Muscle Cell Mediated Therapy for Stress Urinary Incontinence in Males Following Prostate Surgery: An Investigation of Cook MyoSite Autologous Muscle Derived Cells
Phase: PHASE1
Conditions: Urinary Incontinence, Stress, Urination Disorders, Urologic Diseases, Lower Urinary Tract Symptoms, Urological Manifestations
Sponsor: Cook MyoSite

Cook MyoSite, Incorporated  
Version: 13-11-03 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
COMPANY CONFIDENTIAL
Page 1 of 41 
CLINICAL INVESTIGATION PLAN 
Muscle Cell Mediated Therapy for Stress Urinary Incontinence in Males Following Prostate 
Surgery: An Investigation of Cook MyoSite Autologous Muscle Derived Cells  
Global Clinical Number: 13-11 
Version: 13-11-03 
Version Date:  17 November 2015
NCT Number: NCT02291432
Sponsor: 
Cook MyoSite, Incorporated 
105 Delta Drive 
Pittsburgh, PA 15238 USA 

Cook MyoSite, Incorporated  
Version: 13-11-03 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
COMPANY CONFIDENTIAL
Page 2 of 41 
CLINICAL INVESTIGATION PLAN SIGNATURE PAGE 
Global Sponsor Contact: 
This clinical study will be conducted in accordance with the Clinical Investigation Plan (CIP), 
ICH GCP, 21 CFR 312, and other applicable requirements as appropriate. The CIP will be 
revised, as appropriate, based on new information. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 3 of 41 
 
 
CLINICAL INVESTIGATION PLAN SIGNATURE PAGE, CONTINUED 
 
 
 
Principal Investigator: 
 
I hereby confirm that I approve of this Clinical Investigation Plan and agree to comply with its 
terms as laid out in this document. 
 
  
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 4 of 41 
 
 
CONFIDENTIALITY STATEMENT 
 
 
 
This document shall be treated as a confidential document  
for the sole information and use of the  
clinical study team and the  
 Institutional Review Board/Research Ethics Board IRB/REB. 
 
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 5 of 41 
 
Table of Contents  
1.0 
Clinical Investigation Plan Overview ......................................................................8 
2.0 
Objectives of the Clinical Study ............................................................................10 
2.1 
Primary Objectives .....................................................................................10 
2.2 
Secondary Objectives .................................................................................11 
3.0 
Product Description and Intended Use ..................................................................11 
3.1 
General Product Description ......................................................................11 
3.1.1  Dose Justification ............................................................................12 
3.2 
Indication for Use .......................................................................................13 
3.3 
Product Identification and Tracking ...........................................................13 
3.4 
Instructions for Use ....................................................................................13 
4.0 
Summary of Preliminary Studies ...........................................................................15 
5.0 
Risk Analysis and Risk Assessment ......................................................................15 
5.1 
Risks and Foreseeable Adverse Events and Adverse Product Effects .......15 
5.2 
Methods to Minimize Risks ........................................................................15 
6.0 
Design of the Clinical Study ..................................................................................16 
6.1 
Design of Study ..........................................................................................16 
6.2 
Inclusion and Exclusion Criteria ................................................................16 
6.3 
Endpoints ....................................................................................................19 
6.3.1  Primary Endpoints ..........................................................................19 
6.3.2  Secondary Endpoints ......................................................................20 
6.3.3  Rationale for Endpoints ..................................................................20 
6.4 
Variables to be Measured to Demonstrate Achievement of Endpoints ......21 
6.5 
Measures to be Taken to Avoid or Minimize Bias .....................................23 
7.0 
Methods..................................................................................................................23 
7.1 
Patient Assessment and Screening .............................................................23 
7.2 
Patient Consent ...........................................................................................23 
7.3 
Pre-enrollment (Visit 1) – Screening ..........................................................23 
7.4 
Point of Enrollment ....................................................................................24 
7.5 
Medications ................................................................................................24 
7.6 
Biopsy (Visit 2) ..........................................................................................24 
7.6.1  Post-Biopsy Follow-up (Phone) ......................................................25 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 6 of 41 
 
7.7 
Procedure (Visit 3) – Treatment Day 0 ......................................................25 
7.8 
Follow-up....................................................................................................26 
7.8.1  Post-Treatment Follow-up (Phone) – Treatment Day 1-2 ..............26 
7.8.2  Post-Treatment Follow-up (Phone) – Treatment Week 1 ...............26 
7.8.3   Follow-up (Visit 4) – Treatment Month 1 (± 1 week) ....................26 
7.8.4  Follow-up (Visit 5) – Treatment Month 3 (± 1 week) ....................26 
7.8.5  Follow-up (Visit 6) – Treatment Month 6 (- 2, + 4 weeks) ............27 
7.8.6   Follow-up (Visit 7) – Treatment Month 12 (- 2, + 4 weeks) ...........27 
7.8.7   Post-Treatment Follow-up (Phone) – Treatment Month 24 ............27 
7.9 
Duration of Study and Patient Participation ...............................................28 
7.10 
Criteria and Procedures for Withdrawal .....................................................28 
7.11 
Participation Endpoints of the Study ..........................................................28 
8.0  
Statistical Considerations .......................................................................................29 
8.1 
Hypothesis to be Tested ..............................................................................29 
8.2 
Sample Size ................................................................................................29 
8.3 
General Analysis.........................................................................................29 
8.4 
Missing Data ...............................................................................................29 
8.5 
Limitations of the Study .............................................................................29 
9.0 
Deviations from Clinical Investigation Plan ..........................................................30 
10.0 
Data Collection and Reporting ...............................................................................30 
10.1 
Electronic Case Report Forms ....................................................................30 
10.2 
Data Reporting ............................................................................................30 
11.0 
Data Management ..................................................................................................31 
11.1 
Data Entry and Data Review ......................................................................31 
11.2 
Data Monitoring Arrangements ..................................................................31 
12.0 
Procedures for Reporting Adverse Events .............................................................31 
13.0 
Early Termination or Suspension of the Clinical Study ........................................32 
14.0 
Ethical Considerations ...........................................................................................32 
15.0 
Publication Policy ..................................................................................................33 
16.0 
Clinical Study Administration and Investigators ...................................................33 
16.1 
Approvals and Agreements ........................................................................33 
16.2 
Investigators................................................................................................33 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 7 of 41 
 
16.3 
Insurance .....................................................................................................33 
17.0 
References ..............................................................................................................33 
 
Appendices  
A 
Bladder Stress Test 
B 
24-Hour Pad Test 
C 
Written Procedures for Monitoring Studies 
D 
Contact Information 
E 
Definitions 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 8 of 41 
 
1.0 
Clinical Investigation Plan Overview 
This preliminary, prospective, single-arm clinical study will evaluate the safety and potential 
efficacy of Autologous Muscle Derived Cells for Urinary Sphincter Repair (AMDC-USR) for 
the treatment of male stress urinary incontinence (SUI) that develops following prostate surgery.  
 
Prostate surgery can induce iatrogenic sphincter damage resulting in long-term SUI. Therefore, 
augmenting sphincter function may be beneficial to patients. Autologous muscle cell therapy, 
which involves isolation of cells from skeletal muscle biopsies, ex vivo expansion, and 
subsequent injection into the urethral sphincter, may serve as a potential durable therapy. In 
animal studies, muscle derived cells have successfully integrated within tissue to improve 
sphincter function. Intrasphincteric injection of AMDC-USR is expected to produce localized 
tissue changes near the injection site and is not expected to produce a systemic effect. 
 
