CI03: A Clinical Investigation to Evaluate Efficacy of the J3 Bioscience Lubricating Intravaginal Ring VR101 as a Personal Lubricant Device in Women
Phase: NA
Conditions: Sexual Dysfunction, Physiological
Sponsor: J3 Bioscience, Inc.

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 1 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
 
CI03: A Clinical Investigation to Evaluate Efficacy of the J3 Bioscience 
Lubricating Intravaginal Ring VR101 as a Personal Lubricant Device in 
Women 
Original Date: 
July 10, 2019 
Revision: 
Rev 02 
Revision Date: 
January 31, 2020 
Effective: 
January 31, 2020 
 
SPONSOR: 
J3 Bioscience, Inc. (J3 Bio, formerly named ViroPan, Inc.) 
825 North 300 West, Suite N231 
Salt Lake City, Utah 84103 
Email: tmccabe@j3bio.com 
Mobile: 801-550-9956 
Office: 801-931-4756 
Fax: 866-768-9341 
 
OFFICE ADDRESS: 
J3 Bioscience, Inc. 
825 North 300 West, Suite N231 
Salt Lake City, Utah 84103 
Email: tmccabe@j3bio.com 
Mobile: 801-550-9956 
Office: 801-931-4756 
Fax: 866-768-9341 
 
 
AUTHORIZED REPRESENTATIVES (for studies conducted in the EU or elsewhere): 
For studies conducted in the EU: ProMedt Consulting GmbH 
 
CONFIDENTIAL INFORMATION 
 
 
This protocol is for the sole use of the intended recipients only. It contains CONFIDENTIAL, 
PROPRIETARY, and PRIVILEGED information. Unauthorized review, use, disclosure, copying, or 
distribution is strictly prohibited. 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 2 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
 
DECLARATION BY THE INVESTIGATOR 
I have read this protocol and agree that it contains all the necessary details for carrying out this 
investigation. I agree to personally conduct or supervise the investigation as described and will do all in 
my power to complete the investigation within the time designated. I verify that I am suitably qualified 
by my education, training and experience to conduct the investigation. Documentation of my 
qualifications and professional affiliations are contained in my Curriculum Vitae. 
 
I will provide the copies of the protocol and all information relating to pre-clinical and prior clinical 
experience (i.e., Investigator's Brochure) to all staff involved in this investigation. I will discuss this 
material with them to ensure that they are fully conversant with the medical treatment in, and the 
conduct of the investigation, and that they will handle the data and information generated in the 
investigation confidentially. 
 
I agree not to start enrolling participants until a duly appointed Institutional Review Board has issued a 
favorable opinion and the Sponsor has authorized the initiation of enrollment. 
 
I will conduct the investigation in accordance with the provided protocol, the Good Clinical Practice 
guidelines of the FDA, and the spirit of the Declaration of Helsinki, and the moral, ethical, and scientific 
principles that justify medical research. The investigation will be conducted in accordance with the 
relevant laws and regulations relating to clinical investigations and the protection of participants in the 
country(ies) in which the investigation will be performed. All participants will be comprehensively 
informed about the nature of the investigation and of its investigational nature and that they may 
withdraw from the investigation at any time. They will give their written consent to participate before 
entry into the investigation. I will only use the Informed Consent Forms approved by the Institutional 
Review Board and the Sponsor. 
 
I have read the Investigator's Brochure, including the potential risks of the J3 Bio investigational 
Vaginal Lubrication Ring VR101 and I agree to report all adverse events that may occur during the 
investigation. 
 
Where applicable, the information reported in the Case Report Forms (CRFs) will be transcribed from 
my records, reports, and manuscripts. Either I, or an appointed person, will attest to the authenticity 
and completeness of the data and accuracy of the transcriptions by signing and dating the CRFs. I 
agree to the audit and monitoring procedures described in the protocol and contract, which involve 
verification of investigation records against original records and confirmation that the study is 
conducted in accordance with this protocol. I will make available additional background data from my 
records at the request of government regulatory agencies. 
 
I understand that I am obliged to provide to the Sponsor, for the Sponsor's unrestricted use, the 
complete results and all data generated during the investigation, and that all information concerning 
VR101 and the Sponsor's activities, such as patents, formulae, manufacturing procedures, and basic 
unpublished scientific data and information supplied by the Sponsor, including the investigation 
protocol and all investigation results, are strictly confidential and the exclusive property of the Sponsor. 
I will undertake only to use this information to conduct the investigation and not to use it for any other 
purpose without the written agreement of the Sponsor. I will not make any changes to the protocol or 
propose changes to the protocol or any Sponsor-approved documents to the IRB or FDA without the 
written approval of the Sponsor. 
 
I will supply the Sponsor with the investigation data in such a way that the participant cannot be 
personally identified. 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 1 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
 
Investigator Signature:   
 
 
Printed Name:   
 
 
Date:   
 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 2 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
 
List of Abbreviations and Definitions 
 
ADE 
Adverse Device Event (Effect) 
AE 
Adverse Event 
API 
Active Pharmaceutical Ingredient 
CFR 
Code of Federal Regulations 
CHPC 
Center for High Performance Computing 
CIP 
Clinical Investigation Plan 
CI01 
Clinical Investigation 01 (Pilot) 
CI02 
Clinical Investigation 02 (Pivotal) 
CI03 
Clinical Investigation 03 (Pivotal) 
CHA 
Clinical Hazard Assessment 
CRA 
Clinical Research Associate 
CRF 
Case Report Form 
EC 
Ethics Committee 
FDA 
Food and Drug Administration of United States 
FSFI 
Female Sexual Functioning Index 
FSFI-LD 
FSFI Lubrication Domain 
GCP 
Good Clinical Practice 
HEPA 
High-Efficiency Particulate Air 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IDE 
Investigational Device Exemption 
IFU 
Instructions for Use 
IRB 
Institutional Review Board 
ISO 
International Organization for Standardization 
IVR 
Intravaginal Ring 
NCR 
No Carbon Required 
NSR 
Non-Significant Risk 
OHRP 
Office of Human Research Protection 
PI 
Principal Investigator 
QSR 
Quality System Regulation 
SADE 
Serious Adverse Device Event (Effect) 
SAE 
Serious Adverse Event 
SOP 
Standard Operating Procedure 
Sub-I 
Sub-Investigator 
USAE 
Unanticipated Serious Adverse Event 
VHI 
Vaginal Health Index 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 1 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
 
TABLE OF CONTENTS 
Study Summary ........................................................................................................... 10 
1 
SYNOPSIS ............................................................................................................. 12 
1.1 
Sample Size .......................................................................................................................... 12 
1.2 
Investigational Devices .......................................................................................................... 12 
1.3 
Summary of Endpoints (see Section 5.1.1 for details) ........................................................... 12 
1.3.1 
Primary Efficacy Endpoint ............................................................................................... 12 
1.3.2 
Safety Endpoint .............................................................................................................. 12 
1.3.3 
Exploratory Endpoints ..................................................................................................... 12 
1.4 
Summary of Study Schedule and Study Schematic .............................................................. 13 
2 
BACKGROUND ...................................................................................................... 13 
2.1 
Purpose ................................................................................................................................. 13 
2.2 
Scope .................................................................................................................................... 14 
2.3 
Summary of VR101 Bench Testing ....................................................................................... 14 
2.3.1 
Bench Tests/Stability ...................................................................................................... 14 
2.3.2 
Biocompatibility Tests ..................................................................................................... 14 
2.3.3 
Summary of VR101 Preclinical Testing ........................................................................... 15 
2.4 
Summary of VR101 Clinical Studies ...................................................................................... 15 
2.4.1 Summary of VR101 Pilot Study .............................................................................................. 16 
2.4.2 Summary of VR101 Pivotal Investigation (CI02) ..................................................................... 17 
3 
Identification and description of the investigational device ............................. 18 
3.1 
Summary Description of VR101 ............................................................................................ 18 
3.2 
Principles of Operation of VR101 .......................................................................................... 22 
3.3 
VR101 Intended Use ............................................................................................................. 22 
3.4 
Lubricating Agent .................................................................................................................. 22 
3.5 
Supplier of VR101 Devices and Sham Rings ........................................................................ 22 
3.6 
VR101 Identification .............................................................................................................. 22 
3.7 
VR101 Lot Traceability .......................................................................................................... 23 
3.8 
Training and Procedures Required to use VR101 ................................................................. 23 
3.9 
Sham Rings ........................................................................................................................... 23 
4 
Objectives and hypotheses of the clinical investigation ................................... 23 
4.1 
Study Objectives (ECH E3; 8.) .............................................................................................. 23 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 2 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
4.1.1 
Primary Objectives of the Clinical Investigation .............................................................. 23 
4.2 
Hypothesis of the Clinical Investigation ................................................................................. 24 
4.2.1 
Primary Efficacy Hypothesis ........................................................................................... 24 
4.3 
Label Claims to be Assessed in the Clinical Investigation ..................................................... 24 
5 
Study Design ......................................................................................................... 24 
5.1 
General Description of the Clinical Investigation (ICH E3; 9) ................................................. 24 
5.1.1 
Study Endpoints (ICH E9; 2.2.2) ..................................................................................... 24 
5.1.2 
Measures to Minimize Bias ............................................................................................. 25 
5.1.3 
Test Equipment, Maintenance, and Calibration .............................................................. 25 
5.2 
Exposure to VR101 and the Sham Ring ................................................................................ 25 
5.3 
Study Participants ................................................................................................................. 25 
5.3.1 
Inclusion Criteria for Participant Selection (ICH E3; 9.3 ICH E9; 2.2.1) .......................... 25 
5.3.2 
Exclusion criteria for participant selection ....................................................................... 26 
5.3.3 
Points of Enrollment ........................................................................................................ 27 
5.3.4 
Duration of Participation .................................................................................................. 27 
5.3.5 
Randomization and Blinding ........................................................................................... 27 
5.3.6 
Participant Withdrawal / Discontinuation ......................................................................... 28 
5.3.7 
Number of Participants ................................................................................................... 29 
5.3.8 
Estimated Time Needed to Enroll Participants ................................................................ 29 
5.3.9 
Total Study Duration ....................................................................................................... 29 
5.3.10 
Procedures for the Replacement of Participants ............................................................. 29 
5.4 
Procedures ............................................................................................................................ 29 
5.4.1 
Participant Screening ...................................................................................................... 29 
5.4.2 
Participant Enrollment / Recruitment ............................................................................... 29 
5.4.3 
Visit Schedule and Description: Frequency and Timing of Study Variables (ICH E3; 
9.5.1. ICH E9; 2.2.2) .................................................................................................................... 30 
5.4.4 
Interim Follow-Up Call Schedule ..................................................................................... 34 
5.4.5 
Terminal Follow-Up Procedure ....................................................................................... 34 
5.4.6 
FSFI (Female Sexual Function Index) Survey ................................................................ 34 
5.4.7 
Intercourse / Lubricant Use Survey ................................................................................. 35 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 1 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
During Day 7, 14 and 21 Phone Calls and Visit 2, participants will be given a survey to assess: 35 
5.4.8 
Ring Use Log .................................................................................................................. 35 
5.4.9 
Factors That May Influence the Outcome of the Investigation ........................................ 35 
5.5 
Monitoring Plan ..................................................................................................................... 35 
5.6 
Labeling ................................................................................................................................. 36 
6 
Justification For The Clinical Investigation ........................................................ 37 
6.1 
Need for the Proposed Clinical Investigation ......................................................................... 37 
6.2 
Safety of VR101 in Prior Studies ........................................................................................... 37 
6.3 
Justification of Study Endpoints ............................................................................................. 37 
6.3.1 
FSFI-LD .......................................................................................................................... 37 
6.3.2 
Adverse Events / Adverse Device Effects ....................................................................... 38 
7 
Risks and Benefits of VR101 and CI03 ................................................................ 38 
7.1 
Risk Management ................................................................................................................. 38 
7.2 
Clinical Hazard Assessment (CHA) ....................................................................................... 38 
7.3 
Risk-Benefit Ratio .................................................................................................................. 38 
8 
Statistical considerations..................................................................................... 38 
8.1 
Statistical Hypotheses ........................................................................................................... 38 
8.1.1 
Primary Efficacy .............................................................................................................. 38 
8.1.2 
Exploratory ...................................................................................................................... 39 
8.2 
Analysis Groups .................................................................................................................... 39 
8.2.1 
Target population ............................................................................................................ 39 
8.2.2 
Full Analysis Set (ITT) ..................................................................................................... 39 
8.2.3 
Modified ITT .................................................................................................................... 39 
8.2.4 
Complete Case Set ......................................................................................................... 39 
8.2.5 
Per Protocol Analysis ...................................................................................................... 39 
8.3 
Sample Size Determination (ICH E3; 9.7.2 ICH E9; 3.5) ....................................................... 40 
8.4 
Expected Drop-Out Rates ..................................................................................................... 41 
8.5 
Pass / Fail Criteria of the Clinical Investigation ...................................................................... 42 
8.6 
Adjustment for Multiplicity ...................................................................................................... 42 
8.7 
Disposition of Missing Data (ICH E3; 9.7.1, 11.4.2.2 ICH E9; 5.3. EMA Guideline on Missing 
Data in Confirmatory Clinical Trials, ICH E9 (R1) addendum) ......................................................... 42 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 2 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
8.7.1 
Prevention of Missing Data ............................................................................................. 42 
8.7.2 
Incentive to Complete ..................................................................................................... 43 
8.7.3 
Unavoidable Loss of Data ............................................................................................... 43 
8.7.4 
Missing Data by Groups .................................................................................................. 44 
8.8 
Planned Sensitivity Analyses ................................................................................................. 44 
8.9 
Final Data Validation and Subject Disposition Determination ................................................ 44 
9 
Data Collection and Management ........................................................................ 44 
10 Amendments to the CIP........................................................................................ 45 
11 Deviations from the CIP ........................................................................................ 45 
11.1 
Acceptable Circumstances for Deviations to the CIP ............................................................ 45 
11.2 
Procedure for Disqualification and Replacement of a Principal Investigator .......................... 45 
12 Device Accountability ........................................................................................... 45 
12.1 
Access to Devices ................................................................................................................. 45 
12.2 
Physical Location of Investigational Devices ......................................................................... 46 
12.3 
Use of Devices ...................................................................................................................... 46 
12.4 
Distribution of Devices from the Sponsor to Clinical Sites ..................................................... 46 
12.5 
Device Accountability Log ..................................................................................................... 46 
13 Adverse Events, adverse device effects and device deficiencies and reporting events and 
deficiencies .................................................................................................................. 46 
13.1 
Definitions ............................................................................................................................. 47 
13.2 
Anticipated Adverse Events (AE) .......................................................................................... 48 
13.3 
Anticipated Adverse Device Effects (ADE) ............................................................................ 48 
13.4 
Device Deficiencies ............................................................................................................... 49 
13.5 
Possible Use Errors ............................................................................................................... 50 
13.6 
Unanticipated Serious Adverse Events ................................................................................. 50 
13.7 
Adverse Event Reporting Procedures ................................................................................... 50 
13.7.1 
Unanticipated Adverse Device Effect Reporting ............................................................. 50 
13.7.2 
Adverse Event Reporting ................................................................................................ 51 
13.8 
Resumption of Terminated Studies ....................................................................................... 52 
13.9 
Device Deficiency Reporting ................................................................................................. 52 
13.10 
Follow-Up for Adverse Events ............................................................................................ 52 
13.11 
Communication Plan .......................................................................................................... 52 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 1 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
14 Ethical Considerations ......................................................................................... 53 
14.1 
Institutional Review Board (IRB) ............................................................................................ 54 
14.2 
Responsibilities ..................................................................................................................... 54 
14.2.1 
Principal Investigator ...................................................................................................... 54 
14.2.2 
A Sub-Investigator (Sub-I, e.g., Medical Professional, Associates) ................................ 54 
14.2.3 
Sponsor .......................................................................................................................... 55 
14.2.4 
Monitor ............................................................................................................................ 55 
15 Vulnerable Populations ........................................................................................ 55 
16 Suspension or premature termination of the clinical investigation (Stopping Rules) 55 
17 Conflicts of Interest .............................................................................................. 56 
18 Publication policy ................................................................................................. 56 
19 Records and Reports ............................................................................................ 57 
20 Bibliography .......................................................................................................... 57 
 
Appendix A: FSFI Survey and Scoring Method 
 
Appendix B: VR101 Investigational Labeling / Instructions for Use 
Appendix C: VR101 Clinical Hazard Assessment 
Investigational Sites/PIs: Advanced Clinical Research/aka Velocity Clinical Research 
 
Site 01 – West Jordan, Utah: 
Principal Investigator: 
(Study Doctor) 
Barbara Rizzardi, MD 
Telephone: 
801-542-8190 (24 Hours) 
Address: 
Advanced Clinical Research 
3590 West 9000 South 
Suite 300 
West Jordan, UT 84088 
 
Site 02 – Meridian, Idaho 
Principal Investigator: 
(Study Doctor) 
Mark Turner, MD 
Telephone: 
208-377-8653 (24 Hours) 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 2 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
 
Address: 
Advanced Clinical Research 
2950 East Magic View Drive 
Meridian, ID 836452 
 
 
Institutional Review Board (IRB): 
IntegReview IRB 
3815 S. Capital of Texas Hwy 
Suite 230 
Austin, Texas 78704 
512-326-3001 
 
 
STUDY SUMMARY 
 
Title 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
Short Title 
Efficacy of VR101 as a Personal Lubricant 
Protocol Number 
CI03-CIP 
Phase 
Pivotal 
Methodology 
Randomized, double-blind, sham-controlled, 4-week parallel group 
study 
Study Duration 
7 weeks (including a 2-week open-label extension and a 1-week safety 
follow-up) 
Study Centers 
Study is designed as a multi-center trial (at least 2 sites) with 
approximately equal enrollment 
Objectives 
Primary 
To evaluate the efficacy of VR101 as a personal lubricant for vaginal 
application, intended to moisturize and lubricate, to enhance the ease 
and comfort of intimate sexual activity and supplement the body’s 
natural lubrication (as shown by the proportion of participants with 
FSFI-LD ≥ 4.5 following 4 consecutive weeks of weekly ring use being 
higher for VR101 than the sham). 
Number of 
Participants 
A minimum of 160 females (80 in each arm) will be randomized to 
VR101 or sham ring during the treatment phase of the study 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 1 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring, VR101, as a 
Personal Lubricant Device in Women 
 
Diagnosis and Main 
Inclusion Criteria 
Sexually active women who report with individual question scores of 
between 1 and 3, inclusive, on all FSFI Lubrication Domain questions 
(7, 8, 9, and 10). 
Study Product, 
Route, Regimen 
VR101 is a personal lubrication device, for vaginal application, 
intended to moisturize and lubricate, to enhance the ease and 
comfort of intimate sexual activity, and supplement the body's 
natural lubrication. 
Participants will be instructed to exchange with a new device 
every 7 ± 1 days. 
Duration of 
administration 
6 weeks (4-week double-blind parallel group study plus 2-week open 
label extension) 
Reference Therapy 
VR101 will be compared to a sham ring 
Statistical 
Methodology 
The primary efficacy analysis will be a superiority comparison between 
the proportion of participants who report FSFI-LD (lubrication domain 
score) scores of 4.5 or greater after using VR101 or the sham ring for 4 
weeks. 

