Evaluation of the TULSA-PRO MRI-Guided Transurethral Ultrasound Prostate Ablation Device in Patients With Localized Prostate Cancer: a Prospective, Single-Arm, Pivotal Clinical Study
Phase: NA
Conditions: Prostate Cancer
Sponsor: Profound Medical Inc.

 
 
Clinical Protocol Summary 
 
Evaluation of the TULSA-PRO MRI-Guided Transurethral Ultrasound Prostate 
Ablation Device in Patients with Localized Prostate Cancer: a Prospective, 
Single-Arm, Pivotal Clinical Study 
 
ClinicalTrials.gov ID: NCT02766543 
Document Number: GCP-10283 
Date: 22 Jun 2021   
 
Sponsor: 
Profound Medical, Inc.  
2400 Skymark Avenue 
Unit 6 Mississauga, ON 
L4W 5K5, Canada  
Telephone: +1 (647) 476-1350 x408  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
Table of Contents 
 
1. Protocol Synopsis ......................................................................................................................... 2 
2. Study Schedule ............................................................................................................................. 6 
3. Purpose of the Investigation ........................................................................................................ 9 
3.1  
Work to date .................................................................................................................... 9 
4. 
Investigational Study Objectives and Endpoints .................................................................... 11 
4.1. 
Primary Objectives and Endpoints ................................................................................. 11 
4.2. 
Secondary Objectives and Endpoints ............................................................................. 12 
     4.3.      Economic Data Collection …………………………………………………………………………………………13 
5. 
Statistical Considerations ....................................................................................................... 13 
6.1. 
Study Hypothesis and Sample Size ................................................................................ 13 
6.2. 
Study Population ............................................................................................................ 14 
6.3. 
Outcome Data and Analysis ........................................................................................... 15 
6. 
Investigational Study Plan ...................................................................................................... 15 
6.1. 
Study Design................................................................................................................... 15 
6.2. 
Overview of Study Periods and Visits ............................................................................ 15 
6.3. 
Study Completion and Post-Study Surveillance ............................................................. 15 
     6.4.      Anticipated Duration of the trial ……………………………………………………………………………….16 
7. 
Investigational Site Training ................................................................................................... 16 
8. 
Records and Reports .............................................................................................................. 16 
8.1. 
Data Handling and Record-Keeping ............................................................................... 16 
8.2. 
Record Maintenance and Retention  ............................................................................. 16 
8.3. 
Device Accountability ..................................................................................................... 17 
9. 
Adverse Event Recording/Reporting  ..................................................................................... 17 
10. Site Monitoring Procedures ………………………………………………………………………………………………17 
11. References ............................................................................................................................. 18 
 
 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
Protocol Synopsis 
Protocol Title 
Evaluation of the TULSA-PRO MRI-guided transurethral ultrasound prostate ablation 
device in patients with localized prostate cancer 
Protocol 
Number 
GCP-10100 
Study Design 
Prospective, multi-center, single-arm study 
Sample Size 
Part I - 110 patients target (115 treated) 
Part II -  35 patient (from US sites only) 
Study Period 
Estimated recruitment period: 6-12 months 
Follow-up and analysis of primary endpoints: 12 months 
Interim analysis of secondary endpoints: 12 months 
Total study follow-up: 5 years 
Study 
Population 
Male, age 45 to 80 years, diagnosed with organ-confined prostate cancer 
(see eligibility criteria below) 
Objective 
The primary objective of this study is to further evaluate the safety and efficacy of 
the MRI-guided TULSA-PRO device intended to ablate prostate tissue of patients 
with localized, organ-confined prostate cancer 
Primary 
Endpoints 
Safety Endpoint: Frequency and severity of all adverse events, categorized according 
to their attribution. 
Efficacy Endpoint: Proportion of patients achieving a PSA nadir ≤ 25% of the pre-
treatment baseline value. 
Secondary 
Endpoints 
Erectile Dysfunction Endpoint: Rate of erectile dysfunction, determined by the 
change from baseline of the proportion of patients with IIEF-5 < 17. 
Erection Firmness Endpoint: Rate of erection firmness sufficient for penetration, 
determined by the change from baseline of the proportion of patients with IIEF item 
2 ≥ 2. 
Urinary Incontinence Endpoint: Rate of urinary incontinence, determined by the 
change from baseline of the proportion of patients with EPIC item 5 ≥ 1 (one or 
more pads per day). 
PSA Nadir Endpoint: Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml. 
PSA Stability Endpoint: Proportion of patients with PSA ≤ 0.5 ng/ml at the most 
recent follow-up visit. 
Prostate Volume Endpoint: Prostate volume reduction, evaluated on MRI between 
the treatment day and 12-month follow-up visits. 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
Prostate Biopsy Endpoint: Proportion of patients with negative prostate biopsy at 
the 12-month follow-up visit, determined by TRUS-guided 10-core biopsy. 
IPSS Endpoint: Change in International Prostate Symptom Score (IPSS). 
IIEF Endpoint: Change in International Index of Erectile Function (IIEF-15), and its 
sub-domains. 
EPIC Endpoint: Change in Expanded Prostate Cancer Index Composite (EPIC), and its 
sub-domains. 
Targeting Accuracy Endpoint: Conformal prostate ablation, measured quantitatively 
between the target prostate volume and the ablative heating volume on MRI 
thermometry1. 
CE-MRI Endpoint: Conformal prostate ablation, assessed qualitatively by visualizing 
the peripheral region of enhancement surrounding the non-perfused volume (NPV) 
on contrast-enhanced (CE)-MRI acquired immediately after treatment. 
mpMRI Endpoint: Evaluation of prostate MRI using PI-RADS v2, performed at the 
baseline and 12-month follow-up visits. 
DSMC Safety 
Analysis 
Two safety assessments by an independent Data Safety Monitoring Committee 
(DSMC) will be performed. Study enrolment will continue while data are collected. 
The DSMC reviews will occur when: 
- First 10 patients complete treatment. If 2 or more of the first 10 patients who 
have undergone the TULSA-PRO procedure have a documented rectal fistula then 
the DSMC would recommend stopping the trial. 
- First 10 patients complete 1-month follow-up visit. If ≥ 10% of all patients who 
have undergone the TULSA-PRO procedure at the time of the DSMC analysis have 
a documented rectal fistula, then the DSMB would recommend stopping the trial. 
Eligibility 
Criteria 
Inclusion Criteria 
1. 
Male, age 45 to 80 years 
2. 
Biopsy-confirmed adenocarcinoma of the prostate. Biopsy (minimum 10 cores) 
obtained ≥ 6 weeks and ≤ 6 months before treatment (or at the discretion of PI 
and approval by the Sponsor).  
3. 
Clinical stage ≤ T2b 
4.1     Gleason score ≤ 3 + 4 (Part I only) 
4.2     Gleason score 3+4 (Part II only) 
5.       PSA ≤ 15 ng/ml 
6.       Eligible for MRI [Form GCP-10131] 
7.       Eligible for general anesthesia (ASA category ≤ 3) 
8.       Prostate volume ≤ 90 cc, on Baseline MRI 
9.       Prostate size ≤ 5.0 cm in sagittal length, and ≤ 6.0 cm in axial diameter, on   
Baseline MRI 
10.    Life expectancy ≥ 10 years 
11.    No calcifications in the planned ultrasound beam path, or at the discretion of 
the investigator with approval from the Sponsor. 
 
