Clinical trial NCT04553068
Conditions: Sexually Transmitted Diseases Gonorrhea Chlamydia
Sponsor: Evofem Inc.
Start date: 2020-10-15; Completion date: 2022-07-28
Enrollment: 1892 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study will evaluate whether EVO100 vaginal gel prevents the sexual transmission of CT and GC infection

Detailed description:
In this phase 3 double blind placebo controlled, efficacy study, women who have had a urogenital chlamydia or gonorrhea infection at any time over the 16 weeks preceding the enrollment Visit with one or more risk factors, or found to be positive for either infection at Screening Visit with one or more risk factors will be enrolled. After a screening period of up to 35 days, women will be randomized to receive either EVO100 vaginal gel or placebo. Each woman will participate in the study until she has completed 16 weeks of study medication or observation or tests positive for CT or GC infection.

Arms: arm 1: EVO100 vaginal gel, 5 g arm 2: Placebo vaginal gel, 5 g
Interventions: intervention 1: EVO100 intervention 2: Placebo
Intervention descriptions: intervention 1: EVO100 vaginal gel intervention 2: Placebo vaginal gel

Protocol documents:
Prot_000.pdf: 
Protocol: EVO100-311 
EVO100 vaginal gel 
Evofem, Inc. 06 July 2020 
CONFIDENTIAL AND PROPRIETARY 
Page 1 
PROTOCOL SYNOPSIS 
TITLE OF CLINICAL TRIAL: 
Phase 3 double-blind placebo-controlled efficacy trial of EVO100 vaginal gel for the 
prevention of urogenital Chlamydia trachomatis and Neisseria gonorrhea infection 
INVESTIGATIONAL PRODUCT(S): 
After a screening period of up to 35 days, women will be randomized to receive either EVO100 
or placebo: 
EVO100 vaginal gel (previously known as Amphora) is supplied in individually wrapped 5 g 
single-dose, pre-filled vaginal applicators. EVO100 is a viscous, off white to tan gel of uniform 
consistency. Its active ingredients are lactic acid United States Pharmacopeia (USP), citric acid 
USP, and potassium bitartrate USP.  
Universal placebo gel (UPG) is an isotonic non-buffering gel, containing 2.7% 
hydroxyethylcellulose, sorbic acid, sodium hydroxide, sodium chloride, and purified water and 
supplied in individually wrapped 5 g single-dose, pre-filled vaginal applicators. 
CLINICAL PHASE: Phase 3 
CLINICAL TRIAL OBJECTIVES: 
Primary Objective: 

To evaluate the efficacy of EVO100 vaginal gel in the prevention of urogenital
Chlamydia trachomatis (CT) and Neisseria gonorrhea (GC) infection
Secondary Objectives: 

To assess impact of EVO100 vaginal gel on overall sexual satisfaction and overall
product satisfaction over the course of the clinical study

To evaluate the safety of EVO100
Exploratory Objectives: 

To determine the impact of EVO100 vaginal gel use rate (subject adherence to
instructed use) on the efficacy in the combined infections

To assess other subject satisfaction with EVO100 vaginal gel over the course of the
clinical study
OUTCOME MEASURES: 
Primary: 

A composite endpoint, defined as a comparison between the proportion of subjects who
are defined study successes vs study failures among the intervention groups (EVO100
or placebo) with success defined as subjects completing the trial to Visit 5 without any
CT or GC infection.
Secondary: 
The secondary outcomes for this study will be assessing the following proportion of subjects: 

with overall sexual satisfaction using the female sexual function index (FSFI) overall sexual


Protocol: EVO100-311 
EVO100 vaginal gel 
Evofem, Inc.06 July 2020 
CONFIDENTIAL AND PROPRIETARY 
Page 2 
satisfaction question at Visit 5 and not having a CT or GC infection 

with overall sexual satisfaction using the FSFI overall sexual satisfaction question at visit 5

reporting overall product satisfaction at Visit 5

Incidence of adverse events (AEs) (descriptive analysis)
Exploratory: 
Exploratory assessments include: 

Comparison of compliance with EVO100 vaginal gel usage vs placebo usage during
study (rate of product use adherence vs placebo)

Subgroup analyses of the primary endpoint (the proportion of subjects who are deemed
success vs failure) will be performed for the following:
o
Subjects with 0%, >0% and <20%, ≥20%, ≥40%, ≥60%, ≥80% and 100%
product use adherence

Descriptive analysis of failure components defined as failures for the primary endpoint

Comparison of PROMIS SexFS Satisfaction, Pain and Lubrication subscales with
EVO100 vaginal gel usage vs placebo

Comparison of FSFI Lubrication and Pain subscales with EVO100 vaginal gel usage vs
placebo

Comparison of Patient Global Impression of Change (PGIC) with EVO100 vaginal gel
usage vs placebo
CLINICAL TRIAL DESIGN: 
This is a Phase 3, double-blind, placebo-controlled study in approximately 90 sites in the 
United States (US) and European Union (EU) over approximately 16 weeks of use in women 
age ≥13 years who are at risk of urogenital CT or GC infection. 
TREATMENT DURATION: 
After a screening period of up to 35 days, women will be randomized to receive either EVO100 
or placebo. Each woman will participate in the study until she has completed 16 weeks of 
treatment or observation or tests positive for CT or GC infection. This will include women who 
discontinue treatment but continue other study assessments to Visit 5. The intervention period 
is defined as Visits 1 to 5. There will be a follow-up visit (Visit 6) 4 weeks after the last 
intervention visit. Visits 5 and 6 will be combined for subjects who discontinue the study early. 
These periods are outlined in the Schedule of Assessments (Table 1). The protocol-defined 
period of observation is 20 weeks. 
SAMPLE SIZE: 
Assuming a two-sided alpha of 0.05, the failure rate for control subjects to be 32.5%, and the 
failure rate for the treatment subjects to be 25.5%, a sample of 881 subjects per treatment arm 
is needed (1762 subjects overall) to achieve 90% power. Anticipating approximately 5% of 
subjects will have non-negative CT/GC results in enrollment based on the Phase 2B/3 study 
data, this yields a sample size of 1856 women. 


Protocol: EVO100-311 
EVO100 vaginal gel 
Evofem, Inc. 06 July 2020 
CONFIDENTIAL AND PROPRIETARY 
Page 3 
ANALYSIS POPULATION: 
This study will utilize three analysis populations: Intention-to-treat (ITT), modified 
Intention-to-treat (mITT), and safety. The ITT population will consist of all randomized 
subjects. The mITT population will be the analysis population for the primary endpoint and 
will consist of all randomized subjects who are negative for chlamydia and gonorrhea at 
enrollment and are provided with study product. Lastly, the safety population will be based on 
subjects with documented use of any study product. Analyses using the ITT and mITT 
populations will be performed based on the treatment randomized. Meanwhile, safety analyses 
will be based on the treatment received. 
STUDY POPULATION: 
Study Sites: 
The study will be conducted at up to 90 clinical sites in the US and/or EU. Subjects will be 
selected for the study according to the eligibility criteria detailed below. 
Inclusion Criteria: 
1. Subjects must meet both of the following criteria:
a. Healthy female subjects at least 13 years of age with a urogenital CT and/or GC
infection (documented in a retrievable medical record) within the 16 weeks prior to
enrollment and one or more of the additional risk factors included in point ii below:
i.
Acceptable documentation will include:
1.
Laboratory report(s) confirming CT and/or GC infection
2.
Copy of clinic note from the date of diagnosis confirming CT and/or GC
infection and indicating the date of diagnosis and/or date of treatment
3.
Evidence of dispensed medication (from pharmacy records or clinic notes)
for antibiotic therapy used for treatment of CT and/or GC
ii.
PLUS one or more of the following additional risk factor(s):
1.
13 to 24 years of age at the screening visit
2.
New sex partner within the past 12 weeks (84 days)
3.
More than one current sex partner
4.
Knowledge that current sex partner has multiple partners
5.
Partner with known sexually transmitted infection (STI)
6.
Inconsistent condom use among persons who are not in a mutually
monogamous relationship
b. If medical record of previous infection cannot be obtained within two weeks of
screening date, following three documented attempts to obtain the medical records,
subjects may be enrolled only if they have two or more of the following risk factors,
in addition to self-reported history of infection within 16 weeks prior to enrollment:
i.
13 to 24 years of age at the screening visit
ii.
New sex partner within the past 12 weeks (84 days)
iii.
More than one current sex partner
iv.
Knowledge that current sex partner has multiple partners
v.
Partner with known STI
vi.
Inconsistent condom use among persons who are not in a mutually
monogamous relationship


