: Complete resolution of signs and symptoms with total composite score of 0 on the VSS 
Scale and with no additional antifungal therapy required based on investigator’s judgment. 
• Clinical Improvement: Partial resolution of signs and symptoms with total composite score of 1 or 2 on 
the VSS Scale and with no additional antifungal therapy required based on investigator’s judgement.  
• Clinical Success: At least 50% reduction from Baseline in the total composite VSS score with no 
additional antifungal therapy required based on investigator’s judgment . 
• Clinical Failure: Persistence and/or worsening of signs and symptoms or need for additional antifungal 
therapy (this definition also applies to cycle 2 patients). 
The following mycological outcome definitions will be used for the assessment of subjects with 
mycological response. 
• Mycological Eradication: Negative culture for growth of Candida species . 
• Presumed Eradication: Subject is asymptomatic, therefore cultures not done . 
• Mycological Persistence: Positive culture for growth of Candida species. 


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6.4.2.2. 
Main Analysis Approach 
Frequency and percentage of subjects with total composite score equal or less than 2 on the VSS scale at 
the TOC and FU visits, and total composite score equal or less than 1 on the VSS scale at the TOC and FU 
visits will be summarized. 
Frequency and percentage of subjects with clinical improvement, clinical success, mycological response, 
with both clinical cure and mycological response at TOC and FU visit, with clinical cure at FU visit will be 
summarized.  
The value and absolute change in total composite VSS score from baseline to the TOC and FU visits will 
be summarized with descriptive statistics. 
6.4.3. 
Exploratory Efficacy Analyses 
6.4.3.1. 
Definition of Exploratory Endpoints 
The Quality-of-Life Questionnaire (QOL) used was developed by SCYNEXIS to measure the absolute 
change from Baseline in 6 VVC symptoms. Each symptom was measured on a 10-point visual analog scale 
(0 being None and 10 being Extreme) from patient recall over the preceding week.  In addition, two 
questions were included on Patient Global Impression of Change (PGIC) to measure changes in overall 
health and overall sexual satisfaction since study start. Ratings were on a scale of 1 (Very much improved) 
to 7 (Very much worse). 
Time to resolution of symptom is defined as the time from initiation of study treatment until resolution of 
the symptom, which is measured by VSS score = 0. The data will be collected from initiation of study 
treatment to last FU visit in Cycle 1 and Cycle 2 separately. Time to resolution of any symptom and time to 
resolution of all symptoms will be summarized by treatment for subjects in MITT, ITT and PP population. 
6.4.3.2. 
Main Analysis Approach 
The value and absolute change in QOL score from baseline to the TOC and FU visits will be summarized 
with descriptive statistics for each symptom by visit. The value and absolute change of mean score of QOL 
questions (excluding PGIC) from baseline to the TOC and FU visits will be summarized with descriptive 
statistics by visit. Proportion and 95% CI of each category will be summarized using Clopper-Pearson 
method for 2 PGIC questions by visit. 


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Time to resolution of signs and symptoms after initiation of study drug will be analyzed using Kaplan-
Meier methods. Median survival time at which half of the subjects had reached resolution of symptoms and 
its 95% CI will be reported using Brookmeyer-Crowley method. Pairwise treatment comparisons of 
subjects in group B 3 days vs. subjects in group B 7 days will be performed using log-rank test. 
6.4.3.3. 
Additional Estimates 
For the subgroup analyses by Candida species, only descriptive statistics will be provided; no statistical 
testing will be performed due to possible small sample size. 
All other efficacy data will be summarized, but not subject to formal statistical analysis. 
6.5 Treatment Cycle 2 
A second treatment cycle will be allowed for subjects who did not achieve sufficient clinical improvement 
(e.g. VSS remains ≥3) on the randomized treatment (Cycle 1) as evaluated at the TOC and FU visits. A 
second treatment cycle will also be allowed for subjects with clinical cure/improvement/success who 
experience a recurrence before the last FU visit. During Cycle 2, subjects may receive additional treatment 
with ibrexafungerp for a period up to 14 days as recommended by the investigator and following 
discussion with the sponsor. 
6.5.1. 
Efficacy Analysis (Treatment Cycle 2) 
The proportion of Cycle 2 subjects enrolled in MITT, ITT and PP populations will be summarized in each 
table. 
Secondary, and exploratory efficacy analysis will be analyzed the same as for cycle 1. 
6.6. Safety Analyses 
6.6.1. 
Adverse Events 
A Treatment-emergent adverse event (TEAE) is defined as any AE that occurs on or after the start time of 
the study drug administration. AEs will be coded using the MedDRA 26.0 dictionary.  
A summary of TEAEs will be presented as the number and percentage of subjects with at least one of the 
following: 
• Any AE 
• Any TEAE 


