A Prospective Randomized Efficacy Study Comparing a Pelvic Digital Health System Home Program of Pelvic Floor Muscle Exercise to Kegel Exercises in the Treatment of Stress-Predominant Urinary Incontinence
Phase: NA
Conditions: Stress Urinary Incontinence, Mixed Urinary Incontinence
Sponsor: Renovia, Inc.

 
 
Protocol Version 1.4 
April 18, 2018 
NCT 03632447 
 
A Prospective Randomized Efficacy Study Comparing a Pelvic 
Digital Health System Home Program of Pelvic Floor Muscle 
Exercise to Kegel Exercises in the Treatment of Stress-
Predominant Urinary Incontinence 
 
April 18, 2018 
 

 
 
Protocol Version 1.4 
April 18, 2018 
 
 
 
 
 
 
 
 
Project No.: Renovia-05 
Sponsor No:  
 
 
 
 
A Prospective Randomized Efficacy Study Comparing a Pelvic Digital Health System 
Home Program of Pelvic Floor Muscle Exercise to Kegel Exercises in the Treatment 
of Stress-Predominant Urinary Incontinence 
 
 
 
 
 
 
 
FDA Statement 
The leva Incontinence System is an investigational medical device under development. It has 
been designed to meet the requirements of IEC 60601-1:2005 (3RD Edition), Medical 
Electrical Equipment-Part 1:  General requirements for basic safety and essential 
performance; IEC 60601-1-2:2014 (4th Edition), Medical electrical equipment-Part1-
2:General requirements for basic safety and essential performance-Collateral standard: 
Electromagnetic compatibility-Requirements and tests; and IEC 60601-1-1-11, General 
requirements for basic safety and essential performance-Collateral standard: Requirements 
for medical electrical equipment and medical electrical systems used in the home healthcare 
environment. In addition, all materials that will come into contact with the patient have 
undergone biocompatibility evaluation satisfying ISO 10993-1 requirements. All patient 
contacting materials have been tested, and passed cytotoxicity, sensitization and irritation or 
intra-cutaneous standards. Leva poses little to no risk to the patient if used as instructed.  
  
The PFDx device is an investigational medical device currently used to gather data related to 
pelvic floor health. It uses substantially equivalent technology to the leva Incontinence 
System, an FDA-approved, Class II medical device. Whereas the leva device uses 6 
accelerometer sensors, the PFDx device uses 12 sensors, allowing for a more complete 
evaluation of a woman’s physiology. The PFDx device is shaped as a ring that sits in the 
fornix with a thin, flat strip that descends along and out of the vagina. At the end of the 
device (outside the woman’s body) is a small enclosure that houses a microprocessor and a 
Bluetooth Low Energy radio. The PFDx communicates wirelessly to the associated 
Chromebook ClinApp in a similar manner to the leva device. All sensors related components 
are over-molded with the same biocompatible silicone material used to manufacture 

 
 
Protocol Version 1.4 
April 18, 2018 
the leva device. Given the similarity of PFDx and leva, along with independent risk 
analysis, leva Plus is considered a “non-significant risk device” as defined by 21 CFR 
812.3(m). 
GCP Statement 
This study is to be performed in full compliance with the protocol, Good Clinical Practices 
(GCP), and applicable regulatory requirements. All required study documentation will be 
archived as required by regulatory authorities. 
 
Confidentiality Statement 
This document is confidential. It contains proprietary information of Renovia, Inc. Any 
viewing or disclosure of such information that is not authorized in writing by Renovia, Inc. is 
strictly prohibited. Such information may be used solely for the purpose of reviewing or 
performing this study. 

leva Plus Device  
 
Sponsor No.:   
Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
1 
PROTOCOL REVISION HISTORY 
Date/Name 
Description 
23 March 2018 
Version 1.0  
28 March 2018 
Version 1.1 
6 April2018 
Version 1.2 
18 April 2018 
Version 1.3 
09 May 2018 
Version 1.4 
 
 
 

leva Plus Device  
 
Sponsor No.:   
Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
 
PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES 
A Prospective, Nested, Randomized Efficacy Study Comparing a Pelvic Digital 
Health System Home Program of Pelvic Floor Muscle Exercise to Kegel Exercises 
in the Treatment of Stress-Predominant Urinary Incontinence 
 
 
 
SPONSOR: 
Renovia, Inc. 
263 Summer Street 
5th Floor 
Boston, MA 02210 
 
SPONSOR’S 
REPRESENTATIVES: 
Samantha Pulliam, MD 
Chief Medical Officer 
Tel.:  +1 857-891-3057 
E-mail: sjpulliam@renovia.com  
 
 
 
 
 
Signature 
 Date 
 
 
 

leva Plus Device  
 
Sponsor No.:   
Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
 
A Prospective, Nested, Randomized Efficacy Study Comparing a Pelvic Digital 
Health System Home Program of Pelvic Floor Muscle Exercise to Kegel 
Exercises in the Treatment of Stress-Predominant Urinary Incontinence 
 
 
 