J3 Bioscience, Inc. 
CONFIDENTIAL 
 
 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 12 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
1 SYNOPSIS 
This Clinical Investigation (CI03) is designed to validate the efficacy of the VR101 
lubricating Intravaginal Ring (IVR) as a personal lubricant device. In the proposed clinical 
investigation, participants will be divided into two groups for the study, VR101 device 
and sham ring. Participants will use VR101 devices or sham rings for 28 days in a 
randomized, double-blind, parallel group design. 
 
1.1 
Sample Size 
Participants will be enrolled to ensure at least 160 subjects (80 in each group) are 
randomized to the VR101 device or sham ring group. 
 
As this is a multi-site study, the study coordinator will monitor enrollment to ensure 
nominally equal representation of the 160 subjects across the sites, for example if two 
sites are selected, at least ~1/3 of the participants (54) will be enrolled at each site. 
 
1.2 Investigational Devices 
VR101 devices and sham rings for the clinical investigation will be manufactured by an 
ISO 13485-certified and/or FDA Quality System Regulation (QSR)-compliant vendor. 
 
1.3 Summary of Endpoints (see Section 5.1.1 for details) 
1.3.1 
Primary Efficacy Endpoint 
• 
Proportion of participants that experience increased vaginal lubrication that 
enhances ease and comfort of intimate sexual activity, defined as a FSFI-LD ≥ 
4.5 following 4 consecutive weeks of weekly ring use. 
 
1.3.2 
Safety Endpoint 
• 
All adverse events (AE) and adverse device events (ADEs) will be recorded throughout 
the study and will be assessed for severity and their relatedness to VR101 use. 
1.3.3 
Exploratory Endpoints 
• 
Improvement in FSFI total score 
• 
Improvement in all FSFI domains (except lubrication), which include desire, 
arousal, orgasm, satisfaction, and pain domains 

J3 Bioscience, Inc. 
CONFIDENTIAL 
 
 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 13 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
1.4 
Summary of Study Schedule and Study Schematic 
 
 
 
 
Figure 1. Study Schematic 
 
• 
After a participant has read and signed the Informed Consent Document and has 
met all inclusion and exclusion criteria, she will be randomized into either the 
VR101 device or sham ring group. 
• 
Participants will be instructed to use the randomly assigned device continuously 
and exchange with a new device every 7 days for the next 4 weeks. 
• 
Study staff will complete a follow-up call with participants on the 7th, 14th, and 21st 
day following randomization to remind them to remove their current device and 
insert a new ring. 
• 
Participants will return for a final study visit on day 28 ± 2 where the FSFI survey 
will be administered. 
• 
Participants will be offered two additional VR101 devices for a 2-week open-label 
extension. 
• 
A final follow-up call will occur 1 week after the end of the open-label extension. 
 
2 BACKGROUND 
2.1 Purpose 
The purpose of this Clinical Investigation, internally designated CI03, is to evaluate efficacy of 
the J3 Bioscience, Inc. (J3 Bio) lubricating intravaginal ring, VR101, as a personal lubricant 
device in women. After reviewing results obtained in CI01, “VR101: A Pilot Study to Evaluate 
the Preliminary Feasibility and Safety of a Lubricating Intravaginal Ring to Relieve the 
Symptoms of Vaginal Dryness,” and in CI02, “A Pivotal Clinical Investigation to Evaluate the 
Weekly Phone 
Call Check-in 
and   
Reminders 
4-Week FSFI 
(N = ~150) 
2-week 
open-label 
extension 
of VR101 
devices 
 
Baseline FSFI 
Randomization 
Initiation/Training 
on Ring Use 
(N = ~160) 
Visit 1 (Day 0) 
 
4-Week 
Treatment Phase 
Visit 2 (Day 28 + 2) 
Stop Open-Label 
(Day 42 + 2). Final 
Phone Call / Check-In 
(Day 49 + 2) 

J3 Bioscience, Inc. 
CONFIDENTIAL 
 
 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 14 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
Safety and Efficacy of J3 Bio Lubricating Intravaginal Ring (VR101) in Relieving Symptoms of 
Vaginal Dryness,” FDA and J3 Bio agreed that VR101 safety had been successfully 
demonstrated. 
 
CI03 is designed to further evaluate VR101 efficacy and will enable continued monitoring of 
VR101 safety. The combined safety and efficacy data from CI01, CI02, and CI03 will be used to 
support a premarket 510(k) notification to the FDA to enable regulatory clearance of the device 
in the United States (US). The investigation is designed to comply with the requirements of ISO 
14155, allowing the investigation to also support regulatory submissions and registrations in 
other countries. 
 
2.2 
Scope 
This procedure applies to the clinical investigation of VR101, Lubricating Intravaginal Ring 
manufactured by J3 Bio, to establish the efficacy of VR101 as a personal lubricant device and 
its substantially equivalent safety and efficacy to the predicate device, Replens® Long-lasting 
Vaginal Moisturizer in Pre-filled Applicators (Replens). Results may be applicable to other 
versions of J3 Bio device designs. Justification for applicability of results to other designs will be 
documented in the Design History File and/or Technical File, as appropriate. 
 
2.3 
Summary of VR101 Bench Testing 
2.3.1 
Bench Tests/Stability 
The following characteristics of VR101 devices have been evaluated and found to be within 
specifications or required ranges for up to 54 months (real-time equivalent): 
• 
Visual appearance 
• 
Dimensions 
• 
Mechanical force required to compress VR101 
• 
Tensile strength 
• 
In vitro release of glycerol 
 
Condom compatibility also was evaluated and found to be acceptable per ASTM D7661-10. 
 
2.3.2 
Biocompatibility Tests 
The biocompatibility of VR101 has been evaluated per ISO 10993. Results of all tests 
performed either on the VR101 test articles or VR101 components, as appropriate, were 
acceptable, indicating VR101 and its components will not elicit an unacceptable biological or 
toxicological response under anticipated end-use conditions. Additionally, cytotoxicity testing 
sponsored by Thermedics, Inc. (now Lubrizol Advanced Materials, Cleveland, OH) of the raw 
Tecophilic® HP-60D-35 polymer (also sold as Excipient Grade Thermoplastic Urethane 
Pathway® Polymer PY-PT42DE35) was performed at Toxikon Laboratories (Bedford, MA). The 
extracts of the polymer test article showed no evidence of reactivity in these studies. Thus, the 

J3 Bioscience, Inc. 
CONFIDENTIAL 
 
 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 15 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
raw polymer test article is considered non-cytotoxic under the conditions of this sensitive 
screening test. 
 
Based on the results obtained in the ISO 10993 and FDA-recommended studies, J3 Bio 
concludes that the biological and toxicological risks associated with the use of VR101 are low 
and acceptable, justifying the continued use of VR101 in a clinical investigation. 
 
2.3.3 
Summary of VR101 Preclinical Testing 
J3 Bio and the University of Utah (Department of Bioengineering) conducted nonclinical in vivo 
efficacy studies in a sheep model to support the development of and establish feasibility of 
VR101 use in providing vaginal moisturization and lubrication. The model was selected because 
there are similarities between human and sheep vaginal size and shape. Studies were 
performed to assess the release of the lubricant solution and the ability of VR101 to moisturize 
and lubricate the sheep vaginal tract. Vaginal fluid was collected for up to 7 days using standard 
techniques during insertion of either VR101 or “placebo” (empty reservoir, non-glycerol- 
releasing) hydrophilic polyurethane (HPU) sham ring to assess potential effectiveness. Over the 
7-day study period, sheep treated with VR101 exhibited a statistically significant increase in 
available vaginal fluid versus placebo-treated and baseline control subjects. Collected fluid 
volumes were 4.6-fold higher in VR101-treated animals compared to placebo-treated animals. 
These results indicate that use of the VR101 device may increase vaginal fluid volumes in 
humans and supported the evaluation of VR101 in subsequent clinical investigations. 
 
2.4 Summary of VR101 Clinical Studies 
Two clinical investigations have been performed on VR101 to-date and are summarized in 
Table 1 and Sections 2.4.1 and 2.4.2. 
 
TABLE 1 SUMMARY OF COMPLETED VR101 CLINICAL TRIALS 
Study 
Subjects 
Enrolled 
Design 
Regimen 
Objective(s) 
Diagnosis / 
Key Eligibility Criteria 
Primary 
Endpoints/Outcomes 
CI01 - Pilot 
21 
Open-Label 
VR101, 2 devices 
used consecutively 
for 7 days each (14 
days total) 
Obtain preliminary data on the 
ability of the VR101 to relieve 
the symptoms of vaginal 
dryness in post- and 
perimenopausal women. 
Women over the age of 40 
Self-reported peri- or post- 
menopausal women with 
self-reported vaginal 
dryness 
Statistical improvement in 
modified VHI (without pH) on 
day 3 and day 14 
90% reduction in vaginal 
dryness frequency after 2 
weeks of use 
No serious adverse events 
in study population 

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Study 
Subjects 
Enrolled 
Design 
Regimen 
Objective(s) 
Diagnosis / 
Key Eligibility Criteria 
Primary 
Endpoints/Outcomes 
CI02 – 
Efficacy 
72 
Randomized, 
Double-Blind 
Crossover, 
Sham- 
Controlled 
VR101 and sham 
ring, 4 devices 
used consecutively 
for 7 days each (28 
days total) 
To demonstrate the efficacy of 
VR101 in treating the 
symptoms of vaginal dryness 
To validate potential labeling 
claims regarding VR101 use: 
VR101 relieves the symptoms 
of vaginal dryness for up to 7 
days. 
VR101 is easy to use by 
following the provided 
instructions. 
Women over the age of 35 
who self-reported having 
experienced vaginal 
dryness symptoms that 
interfered with daily 
activities, including but not 
limited to sexual activity, in 
the last 60 days; and 
whose clinician-assigned 
baseline Vaginal Health 
Index (VHI) score was 22 
or lower. 
Primary efficacy endpoint 
(superior VHI improvement 
vs sham after 28 days of 
use) not met, but efficacy 
suggested through post-hoc 
analyses 
VR101 is comfortable during 
use. 
To demonstrate that VR101 
may be used by following the 
provided instructions, justifying 
its over-the-counter (OTC) use. 
To further the 
scientific/technical 
understanding of VR101 by 
surveying user’s experiences 
CI02 – Long- 
Term Safety 
57 
Open-Label 
VR101, 13 
devices* used 
consecutively, each 
for 7 days (91 days 
total) 
To assess the safety of VR101 
when used to treat the 
symptoms of vaginal dryness. 
No serious adverse events 
in 890 VR101 insertions 
*Total, in one study group this included the 4 devices used in the crossover portion of CI02. 
 
2.4.1 Summary of VR101 Pilot Study 
J3 Bio successfully completed the first-in-human pilot clinical investigation (CI01) in 21 
consenting peri- and post-menopausal women to assess preliminary safety and feasibility of use 
of VR101 in relieving the symptoms of vaginal dryness. In the study, participants were instructed 
to use two VR101 devices consecutively, each for 7 consecutive days, for a total of 14 
continuous days of VR101 use. 

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Encouraging results were achieved when assessing relief of vaginal dryness objectively using a 
modified composite Vaginal Health Index (VHI) score, which equally weighted clinical 
assessments of vaginal elasticity, fluid volume, epithelial integrity and moisture. Across the 
study population, mean composite modified VHI scores increased versus baseline values 
collected before device insertion during Visit 1 at each subsequent visit, with statistically 
significant increases (p ≤ 0.05, one-tailed, normally approximated Wilcoxon signed-rank test) 
observed 3 and 14 days, respectively, after the insertion of the first VR101. 
 
Participating women also were asked to report the frequency of their vaginal dryness symptoms 
throughout the study. Once participants started using VR101, the reported frequency of vaginal 
dryness symptoms decreased from 4 days per week to an average of 1.3 days during the first 7 
days of ring use, 0.4 days during the second 7 days of ring use (all p < 0.005, one-tailed, 
normally approximated Wilcoxon signed-rank test). 
 
Regarding safety, no serious safety concerns or adverse events were noted or reported by the 
participants or clinical study staff. Moreover, all 21 participants that enrolled successfully 
completed the study, including follow-up. 
 
2.4.2 Summary of VR101 Pivotal Investigation (CI02) 
CI02 was designed to evaluate the safety and efficacy of VR101 and establish its substantial 
equivalence to the predicate device, Replens® Long-lasting Vaginal Moisturizer in Pre-filled 
Applicators (Replens). In total, 72 women were enrolled in CI02 who self-reported experiencing 
vaginal dryness symptoms within the past 60 days that interfered with daily activities. 
 
Participants were randomized upon enrollment to one of two crossover groups and were 
instructed to use either four each VR101 lubricating devices or four each sham rings 
consecutively, each for 7 days and a total of 28 days. After a 3-week washout period, 
participants then crossed over to use of their respective alternate device (sham ring or VR101 
device) and were again instructed to use four rings or devices consecutively for 7 days each (28 
days total use). Participants were then asked to continue use of VR101 for at least 13 
consecutive weeks to assess VR101 safety during long-term, repeated, continuous use. 
Participants who finished the crossover period using VR101 last were asked to continue VR101 
use for an additional 9 weeks (13 weeks total), while participants who finished using the sham 
ring last were switched back to VR101 use for 13 additional weeks (17 weeks total, 13 of them 
consecutive). 
 
Of 890 each VR101 devices used in CI02, no SADEs were observed during the investigation, 
nor have any been recorded with use of VR101 to date. 
 
Efficacy primarily was assessed using the composite Vaginal Health Index (VHI), previously 
published by Bachmann et al. (1991 and 1992). During the double-blind crossover portion of 

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CI02, VR101 improved composite Vaginal Health Index scores, when used for 28 days over 
baseline scores (Change in VHI (ΔVHI) = +1.76 ± 3.32, p < 0.0001, paired t-test vs baseline, N 
= 66). However, missing data in CI02 greatly contributed to a failure to meet the primary efficacy 
endpoint under the original statistical analysis plan. 
 
In 5 total post hoc mixed model analyses, the p-values calculated in assessment of the primary 
efficacy endpoint were similar and concluded a significant difference in 28-day VHI treatment 
effect between use of VR101 and the sham ring (0.01 ≤ p ≤ 0.02). 
 
The following patient-reported endpoints were also assessed to provide additional assessments 
of efficacy and usability and to substantiate labeling claims: 
• 
Participants reported a significantly lower vaginal dryness severity during the final 24 
hours of their first VR101 use when compared to the 7 days prior to ring use (p < 0.0001, 
paired t-test). 
• 
Ninety-three percent (93%) of participants reported that VR101 was easy to use by 
following the provided instructions when using their first VR101 device. 
• 
When queried in daily diaries if VR101 was comfortable during use, participants 
responded favorably 88% of the time. 
 
3 IDENTIFICATION AND DESCRIPTION OF THE INVESTIGATIONAL 
DEVICE 
3.1 Summary Description of VR101 
VR101 is a clear, flexible, torus-shaped lubricating intravaginal ring (IVR); see Figure 2, Device 
Image, and Figure 3, VR101 Schematic Drawing). VR101 is manufactured from hollow tubing 
formed from Excipient Grade Thermoplastic Urethane Pathway® Polymer PY-PT42DE35 
(identical to Tecophilic® HP-60D-35, Lubrizol Advanced Materials, Cleveland, OH) by hot-melt 
extrusion. 

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Figure 2. Top View of VR101 

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Figure 3. VR101 Manufacturing Drawing with Specifications 
 
The VR101 manufacturing process consists of extruding tubing from Excipient Grade 
Thermoplastic Urethane Pathway® Polymer PY-PT42DE35 (formerly Tecophilic HP-60D- 
35) and cutting the extruded tubing into short segments that are the length of the 
eventual circumference of the finished VR101 devices. The tubing segments are filled 
with a solution of 87/10/3 (wt %) USP grade glycerol/USP grade water/USP grade 
sodium chloride solution. The ends of the tubing are subsequently thermally fused to 
form a continuous ring. The filled ring is placed into a mold and briefly heated in an 
annealing step to release stresses and form the ring into its final circular shape. The 
rings are packaged in foil-backed polyethylene pouches containing 0.25 mL of a 
glycerol/water solution. 
 
Device dimensions are comparable to commercially available IVRs. Table 2 lists the 
dimensions of VR101. 

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Table 2. Nominal Dimensions of VR101 
Ring Characteristic 
Dimension 
Outer Diameter (ring) 
55 mm 
Cross-Sectional Diameter (tubing) 
5.50 mm 
Wall thickness (tubing) 
0.65 mm 
 
Table 3 identifies composition and weight of VR101. 
 
Table 3: Nominal Composition and Weight of VR101 
Device Component 
Weight 
Tubing (Pathway® PY-PT42DE35) 
2.0 g 
Lubricant Solution (Liquid Core) 
2.5 g (total) 
Glycerol, USP 
2.2 g 
Water, USP 
0.2 g 
Sodium Chloride, USP 
0.1 g 
Total Mass 
4.5 g 
 
Table 4 provides the specifications for VR101 constituents. VR101 does not contain any 
drugs or active pharmaceutical ingredients (APIs). 
 