Protocol: EVO100-311 
EVO100 vaginal gel 
Evofem, Inc. 06 July 2020 
CONFIDENTIAL AND PROPRIETARY 
Page 4 
2. Ability to understand the consent process and procedures. For minors, the ability to
obtain consent from parents/legal guardian and assent by minor subjects as applicable
according to local regulations.
3. Agree to be available for all study visits including Visit 5 and follow-up Visit 6 and
comply with follow-up on staff appointment reminders
4. Negative pregnancy test
5. Negative CT and GC nucleic acid amplification test (NAAT) at screening or positive
CT or GC NAAT and receives standard of care (SOC according to CDC or World
Health Organization [WHO] guidelines) treatment prior to enrollment with subsequent
negative CT and GC NAAT testing at enrollment visit
6. Agree to use a woman-controlled method of contraception that is not directly delivered
to the vaginal mucosa (with the exception of a vaginal ring) throughout the duration of
the study, such as oral contraceptives, birth control implants, intrauterine devices
(IUDs), or tubal ligation. Condom use only is not an acceptable form of contraception
for this study
7. Able and willing to comply with all study procedures, including the use of eDiaries and
reporting of all Adverse Events and concomitant medications.
8. Reports vaginal sexual intercourse with a male partner at least three times per month in
the previous month and anticipates vaginal sexual intercourse regularly for the duration
of the study
9. Agree to abstain from douching or any form of vaginal suppository use (other than
investigational product) during course of study
Exclusion Criteria: 
1. Participation in any study with an investigational compound or device within 30 days
prior to signing informed consent.
2. Used Phexxi (lactic acid, citric acid, and potassium bitartrate) as a contraceptive
vaginal gel within 7 days prior to enrollment (may be enrolled at a later date if all other
criteria are met).
3. In the opinion of the Investigator, has a history of substance or alcohol abuse in the last
12 months
4. In the opinion of the Investigator, has issues, conditions, or concerns that may
compromise the safety of the subject, impact the subject’s compliance with the protocol
requirements, or confound the reliability of the data acquired
5. Is a close relative of or is an Evofem, approved contract research organization (CRO),
ICON, or clinical site employee regardless of direct involvement in research activities
6. Pregnant (or actively trying to become pregnant) or breastfeeding
7. Women who have undergone a total hysterectomy (had uterus and cervix removed).
However, women with subtotal hysterectomy with an intact cervix may be enrolled
8. Inability to provide informed consent or assent
9. Has a history or expectation of noncompliance with medications or intervention
protocol
10. Has engaged in sexual vaginal intercourse or douching, or used of any form of vaginal
suppository or intravaginal device (with the exception of contraceptive vaginal ring or
tampons) for 24 hours prior to enrollment (may be enrolled at a later date if all other
criteria are met)


Protocol: EVO100-311 
EVO100 vaginal gel 
Evofem, Inc. 6 July 2020 
CONFIDENTIAL AND PROPRIETARY 
Page 5 
11. Menstruating at enrollment (may be enrolled at a later date if all other criteria are met)
12. Is currently being treated, or has been treated, for a period of 21 days prior to
enrollment, with any antibiotics. Note: Subjects will not be discontinued from study
treatment post-randomization if treated with antibiotics for an infection other than CT
or GC.
13. In the opinion of the Investigator, has signs/symptoms that indicate persistence of CT
or GC infection diagnosed at screening, new interval infection, and/or a failure to
comply with or complete the prescribed treatment regimen following a positive
screening NAAT
14. Women who regularly use douches, vaginal medications, vaginal products, or
suppositories who do not agree to stop these products for the duration of the study
15. Women who are currently using contraceptive products that are directly delivered to the
vaginal mucosa (with the exception of contraceptive vaginal ring), such as diaphragms,
spermicides, or any vaginally applied or inserted products containing nonoxynol-9
(N-9) or Phexxi (lactic acid, citric acid and potassium bitartrate)
16. Vulnerable populations, including children <13 years of age, pregnant women,
prisoners, institutionalized persons, persons without decisional capacity, persons
without phone and/or without domicile (homeless).


Protocol: EVO100-311 
EVO100 vaginal gel 
Evofem, Inc. 06 July 2020 
CONFIDENTIAL AND PROPRIETARY 
Page 6 
Figure 1 
Schematic Flow of Study Design 
Abbreviations: CT = Chlamydia trachomatis, GC = Neisseria gonorrhea, NAAT = nucleic acid 
amplification test
Screening 
Visit 0 
Weeks -5 to 
0 
Informed Consent 
CT/GC NAAT 
CT/GC NAAT 
Results 
Positive 
Negative 
Standard of 
Care Treatment 
Enrollment 
Eligibility Criteria 
Visit 1: Assessments/Procedures/CT/GC NAAT 
Randomization 
Intervention 
Period 
Visits 1 to 5 
Weeks 0 to 
16 
EVO100 Gel 
N=928 
Placebo Gel 
N=928 
Visits 2 to 5 Assessments/Procedures 
Follow-up 
Visit 6 
Week 20 
Visit 6 Assessments/Procedures 

SAP_001.pdf: 
Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final V2.0, Date: 06APR2022 
Page 1 of 40 
 
 
Protocol Title: 
Phase 3 double-blind placebo-controlled efficacy trial of 
EVO100 vaginal gel for the prevention of urogenital Chlamydia 
trachomatis 
and 
Neisseria 
gonorrhoeae 
infection 
(EVOGUARD) 
Protocol Number: 
EVO100-311 
Protocol Version, Date 
Version 4.0, May 26, 2021 
Document Version, Date: 
Final Version 2.0, April 6, 2022 
 
 
 
 
 
Prepared by: 
Premier Research 
 
On behalf of: 
Evofem, Inc. 
 
 
Confidentiality statement: 
 
The information provided in this document is strictly confidential. 
 
The recipients of the SAP must not disclose the confidential information contained 
within this document or any related information to other persons without the 
permission of the sponsor. 
 
In addition, the recipients of the SAP must keep this confidential document in a 
controlled environment which prevents unauthorized access to the document. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final V2.0, Date: 06APR2022 
Page 2 of 40 
 
SIGNATURE PAGE 
 
 
 
 
 
 
 
 
8 EDT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
4 EDT 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2 PDT 
Prepared at Premier Research by: 
 
07-Apr-2022 | 10:33:
Samantha Nemeth, Senior Statistician 
Date 
(DD Mmm YYYY) 
Reviewed at Premier Research by: 
 
07-Apr-2022 | 11:17:
Clint Dart, VP Biostatistics and Programming 
Date 
(DD Mmm YYYY) 
Approved at Evofem, Inc. by: 
 
07-Apr-2022 | 08:32:0
Catherine Maher, VP Regulatory Affairs & PV 
Date 
(DD Mmm YYYY) 


Statistical Analysis Plan 
Protocol Number:: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 3 of 40 
 
 
 
REVISION HISTORY 
 
 
Version/Date 
Version name 
Section 
Changes implemented 
Final Version 1.0/ 
23-SEP-2020 
Initial 
approved 
version 
N/A 
Baseline version 
Final Version 2.0/ 
06-APR-2022 
Additional verbiage for duplicate patients, safety population 
defined 
using 
distributed/returned 
product, 
separate 
secondary endpoints of CT and GC Only, invalid status 
missing at Visit 5, EMA verbiage, subset analysis regarding 
documentation status, subset analysis by age group, visit 
flexibility for handling COVID-19 patients, GU TEAE 
description, additional subject adherence category, and Table 
of Contents for Data Displays 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 4 of 40 
 
TABLE OF CONTENTS 
SIGNATURE PAGE ..................................................................................................................... 2 
REVISION HISTORY .................................................................................................................. 3 
TABLE OF CONTENTS ............................................................................................................... 4 
LIST OF ABBREVIATIONS ........................................................................................................ 6 
1 INTRODUCTION ................................................................................................................... 7 
2 STUDY OBJECTIVES ............................................................................................................ 8 
2.1 Primary Objective ........................................................................................................... 8 
2.2 Secondary Objective(s) ................................................................................................... 8 
2.3 Exploratory Objective(s) ................................................................................................. 8 
3 STUDY DESIGN .................................................................................................................... 9 
3.1 General Study Design ..................................................................................................... 9 
3.2 Randomization and Blinding ........................................................................................ 11 
3.3 Study Treatments and Assessments .............................................................................. 11 
4 STUDY ENDPOINTS ........................................................................................................... 15 
4.1 Primary Endpoint .......................................................................................................... 15 
4.2 Secondary Endpoint ...................................................................................................... 15 
4.3 Exploratory Endpoints .................................................................................................. 15 
5 SAMPLE SIZE AND POWER .............................................................................................. 17 
6 ANALYSIS POPULATIONS ................................................................................................ 18 
6.1 Intention-To-Treat Population (ITT) ............................................................................ 18 
6.2 Modified Intention-To-Treat Population (mITT) ......................................................... 18 
6.3 Safety Population (Safety) ............................................................................................ 18 
6.4 Protocol Deviations/Violations and Exclusions from Analysis Sets ............................ 18 
6.5 Duplicate Patients ......................................................................................................... 18 
7 Statistical Considerations and analysis .................................................................................. 19 
7.1 Derived Variables ......................................................................................................... 19 
7.2 Handling of Missing Data and Outliers ........................................................................ 23 
7.2.1 Missing Data Analysis Methods ....................................................................... 23 
7.2.2 Handling of Missing or Incomplete Dates ........................................................ 23 
8 STATISTICAL METHODS .................................................................................................. 25 
8.1 General Statistical Conventions .................................................................................... 25 
8.2 Subject Disposition ....................................................................................................... 25 
8.3 Protocol Deviations ....................................................................................................... 25 
8.4 Demographics and Baseline Characteristics ................................................................. 26 
8.4.1 Demographics ................................................................................................... 26 
8.4.2 Baseline and Disease Characteristics ................................................................ 26 
8.4.3 Medical History ................................................................................................ 26 
8.4.4 Concomitant Medications ................................................................................. 26 
8.5 Extent of Exposure ........................................................................................................ 27 
8.5.1 Treatment Adherence ........................................................................................ 27 
8.6 Efficacy Analyses ......................................................................................................... 27 
8.6.1 Analysis Methods - Multiplicity ....................................................................... 27 
8.6.2 Analysis of Primary Endpoints ......................................................................... 27 
8.6.3 Analysis of Exploratory Endpoints ................................................................... 29 
8.6.4 Other Analysis .................................................................................................. 31 
8.7 Safety Analyses ............................................................................................................. 31 
8.7.1 Adverse Events ................................................................................................. 31 
8.7.2 Clinical Laboratory Evaluations ....................................................................... 32 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 5 of 40 
 