Signature 
 Date 
 
 
 

leva Plus Device  
 
Sponsor No.:   
Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
2 
TABLE OF CONTENTS 
1 PROTOCOL REVISION HISTORY ................................................................................ 4 
PRINCIPAL INVESTIGATOR AND SPONSOR – SIGNATORIES ....................................... 5 
2 TABLE OF CONTENTS ................................................................................................. 7 
3 SYNOPSIS ..................................................................................................................... 9 
4 STUDY EVENTS FLOW CHART ..................................................................................11 
5 ABBREVIATIONS .........................................................................................................11 
6 BACKGROUND ............................................................................................................13 
7 STUDY OBJECTIVE AND ENDPOINT .........................................................................14 
7.1 Study Objective .....................................................................................................14 
7.2 Study Endpoint(s)..................................................................................................14 
8 INVESTIGATIONAL PLAN ...........................................................................................15 
8.1 Overall Study Design and Plan..............................................................................15 
8.1.1 
Confinement and Return Visits ................................................................19 
8.2 Risks and/or Benefits to Subjects ..........................................................................19 
8.3 Selection of Study Population ...............................................................................21 
8.3.1 
Inclusion Criteria ......................................................................................21 
8.3.2 
Exclusion Criteria .....................................................................................21 
8.3.3 
Removal of Subjects from the Study ........................................................22 
8.3.4 
Prohibitions and Concomitant Therapy ....................................................22 
8.4 Treatments ............................................................................................................22 
8.4.1 
Treatment Administered ..........................................................................22 
8.4.2 
Treatment Compliance ............................................................................22 
9 STUDY PROCEDURES ................................................................................................23 
9.1.1 
Adverse Events .......................................................................................23 
9.1.1.1 Monitoring ..................................................................................23 
9.1.1.2 Serious Adverse Event ..............................................................23 
10 DATA ANALYSIS .........................................................................................................24 
10.1 Statistical Methods ................................................................................................24 
10.1.1 
Determination of Sample Size .................................................................24 
10.1.2 
Subjects to Analyze .................................................................................24 
10.2 Safety Evaluation ..................................................................................................24 
11 STUDY ADMINISTRATION ..........................................................................................25 
11.1 Ethics ....................................................................................................................25 
11.1.1 
Institutional Review Board .......................................................................25 
11.1.2 
Ethical Conduct of the Study ...................................................................25 

leva Plus Device  
 
Sponsor No.:   
Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
11.1.3 
Subject Information and Consent .............................................................25 
11.2 Termination of the Study .......................................................................................25 
11.3 Data Quality Assurance.........................................................................................25 
11.4 Direct Access to Source Data/Documents .............................................................25 
11.5 Study Device Supplies, Packaging and Labeling ...................................................25 
11.6 Data Handling and Record Keeping ......................................................................26 
11.7 Publication Policy ..................................................................................................26 
12 REFERENCES ..............................................................................................................26 
 
 
 
 

leva Plus Device  
 
Sponsor No.:   
Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
 
3 
SYNOPSIS 
Device: 
Leva PLUS Pelvic Digital Health System 
Clinical Indication: 
Urinary Incontinence 
Study Objective: 
Primary objectives:  
• 
Compare the efficacy of using a novel intravaginal 
system (leva® Plus Pelvic Digital Health System TM) to 
perform pelvic floor muscle exercises (PFME) compared 
to a Kegel exercise home program in women with stress-
predominant urinary incontinence (SUI).  
 
HYPOTHESIS: The leva® Plus Pelvic Digital Health 
System is superior to a home PFME program in the 
treatment of stress-predominant urinary incontinence. 
HYPOTHESIS: The leva® Plus Pelvic Digital Health 
System leads to more significant improvements in pelvic 
floor muscle performance than a home PFME program. 
 
 
• 
Evaluate the contribution of the Digital Health Platform in 
adherence and treatment of SUI for long term 
maintenance therapy. 
 
HYPOTHESIS: The Digital Health Platform improves 
adherence to a long-term maintenance program of pelvic 
floor muscle exercises.  
 
Summary of Study 
Design: 
A prospective, randomized, nested study.  
Screening of subjects will occur in up to 1 study visits to 
determine study eligibility. 
Subjects will be randomized to Kegel exercises (control group) 
or study device/digital health system use (treatment group).  
Subjects randomized to the treatment group will be further 
randomized to follow up with digital reminders or follow up 
without digital reminders after 8 weeks of leva Plus use.  
Up 
to 
225 
subjects 
(inclusive 
of 
all 
sites) 
meeting 
inclusion/exclusion criteria at Screening will complete a baseline 
assessment including pelvic examination, evaluation with the 
PFDx Device and a packet of validated surveys and will then 
complete 8 weeks of training either with a study device (the 
treatment group) or with Kegel exercises (the control group) to 
improve the strength of their pelvic floor muscles.  
All subjects will return to the clinic to complete a packet of 
surveys to assess improvements in the symptoms of their 
urinary incontinence at week 4 and undergo a pelvic floor 

leva Plus Device  
 
Sponsor No.:   
Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
muscle assessment using the PFDx device to measure pelvic 
floor movement. All subjects will return to the clinic for an end-
of-study visit at week 8 including a pelvic floor assessment 
using the PFDx device to measure pelvic floor movement, 
physical examination, and complete a packet of surveys.  Follow 
up emails or mailings for additional survey completion will occur 
6 and 12 months after the study.  
Blinding: 
Examiners at study visits will be blinded to randomization 
Number of Subjects: 
Up 
to 
225 
subjects 
(inclusive 
of 
all 
sites) 
meeting 
inclusion/exclusion criteria at Screening visit will return to the 
clinic to participate in the treatment phase of the study.  
Study Treatment: 
leva  Plus Pelvic Digital Health SystemTM 
Key Assessments: 
The following analyses will be performed: 
Efficacy: 
• 
PFDx device pelvic floor muscle evaluation 
• 
Voiding diary 
• 
Brinks Score 
• 
Survey evaluations of incontinence including: 
o MESA 
o PFDI 
o WHODAS 
o PISQ-IR 
o McGill Pain Questionnaire  
o SESPPFE 
o Patient Global Impression of Severity (PGI-S) Scale 
o Patient Global Impression of Improvement (PGI-I) 
o PFIQ 
Safety and Tolerability: 
o 
Subjects will be monitored for adverse events and 
serious adverse events.  

