A Prospective Multi-center Clinical Study Evaluating the Use of PD G 506 A and the Eagle V1.2 Imaging System for the Visualization of Carcinoma During Breast Conserving Surgery
Phase: PHASE3
Conditions: Breast Neoplasm Female, Breast Cancer
Sponsor: SBI ALApharma Canada, Inc.

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: i of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
 
 
 
SBI ALApharma Canada 
Inc. 
 
 
SBI-CIP 20-002  
A prospective multi-center clinical study evaluating the use 
of PD G 506 A and the Eagle V1.2 Imaging System for the 
visualization of carcinoma during breast conserving surgery 
 
 
Revision:
v1.8
Status: 
Approved 
Approval Date: 
11 March, 2024 
 
 
 
 
 
 
NCT04815083 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 2 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
CLINICAL STUDY PROTOCOL 
 
 
A prospective multi-center clinical study evaluating the use 
of PD G 506 A and the Eagle V1.2 Imaging System for the 
visualization of carcinoma during breast conserving surgery 
 
 
Protocol Number: SBI-CIP 20-002 
Amendment Number: 8 
 
Short Study Name: Fluorescence imaging of carcinoma during breast conserving 
surgery 
 
Sponsor:  
SBI ALApharma Canada Inc.  
180 Dundas St. W., Suite 430 
Toronto, Ontario, M5G 1Z8 
Canada 
 
Protocol Version: 1.8 
 
Previous Protocol Versions: 1.7 
 
 
 
 
 
 
 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 3 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
Title 
A prospective multi-center clinical study evaluating the use of PD G 506 A and the 
Eagle V1.2 Imaging System for the visualization of carcinoma during breast 
conserving surgery 
Protocol Number
SBI-CIP 20-002
Version Date
Mar 11, 2024
Version Number
1.8
 
1. Investigator Signature: 
I agree to conduct the study in accordance with the relevant, current protocol. 
I agree to personally conduct or supervise this study. 
I agree to perform and conduct the study as described in the protocol and in accordance with the 
relevant laws/regulations and standards outlined in the Clinical Trial Agreement. 
I will ensure that the requirements relating to obtaining informed consent and Ethics Committee 
(EC) or Institutional Review Board (IRB) review and approval are met. 
I agree to maintain adequate and accurate study records and to make those records available for 
inspection by the Sponsor, the Sponsor’s authorized representatives, and/or other applicable 
regulatory entities. 
I agree to promptly report to the EC/IRB all changes to the study and all unanticipated problems 
involving risks to human subjects or others. Additionally, I will not make any changes to the study 
without Sponsor and EC/IRB approval, except where necessary to eliminate apparent immediate 
hazards to study patients. 
I agree to ensure that all staff members involved in the conduct of this study are informed about 
their obligations in meeting the above commitments. 
 
Principal Investigator: ________________________________________ (print name and title) 
Signature: __________________________ Date (DD/MMM/YYYY): ___________________ 
 
Sponsor Signatory: 
 
 
__________________________________  
 
__________________________ 
Dr. Ralph DaCosta, PhD 
 
 
 
 
Date (DD/MMM/YYYY) 
CEO and CTO SBI ALApharma Canada Inc. 
 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 4 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Table of Contents 
1. 
REVISION HISTORY...................................................................... ERROR! BOOKMARK NOT DEFINED. 
2. 
INVESTIGATOR SIGNATURE: ..................................................................................................................... 3 
3. 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ........................................................... 8 
4. 
LIST OF ABBREVIATIONS .......................................................................................................................... 11 
5. 
GENERAL INFORMATION ......................................................................................................................... 13 
5.1. 
IDENTIFICATION OF THE CLINICAL INVESTIGATIONAL PLAN (CIP) ........................................................... 13 
5.2. 
SPONSOR INFORMATION ............................................................................................................................ 13 
5.3. 
IDENTIFICATION OF INVESTIGATORS ......................................................................................................... 13 
5.4. 
CONTRACT RESEARCH ORGANIZATION ..................................................................................................... 13 
5.5. 
REB/IRB CONTACT INFORMATION ........................................................................................................... 13 
5.6. 
LABORATORY CONTACT INFORMATION .................................................................................................... 13 
5.7. 
PHARMACOVIGILANCE/MEDICAL INQUIRIES ............................................................................................. 13 
5.8. 
MONITORING INFORMATION ..................................................................................................................... 14 
6. 
DEFINITIONS ................................................................................................................................................. 15 
6.1. 
ESSENTIAL/FUNDAMENTAL DEFINITIONS .................................................................................................. 15 
6.2. 
ADDITIONAL DEFINITIONS ........................................................................................................................ 19 
7. 
INTRODUCTION ............................................................................................................................................ 22 
7.1. 
STUDY RATIONALE ................................................................................................................................... 22 
7.1.1. 
Clinical Need .................................................................................................................................. 22 
7.1.2. 
Fluorescence Imaging During Surgery ........................................................................................... 22 
7.1.3. 
Previous Clinical Experience .......................................................................................................... 23 
7.2. 
POTENTIAL RISKS AND BENEFITS .............................................................................................................. 25 
7.2.1. 
Previous clinical trials using ALA HCl ........................................................................................... 25 
7.2.2. 
Anticipated adverse drug effects ..................................................................................................... 25 
7.2.3. 
Residual device risk and mitigation ................................................................................................ 25 
7.2.4. 
Anticipated adverse device effects .................................................................................................. 26 
7.2.5. 
Anticipated clinical benefit ............................................................................................................. 26 
7.2.6. 
Risks associated with participation and risk-to-benefit ratio .......................................................... 26 
8. 
OBJECTIVES AND ENDPOINTS ................................................................................................................. 28 
8.1. 
PRIMARY OBJECTIVE AND ENDPOINT ........................................................................................................ 28 
8.2. 
SECONDARY OBJECTIVES AND ENDPOINTS ............................................................................................... 29 
8.2.1. 
Key Secondary Objectives ............................................................................................................... 29 
8.2.2. 
Secondary Objectives ...................................................................................................................... 32 
8.3. 
EXPLORATORY OBJECTIVES AND ENDPOINTS ........................................................................................... 39 
8.4. 
SAFETY OBJECTIVES AND ENDPOINTS ....................................................................................................... 45 
9. 
STUDY DESIGN .............................................................................................................................................. 46 
9.1. 
DESCRIPTION OF THE STUDY DESIGN ........................................................................................................ 46 
9.2. 
PATIENT AND STUDY COMPLETION ........................................................................................................... 47 
9.3. 
MINIMIZING BIAS ...................................................................................................................................... 47 
9.4. 
SCIENTIFIC RATIONALE FOR STUDY DESIGN ............................................................................................. 48 
9.5. 
JUSTIFICATION FOR DOSE .......................................................................................................................... 49 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 5 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
10. 
STUDY POPULATION .............................................................................................................................. 50 
10.1. 
DESCRIPTION OF THE POPULATION TO BE STUDIED .................................................................................... 50 
10.2. 
INCLUSION CRITERIA ................................................................................................................................. 50 
10.3. 
EXCLUSION CRITERIA ................................................................................................................................ 51 
10.4. 
SCREEN FAILURES ..................................................................................................................................... 52 
11. 
TREATMENTS ........................................................................................................................................... 52 
11.1. 
TREATMENTS ADMINISTERED ................................................................................................................... 52 
11.1.1. 
Investigational Drug and Placebo .................................................................................................. 52 
11.1.2. 
Investigational Drug Acquisition .................................................................................................... 52 
11.1.2.1. 
Formulation, Appearance, Packing and Labeling ...................................................................................... 53 
11.1.2.2. 
Product Storage and Stability ..................................................................................................................... 53 
11.1.2.3. 
Preparation of the Investigational Drug ..................................................................................................... 54 
11.1.2.4. 
Dosing and Administration of the Investigation Drug ............................................................................... 54 
11.1.2.5. 
Preparation and Administration of the Placebo .......................................................................................... 55 
11.1.2.6. 
Route of Administration............................................................................................................................. 55 
11.1.2.7. 
Handling/Storage/Accountability ............................................................................................................... 55 
11.1.3. 
Investigational Medical Devices ..................................................................................................... 56 
11.1.3.1. 
Handling/Storage/Accountability ............................................................................................................... 58 
11.2. 
METHOD OF TREATMENT ASSIGNMENT .................................................................................................... 59 
11.3. 
BLINDING .................................................................................................................................................. 59 
11.4. 
TREATMENT COMPLIANCE ........................................................................................................................ 60 
11.5. 
CONCOMITANT THERAPY .......................................................................................................................... 60 
11.6. 
PROPHYLACTIC MEDICATIONS, TREATMENTS AND PROCEDURES ............................................................. 60 
11.7. 
WARNINGS AND PRECAUTIONS ................................................................................................................. 60 
11.8. 
PROHIBITED MEDICATIONS, TREATMENTS AND PROCEDURES .................................................................. 61 
12. 
TERMINATION OF PARTICIPATION/WITHDRAWAL CRITERIA .............................................. 61 
12.1. 
HANDLING OF PARTICIPANT WITHDRAWALS OR TERMINATION ................................................................ 61 
12.2. 
LOSS TO FOLLOW UP ................................................................................................................................. 62 
13. 
STUDY PROCEDURES AND SCHEDULE ............................................................................................ 62 
13.1. 
SCHEDULE OF ACTIVITIES ......................................................................................................................... 62 
13.2. 
SCREENING (DAYS -90 TO DAY 0) ............................................................................................................. 66 
13.3. 
ENROLMENT AND RANDOMIZATION (NO VISIT, DAYS -30 TO DAY 0) ........................................................ 67 
13.4. 
SURGICAL PROCEDURE (DAY 1) ................................................................................................................ 68 
13.4.1. 
Pre-operative Procedures ............................................................................................................... 68 
13.4.2. 
Standard of Care Intraoperative Procedures .................................................................................. 69 
13.4.3. 
Study-Specific Intraoperative Procedures ...................................................................................... 70 
13.4.4. 
Peri-operative Procedures .............................................................................................................. 73 
13.4.4.1. 
Bisected Specimen Biopsy Collection ....................................................................................................... 73 
13.4.4.2. 
Specimen Grossing .................................................................................................................................... 74 
13.4.5. 
Post-Operative Procedures ............................................................................................................. 74 
13.5. 
DAY 2 FOLLOW-UP (24 HOURS +24 HOURS POST-SURGERY) ...................................................................... 75 
13.6. 
POST-OPERATIVE PATHOLOGY PROCEDURES (NO VISIT) ........................................................................... 75 
13.6.1. 
Specimen Blocking and Assessment ................................................................................................ 75 
13.6.2. 
Specimen Handling, Storage and Future Research ........................................................................ 76 
13.7. 
WEEK 2 VISIT (DAY 10 - 14) ..................................................................................................................... 77 
13.8. 
3-MONTH FOLLOW-UP (DAY 80 – 90) ....................................................................................................... 78 
13.9. 
EXTENSION PHASE .................................................................................................................................... 78 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 6 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13.9.1. 
6-Month Follow-up (Day 168 – 182) .............................................................................................. 78 
13.9.2. 
1- Year Follow-up (Day 365 – 379) ................................................................................................ 79 
13.10. 
EARLY TERMINATION VISIT ................................................................................................................. 79 
13.11. 
UNSCHEDULED VISIT ............................................................................................................................ 79 
14. 
ASSESSMENT OF SAFETY ..................................................................................................................... 80 
14.1. 
SPECIFICATION OF SAFETY PARAMETERS .................................................................................................. 80 
14.1.1. 
Definition of Adverse Events ........................................................................................................... 80 
14.1.2. 
Definition of Serious Adverse Events .............................................................................................. 81 
14.1.3. 
Definition of an Adverse Drug Reaction ......................................................................................... 81 
14.1.4. 
Definition of UADE/ SUSAR ........................................................................................................... 82 
14.1.5. 
Definition of Unanticipated Problem .............................................................................................. 82 
14.2. 
CLASSIFICATION OF AN ADVERSE EVENT .................................................................................................. 83 
14.2.1. 
Severity of Event ............................................................................................................................. 83 
14.2.2. 
Clarification of the difference in meaning between “severe” and “serious” ................................. 83 
14.2.3. 
Relationship to Study Intervention .................................................................................................. 84 
14.2.4. 
Outcome .......................................................................................................................................... 84 
14.2.5. 
Expectedness ................................................................................................................................... 85 
14.2.5.1. 
Expectedness of Adverse Event associated with PD G 506 A ................................................................... 85 
14.2.5.2. 
Expectedness of Adverse Events associated with Eagle V1.2 Imaging System ......................................... 85 
14.2.5.3. 
Obligations of the PI .................................................................................................................................. 85 
14.2.5.4. 
Obligations of the Sponsor ......................................................................................................................... 86 
14.2.6. 
Unanticipated Problem ................................................................................................................... 86 
14.2.7. 
Investigational Product Deficiencies .............................................................................................. 86 
14.3. 
TIME PERIODS AND FREQUENCY FOR EVENT ASSESSMENT AND FOLLOW-UP ........................................... 86 
14.4. 
REPORTING PROCEDURES .......................................................................................................................... 87 
14.4.1. 
Documentation Procedures and Reporting Obligations to the Sponsor ......................................... 87 
14.4.1.1. 
Adverse Events .......................................................................................................................................... 87 
14.4.1.2. 
Serious Adverse Event Reporting (Eagle V1.2 and PD G 506 A) ............................................................. 88 
14.4.1.3. 
Other Events to be reported within the same timelines as SAEs (PD G 506 A only)................................. 88 
14.4.1.4. 
Investigational Product Complaints ........................................................................................................... 89 
14.4.2. 
Regulatory Reporting of Adverse Events to Competent Authorities (Health Canada & FDA) and 
Ethic Committees (REBs & IRBs) ...................................................................................................................... 91 
14.4.2.1. 
Summary of Regulatory Reporting Obligations ......................................................................................... 91 
14.4.2.2. 
PD G 506 A: SUSAR Reporting ................................................................................................................ 92 
14.4.2.3. 
Eagle V1.2: SAR/ UADE Reporting .......................................................................................................... 93 
14.4.2.4. 
Unanticipated Problem (UP) Reporting ..................................................................................................... 93 
14.5. 
STUDY PAUSING RULES............................................................................................................................. 94 
14.6. 
SAFETY OVERSIGHT .................................................................................................................................. 95 
15. 
CLINICAL MONITORING ...................................................................................................................... 95 
16. 
STATISTICAL CONSIDERATIONS ....................................................................................................... 96 
16.1. 
GENERAL CONSIDERATIONS ...................................................................................................................... 96 
16.2. 
SAMPLE SIZE ESTIMATION ........................................................................................................................ 96 
16.3. 
DEFINITIONS OF UNITS OF ANALYSIS ........................................................................................................ 97 
16.4. 
ANALYSIS POPULATIONS ......................................................................................................................... 100 
16.4.1. 
Modified Intention to Treat Analysis Population .......................................................................... 100 
16.4.2. 
Safety Population .......................................................................................................................... 100 
16.4.3. 
Primary Specimen Biopsy Population........................................................................................... 100 
16.4.4. 
Timepoints of Efficacy Analyses .................................................................................................... 100 
16.4.4.1. 
Fluorescence Assessment at the End of SoC ............................................................................................ 100 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 7 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
16.4.4.2. 
End of FGR ................................................................................................. Error! Bookmark not defined. 
16.4.4.3. 
Entire Resection ....................................................................................................................................... 102 
16.5. 
FORMULAS .............................................................................................................................................. 103 
16.6. 
PRIMARY AND KEY SECONDARY ENDPOINT ANALYSES .......................................................................... 103 
16.6.1. 
Primary Endpoint: ........................................................................................................................ 103 
16.6.2. 
Key Secondary Endpoints: ............................................................................................................ 104 
16.7. 
SECONDARY AND EXPLORATORY ENDPOINT ANALYSIS .......................................................................... 105 
16.8. 
SAFETY ANALYSIS .................................................................................................................................. 106 
17. 
   DATA MANAGEMENT ....................................................................................................................... 106 
18. 
DEVIATION FROM THE CLINICAL INVESTIGATION PLAN ..................................................... 107 
18.1. 
PROCEDURES FOR REPORTING DEVIATIONS ............................................................................................ 107 
19. 
AMENDMENTS TO THE CLINICAL INVESTIGATION PLAN ..................................................... 107 
19.1. 
     PROCEDURES FOR REPORTING AMENDMENTS ..................................................................................... 107 
20. 
DATA HANDLING AND RECORD KEEPING.................................................................................... 108 
20.1. 
DATA COLLECTION AND MANAGEMENT RESPONSIBILITIES .................................................................... 108 
20.2. 
STUDY RECORDS RETENTION .................................................................................................................. 108 
21. 
REFERENCES .......................................................................................................................................... 110 
22. 
APPENDICES ........................................................................................................................................... 116 
APPENDIX 1. SYNOPSIS ................................................................................................................................... 116 
APPENDIX 2. STUDY WORKFLOW ............................................................................................................... 121 
APPENDIX 3. SUN PROTECTION INSTRUCTIONS AND LIST OF OTHER COMMON 
PHOTOSENSITIZING MEDICATIONS WHICH SHOULD BE AVOIDED .................................................. 131 
APPENDIX 4. STUDY GOVERNANCE CONSIDERATIONS ...................................................................... 133 
APPENDIX 5. CONTRACEPTIVE GUIDANCE AND COLLECTION OF PREGNANCY 
INFORMATION ..................................................................................................................................................... 138 
APPENDIX 5 TABLE 5.1: HIGHLY EFFECTIVE CONTRACEPTIVE METHODS .................................... 139 
APPENDIX 6. BREAST-Q VERSION 2.0 © - BREAST CONSERVING THERAPY MODULE ............... 141 
APPENDIX 7. PROTOCOL AMENDMENT HISTORY ................................................................................ 143 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 8 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
2. Protocol Amendment Summary of Changes Table 
 
DOCUMENT HISTORY 
Document 
Version/Date 
Original Protocol  
1.0 
Amendment 1 
1.1/January 7, 2021 
Amendment 2 
1.2/March 28, 2021 
Amendment 3 
1.3/April 14, 2021 
Amendment 4 
1.4/September 30, 2021 
Amendment 5 
1.5/March 24, 2022 
Amendment 6 
1.6/November 25, 2022 
Amendment 7 
1.7/November 13, 2023 
Amendment 8 
1.8/March 11, 2024 
 
 
Amendment # (DD-MMM-YYYY):  Amendment 8 (11-Mar-2024), Version 1.8 
 
Overall Rationale for Amendment: Improve study logistics (in response to site feedback). 
Removal of optional procedures (specimen tagging) and removal of images required from the 
cavity after lumpectomy is performed (primary cavity).  
Change in primary endpoint and key secondary endpoints, as well as changes in the sample size 
calculation taking into consideration only the primary outcome (P 1.1 – conversion rate among all 
patients included in the study) These changes were made to corroborate with FDA 
recommendations in the type D meeting (03 Aug 2023).  
Removing the modified ASTRO/SSO definitions and all endpoints related to the modified 
guideline, as well as the modified definition of true positive and true negative.  
Defining positive margins as per the latest consensus from the Society of Surgical Oncology 
(ASTRO/SSO). Removal of some of the surgeon’s assistant requirements, such as training on the 
sterile field and suturing experience.   
In addition, extending diagnostic imaging requirements to 90 days prior to the surgery date (drug 
administration).  
 
Summary of Changes 
 
Section
Changes/rationale
General  
1. Reorganisation of protocol numbering for sections – starting with revision history for 
section 1.  
 
2. Updating the table of content to reflect all changes made in the protocol. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 9 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Section 4  
1. Study Synopsis:  
- 
Moved to Appendix 1 – To improve the flow of the protocol and to have the 
synopsis easily accessible for investigators and research teams.  
 
2. Schedule of Activities (SOA):  
- 
Moved to section 13, to be part of the study procedures and schedule. 
Section 5 
1. Moved before definitions to improve the readability (flow) of the protocol.  
Section 6 
Definitions: 
 
1. Reorganised definitions to include essential/fundamental definitions (6.1) and additional 
definitions (6.2).  
- 
Adding essential definitions at the beginning of the list to introduce the basic 
definitions for the study and facilitate readability.  
- 
Adding “additional” definition as the more complex definitions that requires 
previous comprehension from the essential definitions. 
 
2. Updated definitions for surgical cavity, shave types, final margins, true positive/negative 
and re-excisions. 
- 
Making the definitions more clear and comprehensive. 
 
3. Redefined positive margins according to the 2014 & 2016 SSO/ASTRO guidelines  
- 
Better define the guidelines that will be used in the study to define positive 
margins and calculate endpoints as well as study analysis. 
 
4. Removed modified SSO/ASTRO guidelines for positive margin and all the endpoints 
related to the modified definition (p2.29, p2.30 and p2.31). 
 
5. Removed modified true positive and modified true positive definitions. 
Section 8  
Objectives and Endpoints: 
 
1. Updated Primary and secondary objectives and endpoints as per FDA recommendations 
in the type D meeting held in Aug/2023. 
 
2. Updated Primary Endpoint as Requested by FDA (P.1.1) – conversion rate among all 
patients for the study. 
 
3. Updated key secondary objectives and endpoints (5.2.1) – P (2.1; 2.2;2.3):  
- 
Sensitivity, Specificity and Conversion rate among patients with positive margin 
after SoC as per FDA recommendations. 
 
4. Updated numbering of secondary endpoints. 
 
5. Removed endpoints p2.29, p2.30 and p2.31: 
-
Related to modified SSO/ASTRO guideline assessment.

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 10 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
6. Removed endpoint 23: 
- 
Related to assessment of optional procedure – Specimen Tagging. The 
assessment will no longer be performed for the study. 
 
7. Removed endpoints 9 and 10:  
- 
Related to modified true positive and modified true negative definitions. 
 
8. Corrected the “Specificity” formula in endpoint P(2.6) which was previously P(2.4) in 
v1.7. 
Section 13 
Study Procedures and Schedule: 
 
1. Enrollment and randomization: 
- 
Extending the diagnostic imaging timeline from ≤ 45 to ≤ 90 days prior to Day 
1. This will improve site logistics, patient screening and study workflow. 
 
2. Intra-operative procedures: 
a) Removal of Specimen Tagging: 
- 
To reduce the OR time for the patient as well as for the surgeons and to allow 
the surgeon’s assistant to be an individual that does not need to be trained in 
suturing, which will improve site recruitment as well as patient recruitment.  
 
b) Removal of the requirement to image the primary cavity: 
- 
To allow the surgeon’s assistant to be an individual that does not need to be 
trained to operate in the sterile field.  
Section 16 
Statistical Considerations:  
 
1. Sample size estimation (16.2):  
- 
Readjusted the primary outcome that is now driving the sample size of the study 
– primary endpoint P(1.1) and recalculated the sample size taking into 
consideration the 1% null hypothesis threshold recommended by the FDA in the 
last type D meeting (Aug/2023). 
 
2. Modified intention to treat analysis population (16.4.1): 
- 
Adjusted the definition as per FDA’s recommendation dated 22/11/2021. 
Appendix 2 
1. Adjusted Study Workflow to Reflect the Changes made in the Protocol: 
 
a) Removed the intra-operative procedure: Specimen tagging. 
 
b) Removed imaging of the primary cavity. 
 
c) Readjusted the wording and numbering to make the steps more clear and concise.  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 11 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
  
3. List of Abbreviations 
A
anterior
AE
adverse event
AF
autofluorescence
ALA
aminolevulinic acid
ALA HCl
aminolevulinic acid hydrochloride
ALAT 
alanine transaminase
ASAT
aspartate aminotransferase
ASTRO
American Society for Radiation Oncology
BCS
breast conserving surgery
BW
body weight
CCD
Contact Charging Device
CIP
clinical investigational plan
CRF
case report form
CSP
clinical study protocol
CSS
Custom Sterile Sleeve
CTCAE
Common Terminology Criteria for Adverse Events 
DCC
data control centre
DCIS
ductal carcinoma in situ
DIB
Dark Imaging Box
DIS
Dark Imaging Sheet
DOR
diagnostic odds ratio
DSMB
data safety monitoring board
ECG
electrocardiogram 
ECH 
External Communication Hub 
eCRF
electronic case report form
EDC
electronic data capture 
EPR
electronic patient record
FDA
Food and Drug Administration
FOV
field of view
FL
fluorescence 
FN
false negative
FNo
false negative orientation
FNps
false negative primary specimen
FP
false positive 
FPo
false positive orientation
FPps
false positive primary specimen
GCP
Good Clinical Practice

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 12 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
GGT
gamma-glutamyl transferase 
GMP
Good Manufacturing Practice
HCl
hydrochloride
HFC 
Handheld Fluorescence Camera 
I
inferior
IV
intravenous
ITT
intention-to-treat
L
lateral
LED
light emitting diode
M
medial
mITT
modified intention-to-treat
NPV
negative predictive value
P
posterior
PA
pathologist’s assistant
PI
principal investigator
PMCC
Princess Margaret Cancer Centre
PO
per os
PPIX
protoporphyrin IX
PPV
positive predictive value
PSC
Protective Storage Cradle
REB/IRB
Research Ethics Board / Institutional Review Board
S
superior
SAE
serious adverse event
SPF
sun protection factor
SoC
standard of care
SSO
Society for Surgical Oncology
SUSAR
Suspected Unexpected Serious Adverse Reaction
TN
true negative
TNo
true negative orientation
TNps
true negative primary specimen
TP
true positive
TPo
true positive orientation
TPps
true positive primary specimen
UHN
University Health Network
UV
ultraviolet
WL
white light
WOCBP
women of child-bearing potential
UP
unanticipated problem
UADE
Unanticipated Adverse Device Effect
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 13 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
4. General Information 
4.1. Identification of the Clinical Investigational Plan (CIP) 
 
Protocol title: A prospective multi-center clinical study evaluating the use of PD G 506 A and the 
Eagle V1.2 Imaging System for the visualization of carcinoma during breast conserving surgery 
4.2. Sponsor Information 
 
Sponsor: SBI ALApharma Canada Inc.  
4.3. Identification of Investigators  
Lists of Investigators responsible for conducting the trial, clinical laboratories and other medical 
and/or technical departments and/or institutions involved in the trial are provided as separate 
documents.  
4.4. Contract Research Organization 
Name : 
Allucent 
Contact : 
Andrew Daleus 
Address :  
9900, boulevard Cavendish, bureau 300 
 
 
St-Laurent, QC, H4M 2V2, Canada 
 
 
4.5. REB/IRB Contact Information 
List of REB/IRBs responsible for reviewing the trial are provided as separate documents.  
4.6. Laboratory Contact Information 
List of clinical laboratories involved in the trial are provided as separate documents.  
4.7. Pharmacovigilance/Medical Inquiries   
Name:  
spmd – strategies for health, Inc. 
Contact: 
Dr. Diana Witticke (PV Project Management) 
Dr. med. Martin Sujatta (Medical Safety) 
Email:  
SBI-ALApharma-PhV@spmd-safety.com 
Fax: 
 
+1 978 338 0668 
Address: 
50 Dunham Rd. Suite 3200 
 
 
Beverly, MA 01915, USA 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 14 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
4.8. Monitoring Information 
Name:  
Allucent 
Contact: 
Andrew Daleus 
Address: 
9900, boulevard Cavendish, bureau 300 
 
 
St. Laurent, QC, H4M 2V2, Canada 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 15 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
5. Definitions 
5.1. Essential/Fundamental Definitions  
 
a) Definitions of surface and orientations 
Surface 
 
A border (i.e., one of many borders) of a cavity or excised tissue specimen that 
was surgically resected during the excision of said specimen.  
 
A surface is defined as inside (deep) surface, which is the contiguous margin of 
the most recently resected tissue. The outside (superficial) surface is the margin 
that was continuous with the remaining breast tissue.  
Orientation 
An orientation is comprised of two contiguous tissue surfaces that have been 
resected or separated surgically.  
 