8.7.3 Physical Examinations ...................................................................................... 32 
8.8 Monthly Safety Reports ................................................................................................ 32 
9 CHANGES TO PLANNED ANALYSIS FROM STUDY PROTOCOL ............................. 33 
10 TABLE OF CONTENTS FOR DATA DISPLAYS .............................................................. 34 
11 REFERENCES ...................................................................................................................... 40 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 6 of 40 
 
LIST OF ABBREVIATIONS 
 
Abbreviation 
or 
special term 
Explanation 
AE 
ATC 
BMI 
CI 
CSR 
CT 
eDiary 
FDA 
FSFI 
GC 
GCP 
HIPAA 
ICH 
ITT 
IWRS 
MedDRA 
mITT 
NAAT 
Adverse Event 
Anatomical Therapeutic Chemical 
Body Mass Index 
Confidence Interval 
Clinical Study Report 
Chlamydia trachomatis 
Electronic Diary 
US Food and Drug Administration 
Female Sexual Function Index 
Neisseria gonorrhoeae 
Good Clinical Practice 
Health Insurance Portability and Accountability Act 
International Conference on Harmonisation 
Intention to Treat 
Interactive Web Response System 
Medical Dictionary for Regulatory Activities 
Modified Intention-to-Treat 
Nucleic Acid Amplification Test 
PGIC 
PT 
SAE 
Patient Global Impression of Change 
Preferred Term 
Serious Adverse Event 
SAP 
SexFS 
Statistical Analysis Plan 
Brief Profile Sexual Function and Satisfaction 
SOC 
System Organ Class 
TEAEs 
Treatment Emergent AEs 
TFLs 
Tables Listings and Figures 
uHCG 
urinary β-human chorionic gonadotrophin 
WHO 
World Health Organization 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 7 of 40 
 
1 
INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide detailed descriptions of the 
statistical methods, data derivations and data displays for study protocol EVO100-311 Version 
4.0 “Phase 3 double-blind placebo-controlled efficacy trial of EVO100 vaginal gel for the 
prevention of urogenital Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infection 
(EVOGUARD)” dated 26MAY2021 for clinical study report (CSR) analysis. The table of 
contents and templates for the tables listings and figures (TFLs) will be produced in a separate 
document. 
Any deviations from this SAP will be described and justified in the Clinical Study Report (CSR). 
The preparation of this SAP has been based on International Conference on Harmonisation (ICH) 
E9. 
All data analyses and generation of TFLs will be performed using SAS version 9.4 or higher. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 8 of 40 
 
2 
STUDY OBJECTIVES 
 
2.1 
Primary Objective 
• To evaluate the efficacy of EVO100 vaginal gel in the prevention of urogenital 
Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (GC) infections. 
2.2 
Secondary Objective(s) 
• To evaluate the safety of EVO100. 
2.3 
Exploratory Objective(s) 
• To assess the impact of EVO100 vaginal gel on overall sexual satisfaction and overall 
product satisfaction over the course of the clinical study. 
• To determine the impact of EVO100 vaginal gel use rate (subject adherence to instructed 
use) on the efficacy in the combined infections. 
• To assess other subject satisfaction with EVO100 vaginal gel over the course of the 
clinical study. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 9 of 40 
 
3 
STUDY DESIGN 
 
3.1 
General Study Design 
At total of 1730 women, ages ≥18, who had a documented urogenital CT or GC infection or an 
undocumented self-reported CT or GC infection with risk factors, at any time over the 17 weeks 
preceding the enrollment visit, or positive at screening visit will be enrolled. A high prevalence 
of CT infection has been observed in those who were treated for urogenital chlamydial infection 
during the preceding several months. The second infection may result from infection through an 
untreated partner or exposure through a new partner. By including only women who have had a 
CT or GC infection within the past 17 weeks, this study targets those at high risk for infection. 
At screening, subjects will be tested for a current GC/CT infection by nucleic acid amplification 
test (NAAT) via vaginal swab. Those negative for current infection will be enrolled. Those who 
test positive for CT/GC infection at screening will receive standard of care treatment. To meet 
eligibility criteria, these subjects will not be enrolled until 3 to 4 weeks after screening (at least 
21 days after treatment). 
Eligible participants will be enrolled and randomized 1:1 (865 subjects per treatment arm) to 
either EVO100 Gel, 5g or HEC placebo 5 g supplied in a pre-filled, single-dose applicator. A 
baseline vaginal pH and a full gynecologic examination (including bimanual and speculum) will 
be obtained at enrollment. 
Subjects are instructed to apply EVO100 or placebo gel immediately before or up to one hour 
prior to coitus for the duration of the 16-week intervention period. EVO100 or placebo is to be 
re-applied in the same manner for each occurrence of sexual intercourse. Subjects will keep an 
electronic diary (eDiary) to document sexual activity and product use. 
Every 4 weeks (5 visits), all subjects will return to the clinic for repeat CT/GC NAAT (vaginal 
swab), urine pregnancy (urinary β-human chorionic gonadotrophin [uHCG]) testing, eDiary 
review, and return of unused investigational product. At Visits 2 to 4, subjects will be re-supplied 
with EVO100 or placebo gel. At Visit 5, subjects will return unused investigational product and 
continue to use their eDiaries but will not be resupplied with EVO100 or placebo gel. 
Subjects will return for a follow-up visit 4 weeks after the intervention period or after their last 
dose of study medication. At this time, CT/GC NAAT (vaginal swab), pregnancy (uHCG) 
testing, gynecological exam, and eDiary review will be performed. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 10 of 40 
 
 
 
 
Screening and Eligibility 
Subjects who consent may be screened if they have a known case of CT or GC within 17 weeks 
of enrollment, or suspicion of current CT or GC infection (subsequently confirmed with NAAT 
test at Screening Visit). Subjects randomized within 35 days of initial screening do not need to 
be re-screened. 
Intervention and Follow-up Period 
The intervention period is defined as Visits 1 to 5. There will be one follow-up visit (Visit 6), 4 
weeks after the last intervention visit or last dose of study product. These periods are outlined in 
the schedule of assessments (Table 2). The protocol-defined period of observation is 20 weeks. 
In the event a subject has CT or GC infection diagnosed at a local healthcare facility during the 
period between visits, the infection and treatment will be documented and every effort to obtain 
a medical record will be made. These subjects will be considered as failures. 
Safety Follow-up After Protocol-defined Period of Observation 
This period includes safety follow-up as required by Good Clinical Practice (GCP) and standard 
clinical study practice. Adverse events determined to be at least possibly related to the 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 11 of 40 
 
investigational product continuing after the final study visit (Visit 6) will be followed until 
resolution or stable status as determined by the Investigator. 
Study Conduct Strategies due to Coronavirus Disease -2019 
Based on the US Food and Drug Administration (FDA) guidance, Coronavirus disease 2019 
(COVID-19) strategies are planned for this study to ensure adherence to best practices for study 
conduct. 
3.2 
Randomization and Blinding 
This is a Phase 3 placebo-controlled randomized study with 865 subjects per intervention arm, 
for a total of 1730 subjects. The 1730 subjects will be randomized using an Interactive Web 
Response System (IWRS) in a 1:1 fashion across the two intervention groups, EVO100 or 
placebo. Randomization will be stratified by prior infection documentation status 
(available/present versus unavailable/not present), and all documentation of this procedure and 
output will be saved with the IWRS vendor until the end of the study. Randomization will occur 
following enrollment and prior to issuance of investigational product to subjects. 
Investigators and subjects in both intervention groups will remain blinded to their intervention 
assignment (EVO100 or placebo) over the entire duration of the study (double-blind). The 
Sponsor, Evofem, Inc., will prepare the investigational product as well as placebo and supply 
these products in ready-to-dispense status. 
Any request from the Investigator for information about treatment dispensed to study subjects 
must be approved by the medical monitor. 
If the code must be broken in the case of an emergency for management of a subject, the 
Investigator must provide a written request with record of the circumstances surrounding the 
event, including the purpose, date, and personnel involved. Emergency unblinding will be 
available by using the IWRS. An emergency treatment disclosure is a reportable event that must 
be reported to the Medical Monitor within 24 hours of the event. 
Otherwise, blinding will not be broken until all subjects have completed the final study visit and 
the database has been locked and approved. 
3.3 
Study Treatments and Assessments 
Following screening, enrollment, and randomization, subjects will be issued a 4-week supply of 
investigational product based on the individual subject’s projected usage. After a screening 
period of up to 35 days, women will be randomized to receive either EVO100 or placebo: 
EVO100 vaginal gel is supplied in individually wrapped 5 g single-dose, pre-filled vaginal 
applicators. EVO100 is a viscous, off white to tan gel of uniform consistency. Its active 
ingredients are lactic acid United States Pharmacopeia (USP), citric acid USP, and potassium 
bitartrate USP. 
Subjects will be asked how many pre-filled applicators they need, based on their anticipated 
number of sexual encounters per 4 weeks. Up to 3 boxes may be dispensed to meet their 
anticipated need. Additional boxes may be dispensed between visits, if needed. 
At visits 2 through 4, during the intervention period, subjects will return all unused product and 
will be issued a new 4-week supply of investigational product based on projected usage. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 12 of 40 
 