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Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
4 
STUDY EVENTS FLOW CHART 
Intervention and 
outcomes 
Screening 
Visit 
Baseline 
4 weeks 
8 
weeks  
6 
months  
12 
months 
Eligibility and informed 
consent 
x 
 
 
 
 
 
Urine Pregnancy Test (if 
indicated) 
x 
 
 
 
 
 
UDI-6 
x 
 
 
 
 
 
Medical History 
x 
* 
 
 
 
 
MESA questionnaire 
x 
 
 
 
 
 
POP-Q 
x# 
 
 
x 
 
 
Brinks Scale 
 
x* 
 
x 
 
 
Primary Outcome 
Measures (PFDI, PGI-I, 
PGI-S) 
 
x 
x 
x 
x 
X 
PFDI, 
WHODAS, 
PISQ-IR, McGill Pain 
Questionnaire  
SESPPFE, 
PGI-S,  
PGI-I, 
PFIQ 
 
 
x 
x 
x 
x 
X 
PFM performance 
assessment (PFDx) 
 
x 
x 
x 
 
 
3-day voiding diary  
x (before 
baseline 
visit) 
 
 
x 
 
 
CGI-S, CGI-I 
x 
 
 
x 
 
 
Complications 
 
 
x 
x 
 
 
Follow up questions 
detailing further 
treatments for SUI 
 
 
 
 
x 
X 
*May be done at screening visit if < 3 months prior to baseline visit 
# May be from a visit within 3 months of baseline visit. 
 
5 
ABBREVIATIONS  
AE 
Adverse event 
CFR 
Code of Federal Regulations 
CGI-I 
Clinical Global Impression of Improvement 
CRF 
Case Report Form 
CRU 
Clinical Research Unit 
EOS 
End of Study 

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Renovia, Inc. 
 
Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization 
IRB 
Institutional Review Board 
MESA 
Medical, Epidemiologic and Social Aspects of Aging 
N 
PFDI 
Number of subjects 
Pelvic Floor Distress Inventory 
PFIQ 
Pelvic Floor Impact Questionnaire 
PGI-I 
Patient’s Global Impression of Improvement 
PGI-S 
Patient’s Global Impression of Severity 
PI 
PISQ-IR 
POP-Q 
Principal Investigator 
Pelvic Organ Prolapse/Incontinence Sexual Questionnaire 
Pelvic Organ Prolapse- Quantitative 
QA 
QUID 
Quality Assurance 
Questionnaire for Female Urinary Incontinence Diagnosis 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
SESPPFE 
Standard deviation 
Self-Efficacy Scale for Practicing Pelvic Floor Exercises 
UAE 
Unexpected adverse event 
US 
United States 
WHODAS 
World Health Organization Disability Assessment 
 
 
 
 
 
 
 
 
 

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Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
6 
BACKGROUND  
Pelvic floor muscle exercises (PFME), also known as Kegel exercises, are the first line 
conservative treatment for pelvic floor disorders, specifically stress urinary incontinence(SUI) 
within the urogynecology community. Studies have shown that performing PFME and/or 
pelvic floor physical therapy (PFPT) is the most effective non-invasive treatment for SUI.  
Some women have trouble identifying and contracting the correct muscles when performing 
PFME. The leva Pelvic Digital Health System TM is an innovative device that allows women 
to have real-time visual verification that PFME is performed correctly and consistently by 
guiding women through pelvic floor muscle lifting. The leva Pelvic Digital Health System TM 
also measures and records the results of every PFME session performed while using the 
device thus encouraging patient compliance. Data generated during exercise is transmitted 
to a safe, HIPAA compliant database in a cloud, from which an algorithm used to evaluate 
adherence can be used to provide automatic reminders and education via text message to 
encourage participation. In the proposed study we hypothesize that the leva Digital Health 
Platform:  
• 
improves adherence to a long-term maintenance program of pelvic floor muscle 
exercises.  
• 
leads to more significant improvements in pelvic floor muscle performance than a 
home PFME program.  
 
There are other alternative biofeedback devices that are home-based and approved by the 
FDA, however these are expensive and may not be covered by insurance.  There is no 
research to demonstrate that these devices are better than a PFME with or without 
supervision of a pelvic floor Physical Therapist. The leva device has a unique way of 
verifying muscle contraction that is not focused on strength, but rather vertical displacement 
with muscle contraction. 
 

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Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
7 
STUDY OBJECTIVE AND ENDPOINT 
7.1 
Study Objective 
Primary objectives:  
 
• 
Compare the efficacy of using an innovative intravaginal system (leva® Digital Pelvic 
SystemTM) to perform pelvic floor muscle exercises (PFME) compared to a Kegel 
exercise home program in women with stress-predominant urinary incontinence 
(SUI).  
HYPOTHESIS: The leva® Plus Pelvic Digital Health System is superior to a home 
PFME program in the treatment of stress-predominant urinary incontinence. 
 