Patients will receive intrasphincteric injection of a single treatment of 150 x 106 AMDC-USR. 
For entrance into the study, patients must meet the study inclusion criteria and must not meet any 
of the exclusion criteria. Patients will have quantitative and qualitative measures of incontinence 
assessed before treatment and at various times after treatment. 
 
The study will treat up to 30 patients at up to 5 clinical sites. Enrollment is expected to be 
completed within 2.5 years of initiating the study. Patients will be followed for 24 months post-
treatment. The first 3 patients at each site must reach 1-month follow-up before subsequent 
patients can be treated at that site. 
 
Male patients at least 18 years of age who have undergone prostate surgery at least 12 months 
prior to screening and who present with symptoms of SUI will be screened for eligibility for 
study participation. To participate, patients must meet all inclusion criteria and none of the 
exclusion criteria.  Eligible patients will have muscle tissue harvested using a needle biopsy 
technique during an outpatient procedure. The harvested muscle tissue will be placed in a 
hypothermic medium and transported to the manufacturer for cell processing in their laboratory 
in Pittsburgh, PA (USA). The muscle derived cells (MDC) will be isolated and expanded in 
culture over several weeks to a final dose of 150 x 106 ± 20% AMDC-USR.  
 
Due to the personalized nature of each autologous product, some products may not meet all 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 9 of 41 
 
release specifications of purity and dose.  If a product meets all predefined safety criteria, the 
product may be offered to the patient at the physician’s discretion. Affected patients will be 
notified prior to their injection procedure and must provide consent of their willingness to 
receive an injection of product that does not meet all target criteria. 
 
After reaching the desired concentration, the isolated and expanded AMDC-USR will be frozen 
and shipped back to the investigating physician. The physician will thaw the AMDC-USR and 
dilute the sample with an approximately equal volume of physiological saline. Under direct 
vision, the resulting suspension will be injected into the patient’s urethral sphincter in a brief 
outpatient procedure. 
 
Patients will be assessed for safety and improvement in urinary incontinence symptoms at 
1, 3, 6 and 12 months following treatment. Adverse events will be assessed at all follow-up 
visits, as well as during follow-up calls at 1-2 days, 1 week, and 24 months. A study overview is 
depicted in Figure 1.1. 
 
The primary safety measures will be the incidence of study product-related serious adverse 
events (SAEs) and the incidence of study product-related, biopsy procedure-related, and 
injection procedure-related adverse events and post-void residual (PVR) urine volume. 
Secondarily, potential efficacy will be evaluated based on reduction in the amount of urine 
leakage, as assessed by a 24-hour pad test at 1, 3, 6, and 12 months following treatment. Changes 
in patient-reported incontinence symptom severity, quality of life (QOL), and erectile 
dysfunction (ED) symptoms will also be assessed at 1, 3, 6, and 12 months following treatment.  
  
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 10 of 41 
 
 
 
Informed consent is obtained 
 
 
 
 
 
 
Screening exams, assessments and tests to confirm eligibility 
 
 
 
 
 
 
Patient meets inclusion criteria and does not meet exclusion criteria 
 
 
 
 
Patient undergoes biopsy (formal enrollment) 
 
 
 
 
 
 
1-week telephone follow-up 
 
 
 
 
 
 
Injection treatment with AMDC-USR 
(n ≤ 30) 
 
 
 
 
1-2 day telephone follow-up 
 
 
 
 
1-week telephone follow-up 
 
 
 
 
1-month follow-up 
 
 
 
3-month follow-up 
 
 
 
6-month follow-up 
 
 
12-month follow-up 
 
 
24-month telephone follow-up 
 
Figure 1.1. Study flow diagram 
2.0 
Objectives of the Clinical Study 
2.1 
Primary Objectives  
The primary objective of this study is to evaluate the safety of AMDC-USR during the 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 11 of 41 
 
24 months following treatment of SUI in male patients who have undergone prior prostate 
surgery. 
 
Safety will be determined by the frequency and severity of adverse events related to study 
procedures and study product through 24 months following treatment of SUI in male patients 
who have undergone prior prostate surgery. PVR volume will be assessed through 12 months 
post-treatment to monitor potential retention or obstruction. 
2.2 
Secondary Objectives 
In addition to the primary objective listed above, the following secondary objectives will be 
evaluated in this clinical study:  
 
 Efficacy of AMDC-USR in the reduction of SUI symptoms at 1, 3, 6, and 12 months 
post-treatment 
 Effect of AMDC-USR on QOL at 1, 3, 6, and 12 months post-treatment 
 
Additionally, information on ED symptoms will be collected at 1, 3, 6, and 12 months post-
treatment. 
3.0 
Product Description and Intended Use 
3.1 
General Product Description 
Please reference the Investigator’s Brochure for a detailed description of the product and dose to 
be used in the clinical study. 
 
 
 
 
 
 
Cook MyoSite, Incorporated will perform cell processing and preparation of cell suspensions for 
study use in their cell processing facility in Pittsburgh, Pennsylvania (USA). Cell processing will 
begin with isolation of cells from the patient’s tissue. The cells will then be grown in culture and 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 12 of 41 
 
expanded in number. The culture process produces a final cell culture that is enriched in 
myogenic cell content. Cell culture will be performed in medium consisting of physiological 
saline solution with cell nutrients. Cell processing will follow current Good Manufacturing 
Practice (cGMP) methodologies to prevent contamination and to preserve tissue function and 
integrity. These practices will include defined procedures for tissue and cell handling, 
processing, and identification. 
 
Each AMDC-USR study agent vial supplied to the clinical site will contain cryogenically 
preserved autologous muscle derived cells, prepared to ± 20% of the stated total viable cellular 
dose at the time of packaging, 
 
 
 
Each study agent vial will be thawed at the clinical site prior to use and diluted with 
an approximately equal volume (2 mL) of injectable sodium chloride (saline) at physiological 
concentration, 
  
 
Materials contacting the patient’s urethral tissue will include the patient’s own muscle derived 
cells, the cryogenic medium in which the cells are suspended and shipped, and the physiological 
saline used to dilute the mixture for injection. 
3.1.1 Dose Justification 
A dose of 150 x 106 AMDC-USR was chosen 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 13 of 41 
 
  
Systemic adverse effects attributable to AMDC-USR have not been observed following 
intrasphincteric injection of AMDC in non-clinical1 and clinical2-4 studies. Therefore, delivery 
into the urethral sphincter of men is unlikely to produce systemic responses.  
 
Because the risk to patients from adverse effects from the cells is expected to be the same as in 
other studies for sphincter-related indications, a dose with potential beneficial effect will be 
evaluated in the initial study. 
3.2 
Indication for Use  
The AMDC-USR treatment is indicated for reduction in symptoms of urinary incontinence and 
improvement in patient QOL in men with stress urinary incontinence. 
3.3 
Product Identification and Tracking  
Products under investigation will be tracked by the clinical site throughout the course of the 
study through the use of a product log, which includes information such as lot numbers, quantity, 
and disposition of products. Additionally, information such as the quantity and lot number(s) of 
products used in patients will be recorded on Case Report Forms (CRFs). 
 