An orientation is described based on the anatomical location of the contiguous 
tissues (e.g. Superior, Medial, Posterior, Lateral, Inferior, Anterior) 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 16 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
 
S = superior (towards the head) 
M = medial (towards the midline of the body) 
P = posterior (towards the chest wall) 
L = lateral (towards the ipsilateral arm) 
I = inferior (towards the feet) 
A = anterior (towards the front of the patient)
b) Definition of cavity and excised tissue 
Cavity  
(Surgical 
Cavity) 
The tissue void in the breast remaining after tissue has been resected as part of a 
breast conserving surgery procedure. A cavity is composed of 6 anatomical 
cavity surfaces (Superior, Medial, Posterior, Lateral, Inferior, Anterior). 
Final Cavity 
after FGR 
The cavity after FL-guided resection (FGR) is complete. If no FL-driven cavity 
shave specimens are collected in a patient randomized to receive FGR, then the 
final cavity after FGR is equivalent to the final cavity after SoC. 
Final Cavity 
after SoC 
The cavity after SoC resection is complete (including resection of the primary 
specimen and any SoC-driven cavity shave specimen(s).  
Positive 
Cavity 
A positive cavity occurs when postoperative analysis identifies carcinoma that is 
positive on histopathology either inside the surgical cavity during SoC 
lumpectomy or after FGR resection.  
S
I
L
M
P
Viewed from the anterior perspective
A
S
I
L
M
P
Viewed from the anterior perspective
A
S
I
L
M
P
A
Viewed from the lateral perspective

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 17 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Cavity 
Shave 
Specimen(s) 
Tissue specimen(s) excised from the cavity after the primary specimen has been 
removed; cavity shave specimen(s) 
 
The surfaces of a cavity shave specimen are described with reference to the 
primary specimen (not relative to the cavity/patient). The outside surface of a 
cavity shave specimen is the surface that was continuous with the remaining 
breast tissue. The inside surface of a cavity shave margin is the surface that is 
continuous with most recently resected tissue.
Primary 
Specimen 
Also known as the “lump” or main mass refers to the primary piece of tissue 
resected during a standard of care lumpectomy. It contains most (or all) of the 
primary tumor mass
Shave types 
(Excised 
tissue) 
I. 
Shave: any tissue removed from the lumpectomy cavity walls after the 
main specimen is removed. 
II. 
Standard of care (SoC) cavity shave: any piece of tissue excised from a 
specific location of the lumpectomy cavity wall after the primary 
specimen has been removed, as per surgeon’s decision per SoC. 
III. 
Fluorescence-driven shave specimen(s): any piece of tissues excised 
from a specific location of the lumpectomy cavity wall indicated by PD 
G 506 A-induced tissue fluorescence after SoC resection has been 
completed. 
c) Definition of margins and re-excision 
Margin 
Assessment 
The procedure(s) performed to evaluate the outside surface of the last resected 
tissue(s) and/or cavity. Given that FL-guided resection occurs after completion 
of SoC, margin assessment may be based on SoC methods (SoC margin 
assessment) or FL-imaging (FL margin assessment).  
SoC margin assessment may include WL palpation, visualization, specimen 
radiology and intraoperative ultrasound (patients undergoing intraoperative 
histopathological assessment are excluded from participating). 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 18 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Final 
Margin(s) 
Final margin is comprised of the outside surface of the last resected tissue(s) for 
each anatomical surface and the final cavity at that margin.  
 
Final margins are evaluated to determine whether the patient has positive or -
negative margins based on postoperative clinical pathology assessment.  
 
For each patient, final margins after SoC and final margins after FGR will be 
evaluated histopathologically.  
 
If there are no FL-driven cavity shave specimens collected in a patient 
randomized to receive FGR, then the final margins after FGR are equivalent to 
the final margins after SoC. 
Positive 
Margins 
Determined postoperatively wherein histopathological analysis identifies 
carcinoma within a defined distance from the inked surface of an excised tissue 
specimen. 
 
Positive margins are defined using the latest consensus from the Society of 
Surgical Oncology as follows: 
 
-For invasive cancer with or without associated ductal carcinoma in situ 
(DCIS): cancer cells or DCIS present on ink (per Moran et al. 20141) 
-For pure DCIS lesions: DCIS present less than 2 mm from ink (per Morrow et 
al. 20162).
True 
Positive 
Orientation 
and True 
Negative 
Orientation 
 
a. A TP orientation contains at least 1 True Positive surface. 
b. A FN orientation contains at least 1 False Negative surface and no True 
Positive surface. 
c. A FP orientation contains at least 1 False Positive surface and no True 
Positive or False Negative surfaces. 
d. A TN orientation contains only True Negative surfaces.
Surface histopathology status 
Positive 
Negative 
Surface 
fluorescence 
status 
Positive 
True positive (TP) 
 False positive (FP) 
Negative 
False Negative (FN)  True Negative 
(TN) 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 19 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Re-excisions 
A re-excision is defined as a surgical procedure performed in the ipsilateral 
breast following the primary lumpectomy because of positive margins found 
from the initial lumpectomy procedure. The re-excision procedure can be a 
separate surgical procedure to excise further breast tissue or a mastectomy.
 
5.2. 
Additional Definitions 
Fluorescence-
Guided Resection 
(FGR) 
Resection of tissue based on the results of PD G 506 A- induced PpIX 
fluorescence imaging using the Eagle V1.2 Imaging System and the 
surgeon’s best clinical judgement. FGR is performed after SoC is 
declared complete by the surgeon.  
Any patient that undergoes fluorescence imaging with the intent to resect 
tissue is considered to have undergone FGR, even if no FL-driven cavity 
shave specimens are resected. 
Fluorescence (FL) 
Positive Surface 
Determined intraoperatively wherein the surgeon identifies PD G 506 A- 
induced PpIX fluorescence on any specimen surface or cavity surface 
when performing imaging with the Eagle V1.2 Imaging System. 
FL-positive 
orientation 
An orientation wherein either (or both) of the two surfaces which make 
up said orientation were determined intraoperatively to be positive for 
PD G 506-A-induced PpIX fluorescence (FL-status = FL-positive). 
FL-negative 
orientation 
An orientation wherein both of the two surfaces which make up said 
orientation were determined intraoperatively to be negative for PD G 
506-A-induced PpIX fluorescence (FL status = FL-negative).
FL-positive 
orientation- 
in vivo 
Orientation with FL-positive status of the cavity surface (or the inside 
surface of a cavity shave specimen if removed due to FGR); 
fluorescence is assessed in vivo
FL-negative 
orientation- 
in vivo 
Orientation with FL-negative status of the cavity surface (or the inside 
surface of a cavity shave specimen if removed due to FGR); 
fluorescence is assessed in vivo
FL-positive 
orientation- 
ex vivo 
Orientation with FL-positive status of the surface of the primary 
specimen or outside surface of a cavity shave specimen; fluorescence is 
assessed ex vivo
FL-negative 
orientation- 
ex vivo 
Orientation with FL-negative status of the surface of the primary 
specimen or outside surface of a cavity shave specimen; fluorescence is 
assessed ex vivo

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 20 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Inking –  
Specimen or 
Surface 
A procedure performed as part of SoC, wherein a specific colour of ink 
is applied to a specific surface or margin of a tissue specimen for the 
purposes of orienting tissue blocks during histopathological analysis.  
Up to six colours may be used to orient the primary specimen or shaves. 
Index Surgery/ 
Surgical Procedure 
The first surgery performed to remove a primary breast cancer. 
In vivo 
Fluorescence 
assessment / inside 
surface 
Determination of the FL status of tissue based 
on FL imaging of tissue that is inside the patient 
(not yet resected). 
The inside surface of cavity shave specimen(s) 
and the final cavity after FGR can undergo in 
vivo FL assessment.  
Ex vivo 
Fluorescence 
assessment / outside 
surface 
Determination of the FL status of tissue based 
on FL imaging of resected tissue specimen(s) 
after removal from the patient (i.e., outside the 
patient). 
The outside surface of the primary specimen, 
final margins after SoC and outside surface of 
cavity shave specimen(s) can undergo ex vivo 
FL assessment.
Orientation-level 
endpoint 
An endpoint for which orientation-based analysis is performed. An 
orientation-level analysis would evaluate each orientation as a single 
data point with a total of at least 5 orientations per patient (in cases 
where an area of skin is removed with the lump, there may be n = 5 data 
points per patient). Orientation-level analysis evaluates efficacy based 
on the performance characteristics (accuracy) in each anatomical 
location of the entire surgical cavity. 
Patient-level 
endpoint 
An endpoint for which patient-based analysis is performed. A patient-
level analysis evaluates each patient as a single data point. 
Surgeon 
The surgeon responsible for performing the SoC breast conserving 
surgery procedure and real-time intraoperative interpretation of the Eagle 
V1.2 Imaging System data.

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 21 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Surgeon’s Assistant 
The individual responsible for performing Eagle V1.2 Imaging System 
fluorescence imaging of the primary specimen and any SoC cavity shave 
specimens prior to opening of the randomization envelope.  
 
The surgeon’s assistant may be a qualified staff surgeon, surgical 
fellow, resident, nurse, physician’s assistant, research manager or 
research coordinator. 
True Positive 
Orientation (TPo) 
Orientation that is fluorescence positive and histopathology positive. 
True Negative 
Orientation (TNo) 
Orientation that is fluorescence negative and histopathology negative. 
False Positive 
Orientation (FPo) 
Orientation that is fluorescence positive and histopathology negative. 
False Negative 
Orientation (FNo) 
Orientation that is fluorescence negative and histopathology positive. 
True Positive 
Patient 
Patient has at least one TP orientation without any FN orientations 
True Negative 
Patient 
Patient has all TN orientations 
False Positive 
Patient 
Patient has at least one FP orientation without any FN or TP 
orientations
False Negative 
Patient 
Patient has at least one FN orientation 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 22 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
6. Introduction 
6.1. Study Rationale 
6.1.1.  Clinical Need 
Breast conserving surgery (BCS) is performed on patients with breast cancer to resect and 
completely remove the primary malignancy while conserving as much of the surrounding normal 
tissue as possible. Currently, surgeons rely on a multitude of methods to assess the adequacy of 
the margins intra-operatively including visual assessment and palpation, specimen radiology, 
intraoperative ultrasound and intraoperative histopathology (in specific cases). There is no 
consensus on intraoperative resection adequacy and definitive  margin assessment requires 
histopathological assessment, which is not real-time and impractical in the intra-operative setting. 
Despite intra-operative measures to obtain clean margins in BCS, the need for re-excision via a 
subsequent surgery is not uncommon. In Canada, 57,840 BCS procedures were performed between 
2007-2010 for primary invasive unilateral breast cancer (before 2014 ASTRO/SSO guidelines3), 
with 23% of patients requiring re-excision (n=38,517; range:17-56%) within 1 year of the index 
BCS to establish acceptable clear/negative margins4, 5. The average US re-excision rate for 
invasive breast cancer or ductal carcinoma in situ (DCIS) was 23.6% (range: 18.4-26.5%) between 
20046￼7￼.8￼ and risk of local 4, 9-16￼. Re-excisions due to final positive margins also increase 
the risk of disease local recurrence and decrease disease-specific survival4, 9-15￼. 17, 18￼. 
Optimizing surgery to improve resection guidance and positive margin assessment during initial 
BCS would be highly 19￼, leading to a decreased need for 2nd or subsequent surgeries.  
 
Emerging technologies (including drugs and devices) have aimed to address the need for real-time 
margin assessment during BCS. Among these, only MarginProbe (Dune Medical) and OTIS 
(Perimeter Medical Imaging) have received FDA clearance. MarginProbe is indicated for the 
detection of carcinoma at the margins of tissue, but requires time consuming evaluation of tissues 
using a probe with a small sampling area that produces an auditory (non-image based) output 
indicating the presence or absence of carcinoma.  OTIS provides an image output but is indicated 
for imaging  tissue microstructures, not carcinoma. Both technologies are limited to the evaluation 
of the surgical specimen and cannot be used to evaluate residual disease in the surgical cavity. 
Thus, an urgent clinical need exists for real-time intraoperative (imaging) methods to assess both 
the surgical cavity and excised specimens during BCS.  
6.1.2.  Fluorescence Imaging During Surgery 
The pro-drug ALA is a non-fluorescent non-protein amino acid that is converted into the 
fluorophore protoporphyrin IX (PpIX) as part of the heme biosynthesis pathway and preferentially 
accumulates in malignant tissue such as in cultured breast cancer cell lines of a variety of 
phenotypes20. This selectivity has been demonstrated to extent to murine breast cancer models 
where it was found to be a good marker for early tumorigenic processes in the mouse mammary 
gland. In a number of clinical trials, ALA has been administered orally for the purpose of 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 23 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
fluorescence-based imaging of a variety of other cancer types  such as rectal carcinomas (n = 2)21, 
malignant gliomas (n > 500)22-32, and palpable breast tumours (n = 16 and n=7)33, 34. In the case of 
malignant gliomas, a multicentre Phase III randomized controlled study (n = 322) demonstrated 
complete tumour resection in 65% of the ALA HCl dosed patients undergoing fluorescence-
guided resection (FGR) compared with 36% in those that underwent conventional resection based 
solely on white light guidance (clinicaltrials.gov identifier: NCT00241670)32. ALA HCl has 
received marketing authorization by SBI ALApharma Canada’s affiliate companies for use in 
patients undergoing surgery for high grade glioma in over 40 countries, including GLEOLANTM  
in the United States of America35, 36.  
6.1.3. Previous Clinical Experience 
Fluorescence imaging of breast cancer was previously investigated in an investigator-initiated trial 
(PI: Dr. Wey Leong), conducted at Princess Margaret Cancer Centre, Toronto, Canada (Study #10-
0633, clinicaltrais.gov identifier: NCT01837225), using a handheld and portable fluorescence 
imaging device, called PRODIGI, in patients undergoing BCS (both lumpectomies and 
mastectomies). This device was developed by Dr. Ralph DaCosta at Princess Margaret Cancer 
Center, University Health Network, and uses violet-blue light (405 nm) to excite fluorescence 
which is detected at 500-550 nm (green) and 600-660 nm (red) in real time using an optically-
modified high-resolution consumer-grade digital camera.  
 
In the first stage of Study #10-0633 in which patients did not receive ALA HCl, PRODIGI 
autofluorescence imaging of excised breast tissue specimens demonstrated healthy breast 
connective tissue appeared bright green autofluorescent and adipose tissue appeared dull pinkish-
brown autofluorescent. However, tissue autofluorescence alone resulted in poor tumour-to-normal 
tissue contrast. The conclusion of this stage of the study was that an exogenous (fluorescence) 
contrast would be required to achieve the desirable tumor-to-normal imaging contrast. 
 
In the second stage of Study #10-0633, ALA HCl was investigated as a fluorescence contrast agent 
to improve the detection of breast carcinoma compared with autofluorescence alone. Study patients 
were randomly assigned to one of three dose cohorts (n = 15/cohort): 0 mg/kg (Cohort 1, 
autofluorescence only), 15 mg/kg (Cohort 2), or 30 mg/kg (Cohort 3) of ALA HCl. Analysis of 
the ex vivo specimen(s) only (lumpectomy or mastectomy) was performed in the first n = 5 patients 
in each cohort. In the subsequent n = 10 patients/cohort both intraoperative white light and 
fluorescence imaging of the surgical cavity, as well as ex vivo fluorescence and white light imaging 
of the excised specimen were performed.   
 
The primary objective of the second stage of Study #10-0633 was to determine preliminary 
sensitivity and specificity estimates of ALA HCl-induced PpIX fluorescence, as visualized with 
the PRODIGI imaging device in ex vivo specimens. ALA HCl substantially improved tumour-to-
normal tissue contrast relative to autofluorescence alone. At final analysis of all patients who 
received ALA HCl, a total of 93 biopsies were collected in areas of healthy tissue, tumour tissue 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 24 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
and tumour adjacent tissue. The sensitivity and specificity to detect breast carcinoma in the ex vivo 
specimens based on ALA HCl-induced red PpIX fluorescence using 15 or 30 mg/kg BW ALA 
HCl is presented in Table 6.1:  
 
Table 6.1: Diagnostic measures ALA HCl-induced red PpIX fluorescence to detect breast 
cancer tumours using PRODIGI  
 
Low Dose  
(15 mg/kg) 
High Dose  
(30 mg/kg) 
 
-Tumor 
+Tumor 
-Tumor 
+Tumor 
-Red FL 
22
7
20
7
+Red FL 
4
13
5
15
PPV % (95%CI) 
76.5% (50.1 – 93.2)
75.0% (50.9 – 91.3)
NPV % (95%CI) 
75.9% (56.5 – 89.7)
74.1% (53.7 – 88.9)
Sensitivity % (95%CI) 
65.0% (40.8 – 84.6) 
68.2% (45.1 – 86.1) 
Specificity % (95%CI) 
84.6% (65.1 – 95.6) 
80.0% (59.3– 93.2) 
 
The secondary objective of Study #10-0633 was to evaluate the safety and feasibility of 
intraoperative fluorescence imaging of the surgical cavity following excision of the lumpectomy 
or mastectomy specimen. No adverse events were associated with the experimental procedures 
(ingestion of ALA HCl and intraoperative imaging) and there was minimal interruption to the 
standard clinical workflow. Intraoperative imaging added ~5-10 minutes to the procedure time. 
However, while the initial design of the PRODIGI device was optimal for imaging of flat surfaces 
such as those of the resected specimens, it did not perform as well for intracavity imaging. As a 
result of its bulky form factor, PRODIGI could not enter the surgical cavity and the illumination 
of the cavity surface using 405 nm light was not optimal for imaging within an enclosed space, 
such as the surgical cavity.  
 
To overcome this challenge, a next generation prototype (Eagle 1.1 Imaging Device) was designed 
for testing in combination with 20 mg/kg body weight (BW) ALA HCl in the third stage of Study 
#10-0633. Eagle 1.1 Imaging Device has a smaller form factor and is intended to enter and image 
inside the surgical cavity; however, the white light and fluorescence imaging capabilities are not 
integrated into a single device. For example, there are two distinct devices which are designed to 
perform white light and fluorescence imaging, respectively. The reason for this was to enable 
technical optimization of both imaging modalities separately, prior to physically combining both 
white light and fluorescence imaging functions into a single handheld device design. 
 
To this end, SBI ALApharma Canada Inc. has developed and manufactured the Eagle V1.2 
Imaging Device which has an optimized design that integrates the white light and fluorescence 
imaging functions and an improved user interface based on results of formative human factors 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 25 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
testing. Additionally, a suite of accessories have been developed to improve the usability of the 
device in the intraoperative setting during FGR. Collectively, the imaging device and accessories 
are referred to as the “Eagle V1.2 Imaging System”.  
6.2. Potential Risks and Benefits  
A detailed description of the chemistry, pharmacology, efficacy, and safety of PD G 506 A is 
provided in the Investigator’s Brochure and a detailed description of the Eagle V1.2 Imaging 
System performance testing and safety is found in the Instructions for Use.   
6.2.1. Previous clinical trials using ALA HCl 
No major side effects are anticipated from the consumption of ALA HCl (based on previous 
studies33). A Phase I study involving 21 healthy male subjects compared the absolute 
bioavailability of oral (20 mg/kg BW) relative to i.v. (2 mg/kg BW) ALA HCl administration and 
evaluated the duration of photosensitization of the skin by observing the minimal erythemal dose 
and corresponding PpIX plasma concentrations after oral treatment. Just 1 adverse event (AE) 
occurred in 1 subject 2.02 hours after oral administration. The symptom was mild nausea, assessed 
as probably drug related. The AE resolved without any action taken after 3 hours. There were no 
effects of the ALA HCl on laboratory values of clinical chemistry, hematology, and urinalysis; 
vital signs; electrocardiogram (ECG) parameters; or physical findings. Overall, both oral and i.v. 
formulations were assessed as safe and tolerable. 
 
The administration of low (< 60 mg/kg BW) doses of ALA has no known long-term risks and is 
associated with minimal side effects38.  In the case of 139 patients given 20 mg/kg orally for 
contrast in malignant glioma33 a toxicological safety analysis noted no concerns.  Oral doses of 40 
mg/kg34 were also well tolerated, with transient minor side effects (facial erythema, peri-nasal 
swelling) dissipating within 72 hours of the applied dose.  The same study also reported 5 patients 
who received doses as high as 60 mg/kg, which increased the intensity (but not the duration) of 
these side effects and was also associated with nausea in 3 of the 5 patients.  
6.2.2. Anticipated adverse drug effects 
Detailed information about anticipated adverse drug effects can be found in the Investigator’s 
Brochure. 
6.2.3. Residual device risk and mitigation 
There is a potential risk that the imaging end of the Eagle V1.2 Imaging System may reach up to 
50 degrees Celsius (122 degrees Fahrenheit) if used for a long time without turning off the white 
or blue lights on the camera. This temperature may cause burns.  
 
No burns linked to the use of the Eagle V1.2 Imaging System have been reported. To minimize 
this risk, the Eagle V1.2 Imaging System has temperature indicators to alert the user of increases 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 26 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
in temperature before the imaging end reaches a temperature that may burns. Additionally, the 
lights will automatically turn off to minimize the risk of burns. 
 
All users will be trained on how to use the Eagle V1.2 Imaging System in a way that minimizes 
the risk of causing burns. 
 
Intraoperative imaging will be performed of the surgical cavity and excised tissue (lumpectomy, 
standard of care revisions and FL-guided revisions) following SoC BCS. The Eagle V1.2 Imaging 
Device will be covered in a custom sterile surgical sleeve in order to maintain sterility of the sterile 
operating field. The previous study conducted at Princess Margaret Cancer Centre (study #10-
0633) has demonstrated no adverse events or any effect on standard histopathological analysis of 
specimens for clinical diagnosis related to the study imaging procedure.  
6.2.4. Anticipated adverse device effects 
There are no known or anticipated adverse device effects.  
6.2.5. Anticipated clinical benefit 
Study patients who receive PD G 506 A (i.e., all participants in Part A and Part B patients 
randomized to Arm 2) may experience a clinical benefit as a result of their participation in the 
study. Arm 2 patients with residual carcinoma in the cavity or on the final margins after SoC may 
have the residual carcinoma in the cavity resected and/or the final margins converted from 
carcinoma-positive after SoC to carcinoma-negative as a result of FGR. If FGR improves 
(decreases) the positive margin rate after surgery, Arm 2 patients may also benefit from not having 
to undergo a second surgery to achieve negative margins.  
6.2.6. Risks associated with participation and risk-to-benefit ratio 
Patients choosing to participate in this trial may experience side effects related to the 
investigational drug. To minimize the potential photosensitizing effect of PpIX, patients will be 
provided with oral and written instructions on how to protect themselves from possible 
photosensitivity reactions within the first 48 hours following ingestion, including avoiding 
exposure to sunlight, wearing sunscreen while outside, maintaining dim lighting, and wearing 
protective clothing (e.g. clothes covering the limbs, hat). Additional sunscreen will be given to the 
patient to take home following discharge.  
 
Patients choosing to participate in this trial may experience a slightly longer surgical procedure 
(~5-10 minutes) than those not participating in this trial. Arm 1 participants will receive SoC BCS. 
In all Part A study patients and in Part B patients randomized to Arm 2, additional cavity shave 
margins will be resected when red fluorescence is observed following SoC BCS. FL-guided cavity 
shave specimens will be collected when red fluorescence is observed on any cavity surface and/or 
specimen surface (e.g. anterior, posterior, lateral, medial, inferior, superior) until no additional red 
PpIX fluorescence is observed or the clinician determines resection of additional tissue is either 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 27 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
not possible or not in the patient’s best interest based on the surgeon’s clinical judgement. All Part 
A patients and patients randomized to Arm 2 in Part B may have additional tissue removed from 
their breast as compared to SoC as a result of the FGR, which may affect the cosmetic outcome of 
the procedure. However, the literature suggests that resection of non-targeted (circumferential) 
cavity shave specimens following SoC decreases the rate of positive margins with no or minimal 
effect on cosmesis37, 38. Arm 2 participants will undergo directed shaving of fluorescence-positive 
margins and therefore are not expected to experience any negative impact on cosmetic outcomes. 
Obtaining cavity shave specimens is a standard procedure performed as part of SoC margin 
assessment (e.g. in response to a positive specimen radiographic finding).  
 
Overall, there is minimal risk associated with participation in the study and participants may 
benefit from having the need for a second surgery due to histopathology-positive margins 
following the index surgical procedure eliminated (in Part A patients and Part B Arm 2 patients). 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 28 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
7. Objectives and Endpoints  
7.1. Primary Objective and Endpoint 
 
Primary 
Objective 
Primary Endpoint 
Parameter Description 
Parameter Formula 
Abbreviated 
Description 
1. To evaluate the efficacy 
of PD G 506 A by 
demonstrating the clinical 
usefulness of PDG 506A 
to identify additional 
malignant breast tissue 
during BCS after SoC  
Percentage of patients with at least one 
histopathology-positive margin following 
SoC who then have ALL histopathology-
negative margins following FGR, among all 
patients imaged. 
 
P(1.1) Conversion Rate =  
 
# patients with at least one 
histopathology-positive margin 
following SoC and 
histopathology negative final 
margins after FGR 
All patients imaged (Arm 2) 
x 100%
Conversion rate among 
all patients 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 29 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
7.2. Secondary Objectives and Endpoints 
7.2.1. Key Secondary Objectives 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 30 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
1. To evaluate the efficacy of 
PD G 506 A by 
demonstrating the clinical 
usefulness of PDG 506A to 
identify additional malignant 
breast tissue during BCS  
(Arm 2 only). 
Percentage of patients with at least one 
histopathology-positive margin 
following SoC who then have 
histopathology-negative margins 
following FGR (participant-level 
analysis; Arm 2 only). 
P(2.1) =  
# patients with at least one 
histopathology-positive margin 
following SoC and 
histopathology negative final 
margins after FGR 
# patients with histopathology 
positive final margins after 
SoC 
 
x 
100% 
 
Conversion rate among patients 
with SoC positive margins 
 
To characterize the 
diagnostic performance of 
PDG 506A  to identify 
malignant breast tissue (Arm 
2 only). 
2. Patient-level specificity of PD G 506 
A-induced fluorescence (following SoC 
BCS) to determine the presence or 
absence of residual cancer in the 
surgical cavity at the initial fluorescence 
assessment at the end of SoC as 
compared to the final margin 
histopathology. 
      
P(2.2) Specificity =  
TN Patient  
TN Patient + FP Patient  
x 
100% 
Patient-level specificity to identify 
residual carcinoma at the initial 
fluorescence assessment at the end 
of SoC 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 31 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
3.Patient-level  sensitivity of PD G 506 
A-induced fluorescence (following SoC 
BCS) to determine the presence or 
absence of residual cancer in the 
surgical cavity at the initial fluorescence 
assessment at the end of SoC as 
compared to the final margin 
histopathology. 
 