Table 4. Detailed Specifications for VR101 Constituents 
Ring 
Component 
Material Description 
Tubing 
Hydrophilic aliphatic polyether urethane (HPU) tubing, 
extruded from Lubrizol medical grade Pathway™ PY- 
PT42DE35 
Lubricant Solution (present in the Lumen of VR101, also referred to as 
“Liquid Core”) 
Glycerol 
Glycerol, Synthetic 
Chemical Abstract Services: CAS #: 56-81-5 
Molecular Formula: C3H8O3 
Meets relevant standards listed in: 
• 
EP: European Pharmacopeia 
• 
USP: United States Pharmacopeia 
• 
BP: British Pharmacopeia 
• 
JP: Japanese Pharmacopoeia 
Certified free from Bovine and Transmissible Spongiform 
Encephalopathy 
Water 
Water, Deionized 
CAS # 7732-18-5 
Molecular Formula: H2O 
Meets relevant standards listed in: 
• 
EP: European Pharmacopeia 
• 
USP: United States Pharmacopeia 
• 
JP: Japanese Pharmacopoeia 

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Table 4. Detailed Specifications for VR101 Constituents 
Sodium 
Chloride 
Sodium Chloride 
CAS # 7647-14-5 
Molecular Formula: NaCl 
Meets relevant standards identified in: 
• 
EP: European Pharmacopeia 
• 
USP: United States Pharmacopeia 
 
3.2 Principles of Operation of VR101 
Upon insertion, the glycerol solution in the VR101 device begins to pass through the 
semipermeable polyurethane ring wall into the vagina where it provides lubrication and 
moisture. The release of the glycerol solution is prolonged as its transport into the vagina 
is modulated by the presence of the polyurethane ring wall. 
 
3.3 VR101 Intended Use 
VR101 is a personal lubrication device, for vaginal application, intended to moisturize 
and lubricate, to enhance the ease and comfort of intimate sexual activity, and 
supplement the body's natural lubrication. 
 
3.4 Lubricating Agent 
Glycerol is a lubricating agent, generally recognized as safe (GRAS) by the FDA, with a 
long history of safe clinical use in vaginal applications. The intended duration of vaginal 
lubrication (7 consecutive days) provided by each VR101 device is based on the results 
of preclinical evaluations in sheep and two clinical investigations in women. See 
Sections 2.3.3 and 2.4 above for summaries of the preclinical and pilot clinical studies, 
respectively. 
 
3.5 Supplier of VR101 Devices and Sham Rings 
VR101 devices and sham rings manufactured by an ISO 13485-certified and/or FDA 
Quality System Regulation (QSR)-compliant vendor and will supply the products for the 
clinical investigation. 
 
3.6 VR101 Identification 
The individual packages containing each investigational device or sham ring will be 
labeled with the device name ("VR101 Lubricating Intravaginal Ring") and expiration 
date. They also will be labeled with the statement “for investigational use only” (see 
Section 5.6, below). 

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3.7 VR101 Lot Traceability 
VR101 devices are assigned a unique lot identifier by the contract manufacturer or J3 
Bio. All components used in the finished devices are traceable to their suppliers and 
supplier lot numbers. 
 
3.8 Training and Procedures Required to use VR101 
No medical or surgical intervention or clinician involvement is required to use VR101 
safely and effectively. VR101 is designed to be self-inserted by users of the device and 
remain in place for up to 7 consecutive days. After 7 days, the ring is removed by the 
user, discarded, and, at the user’s discretion, replaced with a fresh VR101 ring. 
 
VR101 is intended to be available as an over-the-counter (OTC) product that will not 
require healthcare professional assistance or supervision for use. The user will not be 
assisted with use of the device. As such, the user must be able to insert and remove the 
device solely based on reading the provided instructions for use (IFU) and labeling. All 
applicable warnings, precautions and contraindications are listed on the IFU. 
 
3.9 Sham Rings 
To demonstrate that efficacy results from this study are clinically meaningful, 
lubricating/moisturizing effects not directly resulting from VR101 must be adequately 
controlled. Therefore, performance of VR101 will be compared that of a sham ring. 
 
Sham rings will be manufactured identically to VR101, except: 
 
• 
Tubing will be manufactured with Biomerics Quadraflex ALE-91A, an inert (non- 
hydrophilic) aliphatic polyether urethane. ALE-91A has identical manufacturer- 
reported flexural modulus (per ASTM D790) to Tecophilic HP-60D-35 (Pathway 
PY-PT42DE45), is non-hemolytic (per ASTM D756), is non-cytotoxic (per ISO 
10993-5), and has been used to manufacture FDA-approved, long-term (>30 
day) implantable medical devices. 
• 
No lubricating solution will be added to the device lumen or the device package. 
 
4 OBJECTIVES AND HYPOTHESES OF THE CLINICAL 
INVESTIGATION 
4.1 Study Objectives (ECH E3; 8.) 
4.1.1 
Primary Objectives of the Clinical Investigation 
To evaluate the efficacy of VR101 as a personal lubricant for vaginal application, 
intended to increase vaginal lubrication and enhance the ease and comfort of 
intimate sexual activity. 

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4.2 Hypothesis of the Clinical Investigation 
4.2.1 
Primary Efficacy Hypothesis 
Compared to the sham device, a significantly greater proportion of participants who use 
VR101 for 4 consecutive weeks will experience increased vaginal lubrication that 
enhances ease and comfort of intimate sexual activity as assessed by the Lubrication 
domain of the FSFI (FSFI-LD > 4.5). 
 
4.3 Label Claims to be Assessed in the Clinical Investigation 
Successful confirmation of the Primary Efficacy Hypothesis will also validate the following 
proposed VR101 Label Claims: 
• 
Use one ring every 7 days to provide lubrication during sexual activity or intercourse 
• 
Use one ring every 7 days to reduce discomfort during sexual activity or intercourse 
• 
Use one ring every 7 days for increased comfort and lubrication 
• 
Helps replenish vaginal lubrication when used once every 7 days 
• 
Provides vaginal lubrication when used once every 7 days 
5 STUDY DESIGN 
5.1 General Description of the Clinical Investigation (ICH E3; 9) 
Clinical Phase: Pivotal 
 
Sample Size: At least 160 participants will be randomized (1:1 ratio) into two groups to 
use either VR101 or the sham ring. 
 
Study Population: Sexually active women who report experiencing lack of lubrication 
during intercourse, give consent to participate and meet all inclusion/exclusion criteria. 
 
Study Type: Multi-center, double-blind, sham-controlled parallel group study (followed by 
optional open-label extension). 
 
Study Products: VR101 devices and sham rings (see descriptions above) 
 
Study Regimen: Participants will be randomly assigned to receive either VR101 or the 
sham ring. Participants will then use 4 devices consecutively for 7 days each, (28 days 
total). Participants will be allowed to use VR101 for 2 weeks following the double-blind 
study in an open-label extension. 
 
5.1.1 
Study Endpoints (ICH E9; 2.2.2) 
• 
Primary: Proportion of participants that experience increased vaginal lubrication 
that enhances ease and comfort of intimate sexual activity, defined as an FSFI-LD 
≥ 4.5 with 4 consecutive weeks of weekly ring use. 

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• 
Exploratory: Improvement in the Female Sexual Function Index (FSFI) total composite 
score (Rosen 2000) and its domains (Desire, Arousal, Lubrication, Orgasm, Satisfaction 
and Pain) during 28 days of use. 
 
• 
Safety endpoints monitored: 
o Any adverse events and adverse device effects (ADE) 
5.1.2 
Measures to Minimize Bias 
• 
Participants will not have access to their previous responses, and thus, in any 
given FSFI survey participants will be unable to directly reference their previous 
responses. 
• 
All participants, regardless of randomization status, will be presented with the 
same study materials, including device packaging and labeling, will undergo the 
same measurements, and will be presented with the same survey questions. 
5.1.3 
Test Equipment, Maintenance, and Calibration 
No test equipment is needed for evaluation of safety or efficacy of device use. 
 
5.2 Exposure to VR101 and the Sham Ring 
Participants will use VR101 for up to 42 (±2) days or the sham ring for up to 28 (±2) 
days. 
 
5.3 Study Participants 
5.3.1 
Inclusion Criteria for Participant Selection (ICH E3; 9.3 ICH E9; 
2.2.1) 
 
Clinical Investigation Participants Must: 
1. Completely understand and sign the informed consent form (ability to read and 
understand the consent form in the English language). 
2. Be at least 21 years of age. 
3. Express willingness to comply with the entire study visit schedule (see Table 7 in 
study procedures section). 
4. Over the course of the study: 
a. Abstain from the use of any vaginal moisturizers or lubricants or any other 
topically applied vaginal products not provided by study staff during the 
entirety of study participation 
b. Abstain from using lubricated or spermicide-containing male or female 
condoms 
c. Abstain from vaginal intercourse with a male partner using a lubricated 
condom 

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d. Abstain from any oral sex during or prior to vaginal intercourse with a 
male partner. 
e. Must not initiate, modify or discontinue a regimen of HRT (hormone 
replacement therapy) or estrogen-containing birth control. 
 
NOTE: women who have been using non-vaginal HRT or estrogen- 
containing birth control (e.g., oral, transdermal) on a regular dosing 
interval continuously for at least 3 months may continue on the same 
regimen during the study 
 
f. 
Abstain from use of any other vaginally-placed devices (e.g. ring, 
diaphragm, cervical cap, pessary products) 
g. If able to get pregnant, use an approved method of contraception (per 
remainder of I/E criteria) to reduce their risk of becoming pregnant during 
the study. 
 
5. In the previous 3 months, have had or attempted sexual intercourse with a male 
partner a minimum of twice per month (on average). 
6. Respond to all 4 individual FSFI Lubrication Questions (7 - 10) with a score of 1, 
2, or 3. 
7. Attempt sexual intercourse at least 4 times during the 4-week double-blind study. 
 
5.3.2 
Exclusion criteria for participant selection 
Participants self-reporting any of the following will be ineligible for study entry: 
1. Current use of HRT (Hormone Replacement Therapy) or any estrogen-containing 
birth control products, unless not applied vaginally and the participant has been 
on a regular dosing interval for at least 3 months prior and is willing to continue 
the same regimen without modification throughout study participation. 
2. Vulvar or vaginal procedures (biopsies, radiation) in the last 3 months. 
3. Active vulvar or vaginal infections/lesions or complaints, as well as undiagnosed 
abnormal genital bleeding. 
4. History of chronic pelvic pain, interstitial cystitis, vulvar vestibulitis, pelvic 
inflammatory disease within the past 3 months. 
5. Known current cervical or vaginal infection. 
6. Participants who have given birth or terminated pregnancy in the past 6 weeks. 
7. Postpartum or post-abortion endometritis, unless symptoms resolved at least 3 
months prior to study entry. 
8. Current persistent, abnormal vaginal bleeding. 
9. History of inability to place a vaginal ring. 
10. History of any abnormality of the vagina resulting in distortion of the vaginal canal 
or incompatibility with vaginal ring placement. 

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11. Body habitus or history of lower genital tract abnormalities or prior surgeries, 
which may not allow the vagina to be appropriately accessed. 
12. Known or suspected allergy or hypersensitivity to polyurethanes or glycerol. 
13. Known current alcohol or illicit drug abuse. 
14. Participants who have not recovered from adverse events due to chemotherapy 
or radiation treatment for cancer. 
15. Uncontrolled intercurrent illness including, but not limited to, ongoing or active 
infection of the urogenital tract, symptomatic congestive heart failure, unstable 
angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that 
would limit compliance with study requirements. 
16. Any condition that in the opinion of the investigator or study staff that would 
constitute contraindications to participation in the study or would compromise 
ability to comply with the study protocol. 
17. Current use of a vaginally-placed device (e.g. ring, pessary, cervical cap or 
diaphragm) unless willingness to discontinue for the study duration is expressed. 
18. Pregnancy or plans to become pregnant in the next 6 months. 
19. Current breastfeeding. 
20. Participation in a previous ViroPan or J3 Bioscience clinical trial for VR101 (i.e. CI01, CI02) 
 
NOTE: IUD (Intrauterine Device) users may be enrolled provided they commit to 
exercising caution when removing VR101, as IUD strings have been noted to interfere 
with VR101 removal. 
 
NOTE: Participants who have previously undergone anterior and/or posterior vaginal 
repair and have received a vaginal mesh implant may have difficulty placing VR101 but 
are not automatically excluded from the study. 
 
5.3.3 
Points of Enrollment 
Participants will be considered to be enrolled upon providing consent, meeting all 
inclusion/exclusion criteria and signing the Informed Consent Form. 
 
5.3.4 
Duration of Participation 
Participants will be enrolled in the study for a total of up to 49 days. The study will 
consist of a 28-day randomized trial where participants will use either VR101 or the 
sham ring followed by a 14-day open-label portion and a follow-up phone call 7 days 
after the open-label portion. 
 
5.3.5 
Randomization and Blinding 
Each enrolled subject randomly assigned in a 1:1 ratio to receive either VR101 devices 
or sham rings. A randomization schedule (separate for each site) will be prepared for 
treatment group assignment of each subject. The subject’s randomization number will be 

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unique. This number is not the same as the subject identification (ID) number which is 
assigned at the time of informed consent. 
The subject ID number identifies the subject and consists of the site number plus subject 
number for that site. The randomization number identifies the treatment; the 
randomization schedule provides the correspondence between the subject ID number 
and the randomized treatment identification (VR101 or sham). 
 
The trial will be double-blind, meaning the subject and Investigator/staff will not have 
access to or knowledge of the subject’s treatment assignment. Further, since the 
Sponsor will create and securely maintain the randomization schedules, the Sponsor 
and Sponsor’s representatives will not be made aware of a given subject’s 
randomization number until the blind is broken. The Sponsor will ensure that the Study 
Monitor does not ever have access to the randomization assignments. 
 
As this is a multi-site study, the study coordinator will monitor enrollment to ensure 
nominally equal representation of the 160 subjects across the sites, for example if two 
sites are selected, at least 1/3 of participants (53) would be enrolled at each site. 
Additionally, the Sponsor will create and securely maintain a separate randomization 
schedule for each site to ensure appropriate site representation in the study groups. 
 
5.3.6 
Participant Withdrawal / Discontinuation 
Participants may voluntarily withdraw from the investigation for any reason at any time. 
However, every effort will be made to schedule an Early Termination visit and collect 
final outcome measures as well as ascertain the reason for withdrawal. 
 
Participants who withdraw from the study (or are removed by an investigator) due to an 
Adverse Event will be followed as described in Section 13.10. 
 
Participants who begin a menstrual period during ring use should discontinue ring use 
and insert a new ring within 24 hours of cessation of menstruation. When a new ring is 
inserted, ring exchange will still occur on scheduled days (see Section 5.4.3). For 
example: If the new ring is inserted on day 6, 13, or 20, she will not need to change 
again on day 7, 14 or 21 (respectively) because leaving the ring in will still comply with 
the margin of error in the Visit Schedule. 
 
Participants who become pregnant during the study will be instructed to discontinue use 
of study product and will be dropped from the study. Study staff will refer any such 
participants to a clinical facility for follow-up. 

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A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
5.3.7 
Number of Participants 
Enrollment will continue until at least 160 participants have been randomized into the 
study. For a 2-site study, at least 53 (~1/3 of total) participants must be enrolled at each 
study site. 
 
5.3.8 
Estimated Time Needed to Enroll Participants 
Based on previous studies, we anticipate that enrollment of 160 participants can be 
completed in approximately 2 months. 
 
5.3.9 
Total Study Duration 
The clinical investigation is expected to last approximately 3 to 4 months. 
 
5.3.10 
Procedures for the Replacement of Participants 
Participants will not be replaced. Data from all randomized participants will be reviewed 
prior to data lock. Analysis groups and methods for dealing with any missing data will be 
assigned prior to unblinding for the primary and secondary efficacy analyses. Refer to 
the Draft Statistical Analysis Plan (SAP) for further details. The SAP for this study will be 
finalized and approved prior to final data analysis. 
 
5.4 Procedures 
5.4.1 
Participant Screening 
Participants will be screened according to study site procedures. 
 
5.4.2 
Participant Enrollment / Recruitment 
• 
Interested women will be invited to learn more about this study. If an interested 
possible participant calls the study coordinator, the potential participant may be 
given information over the phone and emailed (or mailed) the informed consent 
form for review. 
• 
The study information will be presented to potential participants and explained. 
Study Visit 1 will be scheduled if interest persists and the potential participant 
meets basic inclusion/exclusion criteria. Staff may email the informed consent 
form (ICF) to the potential investigation participant for review before her 
scheduled visit. 
• 
A signed copy of the informed consent form (ICF) will be provided to the 
participant. 
• 
The ICF will be stored with the participant’s record or as part of the required 
investigation documentation. 

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A Clinical Investigation to Evaluate Efficacy of the J3 
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5.4.3 
Visit Schedule and Description: Frequency and Timing of Study 
Variables (ICH E3; 9.5.1. ICH E9; 2.2.2) 
Participants must return to the clinic for determination to return unused study product 
and take a final FSFI survey per the schedule shown in Table 7. At that time, all 
participants will be given the opportunity to use active VR101 rings for a 2-week period. 

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A Clinical Investigation to Evaluate Efficacy of the J3 
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Table 7. Schedule of Events 
Baseline 
Treatment 
Discontinuation/ 
Follow-Up 
Visit 
1 
PC 
PC 
PC 
2 
Early 
Term*** 
Final PC 
Day (Nominal) 
0 
7±1 
14±1 
21±1 
28±2 
Study 
Withdrawal 
49±2 
(35±2)* 
Informed Consent 
X 
Assign Subject 
Number 
X 
I/E Criteria 
X 
Demographics 
X 
Height & Weight 
X 
Concomitant 
Therapy 
X 
X 
X 
Pregnancy Test 
X 
X 
X 
Administer Non- 
Lubricated Condoms 
(if needed) 
X 
Brief Medical History 
X 
FSFI Survey 
X 
X 
X 
Intercourse / 
Lubricant Use 
Survey 
X 
X 
X 
X 
X 
Dispensing of 
Randomized Product 
/ Insertion of 1st Ring 
in Clinic 
X 
Removal of Final 
Randomized Ring / 
Dispensing of Open- 
Label Product 
Insertion of 1st Ring 
in Clinic 
X** 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
Ring Use Log 
X 
X 
X 
X 
X 
X 
X** 
Ring Change 
Reminder 
X 
X 
X 
Returned Ring 
Collection 
X 
X 
*If a participant does not elect to participate in the open-label extension, the follow-up will occur on day 
35±2 instead of day 49±2. 
**Only if the participant elects to participate in the open-label extension 
***Only if a participant decides to withdraw participation before reaching Day 26 

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Visit 1 – Study Start / Randomization (Day 0) 
1. Assign a Subject Number to the prospective participant and complete initial 
screening procedures. 
2. Participants will be administered the FSFI survey (see Section 5.4.6) by a trained 
member of the study staff. Complete this as early as possible in the Visit, e.g., as 
soon as consent is obtained. 
3. A staff member will conduct a Concomitant Therapy assessment, during which 
they will assess and record if any hormonal therapies are currently being used or 
have been used in the past 3 months (these may or may not disqualify the 
participant from enrollment, refer to Inclusion / Exclusion Criteria above). During 
this assessment, women still able to get pregnant will be asked about their 
current birth control method. If the method is allowed by inclusion / exclusion 
criteria (see above), they will be instructed to continue their same method. If no 
birth control is currently used, or their preferred method is to use condoms, they 
will be offered non-lubricated condoms as to allow them to participate in the 
study. 
4. As part of the demographic assessment, participants will be queried as to their 
menopausal status. If a prospective participant is still able to get pregnant, 
she will be asked to provide a urine sample for a pregnancy test. 
5. If participant meets all inclusion and exclusion criteria, they will be enrolled and 
given a numbered package of randomized study product. All packages will be 
identical in appearance and will contain 6 individually packaged study devices 
(either VR101 or sham ring). All packages will contain a unique number, which 
will be recorded by study staff. 
6. Enrolled participants will be shown to a private clinic area or restroom to self- 
insert one of the devices from the package. Participants will be asked to insert 
one of these rings per the instructions for use and without clinician input. If a 
participant has difficulty with placement, she can ask for further instruction or 
choose to not place the ring and will be withdrawn from the study (this will be 
recorded on an Early Termination CRF and reported to the Sponsor). If the ring 
was successfully placed, the participant will be instructed to leave the first ring in 
the vagina for 7 days. 
NOTE: Used rings / packaging are not intended to be collected by study staff. However, 
the site Study Coordinator may consult the Sponsor to determine if used devices / 
packaging should be collected in case of any unusual patient reports / adverse events. 
 