Each product is manufactured individually and labeled with a unique product code for 
identification and traceability. All cell preparations will be transported in identical vials with the 
same volume of transport medium and reconstituted to the same final volume prior to injection. 
Vials will be identified by a product code containing lot number, patient initials, and six unique 
digits. Additional procedures have also been established to ensure traceability. 
3.4 
Instructions for Use   
 The study procedure guidelines, which will be provided to physicians and appropriate study staff 
at the time of training, must be followed for step-by-step instructions for performing the 
following: 
                                                 
1 Please reference the Investigator’s Brochure, Section 5.3, Toxicology. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 14 of 41 
 
 Obtaining the muscle biopsy 
 Packaging and shipping the muscle biopsy 
 Complete instructions including storage and handling requirements 
 Resuspending the final product (AMDC-USR) 
 
Muscle Biopsy 
 
The biopsy procedure will involve minor surgery to collect approximately 50-250 mg of the 
vastus lateralis muscle using a sampling needle. Prior to the biopsy, patients who are currently 
taking any form of anticoagulant medication must stop using the medication as per standard of 
care for outpatient surgery procedures. Antianxiety medication, analgesia, or minimal sedation 
may be provided according to each site’s standard of care.
 
 
 
Several passes of the biopsy needle may be required to obtain a satisfactory sample of muscle 
tissue. Additionally, if the first biopsy does not produce an adequate sample for product 
isolation, it may be necessary for the patient to return for another biopsy procedure. The 
maximum permissible number of biopsy needle passes and the total number of biopsies is 
contingent upon patient tolerance and the satisfactory procurement of muscle tissue.  
 
Using aseptic technique, the biopsy tissue will be transferred to the Biopsy Medium Vial. The 
Biopsy Medium Vial will be closed and packaged according to the study procedure guidelines 
for shipment to Cook MyoSite, Incorporated. 
 
Dilution and Preparation for Injection 
 
The frozen product will be thawed for at least 8-10 minutes at room temperature. The 2 mL of 
cell suspension will be diluted with 2 mL of physiological saline for an approximate total volume 
of 4 mL. The entire vial contents will be used for injection. 
 
Cell Injection 
 
The study agent (AMDC-USR) will be injected into the urethral sphincter. A course of 
prophylactic antibiotics will be given prior to the injection procedure. Ultrasound may be 
performed to aid in the injection procedure. Under direct vision, multiple injections will be 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 15 of 41 
 
performed to circumferentially distribute AMDC-USR within the striated muscle of the urethral 
sphincter. Materials contacting the urethral tissue will include the patient’s own AMDC-USR, 
the cryogenic medium in which the AMDC-USR are suspended and shipped, and the 
physiological saline used to dilute the mixture for injection. Prior to the injection, patients who 
are currently taking any form of anticoagulant medication must stop using the medication as per 
standard of care for outpatient surgery procedures. Antianxiety medication, analgesia, or minimal 
sedation may be provided according to each site’s standard of care or physician’s discretion. 
 
After the injection is completed, the injected area will be examined for any excessive bleeding or 
excessive trauma. The patient will be asked to void, and an ultrasound/bladder scan will be 
performed to determine PVR urine volume.  
4.0 
Summary of Preliminary Studies 
 
Please reference the Investigator’s Brochure for a summary of non-clinical testing and a 
summary of previous clinical experiences with this product or similar products. 
5.0 
Risk Analysis and Risk Assessment 
5.1 
Risks and Foreseeable Adverse Events and Adverse Product Effects 
Please reference the Investigator’s Brochure for a list of specific risks of study procedures and 
study products. 
5.2 
Methods to Minimize Risks  
Only trained healthcare professionals who are experienced with cystoscopy and urethral injection 
will administer this product. Patients will be selected according to the indication and in 
accordance with inclusion/exclusion criteria outlined in this document. Adherence to and training 
on the research clinical investigation plan (CIP) are necessary to reduce material- and procedure-
related risks. Routine catheterization and venipuncture will be performed by qualified personnel. 
 
The product design, non-clinical testing, clinical study design, and study procedure guidelines 
are intended to minimize the risks associated with the use of this product. The risks of the study 
have been minimized and the potential benefits outweigh the risks. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 16 of 41 
 
6.0 
Design of the Clinical Study 
6.1 
Design of Study 
This preliminary, prospective, single-arm clinical study will evaluate the safety and potential 
efficacy of AMDC-USR for the treatment of male SUI that develops following prostate surgery. 
 
The study will treat up to 30 patients (treated with 150 x 106 AMDC-USR) at up to 5 clinical 
sites. Enrollment is expected to be completed within 2.5 years of initiating the study. Patients 
will be followed for 24 months post-treatment. The first 3 patients at each site must reach 1-
month follow-up before subsequent patients can be treated at that site. 
6.2 
Inclusion and Exclusion Criteria 
Patient eligibility for enrollment shall be based on known information at the time of the 
screening. Information obtained at a later date may contradict these criteria, but this will not be 
considered a deviation to the CIP. 
 
Inclusion Criteria  
 
A patient is deemed suitable for inclusion in the study if the patient meets the following criteria: 
 
1. Male, at least 18 years old, with primary symptoms of SUI following prostate 
surgery that occurred at least 12 months prior to enrollment, as confirmed by 
medical history and clinical symptoms, including a focused incontinence 
evaluation. 
2. Patient has undergone prostate surgery, such as radical prostatectomy or prostate 
resection, but has not undergone radiation therapy, cryotherapy, or high-intensity 
focused ultrasound of the prostate. 
3. SUI severity must be ≥10 g and <400 g of urine leakage over 24 hours, as 
determined by a 24-hour pad test during screening. 2 
                                                 
2 Moore, et al.5 suggest > 4 g as a minimum pad weight gain for incontinence in men, but that the upper limit for 
normal pad weight gain should be 8 g. Thus, > 8 g would be considered incontinence in men. Kumar, et al.6 suggest 
> 400 g/24 h is high-grade incontinence (or total incontinence), and recommend men in this category receive an 
artificial urinary sphincter. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 17 of 41 
 
4. 
Patient has failed to achieve acceptable resolution of SUI symptoms following 
prior therapy. 
 
Exclusion Criteria 
 
A patient is excluded from enrollment into the study if any of the following are true: 
 
Patient History-based Criteria: 
 
1. Simultaneously participating in another investigational drug or device study or has 
completed the follow-up phase for the primary endpoint of any previous study less than 
30 days prior to the first evaluation in this study. 
2. Previously treated with an investigational device, drug, or procedure for urinary 
incontinence within 6 months prior to signing consent. 
3. Has ever been treated with a cell therapy for urinary tract dysfunction. 
4. Has an artificial sphincter. 
5. Previously treated with a periurethral balloon or adjustable sling for urinary incontinence. 
6. Symptoms of stress urinary incontinence prior to prostate surgery. 
7. Symptoms of only urge urinary incontinence as noted by basic evaluation of etiology 
from patient medical history, including a focused incontinence history. 
8. Symptoms of overflow incontinence as noted by basic evaluation of etiology from patient 
medical history, including a focused incontinence history. 
9. Symptoms of urinary incontinence in which stress urinary incontinence is not the 
predominant factor.  
10. Routinely has more than 2 episodes of awakening to void during normal sleeping hours. 
11. Urinary incontinence of neurogenic etiology or uncorrected congenital abnormality 
leading to urinary incontinence. 
12. Indwelling urinary catheter or requires intermittent catheterization for bladder emptying. 
13. Neuromuscular disorder (e.g., Parkinson’s disease, muscular dystrophy, multiple 
sclerosis) that could lead to urinary incontinence. 
14. Morbidly obese (BMI ≥ 35). 
15. Uncontrolled diabetes. 
16. Adult nocturnal enuresis. 
17. Severe, chronic constipation. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 18 of 41 
 