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• Treatment-related TEAE 
• Serious TEAE 
• Treatment-related serious TEAE 
• TEAE leading to study drug withdrawal 
• TEAE leading to death 
TEAEs will be summarized by SOC and preferred term for each treatment group. For subjects with the 
same SOC and preferred term occurring more than once, the first occurrence will be tabulated. TEAEs will 
also be presented for each preferred term by maximum severity, by highest relationship to study drug, and 
for serious AEs. In the overall summary, additionally, the number and percentage of patients with at least 
one severe TEAE, with at least one moderate TEAE but no severe TEAE and with only mild TEAEs will 
be provided. 
6.6.2. 
Clinical Laboratory Assessments 
Laboratory data will be presented as per the international system of units, universally abbreviated as SI 
(from the French ‘system international’). 
Hematology and blood chemistry will be summarized using descriptive statistics by treatment group and 
visit. Change from baseline values will be summarized similarly by treatment group for each post-baseline 
scheduled visit. Number and percentage of subjects with urine pregnancy test will be provided by treatment 
group and visit. 
Shift tables from baseline to post-baseline for hematology and blood chemistry assessment, describing 
shifts to abnormality (low, normal, or high), will be provided. The number of subjects with a non-missing 
result at both baseline and a specific post-baseline scheduled visit will be used as denominator for that 
post-baseline scheduled visit. 
Separate listings of all hematology, blood chemistry and urine pregnancy data will be provided. In 
addition, separate listings for hematology, blood chemistry, and urine pregnancy data will be provided for 
each parameter where a subject had at least one abnormal result. 
All laboratory tests required at screening and/or baseline only will be listed. 


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6.6.3. 
Physical Examinations and Clinical Assessment of Signs and Symptoms 
Physical Examination will be presented in a subject listing, with abnormal values flagged and abnormal 
description listed if any. Clinical assessment of signs and symptoms at each visit will be summarized and 
listed by subject. 
6.7. Patient Profile 
Patient profile will be provided for all subjects. Please refer to the separate patient profile sample 
document. 
 
 


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7. APPENDIX 1: VULVOVAGINAL SIGNS AND SYMPTOMS SCALE 
 
 
 
 


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8. APPENDIX 2: QUALITY OF LIFE 
8.1. SECTION 1 
The following questions ask about your VVC symptoms and their impact on your overall 
wellness. Please indicate with a cross on the line below how you would rate your symptoms over 
the past 7 days. 
 
 
1. How would you rate your vaginal itching over the past 7 days? 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
 
No vaginal 
itching 
Extreme 
vaginal itching 
 
 
 
 
2. How would you rate your vaginal burning over the past 7 days? 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
No vaginal 
burning 
Extreme vaginal 
burning 
 
 
 
 
3. How would you rate your vaginal irritation over the past 7 days? 


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0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
No vaginal 
irritation 
Extreme vaginal 
irritation 
 
 
 
 
4. How would you rate your vaginal discharge over the past 7 days? 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
No vaginal 
discharge 
Extreme vaginal 
discharge 
 
 
 
 
5. How would you rate your pain or discomfort during urination over the past 7 days? 
 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
No pain or 
discomfort 
Extreme pain or 
discomfort 
 
 
 
 
 
6. How would you rate your pain or discomfort during sexual intercourse over the last 7 
days? 


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0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10  
∆ 
Not Applicable (N/A) 
 
No pain or 
discomfort 
Extreme pain or 
discomfort 
 
 
 
 
7. To what extent have your VVC symptoms affected your willingness to engage in sexual 
intercourse over the last 7 days? 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
 
∆ 
Not Applicable (N/A) 


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Not affected 
Extremely affected 
 
 
 
8. To what extent have your VVC symptoms affected your overall 
mood; for example, feeling anxious and/or depressed over the last 7 
days? 
 
 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
 
Not affected 
Extremely affected 
 
 
 
 
 
 
8.2. SECTION 2 
The following questions ask about changes in your life related to your VVC 
symptoms since beginning this study. Please check the box next the number that 
best describes your experience. 
 
 
9. Since beginning this study, how would you describe the change in your 
overall sexual satisfaction related to your VVC?