 
 
P(2.3) Sensitivity =  
TP Patient  
TP Patient + FN Patient 
x 
100% 
Patient-level sensitivity to identify 
residual carcinoma at the initial 
fluorescence assessment at end of 
SoC 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 32 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
7.2.2. Secondary Objectives 
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
4. To characterize the 
diagnostic performance of 
imaging of PD G 506 A  to 
identify malignant breast tissue 
(Arm 2 only) 
Orientation-level diagnostic 
performance of PD G 506 A-induced 
fluorescence to determine the presence 
or absence of residual cancer in the 
surgical cavity at the end of SoC as 
compared to the final margin 
histopathology. 
P(2.4) 
  
 
x 
100% 
Orientation level diagnostic 
performance to identify 
carcinoma with FGR after 
SoC 
P(2.4)  
x 
100% 
P(2.4)  
x 
100% 
P(2.4)  
x 
100% 
5. To characterize the 
diagnostic performance of 
imaging of PD G 506 A  to 
identify malignant breast tissue 
(Arm 2 only) 
Orientation-level diagnostic 
performance of PD G 506 A-induced 
fluorescence to determine the presence 
or absence of residual cancer in the 
surgical cavity at the end of FGR as 
compared to the final margin 
histopathology. 
P(2.5) Sensitivity =  
x 
100% 
Orientation level diagnostic 
performance to identify 
carcinoma at the end of FGR 
P(2.5) Specificity =  
x 
100% 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 33 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
P(2.5) PPV =  
x 
100% 
 
P(2.5) NPV =  
x 
100% 
 
6. To characterize the 
diagnostic performance of 
imaging of PD G 506 A  to 
identify malignant breast tissue 
(Arm 2 only). 
Patient-level sensitivity of PD G 506 
A-induced fluorescence (following SoC 
BCS) to determine the presence or 
absence of residual cancer in the 
surgical cavity at the end of FGR as 
compared to the final margin 
histopathology.
P(2.6) Sensitivity =  
 
x 
100% 
 
Patient-level sensitivity to 
identify residual carcinoma 
after FGR is complete. 
Patient-level specificity of PD G 506 
A-induced fluorescence (following SoC 
BCS) to determine the presence or 
absence of residual cancer in the 
surgical cavity at the end of FGR as 
compared to the final margin 
histopathology.
P(2.6) Specificity =  
 
x 
100% 
 
Patient-level specificity to 
identify residual carcinoma 
after FGR is complete. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 34 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
7. To characterize the 
diagnostic performance of PD 
G 506 A  to identify malignant 
breast tissue (Arm 2 only). 
Patient-level Positive Predictive Value 
(PPV) of PD G 506 A-induced 
fluorescence (following SoC BCS) to 
determine the presence or absence of 
residual cancer in the surgical cavity at 
the initial fluorescence assessment at 
end of SoC as compared to the margin 
histopathology.
P(2.7) PPV =  
 
 
x 
100% 
Patient-level PPV to identify 
residual carcinoma at the 
initial fluorescence 
assessment at end of SoC. 
Patient-level Negative Predictive Value 
(NPV) of PD G 506 A-induced 
fluorescence (following SoC BCS) to 
determine the presence or absence of 
residual cancer in the surgical cavity at 
the initial fluorescence assessment at 
end of SoC as compared to the margin 
histopathology.
P(2.7) NPV =  
  
 
x 
100% 
Patient-level NPV to identify 
residual carcinoma at the 
initial fluorescence 
assessment at end of SoC. 
 
8. To characterize the 
diagnostic performance of PD 
G 506 A  to identify malignant 
breast tissue (Arm 2 only). 
 
 
 
Patient-level diagnostic performance 
characteristics of sensitivity, 
specificity, PPV and NPV to determine 
the presence or absence of cancer in the 
surgical cavity after SoC BCS. 
 
For this analysis, all orientations 
following SoC through the end of FGR 
are considered in definitions of TP 
Patient, TN Patient, FP Patient and FN 
Patient. 
 
P(2.8) Sensitivity =  
x 
100% 
Patient-level diagnostic 
performance of PD G 506 A 
to detect cancer after SoC 
BCS. 
P(2.8) Specificity =  
x 
100% 
P(2.8) PPV = 
x 
100% 
P(2.8) NPV =  
x 
100% 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 35 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
9 To characterize the 
diagnostic performance of PD 
G 506 A  to identify malignant 
breast tissue (Arm 2 only). 
Percentage of patients assessed as 
residual tumor negative at the end of 
FGR (i.e., the final surgical cavity after 
FGR is completely FL-negative as are 
the corresponding final margin 
surfaces) who had positive margins on 
histopathology.  
P(2.9a) =  
              FN Patient 
#patients assessed residual tumor 
negative by FL imaging at the end of 
surgery(i.e., TN patient + FN patient)
x100% 
Patient-level false negative 
rate of carcinoma at the end 
of FGR. 
P(2.9b) =  
                     FN Patient 
       All patients imaged (Arm 2) 
x100% 
 
10. To characterize the 
diagnostic performance of PD 
G 506 A  to identify malignant 
breast tissue after SoC BCS 
(Arm 2 only). 
 
Percentage of patients assessed as 
residual tumor positive by FL imaging 
at the initial fluorescence assessment at 
end of SoC (i.e., at least one orientation 
having a surface that was FL-positive 
either in the cavity or on the 
corresponding final shave or specimen 
margin at the end of SoC) who had 
negative margins on pathology 
following SoC and no cancer identified 
in any FL-guided shave specimen. 
 
P (2.10a)  =  
# patients with ≥ 1 FL-positive 
orientation at the end of SoC and all 
carcinoma-negative final margins 
after SoC and carcinoma-negative FL-
driven cavity shave specimens 
# patients assessed residual tumor 
positive by FL imaging at the end of 
SoC 
x100% 
Percentage of patients in 
whom SOC final margins 
were carcinoma negative and 
all FL-driven shave 
specimens were carcinoma-
negative (patient-level false 
positive rate). 
P (2.10b)  =  
# patients with ≥ 1 FL-positive 
orientation at the end of SoC and all 
carcinoma-negative final margins 
after SoC and carcinoma-negative FL-
driven cavity shave specimens 
  All patients imaged (Arm 2)
x100% 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 36 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
11. To determine how often 
FGR with PD G 506 A will 
result in the removal of any 
additional carcinoma  
 
Percentage of patients with 
histopathology-negative margins at the 
initial fluorescence assessment at the 
end of SoC who have at least one 
orientation that was both FL-positive 
and histopathology-positive. 
 
This analysis is only done in those 
patients who have a FL driven shave 
obtained as a result of FL-positive 
orientation identified after SoC.  
Patients who have cancer anywhere in a 
FL driven shave obtained as a result of 
the FL-positive orientation can 
contribute to the numerator of this 
endpoint.
P(2.11a)  =  
 
x100% 
Percentage of patients with 
carcinoma-negative margins 
after SoC found to have 
residual tumor following 
SoC that was identified 
intraoperatively with 
combined FL imaging. 
P(2.11b)  =  
 
x100% 
12.To characterize the 
diagnostic performance of PD 
G 506 A  to identify malignant 
breast tissue after SoC BCS 
(Arm 2 only). 
 
Percentage of patients with no 
fluorescence identified at the initial 
fluorescence assessment at the end of 
SoC (in either the cavity or on the 
corresponding final margin surfaces 
after SoC) in whom all final margins 
after SoC are histopathologically 
confirmed to be negative for 
carcinoma. 
 
P(2.12a) =  
x100% 
 
P(2.12b) =  
x100% 
13. To characterize the 
diagnostic performance of in 
vivo imaging of PD G 506 A  
Patient-level in vivo diagnostic 
performance of PD G 506 A-induced 
fluorescence (following SoC BCS) to 
P(2.13) Sensitivity =  
x100% 
Patient-level in vivo 
diagnostic performance to 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 37 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
to identify malignant breast 
tissue (Arm 2 only). 
determine the presence or absence of 
residual cancer in the surgical cavity at 
the end of FGR as compared to the 
final margin histopathology. 
 
Only FL-positive orientation-in vivo 
and FL-negative orientation-in vivo 
orientations are included in the patient-
level diagnostic performance 
definitions for this analysis. FL-
assessment of in vivo tissue in the final 
cavity will be compared to 
histopathological status of final 
margins of the ex vivo tissue 
specimens.
P(2.13) Specificity =  
 
x100% 
identify residual carcinoma 
after FGR is complete. 
P(2.13) PPV = 
 
x100% 
P(2.13) NPV =  
 
 
x100% 
14. To determine the 
frequency with which 
fluorescence is found only on 
one of the opposing surfaces in 
an orientation. 
Percentage of orientations where in 
vivo FL imaging disagrees with ex vivo 
FL imaging (e.g., FL-negative cavity 
surface but FL-positive corresponding 
shave or specimen margin surface, or 
vice versa).  FL imaging at all points 
during the surgery (not just at the end) 
are used for this endpoint.  
P(2.14) = 
x100% 
Percentage of orientations 
with discordant FL status. 
15. To characterize the impact 
of FGR on the rate of 2nd 
surgery within 1 year 
Percentage of patients receiving a 2nd 
surgery on the ipsilateral breast within 
1 year of index BCS to remove 
P(2.15a) Arm 1 only =  
 
 
x100% 
Patient-level re-operation 
rate due to suspected residual 
disease. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 38 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
following index BCS (Arm 1 
and Arm 2). 
 
 
suspected residual disease (patient-level 
analysis; Arm 1 and Arm 2). 
P(2.15b) Arm 2 only =  
 
 
x100% 
16. To characterize the impact 
of FGR on the rate of 2nd 
surgery shortly after index 
BCS (Arm 1 and Arm 2). 
 
Percentage of patients receiving an 
early 2nd surgery (planned or actual) on 
the ipsilateral breast related to positive 
final margins prior to radiation or 
medical management (patient-level 
analysis; Arm 1 and Arm 2).  
 
P(2.16a) Arm 1 only =  
 
 
 
x100% 
Patient-level early re-
operation rate. 
P(2.16b) Arm 2 only =  
 
 
x100% 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 39 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Secondary Objectives 
Parameter Description 
Parameter Formula 
 
Abbreviated Description 
17. To characterize the impact 
of FGR during BCS on the 
amount of tissue removed 
(Arm 1 and Arm 2). 
Sum of the weight (mg) of all tissue 
removed based on SoC compared to the 
sum of the weight (mg) of all tissue 
removed based on FGR (patient-level 
analysis; Arm 1 and Arm 2). 
P(2.17a) = 
Mean SoC tissue weight (mg) Arm 1 and Arm 
2:  
SoC tissue weight = Primary specimen (mg) + 
SoC-driven cavity shave specimen(s) (mg) 
 
P(2.17b) = 
Mean FGR tissue weight (mg) Arm 2 only: 
Total tissue weight = FL-driven cavity shave 
specimen(s) (mg)
Amount of tissue removed 
with FGR beyond SoC. 
 
18.To characterize the impact 
of FGR during BCS on the 
patient-reported cosmetic 
outcome (Arm 1 and Arm 2). 
Patient satisfaction with the cosmetic 
outcome of breast conserving surgery 
performed based on SoC in 
combination with PD G 506 A and the 
Eagle V1.2 Imaging System compared 
to SoC (patient-level analysis; Arm 1 
and Arm 2) 
This endpoint will be assessed at 3, 6, 
and 12 months.
P(2.18a) = 
Mean Breast-Q Breast Conserving Therapy 
Module satisfaction with breasts score before 
and after SoC surgery. 
P(2.18b) = 
Mean Breast-Q Breast Conserving Therapy 
Module satisfaction with breasts score before 
and after SoC surgery + FGR. 
Patient satisfaction. 
 
 
7.3. Exploratory Objectives and Endpoints 
 
Exploratory Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
19. To characterize the 
diagnostic performance 
of ex vivo imaging of 
PD G 506 A  to identify 
Patient-level ex vivo diagnostic 
performance of PD G 506 A-induced 
fluorescence to determine the 
presence or absence of residual 
P(E.19) Sensitivity =  
TP Patient (ex vivo) 
TP Patient (ex vivo) + FN Patient 
(ex vivo) 
x 100% 
Patient-level ex vivo specificity to 
identify residual carcinoma after 
FGR is complete. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 40 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Exploratory Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
malignant breast tissue 
(Arm 2 only). 
cancer in the surgical cavity at the 
end of FGR as compared to the final 
margin histopathology.  
 
Only FL-positive orientation- ex vivo 
and FL-negative orientation- ex vivo 
orientations are included in the 
patient-level diagnostic performance 
definitions for this analysis. 
P(E.19) Specificity =  
TN Patient (ex vivo) 
TN Patient (ex vivo) + FP Patient 
(ex vivo) 
x 100% 
P(E.19) PPV =  
TP Patient (ex vivo) 
TP Patient (ex vivo) + FP Patient 
(ex vivo) 
x 100% 
P(E.19) NPV =  
TN Patient (ex vivo) 
TN Patient (ex vivo) + FN Patient 
(ex vivo) 
x 100% 
20. To determine the 
frequency with which 
PD G 506 A-induced 
fluorescence is 
visualized but that 
tissue is not resected 
(Arm 2 only). 
 
Percentage of patients who did not 
have a FL-guided shave although 
indicated by FL imaging. 
  
P(E.20a)  =  
#Patients with ≥ 1 FL-positive 
orientation where no FL-
driven shave was resected 
#Patients with ≥1 FL-positive 
orientation
x 100% 
Fluorescence-positive tissue that 
cannot be resected. 
P(E.20b)   =  
#Patients with ≥ 1 FL-positive 
orientation where no FL-
driven shave was resected 
#Patients in Arm 2 
x 100% 
P(E.20c) Clinical outcomes (e.g., positive 
final margin rate, need for 2nd surgery) will 
also be reported for patients ≥ 1 FL-positive 
orientation but the FL-driven shave(s) was not 
resected 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 41 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Exploratory Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
21. To characterize the 
diagnostic performance 
of imaging of PD G 506 
A  to identify malignant 
breast tissue (Arm 2 
only). 
Percentage of FL guided shaves that 
had no cancer on histopathology. 
P(E.21)  =  
# FL-driven shave 
specimens with no 
carcinoma anywhere   
# of FL-driven shave 
specimens 
 
x 100% 
Carcinoma negative FL-driven 
shave specimens. 
22. To investigate the 
depth of carcinoma 
tissue that can be 
visualized by PD G 506 
A using the Eagle V1.2 
Imaging System.
Depth of tumor identified by FL 
imaging relative to the inked surface, 
reported by tumor type (invasive 
carcinoma and DCIS), using 
descriptive statistics (e.g., mean, 
median, and range).  
-- 
Depth of FL visualization. 
23. To investigate the 
depth of carcinoma 
tissue that can be 
visualized by PD G 506 
A using the Eagle V1.2 
Imaging System. 
 
Percentage of specimens where 
invasive carcinoma was located only 
below the inked surface (i.e., inked 
surface cancer free) for the surfaces 
imaged ex vivo (primary specimen or 
shave specimens) where FL detected 
invasive carcinoma.  
 
P(E.23)=  
#FL-positive orientations-ex vivo 
where invasive carcinoma was 
located only below the inked 
surface (i.e., inked surface cancer 
free) 
#FL-positive orientations ex vivo 
with invasive carcinoma 
 
x 100% 
Fluorescence visualization of 
invasive carcinoma below the 
imaged surface. 
24. To investigate the 
depth of carcinoma 
tissue that can be 
visualized by PD G 506 
A using the Eagle V1.2 
Imaging System. 
Percentage of specimens where DCIS 
was only located deeper than 2 mm 
below the inked surface (i.e., DCIS 
not within 2 mm of the inked 
surface) for the surfaces imaged ex 
vivo (primary specimen or shaves) 
where FL detected DCIS.  
 
P(E.24) =  
#FL-positive DCIS orientations-
ex vivo where DCIS was only 
located deeper than 2 mm below 
the inked surface (i.e., DCIS not 
within 2 mm of the inked surface) 
#FL-positive orientations-ex vivo 
with DCIS 
 
 
x 100% 
Fluorescence visualization of DCIS 
> 2 mm below the imaged surface. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 42 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Exploratory Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
25. To characterize the 
diagnostic performance 
of imaging of PD G 506 
A  to identify malignant 
breast tissue (Arm 2 
only). 
For those primary specimens 
containing cancer anywhere on the 
bisected surfaces, the proportion that 
displayed fluorescence in any 
area/region.   
 
Primary specimen examination will 
only be conducted at a subgroup of 
clinical sites.
P(E.25)=  
# sectioned primary specimens 
with carcinoma anywhere and 
positive fluorescence anywhere 
# sectioned primary specimens 
with carcinoma anywhere 
x 100% 
Sensitivity of PD G 506 A to 
identify carcinoma inside the 
primary specimen. 
26. To characterize the 
diagnostic performance 
of PD G 506 A using 
the Eagle V1.2 Imaging 
System to identify 
malignant breast tissue 
in the primary specimen 
(Arm 2 only). 
 
Diagnostic performance of PD G 506 
A-induced fluorescence to determine 
the presence or absence of cancer 
inside the sectioned primary 
specimen. 
 
Primary specimen examination will 
only be conducted at a subgroup of 
clinical sites. 
P(E.26) Sensitivity =  
TP 
TP + FN 
x 100% 
 
Diagnostic performance of PD G 
506 A to detect cancer in the 
primary specimen. 
P(E.26) Specificity =  
TN  
TN  + FP
x 100% 
 
P(E.26) PPV =  
TP 
TP + FP  
x 100% 
 
P(E.26) NPV =  
TN  
TN  + FN 
x 100% 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 43 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Exploratory Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
27. To characterize the 
diagnostic performance 
of ex vivo imaging of 
PD G 506 A  to identify 
malignant breast tissue 
(Arm 2 only). 
Sensitivity, specificity, NPV, and 
PPV of ex vivo FL imaging of 
primary specimen margin surfaces 
and all cavity shave specimen(s) 
(SoC or FL-guided).   
  
SSO/ASTRO definitions of 
histopathology positive/negative will 
be used. 
 
P(E.27) Sensitivity =  
TP Orientation (ex vivo) 
TP Orientation (ex vivo) 
+  
FN Orientation (ex vivo) 
x 100% 
 
Orientation-level ex vivo diagnostic 
performance for all specimens 
using SSO/ASTRO definitions 
(direct ground truth only). 
 
P(E.27) Specificity =  
TN Orientation (ex vivo) 
TN Orientation (ex vivo) 
+  
FP Orientation (ex vivo) 
x 100% 
P(E.27) PPV =  
TP Orientation (ex 
vivo) 
TP Orientation (ex 
vivo) +  
FP Orientation (ex 
vivo) 
x 100% 
P(E.27) NPV =  
TN Orientation (ex vivo) 
TN Orientation (ex vivo) 
+  
FN Orientation (ex vivo) 
x 100% 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 44 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Exploratory Objective 
Parameter Description 
Parameter Formula 
Abbreviated Description 
28. To characterize the 
diagnostic 
performance of ex vivo 
imaging of PD G 506 
A  to identify 
malignant breast tissue 
(Arm 2 only). 
 
Sensitivity, specificity, NPV, and 
PPV of ex vivo FL imaging of the 
imaged surfaces of the primary 
bisected specimen as compared to the 
histopathology of the corresponding 
biopsies.     
P(E.28) Sensitivity =  
TP primary specimen biopsy  
TP primary specimen biopsy 
+   
FN primary specimen 
biopsy 
x 100% 
 
Diagnostic performance inside the 
primary specimen. 
 
P(E.28) Specificity =  
TN primary specimen biopsy  
TN primary specimen biopsy 
+  
FP primary specimen biopsy 
          
x 100% 
P(E.28) PPV =  
TP primary specimen biopsy  
TP primary specimen biopsy 
+  
FP primary specimen biopsy 
          
x 100% 
P(E.28) NPV =  
TN primary specimen 
biopsy  
TN primary specimen 
biopsy +  
FN primary specimen 
biopsy 
          
x 100% 
 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 45 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
7.4. Safety Objectives and Endpoints  
Safety 
Objective 
Safety Endpoints 
Parameter 
Description 
Parameter Formula 
Abbreviated Description 
Characterize the safety of PD G 506 A 
and the Eagle V1.2 Imaging System in 
patients undergoing fluorescence imaging 
during breast cancer surgery (Arm 1 and 
Arm 2). 
Rate 
of 
procedure-
related WHO grade 3-5 
adverse events. 
P(S.1) = # of procedure related AEs (WHO grade ≥3) 
Safety of the procedure. 
 
Rate 
of 
drug-related 
WHO grade 3-5 adverse 
events.
P(S.2) = # of drug related AEs (WHO grade ≥3) 
Safety of the drug. 
Rate of device-related 
WHO grade 3-5 adverse 
events.
P(S.3) = # of device related AEs (WHO grade ≥3) 
Safety of the device. 
 
Safety assessments will include: 
● Adverse events 
● Serious adverse events 
● Blood analysis: complete blood count, aspartate aminotransferase, alanine transaminase, total bilirubin level, creatinine 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 46 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
8. Study Design  
8.1. Description of the Study Design 
This pivotal study is a 2-part, double -blind (pathologist(s) & patient – blinded) randomized 
placebo-controlled trial (Arm 1: placebo + SoC BCS, Arm 2: SoC BCS + Eagle V1.2 Imaging 
System + PD G 506 A) to evaluate the patient-level clinical usefulness, as well as patient- and 
orientation-level diagnostic performance and safety of PD G 506 A-induced fluorescence for the 
real-time visualization of carcinoma missed by SoC lumpectomy for breast cancer.  Part A is an 
open-label training phase of the study to optimize workflow and train surgeon’s and surgeon’s 
assistant on the day 1 study-specific procedures; Part B of the study is randomized and double -
blind and will serve as the pivotal portion of the study. The Eagle V1.2 Imaging System will be 
used for the visualization of fluorescence.  SBI ALApharma Canada requires completion of the 
Investigator Training Program to ensure the controlled distribution and safe use of PD G 506 A 
investigational drug and the Eagle V1.2 Imaging System investigational medical device to trained 
surgeons for use in clinical trials.  
 
Part A will not be randomized; all participants in Part A will receive PD G 506 A. The Day 1 
procedures for  Part A patients will be carried out with support and oversight from the Sponsor. 
Part A will include approximately 75 patients. Data acquired from the first 30 patients in Part A 
will be used to optimize the study workflow and to confirm the sample size for Part B. The 
remaining approximately 45 patients on Part A will be allocated to training for surgeon’s and 
surgeon’s assistants prior to their enrolling patients into Part B. All surgeon’s and surgeon’s 
assistants must complete at least 1 procedure in Part A, before enrolling a patient into Part B. A 
given site can only be enrolling patients for either Part A or Part B at any given time. In the event 
a new surgeon is brought onto the study after the site has begun enrolling patients into Part B, they 
must shadow a study surgeon for at least one Arm 2 patient procedure. In the event a new 
surgeon’s assistant is brought onto the study after the site has begun enrolling patients into Part 
B, they must shadow a study surgeon assistant for at least one patient procedure before 
participating in as the surgeon’s assistant.  
 
Only data from participants in Part B will be used for the analyses of primary and secondary 
efficacy. Data from all participants in both Part A and Part B will be used for the evaluation of 
safety. 
 
In Part B of the study, participants will be randomized in a ratio of 1:6 (Arm 1 [SoC]: Arm 2 [PD 
G 506 A]).  
 
The randomization will be stratified by breast cancer type (invasive carcinoma with or without in 
situ carcinoma vs. in situ carcinoma alone). This will ensure an approximate ratio of 1:6 within 
each type of breast cancer. Preoperative diagnosis based on diagnostic tissue sampling performed 
during screening (e.g. percutaneous core needle biopsy, fine-needle aspiration cytology) will be 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 47 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
used for stratification. Permuted blocks will be used to construct the randomization schedule and 
the randomization will be implemented using an interactive web response system. 
 
Data from the SoC arm (Arm 1) will not be used for statistical analysis of the primary and most 
secondary endpoints. The purpose of the SoC arm is to compare resected tissue weight, patient 
reported cosmetic outcomes, re-excision prior to initiation of adjuvant therapies, re-excision within 
1-year of index BCS, and safety between study arms as well as to minimize bias introduced into 
the SoC procedure if the surgeon is aware that they have an opportunity to revise the margins 
further after SoC is complete. A 3-month, 6-month and 1-year follow-up  will be performed to 
evaluate patient reported cosmetic outcomes as well as the rate of re-excision across both study 
arms. The 6-month and 1-year follow-up data will be collected as an extension phase to the study, 
meaning database lock and analysis of all other endpoints will be performed following the last 
patient’s 3-month follow-up data is collected. Analysis of 6-month and 1-year data will occur after 
the last patients 1-year visit. The clinical study report will be appended to include the 6-month and 
1-year data, when available. 
8.2. Patient and Study Completion 
A study patient is considered to have completed the study if she has completed all phases of the 
study, including the post-operative follow-up visit (10 -14 days after their surgical procedure), and 
data through the 1-year follow-up has been retrieved and recorded.  A study site will be closed 
only after all follow-up data through 1-year are collected on all patients from that site. 
 
For analyses of Primary and Secondary efficacy endpoints, the end of the study is defined by the 
receipt of the 3-month follow-up data from the last patient in the study. The end of the extension 
phase of the study is defined as the date the 1-year follow-up data is retrieved and recorded for the 
last participant in the study.  
8.3. Minimizing Bias 
The following precautions are in place to minimize bias in data collection: 
 No personnel involved with the surgical procedure (i.e., surgeon, surgeon’s assistant) will 
be aware of the participant’s randomized treatment assignment nor be present when the 
participant is provided with the study drug to ingest.  
o Blinded research personnel will be instructed not to solicit any information from 
the participant regarding the taste and/or smell of the investigational drug. 
 The participant will be blinded to whether they have been randomized to Arm 1 or Arm 2 
for the duration of the study. 
 The surgeon will be blinded to whether a participant has been randomized to Arm 1 or 
Arm 2 until the time at which the surgeon declares the SoC lumpectomy is complete. 
 The individual (e.g. pathologist’s assistant, pathologist) processing the surgical 
specimen(s) will be blind to the manner (e.g. SoC vs. FGR) by which samples are obtained 
and the FL status of the samples. This individual will also be blind to the fluorescence 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 48 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
imaging data collected of the bisected/serially sectioned primary specimen during the 
perioperative procedures. 
 The pathologist performing the histopathological evaluation will be blind to the manner  
(e.g. SoC vs. FGR) by which the samples are obtained and the FL status of the samples. 
 To ensure FL-imaging does not influence SoC margin assessment, intraoperative data 
collection tools will document the completion of SoC prior to the surgeon being given 
access to any previously acquired FL imaging data and performing additional FL imaging.  
8.4. Scientific Rationale for Study Design 
ALA is an endogenous molecule and a precursor of heme. Exogenous administration of ALA 
leads to accumulation of PpIX in cells.  
 
 
 
Figure 8.1 Biosynthesis of Heme39-41.  
Heme biosynthesis with ALA as the starting product. Enzymes involved are: 1, ALA synthase; 2, porphobilinogen 
synthase; 3a, PBGD; 3b, uroporphyrinogen-III synthase, 4, uroporphyrinogen decarboxylase; 5, copro-
porphyrinogen oxidase; 6, protoporphyrinogen oxidase; 7, ferrochelatase. 
 
The primary pharmacodynamic effect of exogenous ALA HCl administration is the specific 
accumulation of porphyrins, especially PpIX. This accumulation is due to an increase in the 
biosynthesis of these porphyrins. Figure 8.1 shows a schematic representation of heme 
biosynthesis. 
 
Since mammalian cells require hemoproteins, i.e. cytochromes, for aerobic energy metabolism 
(oxidative phosphorylation), all nucleated cells have at least a minimal capacity to synthesise 
heme. Moreover, heme is the prosthetic group of several other key proteins, such as hemoglobin, 
Mitochondria
Cytoplasm
Hemoglobin
Glycine + Succinyl CoA
Aminolevulinic acid
Protoporphyrin IX
Protoporphyrinogen IX
Coporphyrinogen III
Uroporphyrinogen III
Porphobilinogen
1
2
3a, 3b
4
5
6
7

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 49 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
myoglobin, catalase, and peroxidase. Heme biosynthesis is tightly controlled by various feedback 
loops. In hepatocytes, feedback inhibition of ALA synthase is mediated by a free heme pool42, i.e. 
free heme is involved in the regulation of its own synthesis. Therefore, the rate of PpIX synthesis 
is also mediated by the availability of free heme. Details of the regulation of heme biosynthesis 
have been reviewed42-44. 
 