18. Compromised immune system due to disease state, chronic corticosteroid use, or other 
immunosuppressive therapy. 
19. History of pelvic organ radiation (e.g., brachytherapy, transurethral microwave therapy 
[TUMT], transurethral radiofrequency needle ablation [TUNA]). 
20. History of high-intensity focused ultrasound (HIFU) treatment of the prostate. 
21. History of cryotherapy treatment of the prostate. 
22. Medical condition or disorder that may limit life expectancy or that may cause CIP 
deviations (e.g., unable to perform self-evaluations or accurately report medical history, 
urinary symptoms, or data). 
23. History of bleeding diathesis or uncorrectable coagulopathy. 
24. Known allergy or hypersensitivity to bovine proteins or allergens, gentamicin sulfate, or 
ampicillin that medically warrants exclusion as determined by the physician. 
25. Unstable prostate-specific antigen (PSA) for 12 months as determined by the physician. 
26. Any non-skin cancer that has necessitated treatment within the past 12 months. 
27. Known history of abnormal detrusor activity. 
28. Known history of adult vesicoureteral reflux. 
 
Patient Physical Examination or Testing-based Criteria: 
 
1. Does not have a viable mucosal lining along the urinary tract. 
2. Current or history of fistula involving the urethra, bladder, or rectum. 
3. Urethral stricture or bladder neck contracture requiring intervention to reopen (planned 
intervention or history of intervention) 
4. Current or history of bladder stones. 
5. Failure to produce a leak during the bladder stress test. 
6. Moderate or severe urethral fibrosis at likely injection site. 
7. Voiding difficulty (complains of difficulty emptying the bladder following 
ultrasound/bladder scan).  
8. PVR urine volume ≥ 100 mL,7 determined by ultrasound/bladder scan, after repeated 
testing (i.e., the patient was asked to revoid and the PVR volume was still ≥ 100 mL).  
9. Tests positive for Hepatitis B (required tests: Hepatitis B Surface Antigen [HBsAg] and 
Anti-Hepatitis B Core Antibody [Anti-HBc]), Hepatitis C (required test: Hepatitis C 
Antibody [Anti-HCV]), HIV (required tests: HIV Type 1 and 2 Antibodies [Anti-HIV-1, 
2]), and/or Syphilis.  
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 19 of 41 
 
Patient’s Current Status-based Criteria: 
 
1. If previously treated for prostate cancer, evidence of recurrent prostate cancer as 
determined by the physician during screening. 
2. Does not use external collection device for SUI symptoms (e.g., pads, condom catheter, 
etc). 
3. Cannot be, or is not willing to be, maintained on a stable dose or frequency of medication 
known to affect lower urinary tract function, including but not limited to, 
anticholinergics, beta 3 adrenergic receptor agonists, tricyclic antidepressants, SNRI or 
SSRI antidepressants, diuretics, or alpha-adrenergic blockers, or phosphodiesterase type-
5 inhibitors, for at least 2 weeks prior to screening; or use of these medications is likely to 
change during the 12 months following treatment. 
4. Cannot, or is not willing to, maintain the current treatment regimen for existing 
conservative therapy (e.g., pelvic floor muscle training routine, incontinence 
medications), excluding penile clamps. 
5. Cannot, or is not willing to, stop use of penile clamp during the course of the study. 
6. Requires prophylactic antibiotics for chronic urinary tract infections, cystitis, urethritis, 
prostatitis, orchitis, epididymitis, or balanitis, or has required 2 or more courses of 
antibiotics for lower urinary tract infections in the 2 months prior to signing consent. 
7. Any condition, including current infection, which could lead to significant postoperative 
complications.  
8. Current or acute conditions involving cystitis, urethritis, prostatitis, balanitis, orchitis, or 
epididymitis. 
9. Refuses to provide written informed consent. 
10. Not at least 18 years of age.  
11. Not available for, or willing to comply, with the baseline and follow-up evaluations as 
required by the CIP.  
6.3 
Endpoints 
6.3.1 Primary Endpoints 
The primary safety endpoints include: 
 
 Study product-related SAEs reported through 24-month follow-up; 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 20 of 41 
 
 Study product-related, biopsy procedure-related, and injection procedure-related adverse 
events reported through 24-month follow-up; and 
 PVR urine volume reported through 12-month follow-up. 
6.3.2 Secondary Endpoints 
The secondary endpoints include:  
 
 Reduction in amount of urine leakage, as assessed by 24-hour pad test at 1, 3, 6 and 
12 months post-treatment;  
 Change in patient-reported incontinence symptom severity, as assessed by questionnaires 
at 1, 3, 6 and 12 months post-treatment; and 
 Change in patient-reported QOL, as assessed by questionnaires at 1, 3, 6 and 12 months 
post-treatment. 
 
Changes in ED symptoms will also be assessed at 1, 3, 6 and 12 months post-treatment. 
6.3.3 Rationale for Endpoints 
This is a preliminary study to assess the safety of intrasphincteric injection of AMDC-USR in 
male patients. Safety assessment will be based on the occurrence of product- and study 
procedure-related adverse events. Additionally, PVR volume will be assessed throughout the 
study to monitor potential retention or obstruction.   
 
Efficacy measurements will be used in this study to assess the severity level of an individual’s 
incontinence symptoms and the extent to which incontinence symptoms impair quality of life. 
Measures to assess incontinence include a 24-hour pad test, the International Consultation on 
Incontinence Questionnaire (ICIQ),8,9 the Incontinence Quality of Life (IQOL) questionnaire,9,10 
the Patient Global Impression of Severity (PGI-S),11,12 the Patient Global Impression of 
Improvement (PGI-I),11,12 and the International Prostate Symptom Score (I-PSS).13,14 
 
Since SUI and ED can be comorbidities that develop following prostate surgery, the 5-Item 
International Index of Erectile Function (IIEF-5)15 questionnaire will be used to monitor 
symptoms of ED.  

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 21 of 41 
 
6.4 
Variables to be Measured to Demonstrate Achievement of Endpoints 
Safety endpoints will be measured as follows: 
 
 Study product-related SAEs reported through 24-month follow-up;  
 Study product-related, biopsy procedure-related, and injection procedure-related adverse 
events reported through 24-month follow-up; and 
 Ultrasound/bladder scan determination of PVR volume on the day of injection and at 1, 3, 
6 and 12 months post-treatment. 
 
The secondary efficacy endpoints will be measured as follows: 
 
 Reduction in amount of urine leakage from baseline as assessed by 24-hour pad test at 1, 
3, 6 and 12 months; 
 Change from baseline in patient-reported outcomes for incontinence symptom severity 
and QOL will be measured by ICIQ, IQOL score and subscores, I-PSS, and PGI-S score 
at 1, 3, 6 and 12 months; and  
 Change in patient-reported incontinence symptom severity will also be measured by PGI-
I score at 1, 3, 6 and 12 months. 
 