Unopened kits may be re-dispensed to the same subject, provided the subject follows specified 
storage instructions. The staff may also re-dispense to the same subject individually wrapped 
product from an open kit provided specified storage instructions have been followed and the staff 
completes product accountability reconciliation activity. Subjects may be issued additional 
investigational product, as needed, should their supply be exhausted prior to the next study visit; 
however, excessive product usage should be brought to the attention of the Investigator and 
Sponsor. At Visit 5, subjects will return all unused product. 
Table 1 shows the study dosing for each intervention group. 
Table 1: Investigational Product Dosing 
 
Intervention 
Group 
EVO100 vaginal gel 
Placebo 
Group A 
865 subjects, 5 g dose applied up to 
1 hour prior to coitus 
N/A 
Group B 
N/A 
865 subjects, 5 g dose applied up to 1 
hour prior to coitus 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 13 of 40 
 
Table 2: Schedule of Study Assessments 
 
Intervention Period(1) 
Study Visit (V) 
Screening 
Visit 0(2) 
Enrollment/ 
Visit 1(3) 
Visit 2(3) 
Visit 3(3) 
Visit 4(3) 
Visit 5(3)(5) 
Post-Intervention 
Follow-up/Visit 6 
Study Week 
-5.0 to 0 
weeks 
(-35 to 0 
days) 
0 
4(4) 
8(4) 
12(4) 
16(4) 
20 
Investigational Product Dispensed 
X 
X 
X 
X 
Informed Consent/HIPAA 
X 
Demographic Information 
X 
Inclusion/Exclusion 
X 
X 
Confirm Eligibility Criteria 
X 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
AE Assessment 
X 
X 
X 
X 
X 
X 
X 
Medical/Sexual History 
X 
X 
X 
X 
X 
X 
X 
Last Menstrual Period 
X 
X 
X 
X 
X 
X 
X 
Physical Exam 
X 
Targeted Physical Exam(6) 
X 
X 
X 
X 
X 
Body Weight/Height 
X 
Vital Signs 
X 
Gynecologic Exam 
X 
X⁷ 
X⁷ 
Urine HCG 
X 
X 
X 
X 
X 
X 
X 
Vaginal pH 
X 
Self-collected CT/GC NAAT 
X 
X 
X 
X 
X 
Clinician-collected CT/GC 
NAAT 
X 
X 
eDiary Setup 
X 
eDiary Review 
X 
X 
X 
X 
X 
Female Sexual Function Index 
(FSFI) 
X 
X 
X 
X 
X 
X 
X 
PROMIS Sexual FS (PROMIS® 
Brief Profile Sexual Function and 
Satisfaction) 
X 
X 
X 
X 
Subject Sexual Impact 
Questionnaire 
X 
X 
X 
X 
X 
Product Satisfaction 
Questionnaire 
X 
X 
X 
X 
X 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 14 of 40 
 
Patient Global Impression of 
Change (PGIC) 
X 
X 
X 
Return Unused Study Product 
X 
X 
X 
X 
Abbreviations: AE = adverse event, CT = Chlamydia trachomatis, eDiary = electronic diary, GC 
= Neisseria gonorrhoeae, HCG = human chorionic gonadotropin, HIPAA = Health Insurance 
Portability and Accountability Act, NAAT = nucleic acid amplification test; V = study visit. 
(1) The intervention period is defined as Visits 1 to 5. In the event a subject has CT or GC infection 
diagnosed at a local healthcare facility during the period between visits, the infection and 
treatment will be documented and every effort to obtain a medical record will be made. 
(2) Screening period may be up to 35 days. If subjects NAAT results are positive, they will be first 
treated by SOC then will return 3-4 weeks after Screening Visit (at least 21 days after treatment) 
for Enrollment/Visit 1. If the screening period extends past 35 days, subjects will not be enrolled 
and will need to be rescreened. 
(3) Subjects must be asked to abstain from vaginal intercourse in the 24 hours preceding Study 
Visits 2 through 5. 
(4) Subjects will be asked to return ±7 days within each visit window. 
(5) The procedures for Visit 5 should be followed for the Early Termination Visit. 
(6) For unscheduled visits: includes provision to contact subjects or allow unscheduled visits for 
managing AEs. 
(⁷ ) The gynecologic examination will be conducted during unscheduled visits, as necessary and 
during end of study and end of treatment visits. The gynecologic examination will not be 
conducted if the end of study/end of treatment visit is remote due to COVID-19. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 15 of 40 
 
4 
STUDY ENDPOINTS 
 
4.1 
Primary Endpoint 
• The primary efficacy endpoint is the proportion of subjects who are defined as study 
successes versus study failures among the intervention groups (EVO100 or placebo). 
Estimand Framework 
o FDA Submission 
 Success is defined as subjects completing the trial to Visit 5 without any 
of the following: CT/GC infection, usage of prohibited antibiotics during 
the study, an invalid CT/GC test at Visit 5. 
 The mITT population will be used, and the Chi-Square test will be used to 
compare the failure rates in EVO100 and placebo. 
o EMA Submission 
 The parallel primary efficacy endpoints define success through Visit 5 as: 
• CT Infection Endpoint: 
o The proportion of subjects without a CT infection, CT 
prohibited antibiotics, or invalid Visit 5 CT test. 
• GC Infection Endpoint 
o The proportion of subjects without a GC infection, GC 
prohibited antibiotics, or invalid Visit 5 GC test. 
 The mITT population will be used and the Chi-Square test will be used to 
compare the failure rates in EVO100 and placebo. 
Note: These two parallel primary endpoints enable efficacy to be assessed 
separately for CT and GC. In this way, if the study is successful for either CT 
or GC but not for both, an indication for prevention of just one of the two 
pathogens could still be granted. Both primary endpoints will be tested at the 
0.05 significance level (with no adjustments for multiplicity of statistical 
testing). 
4.2 
Secondary Endpoint 
The secondary outcome for this study will be assessing the incidence of AEs (descriptive 
analysis). 
Secondary outcomes for the FDA submission will include the separate CT and GC infection 
endpoints used in the EMA primary endpoint. 
4.3 
Exploratory Endpoints 
Exploratory assessments include: 
• Comparison of the proportion of subjects with overall sexual satisfaction using the 
female sexual function index (FSFI) overall sexual satisfaction question at Visit 5 and 
not having a CT or GC infection. 
• Comparison of the proportion of subjects with overall sexual satisfaction using the FSFI 
overall sexual satisfaction question at Visit 5. 
• Comparison of the proportion of subjects reporting overall product satisfaction at Visit 
5. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 16 of 40 
 
• Comparison of compliance with EVO100 vaginal gel usage versus placebo usage during 
study (rate of product use adherence versus placebo). 
• Subgroup analyses of the primary endpoint (the proportion of subjects who are defined 
success versus failure) will be performed for the following: 
o Subjects with 0%, >0% and <20%, ≥20% and <40%, ≥40% and <60%, ≥60% and 
<80%, ≥80% and <100%, ≥80% and ≤100%, and 100% product use adherence. 
• Descriptive analysis of failure components for the FDA and EMA primary endpoints. 
• Comparison of PROMIS Sexual Function and Satisfaction (PROMIS SexFS), Pain and 
Lubrication subscales with EVO100 vaginal gel usage versus placebo. 
• Comparison of FSFI Lubrication and Pain subscales with EVO100 vaginal gel usage 
versus placebo. 
• Comparison of Patient Global Impression of Change (PGIC) with EVO100 vaginal gel 
usage versus placebo. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 17 of 40 
 
5 
SAMPLE SIZE AND POWER 
The primary analysis is a comparison between proportion of subjects who are defined study 
successes versus study failures (success defined as subjects completing the trial to Visit 5 without 
any CT or GC infection and no use of prohibited antibiotics; failures defined as subjects with CT 
infection, GC infection, use of prohibited antibiotics, or loss to follow-up) among the intervention 
groups (EVO100 or placebo). 
It is assumed that the proportion of subjects who will have CT infection, GC infection, use of 
prohibited antibiotics, or loss to follow-up will be 30.5% for active treatment versus 37.5% for 
placebo group based on the Phase 2B/3 study (EVO003) with equal lost to follow-ups assumed 
in both intervention groups. Using a Chi-Square test for the primary endpoint, 821 analyzable 
subjects per treatment group (1642 subjects total) will yield approximately 85% power to detect 
a rate difference of 7% with a 2-sided 5% type I error rate. Given the assumption that 5% of 
subjects are found to be positive at enrollment, the total sample size planned for this study is 
1730 subjects. With an assumed screen failure rate of approximately 27.8%, 2397 subjects are 
estimated to be needed for screening. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 18 of 40 
 
6 
ANALYSIS POPULATIONS 
This study will utilize three analysis populations: Intention-to-treat (ITT), modified Intention-to- 
Treat (mITT), and safety. 
 
6.1 
Intention-To-Treat Population (ITT) 
The ITT population is defined as all randomized subjects. Analyses with this population will be 
performed based on the treatment randomized. 
6.2 
Modified Intention-To-Treat Population (mITT) 
The mITT population is defined as all randomized subjects who are negative for chlamydia and 
gonorrhoeae at enrollment and are provided with study product. Analyses with this population 
will be performed based on the treatment randomized. 
 
6.3 
Safety Population (Safety) 
Safety population will be based on subjects documented to have been distributed any study 
product. Subjects with proof that no study product was taken (e.g., all study drug returned) will 
not be included in the Safety population. Analysis with this population will be performed based 
on the treatment actually received. 
6.4 
Protocol Deviations/Violations and Exclusions from Analysis Sets 
A cumulative list of protocol deviations will be reported in the Clinical Study Report. 
6.5 
Duplicate Patients 
Patients found to have been enrolled more than once during the study (either at same site or 
different sites) will only have screenings/visits associated with their first enrollment counted in 
the study population. Any additional screenings/enrollments/visits attached to a subsequent 
enrollment (or attempted enrollment) will be excluded from all analyses and analysis 
populations. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 19 of 40 
 
7 
STATISTICAL CONSIDERATIONS AND ANALYSIS 
 
7.1 
Derived Variables 
The below table provides a list of derived variables for demographic and baseline 
characteristics. 
 