In animal studies, PpIX has been proven to be the predominant metabolite after exogenous ALA 
administration by means of in vivo and ex vivo fluorescence spectroscopy45-48 as well as HPLC 
analysis of tissue extracts49-51. However, considerable amounts of hydrophilic porphyrins, e.g. 
uroporphyrin and coproporphyrin, have been identified in experimental tumours52-55 and tissue 
cultures56.  
 
Literature data show that malignant cells accumulate more ALA-induced PpIX than non-malignant 
cells from which they are derived20, 57-61. This may be related to different enzyme profiles in 
abnormal and normal tissue. Increased activity of porphobilinogen deaminase (PBGD or hydroxy-
methylbilane synthase), as well as reduced activity of ferrochelatase, may contribute to enhanced 
PpIX accumulation54, 62, 63. The specific mechanisms, however, have not been elucidated. Since 
ferrochelatase converts PpIX into heme by the insertion of ferrous iron into the porphyrin 
macrocycle, iron availability in situ may also limit the activity of ferrochelatase in cells and 
tissues64, 65, thereby contributing to the enhanced accumulation of PpIX in malignant cells. PpIX 
accumulates preferably in tissues and tumours of both epithelial and mesenchymal origin33, 41, 45.  
 
PpIX has maximum light absorption from violet light at 405 nm. To induce maximum fluorescence 
(without emitting high levels of harmful UV light), the Eagle V1.2 Imaging System utilizes violet 
LEDs with a narrow range of wavelengths centered around 405 nm to excite the PpIX. Using 
violet-blue light excitation (peak emission 405 nm), the Eagle V1.2 Imaging System can visualize 
ALA-induced red PpIX fluorescence emitted by malignant cells in patients who have received 
oral-ALA prior to surgery. 
 
The increased accumulation of PpIX in malignant cells (compared of healthy cells) as well as the 
unique photophysical properties of PpIX which allows it to be detected with an appropriately 
configured device, this provides surgeons a means by which to visualize breast carcinoma in real-
time. This phase 3 pivotal trial will evaluate the clinical usefulness, diagnostic performance and 
safety of PD G 506 A for the visualization of breast carcinoma during BCS.  
8.5. Justification for Dose 
The 20 mg/kg ALA HCl dose is supported by the safety data from Gleolan in the visualization of 
glioma, the global post-marketing data in glioma and bladder cancer and Parts 1 and 2 Study #10-
0633 (Princess Margaret Cancer Centre – Investigator-Initiated Trial).  
 
In Parts 1 and 2 of Study #10-0633, both the 15 mg/kg and 30 mg/kg doses of PD G 506 displayed 
similar measures of diagnostic accuracy and no major adverse events occurred with either dose. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 50 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Both doses were lower than the only dose of ALA (40 mg/kg) previously reported for clinical use 
in breast cancer33.  
 
Therefore, it was decided that a dose between the low and high doses, and identical to the dose 
previously approved by FDA for Gleolan would be appropriate for PD G 506 A as well, leading 
to the selection of the 20 mg/kg dose for the proposed study.  
 
Based on ALA pharmacokinetics the optimal imaging timeframe for fluorescence detection occurs 
over a period between 3-5 hours after administration when ALA has been sufficiently converted 
into PpIX and is still retained in the cells21, 66. In studies of FGR in glioma, patients are typically 
administered ALA HCl approximately 3 hours prior to anesthesia23, 25, 32.  
 
As described in Section 10.1.2.4, PD G 506 A will be administered approximately 3 hours prior 
to anesthesia, with a minimum time of 2 hours and a maximum time of 4 hours. This dosing time 
aligns with the previously characterized optimal imaging timeframe21, 66 and is consistent with 
FDA-approved Gleolan labeling.  
 
Ultimately, the proposed Phase 3 study is required to objectively test if the 20 mg/kg dose will 
deliver the anticipated clinical usefulness and diagnostic accuracy.  
9. Study Population 
9.1. Description of the population to be studied 
Participants will be adult female surgical patients with breast cancer undergoing BCS. 
9.2. Inclusion criteria 
1. Female, 18 years or older 
2. Histologically or cytologically confirmed primary breast cancer (includes invasive 
lobular carcinoma, invasive ductal carcinoma, inflammatory breast cancer, papillary 
breast cancer, adenoid cystic carcinoma of the breast, mucinous breast cancer, 
metaplastic breast cancer, cribriform carcinoma and ductal carcinoma in situ, alone or 
in combination with invasive disease)  
3. Scheduled for a lumpectomy (including bilateral lumpectomy) of a breast malignancy 
[eligibility for breast conserving surgery/partial mastectomy based on clinical staging 
using TNM staging system (AJCC Cancer Staging Manual: Breast Cancer, 8th 
Edition67)]. 
4. Patient must have normal organ and bone marrow function and be appropriate 
surgical candidate per site standard of care 
5. Women of child-bearing potential must agree to use adequate contraception (hormonal 
or barrier method of birth control, abstinence) starting the day entering the study, and 
for the duration of the study period (until the Week 2 visit) 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 51 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
9.3. Exclusion criteria 
Disease and SoC treatment: 
1. Currently on (neo)adjuvant therapy to treat another cancer 
2. Receiving or intended to receive neoadjuvant therapy to treat the primary breast cancer 
(including chemotherapy, endocrine therapy and radiotherapy)  
3. Stage 4 cancer, inclusive of metastatic disease  
4. Non-invasive diseases of the breast (includes lobular carcinoma in situ, phyllodes and 
Paget’s disease of the breast)  
5. Patients who have had the following procedures performed on the involved breast: 
a) Surgery for a benign lesion(s) within 1 year of the BCS date 
b) Breast implants inserted within 1 year of the BCS date 
c) Breast reduction, surgery for malignant disease or mastectomy (at any time prior to 
the BCS date) 
d) Surgery for a benign lesion(s) or insertion of implants >1 year prior to the BCS date 
and who have signs of ongoing inflammation, active tissue healing and/or extensive 
scarring   
e) Radiation at any time prior to the BCS date and who have signs of 
ongoing inflammation, active tissue healing and/or extensive scarring   
6. Patients for whom intraoperative frozen section analysis is planned 
 
Concomitant diseases: 
7. Patients who have not recovered from adverse events due an investigational 
pharmaceutical or diagnostic agents administered more than 30 days prior to their 
scheduled surgical procedure  
8. History of hypersensitivity to ALA HCl or porphyrins 
9. Known or documented personal or family history of porphyria 
10. Patient has a recording of any parameter as defined below: 
Bilirubin: Above upper limit of normal 
AST (SGOT): > 2.5 X institutional upper limit of normal 
ALT (SGPT): > 2.5 X institutional upper limit of normal 
11. Patient has an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m2, 
calculated using the MDRD (Modification of Diet in Renal Disease Study) equation 
for estimating GFR. 
12. Uncontrolled concurrent illness, that in the opinion of the Investigator would prevent 
the patient from participation in the study, including but not limited to:  
a. Ongoing or active infection; 
b. Cardiovascular disease (e.g. symptomatic congestive heart failure, unstable 
angina pectoris, cardiac arrhythmia). 
13. Patients who have the following collagen vascular diseases:  
a. Lupus  
b. Scleroderma 
c. Sjogren’s Syndrome 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 52 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Concomitant medications: 
14. Use of an investigational drug within 30 days of their scheduled surgical procedure  
15. Simultaneous use of other potentially phototoxic substances (such as St. John’s wort, 
griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, 
quinolones and tetracyclines), and topical preparations containing ALA for 24 hours 
during the perioperative period. 
 
Consent/compliance/other: 
16. Social or medical situations including uncontrolled psychiatric illnesses that would in 
the opinion of the Investigator limit compliance with study requirements (e.g. ability 
to travel for follow-up)  
17. Patients who are pregnant or become pregnant (it is unknown if ALA HCl is 
teratogenic or has abortifacient effects) 
18. Patients who are breast feeding (there is an unknown but potential risk for adverse 
events in nursing infants secondary to treatment of the mother with ALA HCl, 
breastfeeding should be discontinued if the mother is treated with ALA HCl) 
19. Inability to consent  
9.4. Screen Failures  
Screen failures are defined as patients who consent to participate in the clinical study but are not 
subsequently randomly assigned to study treatment. A minimal set of screen failure information is 
required to ensure transparent reporting of screen failure participants to meet the Consolidated 
Standards of Reporting Trials (CONSORT) publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details and 
eligibility criteria. 
 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened if the eligibility criteria leading to the screen failure has changed since initial 
screening and the patient has not yet undergone surgery. 
10. Treatments 
10.1. Treatments Administered 
10.1.1. 
Investigational Drug and Placebo 
10.1.2. 
Investigational Drug Acquisition 
The investigational drug will be provided to the PI by SBI ALApharma Canada Inc. The 
investigational drug will be acquired from SBI Pharmaceuticals Co., Ltd. (Tokyo, Japan) and 
imported with appropriate regulatory authorization from the importing country.   

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 53 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
10.1.2.1. 
Formulation, Appearance, Packing and Labeling 
The formulation intended for oral administration is aminolevulinic acid hydrochloride (ALA HCl) 
dissolved in drinking water. The investigational drug is supplied as 1.5 g of granulated 
aminolevulinic acid hydrochloride (equivalent to 1.17 g aminolevulinic acid), for oral solution in 
a white, aluminum/polyethylene laminated film sachet.   
 
A single filled sachet is provided in a cardboard sleeve which is placed into a cardboard box and 
labeled as follows: 
 
 
 
 
The container from which the PD G 506 A or placebo will be consumed will be prepared by the 
site pharmacy and labeled as follows: 
 
PD G 506 A or placebo in drinking water for (PATIENT NAME HERE) 
Dosage: 20 mg/kg  
Reconstituted solution: 30 mg/ml 
Preparation Date: MM/DD/YYYY 
Expiry Date: MM/DD/YYYY 
Store at 25 degrees Celsius 
Study Participant #: 
Study Randomization #: 
 
10.1.2.2. 
Product Storage and Stability 
PD G 506 A should be stored at controlled room temperature [25°C (77°F) with excursions 
permitted to 15-30°C (59-86°F)].  The shelf-life at these storage conditions is 60 months. The 
supplied sachets will have an expiration date listed on the interior and exterior labels.   
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 54 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Following reconstitution in drinking water, the solution of PD G 506 A can be stored for up to 
24 hours at controlled room temperature [25°C (77°F) with excursions permitted to 15-30°C (59-
86°F)] prior to administration. 
10.1.2.3. 
Preparation of the Investigational Drug 
PD G 506 A powder must be reconstituted prior to administration (≤ 24 hours) according to the 
following instructions:  
 
1. Determine the total number of sachets needed to achieve the intended dose for the patient 
according to the equation below (rounded up to the nearest whole sachet):  
 
# 𝑠𝑎𝑐ℎ𝑒𝑡𝑠= 𝑃𝑎𝑡𝑖𝑒𝑛𝑡 𝑊𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔)
75 𝑘𝑔/𝑠𝑎𝑐ℎ𝑒𝑡
 
 
2. Carefully tear open the sachet and transfer the entire contents to a suitably sized, glass 
container (e.g., flask, graduated cylinder).  To facilitate storage after reconstitution, the 
volumetric measuring device/container should have a suitable closure (e.g., stopper).   
3. Using an appropriate volumetric measuring device (e.g., flask, graduated cylinder, dosing 
syringe), measure 50 mL of drinking water per sachet used and add to the container of 
PD G 506 A powder.  
4. Gently swirl the container to completely dissolve PD G 506 A.  
5. The resulting reconstituted solution is clear and colorless to slightly yellowish and contains 
30 mg of ALA HCl per mL of solution.  
6. If required, replace the closure of the appropriately labeled reconstitution container and 
store reconstituted solution for up to 24 hours at room temperature prior to administration.   
10.1.2.4. 
Dosing and Administration of the Investigation Drug 
Calculate the administration volume, in mL, to achieve the intended dose according to the 
following: 
𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑉𝑜𝑙𝑢𝑚𝑒 (𝑚𝐿) = 
௉௔௧௜௘௡௧ ௐ௘௜௚௛௧ (௞௚)× ଶ଴ ௠௚/௞௚
ଷ଴ ௠௚/௠௅
 
For the calculation of administration volume, the patient’s body weight, measured ≤ 7 days prior 
to administration of the study drug, should be used. 
 
Using a disposable volumetric syringe, remove the administration volume of reconstituted solution 
(prepared according to Section 10.1.2.4 from the dosing container and transfer to a separate amber 
oral dosing container. Administer orally 3 hours (range 2 to 4 hours) prior to induction of 
anesthesia.  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 55 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
10.1.2.5. 
Preparation and Administration of the Placebo 
Participant’s randomized to Arm 1 will receive drinking water as the placebo. Calculate the 
administration volume, in mL, according to the following: 
               
                        𝐴𝑑𝑚𝑖𝑛𝑖𝑠𝑡𝑟𝑎𝑡𝑖𝑜𝑛 𝑉𝑜𝑙𝑢𝑚𝑒 (𝑚𝐿) = 
௉௔௧௜௘௡௧ ௐ௘௜௚௛௧ (௞௚)× ଶ଴ ௠௟
ଷ଴ ௞௚
 
10.1.2.6. 
Route of Administration 
The investigational drug and placebo will be provided by an oral route of administration. 
10.1.2.7. 
Handling/Storage/Accountability 
1. The investigator or trained designee must confirm appropriate temperature conditions have 
been maintained during transit for all investigational drug received and any discrepancies 
are reported and resolved before use of the study treatment. 
2. Only participants enrolled in the study may receive the investigational drug and only 
authorized site staff may supply or administer the investigational agent.  
3. The investigational agent must be stored in a secure, environmentally controlled, and 
monitored (manual or automated) area in accordance with the labeled storage conditions 
with access limited to authorized site staff. 
4. The investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance (i.e., 
receipt, reconciliation, and final disposition records). 
5. Further guidance and information for the final disposition of unused investigational drug 
are provided in the Study Pharmacy Manual.  
 
The site will return any unused investigational drug to SBI ALApharma Canada Inc. under the 
following circumstances: the study is completed or discontinued; the drug is expired; the drug is 
damaged or unfit for use (e.g., change in colour). Excess prepared drug that is left over following 
a participant’s surgical procedure will be disposed of in accordance with the site’s disposal policies 
and procedures.  
 
In the event that there is a deviation in the investigational drug accountability procedures (e.g. 
temperature deviation), as defined by SBI ALApharma Canada Inc., the 3rd party responsible for 
dispensing the investigational drug (e.g. trial site pharmacist) will not dispense the drug and will 
notify the Sponsor (SBI ALApharma Canada Inc.) within 1 business day of identification of the 
deviation. The Sponsor (SBI ALApharma Canada Inc.), in consultation with the site, will 
determine the appropriate course of action.  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 56 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
10.1.3. 
Investigational Medical Devices 
1. The sponsor (SBI ALApharma Canada Inc). manufactured medical devices provided for 
use in this study include the following components of the Eagle V1.2 Imaging System: 
a. Handheld Fluorescence Camera (HFC) (Figure 10.1 ): A handheld, battery-
powered, imaging camera with 405 nm and white light illumination light sources 
and dual imaging sensors with optical filters for imaging of PD G 506 A-induced 
PpIX fluorescence and standard full spectrum visible (white) light, respectively. 
When performing fluorescence imaging, red (PpIX) fluorescence from malignant 
cells is detected simultaneously against a background tissue (green) 
autofluorescence emitted mainly by connective tissues (which do not produce 
excess PpIX), thereby producing a composite fluorescence image (or video); noting 
that adipose tissue appears dull-brown in colour in fluorescence images of breast 
tissues. To accomplish this, a custom dual bandpass emission filter is placed in front 
of the camera sensor. The two regions of light that are being imaged are green (500 
– 545 nm) and red (600 – 660 nm). The Handheld Fluorescence Camera has 
mechanical buttons to capture images and videos as well as switch between white 
light and FL imaging modes. The device’s built-in color touchscreen is used to view 
and annotate images and videos in real-time. The device can be connected to an 
external monitor for viewing of images and videos on a larger screen visible to all 
members of the operating room team in real-time. The information displayed on the 
monitor is a mirror of the information displayed on the device screen.  
b. Custom Sterile Sleeve (CSS): A clear plastic film with an optically transparent 
cap used to enclose the Handheld Fluorescence Camera and maintain sterility, 
enabling the intraoperative use of the device in a sterile surgical environment. The 
Custom Sterile Sleeve is a patient contacting single-use accessory (ISO 10993-1: 
external communicating device, in contact with tissue, for a limited duration ≤ 24 
hours). 
c. Dark Imaging Box (DIB): An accessory to be used to create a dark environment 
to enable fluorescence imaging of excised tissue specimens when ambient light 
levels are not acceptable for fluorescence imaging. The Dark Imaging Box consists 
of a reusable imaging stand and a detachable single-use black plastic drape. 
d. Dark Imaging Sheet (DIS): A nonfluorescent plastic sheet to be used as a 
consistent and standardized background for performing fluorescence imaging of 
excised tissues placed upon it. The Dark Imaging Sheet is a single-use accessory 
that will be used within a sterile environment.  
e. Contact Charging Device (CCD): Charging station that uses a charging pin 
connection for charging the Handheld Fluorescence Camera’s battery 
f. Protective Storage Cradle (PSC): Stand used for holding the Handheld 
Fluorescence Camera while not in use and protecting the device during 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 57 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
transportation. The stand is compatible with conventional sterilization methods to 
allow for use in a sterile surgical environment. 
     
 
Figure 10.1 Handheld Fluorescence Camera 
Renderings of the (A) front (target-facing), (B) back (user-facing) and (C) side of the Handheld Fluorescence Camera, 
including the distal imaging tip (A, inset) and the mechanical buttons which control image/video capture, imaging 
mode, and device power (B). (D) Representative photograph of user-facing side of  Handheld Fluorescence Camera 
being used to perform fluorescence imaging in a dark environment.  
g. External Communication Hub (ECH): Intended to simultaneously display the 
image/video seen on the Handheld Fluorescence Camera’s display on the larger 
ECH Display Monitor through a wireless connection. The ECH is comprised of: 
 ECH Display Monitor 
 ECH PC – a small form factor computer with encrypted USB Flash Drive  
(32 Gb)  and numeric pad 
A
B
Optical imaging end
LEDs 
ON/OFF
Image/video 
capture
Sealed USB 
connection port 
Main body
Imaging barrel
Distal imaging tip
Violet-blue LEDs (x4)
(Inactive) IR LEDs (x2)
White light LEDs (x2)
Temperature sensor
Ambient light sensor
White light camera sensor
Fluorescence camera sensor
Range Finder
D
C
AMOLED
imaging
screen

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 58 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 ECH Router 
 ECH HDMI Link Assembly, and ECH USB Cable 
 ECH Power Supplies and Extension Cables 
 ECH Power Bar 
 Cart (ECH Cart) 
 The  ECH supports connecting up  to two (2)  Handheld  Fluorescence  
Cameras  at once. When  two (2) Handheld Fluorescence Cameras are 
connected, the ECH can: save data captured on either device; be used to 
review data from one HFC on the other HFC, and vice versa; cast (i.e. 
mirror) the display from only 1 HFC at a time.  
2. Instructions for medical device use are provided in the Eagle V1.2 Imaging System 
Instructions for Use document. 
3. All medical device incidents, including those resulting from malfunctions of the device, 
must be detected, documented, and reported by the investigator throughout the study (see 
Section 13). 
10.1.3.1. 
Handling/Storage/Accountability 
The Eagle V1.2 Imaging System labels and labeling will be clearly identified by the 
Sponsor/Manufacturer as an investigational device. The PI and designees are responsible for 
maintaining control over the investigational device equipment maintained by the site. The 
investigational equipment must be segregated and provided only to participating investigators. 
 
The following procedures will be followed to account for devices used in the clinical trial: 
 All Handheld Fluorescence Cameras will be serialized 
 The serial IDs of all serialized components of the Eagle V1.2 Imaging System will be 
recorded by the sites in the Device Accountability and Device Return/Repair/Destruction 
logs which will identify the storage location, date shipped, requested by, assigned to, date 
returned and include a record any issue(s) found with the system 
o These logs must be stored in the same location as the Eagle V1.2 Imaging System 
 Device serial numbers will be recorded on the Intraoperative Data Collection Tool at the 
beginning of each procedure 
 All devices will be issued an RMA (return material authorization) number for return that 
will be listed on the packing slip when shipping. Details about cleaning before returning, 
should be documented in the Device Return/Repair/Destruction and communicated to the 
Sponsor prior to shipment. 
 All devices will be shipped in a protected case 
 The Eagle V1.2 Imaging System is to be used for the trial purpose only 
 
Investigators will be responsible for maintaining all devices dedicated to the trial according to the 
study protocol and device manual/instructions for use to ensure optimal performance. The need 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 59 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
for any non-routine maintenance will be reported by the investigator to the device manufacturer 
(SBI ALApharma Canada Inc.) as soon as the issue is observed. The device manufacturer will be 
responsible for performing and documenting any routine and non-routine device maintenance. 
 
10.2. Method of Treatment Assignment 
All participants will be centrally assigned to randomized study treatment using an Interactive 
Voice/Web Response System (IVRS/IWRS). Before the study is initiated, the telephone number 
and call-in directions for the IVRS and/or the log in information & directions for the IWRS will 
be provided to each site. Study treatment will be dispensed at the Day 1 study visit as summarized 
in the Schedule of Activities. Unused dispensed reconstituted investigational drug should be 
disposed of and should not be re-dispensed to another participant.  The IVRS/IWRS will be used 
for both Part A and Part B as the first step for enrollment of a participant; all subjects in Part A 
will receive PD G 506 A and in Part B subjects will be randomized to receive PD G 506 A or 
placebo. 
10.3. Blinding 
Part A of the study is not blinded as all participants will receive PD G 506 A.  Although surgeons 
will not be blinded to treatment in Part A, they will follow all of the same procedures as in Part B 
and will not perform any fluorescence assessments until SoC resection is complete.  In the main 
study, Part B, the participants and pathologist(s) (and pathologist’s assistant) will be blinded to the 
treatment assignment for the duration of the trial. The surgeon and surgeon’s assistant will be 
blinded to the treatment assignment up until the time that the SoC lumpectomy procedure is 
complete, at which point they will be unblinded. The surgeon will also be blinded to the 
fluorescence imaging data collected by the surgeon’s assistant during SoC (e.g. imaging data of 
the, primary specimen and SoC-driven cavity shaves) until such time that they are intentionally 
unblinded per protocol.  
 
At clinical sites where specimen biopsies are collected from inside the sectioned specimen, the 
individual grossing the specimen (e.g. pathologist’s assistant) will remain blind to the fluorescence 
imaging data collected by the surgeon or surgeon’s assistant. 
 
In order to maintain this blind, an otherwise uninvolved 3rd party (e.g. pharmacist) will be 
responsible for the reconstitution and dispensation of the study drug and dispensation of the 
placebo (drinking water) and will endeavor to ensure that there are no differences in time taken to 
dispense following randomization.  The investigational drug or placebo will be administered by a 
blinded qualified medical professional (e.g. nurse). Neither the surgeon nor surgeon’s assistant 
can administer the study drug due to the potential risk that the patient’s reaction to consuming the 
investigational product accidentally unblinds the individual dosing them. 
 
The sponsor must be notified before the blind is broken unless identification of the study treatment 
is required for a medical emergency in which the knowledge of the specific blinded study treatment 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 60 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
will affect the immediate management of the participant’s condition. In this case, the investigator 
must notify the Sponsor’s pharmacovigilance vendor, spmd (spmd will notify the Sponsor) within 
24 hours after breaking the blind. The date and reason that the blind was broken must be recorded 
in the source documentation and electronic case report form (eCRF), as applicable.  
 
For participants that are withdrawn or are terminated, the investigator may be unblinded to the 
treatment allocation following documentation of the participants withdrawal/termination. 
 
If any member of the blinded research team (e.g. surgeon, surgeon’s assistant, research nurse or 
pathologist) is inadvertently unblinded at any time other than as defined by the study protocol, data 
collection will continue as per protocol. The time that the blind was broken and individual that 
was unblinded will be noted in the eCRF. 
 
In the event of a Quality Assurance audit, the auditor(s) will be allowed access to unblinded study 
treatment records at the site(s) to verify that randomization/dispensing has been done accurately. 
10.4. Treatment Compliance 
To minimize the risk of a phototoxic skin reaction all participants will be required to comply with 
written sun/light protection instructions provided by the Sponsor (SBI ALApharma Canada Inc.). 
See Appendix 3 for more details.  
10.5. Concomitant Therapy 
Any medication for concomitant diseases of the patient will be allowed during the course of the 
clinical study. 
 
Participants will be provided with sunscreen to apply prior to leaving the hospital and for a 
minimum of 48 hours after administration of investigational drug when exposed to sunlight. 
10.6. Prophylactic Medications, Treatments and Procedures 
The participant may be administered antiemetics to mitigate the side effects of PD G 506 A, as 
medically required. 
 
Participants will be advised to keep out of direct sunlight for at least 48 hours and given a small 
bottle of sunscreen (minimum sun protection factor (SPF) 60) as further prevention against photo-
sensitization.  Sunscreen will be self-administered by participants. While in the hospital and when 
possible, participants will be exposed to low light environment conditions (e.g. inpatient room will 
be turned off) following administration of the investigational drug. 
10.7. Warnings and Precautions 
Reduce direct exposure to sunlight or room lights for at least 48 hours after oral administration of 
the investigational drug. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 61 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
10.8. Prohibited Medications, Treatments and Procedures 
Patients taking PD G 506 A who are exposed to a photosensitizing agent may experience a 
phototoxic skin reaction.  Due to the risk of possible phototoxic reactions, study participants should 
avoid administering phototoxic drugs such as St. John’s Wort, griseofulvin, thiazide diuretics, 
sulfonylureas, phenothiazines, sulphonamides, quinolones, and tetracyclines, and topical 
preparations containing ALA for 24 hours before and after administration of investigational drug. 
 
Information regarding use of prohibited medications, treatments and procedures will be collected 
during screening and at all study visits. Treatment with any the above listed medications will not 
be permitted unless discussed with and approved by the investigator and Sponsor. If treatment with 
any of the above listed medications is commenced prior to administration of the study drug, the 
participant will be terminated early. If treatment with any of the above listed medications is 
commenced following administration with study drug, early termination will require discussion 
and approval by the investigator and sponsor. 
11. Termination of Participation/Withdrawal Criteria 
 
The following criteria apply to participants who have been enrolled in the study.  An enrolled 
participant will be automatically withdrawn from the study if their surgery is re-scheduled at a site 
other than a study site or if their treatment plan is modified such that they no longer meet the study 
eligibility criteria. A participant may verbally withdraw at any time by contacting her surgeon or 
appropriate study staff (e.g. study coordinator).   
 
An investigator may terminate a patient’s participation in the study if: any clinical AE, laboratory 
abnormality, or other medical condition or situation occurs such that continued participation in the 
study would not be in the best interest of the participant.  
 
Reasons for withdrawal or termination will be recorded in the participant’s study record.  
11.1. Handling of Participant Withdrawals or Termination  
All data collection relating to a withdrawn or terminated participant, excluding safety data for 
participants that have received PD G 506 A, will cease at the time of withdrawal/termination. 
Clinical care in all withdrawn or terminated participants will continue as per standard of care.     
 
In order to maintain the required number of study subjects, any participant that withdraws or is 
terminated prior to completion of the Week 2 visit will be replaced. Participants that withdraw or 
are terminated after the Week 2 visit but prior to the 1 year follow-up will not be replaced.  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 62 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
11.2. Loss to Follow Up 
A participant will be considered lost to follow-up if they fail to return for scheduled visits and are 
unable to be contacted by the study site.  
 