1 Conformal prostate ablation is measured using the Dice Similarity Coefficient (DSC), linear accuracy and precision, 
and volumetric over-/under-heating of the target prostate volume 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
Exclusion Criteria 
1. 
Evidence (including Baseline MRI and bone scan) of extracapsular extension, 
sphincter involvement, seminal vesicle invasion, lymph node invasion or 
metastases 
2. 
Suspected tumour on Baseline MRI within 3 mm of the prostatic urethra, or in 
the prostate apex within 3 mm from the sphincter plane 
3. 
Prior definitive treatment of prostate cancer 
4. 
Prior transurethral resection of the prostate (TURP) 
5. 
Use of 5-alpha reductase inhibitors (5-ARIs) or hormone therapy within 3 
months prior to the baseline visit. Baseline PSA must be established after a 
minimum of 3 months following 5-ARIs discontinuation. Additionally, use of 5-
ARIs is not permitted following treatment during the study follow-up period. 
6. 
Prostate calcifications > 1 cm in largest diameter, on Baseline Ultrasound 
7. 
Cysts > 1 cm in largest diameter, on Baseline MRI 
8. 
Bleeding disorder (International Normalized Ratio (INR) > ULN and partial 
thromboplastin time (PTT) > ULN) 
9. 
Abnormal coagulation and current anticoagulant therapy. Patients whose 
anticoagulation therapy can be temporarily reversed within 7 days prior to 
treatment are eligible. Platelet inhibitors (ie: ASA) and heparin are not 
exclusion criteria. 
10. Acute unresolved Urinary Tract Infection (UTI) 
11. Interest in future fertility 
12. History of any other malignancy other than skin cancer, or low grade bladder 
cancer2 which has been completely resected, within the previous 2 years. 
Patients that have had curative treatment of a previous malignancy and no 
recurrence of that malignancy within the past 2 years will be allowed. 
13. Patients with peripheral arterial disease with intermittent claudication or 
Leriches Syndrome (i.e. claudication of the buttocks or perineum) 
14. Patients with diabetes who have evidence of complications from their 
diabetes, such as end organ sequelae of diabetes (ie: severe peripheral 
vascular disease, diabetic retinopathy), or Hemoglobin A1c > 7%. 
15. History of any major rectal or pelvic surgery or radiotherapy 
16. History of ulcerative colitis or other chronic inflammatory conditions affecting 
rectum (includes rectal fistula, anal stenosis) 
17. Documented clinical prostatitis requiring therapy within 6 months prior to 
Treatment 
18. History of urethral and bladder outlet disorders, including urethral stricture 
disease, urethral diverticulae, bladder neck contracture, urethral fistulae, 
urethral stenting, urethral sling, urethroplasty or chronic indwelling urethral 
catheter 
19. Patients with artificial urinary sphincter or any penile implant 
20. Severe neurogenic bladder 
21. Untreated bladder stones 
22. History of acute urinary retention within the last 12 months 
23. Active untreated gross hematuria for any cause 
 
2 Study subjects with previous history of low grade bladder cancer that has been completely resected within the 
previous 2 years will be allowed to undergo surveillance cystoscopy, as scheduled, except for a period of 1 month 
after the study treatment or within 1 week of any study visit. 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
24. Post Void Residual (PVR) bladder volume > 250 mL, confirmed on repeat 
evaluation 
25. Obstructing median lobe enlarged out of proportion to the rest of the prostate 
and protruding significantly into the bladder, sometimes referred to as “ball 
valve” median lobe, determined on Baseline MRI 
26. Any prostate related investigational therapy within 6 months of Visit 1 
27. History of Parkinson’s disease or multiple sclerosis 
28. History of drug abuse 
29. Known infectious disease including HIV positivity or AIDS-related illness, HBV 
and HCV 
30. Current unilateral or bilateral hydronephrosis 
31. Allergy or contraindications to administration of the GI anti-spasmodic drug:  
a. Patients in the USA: Glucagon 
Contraindications: Pheochromocytoma (adrenal gland tumour), chronic 
hypoglycemia, insulin releasing tumour, hypersensitivity to glucagon, 
allergy to glucagon, lactose or glycerin. 
b. Patients in Canada and Europe: Buscopan (Hyoscine) 
Contraindications: Porphyria/Myasthenia Gravis, Heart attack within 
the last 6 months, poorly controlled angina requiring medication, heart 
failure not controlled with medication, hypersensitivity to hyoscine 
butylbromide, or atropinics. 
32. Contraindications to administration of gadolinium-based MRI contrast agent 
(e.g. Magnevist), such as chronic, severe kidney disease (glomerular filtration 
rate (GFR) <30 mL/min/1.73m2), acute kidney injury, history of Sickle Cell 
Disease, history of anemia (low red blood cell count), or intolerance/allergy to 
the contrast agent 
33. Other severe, acute or chronic medical or psychiatric condition or laboratory 
abnormality that may increase the risk associated with study participation or 
study drug administration, or may interfere with the interpretation of study 
results, which in the judgment of the investigator would make the patient 
inappropriate for entry into this study. 
 