Variables 
Formula 
Demographic and Baseline characteristics 
Age at informed consent (in 
years) 
integer ((date of informed consent – date of birth + 1)/ 
365.25) 
Body 
(kg/m2) 
mass 
index 
(BMI) weight (kg)/[height (m)]^2 
Patient-Reported Outcome Scoring 
PROMIS 
SexFS 
Pain 
Subscale (vaginal discomfort) 
In the last 30 days 
Question SFSCR202: 
Did you have any type of sexual activity? 
1=No 
2=Yes 
Question SFVAG202: 
When you have had sexual activity, how much discomfort 
have you felt inside your vagina? 
1=None 
2=A little bit 
3=Some 
4=Quite a bit 
5=A lot 
Question SFVAG206: 
When you have had sexual activity, how much pain have 
you felt inside your vagina? 
1=None 
2=A little bit 
3=Some 
4=Quite a bit 
5=A lot 
Scoring conversion table 
Conditional on 2=yes for SFSCR202 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 20 of 40 
 
 
PROMIS SexFS Lubrication 
Subscale 
In the last 30 days 
Question SFSCR202: 
Did you have any type of sexual activity? 
1=No 
2=Yes 
Question SFLUB001: 
How often did you become lubricated (“wet”) during 
sexual activity or intercourse? 
5=Almost always or always 
4=Most of the time (more than half the time) 
3=Sometime (about half the time) 
2=A few time (less than half the time) 
1=Almost never or never 
Question SFLUB004: 
How difficult was it to maintain your lubrication 
(“wetness”) until completion of sexual activity or 
intercourse? 
1=Extremely difficult or impossible 
2=Very difficult 
3=Difficult 
4=Slightly difficult 
5=Not difficult 
Scoring conversion table 
Conditional on 2=yes for SFSCR202 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 21 of 40 
 
 
FSFI Pain Subscale 
FSFI Q17: 
Over the past 4 weeks, how often did you experience pain 
during vaginal penetration? 
0=Did not attempt intercourse 
1=Almost always or always 
2=Most times (more than half the time) 
3=Sometimes (about half the time) 
4=A few times (less than half the time) 
5=Almost never or never 
FSFI Q18: 
Over the past 4 weeks, how often did you experience pain 
following vaginal penetration? 
0=Did not attempt intercourse 
1=Almost always or always 
2=Most times (more than half the time) 
3=Sometimes (about half the time) 
4=A few times (less than half the time) 
5=Almost never or never 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 22 of 40 
 
FSFI Q19: 
Over the past 4 weeks, how would you rate your level 
(degree) of discomfort or during or following vaginal 
penetration? 
0=Did not attempt intercourse 
1=Very high 
2=High 
3=Moderate 
4=Low 
5=Very low or none at all 
Pain Score = (FSFIQ17+ FSFIQ18+ FSFIQ19)*0.4 
FSFI 
SexFS 
Lubrication 
Subscale 
FSFI Q7: 
Over the past 4 weeks, how often did you become 
lubricated (“wet”) during sexual activity or intercourse? 
0=No sexual activity 
1=Almost always or always 
2=Most times (more than half the time) 
3=Sometimes (about half the time) 
4=A few times (less than half the time) 
5=Almost never or never 
FSFI Q8: 
Over the past 4 weeks, how difficult was it to become 
lubricated (“wet”) during sexual activity or intercourse? 
0=No sexual activity 
1=Extremely difficult or impossible 
2=Very difficult 
3=Difficult 
4=Slightly difficult 
5=Not difficult 
FSFI Q9: 
Over the past 4 weeks, how often did you maintain your 
lubrication (“wetness”) until completion of sexual activity 
or intercourse? 
0=No sexual activity 
1=Almost always or always 
2=Most times (more than half the time) 
3=Sometimes (about half the time) 
4=A few times (less than half the time) 
5=Almost never or never 
FSFI Q10: 
Over the past 4 weeks, how difficult was it to maintain 
your lubrication (“wetness”) until completion of sexual 
activity or intercourse? 
0=No sexual activity 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 23 of 40 
 
1=Extremely difficult or impossible 
2=Very difficult 
3=Difficult 
4=Slightly difficult 
5=Not difficult 
Lubrication Score = (FSFIQ7+FSFIQ8+FSFIQ9+ 
FSFIQ10)*0.3 
 
7.2 
Handling of Missing Data and Outliers 
7.2.1 Missing Data Analysis Methods 
For the primary and exploratory endpoint analyses using CT/GC infection, any subject that does 
not have a known infection status through Visit 5 (eg, is deemed lost to follow-up) will be 
considered a failure. Likewise, any subject that uses prohibited antibiotics during the treatment 
period of the study (through Visit 5) regardless of CT/GC infection status will be considered a 
primary endpoint failure. Lastly, any patient who receives an invalid CT/GC test result at Visit 5 
will be considered a failure. All other analyses will be conducted using data as observed in the 
study with no imputation. 
For the EMA parallel primary endpoints and the FDA secondary endpoint analyses of separate 
CT and GC infections, any subject that does not have a known infection status through Visit 5 
(eg, is deemed lost to follow-up or discontinued but was not lost to follow-up) will be assumed 
to have not had a CT/GC infection. Any subject that uses prohibited medications for CT or GC 
will be considered failures in those respective endpoints. Lastly, any patient who received an 
invalid CT/GC test result at Visit 5 will be considered a failure. All other analyses will be 
conducted using data as observed in the study with no imputation. 
7.2.2 Handling of Missing or Incomplete Dates 
Imputation rules for missing or partial AE start date are defined below: 
If only Day of AE start date is missing: 
If the AE start year and month are the same as that for the first dose date, then: 
 If the full (or partial) AE end date is NOT before the first dose date or AE end date is 
missing, then impute the AE start day as the day of first dose date; otherwise, impute the 
AE start day as 1. 
 If the full (or partial) AE end date IS before the first dose date, the AE will be classified 
as a pre-treatment AE. 
Compare the imputed AE start date with TE period to determine whether the AE is pre-treatment 
AE, TEAE or post-treatment AE. 
If Day and Month of AE start date are missing: 
If AE start year = first dose year, then: 
 If the full (or partial) AE end date is NOT before the first dose date or AE end date is 
missing, then impute the AE start Month and Day as the Month and Day of first dose 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 24 of 40 
 
date; otherwise, impute the AE start Month as January and the Day as 1. 
 If the full (or partial) AE end date IS before the first dose date, the AE will be classified 
as a pre-treatment AE. 
Compare the imputed AE start date with TE period to determine whether the AE is pre-treatment 
AE, TEAE or post-treatment AE. 
If Year of AE start date is missing: 
If the year of AE start is missing or AE start date is completely missing, then query site with no 
imputation. Also compare the full (or partial) AE end date to the first dose date. If the AE end 
date is before the first dose date, then the AE should be considered as a pre-treatment AE. 
Otherwise, the AE will be considered as TEAE. 
Imputation rules for missing or partial medication start/stop dates are defined below: 
Missing or partial medication start date: 
 If only DAY is missing, use the first day of the month. 
 If DAY and Month are both missing, use the first day of the year. 
 If DAY, Month and Year are all missing, use a date before the first dose date. 
Missing or partial medication stop date: 
 If only DAY is missing, use the last day of the month. 
 If DAY and Month are both missing, use the last day of the year. 
 If DAY, Month and year are all missing, assign ‘continuing’ status to stop date. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 25 of 40 
 
8 
STATISTICAL METHODS 
 
8.1 
General Statistical Conventions 
All statistical procedures will be completed using SAS version 9.4 or higher. 
Unless otherwise stated, all statistical testing will be two-sided and will be performed using a 
significance (alpha) level of 0.05. Two-sided 95% confidence intervals (CIs) will be provided 
when relevant. 
For continuous variables, descriptive statistics will include the number of non-missing values (n), 
mean, standard deviation, median, minimum, and maximum. For categorical variables, 
descriptive statistics will include counts and percentages per category. All summaries will be 
presented by treatment group and overall, unless otherwise specified. 
Baseline values for all parameters will be the most recent value prior to administration of study 
product or speculum examination. 
All subject data will be presented in individual subject data listings. Unless otherwise stated, 
unscheduled visit results will be included in date/time chronological order, within subject listings 
only. All listings will be sorted by investigational site, subject number, and visit. The treatment 
group (EVO100, Placebo) as well as subject’s age and sex (if available) will be stated on each 
listing. With respect to study tables, the mITT population will be used for efficacy analyses; 
safety population will be used for safety analyses. 
8.2 
Subject Disposition 
Subject disposition information will be summarized by treatment group and overall. The number 
and percent of subjects who are randomized, who complete the study treatment, who complete 
the study and who withdraw early from the treatment and study will be presented. 
The primary reason for early withdrawal from treatment and/or the study will also be tabulated. 
The number of subjects randomized will be used as the denominator for the percentage 
calculation. 
The number and percent of subjects in each analysis set will also be tabulated. 
Subject disposition including primary reason to indicate why subject was not randomized will be 
listed. 
The number of subjects excluded from ITT, mITT, Safety analyses sets and reasons for exclusion 
will be summarized by treatment group and overall. Listings will also be provided for subjects 
excluded from the analysis set with reasons for exclusion. 
8.3 
Protocol Deviations 
All key protocol deviations identified will be summarized by treatment group and overall based 
on ITT population. 
A listing will include the inclusion/exclusion criteria violated at screening and enrollment visits 
as well as other key protocol deviations. 
To explore potential changes in study conduct due to COVID-19 (e.g., flexibility regarding 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 26 of 40 
 