• 
Compare the effect of the Leva® Plus Pelvic Digital Health System with home PFME 
program on measures of pelvic floor muscle performance 
HYPOTHESIS: The leva® Plus Digital Pelvic System leads to more significant 
improvements in pelvic floor muscle performance than a home PFME program 
 
• 
Evaluate the contribution of the Digital Health Platform in adherence and treatment of 
SUI for long term maintenance therapy. 
HYPOTHESIS:  The Digital Health Platform improves adherence to a long-term 
maintenance program of pelvic floor muscle exercises.  
. 
 
 
7.2 
Study Endpoint(s) 
Efficacy: 
Efficacy, the primary outcome will be evaluated following 8- weeks of treatment at an in-
person interview by study personnel blinded to randomization, and then again by phone and 
email or mail at 6- and 12- months.  Two validated measures will be used to evaluate 
primary outcomes.  First, the patient global impression of improvement (PGI-I), with success 
was defined as a response of “much better” or “very much better”.  Second, the Pelvic Floor 
Distress Inventory (PFDI-20) urinary distress inventory (UDI-6), with success defined as the 
absence of bothersome stress incontinence symptoms as indicated by an answer of “no” to 
the stress incontinence subscale items OR a response of “yes” but with a bother of “not at 
all” or “somewhat.  Other responses will not be considered successes.  
 
Safety and Tolerability: 
1. Reported Adverse Events (AEs) and Serious Adverse Events (SAEs) 

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Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
8 
INVESTIGATIONAL PLAN 
8.1 
Overall Study Design and Plan 
• 
A prospective, nested, randomized multicenter controlled study to evaluate the 
efficacy of using the leva® Plus Digital Pelvic System to perform PFME in 
comparison to Kegel exercises.  
• 
Subjects will be patients referred to a Urogynecologist’s office for evaluation.  
• 
Following completion of baseline screening and consent, patients will be randomized 
by study coordinators at the baseline office visit using an automated randomization 
system.   
• 
Patient population: women with moderate to severe SUI or stress-dominant mixed 
urinary incontinence.  
• 
The duration of participation is 8- weeks, with expected post-intervention follow up 
surveys 6- and 12-months after study terminus.  
• 
Up to 75 participants per site will be enrolled for a total of 225 subjects in the trial.  
 
 
STUDY ENROLLMENT 
The women interested in the study will be screened for participation based on 
inclusion/exclusion criteria and the MESA questionnaire identifying stress or stress-dominant 
mixed incontinence, and the UDI-6 (score > 25).  
 
Screening visit: The study will be explained by the study staff and the consent will be 
reviewed with prospective participants.   
 
1) The following questionnaires will be administered: 
a. MESA 
b. UDI-6 
2) Pelvic exam will be performed including: 
a. POP-Q (acceptable to report from an exam within 3 months of baseline) 
b. Pelvic floor muscle assessment (Brink Scale) (may be performed at baseline 
or screening visit (if screening < 3 months prior to baseline) 
3) If the eligibility requirements are met, patients should be given a 3-day voiding diary 
(acceptable if reported within 3 months of baseline visit) 
 
The consent will be obtained by the licensed physician investigators or study assistants. 
Study participation will be entirely voluntary. 
 
STUDY PROCEDURES 
Once patients have undergone the appropriate screening evaluation, met criteria for study 
participation, and provided informed consent, subjects will be randomized to one of two 
study arms.  The “Kegel” arm will involve patient education and performance of Kegel 
exercises, the current standard of care.  The “Leva” arm of the study will undergo patient 
education and performance of pelvic floor muscle exercises using the Leva system.  
Subjects in the “Leva” arm will be sub-randomized to one of two long term follow up plans, 
follow up without reminders or follow up using automated reminders by text message.  
 

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Project No.: Renovia-05 
 
Protocol Version 1.4 
April 18, 2018 
Subjects will complete validated standardized quality of life questionnaires and pelvic floor 
muscle testing using the PFDx device at in-office visits at baseline, 4 weeks and 8- weeks. 
They will record 3-day voiding diaries at baseline and at 8-weeks.  Beyond 8- weeks 
subjects will be asked to participate in follow-up calls at 6 and 12 months and complete 
validated standardized quality of life questionnaires by mail or email.  Patients who were 
randomized to the Leva arm of the study and were sub-randomized to the “follow up 
reminder” will receive weekly reminders to perform their pelvic floor exercises using the Leva 
device 
 
The study will be funded by Renovia, who will provide leva Plus and PFDX devices for the 
study and subject re-numeration.  
 
$50 for the baseline visit with the study team 
$50 for the 4-week follow up visit 
$100 for the 8-week final study visit 
$50 for the completion of >80% of the study exercises  
$50 upon completion and return of surveys at 6 months 
$50 upon completion and return of surveys at 12 months. 
 
Please note that $300 compensation is provided for every subject who 
completes the study in its entirety. This compensation level will increase to $350 
for those subjects in either arm who attest to completion of >80% of the study 
exercises.  
 
 
Initial payment will occur by the site and in a manner consistent with individual site policy 
after the completion of the 8-week final study visit.  Compensation will occur immediately 
following the return of completed 6-month and 12-month surveys.   
If the subject leaves study early, the subject will receive a pro-rated amount based on the 
study milestones completed. Subjects will be compensated $25 for unscheduled return 
visits. 
Subjects will be reimbursed for parking costs associated with their visits. 
 