In addition, change from baseline in patient symptoms of ED will be measured by the IIEF-5 
questionnaire at 1, 3, 6 and 12 months. Patient clinical information including details of prior 
procedures for prostate surgery, underlying reason for prostate surgery, underlying disease 
severity, and any procedures or revisions following the incident procedure to address disease or 
SUI symptoms will be collected and evaluated as appropriate. 
 
The clinical data will be collected on standardized Case Report Forms (CRFs). The schedule for 
assessments is summarized in Table 6.1.  
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 22 of 41 
 
Table 6.1. Data collection schedule 
 
Screening 
Biopsy 
Post-
biopsy 
Treatment 
Post-treatment 
Visit 1 
Visit 2 
Phone 
Visit 3 
Phone 
Phone 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Phone 
Week 
1-8a 
Week 
2-10 
Week  
3-11 
Day 0 
Day  
1-2 
Week  
1 
Month 
1 
Month 
3 
Month 
6 
Month 
12 
Month 
24 
Event 
Screening 
Biopsy 
Follow-
up 
Injection 
Follow-
up 
Follow-
up 
Office 
Visit 
Office 
Visit 
Office 
Visit 
Office 
Visit 
Follow-
up 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
Exclusionb 
X 
 
 
 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
 
 
Clinical 
Assessment 
X 
 
 
 
 
 
X 
X 
X 
X 
 
Physical 
Examination 
X 
 
 
 
 
 
 
 
 
 
 
Vital Signs 
X 
 
 
 
 
 
 
 
 
 
 
Medication Log 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Urine Culturec 
 
 
 
X 
 
 
 
 
 
 
 
Bladder Stress 
Test 
X 
 
 
 
 
 
 
 
 
X 
 
24-hour Pad Test 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Post-void 
Residual Volume 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Questionnairesd: 
ICIQ, IQOL, 
PGI-S, I-PSS, 
IIEF-5 
X 
 
 
X 
 
 
X 
X 
X 
X 
 
Questionnaired: 
PGI-I 
 
 
 
 
 
 
X 
X 
X 
X 
 
Blood Samples 
Xf 
 
 
 
 
 
X 
 
 
X 
 
Cystoscopy 
Xe 
 
 
X 
 
 
 
 
 
X 
 
Muscle Biopsy 
 
X 
 
 
 
 
 
 
 
 
 
Injection 
 
 
 
X 
 
 
 
 
 
 
 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Telephone 
Follow-up 
 
 
X 
 
X 
X 
 
 
 
 
X 
a It is recommended that screening tests conducted in Visit 1 be completed within 8 weeks preceding the biopsy 
visit.  
b An electronic case report form system tracks inclusion/exclusion screening information.  
c This test must be completed if the urinalysis is positive for nitrites or leukocyte esterase on the day of scheduled 
injection. Urine culture may also be performed at screening and at follow-up visits if nitrites or leukocyte esterase is 
detected by dipstick; however, urine culture is not required. 
d Questionnaires will be collected in a paper format. 
e An existing cystoscopy evaluation can be used if performed within 6 months prior to the time of consent. 
f If the biopsy procedure is scheduled more than 30 days after the most recent bloodborne pathogen tests were 
completed, the bloodborne pathogen tests (i.e. hepatitis B, hepatitis C, HIV, and syphilis) must be repeated before 
the biopsy procedure to confirm the patient’s continued eligibility for study participation. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 23 of 41 
 
6.5 
Measures to be Taken to Avoid or Minimize Bias 
This preliminary, prospective, single-arm study is intended to collect information regarding the 
safety and potential efficacy of intrasphincteric injection of AMDC-USR for the treatment of 
male SUI that develops following prostate surgery. Study patients will be enrolled at up to 5 sites 
and uniform definitions will be used for study endpoints.  
7.0 
Methods 
7.1 
Patient Assessment and Screening 
Male patients who present with SUI symptoms that developed following prostate surgery that 
occurred at least 12 months prior to enrollment may be considered for participation in this study. 
7.2 
Patient Consent 
Patients who appear to meet the inclusion criterion and none of the exclusion criteria will be 
invited to participate in this study. All patients eligible for entry into the study will have the 
clinical study, as well as potential risks and benefits of their participation in the study, explained 
to them. Each patient who agrees to participate will be required to sign and date an informed 
consent document prior to any study-specific testing or procedure. If new information is obtained 
during the clinical study, any patient who has not exited the study will be informed about the 
new information, and will be reconsented at the discretion of the investigator or the site’s 
IRB/REB. 
7.3 
Pre-enrollment (Visit 1) – Screening  
Screening tests may be completed in up to 3 screening visits to accommodate site-specific 
scheduling. It is recommended that screening tests conducted in Visit 1 be completed within 
8 weeks preceding the biopsy visit. Bloodborne pathogen testing must be completed within 
30 days before the biopsy procedure. If more than one visit is required, adverse events that occur 
after the patient signs the consent form shall be recorded during subsequent visits.   
After providing informed consent, the patient will have a medical history (including a urinary 
incontinence-focused history), a physical examination (including assessment of vital signs), a 
clinical assessment, and a medication assessment. Urine samples will be collected to test for 
nitrites and leukocyte esterase. If the urine test is positive for leukocyte esterase or nitrites, then a 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 24 of 41 
 
urine culture may be performed. The patient will undergo a bladder stress test (please refer to 
Appendix A for the Instructions for the Bladder Stress Test) and will complete a 24-hour pad 
test. Patients will be instructed on how to perform the 24-hour pad test (please refer to Appendix 
B for the Instructions for the 24-Hour Pad Test) and will be provided with sufficient preweighed 
pads to complete the test. The completed 24-hour pad test must be returned before or at the next 
scheduled screening visit. A PVR urine volume will be measured with ultrasound/bladder scan. 
Patients will complete the following questionnaires: ICIQ, IQOL, PGI-S, I-PSS, and IIEF-5. 
Blood samples will be collected to assess for PSA levels, bloodborne pathogens, hematocrit, 
hemoglobin, WBC count, blood urea nitrogen (BUN) or urea, and creatinine.  Patients will 
undergo cystoscopy for evaluation of the appearance of urethral and bladder tissue. An existing 
cystoscopy evaluation can be used if performed within 6 months prior to the time of consent. It is 
recommended that screening tests be performed from the least invasive test to the most invasive. 
Adverse events reported by the patient after informed consent is obtained will be recorded. 
7.4 
Point of Enrollment 
Patients are considered enrolled in the study at the time of the biopsy procedure. 
7.5 
Medications 
Patients may be given medication (including for pain or anxiety) according to each institution’s 
standard of care or at the physician’s discretion. Additionally, patients should be maintained on a 
stable dose or frequency of medication known to affect lower urinary tract function or erectile 
dysfunction, including but not limited to, anticholinergics, beta 3 adrenergic receptor agonists, 
tricyclic antidepressants, SNRI or SSRI antidepressants, diuretics, or alpha-adrenergic blockers, 
or phosphodiesterase type-5 inhibitors, for at least 2 weeks prior to screening assessments and 
throughout the study. A course of prophylactic antibiotics will be given prior to the injection 
procedure. 
7.6 
Biopsy (Visit 2) 
After patient eligibility is confirmed, patients will return to the clinic for an outpatient procedure 
in which muscle tissue is obtained using a needle biopsy technique. Note that several passes of 
the biopsy needle may be required to obtain a satisfactory sample of muscle tissue. Additionally, 
if the first biopsy does not produce an adequate sample for product isolation, it may be necessary 
for the patient to return for another biopsy procedure. The maximum permissible number of 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 25 of 41 
 