  
 
 
 
 
 
 
 
 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
2. Study Schedule 
Visit 
No 
Visit Type 
Window Allowance 
Office Visit, Lab Tests & Patient 
Forms 
Imaging 
0 
Screening 
Biopsy ≥ 6 weeks and ≤ 
6 months before  
treatment (or at the 
discretion of PI and 
approval by the 
Sponsor) 
- PSA3 
- Prostate biopsy (min. 10 cores) 
(Can use previous documented 
results) 
- Informed Consent Form (ICF) 
- Economic Data Collection7 
- Baseline Prostate MRI 
evaluated for 
malignant lesions 
using PI-RADS v2, and 
to assess prostate size, 
cysts4, extracapsular 
extension, sphincter 
involvement, seminal 
vesicle invasion, lymph 
node invasion and 
metastases 
- Baseline Prostate 
Ultrasound5 to assess 
calcifications 
- Baseline Bone Scan to 
assess metastases, 
only if patient has 
clinical stage T2 and 
PSA > 10 ng/ml 
- MRI, Ultrasound and 
Bone Scan ≤ 6 months 
before treatment 
- If performed after the 
biopsy, MRI and 
Ultrasound must be 
> 6 weeks after biopsy 
- Can use previously 
documented results 
1 
Eligibility & Baseline 
≤ 6 weeks before 
treatment  
- Inclusion, exclusion assessment  
- Medical history 
- Physical Examination 
- PSA3 (Screening PSA can be used 
as Baseline PSA, at the discretion 
of the PI and if acquired within 3 
months prior to treatment) 
- Urine Culture 
- Blood and Urine analysis 
- Uroflowmetry/PVR volume 
- Concomitant medication 
- Adverse Events  
- Quality of life questionnaire 
- Demographics questionnaire 
- Pre-treatment bowel preparation 
instructions given to patient 
- Economic Data Collection7 
2 
Treatment 
≤ 6 weeks after 
baseline visit 
- PSA3 
- Supra-pubic catheter placement 
- Overnight admission at discretion 
of PI 
- Concomitant medication 
- Adverse events 
- Economic Data Collection7  
- Prostate MRI for 
planning and 
treatment 
 
3 Activities and procedures that can elevate PSA levels must be avoided prior to any study related PSA test. For 
example, PSA should be obtained prior to any Digital Rectal Exam (DRE), cystoscopy or biopsy. Additionally, 
patients should be instructed to avoid vigorous exercise, riding a bicycle, sexual activity and ejaculation for at least 
48 hours prior to any scheduled study related PSA test. 
4 At the discretion of the PI, the assessment of prostate cysts may be done by Ultrasound instead of MRI. 
5 At the discretion of the PI, the Baseline Prostate Ultrasound to assess calcifications may be replaced by a 
Computer Tomography (CT) imaging exam. 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
Visit 
No 
Visit Type 
Window Allowance 
Office Visit, Lab Tests & Patient 
Forms 
Imaging 
3 
Catheter Removal 
Between 
1 and 4 weeks 
- Catheter removal at the 
discretion of the PI and following 
clamping for 24 hours to verify 
ability to void 
- Concomitant medication 
- Adverse events  
- Economic Data Collection7 
 
4 
1-month follow-up 
5 weeks 
± 1 week 
- Physical examination 
- PSA3 
- Blood and Urine analysis 
- Concomitant medication 
- Adverse events  
- QOL questionnaire 
- Economic Data Collection7 
 
5 
3-month follow-up 
3 months 
± 2 weeks 
Note: Visit may be performed by 
telephone and mail6 
- Concomitant medication (may be 
performed by telephone) 
- Adverse events  (may be 
performed by telephone) 
- QOL questionnaire (may be 
performed by mail or telephone) 
- PSA3 (may be performed at local 
clinic) 
- Physical examination (if visit 
occurs in person)  
- Economic Data Collection7 
 
6 
6-month follow-up 
6 months 
± 1 month 
- Physical examination 
- PSA3 
- Concomitant medication 
- Adverse events  
- QOL questionnaire 
- Economic Data Collection7 
 
 
6 If there are no significant ongoing adverse events at the 1-month visit, then this visit may be performed by 
telephone and mail, at the discretion of the PI. 
7 Economic data are costs associated with the patients’ involvement in the study. This can include the procedure 
and labs etc. that are done at every visit which are documented in de-identified UB-04 Forms  provided by the site. 
Economic data collection is optional for the patient and will only be collected if the patient signs the optional 
portion of the consent form.  

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
Visit 
No 
Visit Type 
Window Allowance 
Office Visit, Lab Tests & Patient 
Forms 
Imaging 
7 
12-month follow-up 
12 months 
± 1 month 
- Physical examination 
- Transrectal Ultrasound (TRUS) 
guided 10-core prostate biopsy  
- PSA3 (prior to biopsy) 
- Uroflowmetry/PVR volume (prior 
to biopsy) 
- Concomitant medication 
- Adverse events  
- QOL questionnaire 
- Economic Data Collection7 
- Follow-up Prostate 
MRI evaluated using 
PI-RADS v2 (prior to 
biopsy) 
8 
2-year follow-up 
24 months 
± 2 months 
- Physical examination 
- PSA3 
- Concomitant medication 
- Adverse events  
- QOL questionnaire 
- Economic Data Collection7 
 
9 
3-year follow-up 
36 months 
± 2 months 
- Physical examination 
- PSA3 
- Concomitant medication 
- Adverse events  
- QOL questionnaire 
- Economic Data Collection7 
 