Screening window, visit time-frames, and follow-up were allowed in order to capture more 
touchpoints within a patient’s timeline during the study), an additional analysis will be performed 
to recognize and indicate the impact of participation of subjects by COVID-19. The impact of 
COVID-19 will be summarized by treatment group and overall by visit for all subjects in ITT 
population. This table will present the subjects affected by COVID-19 in all aspects (e.g., missed 
visit and/or assessment due to COVID-19, remote visit due to COVID-19, modified assessment 
due COVID-19). In addition, key protocol deviations related to COVID-19 will also be 
summarized using ITT population. 
A by-subject listing will also be provided for all subjects that have their participation impacted 
by COVID-19. 
8.4 
Demographics and Baseline Characteristics 
8.4.1 Demographics 
Demographic variables include age, race, ethnicity, height, weight, BMI and will be summarized 
and listed using ITT population. Continuous measures will be summarized treatment group and 
overall using descriptive statistics (n, mean median, standard deviation, minimum, and 
maximum). Categorical variables will be summarized by treatment group and overall using 
frequency counts and percentages. All demographic information will be presented in a subject- 
level listing. 
8.4.2 Baseline and Disease Characteristics 
The baseline characteristics includes CT/GC infection history, gynecological exam details, 
current contraceptive methods used, vaginal pH, CT/GC NAAT sample result, risk factors and 
vital signs. Categorical variables summarized using frequency counts and continuous variables 
will be summarised by descriptive statistics using ITT population. Baseline characteristics will 
be listed. 
8.4.3 Medical History 
A summary of medical/surgical/gynecologic/sexual health history will be presented by system 
organ class and preferred term (PT) using Medical Dictionary for Regulatory Affairs® 
(MedDRA) version 23 or higher based on ITT population. Medical history will be listed. 
8.4.4 Concomitant Medications 
Concomitant medications will be assessed and includes any medication that would be taken 
during the study including all over the counter medications, vitamins, and nutritional 
supplements. 
Medications used in this study will be coded by using latest version of World Health Organization 
(WHO) drug dictionaries. 
Concomitant medications will be summarized descriptively using frequency tables by anatomical 
therapeutic chemical (ATC) class level 2 and preferred name by treatment group and overall 
based on ITT population. Concomitant medications will be listed. Additionally, a listing of 
subjects taking prohibited medications for intercurrent infections other than CT or GC will be 
provided. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 27 of 40 
 
8.5 
Extent of Exposure 
8.5.1 Treatment Adherence 
Adherence with treatment gel usage during study (rate of product use adherence) will be 
estimated using the eDiary data. 
Adherence ratio will be calculated as = [# of times product is properly used as noted in the eDiary 
/ # of coital events noted during the treatment phase in the eDiary]. 
Study product adherence (compliance) will be calculated as: 100x [adherence ratio as calculated 
above]. The maximum percentage of doses used will be 100%. 
Study drug compliance, number of times of product use (determined via eDiary), and number of 
times sexual intercourse occurred will be summarized descriptively by treatment group and 
overall using mITT population. 
Study drug compliance will be summarized in categories “0%”, “>0% and <20%”, “≥20% and 
<40%”, “≥40% and <60%”, “≥60% and <80%”, “≥80% and <100%”, “≥80% and ≤100%”, and 
“100%” using frequency count and percentages. For the purposes of the frequency table, each 
compliance group will be deemed mutually exclusive (e.g., compliance rate of 41% would be in 
the ≥40% category only and would not be counted in the ≥20% category). 
Study product distribution details and subject diary data will be listed. 
 
8.6 
Efficacy Analyses 
This section addresses separately the analyses to be conducted on the primary, secondary, and 
exploratory efficacy endpoints. 
8.6.1 Analysis Methods - Multiplicity 
FDA Submission: 
To control for multiple testing issues, a hierarchical testing strategy will be employed for 
exploratory endpoints that evaluate the efficacy of EVO100 vaginal gel in the prevention of 
urogenital CT and GC infection by assessing the proportions of subjects with: 
• Overall sexual satisfaction using the FSFI overall sexual satisfaction question at Visit 5 
and not having a CT or GC infection (Endpoint A), and 
• Overall sexual satisfaction using the FSFI overall sexual satisfaction question at Visit 5 
(Endpoint B). 
If the primary endpoint is successful, then Endpoint A will be tested using a two-sided 
alpha=0.05. Endpoint B will be tested in succession if Endpoint A has a successful outcome. 
 
EMA Submission: 
For the EMA analysis, the primary endpoint can be either of the parallel primary endpoints for 
CT only and GC only. If either parallel primary endpoint is successful, then Endpoint A (same 
as above) will be tested using a two-sided alpha=0.05. Endpoint B (same as above) will be tested 
in succession if Endpoint A has a successful outcome. 
8.6.2 Analysis of Primary Endpoints 
FDA Submission 
For the primary analysis, the proportion of subjects who are defined study successes (i.e., have 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 28 of 40 
 
all of the following through Visit 5: no CT/GC infection, no use of prohibited antibiotics, not lost 
to follow-up/otherwise discontinued, and no invalid CT/GC test at Visit 5) will be compared 
between the intervention groups (EVO100 or placebo) using a Chi-Square test. The primary 
efficacy analysis will be completed using the subjects deemed analyzable* from the mITT 
population. 
*All subjects in the mITT population are deemed analyzable for the purpose of the primary 
endpoint analysis. Those subjects who are in ITT but not in mITT will be excluded from said 
analysis. The primary analysis will be performed using all subjects in the mITT population. 
The primary statistical hypothesis being tested is that there is no difference in the proportion of 
subjects deemed study success in the EVO100 intervention group versus placebo. In statistical 
terms: 
H0: pEVO100 = pplacebo, HA: pEVO100 ≠ pplacebo 
where, pEVO100 and pplacebo denote the proportion of subjects deemed a study success while 
on EVO100 or placebo, respectively. Denominators for percentages are number of subjects in 
the mITT population in each intervention group. To test superiority over placebo, the percentage 
of study successes will be compared against placebo based using Chi-Square test. The estimated 
difference in proportions, 95% confidence interval, and p-value will be presented. A two-sided 
5% type I error rate (α=0.05) will be used. The Fisher’s Exact test will be conducted in place of 
the Chi-Square test if necessary due to issues with the expected cell counts. 
For the primary endpoint and exploratory analyses using CT/GC infection, any subject that does 
not have a known infection status through Visit 5 (i.e., at least through study day 105) (e.g., is 
deemed lost to follow-up) will be considered a failure. Likewise, any subject that uses prohibited 
antibiotics during the treatment period of the study regardless of CT/GC infection status will be 
considered a primary endpoint failure. Lastly, a patient having an invalid CT/GC test at Visit 5 
will be considered a failure. 
Secondary analyses of CT only and GC only endpoints will be performed as specified in the 
below EMA analysis section. See that section for more details. 
In addition, a sensitivity analysis will be provided for the primary endpoint. For the sensitivity 
analysis, the proportion of subjects who are defined as study successes will be irrespective of the 
use of prohibited antibiotics. Success will be defined as no CT/GC infection through Visit 5 (i.e., 
at least through study day 105). The statistical analysis described for the primary endpoint will 
be used for the secondary and sensitivity analyses. 
A listing will be provided for CT/GC NAAT sample result. 
EMA Analysis 
For the parallel primary analyses, the proportion of subjects who are defined study successes will 
be compared between intervention groups (EVO100 or placebo) using a Chi-Square test. The 
primary efficacy will be completed using the subjects deemed analyzable* from the mITT 
population. 
*All subjects in the mITT population are deemed analyzable for the purpose of the primary 
endpoint analysis. Those subjects who are in ITT but not in mITT will be excluded from said 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 29 of 40 
 
analysis. The primary analysis will be performed using all subjects in the mITT population. 
For the CT infection endpoint, success will be defined as having no CT infection, taking no CT 
prohibited medications, and no invalid CT test at Visit 5. For the GC infection endpoint, 
successes will be defined as having no GC infection, taking no GC prohibited medications, and 
no invalid GC test at Visit 5. 
The primary statistical hypothesis being tested is that there is no difference in the proportion of 
subjects deemed study success in the EVO100 intervention group versus placebo. In statistical 
terms: 
H0: pEVO100 = pplacebo, HA: pEVO100 ≠ pplacebo 
where, pEVO100 and pplacebo denote the proportion of subjects deemed a study success while 
on EVO100 or placebo, respectively. Denominators for percentages are number of subjects in 
the mITT population in each intervention group. To test superiority over placebo, the percentage 
of study successes will be compared against placebo based using Chi-Square test. The estimated 
difference in proportions, 95% confidence interval, and p-value will be presented. A two-sided 
5% type I error rate (α=0.05) will be used. The Fisher’s Exact test will be conducted in place of 
the Chi-Square test if necessary due to issues with the expected cell counts. 
For the primary endpoint, any subject that does not have a known infection status through Visit 
5 (i.e., at least through study day 105) (e.g., is deemed lost to follow-up/otherwise discontinued) 
will be considered as having a negative CT/GC test through Visit 5. 
8.6.3 Analysis of Exploratory Endpoints 
The following summary and analysis will be provided for the exploratory endpoint using mITT 
population: 
Patient-reported outcomes measures for this study are to evaluate the efficacy of EVO100 vaginal 
gel in the prevention of urogenital CT and GC infection by assessing the following proportions 
of subjects: 
• With overall sexual satisfaction using the FSFI overall sexual satisfaction question at 
Visit 5 (i.e., at least through study day 105) and not having a CT or GC infection using 
FDA primary endpoint rules. 
• With overall sexual satisfaction using the FSFI overall sexual satisfaction question at 
Visit 5 (i.e., at least through study day 105). 
• Reporting overall product satisfaction at Visit 5 (i.e., at least through study day 105). 
• A subset analysis of the primary endpoint (FDA rules) looking at results based on prior 
infection documentation will be performed. 
Above endpoints will be compared against placebo based on Chi-Square test. The estimated 
difference in proportions, 95% confidence interval, and p-value will be presented. A two-sided 
5% type I error rate (α=0.05) will be used. The Fisher’s Exact test will be conducted in place of 
the Chi-Square test if necessary due to issues with the expected cell counts. 
From the FSFI questionnaire, question (#16) “over the past 4 weeks, how satisfied have you been 
with your overall sexual life?” will be considered for sexual satisfaction. The question from 
product satisfaction questionnaire “How satisfied are you with the study product?” will be used 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 30 of 40 
 