The following actions must be taken if a participant fails to return to the clinic for a required study 
visit: 
● The site must attempt to contact the participant and reschedule the missed visit as soon as 
possible and counsel the participant on the importance of maintaining the assigned visit 
schedule and ascertain whether or not the participant wishes to and/or should continue in 
the study. 
● Before a participant is deemed lost to follow up, the investigator or designee must make 
every effort to regain contact with the participant (where possible, 3 telephone calls and, if 
necessary, a certified letter to the participant’s last known mailing address or local 
equivalent methods). These contact attempts should be documented in the participant’s 
medical record. 
● Should the participant continue to be unreachable, they will be considered to have 
withdrawn from the study with a primary reason of lost to follow-up.  
For the purposes of the 6-month and 1-year follow-up, any participant who may have died within 
6-months or 1 year of their index BCS procedure or for whom follow-up data cannot be retrieved 
(either through medical record review and/or telephone contact with the participant), will be 
considered lost to follow-up for the extension phase of the study. Data from participants that are 
lost to follow-up for the extension phase will still be used for analysis of all endpoints that are 
based upon data collected through the Month 3 visit. 
12. Study Procedures and Schedule 
● Immediate safety concerns should be discussed with spmd immediately upon occurrence or 
awareness to determine if the participant should continue or discontinue study treatment. 
● Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct. 
● All screening evaluations must be completed and reviewed to confirm that potential 
participants meet all eligibility criteria. The investigator will maintain a screening log to record 
details of all participants screened and to confirm eligibility or record reasons for screening 
failure, as applicable.  
● Procedures conducted as part of the participant’s routine clinical management (e.g. diagnostic 
imaging and histopathology, bloodwork) and obtained before signing of the ICF may be 
utilized for screening or baseline purposes provided the procedures met the protocol-specified 
criteria and were performed within the time frame defined in the Schedule of Activities. 
12.1. Schedule of Activities  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 63 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
Figure12.1: 
Schematic of Study Visits and Procedures through Week 2 Visit 
 
 
 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 64 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Table 5.1: Schedule of Study Assessments and Procedures. 
List of study specific assessments and procedures to be performed at each study visit. 
Study Assessment or 
Procedure 
Baseline 
     Day 1 
Day 2 
Week 2 
3-month 
Follow-upr 
6-month 
Follow-up 
1 Year 
Follow-up 
(In-Person Visit not Required) 
     ≤ 90 to 
Day 0 before 
procedure 
Before 
PD G 506 A 
dosing & 
surgical 
procedure 
PD G 506 A 
dosing 
Surgical 
procedure 
After 
PD G 506 A 
dosing & 
surgical 
procedure 
24 – 48 hours 
post-
proceduren 
10 days – 14 
days post-
procedure 
(Last In-Person 
Study Visit) 
80 – 90 days 
post-
procedure 
168 – 182 
days post-
procedure 
365 – 379 
days post-
procedure 
Informed consent
X
Eligibility criteria
X
X
Demographics and 
Medical history
X 
 
 
 
 
 
 
 
 
 
Randomization
X
Adverse event evaluations
X
X
X
X
Xo
X
Xp
Concurrent meds
X
X
X
X
Physical Examinationa
Xb
Xb
X
Vital signs
X
X
X
CBC, AST, ALT, TBL, 
creatinine c, d, e 
X 
 
 
 
 
 
X 
 
 
 
IMAGING (at least one of: 
mammography, 
ultrasound, MRI)f, g
X 
 
 
 
 
 
 
 
 
 
Diagnostic tissue sample 
collection (e.g. PCNB, 
FNAC)g, h
X 
 
 
 
 
 
 
 
 
 
Breast-Q questionnaire
X
X
X
X
X
Pregnancy Testi
Xj
Xk
PD G 506 A / placebo l, m
X
Sunscreen application and 
sun protection instructions
 
 
 
 
X 
 
 
 
 
 
SoC lumpectomy
X
Eagle V1.2 Imaging 
System assessment
 
 
 
X 
 
 
 
 
 
 
FL-guided resection
X
Resected tissue weight
X
Pathology assessment 
X

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 65 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Study Assessment or 
Procedure 
Baseline 
     Day 1 
Day 2 
Week 2 
3-month 
Follow-upr 
6-month 
Follow-up 
1 Year 
Follow-up 
(In-Person Visit not Required) 
     ≤ 90 to 
Day 0 before 
procedure 
Before 
PD G 506 A 
dosing & 
surgical 
procedure 
PD G 506 A 
dosing 
Surgical 
procedure 
After 
PD G 506 A 
dosing & 
surgical 
procedure 
24 – 48 hours 
post-
proceduren 
10 days – 14 
days post-
procedure 
(Last In-Person 
Study Visit) 
80 – 90 days 
post-
procedure 
168 – 182 
days post-
procedure 
365 – 379 
days post-
procedure 
(report) of surgical 
specimens
Medical chart review -
additional proceduresq
 
 
 
 
 
 
 
X 
X 
X 
a. 
Physical exam includes (at a minimum): height (baseline visit only), weight, vitals (heart rate, blood pressure), auditory assessment of heart and lungs, assessment of skin, eyes, abdomen and lower 
extremities, assessment of any phototoxic reactions (Day 1, Day 2 and Week 2 visit only). 
b. 
An abbreviated physical exam (including weight, heart rate and blood pressure) may be performed on Day 1 prior to dosing if a complete physical examine (as described in (a)) has been performed no 
more than 7 days prior to surgery. 
c. 
CBC=complete blood count, AST=aspartate aminotransferase, ALT=alanine transaminase, TBL= Total bilirubin level 
d. 
Phosphorus, uric acid, creatinine kinase, & amylase will be added as clinically necessary/indicated. 
e. 
Baseline must be performed no more than 7 days prior to surgery 
f. 
Type of diagnostic imaging test dependent on site SoC 
g. 
May be performed up to 90 days prior to surgery 
h. 
PCNB=percutaneous core needle biopsy, FNAC=fine-needle aspiration cytology 
i. 
Pregnancy test for women of childbearing potential performed one time prior to surgery either within 7 days prior to surgery or the day of surgery prior to dosing 
j. 
If pregnancy test is performed within 7 days prior to surgery a blood pregnancy test must be performed 
k. 
If pregnancy test is performed on the day of surgery prior to dosing either a urine or blood pregnancy test may be performed 
l. 
PD G 506 A to be dosed 3 hours (target range: 2 hours – 4 hours) prior to anesthesia 
m. 
PD G 506 A is dosed as 20 mg/kg BW. Oral administration is one-time only and based on actual body weight, measured ≤ 7 days prior to administration of the study drug 
n. 
For patients that are discharged on Day 1, Day 2 AE and concurrent medication evaluation will be performed via telephone questionnaire 
o. 
Clinical laboratory tests as required to investigate (S)AEs (e.g. blood work) 
p. 
Any unresolved AEs present at Week 2 visit will be followed for an additional 7 days. Any unresolved SAEs will be followed for an additional 30 days. Patients with elevated liver enzymes will be 
followed until levels return to baseline. 
q. 
Medical chart reviewed to identify additional therapies related to the breast cancer diagnosis received since the Week 2 visit and within 1 year following Day 1 (e.g. additional surgeries, chemotherapy, 
radiation therapy, endocrine therapy, immunotherapy). In the event the patient is no longer under the care of the study investigator, the patient will be contacted via telephone. 
r. 
3-month follow-up data must be collected 80-90 days post-procedure or within 7 days prior to commencement of radiation therapy, whichever occurs first. 
s. 
Includes assessment of neurological AEs (neurological AEs observed in the clinical trials of ALA HCl used for the visualization of glioma during surgical resection may be attributable to the greater 
amount of tissue resected in patients in the ALA arm as compared to control and are not expected to occur in breast cancer patients; nevertheless investigators must evaluate potential neurological AEs at 
each AE assessment time point)
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 66 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
12.2. Screening (Days -90 to Day 0) 
Screening will take place within 90 days prior to the index surgical procedure. Screening must be 
completed with sufficient time prior to the scheduled surgery to allow for the investigational drug 
prescription to be filled. Patients will be pre-screened based on their primary diagnosis. Patients 
thought to meet the eligibility criteria  (Section 9.2) will be approached to participate in the study.  
The surgeon or a member of the research staff will go through the informed consent process with 
the patient (Appendix 4). Patients will be given adequate time to consider participation (minimum 
24 hours if requested). Consented patients will be questioned regarding their eligibility to 
participate in the study. If a patient meets any of the exclusion criteria, screening will be ceased, 
and the patient will not be enrolled in the study. Screening will continue for patients that do not 
meet any of the exclusion criteria and at a minimum meet the following inclusion criteria:  
● Female, 18 years or older. 
● Histologically or cytologically confirmed primary breast cancer (including invasive lobular 
carcinoma, invasive ductal carcinoma and mixed invasive and ductal carcinoma in situ) 
OR histology/cytology confirmation pending. 
● Women of child-bearing potential must agree to use adequate contraception (hormonal or 
barrier method of birth control, abstinence) starting the day entering the study, and for the 
duration of the study period (until the Week 2 visit). 
 
Patients meeting the above criteria will be weighed, and their weight will be recorded on the 
screening data collection tool. A note will be made in the patient’s medical record indicating they 
have consented to participate or are considering participation in the study.  
 
Any additional tests beyond standard of care required to confirm eligibility (e.g. blood work) will 
be performed/ordered only after the patient has consented to participate. Screening blood work of 
consented participants must be performed ≤ 7 days prior to administration of the study drug.  
 
Baseline blood work may be collected before obtaining informed consent if both of the following 
criteria are met: 
1. Baseline blood work required to confirm eligibility according to study protocol SBI-CIP 
20-002 is performed as part of the site’s standard of care for all patients undergoing breast 
conserving surgery. 
2. Standard of care baseline blood work is collected ≤ 7 days prior to surgery. 
 
Baseline blood work may NOT be collected before obtaining informed consent if the following 
criterion is met: 
1. Baseline blood work required to confirm eligibility according to study protocol SBI-CIP 20-
002 is NOT performed as part of the site’s standard of care for all patients undergoing breast 
conserving surgery. 
 
The participant’s weight will be collected ≤ 7 days prior to administration of the study drug and 
recorded on the eCRF and communicated to an unblinded qualified medical professional (e.g. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 67 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
pharmacist) responsible for preparing and dispensing the investigational drug or placebo (Sections 
10.1.2.3, 10.1.2.4, 10.1.2.5). Diagnostic imaging may be performed ≤ 90 days prior to 
administration of the study drug. Diagnostic histopathology may be performed ≤ 90 days prior to 
administration of the study drug. 
 
Consented patients will be asked to complete the pre-operative Breast Conserving Therapy Module 
of the Breast-Q survey to establish their baseline score. Patients may complete this survey anytime 
between Day -30 and Day 1 (day of surgery).  
12.3. Enrolment and Randomization (no visit, Days -30 to Day 0) 
Consented patients meeting all eligibility criteria at the time that their surgery is scheduled will be 
enrolled in the study. Sites must submit the Enrolment Form to the study sponsor for review and 
approval a minimum of 2 business prior to the patient’s scheduled surgery. Enrolment and 
randomization will take place with sufficient time prior to the scheduled surgery to allow for the 
investigational drug prescription to be filled. Participants will be notified verbally (in person or 
via telephone) that they have been enrolled in the study. Consented patients that do not meet the 
eligibility criteria at the time their surgery is scheduled will not be enrolled in the study and will 
be notified of such verbally (in person or via telephone). 
 
Study patients scheduled to undergo a bilateral lumpectomy procedure will only have the study 
procedure performed on one breast. The breast to be included in the study will be identified and 
documented by the surgeon at the time of enrolment. 
 
Following enrolment, the surgeon will complete the investigational drug prescription order and 
submit it to the 3rd party responsible for dispensing the investigational drug (e.g. pharmacist). The 
prescription order will specify the dose, date and time of pick-up. The 3rd party responsible for 
dispensing the investigational drug will use the IVRS/IWRS system to identify to which study arm 
a participant has been randomized. 
 
Dissemination of the randomization code will be by sealed, tamper-protected randomization 
envelopes. Specifically, the 3rd party responsible for dispensing the investigational drug (e.g. 
pharmacist) will have unblinded access to the electronic database (EDC). Pharmacists will be 
granted specific EDC permissions that will allow them to see allocation of subjects at their site, to 
either the study drug, or placebo. When preparing the study drug or placebo for administration 3 
hours before the scheduled surgery, the pharmacist will print the Allocation Form off of the EDC. 
This form will indicate subject ID, allocation to active drug or placebo, date and time of study drug 
preparation. The pharmacist will place the Allocation Form into an envelope that has been 
protected from tampering by carbon paper, seal the envelope, and hand it to the study coordinator 
along with the prepared investigational product for the subject. The study coordinator or a 
designate (another member of research team staff other than the surgeon or surgeon’s assistant), 
will administer the investigational product and keep subject under observation for 30 minutes, then 
hand the intact unblinding envelope to the Operating Room staff. Continued monitoring of the 
patient at hourly intervals following the initial 30-min observation post-administration of the study 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 68 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
drug can be done by trained medical personnel (e.g. the patient’s nursing staff). The seal will be 
broken at the end of the SoC lumpectomy procedure (including resection of the primary specimen 
and any SoC-driven cavity shave specimens) by the surgeon’s assistant or a designate (another 
member of the operating room staff) to confirm the participant’s allocation, as detailed in Section 
12.4.3. 
 
12.4. Surgical Procedure (Day 1) 
12.4.1. 
Pre-operative Procedures 
Participants will arrive at the site at least 4 hours prior to surgery. Participant eligibility and 
documented informed consent will be verified. If the day of surgery weight is being used for 
calculating the investigational drug administration volume, it will be collected and communicated 
to an unblinded qualified medical professional (e.g. pharmacist) responsible for preparing and 
dispensing the investigational drug or placebo (Sections 10.1.2.3, 10.1.2.4, 10.1.2.5). If the weight 
used for calculating the investigational drug administration volume was collected prior to day 1 
but within 7 days of surgery (Section 12.2), the participant’s day of surgery weight must still be 
collected and recorded on the eCRF. In women of child-bearing potential (WOCBP) a negative 
pregnancy test result must be documented prior to administration of the investigational drug or 
placebo. The investigational drug or placebo will be administered by a blinded qualified medical 
professional (e.g. nurse). Participants will be administered PD G 506 A or placebo approximately 
3 hours (2 – 4 hr) prior to anesthesia. Neither the surgeon nor surgeon’s assistant can administer 
the study drug due to the potential risk that the patient’s reaction to consuming the investigational 
product accidentally unblinds the individual dosing them. Patients must have an IV line in place 
prior to study drug administration, and must be under medical supervision from the time of dosing 
until the initiation of anesthesia. Baseline heart rate and blood pressure will be collected prior to 
administration and post-administration heart rate and blood pressure will be monitored and 
recorded immediately after and 30 minutes after administration. Post-administration heart rate and 
blood pressure will continue to be collected at least hourly following the measurement at 30-mins 
post dosing, until the initiation of anesthesia. The participant will be observed for 30 minutes 
following administration for any acute (S)AE(s). (S)AE monitoring will continue for the duration 
of the study period (until the Week 2 visit) as described in Section 13 
Instructions will be provided to the patient to immediately report any possible symptoms of 
hypotension (e.g. light headedness, blurry vision, nausea, dizziness, weakness, blurry vision, 
etc.) after receiving the study drug.  
 
While the patient is under medical supervision from the time of P DG 506 A dosing until the 
initiation of anesthesia, trained medical personnel and applicable therapies should be 
immediately available for the treatment of hypotension or any other hypersensitive reactions 
during administration of PD G506A and the post- administration monitoring period. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 69 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Following administration of the investigational drug and prior to surgery all efforts should be made 
to minimize the participant’s exposure to light (e.g. turn room lights off and draw curtains where 
possible).  
 
Instructions will be provided to the participant regarding steps they should take to minimize the 
risk of experiencing a phototoxic reaction due to PD G 506 A including sun/light protection 
instructions and a list of other common photosensitizing medications which should be avoided 
(Appendix 3).   
 
12.4.2. 
Standard of Care Intraoperative Procedures 
In all participants, the surgeon will perform the lumpectomy following best clinical practice. A 
lumpectomy is defined as a wide local excision of the intact tumor surrounded by a cuff of tumor-
free tissue (determined by palpation and visual inspection). This includes the posterior extent of 
the resection; routinely excising posteriorly down the chest wall should not be performed. Anterior 
skin should not be routinely removed unless clinically indicated. Tumor involved margins should 
be revised as separate margins. Separate incisions should be used for the removal of the primary 
tumor and the axillary surgery except when they coincide anatomically. Curvilinear incision, 
concentric with the areolar margin, or transverse incisions are recommended over radial incisions.  
Drains and approximations sutures should not be used in the breast parenchyma. 
For participants who are undergoing sentinel lymph node mapping with blue (or green) dye during 
their BCS, surgeons should avoid injection of blue dye close to the primary tumor bed if feasible.  
This may help reduce the presence of blue dye in the tumor tissue and surgical cavity where 
fluorescence assessments will take place. Current studies demonstrate that the location of dye 
injection distant to the primary tumor bed does not affect the identification of sentinel nodes68.  
Among study patients who are undergoing lymphatic mapping as part of their index BCS, surgeons 
must comment on the presence or absence of blue (or green) dye at each specimen surface 
investigated and in the final cavity surfaces. 
 
The primary specimen will be palpated/inspected, assessed using intraoperative ultrasound (if 
applicable) and where indicated (wire localization/guidance) sent for mammography to assess 
positive margins. Intraoperative pathological assessment of the primary specimen (e.g. touch 
cytology, frozen section, etc.) is not permitted (as defined in the exclusion criteria). Based on the 
results of visual inspection/palpation/imaging (SoC margin assessment), the surgeon will decide 
if additional tissue should be removed (SoC-driven cavity shave specimens).  
The surgeon will remain blinded to all Eagle V1.2 Imaging System assessment data until the SoC 
lumpectomy procedure (including resection of SoC-driven cavity shave specimens) is complete. 
All excised specimens must be accurately oriented using orientation sutures (or clips). 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 70 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Intraoperative inking for orientation is permitted only after all imaging required according to this 
protocol has been completed.  
12.4.3. 
Study-Specific Intraoperative Procedures 
The surgeon and surgeon’s assistant will perform study-specific imaging using the Eagle V1.2 
Imaging System, FGR, and primary specimen biopsy collection (if applicable) as outlined in 
Appendix 2 and described below. Further note, all videos and images will be automatically 
timestamped and the Eagle V1.2 Imaging System does not have an audio recording function to 
annotate actions, therefore all relevant actions must be recorded in the Intraoperative Data 
Collection Tool.  Both Part A and Part B of the study will follow these same procedures.  
 
Imaging acquisition using Eagle V1.2 Imaging System of the excised specimens will occur outside 
the sterile field, using the Dark Imaging Box (DIB). This will allow the surgeon to continue with 
other aspects of the surgical procedure (e.g. lymph node biopsy/dissection, if applicable) while 
specimen imaging is being performed in real-time.  
A second Handheld Fluorescence Camera will be required, as the draped imaging device used to 
image the final cavity must remain in the sterile field until the completion of the procedure. Note: 
all devices used for specimen imaging, including those used outside the sterile field, must be 
draped within the CSS prior to use.  In both scenarios (e.g. imaging inside or outside the sterile 
field), the excised specimen(s) will be placed on the DIS during imaging.  
 
Immediately following resection of the primary specimen and prior to the surgeon performing 
any SoC margin assessment (e.g. palpation, specimen radiography and/or intraoperative 
ultrasound) or collection of any SoC-driven cavity shave specimens, the surgeon’s assistant will 
perform FL imaging of primary specimen inside the DIB. 
This is required in order to: (1) minimize the risk of photobleaching in the SoC specimens and 
surgical cavity while SoC margin assessment is performed and (2) ensure blinding of the surgeon 
is maintained until SoC is complete.  
To ensure the FL imaging results do not affect the surgeon’s clinical decision making with regard 
to SoC margin assessment, the FL imaging results will not be viewed by or shared with the 
surgeon at this stage until the surgeon has formally declared SoC is complete.  
 
 The surgeon’s assistant will collect a FL video of the primary specimen moving 
systematically through each margin of the specimen. During video capture, the surgeon’s 
assistant will capture still images of each of the anatomical surfaces of the primary 
specimen and use the device’s inbuilt image annotation feature  to assign each image an 
anatomical orientation annotation.  
 WL imaging is encouraged if red PpIX fluorescence is detected.  
 
The surgeon will then perform SoC margin assessment and will verbalize their intention to resect 
SoC-driven cavity shave specimen(s) as well as what margin assessment informed that decision. 
In cases where SoC-driven cavity shave specimen(s) are indicated (based on white light 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 71 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
visualization/palpation ± intraoperative ultrasound and/or specimen radiography) the surgeon’s 
assistant will perform FL imaging of all SoC-driven cavity shave specimen(s).  
 The surgeon’s assistant will collect a FL video of both the inside and outside surfaces of 
all SoC-driven cavity shave specimen(s). During video capture, the surgeon’s assistant 
will capture still images of each surface of all SoC-driven cavity shave specimen(s) and 
use the device’s inbuilt image annotation feature to assign each image an anatomical 
orientation annotation. WL imaging is encouraged if red PpIX fluorescence is detected. 
Cavity shave specimens must have an orientation marker (e.g. suture or clip) placed prior 
to imaging such that the surface being imaged (e.g. inside surface vs. outside surface) can 
be identified in the image.  
 
Following SoC margin assessment and resection of all indicated SoC-driven cavity shave 
specimen(s) (if any),  the surgeon will verbalize that the SoC lumpectomy procedure is complete 
(the time will be recorded in the Intraoperative Data Collection Tool) and will proceed to opening 
the randomization envelope. The time the randomization envelope is opened will be noted on the 
Intraoperative Data Collection Tool.  
Following the procedure, the surgeon and surgeon’s assistant will electronically sign the 
Intraoperative Data Collection Tool to acknowledge that the blind was not broken prior to opening 
of the randomization envelope.   
 
In participants randomized to Arm 1 (SoC), no further imaging or cavity shave specimen resections 
will be performed and the procedure will be completed according to SoC.  
In participants randomized to Arm 2 (SoC + PD G 506 A + Eagle V1.2 Imaging System 
assessment), the surgeon will proceed to review all images collected, acquire additional 
images/videos using the Eagle V1.2 Imaging System and perform FGR. 
 
In the event the randomization envelope is opened prior to completion of SoC and the surgeon 
and surgeon’s assistant are accidently unblinded earlier than required per protocol, the surgeon 
will remain blinded to the fluorescence imaging data collected by the surgeon’s assistant during 
SoC to minimize any bias to the surgeon’s practice. The reason and/or events leading to the 
accidental unblinding will be recorded on the Intraoperative Data Collection Tool. 
 
The surgeon will collect a FL video of the final cavity after SoC moving systematically through 
each surface of the cavity. During video capture, the surgeon will capture still images of all cavity 
surfaces and use the device’s inbuilt image annotation feature to assign each image an anatomical 
orientation annotation.  
 
The surgeon will then review all images collected with the surgeon’s assistant and will assign 
(and verbalize) a FL-status to all tissue surfaces imaged, including the primary specimen (all 
anatomical surfaces), all SoC-driven cavity shave specimens (if applicable; inside and outside 
surfaces), and the final cavity after SoC. The FL-status of all tissue surfaces will be recorded in 
the Intraoperative Data Collection Tool. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 72 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
The surgeon will then resect FL-driven cavity shave specimens based on the FL-status of the 
surfaces of the final cavity after SoC and final margins after SoC (outside surface of final SoC 
shave or primary specimen where no SoC driven cavity shave specimen(s) were collected). 
 
 If none of the final margin(s) after SoC and final cavity surface(s) after SoC are classified 
as FL-positive, the surgeon will verbalize the completion of Eagle V1.2 Imaging System 
assessment. 
 If ≥1 are classified as FL-positive, the surgeon will then resect a FL-driven cavity shave 
specimen for each cavity surface where either the final cavity surface after SoC and/or the 
corresponding final margin after SoC was identified as FL-positive.  
 
The surgeon will then perform FL imaging of the inside and outside surface of all FL-driven 
cavity shave specimens resected in the previous step and the corresponding cavity surfaces.  
The surgeon will verbalize which (i.e., S, M, P, L, I, A), if any, of the inside and outside surfaces 
of the FL-driven cavity shave specimens and corresponding cavity surface(s) is considered 
positive for carcinoma based on the visualization of red PpIX FL (i.e. FL-positive).  
 
The FL-status of each specimen surface and cavity surface will be recorded in the Intraoperative 
Data Collection Tool.  
 If none are classified as FL-positive, the surgeon will verbalize the completion of Eagle 
V1.2 Imaging System assessment.  
 If ≥1 are classified as FL-positive, the surgeon will continue to perform FGR as described 
above until such time that either no red PpIX FL is detected on both the outside surface of 
the last round of FL-driven cavity shave specimens and surgical cavity or until no further 
tissue can be removed based on the surgeon’s best clinical judgment and in the interest of 
best medical practice for the patient.  
 If at the completion of Eagle V1.2 Imaging System assessment, red PpIX FL is still 
observed on the final margins after FGR and/or in the surgical cavity and no further 
resection is performed, the anatomical surface(s) of residual fluorescence (i.e., S, M, P, L, 
I, A) and the reason for not performing further FGR will be recorded. 
 
The surgeon will then complete the procedure as per SoC and all samples will be sent for 
histopathological assessment.  
In order to maintain the blinding of the individuals responsible for processing and evaluating the 
specimens (e.g. pathologist’s assistant, pathologist) the conditions under which the cavity shave 
specimens were resected will not be indicated in the labelling.  
In cases where multiple cavity shave specimens were resected from a single anatomical location 
(e.g. S, M, P, L, I, A) labelling will indicate the order in which the shaves were collected such that 
the relative distance of each of the shaves from the primary specimen is known. For example, if 3 
sequential cavity shave specimens are resected from the lateral cavity surface, the first shave 
(resected directly after the primary specimen) will be identified as lateral cavity shave specimen 
1, the second shave (resected directly after lateral cavity shave specimen margin 1) will be 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 73 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
identified as lateral cavity shave specimen 2 and the 3rd shave (resected directly after lateral cavity 
shave specimen 2) will be identified as lateral cavity shave specimen 3.  
 
Throughout the procedure, care will be taken to protect all excised specimens from exposure to 
light by placing specimens in sealed, black/opaque, light protected containers at all times when 
they are not being evaluated. All excised specimens must be marked (e.g. using sutures) for the 
purposes of orientation as per SoC.  For example, the primary specimen can be marked with a 
long lateral and short anterior suture and the cavity shave specimens can be marked with a suture 
on the outside surface of the shave. Sites may use their preferred method of orienting specimens; 
however, the method must ensure the orientation of all specimens is clear to the pathologist 
evaluating the specimens.  
 
 
12.4.4. 
Peri-operative Procedures 
12.4.4.1. 
Bisected Specimen Biopsy Collection 
These procedures will occur at a subset of clinical sites. 
 
This procedure must be performed following completion of SoC and fluorescence imaging of the 
primary specimen. Bisecting of the specimen may be performed by any appropriately trained and 
qualified individual (e.g. surgeon, pathologist, pathologist’s assistant) however interpretation of 
the fluorescence image(s) of the bisected specimen must be performed by the surgeon or 
surgeon’s assistant.  
 
The primary specimen will be palpated and a slice will be made through the centre of the palpable 
mass. In the case of non-palpable tumors, all best efforts will be made to position the slice through 
the centre of the tumor. Serial slicing of the primary specimen (e.g. ‘bread-loafing’) may be 
performed in lieu of bisecting, if serial slicing is part of SoC at the study site. In this case, the slice 
with the largest tumor diameter should be selected for imaging. Imaging will be performed with 
the specimen placed on the DIS.  Fluorescence images will be collected such that the entire surface 
(both sides) of the bisected tissue is captured. While recording a FL-video (to document the 
location where biopsies were collected), the surgeon or surgeon’s assistant will collect a tissue 
biopsy (~ ≤5mm x ≤5mm) in an area of positive- and negative-fluorescence as outlined in Table . 
The imaged surface of the biopsy will be inked with specimen ink to enable proper orienting of 
the biopsy during paraffin embedding. The individual grossing the specimen (e.g. pathologist’s 
assistant) will remain blind to the fluorescence imaging results collected by the surgeon and/or 
surgeon’s assistant.  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 74 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Table 12.1: 
Specimen biopsy collection algorithm  
Fluorescence status 
Palpable mass in section 
Non-palpable mass in section 
Section contains areas of 
both positive- and 
negative-fluorescence 
Collect 1 fluorescence-positive biopsy in an area of brightness positive-
fluorescence. 
 