10 
4-year follow-up 
48 months 
± 2 months 
- Physical examination 
- PSA3 
- Concomitant medication 
- Adverse events  
- QOL questionnaire 
- Economic Data Collection7 
 
11 
5-year follow-up 
60 months 
± 2 months 
- Physical examination 
- PSA3 
- Concomitant medication 
- Adverse events  
- QOL questionnaire 
- Economic Data Collection7 
 
 
 
 
 
 
 
 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
3.0 Purpose of the Investigation  
The purpose of this Pivotal clinical study is to establish the safety and effectiveness of the TULSA-PRO for 
accurate and precise ablation of the prostate gland, with reduced safety margins and in a larger prostate 
cancer population.  
3.1 Work to Date  
Computer simulations 
Initial feasibility of using MRI-TULSA for whole-gland prostate ablation has been evaluated extensively in 
computer simulations, including ultrasound device requirements, MRI thermometry specifications, 
treatment delivery feedback control algorithms and treatment planning strategies [Chopra et al 2005, 
Chopra et al 2006, Burtnyk et al 2009, Kobelevskiy et al 2009, Burtnyk et al 2010a, Burtnyk et al 2010b, 
N’Djin et al 2012a, DOC-10444, DOC-10450, DOC-10455, DOC-10456]. Most recently, the computer 
simulations were validated with the clinical Phase I data, and were used to support the pivotal trial 
treatment parameters [DOC-10699, DOC-10718]. 
Experiments in tissue-mimicking gel phantoms 
Using a prototype system, the feasibility, accuracy and precision of heating tissue to thermal ablation 
using a transurethral ultrasound device under MRI-guidance has been investigated in tissue-mimicking 
gel phantoms [Tang et al 2007, Burtnyk et al 2010b, N’Djin et al 2012b]. Experiments in tissue-mimicking 
gel phantoms are a key component of development, verification and validation of the PMI TULSA-PRO, 
including refinement of the MRI protocol, system validation and clinical site qualification. 
Pre-clinical experiments in the canine prostate model 
Several in-vivo experiments have been performed in the canine prostate model to evaluate the ability of 
MRI-TULSA to treat the prostate under realistic clinical conditions including dynamic changes in blood 
flow and ultrasound attenuation during treatment [Boyes et al 2007, Chopra et al 2008, Chopra et al 
2009, Chopra et al 2010, Siddiqui et al 2010, PMI-10129, Burtnyk et al 2015].  
These studies have established the ability to accurately generate thermal patterns in-vivo that conform 
to target volumes within about 1 mm using closed-loop temperature feedback control in under 30 min. 
Comprehensive histological analysis of the canine prostate tissue after treatment has also revealed the 
close relationship (≤ 3 mm) between acute 100% cell kill, 55°C target temperature on MRI thermometry 
and the peripheral region of enhancement surrounding the NPV on post-treatment CE-MRI.  
Table 1: Summary of number and type of pre-clinical and clinical studies. 
Phase 
Year 
MRI-TULSA System 
MRI System 
Number of Subjects 
Pre-clinical canine 
2006 - 
2009 
Sunnybrook prototype 
GE 1.5T 
13 canines, acute 
4 canines, delayed 48 hours 
Pre-clinical canine 
2010 
PMI TULSA-PRO prototype 
GE 1.5T 
10 canines, acute 
2 canines, delayed 7 days 
2 canines, delayed 14 days 
Pre-clinical canine 
2012 
PMI TULSA-PRO 
Siemens 3T 
8 canines, delayed 28 days 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
Phase 0 clinical 
2009 
Sunnybrook prototype 
GE 1.5T 
8 patients, “treat-and-resect” 
Phase 0 clinical 
2012 
Sunnybrook prototype 
Philips 3T 
4 patients, “treat-and-resect” 
Phase I clinical 
2013 - 
2015 
PMI TULSA-PRO 
Siemens 3T 
30 patients with 12-month 
follow-up 
 