biopsy needle passes, and the total number of biopsies, is contingent upon patient tolerance and 
the satisfactory procurement of muscle tissue. If the biopsy procedure is scheduled for more than 
30 days after the most recently completed bloodborne pathogen tests, the bloodborne pathogen 
tests (i.e., Hepatitis B, Hepatitis C, HIV, and Syphilis) must be repeated before the biopsy 
procedure to confirm the patient’s continued eligibility for study participation. Additionally, the 
medication log will be updated if necessary. Any adverse events occurring since the last visit or 
before, during, or after the biopsy procedure will be recorded and reported as appropriate.  
7.6.1 Post-Biopsy Follow-up (Phone) 
Within 5 business days after the biopsy procedure, patients will be contacted by phone to 
determine whether any adverse events have occurred and whether any updates to the medication 
log are necessary.  
7.7 
Procedure (Visit 3) – Treatment Day 0  
Approximately 12-13 weeks after the muscle biopsy, patients will return to the clinic for a brief 
outpatient procedure. At the start of the visit or before the visit, patients will provide a completed 
24-hour pad test and complete the ICIQ, IQOL, PGI-S, I-PSS, IIEF-5 questionnaires. The 24-
hour pad test and questionnaire data collected on the day of injection will be used as the baseline 
data. Prophylactic antibiotics will be given prior to the injection procedure. Prior to injection, 
patients will have a urine sample collected to test for nitrites and leukocyte esterase. If the urine 
test is positive for leukocyte esterase or nitrites, a urine culture must be performed and the 
injection will be delayed. A negative urine dipstick for leukocyte esterase and nitrites is required 
in order to undergo AMDC-USR injection. Ultrasound may be performed to aid in the injection 
procedure. Under direct vision, multiple injections will be performed to circumferentially 
distribute AMDC-USR within the striated muscle of the urethral sphincter. After the injection is 
completed, the injected area will be examined for any excessive bleeding or excessive trauma. 
Prior to discharge, patients will demonstrate a normal void and will have their PVR urine volume 
determined by ultrasound/bladder scan. The medication log will be updated if necessary. Any 
adverse events occurring since the last visit or before, during, or after the injection procedure 
will be recorded and reported as appropriate. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 26 of 41 
 
7.8 
Follow-up 
Follow-up windows are intended as  recommendations only. They are not absolute and are not 
intended to limit data collection due to scheduling conflicts. 
7.8.1 Post-Treatment Follow-up (Phone) – Treatment Day 1-2  
Within 2 business days after treatment, patients will be contacted by phone to determine whether 
any adverse events have occurred and whether any updates to the medication log are necessary.  
7.8.2 Post-Treatment Follow-up (Phone) – Treatment Week 1 Within five business days after 
treatment, patients will be contacted by phone to determine whether any adverse events have 
occurred and whether any updates to the medication log are necessary.  
7.8.3  Follow-up (Visit 4) – Treatment Month 1 (± 1 week) 
A clinical assessment will be performed. Patients will provide a completed 24-hour pad test, and 
will have a urine sample collected to test for nitrites and leukocyte esterase. If the urine test is 
positive for nitrites or leukocyte esterase, then it is recommended a urine culture be performed. 
Blood samples will be collected to assess PSA levels, hematocrit, hemoglobin, WBC count, 
BUN or urea, and creatinine. PVR urine volume will also be determined via ultrasound/bladder 
scan. If, after multiple void attempts, the PVR volume is ≥ 200 mL, additional evaluation for 
obstruction is recommended. During the visit, patients will complete the following 
questionnaires: ICIQ, IQOL, PGI-S, I-PSS, IIEF-5, and PGI-I. The medication log will be 
updated if necessary. Any adverse events occurring since the last contact will be recorded and 
reported as appropriate. 
7.8.4 Follow-up (Visit 5) – Treatment Month 3 (± 1 week) 
A clinical assessment will be performed. Patients will provide a completed 24-hour pad test, and 
will have a urine sample collected to test for nitrites and leukocyte esterase. If the urine test is 
positive for nitrites or leukocyte esterase, then it is recommended a urine culture be performed. 
PVR urine volume will also be determined via ultrasound/bladder scan. If, after multiple void 
attempts, the PVR volume is ≥ 200 mL, additional evaluation for obstruction is recommended. 
During the visit, patients will complete the following questionnaires: ICIQ, IQOL, PGI-S, I-PSS, 
IIEF-5, and PGI-I. The medication log will be updated if necessary. Any adverse events 
occurring since the last visit will be recorded and reported as appropriate. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 27 of 41 
 
7.8.5 Follow-up (Visit 6) – Treatment Month 6 (- 2, + 4 weeks) 
A clinical assessment will be performed. Patients will provide a completed 24-hour pad test, and 
will have a urine sample collected to test for nitrites and leukocyte esterase. If the urine test is 
positive for nitrites or leukocyte esterase, then it is recommended a urine culture be performed. 
PVR urine volume will also be determined via ultrasound/bladder scan. If, after multiple void 
attempts, the PVR volume is ≥ 200 mL, additional evaluation for obstruction is recommended. 
During the visit, patients will complete the following questionnaires: ICIQ, IQOL, PGI-S, I-PSS, 
IIEF-5, and PGI-I. The medication log will be updated if necessary. Any adverse events 
occurring since the last visit will be recorded and reported as appropriate. 
7.8.6 Follow-up (Visit 7) – Treatment Month 12 (- 2, + 4 weeks) 
A clinical assessment will be performed. Patients will provide a completed 24-hour pad test, and 
will have a urine sample collected to test for nitrites and leukocyte esterase. If the urine test is 
positive for nitrites or leukocyte esterase, then it is recommended a urine culture be performed. 
Blood samples will be collected to assess PSA levels, hematocrit, hemoglobin, WBC count, 
BUN or urea, and creatinine. PVR urine volume will also be determined via ultrasound/bladder 
scan. If, after multiple void attempts, the PVR volume is ≥ 200 mL, additional evaluation for 
obstruction is recommended. The patient will undergo a bladder stress test and have a cystoscopy 
(for evaluation of the appearance of the urethral tissue). During the visit, patients will complete 
the following questionnaires: ICIQ, IQOL, PGI-S, I-PSS, IIEF-5, and PGI-I. The medication log 
will be updated if necessary. Any adverse events occurring since the last visit will be recorded 
and reported as appropriate. 
7.8.7 Post-Treatment Follow-up (Phone) – Treatment Month 24 (-2, +4 weeks) 
24 months after treatment, patients will be contacted by phone to determine whether any adverse 
events have occurred and whether any updates to the medication log are necessary. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 28 of 41 
 
7.9 
Duration of Study and Patient Participation 
Patients are expected to participate in this study for approximately 2.5 years from the time of the 
first screening visit. This duration includes time for screening, biopsy, injection, and 24 months 
of follow-up. 
7.10 
Criteria and Procedures for Withdrawal 
A patient may decide to withdraw from the study at any time either before or after undergoing 
study procedures without prejudice or loss of care. The patient should notify the investigator of 
his desire to withdraw. The investigator will notify the sponsor. The investigator may also decide 
to withdraw a patient from the study at any time based on medical judgment. In all instances of 
withdrawal, data collected up to the time of patient withdrawal, including the study exit form and 
the appropriate study visit, shall be submitted to the data coordinating center and shall include 
the reason why the patient has been withdrawn from the study. Patients will be asked to allow 
access to their medical records for 30 days after the date of withdrawal. Any data collected on 
the patient up to the point of withdrawal plus 30 days may be used in the study. 
 