Collect 1 fluorescence-negative biopsy as far away (at least ≥ 1 cm specimen size 
permitting) from the border of positive-fluorescence are where the fluorescence-
positive biopsy was collected.
Section contains  only 
positive-fluorescence 
Collect 1 fluorescence-positive biopsy in an area of brightness positive-
fluorescence. 
Section contains only 
negative-fluorescence 
Collect 1 fluorescence-negative 
biopsy as far away (at least ≥ 1 cm 
specimen size permitting) from the 
border of palpable mass as is 
possible.
Collect 1 fluorescence-negative biopsy as 
far away (at least ≥ 1 cm specimen size 
permitting) from suspected-carcinoma in 
an area suspected to be normal tissue. 
 
12.4.4.2. 
Specimen Grossing 
All specimens (excluding biopsies taken from the primary specimen) will be individually weighed 
prior to fixation in formalin, and the mass (mg) will be recorded on the Pathology Data Collection 
Tool.  
 
Specimen grossing and fixation will be performed as per SoC, including inking of all surfaces of 
the primary specimen and both the inside and outside surface of all cavity shave specimens. To 
adjudicate the orientation-level endpoints, the inside and outside surfaces of all cavity shave 
specimens must be inked with different colors (visually obvious) of ink. The primary specimen 
and any cavity shave specimens will be submerged in formalin within the site-mandated time post-
resection (i.e. ischemic time).  
12.4.5. 
Post-Operative Procedures 
Prior to discharge, participants will be evaluated for any adverse events. At the 2-week follow-up 
visit the surgeon will assess the participant for any adverse events including any self-reported 
signs/symptoms. All AEs will be reported in the participants medical record and in the eCRF. The 
participant will be administered the post-operative Breast-Q survey.  
 
The participant will be provided sunscreen to apply at time of discharge and for a minimum of 48 
hours following administration of the investigational drug when exposed to sunlight. Application 
of sunscreen at time of discharge will be confirmed and recorded in the case report form. The 
participant may be administered additional medications (e.g. antiemetics) to mitigate the side 
effects of PD G 506 A, as medically required.  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 75 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Participants will receive postoperative treatment (e.g. radiation, chemotherapy, re-operation) as 
per standard of care. All postoperative treatment that is initiated within the study period (until the 
Week 2 visit) will be recorded in the eCRF. 
12.5. Day 2 Follow-up (24 hours +24 hours post-surgery) 
Between 24 – 48 hours after the surgery the participant will be contacted via telephone and asked 
about their adherence to the sun protection instructions, any self-reported adverse events and 
concomitant medications. 
12.6. Post-operative Pathology Procedures (no visit) 
12.6.1. 
Specimen Blocking and Assessment  
The primary specimen will be blocked according to standard procedures. All cavity shave 
specimen(s) will be blocked in total.  
 
Cavity shave specimens must be oriented such that histological sections can be made 
perpendicularly to the inked inside and outside surfaces. Biopsies must be oriented such that 
histological sections can be made perpendicularly to the inked surface (i.e., imaged surface). 
 
Primary Specimen: 
The pathologist will evaluate the primary specimen as per SoC and record the following for each 
anatomical surface (i.e., S, M, P, L, I, A) on the Pathology Data Collection Tool: 
i. 
Presence or absence of carcinoma at each inked surface, 
ii. 
Presence or absence of carcinoma below each inked surface, 
iii. 
Presence or absence of non-malignant abnormal cells (e.g. hyperplastic, dysplastic) at or 
below each inked surface 
 
If carcinoma is present, record the following additional information on the Pathology Data 
Collection Tool: 
i. 
Type(s) of carcinoma (e.g. IDC, ILC, DCIS, if other specify) 
ii. 
Shortest distance from the inked surface to carcinoma 
 
If non-malignant abnormal cells are present, record the following additional information:  
Type(s) of abnormal cells (e.g. hyperplastic, dysplastic, etc.) 
 
Cavity Shave Specimens: 
The pathologist will evaluate all cavity shave specimen(s) and record the following on the 
Pathology Data Collection Tool (note: cavity shave specimen(s) must be histologically assessed 
in total):  
i. 
Presence or absence of carcinoma at or below the inked outside surface of all cavity shave 
specimens  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 76 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
ii. 
Presence or absence of carcinoma at or below the inked inside surface of all cavity shave 
specimens  
iii. 
Presence/absence of non-malignant abnormal cells (e.g. hyperplastic, dysplastic) at or 
below the inked inside surface of all cavity shave specimens 
 
If carcinoma is present, record the following additional information on the Pathology Data 
Collection Tool:  
i. 
Type(s) of carcinoma (e.g. IDC, ILC, DCIS, if other specify) 
ii. 
Shortest distance from each inked surface (i.e., inside and outside surfaces) to 
carcinoma 
 
If non-malignant abnormal cells are present, record the following additional information:  
i. 
Type(s) of abnormal cells (e.g. hyperplastic, dysplastic, etc.) 
 
Tissue Biopsies: 
The pathologist will evaluate all specimen biopsies and record the following on the Pathology Data 
Collection Tool (note: biopsies must be histologically assessed in total):  
i. 
Presence/absence of carcinoma anywhere in a given biopsy 
ii. 
Presence/absence of non-malignant abnormal cells (e.g. hyperplastic, dysplastic) 
anywhere in a given biopsy 
 
If carcinoma is present, record the following additional information on the Pathology Data 
Collection Tool:  
i. 
Type(s) of carcinoma (e.g. IDC, ILC, DCIS, if other specify ) 
ii. 
Shortest distance from the inked surface to carcinoma 
If non-malignant abnormal cells are present, record the following additional information:  
i. 
Type(s) of abnormal cells (e.g. hyperplastic, dysplastic, etc.) 
 
Lastly, the pathologist will report the final margin status in the participants medical record as well 
as the Pathology Data Collection Tool. 
12.6.2. 
Specimen Handling, Storage and Future Research 
All specimens collected as part of this study will be prepared, handled and stored according to the 
site’s policies and procedures. All tissue blocks will be stored on site and may not be destroyed or 
discarded prior to the completion of the study and notification by the sponsor that samples are no 
longer required to be stored. All samples must be logged and tracked over the course of the study 
and stored in a secure location accessible to research team members delegated responsibility for 
handling and storing specimens.  
 
During the study and/or at the end of the study, the Sponsor may request specimens collected as 
part of this study, including unstained histological sections from paraffin embedded tissue blocks 
and/or tissue blocks (if permitted by the site) in order to answer future research questions.  Tissue 
specimens provided for use in future research will be coded, de-identified and linked to the data 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 77 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
collected as part of this clinical study, including for example: patient demographics, disease 
characteristics, surgical pathology data, the type of specimen (e.g. SoC-guided vs. FL-guided), and  
the FL-status and histopathological-status of the tissue block and/or surface from which the tissue 
block was taken. Tissue specimens sent to the Sponsor may be stored indefinitely and may be used 
to answer future research questions that are either related or unrelated to the clinical study protocol 
SBI-CIP 20-002. Tissue specimens may be sent to external laboratories for processing (e.g. 
histological staining) and evaluation (e.g. analysis of stained histological sections). Tissue 
specimens will not be used for any genetic research. If future analyses of specimens leads to 
findings that are relevant to a patient’s ongoing health, the patient’s surgeon will be informed and 
findings will be shared with the patient.  Specimens provided to the Sponsor may also be shared 
with 3rd parties for the purposes of answering future research questions unrelated to the current 
study. Specimens shared with 3rd parties will be coded, de-identified and linked to patient 
demographics, disease characteristics, surgical pathology data. Specimens shared with 3rd parties 
will not be linked to any personally identifiable patient information. 
 
12.7. Week 2 Visit (Day 10 – 14) 
Clinical usefulness and diagnostic performance endpoint data will be collected at the participant’s 
post-operative surgical follow-up visit.  
 
At this visit, the participant will complete the post-operative Breast Conserving Therapy Module 
of the Breast-Q survey. To minimize the potential impact of timing of administration of the Breast-
Q survey post-op questionnaire, all patients will complete the 2-week post-op questionnaire before 
they have met with their surgeon to discuss their surgical pathology report.  
 
The participant’s surgical pathology report will be available at this time. Endpoint data will be 
retrieved from the participant’s surgical pathology report and the study-specific Pathology Data 
Collection Tool. Additional data related to the final pathological tumor staging, pathological 
features/characteristics and nodal involvement will be retrieved from the participant’s surgical 
pathology report and recorded in the eCRF. 
 
The surgeon will question the patient about any patient-reported Aes and use of concomitant 
medications as well as assess and record any ongoing adverse events in the participant’s medical 
record and eCRF.  
 
Blood work (CBC, AST, ALT, TBL, creatinine) will be performed at this visit. If liver enzymes 
are elevated from baseline (and deemed clinically significant according to the Table 12.2 below), 
the patient will be followed until such time that liver enzyme levels return to baseline. Physical 
examination must include assessment of any phototoxicity reactions and any observed 
phototoxicity reactions will be followed until resolution. 
 
Table 12.2: 
Criteria for clinical significant liver enzyme elevation  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 78 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Criteria 
CTCAE v5.0 Grade 2 (moderate) as criterium to judge if 
elevation of liver enzymes should be deemed clinically significant
Bilirubin: above upper limit of normal 
Bilirubin: 
> 1.5 – 3.0x institutional* ULN if baseline normal  
> 1.5 – 3.0x baseline if baseline abnormal
AST: > 2.5x institutional ULN 
AST:  
> 3.0 – 5.0x institutional* ULN if baseline normal  
> 3.0 – 5.0x baseline if baseline abnormal
ALT: > 2.5x institutional ULN 
ALT:  
> 3.0 – 5.0x institutional* ULN if baseline normal  
> 3.0 – 5.0x baseline if baseline abnormal
AP: n/a 
AP: 
> 2.5 – 5.0x institutional* ULN if baseline normal  
> 2.5 – 5.0x baseline if baseline abnormal
*“institutional” is included in the study protocol definition, not part of the original CTCAE definition 
12.8. 3-Month Follow-up (Day 80 – 90) 
The participant will be required to complete the post-operative Breast Conserving Therapy Module 
of the Breast-Q survey within 80 to 90 days post-surgical procedure. If the participant is scheduled 
to receive radiation therapy prior to 80 days post-surgical procedure, the survey will be completed 
within 7 days prior to the initiation of radiation therapy. The survey may be completed during a 
regular clinic visit (if applicable) or sent and returned via mail. A review of the participant’s 
medical record will be performed 3 months (Day 80 – 90) after their index BCS procedure. 
Treatments administered for the purposes of treating the primary breast cancer in the ipsilateral 
breast will be recorded in the eCRF. Treatments may include, but are not limited to, radiation 
therapy, chemotherapy, hormone, immunotherapy and surgery (e.g. re-excision, lumpectomy, 
mastectomy). If, at 3 months follow-up, the participant is no longer under the care of the surgeon 
who performed the index BCS procedure, the participant will be contacted via telephone to collect 
the follow-up data. 
 
12.9. Extension Phase  
12.9.1. 
6-Month Follow-up (Day 168 – 182) 
The participant will be required to complete the post-operative Breast Conserving Therapy Module 
of the Breast-Q survey within 168 to 182 days post-surgical procedure. The survey may be 
completed during a regular clinic visit (if applicable) or sent and returned via mail. A review of 
the participant’s medical record will be performed 6 months (Day 168 – 182) after their index BCS 
procedure. Treatments administered for the purposes of treating the primary breast cancer in the 
ipsilateral breast will be recorded in the eCRF. Treatments may include, but are not limited to, 
radiation therapy, chemotherapy, hormone, immunotherapy and surgery (e.g. re-excision, 
lumpectomy, mastectomy). If, at the 6 month follow-up, the participant is no longer under the care 
of the surgeon who performed the index BCS procedure, the participant will be contacted via 
telephone to collect the follow-up data. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 79 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
12.9.2. 
1- Year Follow-up (Day 365 – 379) 
The participant will be required to complete the post-operative Breast Conserving Therapy Module 
of the Breast-Q survey within 365 to 379 days post-surgical procedure. The survey may be 
completed during a regular clinic visit (if applicable) or sent and returned via mail. A review of 
the participant’s medical record will be performed 1 year (Day 365 + 14 days) after their index 
BCS procedure. Treatments administered for the purposes of treating the primary breast cancer in 
the ipsilateral breast within the 1 year period (365 days) following the index BCS procedure will 
be recorded in the eCRF. Treatments may include, but are not limited to, radiation therapy, 
chemotherapy, hormone, immunotherapy and surgery (e.g. re-excision, lumpectomy, 
mastectomy). If, at the 1 year follow-up, the participant is no longer under the care of the surgeon 
who performed the index BCS procedure, the participant will be contacted via telephone to collect 
the follow-up data. 
12.10. Early Termination Visit  
If early termination occurs prior to administration of the investigational drug (and use of the Eagle 
V1.2 Imaging System) no additional study specific procedures or evaluations are required and no 
early termination visit is required. If early termination occurs following administration of the 
investigational drug (e.g. during the surgery the surgeon decides it is not in the best interest of the 
patient to proceed with the study specific data collection), safety data including AEs and medical 
device problems will be collected and recorded on the procedure day (Day 1). The participant will 
continue to be followed for AEs until the Week 2 Visit. No specific early termination visit is 
required.   
12.11. Unscheduled Visit 
If a participant is seen by their surgeon following their surgery but prior to the Week 2 Visit, the 
surgeon will assess and record AEs (as reported by the participant or observed by the surgeon) 
and concomitant medications. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 80 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13. Assessment of Safety 
13.1. Specification of Safety Parameters 
13.1.1. 
Definition of Adverse Events 
 
Investigational Device: 
Eagle V1.2 Imaging System
Investigational Drug: 
PD G 506 A
Adverse Event: 
Any untoward medical occurrence, unintended 
disease or injury, or untoward clinical signs 
(including abnormal laboratory findings) in 
subjects, users or other persons, whether or not 
related to the investigational medical device 
which includes: 
a) Events related to the investigational medical 
device or the comparator; and 
b) Events related to the procedures involved. 
For users or other persons, this definition is 
restricted to events related to investigational 
medical devices.
Adverse Event: 
Any untoward medical occurrence in a patient or 
clinical investigation subject administered a 
pharmaceutical product and which does not 
necessarily have a causal relationship with this 
treatment. 
 
An adverse event (AE) can therefore be any 
unfavourable and unintended sign (including an 
abnormal laboratory finding, for example), 
symptom, or disease temporally associated with 
the use of a medicinal product, whether or not 
considered related to the medicinal product
(Health Canada Guidance Document 
“Application for Medical Device Investigational 
Testing Authorization”; Effective: 2018/10/01) 
(Health Canada Guidance for Industry “Clinical 
Safety Data Management: Definitions and 
Standards for Expedited Reporting (ICH Topic 
E2A); H42-2/67-8-1995E; Effective: 1995) 
FDA 21CFR312.32
 
Of note: 
● Surgical procedures or other therapeutic interventions themselves are not adverse events, 
but the condition for which the surgery/intervention is required is an adverse event and 
should be documented accordingly. 
● Planned surgical measures and the condition(s) leading to these measures are not adverse 
events, if the condition(s) was (were) known before the period of observation (see Section 
13.3) and did not worsen during study. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 81 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13.1.2. 
Definition of Serious Adverse Events 
 
Investigational Device: 
Eagle V1.2 Imaging System
Investigational Drug: 
PD G 506 A
Serious Adverse Event: 
An Adverse Event that: 
a) Led to death; 
b) Led to serious deterioration in the health of 
the subject, that either resulted in: 
i. 
A life-threatening illness or injury; 
ii. 
A permanent impairment of a body 
structure or a body function; 
iii. 
In-patient or prolonged 
hospitalization; or 
iv. 
Medical or surgical intervention to 
prevent life-threatening illness or 
injury or permanent impairment to a 
body structure or a body function. 
c) Led to foetal distress, foetal death or a 
congenital abnormality or birth defect; 
d) Could have led to death or a serious 
deterioration were it to recur*.
Serious Adverse Event: 
A serious adverse event (experience) or reaction is 
any untoward medical occurrence that at any 
dose: 
● Result in death; 
● Is life-threatening** 
● Requires inpatient hospitalization or 
prolongation of existing hospitalization; 
● Results in persistent or significant disability/ 
incapacity; 
● Is a congenital anomaly/ birth defect; 
● Is medically important*** 
(Health Canada Guidance Document 
“Application for Medical Device Investigational 
Testing Authorization”; Effective: 2018/10/01) 
*added to the definition since those type of events 
are also reportable to Health Canada
(Health Canada Guidance for Industry “Clinical 
Safety Data Management: Definitions and 
Standards for Expedited Reporting (ICH Topic 
E2A); H42-2/67-8-1995E; Effective: 1995) 
**The term “life-threatening” in the definition of “serious” refers to an event in which the patient was at 
risk of death at the time of the event; it does not refer to an event which hypothetically might have caused 
death if it were more severe 
***Important medical events that may not result in death, be life-threatening, or require hospitalization may 
be considered serious when, based upon appropriate medical judgment, they may jeopardize the patient 
or subject OR may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition 
13.1.3. 
Definition of an Adverse Drug Reaction 
Adverse reactions are defined as all noxious and unintended responses to a medicinal product 
related to any dose should be considered adverse drug reactions. Any (S)AEs which are determined 
to be related to the use of PD G 506 A will be considered adverse drug reactions. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 82 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13.1.4. 
Definition of UADE/ SUSAR 
Investigational Device: 
Eagle V1.2 Imaging System
Investigational Drug: 
PD G 506 A
UADE: Unanticipated Adverse Device Effect 
(US-specific definition): 
Means: 
● any serious adverse effect on health or safety 
or any life-threatening problem or death 
● caused by, or associated with, a device,  
● if that effect, problem, or death was not 
previously identified in nature, severity, or 
degree of incidence in the investigational 
plan or application (including a 
supplementary plan or application), 
● or any other unanticipated serious problem 
associated with a device that relates to the 
rights, safety, or welfare of subjects.
SUSAR: Suspected Unexpected Serious 
Adverse Reaction: 
Any adverse event (experience) which is 
considered: 
● serious (Section 13.1.2); 
● causally related to the study medication 
(Section 13.2.3); and 
● unexpected in nature, severity or frequency 
(Section 13.2.6) 
FDA 21CFR812.3 (s) 
Definition in line with: 
(Health Canada Guidance for Industry “Clinical 
Safety Data Management: Definitions and 
Standards for Expedited Reporting (ICH Topic 
E2A); H42-2/67-8-1995E; Effective: 1995) and 
FDA 21CFR312.32
 
13.1.5. 
Definition of Unanticipated Problem 
An unanticipated problem is defined as any incident, experience, or outcome that meets all of the 
following criteria:  
1. Unexpected (in terms of nature, severity, or frequency) given (a) the research procedures 
that are described in the protocol related documents, such as the REB/IRB-approved 
research protocol, IB, and informed consent form and (b) the characteristics of the 
population being studied (i.e., the expected natural progression of any underlying disease, 
disorder or condition of the participant(s) experiencing the adverse event and the 
participant’s predisposing risk factor profile for the adverse event has altered); AND 
2. Related or possibly related to participation in the research (i.e., at least a reasonable 
possibility exists that the incident, experience, or outcome may have been caused by the 
drugs, devices, or procedures involved in the research); AND 
3. Suggests that the research places participants or others at a greater risk of harm 
(including physical, psychological, economic or social harm) than was previously known 
or recognized.  
 
Only a subset of adverse events occurring in research participants will meet the criteria for an 
unanticipated problem (UP).  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 83 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
Note: SUSARs and UADE are considered unanticipated problems per definition. 
13.2.  Classification of an Adverse Event 
13.2.1. 
Severity of Event 
All AEs will be assessed by the PI using the protocol defined grading system. The Common 
Terminology Criteria for Adverse Events (CTCAE) Version 5.0 published by the U.S. Department 
of Health and Human Services (November 27, 2019)69 will be used to grade the severity of AEs.   
 
For AEs not included in the CTCAE defined grading system, the following guidelines will be used 
to describe severity69: 
 
● Grade 1, Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated.  
● Grade 2, Moderate; minimal, local or non-invasive intervention indicated; limiting age- 
appropriate instrumental activities of daily life (ADL)*.  
● Grade 3, Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care 
ADL**.  
● Grade 4, Life-threatening consequence; urgent intervention indicated.  
● Grade 5, Death related to AE. 
 
*Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the 
telephone, managing money, etc.  
**Self-care ADL refers to bathing, dressing and undressing, feeding self, using the toilet, taking 
medications, and not bedridden. 
13.2.2. 
Clarification of the difference in meaning between “severe” and 
“serious” 
The term “severe” is often used to describe the intensity (severity) of a specific event (as in mild, 
moderate, or severe myocardial infarction); the event itself, however, may be of relatively minor 
medical significance (such as severe headache). 
 
This is not the same as “serious”, which is based on the outcome or action criteria usually 
associated with events that pose a threat to life or functioning. 
 
Seriousness (not severity) serves as a guide for defining regulatory reporting obligations. 
 
Spmd, on behalf of SBI ALApharma Canada Inc., will be responsible for reviewing all AE reports 
regarding the PI’s determination of the severity of the event. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 84 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13.2.3. 
Relationship to Study Intervention 
For all collected AEs, the PI will determine the AEs causality based on temporal relationship, 
alternative explanations (e.g. concurrent disease or other drugs) and his/her clinical judgment. 
The degree of certainty about causality will be graded using the categories below.  
 
● Definitely Related – There is clear evidence to suggest a causal relationship, and other 
possible contributing factors can be ruled out. The clinical event, including an abnormal 
laboratory test result, occurs in a plausible time relationship to investigational drug 
administration or study device use and cannot be explained by concurrent disease or other 
drugs, chemicals, or devices.  
● Probably Related – There is evidence to suggest a causal relationship, and the influence 
of other factors is unlikely. The clinical event, including an abnormal laboratory test result, 
occurs within a reasonable time after administration of the drug or use of the study device, 
is unlikely to be attributed to concurrent disease or other drugs, chemicals or devices.  
● Possibly Related – There is some evidence to suggest a causal relationship (e.g., the event 
occurred within a reasonable time after administration of the investigational drug or use of 
the device). However, other factors may have contributed to the event (e.g., the 
participant’s clinical condition, other concomitant events). Although an AE may rate only 
as “possibly related” soon after discovery, it can be flagged as requiring more information 
and later be upgraded to “probably related” or “definitely related,” as appropriate. 
● Unlikely to be related – A clinical event, including an abnormal laboratory test result, 
whose temporal relationship to investigational drug administration or device use makes a 
causal relationship improbable (e.g., the event did not occur within a reasonable time after 
administration of the trial medication) and in which other drugs, chemicals, devices or 
underlying disease provides plausible explanations (e.g., the participant’s clinical 
condition, other concomitant treatments). 
● Not Related – The AE is completely independent of investigational drug administration 
and device use, and/or evidence exists that the event is definitely related to another 
etiology. There must be an alternative, definitive etiology documented by the clinician. 
 
Spmd, on behalf of SBI ALApharma Canada Inc., will be responsible for reviewing all AE reports 
regarding the PI’s determination of the relatedness of the event. 
13.2.4. 
Outcome 
Outcome of the event will be defined according to the following:  
● Recovered/ Resolved: The event has fully resolved at the end of the study*.  
● Recovering/ Resolving: The event is improving but has not fully resolved at the end of the 
study*. 
● Recovered/ Resolved with sequelae: The event has resolved, but retained pathological 
conditions resulting from the prior disease or injury.  
● Not recovered/ not resolved: The event is ongoing at the end of the study*.  
● Fatal: This event is determined to be the cause of death.  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 85 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
● Unknown: Outcome information could not be obtained. 
*or at the time of last observation 
13.2.5. 
Expectedness 
13.2.5.1. 
Expectedness of Adverse Event associated with PD G 506 A 
An AE is considered ‘unexpected’ if it is not listed in IB Section 10.1 “Reference Safety 
Information”, or if it is not listed at the specificity or severity that has been observed. 
 
An AE will be considered unexpected if the: 
● nature,  
● severity, or  
● frequency  
of the event is not consistent with the Reference Safety Information previously described for the 
investigational drug/ product/ procedure.  
 
“Unexpected” also refers to AEs that are mentioned in the study protocol as occurring with a class 
of drugs or as anticipated from the pharmacological properties of the drug, but are not specifically 
mentioned as occurring with the particular drug under investigation. 
13.2.5.2. 
Expectedness of Adverse Events associated with Eagle V1.2 Imaging 
System 
An AE is considered ‘unexpected’ if it is not listed in Section 6.2.4 of this Protocol, or if it is not 
listed at the specificity or severity that has been observed. 
  
An AE will be considered unexpected if the: 
● nature,  
● severity, or  
● frequency  
of the event is not consistent with the Reference Safety Information previously described for the 
Investigational Device. 
 
There are no known or anticipated adverse device effects. 
13.2.5.3. 
Obligations of the PI 
13.2.5.3.1. 
Canada 
spmd, on behalf of SBI ALApharma Canada Inc., will be responsible for determining whether an 
SAE is expected or unexpected (see Figure 13.1). 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 86 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13.2.5.3.2. 
USA 
The US PI will be responsible for determining whether an SAE causally related with the 
Investigational Device is expected or unexpected to fulfill their reporting obligations regarding 
UADEs towards their IRB on Record (see Figure 13.2). 
13.2.5.4. 
Obligations of the Sponsor 
spmd, on behalf of SBI ALApharma Canada Inc., will be responsible for reviewing all SAE reports 
regarding the PI’s determination of the expectedness of the event and determining the 
expectedness. 
 
The Sponsor will also be responsible for determining whether and SAE is expected or unexpected.  
13.2.6. 
Unanticipated Problem  
The PI will be responsible for determining whether events (SAEs and non-AEs) meet the criteria 
of an unanticipated problem (UP) as defined in Section 13.1.5.  
 
In the event that the PI’s classification of the SAE is not an UP, however, SBI ALApharma Canada 
Inc. subsequently determines it is, SBI ALApharma Canada Inc. will report this determination to 
the PI and the PI will submit such reports to their REB/IRB of record. 
 
Sites will maintain a log of all Ups that to not meet the criteria of an (S)AE; this log will be filed 
in the TMF. 
13.2.7. 
Investigational Product Deficiencies  
An investigational product (drug or device) deficiency is defined as an ‘inadequacy of an 
investigational product with respect to its identity, quality, durability, reliability, usability, safety 
or performance including malfunction, use errors or inadequacy of supplied information or 
labelling’.  
13.3. Time Periods and Frequency for Event Assessment and Follow-Up 
The occurrence of an (S)AE may come to the attention of study personnel during study visits and 
interviews of a study participant presenting for medical care, or upon review by a study monitor. 
All AEs including local and systemic reactions not meeting the criteria for SAEs will be captured 
as described in Sections 13.2 and 13.4.2.  
 
Although the neurological AEs observed in the clinical trials of ALA HCl used for the visualization 
of glioma during resection surgery may be attributable to the greater amount of tissue resected in 
patients in the ALA arm as compared to control, Investigators are asked to assess for potential 
neurological AEs, in addition to other AEs, at each AE assessment time point. 
 