Phase 0 “treat-and-resect” clinical studies 
Using the Sunnybrook prototype system, Dr. Laurence Klotz, Chief of Urology, and Dr. Rajiv Chopra, MRI 
physicist, led two Ethics Committee (EC)-approved Phase 0 academic “treat-and-resect” clinical studies 
of MRI-TULSA [Chopra et al 2012, Colquhoun et al 2011, Ramsay et al 2017]. All twelve patients across 
both studies underwent a radical prostatectomy immediately following MRI-TULSA, with acute whole-
mount histological evaluation of the ablation zone correlated to MRI temperature measurements. All 
patients had organ-confined prostate cancer with Gleason score ≤ 7 and PSA ≤ 15 ng/ml. 
Phase I clinical trial 
Most recently, MRI-TULSA was evaluated in a single-arm, prospective Phase I clinical study sponsored by 
PMI to determine the safety and feasibility of the TULSA-PRO in patients with localized prostate cancer 
[Chin et al 2016, Clinical Protocol DOC-10246, FDA IDE G130103, Health Canada ITA 199241, Eudamed 
No. CIV-13-04-010681]. Patient enrolment spanned March 2013 to March 2014 at three trial sites: Dr. 
Joseph Chin at Western University (UWO), London Health Sciences Center, London ON, Canada; Dr. 
Heinz-Peter Schlemmer at the German Cancer Research Center (DKFZ), Heidelberg, Germany; and Dr. 
James Relle at William Beaumont Health System, Royal Oak MI, USA.  
A total of thirty patients underwent prostate ablation with the TULSA-PRO. All patients had biopsy-
proven low-/intermediate-risk prostate cancer with clinical stage T1c – T2a, PSA ≤ 10 ng/ml, Gleason 
score ≤ 6 (USA and Germany) ≤ 3+4 (Canada), and no prior treatment of their prostate Primary 
endpoints were safety (frequency and severity of adverse events) and feasibility (conformal thermal 
ablation on MRI thermometry and CE-MRI). Clinical follow-up included serial PSA, QOL questionnaires 
(IPSS, erectile function domain of the IIEF-15, and bowel habits domain of the UCLA-PCI-SF), 12-month 
prostate biopsy, cystoscopy and MRI. 
Only 2 of 22 patients who underwent 3-year biopsy experienced histological upgrading with respect to 
their 12-month biopsy (GCP-10281).  
Biochemical recurrence (Phoenix criteria of 2 ng/ml above nadir) occurred in 10 patients, with an 
estimated 5-year biochemical recurrence-free survival of 61%. At 5-year follow up, median (IQR) PSA 
decreased from 5.8 ng/mL to a post-treatment nadir of 0.26 ng/mL in patients free of salvage therapy. 
PSA remained stable at 1 years and at 5 years. Among the 10 men who underwent post-TULSA salvage, 
PSA decreased 82% from 6.1 ng/ml to nadir of 0.80 ng/ml (GCP-10281). The estimated 5-year salvage-
free survival was 67%. The estimated five-year disease-specific survival was 100%, with overall survival 
of 97% and metastasis-free survival of 97% (Nair et al 2020). 
Adverse Events (AE) were evaluated according to the Common Terminology Criteria for Adverse Events 
(CTCAE) version 4. There were no intraoperative complications, no rectal injury or fistula, and no severe 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
urinary incontinence. There were no Grade 4 or higher AE, and only one attributable Grade 3 AE 
(epididymitis in 1 patient, resolved with IV-antibiotics). Treatment-emergent Grade 2 erectile 
dysfunction managed with medication was experienced by 10/30 (33%) subjects, ongoing at the final 
visit in 4/16 (25%) men who completed 5-year follow-up. There were no cases of Grade 3 erectile 
dysfunction requiring surgical intervention. Most patients experienced some type of rapidly resolving 
Grade 2 genitourinary event within the first month of treatment such as urinary retention (5 men, 
resolved with catheterization), urgency (5 men, resolved with medication), bladder spasm (4 men, 
resolved with medication), or obstructive micturition (3 men, resolved with catheterization).  At five 
years, 2 men continued to have Grade 2 GU complications: lower urinary tract symptoms managed with 
medication.  Gastrointestinal events were limited to 5 Grade 1 events of bloating, constipation, or rectal 
pain that resolved on their own in the first month [GCP-10281].  
Median (IQR) ultrasound treatment time was 36 (26–44) min and prostate volume 44 (38–48) cc. Spatial 
accuracy and precision of thermal ablation was 0.1 ± 1.3 mm, with the conformal NPV confirmed on CE-
MRI after treatment. Median PSA decreased 87% from 5.8 (3.8–8.0) ng/ml to 0.8 (0.5–1.1) ng/ml at 1 
month, remaining stable at 0.8 (0.6–1.1) ng/ml to 12 months. IPSS and UCLA-PCI-SF bowel habits 
domain scores returned to baseline values by 3 months, remaining stable to 12 months. At 3 months, 
Median (IQR) IPSS was stable from baseline through 5-year follow-up (Nair et al 2020). IIEF-15 erectile 
function domain scores and erections sufficient for penetration (IIEF question 2 ≥ 2) recovered by one 
year and declined thereafter, likely due to the advanced age of this cohort.  UCLA-PCI-SF bowel function 
and bowel bother scores were unchanged.  
The results of the Phase I study demonstrate that MRI-TULSA is a safe and feasible procedure for the 
accurate and precise conformal ablation of prostate tissue. The PMI TULSA-PRO system provides 
accurate treatment planning, real-time thermal dosimetry and precise control of prostate ablation, with 
a well-tolerated side-effect profile. The results of this study are sufficiently compelling to justify further 
study of the TULSA-PRO in a Pivotal clinical trial with a larger prostate cancer patient population and 
reduced safety margins. 
 
4.0 Investigational Study Endpoints and Objectives  
4.1 Primary Objectives and Endpoints 
The primary objective of this study is to further evaluate the safety and effectiveness of the MRI-guided 
TULSA-PRO device intended to ablate prostate tissue of patients with localized, organ-confined prostate 
cancer. 
As part of the safety assessment, special attention will be made to determine the rates of erectile 
dysfunction, erection firmness sufficient for penetration and urinary incontinence, evaluated specifically 
using the corresponding secondary endpoints. 
• 
Safety Endpoint: Frequency and severity of all adverse events will be evaluated by attribution. 
• 
Efficacy Endpoint: Prostate ablation efficacy will be evaluated using the proportion of patients 
achieving a PSA nadir ≤ 25% of the pre-treatment baseline value. 

 
 