Visit #1 – Baseline visit - the participants will undergo the following procedures: 
 
Following completion of baseline evaluation and consent, patients will be randomized by 
study coordinators at the baseline office visit using an automated randomization system. 
 
1) Medical history including GYN history, OB history, medical diagnoses, medications, 
and prior surgical procedures. 
 
2) Questionnaires:  
a. PFDI 
b. PISQ-IR 
c. McGill Pain Questionnaire  
d. SESPPFE 
e. Patient Global Impression of Severity (PGI-S) Scale 
f. WHODAS 

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Protocol Version 1.4 
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g. PFIQ 
 
3) Voiding diary – collection of a 3-day intake and output and symptoms diary 
completed before baseline visit 
 
4) Health Care Provider will perform a Pelvic Organ Prolapse Quantitative (POP-Q) 
assessment (If not completed at screening) 
 
5) The PFDx device will be then used to measure the pelvic floor angles and strength. 
This will be supervised by clinical research personnel blinded to randomization.  
 
6) To optimize blinding to arm, the randomization will occur following the above surveys 
and evaluations. 
 
Following randomization, the subject will participate in one of two main study arms: 
 
.   
 
KEGEL STUDY ARM 
• Subjects randomized to the Kegel Arm will receive standardized written and verbal 
instructions on how to perform three times daily/7 days per week pelvic floor muscle 
exercises and their ability to perform the correct muscle action will be confirmed by 
physical exam (written instructions per the handout, adapted from Voices for PFD).  They 
will be instructed to perform these exercises three times daily throughout the 8-week 
study period, based on a commonly used kegel regimen. These instructions will occur 
during the baseline visit.  Also at the baseline visit, subjects will be informed they will be 
asked to attest to the fact that they performed these exercises twice daily at least 80% of 
the time (approximately 17 times per week).  This attestation will ask the subject to recall 
their adherence; no diary or other record will be required.   
• Subjects will return to the office on week 4 to participate in validated questionnaires and 
undergo a progress evaluation using the PFDx. For clinical questions they will be directed 
to follow up with their physician. Their evaluator will be blinded to their randomization. 
• Subjects will return to the office on week 8- to participate in validated questionnaires, 
undergo progress evaluation using the PFDx, and physical examination including a 
POP-Q and Brinks score, and attest to their adherence. Their evaluator will be blinded to 
their randomization 
• Following week 8, patients will be recommended to continue weekly Kegel exercises, but 
will be free to pursue alternative treatments if desired.  They will participate over the 
phone and via email or mail in validated questionnaires, in addition to reporting what (if 
any) additional therapies they have undergone for treatment of stress urinary 
incontinence at 6 months and 12 months after baseline.  
 
LEVA STUDY ARM 
• Subjects randomized to the leva® Plus Pelvic Digital Health System will receive training 
on the use of the Leva® Plus Digital Health System including installation of the Digital 
Health System app, the completion of a training module, a timed lift test and one full leva 
exercise session of five timed lifts. Training will occur at the baseline visit.  Subjects will 
be instructed to perform the lifts twice a day, for 2 ½ minutes each session, 7 days a 
week for a total of 8- weeks.  Subjects will be informed they will be asked to attest to the 
fact that they performed these exercises twice daily at least 80% of the time 
(approximately 11 times per week).  This attestation will ask the subject to recall their 

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Protocol Version 1.4 
April 18, 2018 
adherence; no diary or other record will be required, although they will also be informed 
that the leva digital system tracks adherence.  During the study period (8-weeks) 
subjects with the leva will contact the Renovia Patient Care Engagement team with any 
technical questions or issues regarding leva use. They will receive regular (6 days/week) 
text messages based on their performance of pelvic floor muscle exercises using the 
Leva device using predetermined algorithm for content.  For any clinical questions they 
will be directed to their physician’s office to speak with a healthcare provider.  
• Subjects will return to the office on week 4 to participate in validated questionnaires (see 
chart) and undergo progress evaluation using the PFDx device. For clinical questions 
they will be directed to follow up with their physician. Their evaluator will be blinded to 
their randomization.     
• Subjects will return to the office on week 8 to participate in validated questionnaires (see 
chart) and undergo progress evaluation using the PFDX device and physical 
examination including a POP-Q and Brinks score, and attest to their adherence.  Their 
evaluator will be blinded to their randomization.  
•  Following week 8, patients will be recommended to continue weekly pelvic floor muscle 
exercises using the leva device but will be free to pursue alternative treatments if 
desired.  Based on initial sub-randomization, subjects will receive periodic standardized 
text messages reminding them to use the leva over the next 10 months or receive no 
additional contact via the leva device.  
• 
At 6- and 12- months they will participate in validated questionnaires (see chart) by 
phone and email or mail, in addition to reporting what (if any) additional therapies they 
have undergone for treatment of stress urinary incontinence at 6 months and 12 months 
after baseline. 
• 
The third party research center will provide a single phone call to the subjects receiving 
the leva plus to ensure the device is functioning properly.  If there are questions 
regarding the device function, a conference call will be undertaken to allow the subject to 
trouble-shoot device function with the sponsor technical specialist.   The sponsor will at 
no time posess protected health information (PHI) 
 