to assess the overall product satisfaction. Responses will be categorized as satisfied (i.e., 
combined responses of very satisfied, moderately satisfied, about equally satisfied and 
dissatisfied) and dissatisfied (i.e., combined response of moderately & very dissatisfied) for the 
comparison. 
Additional exploratory endpoints are: 
• Compliance with EVO100 vaginal gel usage versus placebo usage during study (rate of 
product use adherence and placebo) will be summarised descriptively (see section 8.5 for 
more details). 
• The proportion of subjects who are defined success versus failure (FDA primary 
endpoint) will be summarized using the below adherence categories by treatment groups. 
The estimated difference in proportions, 95% confidence interval, and p-value will be 
presented. 
o Subjects with 0%, >0% and <20%, ≥20% and <40%, ≥40% and <60%, ≥60% and 
<80%, ≥80% and <100%, ≥80% and ≤100%, and 100% product use adherence. 
For the purposes of the frequency table, each compliance group will be deemed 
mutually exclusive. 
• Similar to the FDA primary endpoint analysis, failure components of the primary 
endpoint (i.e., CT infection, GC infection, use of prohibited antibiotics, lost to follow-up, 
or invalid CT/GC test at Visit 5) will be summarized using frequencies and percentages 
with the difference between treatment groups analysed using a Chi-Square test. The 
Fisher’s Exact test will be conducted in place of the Chi-Square test if necessary due to 
issues with the expected cell counts. 
• Responses to the PROMIS SexFS Satisfaction, Pain and Lubrication subscales with 
EVO100 vaginal gel usage and placebo at each visit will be summarized using count and 
percentage. Descriptive summary will also be provided using the derived subscale scores 
(refer section 7.1). In addition, the shifted change from baseline to post baseline response 
will also be summarized. 
• Response to FSFI questionnaire- Lubrication and Pain subscales with EVO100 vaginal 
gel usage and placebo at each visit will also be summarised using count and percentage. 
Response to questions 7, 8, 9, 10 will be considered for lubrication subscale and questions 
17, 18 and 19 will be considered for pain subscales from the FSFI questionnaire. In 
addition, the shifted change from baseline to post baseline response will be summarized. 
• Patient Global Impression of Change (PGIC) with EVO100 vaginal gel usage versus 
placebo will be summarized by treatment group. 
Validation related analyses for the patient-reported outcomes (FSFI, product satisfaction 
questionnaire, PROMIS SexFS etc.) referenced here will be outlined in a separate psychometric 
analysis plan. 
Listings will be provided for PROMIS SexFS, FSFI, product satisfaction questionnaire and 
PGIC. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 31 of 40 
 
8.6.4 Other Analysis 
Condom usage rates and their effect on study successes will be explored. The rate of condom 
usage will be defined as # of coital acts where male condom usage is noted in the eDiary (over 
the course of the treatment phase) / total # of coital acts during the treatment phase. 
To assess the usage rate of condoms during the study, a summary will be presented using 
descriptive statistics for subjects displayed by treatment group. Additionally, a summary of study 
success or failure rates by treatment group and condom usage (none, low, high) will be presented. 
For the purposes of this display, low condom use will be defined as subjects that have a rate that 
is less than or equal to the 50th percentile of subjects using condoms (i.e., no condom use will 
not be used for the 50th percentile calculation). 
8.7 
Safety Analyses 
All safety data will be summarized by intervention group and overall. Safety analyses will be 
conducted on the safety analyses set and will be performed for all safety variables specified in 
the below sections. 
No statistical tests will be performed. 
 
8.7.1 Adverse Events 
All Adverse events (AEs) will be classified by System Organ Class (SOC) and Preferred Term 
(PT) according to the most current version of Medical Dictionary for Regulatory Activities 
(MedDRA version 23.0 or higher). 
Treatment emergent AEs (TEAEs) are defined as any AE that started or worsened on or after the 
first dose of study drug. 
GU TEAEs include: Dysuria, Genital Burning Sensation, Genital Discomfort, Genital Pain, 
Vaginal Discharge, Vulvovaginal Burning Sensation, Vulvovaginal Discomfort, Vulvovaginal 
Erythema, Vulvovaginal Pruritus. 
An overall AE summary tables will be provided, and summary include number of TEAEs and 
number and percentage of subject with any TEAEs, GU TEAEs, related TEAEs, TEAEs leading 
to discontinuation, serious adverse event (SAE), and TEAEs leading to death. 
Additionally, the following summaries will also be provided. 
• TEAEs by SOC and PT 
• GU TEAEs by SOC and PT 
• Related TEAEs by SOC and PT 
• TEAEs by SOC, PT and maximum severity 
• TEAEs leading to treatment discontinuation by SOC and PT 
• Related TEAEs leading to treatment discontinuation by SOC and PT 
• TEAEs leading to death by SOC and PT 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 32 of 40 
 
• Serious TEAEs by SOC and PT 
Where a subject has the same adverse event, based on preferred terminology, reported multiple 
times in the study period, the subject will only be counted once at the preferred terminology level 
in adverse event frequency tables. 
If a subject has multiple adverse events within the same system organ class in the study period, 
the subject will only be counted once at the system organ class level in adverse event frequency 
tables. 
AEs with relationship to study treatment of “certain,” “probable/likely,” “possible,” and “missing 
relationship” will be considered as related AEs. 
In summaries by SOC and PT, adverse events will be sorted by decreasing frequency of overall 
column within each SOC and PT. 
All adverse events will be listed. In addition, AEs leading to discontinuation, leading to death 
and SAEs will also be listed. 
8.7.2 Clinical Laboratory Evaluations 
Specimens collected for NAATs will be processed by the sites and shipped to a central laboratory 
for testing. All other laboratory testing will be performed onsite. 
Vaginal pH, CT/GC NAAT sample result, and urine human chorionic gonadotropin (HCG) will 
be summarized by visit (where applicable) for each treatment group. Listings will be provided as 
well. Separate listings will be provided for urine pregnancy test. 
8.7.3 Physical Examinations 
All physical examination data will be listed using safety population. 
8.8 
Monthly Safety Reports 
Blinded cumulative safety reports will be generated to check for potential safety issues and to 
ensure that there are no safety concerns noted during the course of the study. These will consist 
of AE summaries by SOC and PT along with other safety tables as deemed necessary. 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 33 of 40 
 
9 
CHANGES TO PLANNED ANALYSIS FROM STUDY PROTOCOL 
The following changes to the analysis plan have changed since the approval of the protocol: 
1) Male condom usage summary statistics. 
2) Assessing the effect of male condom usage on study success rates. 
3) Added sensitivity analysis for the primary endpoint to check the impact of the use of 
prohibited medication. 
4) Patients with duplicate enrollments will have their second entries will be excluded from 
all analyses 
5) Added secondary analyses for separate CT and GC Only analyses. These analyses will 
serve as parallel primary endpoints for the EMA marketing authorization application. 
6) An exploratory analysis of the FDA primary endpoint by subgroups of prior infection 
documentation status (available, not available) 
7) A subgroup analysis of the FDA primary endpoint by Age groups (18-24, 25-45, 46-64, 
65+) 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 34 of 40 
 
10 
TABLE OF CONTENTS FOR DATA DISPLAYS 
 
 
Table Number 
14.1.1.1 
Table Title 
Summary of Subject Disposition 
Population 
All Subjects 
14.1.1.2 
Summary of Subjects to Be Excluded from Analysis 
Population 
ITT 
14.1.1.3 
Summary of Protocol Deviations 
ITT 
14.1.1.4 
Summary of Protocol Deviations Related to COVID- 
19 
ITT 
14.1.1.5 
Summary of COVID-19 Impact 
ITT 
14.1.2.1 
Summary of Baseline and Demographic 
Characteristics 
ITT 
14.1.2.2 
Summary of Baseline Disease Characteristics 
ITT 
14.1.2.3 
Summary of Medical/Surgical/Gynecological/Sexual 
Health by System Organ Class and Preferred Term 
ITT 
14.1.3 
Summary of Concomitant Medications by Anatomic 
and Therapeutic Class and Preferred Term 
ITT 
14.1.4 
Summary of Treatment Adherence 
mITT 
14.2.1.1 
Summary of Proportion of Subjects with Success 
(No CT/GC Infection and No Use of Prohibited 
Antibiotics) and/or Failure Through Visit 5 
mITT 
14.2.1.2 
Summary of Proportion of Subjects with Success 
(No CT/GC Infection) and/or Failure Through Visit 
5 – Sensitivity Analysis 
mITT 