Clinical Protocol Summary 
   
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GCP-10283_Rev B                                      
4.2 Secondary Objectives and Endpoints 
There are multiple secondary objectives of this study designed to examine in more detail the safety and 
effectiveness of the TULSA-PRO device, as well as its impact on patient quality of life. Additional 
secondary imaging endpoints evaluate the spatial accuracy and precision of prostate ablation using 
TUSLA-PRO device, as well as changes observed on diagnostic prostate MRI. 
• 
Erectile Dysfunction Endpoint: Rate of erectile dysfunction, determined by the change from 
baseline of the proportion of patients with IIEF-5 < 17. 
• 
Erection Firmness Endpoint: Rate of erection firmness sufficient for penetration, determined by 
the change from baseline of the proportion of patients with IIEF item 2 ≥ 2. 
• 
Urinary Incontinence Endpoint: Rate of urinary incontinence, determined by the change from 
baseline of the proportion of patients with EPIC item 5 ≥ 1 (one or more pads per day). 
• 
PSA Nadir Endpoint: Proportion of patients achieving PSA nadir ≤ 0.5 ng/ml. 
• 
PSA Stability Endpoint: Proportion of patients with PSA ≤ 0.5 ng/ml at the most recent follow-
up visit. 
• 
Prostate Volume Endpoint: Prostate volume reduction, evaluated on MRI between the 
treatment day and 12-month follow-up visits. 
• 
Prostate Biopsy Endpoint: Proportion of patients with negative prostate biopsy at the 12-month 
follow-up visit, determined by TRUS-guided 10-core biopsy. 
• 
IPSS Endpoint: Change in International Prostate Symptom Score (IPSS), between the baseline 
and most recent follow-up visit. 
• 
IIEF Endpoint: Change in the Erectile Function, Orgasmic Function, Sexual Desire, Intercourse 
Satisfaction and Overall Satisfaction domains of the International Index of Erectile Function (IIEF-
15), between the baseline and most recent follow-up visit. 
• 
EPIC Endpoint: Change in Urinary, Bowel, Sexual and Hormonal domains of the Expanded 
Prostate Cancer Index Composite (EPIC), between the baseline and most recent follow-up visit. 
• 
Targeting Accuracy Endpoint: Conformal prostate ablation, measured quantitatively between 
the target prostate volume and the target temperature isotherm on MRI thermometry acquired 
during the TULSA-PRO procedure, and described using three measures of targeting accuracy: 
o Dice Similarity Coefficient (DSC – unitless from 0 to 1), is a statistical validation metric to 
measure the degree of spatial overlap between two regions [Dice 1945]. 
o Over- and under-targeted volumes (outside the target volume ± ½ voxel margin), 
representing the amount of tissue ≥ target temperature outside the target volume and < 
target temperature inside the target volume, respectively. The over- and under-targeted 
volumes are expressed in absolute cc, and as a % of the target volume. 
o Linear targeting in mm, representing the spatial accuracy (average) and precision 
(standard deviation) of the TULSA-PRO to heat the target boundary to the target 
temperature.  
• 
CE-MRI Endpoint: Conformal prostate ablation, assessed qualitatively by visualizing the 
peripheral region of enhancement surrounding the non-perfused volume (NPV) on contrast-
enhanced (CE)-MRI acquired immediately after treatment. 
• 
mpMRI Endpoint: Characterize the effect of the TULSA-PRO ablation on diagnostic multi-
parametric prostate MRI (mpMRI), determined using PI-RADS v2 performed at the Baseline and 
12-month follow-up visits. 
 

 
 
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GCP-10283_Rev B                                      
4.3 Economic Data Collection  
Profound Medical Inc., would also like to collect individual patient-level economic data in order to create 
a TULSA cost model for reimbursement purposes. Economic data include the costs and expenses 
associated with the patient’s participation in the study, including the treatment day and follow-up care. 
Data will be collected using UB-04 forms provided by each site who has consented, enrolled and treated 
patients under this protocol (Protocol Rev D). This portion of the study is optional and all anonymized 
UB-04s will be collected from the site only if the patient provides their consent. Data collected will not 
be published and is for information purposes only.  
 
5.0 Statistical Considerations  
5.1 Study Hypothesis and Sample Size 
It is hypothesized that the use of the TULSA-PRO MRI-guided transurethral ultrasound prostate ablation 
device for ablation of prostate tissue in patients with localized organ-confined prostate cancer would be 
deemed not clinically interesting if 50% of patients or less had a reduction in PSA ≥ 75% (PSA nadir ≤ 
25% of the pre-treatment baseline value). Conversely, the use of the TULSA-PRO MRI-guided 
transurethral ultrasound prostate ablation device for ablation of prostate tissue in patients with 
localized organ-confined prostate cancer would be deemed clinically of interest if this rate was greater 
than 50%. Therefore, using a one-sided, α=0.025 exact test for a single proportion, one would achieve at 
least 80% statistical power to distinguish between H0: p≤50% versus Ha: p>50% with 90 total patients 
(calculated using nQuery Advisor version 7.0), where the performance goal for the success proportion is 
50% and it is expected that p=65%. 
Following completion of the initial study enrolment (Part I), 48% of patients treated (55 of 115) were 
from US sites. In efforts to achieve a study population with majority of American patients, we will target 
35 total patients from up to 4 clinical sites within the United States in Part II of the study enrolment. 
5.2 Study Population 
The population used to evaluate the study primary endpoints (safety and effectiveness) will be the 
modified intent-to-treat (mITT) group. The mITT group consists of all subjects who meet the eligibility 
criteria, have a valid and signed informed consent form, and have received treatment7 with the TULSA-
PRO device according to this clinical protocol. The population used to evaluate the study secondary 
endpoints will be the per protocol (PP) group, except for the Prostate Biopsy Endpoint which will use the 
mITT group. The PP group will be defined as all subjects who are part of the mITT group and have 
completed the 12-month follow-up visit. Any subject who is included in the mITT group but not the PP 
group will be described, including the reasons for exclusion. 
A patient who withdraws before TULSA-PRO treatment delivery will not be included in the mITT group, 
and will be replaced by enrolling an additional patient. If a patient withdraws from the study after 
 
7 Subjects who receive any treatment (ultrasound delivery) with the TULSA-PRO device, even if the therapy is not 
complete, will be considered to have received treatment with the TULSA-PRO device.  

 
 
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GCP-10283_Rev B                                      
treatment delivery, they will be accounted for in the mITT group, regardless of the reason for their 
withdrawal. 
5.3 Outcome Data and Analysis 
Analysis of the study primary endpoints will be performed using data up to the 12-month follow-up 
visits. A formal interim analysis of secondary endpoints will also occur using data up to the 12-month 
follow-up visits. 
Below is a summary of the data analysis methods used to evaluate the outcome of the clinical trial.  
Demography and baseline characteristics 
Demographic and baseline laboratory results will be summarized using descriptive statistics for all 
subjects. 
Primary Endpoint Analyses 
The primary efficacy outcome will be the proportion of patients achieving a PSA nadir ≤ 25% of the pre-
treatment baseline value, representing a clinically meaningful reduction in PSA of at least 75% and clear 
evidence of effective prostate ablation. Given a maximum pre-treatment baseline PSA of 15 ng/ml, a 
reduction of at least 75% would result in a post-treatment PSA less than 4 ng/ml, which is clinically 
significant. Adverse events will be summarized using descriptive statistics, primarily the frequency and 
proportion of events. Given subjectivity in defining erectile dysfunction and urinary incontinence, these 
outcomes will be quantified and reported using the IIEF and EPIC questionnaires.  
Secondary Endpoint Analyses 
All secondary endpoints will be described using summary and descriptive statistics, in tables, lists and 
figures, and 95% confidence intervals will be constructed for select endpoints of interest. Three analyses 
of the Prostate Biopsy Endpoint will be performed, as described below in Section 0. Although PI-RADS v2 
is not specifically designed for post-treatment assessment, it will be used with the additional criteria of 
areas of scar (defined as T2 dark) or fluid (based on T2 bright, DWI no restriction, and DCE-MRI non-
enhancing) assumed to be cancer free.  
Missing Data 
All reasonable methods will be used to try to minimize missing data, however, some missing data is 
expected to occur. Except for PSA, IIEF-5, IIEF item 2, EPIC item 5 and Prostate Biopsy, no interpolation 
of missing data will occur, and endpoints will be assessed using the mITT and PP populations as 
described above. 
Missing PSA data will be interpolated using the Last Value Carried Forward (LVCF) method, where 
missing values are replaced by the last measured PSA value. Similarly, missing IIEF-5, IIEF item 2 and EPIC 
item 5 data will be interpolated using the LVCF method, but only in regards to the Erectile Dysfunction 
Endpoint, Erection Firmness Endpoint and Urinary Incontinence Endpoint. Missing quality of life data will 
not be interpolated for analysis of the IPSS, IIEF and EPIC endpoints. 
 