VISIT CONTENT 
At week 4 all study participants will return to the office to undergo a PFDx evaluation of 
pelvic floor muscle function and complete and return the following questionnaires: 
 
a. PFDI 
b. PISQ-IR 
c. McGill Pain Questionnaire  
d. SESPPFE 
e. Patient Global Impression of Severity and improvement (PGI-S, PGI-I) Scale 
f. WHODAS 
g. PFIQ 
 
 
At week 8 all study participants in both arms will return to the clinic for the PFDx device 
evaluation of pelvic floor muscle function and physical examination including a POP-Q and 
Brinks score, and the following questionnaires: 
 
a) PFDI 
b) PISQ-IR 
c) McGill Pain Questionnaire  
d) SESPPFE 

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Protocol Version 1.4 
April 18, 2018 
e) PGI-S and PGI-I 
f) WHODAS 
g) PFIQ 
h) Attestation of 80% or greater compliance with exercises twice daily as per 
protocol 
 
The 6 and 12 months follow-up by phone and email or mail will include: 
i) PFDI 
j) PISQ-IR 
k) McGill Pain Questionnaire  
l) SESPPFE 
m) PGI-S and PGI-I 
n) WHODAS 
o) PFIQ 
 
PFDx device pelvic floor muscle evaluation for both study arms will include:   
- 
Baseline pelvic floor muscle vaginal angle (at rest) 
- 
Pelvic floor muscle vaginal angle with Valsalva  
- 
Pelvic floor muscle angle with relaxation  
- 
Pelvic floor muscle angle with muscle contraction  
- 
Number of repetitions of contraction in 15 seconds;  
- 
Maximum time a subject can sustain a pelvic floor muscle contraction. 
This evaluation will be conducted using the PFDx device placed in the vagina by the subject 
and conducted by study staff using an automated measurement protocol.  
 
 
8.1.1 Confinement and Return Visits 
The screening and baseline visit may be combined into one visit and take up to 1.5 hours. 
The visit at 4 weeks may take up to 1 hour.  The end-of-study visit may take up to 1.5 hours. 
There are no other scheduled visits for this study. Follow up phone calls may take up to 45 
minutes.  See Study Events Flow Chart (Section 4).  
8.2 
Risks and/or Benefits to Subjects 
 
leva Incontinence System 
The leva Incontinence System TM (leva) is an FDA-
approved, Class II medical device used to help women 
overcome urinary incontinence. It will NOT be used in 
this study, but is the predicate device upon which the 
study devices are based. The device has two main 
components: (1) a tampon-shaped silicone form that is 
inserted into the vagina (the vaginal insert) and has a 
cable with a connector at the end; and (2) a control box 
that connects to the vaginal insert and contains a 
microprocessor and Bluetooth radio (the control box). 
The intravaginal device contains six accelerometer 
sensors placed on a flexible circuit board that is 
encased in a silicone form. The control box reads 
Figure 1. leva Incontinence System 

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positional information from the six sensors in the vaginal insert and communicates that data 
to a mobile phone application (the App).  
 
The leva Incontinence System TM has been tested and found to conform with the 
requirements of IEC 60601-1:2005 (3RD Edition), Medical Electrical Equipment-Part 1:  
General requirements for basic safety and essential performance; IEC 60601-1-2:2007, 
Medical electrical equipment-Part1-2:General requirements for basic safety and essential 
performance-Collateral standard: Electromagnetic compatibility-Requirements and tests; 
and IEC 60601-1-1-11, General requirements for basic safety and essential performance-
Collateral standard: Requirements for medical electrical equipment and medical electrical 
systems used in the home healthcare environment. The results of these tests indicate that 
the device is safe for its intended use. In addition, a biocompatibility evaluation was 
performed to satisfy ISO 10993-1 and FDA requirements. All patient contacting materials 
have been tested, and passed cytotoxicity, sensitization and irritation or intra-cutaneous 
standards.  
. 
 
leva Plus Incontinence System 
The leva Plus Incontinence System TM is a next-
generation device currently under development. 
It has the same Indications for Use and Intended 
Use as the leva Incontinence System TM. The 
primary differences between leva and leva Plus 
are as follows: (1) the leva Plus device combines 
the vaginal insert and control box into a single, 
smaller form that eliminates the need for a cable; 
(2) the leva Plus device has a small, detachable 
battery pack at the base; (3) the leva Plus device 
is made of a biocompatible thermoplastic 
elastomer, 
whereas 
leva 
is 
made 
of 
biocompatible silicone; and (4) the leva Plus 
device uses a Bluetooth Low Energy radio 
whereas the leva devices uses a classic 
Bluetooth 
radio. 
The 
leva 
Plus 
device 
communicates with an iPhone or Android mobile 
phone and provides biofeedback to the patient in 
the same way that leva does.  
 
The leva Plus device has not been submitted to 
FDA for approval yet. However, it is being 
developed under appropriate Design Controls and Risk 
Analysis, as defined by FDA’s 21 CFR 820 and ISO 13485. 
Renovia plans to submit a 510k application to FDA by late 
summer 2017. Given the similarity of leva Plus and leva, along 
with independent risk analysis, leva Plus is considered a “non-
significant risk device” as defined by 21 CFR 812.3(m).  
 