The PI will record all reportable events with start dates occurring any time after the participant has 
signed the informed consent form until the Week 2 Visit. If an (S)AE is recorded at the Week 2 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 87 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Visit the participant will continue to be assessed for an additional 7 (for non-serious AEs) or at 
least 30 calendar days (for SAEs) after the Week 2 visit. If liver enzymes are elevated at the Week 
2 visit (as defined in Section 12.7), the patient will be followed until such time that levels return 
to baseline. At each visit, the surgeon investigator will inquire about the occurrence of AE/SAEs 
since the last visit.  Events will be followed for outcome information (Section 13.2.4). SAEs will 
be followed until resolution or stabilization. Clinical laboratory tests (e.g. blood panels) and other 
relevant medical tests (e.g. ECG) may be ordered to investigate a (S)AE if clinically warranted. 
Events occurring after the Week 2 Visit will not be recorded or reported as part of the study 
protocol.  
13.4. Reporting Procedures 
This section and subsequent sub-sections describe: 
1. Documentation Procedures and Reporting Obligations to the Sponsor; 
2. Regulatory Reporting Obligations to the Competent Authorities (Health Canada & FDA) 
and the Ethics Committees (REBs & IRBs) 
13.4.1. 
Documentation Procedures and Reporting Obligations to the Sponsor 
13.4.1.1. 
Adverse Events 
The Investigator must document all AEs that occur during the observation period set in this 
protocol (Section 13.3) on the pages provided in the eCRF. Additional specific instructions may 
be provided in the investigator file and in the case report form itself. 
 
All AEs (whether serious or not) must be documented on the “Adverse Event” page of the Case 
Report Form (CRF). All AEs will be described using the sign, symptom, or medical diagnosis on 
the AE ICRF in standard medical terminology in order to avoid the use of vague, ambiguous, or 
colloquial expressions. Each AE will be defined as serious or non-serious according to the 
definitions in Section 13.1.2. The investigator will evaluate the severity of each AE and causal 
relationship of the event to the Investigational Device (Eagle V1.2 Imaging System)/ 
Investigational Drug (PD G 506 A)/Surgical Procedure/ Other study-specific procedures (assessed 
only by those with the training and authority to make a diagnosis), and time of 
resolution/stabilization of the event. All AEs occurring while on study beginning after the study 
patient has signed the informed consent form must be documented appropriately regardless of 
relationship. All AEs will be followed to adequate resolution, as defined by the participant’s 
treating surgeon.  
 
Changes in the severity of an AE will be documented to allow an assessment of the duration of the 
event at each level of severity to be performed. AEs characterized as intermittent require 
documentation of onset and duration of each episode.  
 
Adverse Events exempted from reporting: 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 88 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Any medical condition that is present at the time that the participant is screened will be considered 
as baseline and not reported as an AE. However, if the study participant’s baseline condition 
deteriorates during the study any time after administration of the investigational drug, it will be 
recorded as an AE. SAEs and Ups will be recorded in the safety data collection system throughout 
the study.  
13.4.1.2. 
Serious Adverse Event Reporting (Eagle V1.2 and PD G 506 A) 
Aes considered by the participant’s treating surgeon to be a SAE as defined in Section 13.1.2 
(regardless of relatedness) will be reported via the SAE Report Form within 24 hours of awareness 
to: 
 
spmd – safety strategies for health, Inc. 
50 Dunham Rd, Suite 3200 
Beverly, MA 01915 
Email: 
SBI-ALApharma-PhV@spmd-safety.com 
Fax: 
+1 978 338 0668 
 
 
13.4.1.3. 
Other Events to be reported within the same timelines as SAEs (PD G 
506 A only) 
13.4.1.3.1. 
Overdose, Abuse, Misuse, Medication Errors, Occupational Exposure and 
other uses outside what is foreseen in the protocol 
Definition overdose: Administration of a quantity of an investigational medicinal product given 
per administration or cumulatively which is above the maximum recommended dose according to 
the protocol dosing instructions . Clinical judgement should always be applied. 
 
Definition abuse: Persistent or sporadic, intentional excessive use of an investigational medicinal 
product, which is accompanied by harmful physical or psychological effects. 
 
Definition misuse: Situations where the investigational medicinal product is intentionally and 
inappropriately used not in accordance with the protocol dosing instructions. 
 
Definition medication error: Unintended failure in the drug treatment process that leads to or has 
the potential to lead to harm to the patient. 
 
Definition occupational exposure: The exposure to an investigational medicinal product, as a 
result of one’s professional or non-professional occupation. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 89 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Drug overdose, drug abuse, drug misuse, medication errors, occupational exposure and other uses 
outside what is foreseen in the protocol should be reported in the same format (i.e. on SAE Report 
Form) and within the same timelines as a SAE, even if they may not result in an adverse outcome. 
 
13.4.1.3.2. 
Reporting of Pregnancy 
If a participant becomes aware that they are pregnant following consenting to participate and prior 
to receiving the investigational drug, their participation in the study will be terminated 
immediately. If a participant becomes aware that they are pregnant following administration of the 
investigational drug but prior to completing the study, they will complete the study according to 
the protocol. The PI will be responsible for reporting such an event within 24h of becoming aware 
that the participant is pregnant to: 
 
spmd – safety strategies for health, Inc. 
50 Dunham Rd, Suite 3200 
Beverly, MA 01915 
Email: 
SBI-ALApharma-PhV@spmd-safety.com 
Fax: 
+1 978 338 0668 
 
via the SAE Report Form. 
 
The PI will request written permission to follow-up with the participant to pregnancy outcome. 
See Appendix 5 for more detailed information. 
 
Spmd on behalf of SBI ALApharma Canada Inc. will identify missing information and requests 
for follow-up will be sent directly to the Investigator. Spmd will inquire follow-up information in 
regular intervals form the investigators until all queries are resolved or not further information can 
be reasonably expected. 
 
All responses to queries and supply of additional information by the investigator should follow the 
same reporting route and timelines as the initial report. 
 
13.4.1.4. 
Investigational Product Complaints  
Investigators are responsible for reporting any investigation drug and investigational device 
deficiency encountered. Reporting of such deficiencies are required even when they do not 
directly or indirectly contribute or potentially could have contributed to a reportable AE. Reporting 
of deficiencies that meet the criteria of an (S)AE must be reported according to Sections 13.4.1 
and 13.4.2). The PI will be responsible for reporting all other deficiencies in a timely manner, and 
no later than 15 calendar days after becoming aware of the deficiency to: 
 
spmd – safety strategies for health, Inc. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 90 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
50 Dunham Rd, Suite 3200 
Beverly, MA 01915 
Email: 
SBI-ALApharma-PhV@spmd-safety.com 
Fax: 
+1 978 338 0668 
 
spmd will report all non-AE deficiencies to SBI ALApharma Canada Inc., who will investigate 
the deficiency and take corrective and preventative actions if warranted in accordance with GMP 
to protect the safety of participants, users, and other persons. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 91 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13.4.2. 
Regulatory Reporting of Adverse Events to Competent Authorities 
(Health Canada & FDA) and Ethic Committees (REBs & IRBs) 
13.4.2.1. 
Summary of Regulatory Reporting Obligations 
13.4.2.1.1. 
Canada 
 
Figure 13.1: 
(S)AE Reporting Algorithm for Canada (LT= life threatening) 
 
Q1: Is the AE serious? 
A: No  document in eCRF  no further actions required. 
B: Yes  document on SAE Report Form & send to spmd within 24h  document in eCRF  continue with Q2 
 
Q2: Is the event related to the Investigational Device (Eagle V1.2)? 
A: No  no further actions required 
 
B: Yes  fill out “Medical Device Problem Report Form for Health Care Professionals” and send to Health Canada within 72h  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 92 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
13.4.2.1.2. 
USA 
 
Figure 13.2: 
(S)AE Reporting Algorithm for USA (LT= life-threatening; bd= business days) 
 
13.4.2.2. 
PD G 506 A: SUSAR Reporting 
spmd, on behalf of SBI ALApharma Canada Inc. will be responsible for reporting all serious and 
unexpected adverse events, which are judged as having a reasonable suspected causal relationship 
to the Investigation Drug PD G 506 A (Suspected Unexpected Serious Adverse Reaction – 
SUSAR) to the Food and Drug Administration and Health Canada. 
 
Q1: Is the AE serious? 
A: No  document in eCRF  no further actions required. 
B: Yes  document on SAE Report Form & send to spmd within 24h  document in eCRF  continue with Q2 
 
Q2: Is the event related to the Investigational Device (Eagle V1.2)? 
A: No  no further actions required 
B: Yes  continue with Q3 
 
Q3: Is the event expected for the Investigational Device (Eagle V1.2)? 
A: No, event is unexpected  report event as UADE to IRB within 10 working days  
B: Yes, event is expected  not further actions 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 93 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Spmd, on behalf of SBI ALApharma Canada Inc. will be responsible for providing the CIOMS I 
Form (Canada) MedWatch Form (USA) for all SUSARs to the PI for reporting to their REB/IRB 
of Record according to local requirements. 
 
The PI will report: 
● All fatal/ life-threatening SUSARs within 7 calendar days; and  
● All other SUSARs within 15 calendar days; 
 
to their REB/IRB on Record according to local requirements. 
 
13.4.2.3. 
Eagle V1.2 Imaging System: SAR/ UADE Reporting 
spmd, on behalf of SBI ALApharma Canada Inc. will be responsible for reporting all serious 
adverse events, which are judged as having a reasonable suspected causal relationship to the 
Investigational Device Eagle V1.2 Imaging System (Serious Adverse Reaction – SAR) to Health 
Canada. 
 
Spmd, on behalf of SBI ALApharma Canada Inc. will be responsible for reporting all serious and 
unexpected adverse events, which are judged as having a reasonable suspected causal relationship 
to the Investigational Device Eagle V1.2 Imaging System (Unanticipated Adverse Device Effect 
– UADE) to the Food and Drug Administration. 
 
The Canadian PI will report: 
● All SARs within 72 hours to Health Canada using the “Medical Device Problem Report 
Form for Health Care Professionals”; and  
● All fatal/ life-threatening UPs/UADEs within 7 calendar days to their REB on Record 
according to local requirements 
● All other UPs/UADEs within 15 calendar days to their REB on Record according to local 
requirements. 
 
Spmd, on behalf of SBI ALApharma Canada Inc. will be responsible for providing the CIOMS I 
Form (Canada) for all UADEs to the PI for reporting to their REB of Record according to local 
requirements. 
 
The US PI will report: 
● All UADEs within 10 business days to their IRB of Record according to local requirements. 
13.4.2.4. 
Unanticipated Problem (UP) Reporting 
UPs that do not meet the criteria of an AE (e.g. events that place the participant or others at a 
greater risk of physical or psychological harm than was previously anticipated, or have 
implications for the conduct of the study or the integrity of research data) will be reported by the 
PI to their REB/IRB of Record as well as spmd at:  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 94 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
spmd – safety strategies for health, Inc. 
50 Dunham Rd, Suite 3200 
Beverly, MA 01915 
Email: 
SBI-ALApharma-PhV@spmd-safety.com 
Fax: 
+1 978 338 0668 
 
 The following are examples of non-AE Ups which would require reporting the REB/IRB: 
 
● An increase in the rate of occurrence of an expected SAE that is judged by the PI or sponsor 
to be clinically important 
● A major safety finding from a newly completed animal study that indicated significant risk 
to human participants or the specific population being studied 
● Breaches of privacy or confidentiality 
 
13.5. Study Pausing Rules 
Administration of investigational drug within the study will be paused when three grade 3 AEs 
determined to be “probably” or “definitely” related (as determined by the Investigator) to the 
investigational drug or three grade 3 AEs determined to be “probably” or “definitely” related to 
the investigational device are reported in the clinical database. SBI ALApharma Canada Inc. and 
spmd will receive an automatic notification from the clinical database indicating the 3rd such AE 
has been recorded. Spmd will inform investigators within 1 business day of the third grade 3 
“possibly” or “definitely” related event being reported, and administration of study drug and 
enrolment of new study patients will be stopped. In parallel, spmd will inform the DSMB and 
CATO-SMS that the study has been paused. Within 1 business day of being notified that the study 
has been paused, CATO-SMS will provide the DSMB and spmd with AE listing reports. The 
DSMB will provide recommendations to SBI ALApharma Canada Inc. and spmd for proceeding 
with the study, including a recommendation for future suspension of enrolment and study drug 
administration if additional drug- or device-related (“probably” or “definitely”) AEs are reported. 
Spmd will inform the Investigators on the decision of the DSMB. SBI ALApharma Canada Inc. 
will inform the appropriate regulatory authorities of the temporary pause and the disposition of the 
study. 
 
Administration of the investigational drug within the study will also be suspended if any drug- or 
device-related (“possibly”, “probably” and “definitely”; as determined by the Investigator or 
Sponsor) SAE is reported to spmd. Spmd will notify SBI ALApharma Canada Inc. and 
investigators within 1 business day of this SAE being reported. Enrolment of new study patients 
and administration of study drug will be stopped. In parallel, spmd will inform the DSMB and will 
provide the DSMB with the SAE report. The DSMB will provide recommendations for proceeding 
with the study to SBI ALApharma Canada Inc. and spmd. Spmd will inform the Investigators on 
the decision of the DSMB. ALApharma Canada Inc. will inform the appropriate regulatory 
authorities of the temporary pause and the disposition of the study. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 95 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Part A is an open-label training phase of the study to refine workflow and provide training.  SBI 
ALApharma Canada Inc., the Study Steering Committee and the DSMB will be closely monitoring 
the workflow issues as patients are enrolled and will determine when this process has been 
optimized.  It is anticipated that no more than 75 subjects will be required for Part A. If necessary, 
enrollment may be temporarily suspended after completion of the first 30 patients in Part A prior 
to initiating Part B so that sample size estimation can be confirmed and any other necessary 
amendments can be incorporated into the protocol.  
13.6. Safety Oversight 
Safety oversight will be under the direction of the DSMB composed of individuals with the 
appropriate expertise, such as but not limited to: 
● Medical Oncology, Solid Tumor 
● Surgical Oncology 
● Radiation Oncology 
● Clinical Research Nursing 
● Biostatistics 
  
The DSMB will meet at least semi-annually to assess safety data. The DSMB will operate under 
the rules of an approved charter that will be written and reviewed at the organizational meeting of 
the DSMB. Each data element that the DSMB needs to assess will be clearly defined at the 1st 
DSMB meeting. The DSMB will provide its input, in the form of recommendations directly to SBI 
ALApharma Canada Inc. and site PIs. 
14. Clinical Monitoring 
Clinical site monitoring is conducted to ensure that the rights and well-being of human subjects 
are protected, that the reported trial data are accurate, complete, and verifiable, and that the conduct 
of the trial is in compliance with the currently approved protocol/amendment(s), with GCP, and 
with applicable regulatory requirement(s).  
 
The study monitor, in accordance with the sponsor’s requirements, will ensure that the study is 
conducted and documented properly by carrying out the activities outlined in International Council 
for Harmonisation E6, Section 5.18.4 and as detailed in the study Monitoring Plan. 
 
Types of monitoring will include: 
● On-site and/or monitoring 
● Centralized monitoring, including:  
o targeted data verification 
o confirmation of completion of eCRFs 
o query resolution 
o eligibility criteria review 
o adverse event and concomitant medication review 
o screening/enrolment data 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 96 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
o review of anonymized FL imaging data for the purposes of identifying sites 
requiring re-training  
o statistical monitoring to identify missing or invalid data and unusual data patterns 
which may indicate additional on-site monitoring and/or additional training is 
required 
 
Each clinical site will perform internal quality management of study conduct, data collection, 
documentation and completion. Independent audits may be performed as required by the 
sponsor.  
15. Statistical Considerations 
15.1. General Considerations 
Descriptive summaries of variables will be provided where appropriate.  For continuous variables, 
the number of non-missing values (n) and the median, mean, standard deviation, minimum, and 
maximum will be tabulated.  For categorical variables, the counts and proportions of each value 
will be tabulated.  Confidence intervals will also be provided as appropriate. All statistical tests 
will be performed at the 0.05 level. 
 
Further details on all analyses will be provided in the statistical analysis plan (SAP). 
15.2. Sample Size Estimation 
The sample size of Part A has been chosen on pragmatic grounds to be approximately 75 study 
patients.  The number of patients ultimately included in Part A will be decided by the Steering 
Committee and the Sponsor based on the perceived understanding of the protocol by clinical sites 
and the feedback obtained during the Part A training phase. Part A will not be randomized; all 
study patients in Part A will receive PD G 506 A. Data acquired from Part A will be used to 
confirm the Investigators’ understanding of fluorescence guided resection (FGR) procedures in the 
protocol and to confirm the sample size for Part B. Only data from participants in Part B will be 
used for the analyses of primary and secondary efficacy. Data from all patients in both Part A and 
Part B will be used for the evaluation of safety and analyses will include assessments of data from 
Part A and Part B separately, as well as all study patients (Part A and Part B together). 
 
 
 
 
 
 
 
 
 
P(1.1) Conversion Rate among all 
patients =  
 
# patients with at least one 
histopathology-positive margin 
following SoC and histopathology 
negative final margins after FGR 
All patients imaged (Arm 2) 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 97 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
The sample size in Part B of the study is only driven by the primary endpoint P(1.1). The primary 
endpoint is intended to determine the percentage of patients with at least one histopathology-
positive margin after SoC who then have all histopathology-negative margins after FGR 
(conversion rate among all patients in Arm 2). To demonstrate benefit, the point estimate P(1.1) 
must be statistically significantly greater than 1%. By meeting this primary endpoint, we will 
demonstrate that FGR adds clinical benefit above and beyond what is achieved with SoC.  
 
Based on the expected 3% conversion rate estimate for P(1.1), a total of 500 patients will be 
required in Part B of the study to demonstrate statistical significance at a Type 1 error level of 0.05 
with 90% power using a 2-sided Z test for a binomial proportion assuming a null hypothesis 
proportion of 1%. 
 
Using a randomization ratio of 1:6 (Arm 1-SoC; Arm 2: PD G 506 A), a total sample size of 525 
patients (Arm 1: N=72; Arm 2: N=428) would be required, accounting for a 5% loss to follow-up. 
The primary efficacy analysis will be based on the mITT (modified intention-to-treat population), 
which includes all Part B patients randomized to Arm 2 who undergo surgery and have recorded 
surgical histopathology data.   
 
15.3. 
Definitions of Units of Analysis 
The definitions of TP, TN, FP, and FN at the units of analysis of orientation, patient and primary 
specimen are provided in Table 15.1. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 98 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Table 15.1: Levels of Analysis and Diagnostic Performance Definitions 
Diagnostic Performance 
Parameter 
Orientation Level 
Analysis 
Patient Level 
Analysis 
Primary Specimen Level 
Analysis 
Level of Analysis 
Definition 
An orientation-level 
analysis evaluates each 
orientation as a single data 
point with a total of at 
least 5 orientations per 
patient (in cases where an 
area of skin is removed 
with the lump, there may 
be n = 5 data points per 
patient). Orientation-level 
analyses evaluate efficacy 
based on the performance 
characteristics in each 
anatomical location of the 
entire surgical cavity. 
 
An orientation is 
comprised of two 
contiguous tissue surfaces 
that have been separated 
by a scalpel (or other 
surgical tool e.g., 
electrocautery) during 
tissue resection.  The 
tissue surfaces are from 
the primary specimen, 
cavity shave specimens, 
and the final cavity 
surface. An orientation is 
described based on the 
anatomical location of the 
contiguous tissues (e.g. S, 
M, P, L, I, A).
A patient-level 
analysis evaluates 
each patient as a 
single data point. 
A primary specimen level 
analysis evaluates each 
biopsy from the bisected 
primary specimen (i.e., 
primary tumor mass) as a 
single data point.  At 
most, there will be one 
FL-positive and one FL-
negative biopsy per 
patient included in the 
analysis. 
True Positive 
Orientation that is 
fluorescence positive and 
histopathology positive. 
Patient has at least 
one TP orientation 
without any FN 
orientations  
 
Fluorescence is observed 
in the primary specimen 
biopsy that is 
histopathology-positive 
for carcinoma 
True Negative 
FL-negative orientation 
with final margin for that 
orientation from cavity 
shave specimens or 
primary specimen (if no 
shaves taken) negative on 
histopathology
Patient has all TN 
orientations 
No fluorescence is 
observed in the primary 
specimen biopsy that is 
histopathology-negative 
for carcinoma 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 99 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Diagnostic Performance 
Parameter 
Orientation Level 
Analysis 
Patient Level 
Analysis 
Primary Specimen Level 
Analysis 
False Positive 
FL-positive orientation 
with final margin for that 
orientation from cavity 
shave specimens or 
primary specimen (if no 
shaves taken) negative on 
histopathology
Patient has at least 
one FP orientation 
without any FN or 
TP orientations 
Fluorescence is observed 
in the primary specimen 
biopsy that is 
histopathology-negative 
for carcinoma 
False Negative 
FL-negative orientation 
with final margin for that 
orientation from cavity 
shave specimens or 
primary specimen (if no 
shaves taken) positive on 
histopathology
Patient has at least 
one FN orientation 
 
 has at least  
No fluorescence is 
observed in the primary 
specimen biopsy and the 
biopsy is histopathology-
positive for carcinoma  
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 100 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
15.4. Analysis Populations 
The analysis populations and timepoints are described below. 
15.4.1. 
mITT Analysis Population 
The mITT population includes all subjects who are randomized (Arm 1 and Arm 2), dosed (Arm 
2 only), have the fluorescence imaging performed (Arm 2 only) and have recorded surgical 
pathology data.  The mITT will be used for all patient-level and orientation-level analyses. 
Missing data will be imputed, and full detail will be provided in the Statistical Analysis Plan. 
 
15.4.2. 
Safety Population 
The safety population includes all subjects who are randomized (Arm 1 and Arm 2) and receive 
PD G 506 A (Arm 2 only); this population will be used for all safety analyses. 
15.4.3. 
Primary Specimen Biopsy Population 
The primary specimen biopsy population includes all tissue samples where collection of biopsies 
from the primary specimen is performed in accordance with the primary specimen biopsy 
collection algorithm (Table 12.1).  The Point-level Population will be used for the exploratory 
analyses. 
15.4.4. 
Timepoints of Efficacy Analyses 
15.4.4.1. 
Fluorescence Assessment at the End of SoC  
Efficacy endpoints that evaluate diagnostic performance of PD G 506 A at the “initial fluorescence 
assessment at end of SoC” include fluorescence assessments of the outside surface(s) of the last 
resected SoC-driven cavity shave specimens (or the outside surface of the primary specimen if 
no cavity shave specimens are obtained) and fluorescence assessments of the final cavity after 
SoC.   
Histopathology assessments for presence or absence of carcinoma are obtained from the outside 
surface(s) of the last resected SoC driven cavity specimen(s) removed (or the outside surface of 
the primary specimen if no cavity shave specimens are obtained) and the inside surface(s) of the 
first (innermost) FL-driven cavity shave specimen(s), if collected (Figure 15.1). 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 101 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
Figure 15.1. 
Orientations Included in “Initial Fluorescence Assessment at the End of SoC” Endpoints 
and Analyses 
15.4.4.2. 
Fluorescence Assessment During Fluorescence Guided Resection (FGR) 
Efficacy endpoints that evaluate diagnostic performance of PD G 506 A “after SoC” include 
fluorescence assessments of the outside surface(s) of the last resected SoC-driven cavity shave 
specimens (or the outside surface of the primary specimen if no cavity shave specimens are 
obtained) fluorescence assessments of the inside surface(s) and outside surface(s) of all FL-
guided cavity shave specimens, and fluorescence assessment of the final cavity after FGR. 
Histopathology assessments for presence or absence of carcinoma are obtained from the outside 
surface(s) of the last resected FL-guided cavity shave specimen(s) removed (Error! Reference 
source not found.). 
 
 
 
 
Figure 15.2. 
Orientations Included in “Fluorescence Assessment during Fluorescence Guided 
Resection (FGR)” Endpoints and Analyses  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 102 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 Completion of FGR and BCS SurgeryEfficacy endpoints that evaluate the diagnostic 
performance of PD G 506 A at the “completion of FGR and BCS surgery ” include fluorescence 
assessment of the final cavity and the outside surface(s) of the last resected FL-driven cavity 
shave specimens, the outside surface(s) of the last resected SoC-driven cavity shave specimens 
(if no FL-driven cavity shave specimens are taken for the particular orientation), and the outside 
surface(s) of the primary specimen (if no cavity shave specimens are obtained for the particular 
orientation) (Figure 15.2). Histopathology assessments for presence or absence of carcinoma are 
obtained from the outside surface(s) of the last resected specimen(s) removed. 
 
 
Figure 15.2: Orientations Included in “Completion of FGR and BCS” Endpoints and Analyses 
15.4.4.3. 
Entire Resection 
Efficacy endpoints that evaluate diagnostic performance of PD G 506 A over the entire resection, 
incorporate fluorescence assessments of all specimen surfaces and the final cavity. 
Histopathology assessments for presence or absence of carcinoma are obtained from the outside 
surface(s) of the primary specimen, and both inside and outside surfaces of cavity shave 
specimens (Figure 15.3). 
 
 
 
Figure 15.3. 
Orientations Included in “Entire Resection” Endpoints and Analyses 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 103 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
15.5. Formulas 
Detailed formulas for the primary, secondary, and exploratory endpoints can be found in Section 
7. 
15.6. Primary and Key Secondary Endpoint Analyses 
There is one primary endpoint and three co-key secondary endpoints for this study: P(1.1), 
P(2.1), P(2.2) and P(2.3)  See Section 7 for the formulas used. These four endpoints will each be 
tested at the 0.05 level. Only the primary efficacy endpoint test must be significant for the study 
to be considered positive. Information on the analyses and hypotheses are provided below. 
 
15.6.1. 
Primary Endpoint: 
 
1. P(1.1): Conversion Rate Among All Patients 
 
The primary endpoint, P(1.1), is the percentage of participants with negative-margins 
following FGR among all patients following SoC. Participants that are converted from margin-
positive after SoC to margin-negative after FGR will be considered a ‘clinical success’ and 
will be counted towards the numerator of the primary endpoint. If at the completion of Eagle 
V1.2 Imaging System assessment red PpIX FL is still observed on the final margins after 
FGR and/or in the surgical cavity and no further resection is performed, the anatomical 
surface(s) of residual fluorescence (i.e., S, M, P, L, I, A) and the reason for not performing 
further FGR is recorded. In such cases, orientation(s) involving FL observed in the final 
margin after FGR and/or in the surgical cavity will not contribute to the determination of a 
histopathologically-negative final margin for this primary endpoint. 
 
Participants that are margin-positive after SoC and remain margin-positive after FGR will be 
considered a ‘clinical failure’ and will be counted towards the denominator of the primary 
endpoint proportion. See Section 7.1 for the formula. 
 
The number and percentage of patients with negative-margins following FGR among patients 
with positive margins following SoC will be provided along with a two-sided 95% confidence 
interval calculated using the Wilson (score) method. The analysis will be performed using the 
mITT population.  
 
The statistical hypothesis is as follows: Ho : P(1.1) ≤ 1% vs Ha = P(1.1) > 1% 
 
If the lower bound of the Wilson (score) confidence interval is above 1%, the endpoint will be 
assumed to be statistically significant. The result is expected to be >3%. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 104 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
15.6.2. 
Key Secondary Endpoints: 
The secondary endpoints will be tested sequentially at the 0.05 level. 
 