Table Number 
Table Title 
Population 
Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 35 of 40 
 
 
14.2.1.3 
Summary of Proportion of Subjects with Success 
(No CT Only) and/or Failure Through Visit 5 – 
Secondary Endpoint / EMA Primary Endpoint 
mITT 
 
 
14.2.1.4 
Summary of Proportion of Subjects with Success 
(No GC Only) and/or Failure Through Visit 5 – 
Secondary Endpoint / EMA Primary Endpoint 
mITT 
 
14.2.1.5 
Summary of Proportion of Subjects with Success 
(No CT/GC Infection and No Use of Prohibited 
Antibiotics) and/or Failure Through Visit 5 by Age 
mITT 
 
14.2.1.6 
Summary of Proportion of Subjects with Success 
(No CT/GC Infection and No Use of Prohibited 
Antibiotics) and/or Failure Through Visit 5 by Prior 
Infection Documentation 
mITT 
 
14.2.2.1 
Summary of Proportion of Subjects with Overall 
Sexual Satisfaction Using the Female Sexual 
Function Index at Visit 5 and Not Having a CT or 
GC Infection 
mITT 
 
 
14.2.2.2 
Summary of Proportion of Subjects with Overall 
Sexual Satisfaction Using the Female Sexual 
Function Index at Visit 5 
mITT 
 
 
14.2.2.3 
Summary of Proportion of Subjects with Overall 
Product Satisfaction at Visit 5 
mITT 
 
 
14.2.3.1 
Summary of Proportion of Subjects with Success 
(No CT/GC Infection and No Use of Prohibited 
Antibiotic) Through Visit 5 by Adherence Categories 
mITT 
 
 
14.2.3.2 
Summary of PROMIS® v2.0 Brief Profile Sexual 
Function and Satisfaction (Female) – Lubrication 
and Pain Subscales by Visit 
mITT 


Table Number 
Table Title 
Population 
Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 36 of 40 
 
 
 
 
14.2.3.3 
Summary of PROMIS® v2.0 Brief Profile Sexual 
Function and Satisfaction (Female) – All Questions 
by Visit 
mITT 


Table Number 
Table Title 
Population 
Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 37 of 40 
 
 
14.2.3.4 
Shift from Baseline Summary of PROMIS® v2.0 
Brief Profile Sexual Function and Satisfaction by 
Visit 
mITT 
14.2.3.5 
Summary of Female Sexual Function Index – 
Lubrication and Pain Subscales by Visit 
mITT 
14.2.3.6 
Summary of Female Sexual Function Index – All 
Questions by Visit 
mITT 
14.2.3.7 
Shift from Baseline Summary of Female Sexual 
Function Index – Lubrication and Pain Subscales by 
Visit 
mITT 
14.2.3.8 
Summary of Patient Global Impression of Change by 
Visit 
mITT 
14.2.4.1 
Summary Statistics for Subject Level Condom Usage 
Rate During the Study Treatment Phase 
mITT 
14.2.4.2 
Analyses of Subject with Success Rate by Condom 
Usage Rates (No Condom Usage vs. Low Condom 
Usage vs. High Condom Use) 
mITT 
14.3.1.1 
Overall Summary of Treatment-Emergent Adverse 
Events 
Safety 
14.3.2.1 
Summary of Treatment-Emergent Adverse Events by 
System Organ Class and Preferred Term 
Safety 
14.3.2.2 
Summary of GU Treatment-Emergent Adverse 
Events by System Organ Class and Preferred Term 
Safety 
14.3.2.3 
Summary of Treatment-Related Treatment-Emergent 
Adverse Events by System Organ Class and 
Preferred Term 
Safety 


Table Number 
Table Title 
Population 
Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 38 of 40 
 
 
14.3.2.4 
Summary of Treatment-Emergent Adverse Events by 
System Organ Class, Preferred Term, and Maximum 
Severity 
Safety 
14.3.2.5 
Summary of Treatment-Emergent Adverse Events 
Leading to Treatment Discontinuation by System 
Organ Class and Preferred Term 
Safety 
14.3.2.6 
Summary of Treatment-Related Treatment-Emergent 
Adverse Events Leading to Treatment 
Discontinuation by System Organ Class and 
Preferred Term 
Safety 
14.3.2.7 
Summary of Treatment-Emergent Adverse Events 
Leading to Death by System Organ Class and 
Preferred Term 
Safety 
14.3.3.1 
Summary of Serious Treatment-Emergent Adverse 
Events by System Organ Class and Preferred Term 
Safety 
14.3.4.1 
Summary of Observed Values for Clinical 
Laboratory Tests by Visit 
Safety 


Listing 
Number 
Listing Title 
Population 
Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 39 of 40 
 
 
16.2.1.1 
Listing of Subject Disposition 
All Subjects 
16.2.1.2 
Listing of Protocol Deviations 
ITT 
16.2.1.3 
Listing of Protocol Deviations Related to COVID-19 
ITT 
16.2.1.4 
Listing of Analysis Populations and Reasons for 
Exclusion 
ITT 
16.2.4.1 
Listing of Demographics 
ITT 
16.2.4.2.1 
16.2.4.2.2 
Listing of Baseline Characteristics 
ITT 
16.2.4.2.3 
16.2.4.3 
Listing of Medical/Surgical/Gynecological/Sexual 
Health History 
ITT 
16.2.4.4 
Listing of Concomitant Medications 
ITT 
16.2.4.5 
Listing of Vaginal Ring Use 
ITT 
16.2.4.6 
Listing of Subjects with Prohibited Medications for 
Intercurrent Infections Other than CT and GC 
Infection 
ITT 
16.2.4.7 
Listing of Treatment Adherence 
mITT 
16.2.6.1 
Listing of CT/GC Nucleic Acid Amplification Test 
Sample Result 
mITT 
16.2.6.2 
Listing of Female Sexual Function Index 
Questionnaire 
mITT 
16.2.6.3 
Listing of Product Satisfaction Questionnaire 
mITT 
16.2.6.4 
Listing of PROMIS® v2.0 Brief Profile Sexual 
Function and Satisfaction (Female) 
mITT 
16.2.6.5 
Listing of Patient Global Impression of Change 
mITT 
16.2.7.1 
Listing of Adverse Events 
Safety 
16.2.7.2 
Listing of Adverse Events Leading to Study Drug 
Discontinuation 
Safety 
16.2.7.3 
Listing of Adverse Events Leading to Deaths 
Safety 
16.2.7.4 
Listing of Serious Adverse Events 
Safety 


Listing 
Number 
Listing Title 
Population 
Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 40 of 40 
 
 
 
16.2.8.1 
Listing of Laboratory Data 
Safety 
16.2.9.1 
Listing of Subject Diary Entries 
Safety 
16.2.9.2 
Listing of Physical Examination 
Safety 
16.2.9.3 
Listing of Telephone Contact Details 
Safety 
16.2.9.4 
Listing of Pregnancies 
All Subjects 


Statistical Analysis Plan 
Protocol Number: EVO100-311 
Version: Final 2.0, Date: 06APR2022 
Page 41 of 40 
 
 
11 
REFERENCES 
1. 
ICH Topic E3: Structure and Content of Clinical Study Reports (CPMP/ICH/137/95- 
adopted December 1995). 
2. 
ICH Topic E9: Statistical Principles for Clinical Trials (CPMP/ICH/363/96 – adopted 
March 1998). 
3. 
EVO100-311 Protocol Version 2.0, 14SEP2020. 


1 
 
 
 
Protocol Title: 
Phase 3 double-blind placebo-controlled efficacy trial 
of EVO100 vaginal gel for the prevention of urogenital 
Chlamydia trachomatis and Neisseria gonorrhoeae 
infection (EVOGUARD) 
 
Protocol Number: EVO100-311 
 
 
Protocol Version, 
Date 
Version 4.0, May 26, 2021 
 
Document 
Version, Date: 
Final 2.0, April 6, 2022 


SIGNATURE PAGE 
2 
 
 
 
 
Prepared at Premier Research by: 
 
 
 
07-Apr-2022 | 10:33:08 EDT 
 
 
 
 
Samantha Nemeth, Senior Statistician 
Date 
DD Mmm YYYY 
 
 
Reviewed at Premier Research by: 
 
 
07-Apr-2022 | 11:17:54 EDT 
 
 
 
 
 
Clint Dart, VP Biostatistics and Programming 
Date 
DD Mmm YYYY 
 
 
 
Approved at Evofem, Inc. by: 
 
 
 
07-Apr-2022 | 08:32:02 PDT 
 
 
 
 
 
Catherine Maher, VP Regulatory Affairs & PV 
Date 
DD Mmm YYYY 


REVISION HISTORY 
3 
 
 
Version/Date 
Version name 
Section 
Changes implemented 
1.0/ 04Nov2020 
Final 1.0 
Tables & Listings 
Baseline Version 
2.0/ 06Apr2022 
Final 2.0 
Tables and Listings 
GU TEAE table, COVID table, treatment-related TEAE leading to discontinuation 
table, safety population defined using distributed/returned product, separate CT and 
GC endpoints, EMA endpoint language, specifying discontinued but not lost to 
follow-up and invalid test at Visit 5 as failure reasons for FDA primary endpoint, 
subgroup analysis by documentation status, subgroup analysis by age, additional 
subject adherence category, pregnancy listing, vaginal ring use listing, planned 
treatment/actual treatment added as a column to all listings