PFDx  
The PFDx device is an investigational medical device currently 
used to gather data related to pelvic floor health. It uses 
leva Plus Incontinence System. 
Image shows the vaginal insert detached
from the battery pack. 
PFDX device 

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substantially equivalent technology to the leva Incontinence System, an FDA-approved, 
Class II medical device. Whereas the leva device uses 6 accelerometer sensors, the PFDx 
device uses 12 sensors, allowing for a more complete evaluation of a woman’s physiology. 
The PFDx device is shaped as a ring that sits in the fornix with a thin, flat strip that descends 
along and out of the vagina. At the end of the device (outside the woman’s body) is a small 
enclosure that houses a microprocessor and a Bluetooth Low Energy radio. The PFDx 
communicates wirelessly to a laptop or mobile phone, in a similar manner to the leva device. 
All sensors related components are over-molded with the same biocompatible silicone 
material used to manufacture the leva device. Given the similarity of leva Plus and leva, 
along with independent risk analysis, leva Plus is considered a “non-significant risk device” 
as defined by 21 CFR 812.3(m). 
 
 
 
8.3 
Selection of Study Population 
8.3.1 Inclusion Criteria 
Subjects must fulfill all the following inclusion criteria to be eligible for participation in the 
study, unless otherwise specified: 
• 
Female. 
• 
Capable of giving informed consent. 
• 
Self-reported stress-type UI symptoms of >= three months duration 
• 
Diagnosis of stress predominant urinary incontinence based on MESA stress 
symptom score greater than MESA urge symptom score (percent of total possible 
urge score). 
• 
UDI-6 score >/= 25 
• 
Willing to participate in the 8-week study with follow up at 6-and 12-months, 
refraining from the pursuit of treatment for Stress Urinary Incontinence using other 
modalities (i.e. will not wear a pessary, participate in pelvic floor PT or surgery) 
during the first 8- weeks.  
 
8.3.2 Exclusion Criteria 
Subjects must not be enrolled in the study if they meet any of the following criteria: 
• 
Absence of a vagina. 
• 
Age <18 years. 
• 
Stage 3-4 pelvic organ prolapse (as determined by POP-Q). 
• 
Diagnosis of any neuromuscular disease. 
• 
Non-ambulatory. 
• 
Currently pregnant or <12 months post-partum.  
• 
</= 3 months after failed surgery for stress urinary incontinence.  
• 
Previous pelvic floor muscle training (PFMT) within the last 12 months under a 
supervised therapeutic plan of care. 
• 
Currently taking, or has taken within the last 2 months, medication to treat urinary 
incontinence. 
• 
Prior augmentation cystoplasty or artificial sphincter. 
• 
Implanted nerve stimulator for urinary symptoms. 

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• 
Participation in another clinical study within 30 days of screening.  
• 
Impaired cognitive function. 
• 
Contraindication to the use of a vaginal probe. 
• 
Unable to understand instructions on the use of the leva® Plus Pelvic Digital 
Health System. 
• 
Unable to actively recruit the pelvic floor muscles to any degree for attempted 
volitional contraction. 
 
8.3.3 Removal of Subjects from the Study 
Subjects are free to withdraw from the study at any time for any reason.  
In addition, subjects may be withdrawn from the study by the PI in consultation with the 
Sponsor for the following reasons: 
• 
Subject is unable to use the leva device; 
• 
Subject experiences a SAE; 
• 
Protocol violation. 
The clinical report will include reasons for subject withdrawals. 
8.3.4 Prohibitions and Concomitant Therapy 
There are no prohibited therapies, activities or medications except as described in the 
exclusion criteria. All medications taken by subjects during the study will be recorded. 
8.4 
Treatments 
8.4.1 Treatment Administered 
Subjects will train twice daily for 8- weeks using the leva device (for the treatment group) or 
Kegel exercises (for the control group).  
 
8.4.2 Treatment Compliance  
The leva device sends deidentified subject training and testing data to a secure, HIPAA 
compliant database, and subjects will receive periodic text messaging with training trips, 
reminders and motivational messages. Those in the Kegel control group will not be 
monitored for treatment compliance. 

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9 
STUDY PROCEDURES 
The Study Events Flow Chart (Section 4) summarizes the procedures to be performed at 
each visit. Individual procedures are described in detail below. Additional evaluations/testing 
may be deemed necessary by the PI and/or the Sponsor for reasons related to subject 
safety. 
Any nonscheduled procedures required for urgent evaluation of safety concerns take 
precedence over all routine scheduled procedures. 
9.1.1 Adverse Events  
9.1.1.1 Monitoring 
Subjects will be monitored at each study visit for adverse events. A specific enquiry will be 
made at the time of each check-in. The subjects will be queried with an open-ended 
question such as “How are you feeling?” or “How have you been feeling since your last 
visit?”  
9.1.1.2 Serious Adverse Event 
Any SAE will be reported to the Sponsor and the Institutional Review Board (IRB), as 
required. All SAEs will be reported to the Sponsor via fax or e-mail within one working day of 
becoming aware of the event, whether or not the serious events are deemed study 
treatment-related and within 5 working days to the IRB (24 hours of discovery if the event 
involves a death), as required. 
An SAE is any AE or suspected adverse reaction that in the view of either the PI or Sponsor, 
results in any of the following outcomes:  Death, a life-threatening adverse event, inpatient 
hospitalization or prolongation of existing hospitalization, a persistent or significant 
incapacity or substantial disruption of the ability to conduct normal life functions, or a 
congenital anomaly/birth defect. Important medical events that may not result in death, be 
life-threatening, or require hospitalization may be considered serious when, based upon 
appropriate medical judgment, they may jeopardize the subject and may require medical or 
surgical intervention to prevent one of the outcomes listed in the above definition.  
Life-threatening is defined as an AE or suspected adverse reaction that in the view of the PI 
or Sponsor, its occurrence places the patient or subject at immediate risk of death. It does 
not include an adverse event or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death. 
Treatment of SAEs will be performed by a physician, either at the site or at a nearby hospital 
emergency room. Where appropriate, medical test(s) and/or examination(s) will be 
performed to document resolution of event(s). Outcome may be classified as resolved, 
improved, unchanged, worse, fatal, or unknown (lost to follow-up). 
If a SAE occurs to a subject on this study, contact the Sponsor’s Representative listed in 
Section 2. 