7. Study staff will record the date and time that the ring was successfully placed and 
note any assistance needed from study staff (e.g., physical, verbal) so that it can 
be recorded in the Ring Use Log (Section 5.4.8). 
8. Participants will be instructed to exchange with a fresh ring on day 7, day 14 and 
day 21. 

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NOTE: If the ring is expelled (unless on a normal exchange day), the participant will be 
asked to rinse it using tap water and reinsert unless it is not appropriate to reinsert the 
expelled ring (e.g., lost in toilet, soiled). If participant is unable or unwilling to reinsert the 
expelled ring, or if the ring has been out for more than 24 hours, she will be asked to 
store it, if possible, in a provided re-sealable bag and bring it to her next clinic visit. If this 
occurs: 
• 
If expelled After the ring had been inserted for at least 6 days: she will be asked 
to start her next scheduled ring a day early. 
• 
If the ring had only been inserted for 5 days or less: she will be asked to insert a 
new ring, which will be removed on the next scheduled day (e.g., day 7, 14, 21 or 
28). 
Visit 2 – Final visit, Treatment week 4 (Day 28 ± 2) 
1. Participants will be asked to report any Adverse Events (AEs), and whether or 
not they feel the events were related to use of the investigational device. AEs will 
be recorded on the Adverse Event Form. Refer to Section 13 for further detail on 
classification of AEs and adverse device effects (ADEs). 
2. If a participant is still able to get pregnant, she will be asked to provide a urine 
sample for a pregnancy test. 
3. Participants will be administered the FSFI survey (see Section 5.4.6) by a trained 
member of the study staff. 
4. A staff member will conduct a Concomitant Therapy assessment, during which 
they will determine the participant used any unapproved medication (e.g. change 
of dosing frequency of HRT / hormonal birth control). 
5. Following the FSFI Survey, participants will be given the Intercourse / Lubricant 
Use Survey (see Section 5.4.7) to assess frequency of intercourse and assess if 
any unapproved lubrication sources were used. 
6. Participants will be again queried as necessary to complete the Ring Use Log 
(see Section 5.4.8) up to all events that occur during Visit 2. If the participant 
does not continue in the open-label extension, then all information needed to fully 
complete all fields of her Ring Use Log should be collected during Visit 2. 
7. Participants will be asked to return any unused devices to study staff. 
8. A member of the study staff will ensure that all study devices are accounted for, 
i.e., that the number of unused devices returned is reconciled with reported ring 
use. 
9. The participant will then be asked if she would like to participate in an open-label 
extension where she can use VR101 for 2 weeks (two devices, 1 week per 
device). Each participant will be instructed to discontinue use her final VR101 
device at day 42 + 2 and told she will receive a final follow-up call on day 49 + 2. 
10. If the participant would like to continue, a member of the study staff will provide 
her with two VR101 devices. Participants will be again shown to a private clinic 
area or restroom to remove her device and (if she has elected to continue) self- 

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insert one of the devices from the package. Participants will be asked to insert 
one of these rings per the instructions for use and without clinician input. 
However, the participant may elect to take the rings with her and insert later at 
her convenience. The participant should dispose of her used ring in the restroom 
wastebasket, used rings are not intended to be collected by study staff. 
Early Termination Visit 
1. If a participant withdraws consent during the study (before Day 26, attempt to 
schedule a Visit for the participant to return study products and disclose any 
Adverse Events or concomitant therapy changes. Refer to Section 13 for further 
detail on classification of AEs and adverse device effects (ADEs). 
2. During this Visit, if appropriate, participants will be asked to provide a urine 
sample for a pregnancy test. 
3. If consent has not been withdrawn prior to the Study Visit, participants will be 
administered the FSFI study, Intercourse / Lubricant Use Study, and queried as 
needed to complete the Ring Use survey (in that order). 
4. The participant will be queried regarding the reason for her withdrawal and the 
response will be recorded on the Early Termination CRF, record as much detail 
as possible (e.g. lack of lubrication, too much lubrication, difficulty place/remove 
a ring, adverse event (related or unrelated to device), etc.) 
5.4.4 
Interim Follow-Up Call Schedule 
Each participant will be contacted by phone on days 7, 14, and 21 to assess their 
medical condition and to complete the Intercourse / Lubricant Use Survey. Participants 
will also be reminded to remove their current ring and replace with a fresh ring if they 
have not already done so. The study staff member administering the call will also query 
the participant to determine the date and time all ring exchanges (scheduled and un- 
scheduled) and temporary removals re-insertions, and if any assistance was required for 
insertion/removal for any of these exchanges/temporary removals. 
 
5.4.5 
Terminal Follow-Up Procedure 
One (1) week after the last ring is removed, each participant will be contacted to assess 
her medical condition and to complete a brief questionnaire. Each participant will also be 
reminded that she may contact the clinic at any time after the study if she is experiencing 
any discomfort that she believes may be related, directly or indirectly, with use of the 
ring. If the participant participated in the two-week open-label extension, study staff will 
query the participant to complete the ring use log (see Section 5.4.8). If a participant is 
terminated early and returns to the clinic for a final visit (see above), all information and 
rings can be collected during this visit and an additional follow-up call is not needed. 
 
5.4.6 
FSFI (Female Sexual Function Index) Survey 
During both study visits (and an Early Termination Visit, if applicable), each participant will be 
given the FSFI Survey (see Appendix A). 

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5.4.7 
Intercourse / Lubricant Use Survey 
During Day 7, 14 and 21 Phone Calls and Visit 2, participants will be given a survey to 
assess: 
• 
Frequency of Intercourse since last Visit/Call 
• 
Any uses of unapproved lubricants/sources of lubrication since the last Visit/Call 
 
5.4.8 
Ring Use Log 
Study staff shall complete a Ring Use log which details the date and time of all ring insertions 
and removals (scheduled and unscheduled, including temporary insertions and removals) by 
querying participants during each Visit and Phone Call. This log should also note any time that 
assistance was required to place or remove a ring, and record as much detail as possible 
regarding the nature of these events. 
 
NOTE: If a participant does not complete the 2 week open-label extension, study staff does not 
need to collect any information for the Log because no rings will have been used since Visit 2. 
 
5.4.9 
Factors That May Influence the Outcome of the Investigation 
Study Compliance 
If participants do not adhere to the indicated schedules (i.e., device use, surveys, study 
completion, visits to the clinic), then the data collected in the investigation may be 
compromised or incomplete. Therefore, every attempt will be made to assure 
compliance with the visit and device exchange schedule. The treatment of incomplete 
data sets is addressed in the Statistical Analysis Plan (SAP). 
 
Participant Use of Products Excluded from the Study 
Neither clinical personnel nor the Sponsor will have the ability to directly monitor 
participants and ensure that they abstain from using products defined in the exclusion 
criteria (e.g., supplementary lubrication). Participants will be queried in a repeated 
survey throughout the study as to whether they used any unapproved lubrication. A 
Concomitant Therapy assessment will be conducted at each Visit to determine if any 
disqualifying HRT or hormonal birth control products (see Inclusion/Exclusion criteria) 
were used prior to or during the study. 
 
5.5 Monitoring Plan 
The investigation will be monitored in accordance with the principles of Good Clinical 
Practice (GCP).” The monitoring schedule is as follows below. 
 
Initiation of the Investigation 
Each PI and Site will be visited by the Study Monitor and approved by the Sponsor and 
Study Monitor and training provided on the requirements of the study before clinical 
samples may be provided to the PI. 

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Interim Monitoring Visit 
Interim monitoring of each site will occur after approximately [5-10%] participants have 
enrolled in the study at each site (see Monitoring Plan), and again after [30-40%] 
participants have enrolled at each site, and after [30-40%] participants have completed 
the study at each site. An additional monitoring visit will be conducted after the last 
participant at each site has completed the study. Additional visits may be scheduled to 
assure assessments are conducted over the duration of the study. 
 
Monitoring Closeout Visit 
The closeout visit will occur at each site following completion of the final clinical visit. 
Additional monitoring may be scheduled, at the discretion of the Sponsor, if protocol 
deviations or significant adverse events are reported or otherwise identified. 
 
NOTE: Study monitors must not be aware of any participant randomization assignments 
(maintained by the Sponsor) at any time before the Study is opened. 
 
5.6 Labeling 
VR101 device labeling is provided in Appendix B. VR101 labels will include the wording 
“for investigational use only” and other wording and markings to assure compliance with 
FDA and ISO 14155 requirements, as appropriate. 
 
Each VR101 device is individually sealed in a polyethylene-lined foil pouch and labeled 
with a Device Label and Identifier. The sealed pouch is then placed in a polyolefin zip- 
lock bag and the insertion instructions are adhered to the outside of the zip-lock bag. 
Clinical staff may distribute the bags containing the VR101 packaged devices in sealed 
pouches to study participants. 
 
Instructions for use and labeling of sham rings will be identical to those provided for 
VR101 devices. As described above, bundles of 6 each VR101 devices or sham rings 
will be given to participants following enrollment and administration of the initial FSFI 
survey. Only the Sponsor or his or her authorized representative will have knowledge of 
which packaging identifiers correspond to either VR101 or the sham ring. The identity of 
administered rings will not be disclosed to any clinical staff prior to unblinding. 
 
After turning in their unused devices (which may be VR101 devices or sham rings), 
participants who elect to continue in the on-label extension will be provided with a new, 
labeled zip-lock bag (as described above) containing two VR101 devices. 

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6 JUSTIFICATION FOR THE CLINICAL INVESTIGATION 
6.1 Need for the Proposed Clinical Investigation 
Following review of the CI02 Clinical Investigation Report, FDA requested that additional 
data be provided to demonstrate the clinical performance of VR101. 
 
6.2 Safety of VR101 in Prior Studies 
As described in Sections 2.4 and 2.5, two prior Clinical Investigations have been 
performed on VR101, where a total of 933 VR101 devices were used. No serious 
adverse device effects (SADEs) occurred in either clinical investigation (CI01 and CI02) 
study. 
 
6.3 Justification of Study Endpoints 
6.3.1 
FSFI-LD 
As a personal lubricant device, VR101 is intended to supplement the body’s natural 
lubrication to enhance the ease and comfort of intimate sexual activity. The Female 
Sexual Function Index (FSFI) is a survey validated to assess sexual function in women. 
The FSFI contains 19 questions, divided in to 6 characteristic domains: Desire, Arousal, 
Lubrication, Orgasm, Satisfaction, and Pain. Although all of these characteristics may be 
improved by use of a personal lubricant, only the Lubrication domain is directly relevant 
to a lubricant’s intended use. 
 
J3 Bio was asked by FDA to assess VR101 efficacy through analysis of individual 
improvement, rather than a comparison of group mean scores. Thus, we have proposed 
a threshold above which a participant’s LD will be deemed resolved to a clinically 
meaningful degree and the participant considered to be a study “responder” (LD 4.5 out 
of 6). In the FSFI cross-validation study (Wiegel 2005) a lubrication sub score threshold 
of 4.35 out of 6 was noted as an accurate discriminant of overall sexual dysfunction. 
Since 4.5 is the next highest achievable score above 4.35, the primary efficacy 
hypothesis will be supported if the proportion of participants reaching a score of 4.5 or 
better following 4 weeks of VR101 use exceeds that following 4 weeks of sham ring use. 
Participants will only be enrolled in the study if they score 1, 2 or 3 (out of 5) on all 4 
Lubrication Questions at baseline. The lower bound of 1 is justified because a score of 0 
on any question would indicate that the prospective participant had not attempted 
intercourse in the past 3 months, which contradicts one of the key study inclusion 
criteria. For this study to yield reliable results, only participants that demonstrate a 
willingness to attempt intercourse should be enrolled. The upper bound of 3 is justified 
because a score of 3 or less represents a non-satisfactory response to each question as 
follows: 
• 
Q7 and Q9: Lubrication “about half the time” or less during intercourse. 

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A Clinical Investigation to Evaluate Efficacy of the J3 
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Personal Lubricant Device in Women 
 
• 
Q8 and Q10: Difficult, very difficult or extremely difficult to become/stay lubricated 
during intercourse. 
6.3.2 
Adverse Events / Adverse Device Effects 
As in CI02, clinical staff will monitor and report all AEs throughout CI03 and attempt to 
determine their relatedness to VR101 use. This will continue to ensure the VR101 functions 
safely as a personal lubricant device. Refer to Section 13 for classification of AEs and ADEs. 
 
7 RISKS AND BENEFITS OF VR101 AND CI03 
7.1 Risk Management 
J3 Bio employs risk management practices to meet the requirements of ISO 14971. 
 
7.2 Clinical Hazard Assessment (CHA) 
A Clinical Hazard Assessment has been performed and is included as Appendix C. 
 
7.3 Risk-Benefit Ratio 
A benefit/risk assessment is included in the Clinical Hazard Assessment (Appendix C). 
The assessment concludes that “Review of the benefits derived by use of VR101 and 
the risks inherent in its use results in a conclusion that the benefits of device use 
outweigh the risks inherent in anticipated end-use and misuse situations.” 
 
8 STATISTICAL CONSIDERATIONS 
CI03 and the following data analyses are designed to comply with the requirements of ICH E3, 
ICH E6, ICH E9, and with guidance from ICH E9 (R1), allowing the investigation to also support 
regulatory submissions and registrations in other countries or regions. 
 
The formal Statistical Analysis Plan (SAP) will be completed prior to database lock and 
unblinding of the of the study data. 
 
8.1 Statistical Hypotheses 
8.1.1 
Primary Efficacy 
• 
The primary efficacy analysis will be a superiority comparison between the proportion of 
participants in each group who report FSFI-LD (lubrication domain composite) scores of 
4.5 or greater after using VR101 or the sham ring for 4 weeks. 
 
• 
This endpoint will reflect changes in FSFI-LD from baseline (Day 0) to the study endpoint 
(Day 28 ± 2). Inclusion criteria were designed to ensure that all study participants enter 
the study at a dysfunctional level as outlined in Section 6.3. The null hypothesis to be 
tested is that similar numbers of women in each of the study groups will report FSFI-LD 
scores of 4.5 or greater (non-dysfunctional) after 4 weeks of exposure to VR101 or the 

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A Clinical Investigation to Evaluate Efficacy of the J3 
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sham device. The planned test statistic is a test for the difference between two 
proportions, α = 0.05, two-tailed. Rejection of the null hypothesis will be interpreted as 
support for the alternative hypothesis, that there is a non-random, statistically significant 
effect (efficacy) for VR101. 
 
HO: μVR101 = μsham 
HA: μVR101  ≠ μsham 
 
8.1.2 
Exploratory 
An exploratory analysis of individual changes in the Female Sexual Function Index (FSFI) total 
composite score (Rosen 2000) and its domains (Desire, Arousal, Lubrication, Orgasm, 
Satisfaction, and Pain) during 28 days of use will be conducted. Similar to the analyses 
conducted by Rosen 2000, changes in individual scores will be compared for the two groups 
using appropriate parametric (independent-test) or nonparametric (Mann-Whitney) statistical 
methods. 
 
8.2 Analysis Groups 
8.2.1 
Target population 
This is the stratum of subjects who are able to adhere to treatment, in other words, the subset of 
the broader population who would adhere to either treatment being compared, in which failure to 
adhere to treatment would not occur. The representative study target population is women with 
deficient vaginal moisture / lubrication who can independently and consistently use a vaginal ring, 
identified through inclusion and exclusion criteria and successful completion of the 4-week 
treatment phase of the study. 
 
8.2.2 
Full Analysis Set (ITT) 
Includes all randomized subjects. 
 
8.2.3 
Modified ITT 
As close as possible to including all randomized subjects, with the assumption that preservation 
of randomization provides the best foundation for statistical comparisons. Any modification to 
the full analysis set will be determined a priori based on specific experience, prior to data lock 
and unblinding. 
 
8.2.4 
Complete Case Set 
The subset of subjects in the full analysis or ITT set who complete all study visits and for whom 
all outcome measures are available. 
 
8.2.5 
Per Protocol Analysis 
The subset of subjects in the full analysis or ITT set who complied with the protocol sufficiently 
to ensure that these data would be likely to represent the effects of study intervention according 
to the underlying study model, all inclusion and exclusion criteria, device use, responses and 

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A Clinical Investigation to Evaluate Efficacy of the J3 
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complete study visits listed in Table 7, Schedule of Events. Protocol violations and deviations 
will be addressed in a way that is less biased and more interpretable and provides more 
information than naïve analysis of the per-protocol set. A complete demographic and baseline 
measure profile will be obtained for each participant at Enrollment (Day 0) and protocol 
compliance will be assessed weekly. Detailed explanations for non-compliance or failure to 
complete the study will be collected. 
 
8.3 Sample Size Determination (ICH E3; 9.7.2 ICH E9; 3.5) 
• 
As noted in Section 6.3.1, effect size and variability for this study were estimated from 
previous experience with VR101 and the literature on FSFI use in similar populations. 
The primary efficacy endpoint, group difference in proportion of subjects whose FSFI-LD 
scores exceed 4.5 (responders) at the end of the 4-week treatment period assuming a 
Sham Group responder rate of 30% and a VR101 responder rate of at least 64%, alpha 
= 0.01 was used for power and sample size calculations. 
• 
The assumed effect size was based on previous studies with VR101 and a sham ring 
using self-reported measures of vaginal lubrication during intercourse (Section 6.3.1). 
The sample size needed to detect a 0.46 effect size while maintaining the probability of 
correctly rejecting the null hypothesis when it is false (power = 1 – beta) was calculated 
using the power and sample size function for a test between two proportions in Minitab 
17 (Minitab 2017) computer software for prospective study design. 
• 
Based on the power curves generated using this information and expected dropout rates 
(Section 8.4), a minimum of 80 subjects randomized to each group (VR101 or sham) of 
the study will provide adequate power for the primary efficacy analysis and continued 
safety evaluation. Robustness of the proposed sample size is justified by the 
considerable uncertainty that exists for expected variance in the FSFI-LD for this study. 