 
 
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GCP-10283_Rev B                                      
6.0 Investigational Study Plan  
6.1 Study Design 
This study is a prospective, multi-center, single arm clinical trial evaluating the TULSA-PRO MRI-guided 
transurethral ultrasound prostate ablation device for prostate ablation in patients with localized, organ-
confined prostate cancer. Men diagnosed with biopsy-proven, organ-confined, low- to intermediate-risk 
prostate cancer will be eligible for participation in this study, provided they have not received prior 
treatment of their prostate cancer. Subjects must satisfy all inclusion and none of the exclusion criteria 
and provide a signed written informed consent prior to their participation in the study. 
 
6.2 Overview of Study Periods and Visits 
Each subject will participate in eleven patient visits, categorized into four study periods. Clinical 
management of the subjects will be in accordance with standard of care (SOC) at the discretion of the 
Principal Investigator (PI) or their designee. When applicable, CRF sections will be completed based on 
source documentation collected. Results of additional clinically-indicated procedures acquired outside 
of the scheduled study follow-up will be recorded on the Unplanned Study Visit CRF.  
i. 
Pre-Study Baseline 
o Screening: Initial patient assessment for study qualification 
o Study Visit 1: Subject eligibility and baseline assessment 
ii. 
MRI-TULSA Procedure 
o Study Visit 2: Treatment delivery with the TULSA-PRO device 
iii. 
Follow-up Procedures  
o The purpose of each visit and clinical lab tests are outlined in the “Study Schedule”. 
6.3 Study Completion 
Subjects will have completed the study once they have completed their 5-year follow-up visit. Subjects 
who have undergone the prostate ablation treatment and who withdraw from the study prior to the 12-
month follow-up will be asked to complete prostate MRI and biopsy.  
The study primary endpoints will be complete once the 110th subject has undergone treatment and 
completes the 12-month follow-up visit. A formal interim analysis of the secondary endpoints will be 
performed once the 110th subject has undergone prostate ablation treatment and completes the 12-
month follow-up visit. 
Actual enrolment of the first phase was 115 patients. With the addition of a second enrolment phase of 
35 patients, the study will be complete once the last patient (150th subject) has undergone treatment 
and completes the 5-year follow-up visit. 
An independent steering committee (Data and Safety Monitoring Committee, DSMC) will be established 
to review the study outcome. A minimum of two safety assessments by the DSMC will be performed. 
Study enrolment will continue while data are collected and reviewed. 

 
 
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GCP-10283_Rev B                                      
The first DSMC review will occur after the first cohort of ten subjects complete treatment. A complete 
review of the study including all results to date and adverse events, if any, will be completed to assess 
the safety of the TULSA-PRO procedure. The review will also include patients who have decided to 
withdraw from the study. If two or more of the first ten patients who have undergone the TULSA-PRO 
procedure (mITT group) have a documented rectal fistula then the DSMC would recommend stopping 
the trial. 
The second DSMC review will occur after the first cohort of ten subjects complete their 1-month follow-
up visit. A complete review of the study including all results to date and adverse events, if any, will be 
completed to assess the safety of the TULSA-PRO procedure. The review will also include patients who 
have decided to withdraw from the study. If ≥ 10% of all patients who have undergone the TULSA-PRO 
procedure (mITT group) at the time of the DSMC analysis have a documented rectal fistula, then the 
DSMC would recommend stopping the trial. 
6.4 Anticipated Duration of the Clinical Investigation 
Once subject enrolment begins, it is expected that at least twenty procedures will be conducted per 
month using the TULSA-PRO. The primary endpoints of the study are intended to be completed 12 
months after the last patient has undergone the prostate ablation treatment.  
Upon completion of the initial enrolment phase, a total of 115 patients were treated. A second 
enrolment phase consisting of 35 patients will be initiated at selected clinical sites within the United 
States. Once all sites have initiated subject enrolment, it is expected that at least 2-3 TULSA treatments 
will be conducted per month allowing total enrolment to be completed in less than 12 months. 
 
 
7.0 Investigational Site Training   
Profound Medical Inc. (PMI) will provide investigational site training prior to study initiation. Training 
topics will include but are not limited to device usability, Good Clinical Practice (GCP), AE reporting, 
study details and procedures, study documentation, informed consent, and CRF completion. All clinically 
significant changes from baseline will be followed until resolution or stabilization as determined by the 
Principal Investigator (PI) or their designee. 
8.0 Records and Reports  
8.1 Data handling and record-keeping 
All records and reports related to the investigation of PAD-105 will be maintained as per ICH Guidance 
E6: Good Clinical Practice. 
8.2 Record maintenance and retention 
The investigator-sponsor will retain the specified records and reports for up to 2 years after the 
marketing application is approved for the investigational device or PMI will inform the investigator when 
the documents are no longer needed. 