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10 DATA ANALYSIS 
Data will be handled and processed according to Operating Procedures, which are based on 
the principles of GCP. 
10.1 Statistical Methods 
Detailed methodology for summary and statistical analyses of the data collected in this study 
will be documented in the Clinical Study Report. 
10.1.1 Determination of Sample Size 
This planned randomized controlled trial is a tertiary prevention trial, comparing the efficacy 
of the Leva device in the treatment of stress urinary incontinence to standard pelvic floor 
muscle training, consisting of office education and a home exercise program.  Our primary 
outcome is the proportion of subjects who are very much better/much better as measured by 
the PGI-I.  Sample size for 20% difference between groups given a 30% success rate of 
home exercise programs, alpha=0.05, and a power of 0.8, the needed sample size is 93 
patients in each arm. Allowing for an attrition rate of approximately 15%, we require 
approximately 225 patients.  
10.1.2 Subjects to Analyze 
Safety Population: All subjects who were administered at least one training session will be 
included in the safety evaluations. 
 
Efficacy Population: All subjects who had at least one leva testing administration and 
measurement of any of the efficacy assessments post Screening Visit. 
 
10.2 Safety Evaluation 
Safety data will be populated in individual CRFs. All safety data will be listed by subject. 
AEs and SAEs will be monitored throughout the study. All SAEs will be recorded and 
reported. Concomitant medications and medical history will be listed by subject. 

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11 STUDY ADMINISTRATION 
11.1 Ethics 
11.1.1 Institutional Review Board  
This protocol will be reviewed by the institutional review boards of the participating 
institutions,  
11.1.2 Ethical Conduct of the Study 
This research will be carried out in accordance with the protocol, US Code of Federal 
Regulations, GCP, 21 CFR Parts 50 and 56, the ethical principles set forth in the 
Declaration of Helsinki, and the ICH harmonized tripartite guideline regarding 
GCP (E6 Consolidated Guidance, April 1996). 
11.1.3 Subject Information and Consent 
The purpose of the study, the procedures to be carried out and the potential hazards will be 
described to the subjects in non-technical terms. Subjects will be required to read, sign and 
date an ICF summarizing the discussion prior to Screening and will be assured that they 
may withdraw from the study at any time without jeopardizing their medical care. 
Subjects will be given a copy of their ICF. 
11.2 Termination of the Study 
The Principal Investigator reserves the right to terminate the study in the interest of subject 
welfare. The Sponsor may terminate the study for administrative reasons. 
11.3 Data Quality Assurance 
The Principal Investigator will designate personnel responsible for implementing and 
maintaining quality assurance and quality control systems to ensure that the study is 
conducted, and that data are generated, documented and reported in compliance with the 
study protocol, GCP and Good Laboratory Practice requirements as well as applicable 
regulatory requirements and local laws, rules and regulations relating to the conduct of the 
clinical study. 
 
11.4 Direct Access to Source Data/Documents 
The Principal Investigator will ensure that the Sponsor, IRB and domestic and foreign 
regulatory authorities will have direct access to all study sites, source data/documents, and 
reports for monitoring and auditing. If other study-related monitoring should be done by 
other parties, those parties will be required to sign a confidentiality agreement prior to any 
monitoring or auditing. 
11.5 Study Device Supplies, Packaging and Labeling 
The Sponsor will supply sufficient quantities of devices to allow completion of this study. 
Each subject in the “leva” arm will be provided with her own device and may retain the 
device at the end of the study. The Cost of goods value of the device is less than $100.   If 

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the subject does not already own an iPhone or android phone to run the leva software, they 
will be provided an alternative at no cost.   It will be up to the discretion of the Sponsor if the 
alternative device needs to be returned to the study site or can be retained by the subject at 
the end of the study.  Records will be made of the receipt and dispensing of devices 
supplied. This accountability record will be available for inspection at any time. At the 
completion of the study, the original accountability record will be available for review by the 
Sponsor upon request. 
11.6 Data Handling and Record Keeping 
All raw data generated in connection with this study, together with the final report, will be 
retained for at least 5 years after completion of the final report. These documents should be 
retained for a longer period however if required by the applicable regulatory requirements or 
by an agreement with the Sponsor. It is the responsibility of the Sponsor to inform the 
PI/Institution as to when these documents no longer need to be retained. 
11.7 Publication Policy 
All unpublished information given to the Principal Investigator by the Sponsor shall not be 
published or disclosed to a third party without the prior written consent of the Sponsor. 
The data generated by this study are considered confidential information and the property of 
the Sponsor. This confidential information may be published only in collaboration with 
participating personnel from the Sponsor or upon Sponsor’s written consent to publish the 
article.