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A Clinical Investigation to Evaluate Efficacy of the J3 
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Figure 4. Robustness of the proposed sample size 
 
8.4 Expected Drop-Out Rates 
Based on experience with the VR101 in previous clinical investigation studies, we 
anticipate that approximately 70% of subjects screened for the study will meet 
inclusion/exclusion criteria and be enrolled, 95% of those enrolled will be randomized to 
treatment groups and is it estimated that of randomized subjects will complete the 
study, per protocol. 
Comparison p 
 
 
 
 
 
 
 
 
 
 
 
 
 
75 
 
 
 
 
 
 
Sample 
Size 
65 
 
 
 
 
 
 
 
 
Power 

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Not 
meeting 
inclusion 
criteria 
N = ~72 
(30% of 
Screened) 
 
 
 
 
 
 
Figure 5. Estimation of participant distribution and drop-out rates 
 
8.5 Pass / Fail Criteria of the Clinical Investigation 
Demonstration of a statistically significant difference (at a 95% confidence level) between 
the study groups for proportions of subjects scoring 4.5 or higher on the FSFI-LD following 
the 4-week treatment phase. 
 
8.6 Adjustment for Multiplicity 
No adjustment for multiplicity is planned as only one hypothesis will be tested. 
 
8.7 Disposition of Missing Data (ICH E3; 9.7.1, 11.4.2.2 ICH E9; 5.3. EMA 
Guideline on Missing Data in Confirmatory Clinical Trials, ICH E9 (R1) 
addendum) 
8.7.1 
Prevention of Missing Data 
• 
Prevention of missing data is a primary aim of this study design. Subjects will be 
counseled at enrollment on the importance of completing the study and 
Screened 
N = ~228 
Enrolled, Randomized 
(ITT) 
N = ~160 (70% of 228) 
  
 
Early 
Termination 
N = ~8 
 
 
Per Protocol Completers 
N = ~ 150 (95% of 160) 

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communicating all issues and concerns to the study coordinator. In turn, the 
study coordinator will provide a “safe” place for disclosure of intent to withdraw 
from the study so that an Early Termination visit and final outcome measures can 
be collected prior to withdrawal of consent. As long as patient safety is assured, 
non-compliance will not require early discontinuation. 
• 
The importance of completeness and quality of data and standardized 
procedures for handling potential dropouts will be emphasized during directed 
training of investigators and clinic/study personnel. Attrition will not be 
encouraged. 
• 
Case report forms (CRFs) will be designed to capture relevant background 
information as well as objective reasons for early discontinuation when it cannot 
be prevented. 
8.7.2 
Incentive to Complete 
• 
Under the FDA guidance for payment and reimbursement to research subjects, 
(January 2018) the sponsor will provide a study completion bonus equal to the 
payment for one regular study visit for subjects who complete the study per 
protocol (with no missing data). 
• 
Participants who complete the 4-week double-blind study will be given an 
opportunity to continue in a 2-week open-label extension where they will be 
guaranteed to receive VR101. 
8.7.3 
Unavoidable Loss of Data 
• 
It is understood that data may still be missing, for anticipated and unanticipated 
reasons (intercurrent events) that arise during the study. As no universally 
applicable methods for handling missing values are recommended in the 
guidance documents, methods for handling missing values in this study will be 
justified by reasons for missingness and predefined by updating this aspect in the 
statistical analysis plan during the blind review. An investigation will be made 
concerning the sensitivity of the results of analysis to the method of handling 
missing values. 
It is expected that any study subject who begins one of the treatment arms 
following randomization will be included in the primary efficacy analysis. As 
noted, randomization criteria require all inclusion criteria are met and that 
screening (Day 0) FSFI-LD scores are complete. The primary efficacy outcome, 
proportion of subjects who have a “functional” score of 4.5 or more after 4 weeks 
of treatment, is therefore dependent on a post randomization FSFI-LD score. 
 
• 
Where unavoidable, participants who cannot complete 28 days of treatment will 
be scheduled for an End of Treatment visit so that final FSFI-LD scores can be 
collected prior to withdrawal of consent. 

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• 
For subjects who must drop out prior to providing study endpoint efficacy data 
the reason for early discontinuation will be ascertained and recorded in the CRF. 
Prior to data lock and unblinding of the randomization code the status and quality 
of each subject’s study data will be assessed by the sponsor’s data quality team. 
The disposition and assignment of each subject to a study population analysis 
group will occur prior to unblinding. 
 
• 
Where final FSFI-LD data are not available and exceed greater than 5% of the 
values for comparison, a mixed model regression analysis that includes the 
dependent variable and one or more auxiliary variables that reflect plausible 
assumptions around the uncertainty due to missing data will be conducted and 
subjected to sensitivity analysis. 
8.7.4 
Missing Data by Groups 
• 
The reasons why data are missing and whether there are systematic differences in the 
patterns of missing data across the treatment arms will also be summarized. Group 
differences will be examined following unblinding using a data summary table for the 
analysis groups. This information will be used to determine the most appropriate 
sensitivity analyses to test assumptions of the mixed model regression approach for 
missing data. 
8.8 Planned Sensitivity Analyses 
We will assess robustness of the findings based on the ITT or MITT analysis using 
comparison of results under different reference-based assumptions about the missing 
values. The final comparison analyses and associated assumptions will depend on the 
nature and patterns of missing data. These methods will be specified prior to breaking the 
randomization code for analysis. 
 
8.9 Final Data Validation and Subject Disposition Determination 
Prior to breaking the randomization code, the designated data review committee and 
study monitor will review all case records and determine subject disposition, assignment 
to subgroups for data analysis, method of dealing with any missing data, and relevant 
sensitivity analyses for alternate approaches. 
9 DATA COLLECTION AND MANAGEMENT 
Paper CRFs (Case Report Forms) will be used for data collection during the  
study. Paper CRFs will be printed on 2-part NCR (no carbon required) with a copy 
retained by the investigators at the conclusion of the study. 
 
Data from CRFs will be transcribed into an electronic database by the sponsor using 
double data-entry following study opening. Since the hand-written original CRF copies 

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will serve as the official study record, Sponsor/analyst bias does not present concern to 
the study, provided double data-entry and an additional, independent data audit of 
database transfer is performed. 
 
10 AMENDMENTS TO THE CIP 
Amendments to the CIP require written authorization of the Sponsor before they are 
recommended to the IRB(s) for approval. No changes will be made to the devices or the 
CIP without Sponsor and IRB approval. 
 
To revise the CIP, the written proposed changes will be reviewed and approved by the 
Sponsor and submitted to the IRB for approval before any changes to the device, 
treatment procedures, assessment methods, data analysis, or any other procedures 
documented in the CIP may be made, or any additional information may be added. 
 
11 DEVIATIONS FROM THE CIP 
11.1 Acceptable Circumstances for Deviations to the CIP 
Investigators shall not deviate from this CIP, except under the following circumstances: 
• 
Deviations may be made with prior approval of the Sponsor if made in deference 
to participant's rights, safety and well-being, or the scientific integrity of the 
clinical investigation. 
• 
Under emergency circumstances, deviations from the CIP to protect the rights, 
safety and well-being of human participants may proceed without prior approval 
of the Sponsor and the IRB. 
 
Such deviations shall be documented and reported to the Sponsor and the IRB as soon 
as possible. 
 
11.2 Procedure for Disqualification and Replacement of a Principal 
Investigator 
Any PI (Principal Investigator) or Sub-PI who has been documented to consistently 
deviate from this CIP, and/or consistently endanger participant's rights, safety and 
wellbeing, or the scientific integrity of the clinical investigation, may be removed from the 
investigation. 
12 DEVICE ACCOUNTABILITY 
12.1 Access to Devices 
Investigational rings (VR101 devices and sham rings) will be stored in a locked cabinet 
that will only be accessible by the PI and study coordinator. Only the study coordinator 
and designated staff members will have access to this cabinet and to the Device 
Accountability log, which contains the list of device numbers assigned to each subject. 

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12.2 Physical Location of Investigational Devices 
The Sponsor shall keep records to document the physical location of all investigational 
devices from shipment of investigational devices and shams to the investigation sites 
until return or disposal. 
 
12.3 Use of Devices 
Investigational devices and sham rings shall only be used in a manner specified by this 
CIP and the clinical protocol. 
 
12.4 Distribution of Devices from the Sponsor to Clinical Sites 
The Sponsor will deliver a specified number of VR101 and sham samples to each 
clinical site. Each clinical site will maintain Device Accountability Logs (see below), to 
which an entry must be made each time a VR101 or sham ring is given to a participant, 
or unused spare or used VR101 or sham ring is returned to the clinic by a participant. 
 
12.5 Device Accountability Log 
The principal investigator, study coordinator or an authorized designee shall keep a 
Device Accountability Log for VR101 and sham rings which shall include: 
• 
The date of receipt and number of devices received from the Sponsor. 
• 
The lot number or any other unique identifier of the rings received. 
• 
The expiration date of rings received, if applicable. 
• 
The number and unique IDs of rings administered to each participant, along with 
their unique participant identifier, and the date issued. 
• 
The number of unused rings returned by each participant, along with their unique 
participant identifier, device identifiers and the date. 
 
13 ADVERSE EVENTS, ADVERSE DEVICE EFFECTS AND 
DEVICE DEFICIENCIES AND REPORTING EVENTS AND 
DEFICIENCIES 
All Adverse Events reported by participants or observed by a clinician during the study and 
whether or not Device Related, must be recorded using the Adverse Event Form. All Adverse 
Event Forms must be provided to the Sponsor. Certain Adverse Events must be reported to the 
Sponsor, IRB and/or FDA as they occur throughout the study (see below and in Sections 13.7 
through 13.11). 
 
SAEs and SADEs (as defined below) are to be reported to the Sponsor and IRB within 
24 hours of the PI becoming aware of their occurrence. 

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All ADEs (as defined below) are to be reported to the Sponsor within 5 days of their occurrence 
if study staff determines that they are possibly, probably or definitely related to use of an 
investigational device (VR101 or sham ring). 
 
13.1 Definitions 
Definitions below were constructed based on guidance from and definitions provided in 
ISO 14155 and 21 CFR 812.3. 
 
Adverse Event (AE): Any untoward medical occurrence, unintended disease or injury, or 
untoward clinical signs (including abnormal laboratory findings) in subjects, users or 
other persons, whether or not related to VR101 use. 
 
Serious Adverse Event (SAE): An AE that leads to: 
• 
Death 
• 
A serious deterioration in the health of the participant, that resulted in any of the 
following: 
- 
A life-threatening illness or injury 
- 
A permanent impairment of a body structure or a body function 
- 
In-patient or prolonged hospitalization 
- 
Medical or surgical intervention to prevent life-threatening illness or injury 
or permanent impairment to a body structure or a body function 
• 
Fetal distress, fetal death or a congenital abnormality or birth defect. 
 
Adverse Device Effect (ADE): An AE related to use of VR101. 
Serious Adverse Device Effect (SADE): An ADE that results in any of the consequences 
characteristic of a SAE. 
 
Unanticipated Serious Adverse Device Effects (USADE): Any SADE that was not 
previously identified in nature, severity, or degree of incidence in this CIP or application 
(including a supplementary plan or application), or any other unanticipated serious 
problem associated with a device that relates to the rights, safety, or welfare of subjects. 
 
Use Error: Act or omission of an act that results in a different response to VR101 than 
intended or than expected by the user. 
Device Deficiency: Inadequacy of a medical device (VR101) with respect to its identity, 
quality, durability, reliability, safety or performance. 
 
The following table, copied from ISO 14155:2011, summarizes how adverse events will 
be categorized. 

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13.2 Anticipated Adverse Events (AE) 
Following is a list of adverse events that may occur during CI03: 
• 
Discomfort/pain/pressure (vaginal, abdominal) 
• 
Vaginal/cervical tissue irritation 
• 
Itching 
• 
Burning 
• 
Vaginal discharge/excess vaginal secretion 
• 
Malodor 
• 
Non-menstrual vaginal/cervical bleeding 
• 
Nausea 
• 
Coital problems 
• 
Penis discomfort (pain, itching, irritation) 
• 
Increased urinary urge 
• 
Increased incontinence 
• 
Constipation 
• 
Bowel obstruction 
• 
Infection (e.g., Bacterial Vaginosis, Yeast Infection, Urinary Tract Infection) 
 
13.3 Anticipated Adverse Device Effects (ADE) 
Following is a list of adverse events that may be related to the use of VR101 or the 
sham: 
• 
Device-related discomfort/pain 

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• 
Device-related cramping 
• 
Device-related vaginal itching/burning/irritation 
• 
Device-related non-menstrual bleeding 
• 
Toxic-shock syndrome 
• 
Ring adherence to the vaginal wall 
• 
Inability of user to remove the ring 
• 
Bowel obstruction 
• 
Ring breakage that causes injury 
• 
Device-related infection 
• 
Device-related vaginal/cervical/urethral irritation/inflammation 
• 
Device-related malodor 
• 
Device-related vaginal discharge (e.g., excessive lubrication / secretions) 
• 
Device-related incontinence 
• 
Intermittent Nausea 
• 
Intermittent Headache 
• 
Physical interference with other intravaginal or intrauterine devices 
 
Some anticipated ADEs listed above are hypothetical, and some have been observed 
clinically. Refer to reports for CI01 and CI02 for a complete list of observed ADEs (either 
definitely or potentially related to VR101 use) and their frequency. 
 
13.4 Device Deficiencies 
Following is a list of device deficiencies that may be related to failure of VR101 or sham 
to meet its acceptance criteria: 
• 
Outer polymeric ring is damaged - no release of contents 
• 
Outer polymeric ring is damaged - release of contents 
• 
Ring weld fails - no release of contents 
• 
Ring weld fails - release of contents 
• 
Device has rough surfaces 
• 
Device will not stay in place 
• 
Device is contaminated (on removal from package, extraneous matter is 
observed) 
• 
Device is too rigid 
• 
Device is too soft 
• 
Device is too large 
• 
Device is too small 
• 
Device is too slippery 
• 
Device cannot be easily inserted 
• 
Device cannot be easily removed 
• 
Instructions are missing and/or hard to follow 
• 
Packaging is difficult to open 
• 
Device is not biocompatible 

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Per the Clinical Hazard Assessment, the residual risks associated with the above device 
deficiencies are adequately mitigated and/or are outweighed by the potential Clinical 
Benefits of VR101. 
 
13.5 Possible Use Errors 
Following are possible use errors, which do not indicate failure of VR101 or sham to 
meet its specifications: 
• 
Placement of ring in the urinary tract 
• 
Placement of ring in the anus or colon 
• 
Oral contact with the device 
• 
Use of damaged device 
• 
Use of contaminated device (packaging damaged) 
• 
Use of user-contaminated device 
• 
Use of user-damaged device 
 
13.6 Unanticipated Serious Adverse Events 
Unanticipated Serious Adverse Events (USAEs) are adverse events occurring during the 
course of a clinical study that meet the following criteria: 
• 
Serious 
• 
Unanticipated 
• 
Definitely, probably, or possibly related to the investigational device or sham 
An unanticipated adverse event is any adverse event occurring in one or more subjects 
participating in a research protocol, whose nature, severity, or frequency is not 
consistent with either: 
• 
The unknown or foreseeable risk of adverse events associated with the 
procedures involved in the research that are described in the protocol related- 
documents, such as the IRB-approved research protocol, and applicable 
investigator brochure, and the current IRB-approved informed consent document, 
and other relevant sources of information, such as product labeling, including 
instructions for use. 
• 
The expected natural progression of any underlying disease or condition of the 
participant(s) experiencing the adverse event. 
 
13.7 Adverse Event Reporting Procedures 
13.7.1 
Unanticipated Adverse Device Effect Reporting 
The FDA’s Investigational Device Exemption (IDE) regulations define an unanticipated 
adverse device effect (UADE) as, “any serious adverse effect on health or safety or any 
life-threatening problem or death caused by, or associated with, a device, if that effect, 
problem, or death was not previously identified in nature, severity, or degree of incidence 
in the investigational plan or application (including a supplementary plan or application), 

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or any other unanticipated serious problem associated with a device that relates to the 
rights, safety, or welfare of subjects” (21 CFR 812.3(s)). 
 
UADEs must be reported by the clinical investigator to the Sponsor and the reviewing 
IRB, as described below: 
• 
Investigators are required to submit a report of a UADE to the Sponsor and the 
reviewing IRB as soon as possible, but in no event later than 8 working days 
after the investigator first learns of the event (§ 812.150(a)(1). The FDA 
requirement is for reporting within 10 days, which has been reduced by 2 days to 
allow more time for investigation). 
• 
Sponsor must immediately conduct an evaluation of a UADE and must report the 
results of the evaluation to FDA, all reviewing IRBs, and participating 
investigators within 10 working days after the Sponsor first receives notice of the 
effect (§§ 812.46(b), 812.150(b)(1)). 
• 
[From 21 CFR 812.46 (b)(2)]: A Sponsor who determines that an unanticipated 
adverse device effect presents an unreasonable risk to subjects shall terminate 
all investigations or parts of investigations presenting that risk as soon as 
possible. Termination shall occur not later than 5 working days after the Sponsor 
makes this determination and not later than 15 working days after the Sponsor 
first received notice. 
 
13.7.2 
Adverse Event Reporting 
Any adverse event (as identified above), whether anticipated or not, shall be reported by 
the investigator to the Sponsor as soon as possible, but in no case later than 5 days 
from the date of its occurrence. 
 
AE collection will begin after consent has been obtained and continue until the final visit. 
Every AE or symptom will be recorded in the CRF and will include: 
 
• 
Nature (Brief Description) 
• 
Date and Time of onset 
• 
Date and Time of resolution 
• 
Severity 
• 
Probability of relationship to study procedures 
• 
Probability of relationship to the investigational device 
• 
Action Taken 
• 
Outcome 
 
Based on the occurrence and intensity of AEs, coupled with results of any other 
observations, the Investigator, at his/her discretion and following discussion with the 
Sponsor, may decide to withdraw a subject or prematurely end the study for reasons of 

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clinical safety. The date of such termination will be recorded, and appropriate treatment 
instituted at the discretion of the Investigator or sub-Investigator. 
 