 
 
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GCP-10283_Rev B                                      
8.3 Device Accountability  
It is the responsibility of the investigator to ensure that a current record of investigational device 
(product) disposition is maintained at each study site where investigational device is inventoried and 
disposed. Records and logs will be verified during site monitoring visits. 
Upon completion of the study, all unused investigational device and supply must be returned to PMI. 
9.0 Adverse Event (AE) Recording/Reporting  
The procedure, “GCP-10039 – Investigational Regulatory Reporting” outlines AE or SAE assessment and 
country specific reporting timelines. The Principal Investigator(s) will be trained on the procedure to 
ensure that the reporting requirements are understood and will be followed throughout the trial period. 
Sponsor Contact for AE Reporting: 
Attn: Mathieu Burtnyk  
Phone: 647 476 1350 x408 
Email: mburtnyk@profoundmedical.com   
 
10. Site Monitoring Procedures    
Independent monitoring of the clinical study for adherence to the clinical protocol will be conducted 
periodically by qualified staff. 
Representatives of PMI must be allowed to visit all study site locations periodically to assess the data 
quality and study integrity. On site they will review study records and directly compare them with 
source documents, discuss the conduct of the study with the investigator, and verify that the facilities 
remain acceptable. Certain CRF pages and/or electronic files may serve as source documents. 
In addition, the study may be evaluated by PMI Internal auditors and government inspectors who must 
be allowed access to CRFs, source documents, other study files, and study facilities. PMI audit reports 
will be kept confidential. 
The investigator must notify PMI immediately of any inspections scheduled by regulatory authorities, 
and promptly forward copies of inspection reports to PMI. 
 

 
 
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GCP-10283_Rev B                                      
11. References  
Boyes et al 2007 
 
Boyes et al, “Prostate tissue analysis immediately following magnetic 
resonance imaging guided transurethral ultrasound thermal therapy,”, The 
Journal of Urology 178: 1080-5 (2007) 
Burtnyk et al 2010a 
Burtnyk et al, “Simulation study on the heating of the surrounding anatomy 
during transurethral ultrasound prostate therapy: A 3D theoretical analysis of 
patient safety,” Medical Physics 37(6): 2862-75 (2010) 
Burtnyk et al 2010b 
Burtnyk et al, “3D Conformal MRI-controlled transurethral ultrasound prostate 
therapy: validation of numerical simulations and demonstration in tissue-
mimicking gel phantoms,” Phys Med Biol 55(22):6817-39 (2010) 
Burtnyk et al 2015 
Burtnyk et al, “Magnetic resonance imaging guided transurethral ultrasound 
prostate ablation: a preclinical safety and feasibility study 
with 28-Day followup,” The Journal of Urology 193 (2015) 
Chin et al 2016 
Chin et al, “Magnetic Resonance Imaging–Guided Transurethral Ultrasound 
Ablation of Prostate Tissue in Patients with Localized Prostate 
Cancer: A Prospective Phase 1 Clinical Trial,” European Urology (2016) 
Chopra et al 2005 
Chopra et al, “Method for MRI-guided conformal thermal therapy of prostate 
with planar transurethral ultrasound heating applicators,” Physics in Medicine 
and Biology 50: 4957-75 (2005) 
Chopra et al 2006 
Chopra et al, “Analysis of factors important for transurethral ultrasound 
prostate heating using MR temperature feedback,” Physics in Medicine and 
Biology 51: 827-44 (2006) 
Chopra et al 2010 
Chopra et al, “MRI-controlled transurethral ultrasound therapy for localized 
prostate cancer,” Int J Hyperthermia 26(8): 804-21 (2010) 
Chopra et al 2012 
 
Chopra et al, “MR Imaging-controlled transurethral ultrasound therapy for 
conformal treatment of prostate tissue: Initial feasibility in humans,” 
Radiology 265(1): 303-13 (2012) 
Colquhoun et al 
2011 
Colquhoun et al 2011, “The use of MRI-guided transurethral ultrasound 
therapy for the treatment of localized prostate cancer: A phase I study”, AUA 
Abstract 178, The Journal of Urology Supplement 185(4S): e715-6 
Kobelevskiy et al 
2009 
Kobelevskiy et al, “Quantitative measures for evaluation of ultrasound 
therapies of the prostate,” Proceedings of the 9th International Symposium on 
Therapeutic Ultrasound (ISTU), Aix-en-Provence, France (2009) 
Nair et al 2020 
Nair et al, “Five-Year Outcomes from a Prospective Phase I Study of MRI-
guided Transurethral Ultrasound Ablation in Men with Localized Prostate 
Cancer,” [Abstract] (2020).   
N’Djin et al 2012a 
N’Djin et al, “Investigation of power and frequency for 3D conformal MRI-
controlled transurethral ultrasound therapy with a dual frequency multi-
element transducer,” Int J Hyperthermia 28(1): 87-104 (2012) 
N’Djin et al 2012b 
N’Djin et al, “Coagulation of human prostate volumes with MRI-controlled 
transurethral ultrasound therapy: results in gel phantoms,” Medical Physics 
39(7): 4524-36 (2012) 

 
 
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GCP-10283_Rev B                                      
Ramsay et al 2017 
Ramsay et al, “Evaluation of Focal Ablation of Magnetic Resonance Imaging 
Defined Prostate Cancer Using Magnetic Resonance Imaging Controlled 
Transurethral Ultrasound Therapy with Prostatectomy as the Reference 
Standard,” Journal of Urologly 197(1):255-261 (2017) 
Siddiqui et al 2010 
Siddiqui et al, “MRI-guided transurethral ultrasound therapy of the prostate 
gland using real-time thermal mapping: initial studies,” Urology 76(6): 1506-11 
(2010) 
Tang et al 2007 
Tang K et al, “Conformal thermal therapy using planar ultrasound transducers 
and adaptive closed-loop MR temperature control: demonstration in gel 
phantoms and ex vivo tissues,” Physics in Medicine and Biology 52: 2905-19 
(2007)