In the event a patient cannot be contacted for post-treatment assessments, at least 3 attempts may 
be made to locate the patient, and these efforts will be documented. If the patient cannot be 
located, a lost to follow-up entry will be submitted. 
7.11 
Participation Endpoints of the Study 
A patient’s participation in the study will end after any of the following: 
 
 Patient completed all scheduled clinical evaluations to 24 months; 
 Patient withdrew or was lost to follow-up; 
 Patient received nonstudy treatment for SUI (e.g., injection of a bulking agent or 
completed surgery for a sling); 
 Study closed; or 
 Patient died. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 29 of 41 
 
8.0  
Statistical Considerations 
8.1 
Hypothesis to be Tested 
This is a preliminary, prospective, single-arm study to assess the safety of AMDC-USR in males 
with SUI. The study is not powered statistically for any measurable outcomes. 
8.2 
Sample Size 
The study will treat up to 30 patients at up to 5 clinical sites. Because this is a preliminary study, 
no formal statistical determination of sample size was performed. 
8.3 
General Analysis 
Statistical analyses will be performed using SAS
® for Windows
® (release 9.3 or higher) or other 
widely accepted statistical software. Continuous variables will be reported as means and standard 
deviations unless otherwise noted. Categorical variables will be reported as percents. Ninety-five 
percent (95%) confidence intervals for all endpoint variables will be presented. Survival analysis 
techniques such as Kaplan-Meier or Cox Proportional Hazards may be incorporated if censoring 
of data occurs. 
8.4 
Missing Data 
Missing data may be addressed using complete case analysis or multiple imputation. 
8.5 
Limitations of the Study 
This preliminary study with a small sample size may limit the ability to generalize results to a 
larger population. The sample size is insufficient to allow definitive statements regarding 
efficacy. Patients will serve as their own controls with quantitative and qualitative measures of 
incontinence assessed before treatment and compared to the same measures at various times after 
treatment. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 30 of 41 
 
9.0 
Deviations from Clinical Investigation Plan 
Investigators are not allowed to deviate from this CIP without prior authorization by the sponsor 
except under emergency situations when necessary to preserve the rights, safety, or well-being of 
study patients. 
 
Deviations and noncompliances will be recorded together with an explanation. Deviations or 
noncompliances that impact the rights, welfare, or safety of patients shall be reported to the 
sponsor and the IRB/REB as required and as soon as possible. 
 
If appropriate, corrective and preventive actions will be discussed by the sponsor, investigator, or 
the IRB/REB to determine a suitable course of action. 
10.0 
Data Collection and Reporting 
10.1 
Electronic Case Report Forms 
Patient data will be collected and entered by trained personnel at the clinical site into electronic 
Case Report Forms (eCRFs) through an electronic data capturing (EDC) system. This is a secure, 
web-based system, allowing those with permission to access data from any location at any time. 
Source data is to be retained for data entered into the EDC system. Data obtained and 
simultaneously entered into the EDC system may also serve as source documentation. Site 
personnel are required to undergo data entry training and will have unique login names and 
passwords in order to enter patient data. In accordance with 21 CFR Part 11, the EDC system 
creates a secure, computer-generated, time stamped audit trail to record the date and time of 
operator entries and actions that create, modify, or delete electronic records. 
10.2 
Data Reporting 
Progress reports and a final report at the conclusion of the clinical study will be submitted by the 
investigators and sponsor to the regulatory authorities and IRB/REB as required by local 
regulations. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 31 of 41 
 
11.0 
Data Management 
11.1 
Data Entry and Data Review 
Each principal investigator or appropriately trained designee shall enter the clinical data into the 
EDC system on standardized CRFs. Investigators will provide all applicable clinical data and 
documentation to the sponsor. Patient data and documents pertaining to the study will be kept 
and archived by the sponsor. Data will be reviewed for missing data, data consistency, and 
reasonableness of responses. Discrepancies will be resolved through a formal query process 
involving direct contact with investigators or research coordinators. The data coordinating center 
is responsible for database management, data verification, data archiving, and data retention. 
 
As needed to assist the sponsor in its research (e.g., during evaluation of an adverse event), data 
will be accessible to the sponsor, the participating investigators, the manufacturer, and 
companies or individuals the sponsor authorizes. 
 
Cook Research Incorporated the data coordinating center, is physically located in the United 
States. Therefore, information collected within a country outside of the United States will be 
transmitted to the United States. Personal information will be protected by fair trade practices 
and in accordance with all applicable laws.  
11.2 
Data Monitoring Arrangements 
The conduct of the clinical study will be supervised through a process of centralized and on-site 
monitoring. The data coordinating center will remotely monitor the study for data completeness 
and for adverse events. On-site monitoring will be implemented as necessary throughout the 
course of the study. The investigator/institution will provide direct access to source 
data/documents for study-related monitoring, audits, IRB/REB review, and regulatory 
inspection. Written procedures for monitoring the study are maintained by the data coordinating 
center and are summarized in Appendix C. 
12.0 
Procedures for Reporting Adverse Events 
Adverse events are to be reported to the data coordinating center using the appropriate CRF. In 
cases of adverse drug reactions or SAEs, completed forms will be submitted to the data 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 32 of 41 
 
coordinating center as soon as possible upon knowledge of the event. The data coordinating 
center will review the information submitted for possible reporting to the sponsor. Adverse 
events will be assessed in terms of relationship to product, relationship to biopsy procedure, 
relationship to injection procedure, severity, subsequent treatment/intervention required, and 
resolution status. Follow-up of all adverse events will be conducted per institutional standard of 
care. 
 
The sponsor shall, if required according to applicable regulations, report the event to the 
appropriate regulatory authority. (Expedited reporting is required for serious and unexpected 
suspected adverse reactions [SUSARs].) If indicated, all principal investigators and clinical sites 
will be notified of applicable events by the sponsor. The principal investigator or designee will 
notify his/her IRB/REB of applicable events according to institutional guidelines.  
13.0 
Early Termination or Suspension of the Clinical Study 
Any decision to suspend enrollment or terminate the clinical study, either completely or at one or 
more clinical sites, will be made by the sponsor and, if appropriate, the local IRB/REB. If a 
decision is made to terminate the study, all patients who have undergone one or more study 
procedures (i.e., biopsy or injection)  will be followed for 30 days following the most recent 
procedure. Regulatory authorities or the IRB/REB will be notified as required by local 
regulations. 
14.0 
Ethical Considerations 
This clinical study will be conducted in accordance with the ethical principles that have their 
origin in the Declaration of Helsinki and in accordance with 21 CFR 312 and ICH GCP. 
 