13.8 Resumption of Terminated Studies 
Since the device is a non-significant risk (NSR) device, the Sponsor is required to seek 
IRB approval, but not necessarily FDA approval to resume a terminated investigation. 
However, if the investigation was terminated under 21 CFR 812.46(b)(2) (see section 
13.7.1 above), FDA and IRB approval are required to resume a terminated study. 
 
13.9 Device Deficiency Reporting 
All device deficiencies related to the identity, quality, durability, reliability, safety or 
performance of an investigational device shall be documented throughout the clinical 
investigation and appropriately managed by the Sponsor. 
 
Device deficiencies that did not lead to an adverse event but could have led to a medical 
occurrence: 
• 
If either suitable action had not been taken, 
• 
If intervention had not been made, or 
• 
If circumstances had been less fortunate, shall be documented in the Sponsor’s 
records. 
Any device deficiencies (as identified above) shall be reported by the investigator to the 
Sponsor as soon as possible, but in no case later than 5 days from the date of their 
occurrence. 
 
13.10 Follow-Up for Adverse Events 
Participants experiencing device-related adverse events will be followed by investigators 
at the investigation site until the clinical situation associated with the device-related 
adverse event is resolved, stabilizes or becomes chronic. 
 
13.11 Communication Plan 
Adverse events at any of the study sites will be brought to the PI's attention when 
identified. Those that are "reportable" events will be submitted to IRBs. The Sponsor will 
discuss any adverse events that impact the investigation with staff members at all study 
sites. 
Any approved changes to the investigational plan will be communicated to the PI and 
research staff at all IRB-approved study sites. Any changes to procedures will require 
training to ensure that new protocol requirements are met. 

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14 ETHICAL CONSIDERATIONS 
This study is to be conducted according to the ethical principles that have their origin in 
the Declaration of Helsinki and that are consistent with Good Clinical Practice and 
applicable regulatory requirements. 
 
The Investigator is responsible for ensuring that the clinical investigation is performed in 
accordance with the protocol, current guidelines on Good Clinical Practice, and 
applicable regulatory requirements. Good Clinical Practice is a standard for the design, 
conduct, performance monitoring, auditing, recording, analysis and reporting of clinical 
investigations that provides assurance that the data and reported results are credible 
and accurate, and that the rights, integrity, and confidentiality of the investigation 
participants are protected. 
 
A qualified clinician will make any medical decisions and decide what medical care is 
given (if applicable). Each individual involved in conducting the investigation should be 
qualified by education, training, or experience to perform his or her respective tasks. The 
investigation can only start at the Investigator's site after the relevant Institutional Review 
Board has approved the protocol, the Informed Consent Forms and other written 
information is provided to the participants, all study personnel have been suitably 
trained, and contractual arrangements identifying responsibilities are signed. 
 
All participants will be informed that participation is voluntary and that they can cease 
participation at any time without giving a reason and without penalty or loss of benefits to 
which they are entitled. However, the Investigator should try to exclude the possibility 
that a participant withdraws voluntarily because of an Adverse Event. 
 
To participate, the participant must give consent prior to enrollment in the investigation. 
This consent must be given in writing. The person who conducts the informed consent 
discussion must also sign the ICF. With consent, the participant confirms that their 
participation is voluntarily and that they will follow the instructions of the investigator and 
answer the questions asked. Signatures must be personally provided and dated. 
Prior to participation in the investigation, the participant should receive a copy of the 
signed and dated written ICF and any other pertinent written information. The Consent 
form must include all elements required by law, local regulations, Good Clinical Practice 
and International Conference on Harmonization (ICH) guidelines, and Food and Drug 
Administration (FDA) requirements as well as any investigation-specific items. 
 
Neither the Investigator, nor their staff should coerce or unduly influence a participant to 
participate in, or continue participating in, the investigation. Ample time must be allowed 
for the participant to make his or her decision to participate in an investigation and to 
make further enquiries about the investigation. 

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The original signed and dated consent form will be kept by the Investigator. 
 
14.1 Institutional Review Board (IRB) 
Institutional Review Boards safeguard the rights, safety, and well-being of investigation 
participants. Thus, the IRB will obtain, and document receipt of, the following documents 
provided by the Sponsor: 
• 
Clinical Investigation Protocol and, if applicable, substantial amendments. 
• 
Template Informed Consent Form and any other information that the Investigator 
proposes for use in the investigation. 
• 
Participant recruitment procedures (e.g., advertisements). 
• 
Written information to be provided to participants (if applicable). 
• 
Investigator's Brochure. 
• 
Safety information. 
• 
Information about payments and compensation available to participants. 
 
In addition, the PI will keep the following documents on file: 
• 
Investigator's current curriculum vitae and/or other documentation evidencing 
qualifications. 
• 
Any other documents that the IRB may need to fulfill its responsibilities. 
 
J3 Bio (Sponsor) will request that the IRB for the site, or other regulatory authorities, 
where applicable, provide its written procedures and membership or voting lists. The IRB 
shall maintain records of its activities and minutes of its meetings. All relevant records 
pertaining to the investigation shall be kept for a period of at least five (5) years after the 
completion of the investigation and will be made available to regulatory authorities on 
request. 
 
14.2 Responsibilities 
14.2.1 
Principal Investigator 
The Principal Investigator, in general, is the person responsible for the conduct of the 
investigation at an investigation center. If a team of individuals at the site conducts the 
investigation, the Investigator is the responsible leader of the team and will be called 
Principal Investigator (PI). The PI must maintain a signed list of appropriately qualified 
persons to whom he/she has delegated significant investigation-related duties, which 
must be specified. A copy is held in the site's files and the original will be sent to the 
Sponsor (e.g., Delegation of Authority). 
 
14.2.2 
A Sub-Investigator (Sub-I, e.g., Medical Professional, Associates) 
The Sub-Investigator is any individual member of the clinical investigation team 
designated and supervised by the PI at an investigation site to perform critical 
investigation-related procedures and/or make important investigation-related decisions. 

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14.2.3 
Sponsor 
The Sponsor is an individual or organization that takes responsibility for the initiation 
and/or implementation of a clinical investigation. J3 Bio accepts the responsibilities of 
the Sponsor. 
 
14.2.4 
Monitor 
Monitoring is the process of overseeing the progress of a clinical investigation, ensuring 
the rights and well-being of participants, and that the investigation is conducted, 
recorded, and reported in accordance with the protocol. Monitoring adheres to standard 
operating procedures, Good Clinical Practice (GCP) and applicable regulatory 
requirements, and ensures that the investigation data are accurate, complete and 
verifiable from source document collection forms. 
 
Before the investigation starts at the investigative site, J3 Bio's appointed monitor will 
ensure that the investigation site has sufficient capacity and equipment to perform the 
investigation. At agreed upon times, the Investigators will permit the monitor to check 
and verify investigation documentation (source document verification), including the CRF 
and other information prepared for J3 Bio (e.g., logs and reports). The Investigator shall 
make corrections, amendments, or clarifying statements where necessary. Investigation- 
related medical decisions are the responsibility of a qualified clinician or medically 
qualified delegate. A written report will be completed by the monitor for J3 Bio after each 
visit. 
 
The Sponsor and IRB require Curriculum Vitae and other relevant documents confirming 
the qualifications of the PI and Sub-Investigators. Any previous training in the principles 
of Good Clinical Practice (GCP) or experience obtained from work with clinical 
investigations and participant care should be described in the Curriculum Vitae. When 
personnel changes are made, the relevant documentation (e.g., Delegation of Authority) 
must be updated before a new member of the team may perform assigned investigation- 
related activities. 
 
15 VULNERABLE POPULATIONS 
The conduct of this study will not deliberately solicit participation from nor enroll 
participants from vulnerable populations. 
 
16 SUSPENSION OR PREMATURE TERMINATION OF THE 
CLINICAL INVESTIGATION (STOPPING RULES) 
The investigation may be prematurely terminated by the Institutional Review Board, 
regulatory authorities, or the Sponsor, if for example, the perception of the risk to benefit 

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A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
ratio becomes unfavorable for the continuation of the investigation. A decision to cease 
the investigation in all centers is binding to all Investigators. If the investigation is 
prematurely terminated or suspended for any reason the Investigator shall promptly 
inform the participants, ensuring appropriate therapy and follow-up for all participants 
and informing the regulatory authorities (where appropriate) and the institution where the 
investigation was being performed. 
 
Further, the Sponsor may terminate the study at any time in a center: 
• 
if the investigator is non-compliant with the protocol, the regulatory requirements 
or the ICH-GCP; 
• 
if the CRF completion or drug accountability is inadequate, and the investigator is 
unable to take corrective action in any of these cases, or; 
• 
in case of failure to recruit subjects. 
 
If an unwanted effect (adverse reaction) is considered severe by the Investigator and 
endangers the health of all subjects, the study will be discontinued after agreement with 
the Sponsor. 
The entire study may be terminated for medical reasons. In addition, the Sponsor retains 
the right to end the study at any time if the study cannot be carried out as agreed upon 
in the study protocol. In case of premature termination, the Investigators, IRBs and 
regulatory authorities will be informed by the Sponsor. 
The Sponsor also reserves the right to terminate the study at any time for administrative 
reasons. The Sponsor will not reimburse the Investigator for the evaluation of subjects if 
the evaluations are conducted in a manner other than that specified in this protocol. 
 
17 CONFLICTS OF INTEREST 
Any PI or Sub-I who has a conflict of interest with this study (such as patent ownership, 
royalties, or financial gain greater than the maximum allowable by their institution) must 
fully disclose the nature of the conflict of interest in accordance with Sponsor policies 
and applicable federal, state, and local laws and regulations. 
 
18 PUBLICATION POLICY 
Neither complete nor any part of the results of the study obtained under this protocol, nor 
any information provided to the Investigator for the purposes of performing the study, will 
be published or passed on to any third party without the written consent of the Sponsor. 
Any Investigator involved in this study is obligated to provide the Sponsor with complete 
test results and all clinical data obtained from participation in this study. The results of 
this clinical investigation may be submitted for publication at the discretion of the 
Sponsor. 

J3 Bioscience, Inc. 
CONFIDENTIAL 
 
 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 57 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
19 RECORDS AND REPORTS 
Requirements for records and reports shall be identified in the Standard Operating 
Procedures (SOPs) or Good Clinical Practice (GCP) documents that identify the 
responsibilities of the Sponsor, Investigator, and Monitor. 
 
20 BIBLIOGRAPHY 
Bachman GA, Notelovitz M, Gonzalez, SJ, Thompson, C, Morecraft, BA. “Vaginal 
Dryness in Menopausal Women: Clinical characteristics and Nonhormonal Treatment.” 
Clinical Practice in Sexuality, 1991; 7(9): 25-32. 
 
Bachmann GA, Notelovitz, M, Kelly, SJ, Owens, A, Thompson, C. “Long Term 
Nonhormonal treatment of Vaginal Dryness.” Clinical Practice in Sexuality, 1992; 8(8/9): 
3-8. 
 
Minitab 17 Statistical Software (2010). [Computer software]. State College, PA: Minitab, 
Inc. (www.minitab.com). 
 
Rosen R, Brown C, Heiman J, Leiblum S, Meston C, Shabsigh R, Ferguson D, 
D’Angostino R Jr. “The Female Sexual Function Index (FSFI): a multidimensional self- 
report instrument for the assessment of female sexual function.” Journal of Sex & Marital 
Therapy, 2000 Apr-Jun; 26(2): 191-208. 
 
Wiegel M, Meston C, Rosen R. “The Female Sexual Function Index (FSFI): Cross- 
Validation and Development of Clinical Cutoff Scores.” Journal of Sex & Marital Therapy, 
2005; 31(1), 1-20. 

J3 Bioscience, Inc. 
CONFIDENTIAL 
 
 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 Page 
58 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
Appendix A 
FSFI Survey and Scoring Method 
 
(Note: Appendix A is 10 pages long including this page) 

Page 1 (of 5) 
 
 
Female Sexual Function Index (FSFI) © 
 
 
Subject Identifier  
 
Date   
 
 
 
INSTRUCTIONS: These questions ask about your sexual feelings and responses 
during the past 4 weeks. Please answer the following questions as honestly and 
clearly as possible. Your responses will be kept completely confidential. In 
answering these questions the following definitions apply: 
 
Sexual activity can include caressing, foreplay, masturbation and vaginal intercourse. 
 
Sexual intercourse is defined as penile penetration (entry) of the vagina. 
 
Sexual stimulation includes situations like foreplay with a partner, self-stimulation 
(masturbation), or sexual fantasy. 
 
CHECK ONLY ONE BOX PER QUESTION. 
 
Sexual desire or interest is a feeling that includes wanting to have a sexual 
experience, feeling receptive to a partner's sexual initiation, and thinking or 
fantasizing about having sex. 
 
1. Over the past 4 weeks, how often did you feel sexual desire or interest? 
 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
 
2. Over the past 4 weeks, how would you rate your level (degree) of sexual desire 
or interest? 
 
Very high 
High 
Moderate 
Low 
Very low or none at all 

Page 2 (of 5) 
 
 
Sexual arousal is a feeling that includes both physical and mental aspects of sexual 
excitement. It may include feelings of warmth or tingling in the genitals, lubrication 
(wetness), or muscle contractions. 
 
3. Over the past 4 weeks, how often did you feel sexually aroused ("turned on") 
during sexual activity or intercourse? 
 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
 
4. Over the past 4 weeks, how would you rate your level of sexual arousal ("turn 
on") during sexual activity or intercourse? 
 
No sexual activity 
Very high 
High 
Moderate 
Low 
Very low or none at all 
 
5. Over the past 4 weeks, how confident were you about becoming sexually 
aroused during sexual activity or intercourse? 
 
No sexual activity 
Very high confidence 
High confidence 
Moderate confidence 
Low confidence 
Very low or no confidence 
 
6. Over the past 4 weeks, how often have you been satisfied with your arousal 
(excitement) during sexual activity or intercourse? 
 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 

Page 3 (of 5) 
 
 
7. Over the past 4 weeks, how often did you become lubricated ("wet") during 
sexual activity or intercourse? 
 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
 
8. Over the past 4 weeks, how difficult was it to become lubricated ("wet") during 
sexual activity or intercourse? 
 
No sexual activity 
Extremely difficult or impossible 
Very difficult 
Difficult 
Slightly difficult 
Not difficult 
 
9. Over the past 4 weeks, how often did you maintain your lubrication ("wetness") 
until completion of sexual activity or intercourse? 
 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
 
10. Over the past 4 weeks, how difficult was it to maintain your lubrication 
("wetness") until completion of sexual activity or intercourse? 
 
No sexual activity 
Extremely difficult or impossible 
Very difficult 
Difficult 
Slightly difficult 
Not difficult 

Page 4 (of 5) 
 
 
11. Over the past 4 weeks, when you had sexual stimulation or intercourse, how 
often did you reach orgasm (climax)? 
 
No sexual activity 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
 
12. Over the past 4 weeks, when you had sexual stimulation or intercourse, how 
difficult was it for you to reach orgasm (climax)? 
 
No sexual activity 
Extremely difficult or impossible 
Very difficult 
Difficult 
Slightly difficult 
Not difficult 
 
13. Over the past 4 weeks, how satisfied were you with your ability to reach orgasm 
(climax) during sexual activity or intercourse? 
 
No sexual activity 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 
 
14. Over the past 4 weeks, how satisfied have you been with the amount of 
emotional closeness during sexual activity between you and your partner? 
 
No sexual activity 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 

 
15. Over the past 4 weeks, how satisfied have you been with your sexual 
relationship with your partner? 
 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 
 
16. Over the past 4 weeks, how satisfied have you been with your overall sexual life? 
 
Very satisfied 
Moderately satisfied 
About equally satisfied and dissatisfied 
Moderately dissatisfied 
Very dissatisfied 
 
17. Over the past 4 weeks, how often did you experience discomfort or pain during 
vaginal penetration? 
 
Did not attempt intercourse 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
 
18. Over the past 4 weeks, how often did you experience discomfort or pain following 
vaginal penetration? 
 
Did not attempt intercourse 
Almost always or always 
Most times (more than half the time) 
Sometimes (about half the time) 
A few times (less than half the time) 
Almost never or never 
 
19. Over the past 4 weeks, how would you rate your level (degree) of discomfort or 
pain during or following vaginal penetration? 
 
Did not attempt intercourse 
Very high 
High 
Moderate 
Low 
Very low or none at all 
Thank you for completing this questionnaire 
Copyright ©2000  All Rights Reserved 
Page 5 (of 5) 

Page 1 (of 4) 
 
 
FSFI SCORING APPENDIX 
 
 
Question 
Response Options 
 
1. Over the past 4 weeks, how often did 
you feel sexual desire or interest? 
5 = Almost always or always 
4 = Most times (more than half the time) 
3 = Sometimes (about half the time) 
2 = A few times (less than half the time) 
1 = Almost never or never 
 
2. Over the past 4 weeks, how would 
you rate your level (degree) of sexual 
desire or interest? 
5 = Very high 
4 = High 
3 = Moderate 
2 = Low 
1 = Very low or none at all 
 
3. Over the past 4 weeks, how often did 
you feel sexually aroused ("turned on") 
during sexual activity or intercourse? 
0 = No sexual activity 
5 = Almost always or always 
4 = Most times (more than half the time) 
3 = Sometimes (about half the time) 
2 = A few times (less than half the time) 
1 = Almost never or never 
 
4. Over the past 4 weeks, how would 
you rate your level of sexual arousal 
("turn on") during sexual activity or 
intercourse? 
0 = No sexual activity 
5 = Very high 
4 = High 
3 = Moderate 
2 = Low 
1 = Very low or none at all 
 
5. Over the past 4 weeks, how 
confident were you about becoming 
sexually aroused during sexual activity 
or intercourse? 
0 = No sexual activity 
5 = Very high confidence 
4 = High confidence 
3 = Moderate confidence 
2 = Low confidence 
1 = Very low or no confidence 
 
6. Over the past 4 weeks, how often 
have you been satisfied with your 
arousal (excitement) during sexual 
activity or intercourse? 
0 = No sexual activity 
5 = Almost always or always 
4 = Most times (more than half the time) 
3 = Sometimes (about half the time) 
2 = A few times (less than half the time) 
1 = Almost never or never 

Page 2 (of 5) 
 
7. Over the past 4 weeks, how often did 
you become lubricated ("wet") during 
sexual activity or intercourse? 
0 = No sexual activity 
5 = Almost always or always 
4 = Most times (more than half the time) 
3 = Sometimes (about half the time) 
2 = A few times (less than half the time) 
1 = Almost never or never 
 
8. 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 
 
9. Over the past 4 weeks, how often did 
you maintain your lubrication 
("wetness") until completion of sexual 
activity or intercourse? 
0 = No sexual activity 
5 = Almost always or always 
4 = Most times (more than half the time) 
3 = Sometimes (about half the time) 
2 = A few times (less than half the time) 
1 = Almost never or never 
 
10. 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 
1 = Extremely difficult or impossible 
2 = Very difficult 
3 = Difficult 
4 = Slightly difficult 
5 = Not difficult 
 
11. Over the past 4 weeks, when you 
had sexual stimulation or intercourse, 
how often did you reach orgasm 
(climax)? 
0 = No sexual activity 
5 = Almost always or always 
4 = Most times (more than half the time) 
3 = Sometimes (about half the time) 
2 = A few times (less than half the time) 
1 = Almost never or never 
 
12. Over the past 4 weeks, when you 
had sexual stimulation or intercourse, 
how difficult was it for you to reach 
orgasm (climax)? 
0 = No sexual activity 
1 = Extremely difficult or impossible 
2 = Very difficult 
3 = Difficult 
4 = Slightly difficult 
5 = Not difficult 
 
 
 
 
 
 
 
 
 
Page 2 (of 4) 

Page 3 (of 4) 
 
 
13. Over the past 4 weeks, how 
satisfied were you with your ability to 
reach orgasm (climax) during sexual 
activity or intercourse? 
0 = No sexual activity 
5 = Very satisfied 
4 = Moderately satisfied 
3 = About equally satisfied and dissatisfied 
2 = Moderately dissatisfied 
1 = Very dissatisfied 
 
14. Over the past 4 weeks, how 
satisfied have you been with the 
amount of emotional closeness during 
sexual activity between you and your 
partner? 
0 = No sexual activity 
5 = Very satisfied 
4 = Moderately satisfied 
3 = About equally satisfied and dissatisfied 
2 = Moderately dissatisfied 
1 = Very dissatisfied 
 
15. Over the past 4 weeks, how 
satisfied have you been with your 
sexual relationship with your partner? 
5 = Very satisfied 
4 = Moderately satisfied 
3 = About equally satisfied and dissatisfied 
2 = Moderately dissatisfied 
1 = Very dissatisfied 
 
16. Over the past 4 weeks, how 
satisfied have you been with your 
overall sexual life? 
5 = Very satisfied 
4 = Moderately satisfied 
3 = About equally satisfied and dissatisfied 
2 = Moderately dissatisfied 
1 = Very dissatisfied 
 
17. Over the past 4 weeks, how often 
did you experience discomfort or 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 
 
18. Over the past 4 weeks, how often 
did you experience discomfort or 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 
 
19. Over the past 4 weeks, how would 
you rate your level (degree) of 
discomfort or pain 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 

 
 
 
FSFI DOMAIN SCORES AND FULL SCALE SCORE 
 
The individual domain scores and full scale (overall) score of the FSFI can be derived from the computational formula 
outlined in the table below. For individual domain scores, add the scores of the individual items that comprise the domain 
and multiply the sum by the domain factor (see below). Add the six domain scores to obtain the full scale score.  It 
should be noted that within the individual domains, a domain score of zero indicates that the subject reported having no 
sexual activity during the past month. Subject scores can be entered in the right-hand column. 
 
 
Domain 
Questions 
Score 
Range 
Factor 
Minimum 
Score 
Maximum 
Score 
Score 
Desire 
1, 2 
1 – 5 
0.6 
1.2 
6.0 
Arousal 
3, 4, 5, 6 
0 – 5 
0.3 
0 
6.0 
Lubrication 
7, 8, 9, 10 
0 – 5 
0.3 
0 
6.0 
Orgasm 
11, 12, 13 
0 – 5 
0.4 
0 
6.0 
Satisfaction 
14, 15, 16 
0 (or 1) – 5 
0.4 
0.8 
6.0 
Pain 
17, 18, 19 
0 – 5 
0.4 
0 
6.0 
Full Scale Score Range 
2.0 
36.0 
 
 
 
 
 
 
 
 
 
 
 
 
 
Page 4 (of 4) 

Proprietary and Confidential. Do not reproduce, in whole or in part, without written consent of J3 Bioscience, Inc. 
 
 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 59 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
Appendix B 
VR101 Investigational Labeling / 
Instructions for Use 
 
(Note: Appendix B is 11 pages long including this page) 

Proprietary and Confidential. Do not reproduce, in whole or in part, without written consent of J3 Bioscience, Inc. 
 
 
J3 Bioscience, 
Inc. 
Labeling Specification 
VR101 Single-Unit Label 
for devices used in CLINICAL 
INVESTIGATIONS 
LBL 001 
Rev. 01 
Page 1 of 5 
 
 
REVISION LOG 
 
Rev Eff. Date 
CO 
Brief Description of Change 
Author
00 17-03-31 2017-06 Original approval and implementation 
pT 
01 
21-01- 
2020 
CR- 
0005 
Update J3 Bioscience Address, Revised Warning for Pregnancy / 
Breastfeeding 
JTC 
 
 
 
 
 
 
 
 
 
 
Distribution List 
Document Control 
R and D 
Manufacturing 
Quality Assurance 
Regulatory 
Clinical 
Cust. Svc/ Purchasing 
Management 
Lubrizol/ Vesta 
Purchasing 
Control Status of This Document: 
Controlled 
Document must be marked as Original, 
Controlled, Uncontrolled or Draft 

Proprietary and Confidential. Do not reproduce, in whole or in part, without written consent of J3 Bioscience, Inc. 
 
 
J3 Bioscience, 
Inc. 
Labeling Specification 
VR101 Single-Unit Label 
for devices used in CLINICAL 
INVESTIGATIONS 
LBL 001 
Rev. 01 
Page 2 of 5 
 
 
1.0 
Part Number 
LBL 001 
 
2.0 
Name VR101 Single-Unit Label- for devices used in clinical investigations 
 
3.0 
Description 
 
Label to be affixed to packaged VR101 devices for exclusive use in clinical 
investigations 
 
4.0 
General Requirements 
 
4.1 
Color: black lettering/graphics on white label 
 
4.2 
Description, Label Dimensions, and Graphics (markings) per following table: 
 
 
Product 
Code 
Description 
& 
Label Size 
Graphic 
LBL 001 
Single-Unit 
Pouch Label 
with 
Pressure- 
Sensitive 
Adhesive 
Backing 
3.3” 
X 
4.0” 
(Label Stock: 
Avery PN 
8164) 
VR101 Vaginal Lubrication Ring 
Manufactured by: J3 Bioscience, Inc. 
825 North 300 West, Suite N231, Salt Lake City, Utah 84103 
VR101 is a personal lubrication device for vaginal application intended 
to moisturize and lubricate, to enhance the ease and comfort of 
intimate sexual activity, and supplement the body's natural 
lubrication. 
CAUTION: Investigational device limited to investigational use only. 
CONTRAINDICATIONS: Use is restricted to patients enrolled in VR101 
Clinical Study. 
WARNINGS: For vaginal use only. VR101 is not a contraceptive, does 
not contain a spermicide and does not protect from any sexually- 
transmitted infections. Keep out of reach of children. Do not ingest or 
place in mouth. If vaginal irritation occurs, discontinue use. If 
symptoms persist, contact your clinician. Do not use if pregnant or 
breast feeding. 
Store at room temperature. 
LBL 001 R01 2020-01 
Expiration Date: 
SEE INSTRUCTIONS FOR USE 

Proprietary and Confidential. Do not reproduce, in whole or in part, without written consent of J3 Bioscience, Inc. 
 
 
J3 Bioscience, 
Inc. 
Labeling Specification 
VR101 Single-Unit Label 
for devices used in CLINICAL 
INVESTIGATIONS 
LBL 001 
Rev. 01 
Page 3 of 5 
 
 
4.3 
Manufacturing 
4.3.1 Label stock will be provided in sheets, 4 labels per sheet 
4.3.2 Text and Marking will be printed using a laser printer 
 
4.4 
Cosmetics 
4.4.1 Text and markings are to be clear and legible 
 
5.0 
Packaging and Labeling 
 
5.1 
Paper Stock (Avery Product) 
5.1.1 Provided in packaging to protect labels from damage during transit 
5.1.2 Labeled to identify contents 
 
 
5.2 
Printed Labels 
5.2.1 Either apply directly to clinical product, or package in clean Zip Lock (or equivalent) bags 
 
6.0 
Special Requirements 
None 
 
7.0 
Shelf Life 
None known 
8.0 
Inspection and Sampling 
 
8.1 
If purchased with Purchase Order, verify that Purchase Order, packing slip and product 
packaging identify item as J3 Bioscience PN 002, Lot Number, PO Number, Quantity, 
and Manufacturing Date. 
8.1.1  Certificate of Compliance is received with order and has been signed and dated by 
supplier representative.(Not Applicable) 
8.1.2 Qualification Requirements: 
 
First Article Inspection 
 
Supplier Survey 
 
Vendor Site Visit 
 
Material Certification 
 
Certification of Compliance 
 
GMP Certification 

Proprietary and Confidential. Do not reproduce, in whole or in part, without written consent of J3 Bioscience, Inc. 
 
 
J3 Bioscience, 
Inc. 
Labeling Specification 
VR101 Single-Unit Label 
for devices used in CLINICAL 
INVESTIGATIONS 
LBL 001 
Rev. 01 
Page 4 of 5 
 
 
 
MSDS 
 
Other:   
 
8.1.3 Inspection Requirements: 
Each lot to be inspected 
Sample Size: 
 
AQL 2.5 C = 0 
 
100% 
 
N = 1 
 
Other: Verify Avery Part No. of label stock 
 
Verify Color of printed label 
 
Verify text and markings are as indicated in table appearing in Section 
4.2. 
 
8.1.4 Inspection Protocol 
8.1.4.1 Documentation Verification 
Assure correct Avery Part Number of label stock. 
8.1.4.2 Material Inspection 
Not required 
8.2.3.3 Acceptance Criteria 
Label roll stock must be correct Avery Part Number 
Text and markings must be as indicated 
Text and markings must not become illegible when attempts are made to rub them off by 
applying manual pressure with a thumb while moving thumb across the label. 
 
8 
Storage and Handling Requirements 
Store indoors, away from sources of light and heat until applied to pouches. 
10.0 
Acceptable Suppliers 
NOTE: SUPPLIER IDENTIFICATION IS FOR J3B USE ONLY (NOT TO BE 
DISTRIBUTED TO SUPPLIERS). Acceptable suppliers are to be identified on the 
last (separate) page of the Part Specification. This page is not to be used or 
referenced when obtaining quotes from potential suppliers or copied to existing 
suppliers. 

Proprietary and Confidential. Do not reproduce, in whole or in part, without written consent of J3 Bioscience, Inc. 
 
 
J3 Bioscience, Inc. 
For INTERNAL USE 
ONLY 
Labeling Specification 
SUPPLIER IDENTIFICATION 
LBL 001 
Rev. 01 
Page 5 of 5 
 
 
Acceptable Suppliers 
Any supplier of Avery Products 

 
J3 Bioscience, Inc. 
For INTERNAL USE 
ONLY 
Labeling Specification 
SUPPLIER IDENTIFICATION 
LBL 002 
Rev. 01  
Page 1 of 5 
 
 
REVISION LOG 
 
Rev Eff. Date 
CO 
Brief Description of Change 
Author
00 17-03-31 2017-06 Original approval and implementation 
pT 
01 
21-01- 
2020 
CR-0005
• Updated Study Contact Numbers from CI02 to CI03 
• Corrected to reflect non-collection of used rings per CI03 
CIP R01 
JTC 
 
 
 
 
 
 
 
 
 
 
Distribution List 
Document Control 
R and D 
Manufacturing 
Quality Assurance 
Regulatory 
Clinical 
Cust. Svc/ Purchasing 
Management 
Lubrizol/ Vesta 
Purchasing 
Control Status of This Document: 
Controlled 
Document must be marked as Original, 
Controlled, Uncontrolled or Draft 

 
 
 
1.0 
Part Number 
LBL 002 
 
2.0 
Name VR101 Instructions for use- for devices used in clinical investigations 
 
3.0 
Description 
 
IFU (Instructions for Use) to be affixed to or accompany VR101 devices used in 
CI 02. 
 
4.0 
General Requirements 
 
4.1 
Color: black lettering/graphics on white label 
 
4.2 
Description, Label Dimensions, and Graphics (markings) per following table: 
 
 
Product 
Code 
Description 
& 
Label Size 
Graphic 
LBL 001 
IFU printed on either standard 
white paper or on white paper 
with pressure-sensitive adhesive 
backing. Preferred Dimensions 
are 8.5 x 11” 
Other dimensions are 
acceptable, as long as print is > 8 
pt font. 
See Next Page for text of IFU 
J3 Bioscience, Inc. 
For INTERNAL USE 
ONLY 
Labeling Specification 
SUPPLIER IDENTIFICATION 
LBL 002 
Rev. 01  
Page 2 of 5 

 
 
 
VR101 Insertion Instructions 
Prior to use, inspect each package for damage. 
Do not use if package or device appears damaged. 
Read ALL Instructions before inserting and removing VR101. 
 
1. Wash and dry your hands thoroughly. 
2. Remove ring from its pouch. 
3. Before inserting VR101, find a position that is comfortable. You can insert the ring while lying down, squatting, or 
standing with one leg up, whatever position is most comfortable for you. 
4. Hold the ring between your thumb and first finger, pressing opposite sides of the ring together. You may want to twist 
it into a figure 8. 
5. It may help you to hold open the folds of skin around your vagina with your opposite hand while inserting the ring. 
6. Place the tip of the ring in the vaginal opening and then push the folded ring gently into your vagina. Push the ring up 
and toward your back. Do not use any lubrication. 
7. If you feel any discomfort, the ring probably is not inserted far enough. Try gently pushing the ring further into your 
vagina. The ring will not get lost in your body. 
8. When you are finished, wash and dry your hands thoroughly. 
 
Return any rings that you were unable to place for any reason to the clinic at your next visit. 
Before returning a ring to the clinic, place in the original foil-lined pouch if available. If not, place in a zip lock-type bag. 
Warnings: 
• 
Do not use the ring if it appears to be damaged and/or if the package appears open or damaged. 
• 
Do not re-insert a ring that you removed or that was expelled if it appears damaged or contaminated. You may 
wash it in clean water and re-insert it if it is clean. 
VR101 Removal Instructions 
Remove each VR101 ring after 7 days of use. 
1. 
Wash and dry your hands. 
2. 
Choose the position that is most comfortable for you. 
3. 
Put you index finger into your vagina and hook it through the ring and gently pull downward and forward to remove 
the ring. 
4. 
Discard the used ring in the trash and out of reach of children and pets. Do not flush the ring in the toilet. 
5. 
Insert a new ring after removal of the used ring, according to the instructions provided above. 
 
 
Warning: Do not re-insert a ring that you removed or that was expelled if it appears damaged or contaminated. You may 
wash it in clean water and re-insert it if it is clean. Or, use a new ring. Return any rings that were unable to be replaced to 
the clinic during your next visit. 
 
If you have any questions or concerns call the study coordinator: 
 
In Utah: 801-542-8190 
In Idaho: 208-377-8653 
 
LBL 002 R01 2020-01 
J3 Bioscience, Inc. 
For INTERNAL USE 
ONLY 
Labeling Specification 
SUPPLIER IDENTIFICATION 
LBL 002 
Rev. 01  
Page 3 of 5 

 
 
 
4.3 
Manufacturing 
4.3.1 Text and Marking will be printed using a laser printer. 
 
4.4 
Cosmetics 
4.4.1 Text and markings are to be clear and legible. 
 
5.0 
Packaging and Labeling 
 
5.1 
Paper Stock (plain paper or paper with pressure-sensitive adhesive backing) 
5.1.1 Provided in packaging to protect labels from damage during transit. 
5.1.2 Labeled to identify contents 
 
 
5.2 
Printed Labels 
5.2.1 Either apply directly to clinical product (paper stock with adhesive backing) or provide as 
inserts with product (plain paper) or independently (plain paper). 
 
6.0 
Special Requirements 
None 
 
7.0 
Shelf Life 
None known 
8.0 
Inspection and Sampling 
 
8.1 
When purchased with Purchase Order, verify that Purchase Order, packing slip and 
product packaging identify item as J3 Bioscience PN 002, Lot Number, PO Number, 
Quantity, and Manufacturing Date. 
8.1.1 As appropriate, verify Certificate of Compliance is received with order and has been 
signed and dated by supplier representative. 
8.1.2 Qualification Requirements: 
 
First Article Inspection 
 
Supplier Survey 
 
Vendor Site Visit 
 
Material Certification 
 
Certification of Compliance 
 
GMP Certification 
 
MSDS 
J3 Bioscience, Inc. 
For INTERNAL USE 
ONLY 
Labeling Specification 
SUPPLIER IDENTIFICATION 
LBL 002 
Rev. 01  
Page 4 of 5 

 
 
 
 
Other:   
 
8.1.3 Inspection Requirements: 
Each lot to be inspected 
Sample Size: 
 
AQL 2.5 C = 0 
 
100% 
 
N = 1 
 
Other: Verify Color of printed label 
 
Verify text and markings are as indicated in Section 4.2. 
 
8.1.4 Inspection Protocol 
8.1.4.1 Documentation Verification 
Not required 
8.1.4.2 Material Inspection 
Not required 
8.2.3.3 Acceptance Criteria 
Text and markings must be as indicated 
Text and markings must not become illegible when attempts are made to rub them off by 
applying manual pressure with a thumb while moving thumb across the label. 
 