The investigator is responsible for obtaining approval of this clinical study from the relevant 
IRB/REB at his/her associated institution. The clinical study will not begin until a favorable 
opinion of the IRB/REB has been obtained. The investigator is responsible for complying with 
requirements imposed by his/her IRB/REB or regulatory authority. Furthermore, the sponsor and 
the investigator will ensure that local regulations concerning data protection are followed. 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 33 of 41 
 
15.0 
Publication Policy 
Publication policy, rights, and obligations for this study have been negotiated, detailed, and 
defined in the study’s contractual documents with the clinical site and investigators. 
16.0 
Clinical Study Administration and Investigators 
16.1 
Approvals and Agreements 
The sponsor and the principal investigators for each clinical site shall agree to this document and 
any modifications. A justification for any modifications will be documented. Approval and 
agreement will be indicated by signing the signature page provided with this document. 
16.2 
Investigators 
To see a complete list of the sponsor, manufacturer, monitor, and data coordinating center along 
with their contact information, please refer to Appendix D. A complete list of the principal 
investigators and coordinating investigators, along with their qualifications and contact 
information, will be updated and maintained by the data coordinating center. A list of the name 
and address of each reviewing IRB/REB will also be updated and maintained at the data 
coordinating center. 
16.3 
Insurance 
Insurance for the study will be obtained by the sponsor prior to patient enrollment. 
17.0 
References 
Please reference the Investigator’s Brochure for a complete literature review and evaluation. 
 
1. 
Kwon D, Kim Y, Pruchnic R, et al. Periurethral cellular injection: comparison of muscle-
derived progenitor cells and fibroblasts with regard to efficacy and tissue contractility in 
an animal model of stress urinary incontinence. Urology. 2006;68(2):449-454. 
2. 
Carr LK, Steele D, Steele S, et al. 1-year follow-up of autologous muscle-derived stem 
cell injection pilot study to treat stress urinary incontinence. Int. Urogynecol. J. Pelvic 
Floor Dysfunct. 2008;19(6):881-883. 
3. 
Carr LK, Robert M, Kultgen PL, et al. Autologous muscle derived cell therapy for stress 
urinary incontinence: a prospective, dose ranging study. J Urol. 2013;189(2):595-601. 
4. 
Peters KM, Dmochowski RR, Carr LK, et al. Autologous muscle derived cells for 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 34 of 41 
 
treatment of stress urinary incontinence in women. J Urol. 2014; 192(2):469-476. 
5. 
Moore K, Allen M, Voaklander DC. Pad tests and self-reports of continence in men 
awaiting radical prostatectomy: establishing baseline norms for males. Neurourol. 
Urodyn. 2004;23(7):623-626. 
6. 
Kumar A, Litt ER, Ballert KN, Nitti VW. Artificial urinary sphincter versus male sling 
for post-prostatectomy incontinence--what do patients choose? J Urol. 
2009;181(3):1231-1235. 
7. 
Shenot PJ. Urinary Retention. The Merk Manual Web site. 
http://www.merckmanuals.com/professional/genitourinary_disorders/voiding_disorders/u
rinary_retention.html. Updated Nov 2013. Accessed June 4, 2014. 
8. 
Avery K, Donovan J, Peters TJ, et al. ICIQ: a brief and robust measure for evaluating the 
symptoms and impact of urinary incontinence. Neurourol. Urodyn. 2004;23(4):322-330. 
9. 
Donovan J, Bosch, R., Gotoh, M., Jackson, S., Naughton, M., Radley, S., Valiquette, L., 
Batista, J.E., Avery, K. Symptom and Quality of Life Assessment. In: Abrams P, 
Cardozo, L., Khoury, S., Wein, A., ed. Incontinence: Basics & Evaluation. Vol 1: 
International Continence Society; 2005:519-584. 
10. 
Wagner TH, Patrick DL, Bavendam TG, Martin ML, Buesching DP. Quality of life of 
persons with urinary incontinence: development of a new measure. Urology. 
1996;47(1):67-71; discussion 71-62. 
11. 
Yalcin I, Bump RC. Validation of two global impression questionnaires for incontinence. 
Am. J. Obstet. Gynecol. 2003;189(1):98-101. 
12. 
Viktrup L, Hayes RP, Wang P, Shen W. Construct validation of patient global impression 
of severity (PGI-S) and improvement (PGI-I) questionnaires in the treatment of men with 
lower urinary tract symptoms secondary to benign prostatic hyperplasia. BMC Urol. 
2012; 12:30 doi: 10.1186/1471-2490-12-30. Epub 2012 Nov 7. 
13. 
Barry MJ, Fowler FJ, Jr., O'Leary MP, et al. The American Urological Association 
symptom index for benign prostatic hyperplasia. The Measurement Committee of the 
American Urological Association. J Urol. 1992;148(5):1549-1557; discussion 1564. 
14. 
AUA Practice Guideline Committee. AUA guideline on management of benign prostatic 
hyperplasia (2003). Chapter 1: Diagnosis and treatment recommendations. J Urol. 
2003;170(2 Pt 1):530-547. 
15. 
Rosen RC, Cappelleri JC, Smith MD, Lipsky J, Pena BM. Development and evaluation 
of an abridged, 5-item version of the International Index of Erectile Function (IIEF-5) as 
a diagnostic tool for erectile dysfunction. Int. J. Impot. Res. 1999;11(6):319-326. 
 
 
 
 
 
 
 
 
 
 
 
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 35 of 41 
 
APPENDIX A 
Bladder Stress Test 
 
All patients should have a bladder stress test as part of the screening procedures and at the 12-
month follow-up. Similar bladder fill volumes should be used for both tests. 
 
Bladder stress test 
 
 
 
 
 
 
 
 
  
 
 
 
  
 
 
 
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 36 of 41 
 
 
APPENDIX B 
24-Hour Pad Test 
 
All patients will have a 24-hour pad test as part of the screening procedures and at 1-month, 3-
month, 6-month and 12-month follow-ups. The 24-hour pad test should be completed the day 
before each scheduled visit.  
 
24-hour pad test 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
  
 
 
 
 
 
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 37 of 41 
 
APPENDIX C 
Written Procedures for Monitoring Studies 
 
A. Selection of the monitor. 
 
Designated by the sponsor to oversee the clinical study, the monitor may be an employee of 
Cook, an employee of a monitoring organization (CRO), or an independent contractor or 
consultant. The monitor shall be qualified by training and experience to monitor the study in 
accordance with all applicable regulations and standards for conducting clinical studies. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 38 of 41 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 39 of 41 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
The monitor shall immediately notify the sponsor of any conditions of noncompliance with the 
CIP, conditions of the IRB/REB or regulatory authority approval, or the applicable regulations. 
 
 

Cook MyoSite, Incorporated  
Version: 13-11-03 
 
 
AMDC-USR for Male SUI IND Clinical Trial 
 
Version Date: 17 November2015 
 
COMPANY CONFIDENTIAL
 
Page 41 of 41 
 
 
APPENDIX E 
Definitions 
 
Definitions for the following terms are not provided in this CIP, but can be found in the 
applicable regulations and guidances: 
 
Adverse Events 
Adverse Drug Reaction 
Life-threatening Adverse Event or Life-threatening Suspected Adverse Reaction 
Serious Adverse Event or Serious Suspected Adverse Reaction 
Serious Adverse Drug Reaction 
Serious and Unexpected Suspected Adverse Reaction 
Suspected Adverse Reaction 
Unexpected Adverse Event or Unexpected Suspected Adverse Reaction 
Unexpected Adverse Drug Reaction