8 
Storage and Handling Requirements 
Store indoors, away from sources of light and heat until used. 
10.0 
Acceptable Suppliers 
NOTE: SUPPLIER IDENTIFICATION IS FOR J3 Bio USE ONLY (NOT TO BE 
DISTRIBUTED TO SUPPLIERS). Acceptable suppliers are to be identified on the 
last (separate) page of the Part Specification. This page is not to be used or 
referenced when obtaining quotes from potential suppliers or copied to existing 
suppliers. 
Acceptable Suppliers of labels are any suppliers of Avery Products. 
J3 Bioscience, Inc. 
For INTERNAL USE 
ONLY 
Labeling Specification 
SUPPLIER IDENTIFICATION 
LBL 002 
Rev. 01  
Page 5 of 5 

 
J3 Bioscience, 
Inc. 
Clinical Investigation Plan and Protocol CI03 
CI03-CIP 
Rev. 02 
Page 60 of 60 
A Clinical Investigation to Evaluate Efficacy of the J3 
Bioscience Lubricating Intravaginal Ring VR101 as a 
Personal Lubricant Device in Women 
 
Appendix C 
VR101 Clinical Hazard Assessment 
 
(Note: Appendix C is 14 pages long including this page) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
J3 Bioscience, Inc. 
CONFIDENTIAL 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
 
 
Rev Eff. Date 
(yymmdd) 
CO 
Brief Description of Change 
Author 
00 
190325 
2019-03 New Release 
pT 
 
Participants in this risk assessment: 
Function 
Title 
Name 
Management 
CEO 
R Tyler McCabe, PhD 
R&D/Engineering 
Engineer II (Consultant) 
Justin Clark, PhD 
Regulatory/ 
Quality 
Consultant 
Phil Triolo, PhD, RAC 
Clinical 
Advisor 
Margit Janat-Amsbury, MD 
 
 
Distribution List 
Document Control 
R and D/ Engineering 
Manufacturing 
Quality Assurance 
Regulatory 
Clinical 
Cust. Svc/ Purchasing 
Management 
Control Status of This Document: 
Original 
Document must be marked as Original, Controlled, Uncontrolled or 
Draft 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
 
 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
1. Energy Hazards 
Heat exposure 
Device deformed or 
damaged 
Under anticipated typical 
end use conditions and 
conditions of transport and 
storage, device materials 
are not known to degrade. 
Shelf life studies per P02 
R02 VR101 Shelf Life Evaluation 
Residual Risk: None to report to end users 
Radiation exposure 
(exposure to x-rays, 
MRI, other 
diagnostic imaging 
procedures) 
Material degraded or 
discolored or 
Release rate altered 
Device contains no 
ferromagnetic materials 
(and is therefore MRI 
compatible) and is unlikely 
to be damaged by brief 
exposures to low-level 
radiation 
No validation necessary; radiation exposure is not a risk. 
Residual Risk: None to report to end users 
2. Biological Hazards 
High level of 
bioburden 
on product 
Infection 
Product is manufactured and 
packaged in a controlled 
environment by an 
ISO13485:2003-certified and 
FDA QSR-compliant facility. 
Routine monitoring of 
controlled environment 
demonstrates that 
Results of Water Activity studies reported in CPTC M18-5862 
demonstrate that the glycerol-based lubricating and packaging 
solutions do not support microbial growth (Aw is < 0.60). 
Results of bioburden enumeration studies conducted on 
packaged devices stored for up to 21 months demonstrate a 
low and acceptable bioburden. No viable organisms have been 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
environment is in a state of 
control and the potential for 
device contamination with 
viable organisms is low and 
acceptable. 
detected on any packaged VR101 devices. See Bioburden GLP 
Report from NLI Study 1038660-S01. 
Residual Risk: None to report to end users 
Unacceptably high 
level of 
pyrogens on 
product 
Fever 
Material-mediated pyrogen 
study per WuXi Protocol 
900770-27 
Toxicologic risk 
assessments of substances 
extracted from VR101. 
Pyrogenic responses are not a significant concern for devices 
that are placed in the vagina. 
Nonetheless, results of a material-mediated pyrogenicity study 
(See GLP Report for NLI Study 113438-S01) demonstrate that 
the polymeric ring component of VR101 does not elicit a 
pyrogenic response, and a toxicological risk assessment (See 
Table 9 of Gad Consulting Services Report “Biological Safety 
Assessment of VR101 Lubricating Intravaginal Ring”, dated 18 
January 2019) concludes that the constituent materials of 
VR101 are not known to elicit a pyrogenic response. 
Residual Risk: Device is labelled “non-pyrogenic.” 
Device materials 
present an 
unacceptable 
biological risk 
Toxic, immunology, or 
otherwise untoward 
biological response 
Toxicologic risk 
assessments of substances 
extracted from VR101. 
Biocompatibility studies 
performed by NLI to meet 
ISO10993-1 requirements 
and FDA recommendations 
Results of biological safety (biocompatibility) studies 
demonstrated low and acceptable biological and toxicological 
risks. See Gad Consulting Services Report “Biological Safety 
Assessment of VR101 Lubricating Intravaginal Ring”, dated 18 
January 2019. 
No biological or toxicological effects were seen or reported for 
any of the 21 participants in CI01 or 72 participants in CI02, 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
validating the low and acceptable biological and toxicological 
risk associated with VR101 use. See CI02-R, Section 5.5.1. 
Residual Risk: None to report to end users 
3. Environmental Hazards 
Compatibility with 
other devices 
Damage to condoms, 
damage to IUDs, damage 
to other IVRs (intravaginal 
rings) or other devices 
placed intravaginally 
Condoms: Compatibility of 
VR101 lubricating solution 
evaluated per ASTM D7661- 
10. 
Results of studies performed per ASTM D7661-10 demonstrate 
the compatibility of VR101 lubricating solution with male 
polyurethane and natural rubber latex condoms and female 
FC2 Condoms. See Report R05. 
Other Intravaginal Rings: 
Residual risk of use of 
VR101 with other 
intravaginally placed 
devices will be 
documented. 
Residual Risk: IFU documents that the use of VR101 with other 
intravaginally placed devices has not been investigated. 
IUD (Intrauterine Device, 
e.g., ParaGard®) Residual 
risk of use of VR101 with 
other intravaginally placed 
devices will be documented 
Residual Risk: IFU will document that the use of VR101 with 
other intravaginally placed devices has not been investigated. 
Handling of the 
Damage to device, 
Risks associated with the 
Inspection procedures are in place to assure devices meet 
device 
loss of product 
transport and handling of 
specifications before being released to the marketplace. See 
cleanliness, leak of 
the device are low, as the 
Final Release QA Procedure SOP 7.5-04. 
package contents due to 
device is not provided 
damage to product or 
sterile and, therefore, loss 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
packages, resulting in 
infection or change of 
rate of delivery of 
lubricant 
of the integrity of the 
protective packaging is not 
critical to device function. 
Further, the device is 
robust, with no moving 
parts that could be 
damaged and damage to 
the product or packaging 
would be evident to end 
users. Therefore, the risk of 
damage to devices during 
transport is, by design, 
inherently low and 
acceptable 
VR101 devices are lightweight and have no sharp edges or other 
characteristics that could puncture or otherwise compromise 
their primary packaging. Consequently, no tests were necessary 
to confirm the ability of the primary packaging to protect the 
devices. 
Further damage to the package is obvious to end user and the 
user is instructed to inspect packaging for damage before use, 
and to not use product if damage is apparent. 
Residual Risk: The user is instructed to inspect packaging for 
damage before use, and to not use product if damage is 
apparent. 
Adverse storage 
condition 
Loss of product 
cleanliness, leakage of 
fluid due to damage to 
product or packages, 
material degradation 
See above: Risks associated 
with storage of the device 
in adverse storage 
conditions are low, as the 
device is not provided 
sterile and, therefore, loss 
of the integrity of the 
protective packaging is not 
critical to device function. 
Damage to package is obvious to end user and user is 
instructed to inspect package for damage before use, and to 
not use product if damage is apparent. 
Residual Risk: The user is instructed to inspect packaging for 
damage before use, and to not use product if damage is 
apparent. 
Residual Risk: The device is labeled with the symbol for “Keep 
dry.” 
4. Labeling Hazards 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
Inadequate labeling 
Information on label is 
inadequate, lacks clarity 
or readability, and 
results in device misuse. 
Inspection of labeling for 
integrity and legibility 
Query of users during CI01 
and CI02 on the ability to 
use the device by following 
the provided instructions 
for use 
Responses to Questionnaire used in CI01 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU and having any concerns clarified by 
clinical investigation staff. 
Responses to Questionnaire used in CI02 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU without any input from clinicians or 
others. See Report CI02-R, Section 5.5.3, Claim 2. 
Residual Risk: Labels include the symbol for directing the user 
to See Instructions for Use. 
Inadequate or 
wrong information 
in IFU 
Incorrect use of the 
device 
Query of users during CI01 
and CI02 on the ability to 
use the device by following 
the provided instructions 
for use 
Responses to Questionnaire used in CI01 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU and having any concerns clarified by 
clinical investigation staff. 
Responses to Questionnaire used in CI02 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU without any input from clinicians or 
others. See Report CI02-R, Section 5.5.3, Claim 2. 
Residual Risk: Labels include the symbol for directing the user 
to See Instructions for Use. 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
Missing IFU 
IFU not available when 
needed 
IFUs are affixed to each 
packaged device. 
Final inspection procedures at contract manufacturer assure all 
devices are packaged with instructions for use. 
Residual Risk: None to report to end users 
Allergic response to 
natural latex 
present in packaging 
Skin irritation 
Neither the packaging or 
device is constructed of 
materials containing natural 
rubber latex. 
No verification required, as device is not constructed of 
materials containing natural rubber latex. 
Residual Risk: End user is informed that the device is not 
manufactured using natural rubber latex. 
Allergic response to 
device materials 
Allergic response, 
anaphylactic shock 
Device is composed of 
materials that have not 
been shown to elicit an 
allergic response. 
Device evaluated for 
sensitization per WuXi 
protocol 900850-28. 
Results of Sensitization study NLI 669632 demonstrate that the 
device/device materials are not sensitizers. 
Residual Risk: Device is contraindicated for use in individuals 
with known or suspected allergies to polyurethane or glycerol. 
5. Use- and User-related Hazards 
Improper use of 
device 
Device not placed 
properly, expulsion 
Query of users during CI01 
and CI02 on the ability to 
use the device by following 
the provided instructions 
for use. 
Responses to Questionnaire used in CI01 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU and having any concerns clarified by 
clinical investigation staff. 
Responses to Questionnaire used in CI02 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU without any input from clinicians or 
others. See Report CI02-R, Section 5.5.3, Claim 2. 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
Residual Risk: None to report to end users 
Reuse of 
contaminated 
device 
Infection 
Query of users during CI01 
and CI02 on the ability to 
use the device by following 
the provided instructions 
for use. 
Responses to Questionnaire used in CI01 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU and having any concerns clarified by 
clinical investigation staff. 
Responses to Questionnaire used in CI02 demonstrated users’ 
ability to follow provided directions and use device correctly 
after reading the IFU without any input from clinicians or 
others. See Report CI02-R, Section 5.5.3, Claim 2. 
Residual Risks: The IFU states that the device is for single use, 
only. 
Residual Risk: Instructions for use state that if a device is 
expelled, it may be rinsed off and reinserted. 
Physical movement 
of device during 
activities 
Irritation (mechanical) 
Mechanical tests to assess 
device compressibility (STP 
004.) 
Physical dimensions of the 
device are not significantly 
different from those of 
other currently marketed 
Intravaginal rings. 
Results of mechanical tests to assess device compressibility 
(See R02-A) demonstrate the compressibility of the device is 
comparable to that of clinically acceptable devices. 
The physical dimensions of the device are verified before each 
lot is released (See QAP 001). 
Residual Risk: None to report to end users. 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
Device releases too 
much lubricant 
Leakage of vaginal 
fluids/glycerol solution, 
a user inconvenience 
resulting in lesser device 
use and persistence of 
medical conditions 
STP-008 is followed to 
assure a consistent release 
rate in vitro. 
In CI01 and CI02, users 
were asked to rate their 
daily experience with the 
ring on a scale of 1 to 9, 
with a score of 5 
representing a participant 
response that VR101 was 
providing the "right 
amount" of lubrication, and 
a score of 9 representing 
"too much" lubrication. 
Results of in vitro release studies can be found in R02-D. 
In CI01, the mean daily experience score for the entire study 
population was 6.4 indicating that participants, on average, felt 
that the ring was providing sufficient, but marginally more 
lubrication than needed. See Report CI01-R. 
Participants in CI02 scored the release of lubricant favorably, 
see CI02-M01. 
Residual Risk: None to report to end users 
Device is too rigid 
Discomfort resulting in 
decreased or cessation 
of device use and 
persistence of medical 
conditions 
Mechanical tests to assess 
device compressibility (STP- 
004.) 
In CI01 and CI02, 
participants were 
presented with the 
statement "The ring is 
comfortable to me today," 
and asked to record their 
agreement level on a scale 
of 0 to 4 (where 3 = "Agree 
a Lot" and 4 = "Agree 
Results of mechanical tests to assess device compressibility 
(see R02-A) demonstrate the compressibility of the device 
meets specs and is comparable to that of clinically acceptable 
devices. 
For CI01, the mean agreement level of the study population 
ranged from 2.8 to 3.6 throughout the study, and was only less 
than 3 ("Agree a Lot") on 1 out of 14 study days. Furthermore, 
when participants were asked at each of the 3 clinical visits 
where the question was posed what they would change about 
VR101 during and following use, only 1 of 21 participants said 
that they would make the ring softer. 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
Completely") in their 
diaries. 
Results of CI02 also indicate that users generally found the ring 
to be comfortable, see CI02-R, Section 5.5.3, Claim 3). 
Residual Risk: None to report to end users 
Device is too 
small/soft 
Device expulsion 
resulting in an 
inconvenience to user 
and potential for device 
contamination. 
Mechanical tests to assess 
device compressibility (STP 
004.) 
The physical dimensions of 
the device are not 
significantly different from 
other currently marketed 
IVRs. 
Results of mechanical tests to assess device compressibility 
(See R02-A) demonstrate the compressibility of the device 
meets specs and is comparable to that of clinically acceptable 
devices. 
During CI01, only one device was expelled during the study of 
21 participants (42 rings were inserted, validating that the ring 
isn’t too small for most anticipated users. See Report CI01-R). 
Residual Risk: None to report to end users. 
Device absorbs or 
emits substances 
with unpleasant 
odors or encourages 
the concentration of 
substances with 
unpleasant odors 
Unpleasant odor, 
resulting in lesser device 
use and persistence of 
medical conditions 
Participants in CI01 were 
asked to comment on odor, 
and reports of malodor 
were classified as adverse 
events in CI02 
In CI01, participants were asked if they noticed any unusual 
vaginal odor at any time during the Ring was in place. Most 
participants (16 of 21, 76% of the population) reported "no 
odor at all," while 5 participants reported "a little odor." No 
participants reported noticing "a lot of odor." It should be 
noted that, no attempt was made to assess whether 
participants felt that this odor was related to Ring use, or a 
normal occurrence. 
In CI02, one report of mild malodor was reported in 890 ring 
uses that was deemed “possibly related” to ring use by clinical 
staff. Two other reports of malodor were reported but 
determined to be unrelated to ring use by clinical staff (see 
CI02-R, Section 5.1) 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
Residual Risk: None to report to end users. Ring-related 
malodor does not represent a harm to patient safety. 
Chemical reaction 
with analytes of 
interest, or 
interaction with 
microbes 
Interference with 
laboratory tests leading 
to possible 
misdiagnoses 
No clinical assessments of 
the interference of the 
device with laboratory tests 
have been made. 
No examinations or laboratory tests whose results could be 
corrupted by the presence of the device were conducted 
during CI01 or CI02. Reports in the clinical literature strongly 
indicate that the amount of glycerol present in the vagina will 
not affect relevant lab study results. 
Residual Risk: None to report to end users 
Creation of 
environment 
favorable to 
microbial growth 
Increased potential for 
infection 
Devices are manufactured 
and packaged under clean, 
controlled conditions. 
The water activity of VR101 
lubricating solution is low 
and does not support 
microbial growth. 
Test results reported in CPTC M18-5862 demonstrate that the 
water activity of the VR101 lubricating solution remains at 
levels that do not support microbial growth (aw<0.60) over the 
shelf life of the device. 
None of the bioburden study results, reported for packaged 
devices stored for up to 21 months, were positive for microbial 
growth. Samples have been retained for additional bioburden 
testing at longer storage durations. See Bioburden GLP Report 
from NLI Study 1038660-S01 
None of the participants in CI01 reported any infections during 
the 3-week duration of the study, which included two weeks of 
device use and one week of assessment at the conclusion of 
the 2 weeks of use. 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
One infection was reported by a participant in CI02 which 
resolved when VR101 was removed. The participant continued 
on in the investigation and completed it with no lasting effects. 
Residual Risk: None to report to end users 
Material failure due 
to mishandling 
Release of ring contents 
Tensile test per STP-005 
Use of materials with 
known acceptable tensile 
properties 
Biocompatibility of VR101 
device 
Tensile tests confirm manufactured rings resist tensile forces 
much greater than those anticipated during use. See Report 
R02-B. 
Biocompatibility test results demonstrate risks associated with 
release of ring contents (lubricating solution) are low and 
acceptable. 
No VR101 mechanical failures were reported during CI01 (42 
rings used, each for one week) or CI02 (a total of 890 devices 
and 275 shams used). See Reports CI01-R and CI02-R. 
Residual Risk: User is instructed to See Instructions for Use. 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 

 
J3 Bioscience, 
Inc. 
Title: 
Clinical Hazard Assessment 
VR101 
Doc. #: 
CHA 01 
Rev: 00 
 
Hazards Associated with use of VR101, and Verification or Validation that Hazards are Acceptably Mitigated to Justify placing VR101 on the 
market 
Hazardous 
Condition 
Potential Effect 
Mitigation Method/ 
Verification that Method 
has been Implemented 
Verification or Validation that Potential Hazards are Reduced 
to Acceptable Levels and Users are Adequately Informed of 
Residual Risks 
VR101 is difficult to 
remove 
Device is a foreign body 
that can induce 
infection 
Mechanical tests to assess 
device compressibility (STP- 
004.) 
The physical dimensions of 
the device are not 
significantly different from 
other currently marketed 
IVRs. 
Biocompatibility of VR101 
device. 
Results of mechanical tests to assess device compressibility 
(See R02-A) demonstrate the compressibility of the device 
meets specs and is comparable to that of clinically acceptable 
devices. 
Biocompatibility test results demonstrate risks associated with a 
retained ring are low and acceptable (See Gad Consulting 
Services Report “Biological Safety Assessment of VR101 
Lubricating Intravaginal Ring”, dated 18 January 2019) 
During CI02, 6 of 72 participants had difficulty removing the 
ring. 
Residual Risk: IFU contains the following Warning: “Some 
women may find VR101 difficult to remove. If VR101 removal is 
difficult, a partner may assist. If removal by a partner is difficult, 
not possible, or painful, contact your healthcare provider for 
assistance.” 
 
Conclusions 
 
1. All identified risks have been reduced as far as possible and residual risks have been identified to end users in the 
provided labeling. 
 
2. Review of the benefits derived by use of VR101 and the risks inherent in its use results in a conclusion that the benefits of 
device use outweigh the risks inherent in anticipated end-use and misuse situations.