2. P(2.1) Conversion Rate among SoC margin-positive patients 
 
The secondary endpoint, P(2.1), is the percentage of participants with negative-margins following 
FGR among patients with positive margins following SoC. Participants that are converted from 
margin-positive after SoC to margin-negative after FGR will be considered a ‘clinical success’ and 
will be counted towards the numerator and the denominator of this secondary endpoint. If at the 
completion of Eagle V1.2 Imaging System assessment, red PpIX FL is still observed on the final 
margins after FGR and/or in the surgical cavity and no further resection is performed, the 
anatomical surface(s) of residual fluorescence (i.e., S, M, P, L, I, A) and the reason for not 
performing further FGR is recorded. In such cases, orientation(s) involving FL observed in the 
final margin after FGR and/or in the surgical cavity will not contribute to the determination of a 
histopathologically-negative final margin for this primary endpoint. 
 
Participants who are margin-positive after SoC and remain margin-positive after FGR will be 
considered a ‘clinical failure’ and will be counted towards the denominator of the primary endpoint 
proportion. See Section 7.1 for the formula. 
 
The number and percentage of patients with negative-margins following FGR among patients with 
positive margins following SoC will be provided along with a two-sided 95% confidence interval 
calculated using the Wilson (score) method. The analysis will be performed using the mITT 
population.  
 
 
The statistical hypothesis is as follows: Ho: P(2.1) ≤ 3% vs Ha = P(2.1) > 3%. 
If the lower bound of the Wilson (score) confidence interval is above 3%, the endpoint will be 
assumed to be statistically significant.  The result is expected to be >15%. 
 
3. P(2.2): Patient-level Specificity 
 
P(2.2) will be calculated on a patient-level using the mITT Population. 
 
P(2.2) will be calculated as follows: Specificity = 100% x (TNpatient / (TNpatient + FPpatient)) 
 
The patient-level specificity estimate along with a two-sided 95% confidence interval calculated 
using the Wilson (score) method will be provided. 
 
The statistical hypothesis is as follows: Ho: P(2.2) ≤ 70% vs Ha: P(2.2) > 70%  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 105 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
If the lower bound of the confidence interval is above 70%, the endpoint will be assumed to be 
statistically significant.  The patient-level specificity is expected to be >80%. 
 
4. P(2.3): Patient-level Sensitivity  
 
P(2.3) will be calculated on a patient-level using the mITT Population. 
 
P(2.3) will be calculated as follows: Sensitivity = 100% x (TPpatient / (TPpatient + FNpatient)) 
 
The patient-level sensitivity estimate along with a two-sided 95% confidence interval calculated 
using the Wilson (score) method will be provided. 
 
The statistical hypothesis is as follows: Ho: P(2.3) ≤ 50% vs Ha: P(2.3) > 50%  
 
If the lower bound of the confidence interval is above 50%, the endpoint will be assumed to be 
statistically significant.  The patient-level sensitivity is expected to be >70%. 
 
15.7. Secondary and Exploratory Endpoint Analysis  
Secondary and exploratory endpoints based on patient-level data will be analyzed using similar 
methods to the primary and key secondary endpoints, using Wilson (score) confidence intervals.  
Re-operation rates will be compared between treatments using Fisher’s exact tests. 
 
Secondary and exploratory endpoints based on orientation-level, primary specimen-level, and 
point-level data will be analyzed using a weighted estimator, proposed by Lee and Dubin (Lee and 
Dubin, 1994), which takes into account the correlation (clustering) of the margins within a patient. 
This method will be used to calculate the estimates and two-sided 95% confidence intervals. 
 
Descriptive statistics will be used to summarize the weight of resected tissue specimens (SoC 
specimens vs. FGR specimens). Mean total tissue weight (Arm 1 vs. Arm 2) will be compared 
using a two-sample t-test. 
 
Breast-Q survey results will be summarized using actual values and change from baseline values 
using descriptive statistics. The difference in change scores between Arm 1 and Arm 2 will be 
summarized descriptively and presented along with a 95% confidence interval on the difference in 
means.  For the Breast-Q survey results at 3 months, if the lower bound of this confidence interval 
is ≥ - 10 then non-inferiority will be claimed. Results at 6 months and 1 year will be described 
with summary statistics. For the analysis of Breast-Q survey results, the previously defined 
minimal important difference as the reference point for what patients consider a meaningful change 
in Breast-Q scores. The minimal important difference is defined as: “The smallest difference in 
score in a domain of interest that patients perceive as beneficial and which would mandate, in the 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 106 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
absence of troublesome side effects and excessive cost, a change in the patient’s (health care) 
management”70. While patients in Arm 2 are anticipated to have marginally more tissue removed 
as a result of FGR as compared to SoC [analyzed in secondary endpoint P(2.16)], it is not 
anticipated that resection of this additional tissue will negatively affect the patient’s satisfaction 
with the appearance of their breasts as compared to patients in Arm 1. For secondary endpoint 18 
[P(2.18a) & P(2.18b)] we have defined a mean difference in change score ≤ -10 (Arm 1 – Arm 2) 
as meeting our criterion for non-inferiority. Previous studies have reported a minimal important 
difference in Breast-Q scores of 7-871 for the breast satisfaction subscale in breast reconstruction 
patients. To date there are no known publications addressing the minimal important difference 
using the Breast Conserving Therapy module of the Breast-Q survey. While a change score of ≥ -
10 would represent a negative change in breast satisfaction, this risk may still be considered 
acceptable to patients if the intervention is associated with improved clinical outcomes (e.g. 
decreased probability of having positive margins).  
 
Depth of tumor analyses of tissue specimens identified by FL imaging will be summarized using 
descriptive statistics. 
 
Exploratory subgroup analyses will be performed on key efficacy endpoints.  Subgroups will 
include patients who underwent sentinel node mapping with blue dye injection vs. those who did 
not, and patients who underwent comprehensive circumferential shaves during surgery vs. those 
who had selective shaves during BCS.  
15.8. Safety Analysis 
The safety of the procedure and device will be assessed for both Arm 1 and Arm 2.  The rates of 
procedure-related WHO grade 3-5 adverse events, drug-related WHO grade 3-5 adverse events, 
and device-related WHO grade 3-5 adverse events will be summarized descriptively by treatment 
arm.  Additional summaries may be performed.  Full details will be provided in the SAP. 
16.      Data Management 
Data management will be performed according to the Data Management Plan to ensure the 
accuracy, quality and integrity of the data.  
 
eCRFs will be used to capture study assessments and data. The study coordinator or other delegated 
study staff will enter data from source documents into the eCRFs. Training will be provided for 
the electronic data capture (EDC) system. All study staff using the EDC system must have the 
necessary education, training, and experience or any combination of these. The investigator will 
be responsible for documenting employee education, training, and previous experience that pertain 
to the EDC system for all site staff using the EDC system. The investigator must maintain adequate 
security of the EDC system, including documentation that all users have been trained and a list of 
authorized users. To ensure all data entries can be tracked, all personnel responsible for data entry 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 107 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
must obtain a unique user identification (user ID) and password before any data can be entered in 
the eCRFs. Authorized study staff will be assigned a unique user ID only after receiving training.  
 
The investigator must make study data accessible to the site monitor, other authorized 
representatives of the sponsor, and the appropriate regulatory authority inspectors. The eCRF for 
each subject will be checked against source documents at the site by the site monitor, and a final 
copy of the eCRF will be signed by the investigator with an electronic signature. A copy of the 
final eCRFs will be provided to the investigator in PDF after study closure to be kept in the 
investigator’s study files. See the Data Management Plan for additional details.  
17. Deviation from the Clinical Investigation Plan 
17.1. Procedures for Reporting Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol, GCP, or Study Manual 
of Procedures requirements. The noncompliance may be either on the part of the participant, the 
investigator, or the study site staff. As a result of deviations, corrective actions are to be developed 
by the site and implemented promptly. 
 
It is the responsibility of the site to use continuous vigilance to identify and report deviations within 
5 working days of identification of the protocol deviation. All deviations must be addressed in 
study source documents and reported to SBI ALApharma Canada Inc.. Should any deviations from 
the protocol occur, these will be reviewed by SBI ALApharma Canada Inc. for their clinical 
significance. Protocol deviations must be sent to the local REB/IRB per their guidelines. The site 
PI/study staff is responsible for knowing and adhering to their REB/IRB requirements.  
18. Amendments to the Clinical Investigation Plan 
18.1.      Procedures for Reporting Amendments  
No changes to the protocol or Study Manual of Procedures will be permitted (except when specific 
to the protection of the life or physical well-being of a subject in an emergency) without the written 
approval from SBI ALApharma Canada Inc. and the governing REB/IRB. If the event is performed 
without written approval from all parties, the investigator may be terminated from the study.  
 
The investigator will be responsible for submitting sponsor-approved amendments in a timely 
fashion to the REB/IRB.  SBI ALApharma Canada Inc.  will be responsible for notifying/seeking 
approval for any amendments requiring notification of or approval from the governing regulatory 
authority (e.g. Health Canada and/or FDA). SBI ALApharma Sites will notify sites if recruitment 
should be put on hold while an amendment is being reviewed.  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 108 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
19. Data Handling and Record Keeping 
19.1. Data Collection and Management Responsibilities  
Data collection is the responsibility of the clinical trial staff at the site under the supervision of the 
site PI. The investigator is responsible for ensuring the accuracy, completeness, legibility, and 
timeliness of the data reported.  
 
Paper source documents include: 
o Signed informed consent forms  
o Study data collection tools (e.g. Pathology Data Collection Tool), may also be electronic  
o Participant’s medical files (if maintained in paper format) 
o Investigational product accountability records 
 
Electronic source documents include: 
o Participant’s medical files (if maintained in electronic format; e.g. clinic notes, surgical 
notes, surgical pathology report, etc.) 
o Study data collection tools (e.g. Intraoperative Data Collection Tool, Pathology Data 
Collection Tool), may also be paper if electronic is not available 
o Eagle V1.2 Imaging System data  
 
Data reported in the eCRF derived from source documents should be consistent with the source 
documents or the discrepancies should be explained and captured in a progress note and 
maintained in the participant’s official study record.  
 
Clinical data will be entered into the EDC system by sites. The EDC system used for this study 
will be IBM Clinical Development, a 21 CFR Part 11-compliant data capture system. CATO SMS 
will be responsible for data management activities. The data system includes password protection 
and internal quality checks, such as automatic range checks, to identify data that appear 
inconsistent, incomplete, or inaccurate. Clinical data will be entered directly from the source 
documents (participant medical files). 
 
Imaging data (including video and image files) will be uploaded into an electronic image database 
by sites. BioTel Research will be responsible for developing and managing the image database.  
19.2. Study Records Retention 
In Canada, essential study documents will be maintained for a period of 25 years, in accordance 
with section C.05.012 of Canada’s Food and Drug Regulations - Division 5 “Drugs for clinical 
trials involving human subjects''.   
 
In the USA, all study documents are required to be retained for a minimum of 2 years after the last 
approval of a marketing application and until there are no pending or contemplated marketing 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 109 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
applications or until at least 2 years have elapsed since the formal discontinuation of clinical 
development of the investigational device and/or agent in accordance with 21 CFR Parts 312 and 
812. To meet this requirement essential study documents will be maintained for a period of at least 
7 years from the date that the study is closed.  No records will be destroyed without the written 
consent of SBI ALApharma Canada Inc. It is the responsibility of SBI ALApharma Canada Inc. 
to inform the investigator when these documents no longer need to be retained. 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 110 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
20. References 
 
1. 
Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, Klimberg S, Chavez-
MacGregor M, Freedman G, Houssami N, Johnson PL, Morrow M. Society of surgical 
oncology-american society for radiation oncology consensus guideline on margins for 
breast-conserving surgery with whole-breast irradiation in stages i and ii invasive breast 
cancer. International journal of radiation oncology, biology, physics. 2014;88:553-564 
2. 
Morrow M, Van Zee KJ, Solin LJ, Houssami N, Chavez-MacGregor M, Harris JR, 
Horton J, Hwang S, Johnson PL, Marinovich ML, Schnitt SJ, Wapnir I, Moran MS. 
Society of surgical oncology-american society for radiation oncology-american society of 
clinical oncology consensus guideline on margins for breast-conserving surgery with 
whole-breast irradiation in ductal carcinoma in situ. Ann Surg Oncol. 2016;23:3801-3810 
3. 
Moran MS, Schnitt SJ, Giuliano AE, Harris JR, Khan SA, Horton J, Klimberg S, Chavez-
MacGregor M, Freedman G, Houssami N, Johnson PL, Morrow M. Society of surgical 
oncology-american society for radiation oncology consensus guideline on margins for 
breast-conserving surgery with whole-breast irradiation in stages i and ii invasive breast 
cancer. Ann Surg Oncol. 2014;21:704-716 
4. 
Porter G, Wagar B, Bryant H, Hewitt M, Wai E, Dabbs K, McFarlane A, Rahal R. Rates 
of breast cancer surgery in canada from 2007/08 to 2009/10: Retrospective cohort study. 
CMAJ Open. 2014;2:E102-108 
5. 
Breast cancer surgery in canada, 2007 - 2008 to 2009 - 2010. Canadian Institute for 
Health Information. 2012;Ottawa, Ont.: CIHI, 2012 
6. 
Wilke LG, Czechura T, Wang C, Lapin B, Liederbach E, Winchester DP, Yao K. Repeat 
surgery after breast conservation for the treatment of stage 0 to ii breast carcinoma: A 
report from the national cancer data base, 2004-2010. JAMA Surg. 2014;149:1296-1305 
7. 
Landercasper J, Borgert AJ, Fayanju OM, Cody H, 3rd, Feldman S, Greenberg C, 
Linebarger J, Pockaj B, Wilke L. Factors associated with reoperation in breast-conserving 
surgery for cancer: A prospective study of american society of breast surgeon members. 
Ann Surg Oncol. 2019;26:3321-3336 
8. 
Waljee JF, Hu ES, Newman LA, Alderman AK. Predictors of re-excision among women 
undergoing breast-conserving surgery for cancer. Ann Surg Oncol. 2008;15:1297-1303 
9. 
Clough KB, Benyahi D, Nos C, Charles C, Sarfati I. Oncoplastic surgery: Pushing the 
limits of breast-conserving surgery. The breast journal. 2015 
10. 
Agostinho JL, Zhao X, Sun W, Laronga C, Kiluk JV, Chen DT, Lee MC. Prediction of 
positive margins following breast conserving surgery. Breast. 2015;24:46-50 
11. 
Parvez E, Hodgson N, Cornacchi SD, Ramsaroop A, Gordon M, Farrokhyar F, Porter G, 
Quan ML, Wright F, Lovrics PJ. Survey of american and canadian general surgeons' 
perceptions of margin status and practice patterns for breast conserving surgery. The 
breast journal. 2014;20:481-488 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 111 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
12. 
Biglia N, Ponzone R, Bounous VE, Mariani LL, Maggiorotto F, Benevelli C, Liberale V, 
Ottino MC, Sismondi P. Role of re-excision for positive and close resection margins in 
patients treated with breast-conserving surgery. Breast. 2014;23:870-875 
13. 
Wei S, Kragel CP, Zhang K, Hameed O. Factors associated with residual disease after 
initial breast-conserving surgery for ductal carcinoma in situ. Human pathology. 
2012;43:986-993 
14. 
Lovrics PJ, Gordon M, Cornacchi SD, Farrokhyar F, Ramsaroop A, Hodgson N, Quan 
ML, Wright F, Porter G. Practice patterns and perceptions of margin status for breast 
conserving surgery for breast carcinoma: National survey of canadian general surgeons. 
Breast. 2012;21:730-734 
15. 
Thill M, Roder K, Diedrich K, Dittmer C. Intraoperative assessment of surgical margins 
during breast conserving surgery of ductal carcinoma in situ by use of radiofrequency 
spectroscopy. Breast. 2011;20:579-580 
16. 
Hennigs A, Fuchs V, Sinn HP, Riedel F, Rauch G, Smetanay K, Golatta M, Domschke C, 
Schuetz F, Schneeweiss A, Sohn C, Heil J. Do patients after reexcision due to involved or 
close margins have the same risk of local recurrence as those after one-step breast-
conserving surgery? Annals of Surgical Oncology. 2016;23:1831-1837 
17. 
Ananthakrishnan P, Balci FL, Crowe JP. Optimizing surgical margins in breast 
conservation. Int J Surg Oncol. 2012;2012:585670 
18. 
Houssami N, Macaskill P, Marinovich ML, Dixon JM, Irwig L, Brennan ME, Solin LJ. 
Meta-analysis of the impact of surgical margins on local recurrence in women with early-
stage invasive breast cancer treated with breast-conserving therapy. Eur J Cancer. 
2010;46:3219-3232 
19. 
Pleijhuis RG, Graafland M, de Vries J, Bart J, de Jong JS, van Dam GM. Obtaining 
adequate surgical margins in breast-conserving therapy for patients with early-stage 
breast cancer: Current modalities and future directions. Ann Surg Oncol. 2009;16:2717-
2730 
20. 
Millon SR, Ostrander JH, Yazdanfar S, Brown JQ, Bender JE, Rajeha A, Ramanujam N. 
Preferential accumulation of 5-aminolevulinic acid-induced protoporphyrin ix in breast 
cancer: A comprehensive study on six breast cell lines with varying phenotypes. Journal 
of Biomedical Optics. 2010;15:018002 
21. 
Loh CS, MacRobert AJ, Bedwell J, Regula J, Krasner N, Bown SG. Oral versus 
intravenous administration of 5-aminolaevulinic acid for photodynamic therapy. Br J 
Cancer. 1993;68:41-51 
22. 
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ, Group AL-GS. 
Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant 
glioma: A randomised controlled multicentre phase iii trial. Lancet Oncol. 2006;7:392-
401 
23. 
Stummer W, Tonn JC, Goetz C, Ullrich W, Stepp H, Bink A, Pietsch T, Pichlmeier U. 5-
aminolevulinic acid-derived tumor fluorescence: The diagnostic accuracy of visible 
fluorescence qualities as corroborated by spectrometry and histology and postoperative 
imaging. Neurosurgery. 2014;74:310-319; discussion 319-320 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 112 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
24. 
Stummer W, Stepp H, Wiestler OD, Pichlmeier U. Randomized, prospective double-
blinded study comparing 3 different doses of 5-aminolevulinic acid for fluorescence-
guided resections of malignant gliomas. Neurosurgery. 2017;81:230-239 
25. 
Cozzens JW, Lokaitis BC, Moore BE, Amin DV, Espinosa JA, MacGregor M, Michael 
AP, Jones BA. A phase 1 dose-escalation study of oral 5-aminolevulinic acid in adult 
patients undergoing resection of a newly diagnosed or recurrent high-grade glioma. 
Neurosurgery. 2017;81:46-55 
26. 
Richter JCO, Haj-Hosseini N, Hallbeck M, Wardell K. Combination of hand-held probe 
and microscopy for fluorescence guided surgery in the brain tumor marginal zone. 
Photodiagnosis Photodyn Ther. 2017;18:185-192 
27. 
Lau D, Hervey-Jumper SL, Chang S, Molinaro AM, McDermott MW, Phillips JJ, Berger 
MS. A prospective phase ii clinical trial of 5-aminolevulinic acid to assess the correlation 
of intraoperative fluorescence intensity and degree of histologic cellularity during 
resection of high-grade gliomas. J Neurosurg. 2016;124:1300-1309 
28. 
Jaber M, Ewelt C, Wolfer J, Brokinkel B, Thomas C, Hasselblatt M, Grauer O, Stummer 
W. Is visible aminolevulinic acid-induced fluorescence an independent biomarker for 
prognosis in histologically confirmed (world health organization 2016) low-grade 
gliomas? Neurosurgery. 2018 
29. 
Chohan MO, Berger MS. 5-aminolevulinic acid fluorescence guided surgery for recurrent 
high-grade gliomas. J Neurooncol. 2018 
30. 
Wang W, Tabu K, Hagiya Y, Sugiyama Y, Kokubu Y, Murota Y, Ogura SI, Taga T. 
Enhancement of 5-aminolevulinic acid-based fluorescence detection of side population-
defined glioma stem cells by iron chelation. Sci Rep. 2017;7:42070 
31. 
Mansouri A, Mansouri S, Hachem LD, Klironomos G, Vogelbaum MA, Bernstein M, 
Zadeh G. The role of 5-aminolevulinic acid in enhancing surgery for high-grade glioma, 
its current boundaries, and future perspectives: A systematic review. Cancer. 
2016;122:2469-2478 
32. 
Stummer W, Pichlmeier U, Meinel T, Wiestler OD, Zanella F, Reulen HJ. Fluorescence-
guided surgery with 5-aminolevulinic acid for resection of malignant glioma: A 
randomised controlled multicentre phase iii trial. The Lancet. Oncology. 2006;7:392-401 
33. 
Ladner DP, Steiner RA, Allemann J, Haller U, Walt H. Photodynamic diagnosis of breast 
tumours after oral application of aminolevulinic acid. Br J Cancer. 2001;84:33-37 
34. 
Frei KA, Bonel HM, Frick H, Walt H, Steiner RA. Photodynamic detection of diseased 
axillary sentinel lymph node after oral application of aminolevulinic acid in patients with 
breast cancer. Br J Cancer. 2004;90:805-809 
35. 
Adminstration FD. Gleolan highlights of prescribing information 2017;2018 
36. 
Hadjipanayis CG, Stummer W. 5-ala and fda approval for glioma surgery. Journal of 
Neuro-Oncology. 2019;141:479-486 
37. 
Dupont E, Tsangaris T, Garcia-Cantu C, Howard-McNatt M, Chiba A, Berger AC, 
Levine EA, Gass JS, Gallagher K, Lum SS, Martinez RD, Willis AI, Pandya SV, Brown 
EA, Fenton A, Mendiola A, Murray M, Solomon NL, Senthil M, Ollila DW, Edmonson 
D, Lazar M, Namm JP, Li F, Butler M, McGowan NE, Herrera ME, Avitan YP, Yoder B, 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 113 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Walters LL, McPartland T, Chagpar AB. Resection of cavity shave margins in stage 0-iii 
breast cancer patients undergoing breast conserving surgery: A prospective multicenter 
randomized controlled trial. Ann Surg. 2019 
38. 
Gray RJ, Pockaj BA, Garvey E, Blair S. Intraoperative margin management in breast-
conserving surgery: A systematic review of the literature. Ann Surg Oncol. 2018;25:18-
27 
39. 
Ajioka RS, Phillips JD, Kushner JP. Biosynthesis of heme in mammals. Biochim Biophys 
Acta. 2006;1763:723-736 
40. 
Potteir RK, JC. Utilization of 5-aminolevulinic acid in the photodynamic therapy of 
tumors: Biochemical and photobiological aspects. Proc. SPIE. 1994;2078 
41. 
Kennedy JC, Pottier RH. Endogenous protoporphyrin ix, a clinically useful 
photosensitizer for photodynamic therapy. J Photochem Photobiol B. 1992;14:275-292 
42. 
Kappas AS, S; Galbraith, RA; Nordmann, Y. The porphyrias. In: Scriver CR; Baudet AS, 
WS; Valle, D, ed. The metabolic basisi of inherited disease. New York: McGraw; 
1989:1305-1365. 
43. 
Peng Q, Berg K, Moan J, Kongshaug M, Nesland JM. 5-aminolevulinic acid-based 
photodynamic therapy: Principles and experimental research. Photochem Photobiol. 
1997;65:235-251 
44. 
Bottomley SS, Muller-Eberhard U. Pathophysiology of heme synthesis. Semin Hematol. 
1988;25:282-302 
45. 
Stummer W, Stocker S, Wagner S, Stepp H, Fritsch C, Goetz C, Goetz AE, Kiefmann R, 
Reulen HJ. Intraoperative detection of malignant gliomas by 5-aminolevulinic acid-
induced porphyrin fluorescence. Neurosurgery. 1998;42:518-525; discussion 525-516 
46. 
Sroka R, Beyer W, Gossner L, Sassy T, Stocker S, Baumgartner R. Pharmacokinetics of 
5-aminolevulinic-acid-induced porphyrins in tumour-bearing mice. J Photochem 
Photobiol B. 1996;34:13-19 
47. 
Pottier RH, Chow YF, LaPlante JP, Truscott TG, Kennedy JC, Beiner LA. Non-invasive 
technique for obtaining fluorescence excitation and emission spectra in vivo. Photochem 
Photobiol. 1986;44:679-687 
48. 
Goff BA, Bachor R, Kollias N, Hasan T. Effects of photodynamic therapy with topical 
application of 5-aminolevulinic acid on normal skin of hairless guinea pigs. J Photochem 
Photobiol B. 1992;15:239-251 
49. 
Egger NG, Motamedi M, Pow-Sang M, Orihuela E, Anderson KE. Accumulation of 
porphyrins in plasma and tissues of dogs after delta-aminolevulinic acid administration: 
Implications for photodynamic therapy. Pharmacology. 1996;52:362-370 
50. 
Loh CS, Vernon D, MacRobert AJ, Bedwell J, Bown SG, Brown SB. Endogenous 
porphyrin distribution induced by 5-aminolaevulinic acid in the tissue layers of the 
gastrointestinal tract. J Photochem Photobiol B. 1993;20:47-54 
51. 
Van Hillegersberg R, Van den Berg JW, Kort WJ, Terpstra OT, Wilson JH. Selective 
accumulation of endogenously produced porphyrins in a liver metastasis model in rats. 
Gastroenterology. 1992;103:647-651 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 114 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
52. 
Xu S, Menon IA, Becker MA, Wiltshire JD, Haberman HF, Chen Z, Gaspari AA. 
Endogenous porphyrins in murine skin and transplanted pam-212 squamous cell 
carcinoma tissues after injection of delta-aminolevulinic acid. Chin Med J (Engl). 
1995;108:286-290 
53. 
Dietel W, Fritsch C, Pottier RH, Wendenburg R. 5-aminolaevulinic-acid-induced 
formation of different porphyrins and their photomodifications. Lasers Med Sci. 
1997;12:226-236 
54. 
Hua Z, Gibson SL, Foster TH, Hilf R. Effectiveness of delta-aminolevulinic acid-induced 
protoporphyrin as a photosensitizer for photodynamic therapy in vivo. Cancer Res. 
1995;55:1723-1731 
55. 
Fukuda H, Paredes S, Batlle AM. Tumour-localizing properties of porphyrins. In vivo 
studies using free and liposome encapsulated aminolevulinic acid. Comp Biochem 
Physiol B. 1992;102:433-436 
56. 
Fukuda H, Paredes S, Batlle AM. Tumor-localizing properties of porphyrins. In vitro 
studies using the porphyrin precursor, aminolevulinic acid, in free and liposome 
encapsulated forms. Drug Des Deliv. 1989;5:133-139 
57. 
Campbell DL, Gudgin-Dickson EF, Forkert PG, Pottier RH, Kennedy JC. Detection of 
early stages of carcinogenesis in adenomas of murine lung by 5-aminolevulinic acid-
induced protoporphyrin ix fluorescence. Photochem Photobiol. 1996;64:676-682 
58. 
Riesenberg R, Fuchs C, Kriegmair M. Photodynamic effects of 5-aminolevulinic acid-
induced porphyrin on human bladder carcinoma cells in vitro. Eur J Cancer. 
1996;32A:328-334 
59. 
Wyss-Desserich MT, Sun CH, Wyss P, Kurlawalla CS, Haller U, Berns MW, Tadir Y. 
Accumulation of 5-aminolevulinic acid-induced protoporphyrin ix in normal and 
neoplastic human endometrial epithelial cells. Biochem Biophys Res Commun. 
1996;224:819-824 
60. 
Uekusa M, Omura K, Nakajima Y, Hasegawa S, Harada H, Morita KI, Tsuda H. Uptake 
and kinetics of 5-aminolevulinic acid in oral squamous cell carcinoma. Int J Oral 
Maxillofac Surg. 2010;39:802-805 
61. 
Morita M, Tanaka H, Kumamoto Y, Nakamura A, Harada Y, Ogata T, Sakaguchi K, 
Taguchi T, Takamatsu T. Fluorescence-based discrimination of breast cancer cells by 
direct exposure to 5-aminolevulinic acid. Cancer Med. 2019;8:5524-5533 
62. 
Gibson SL, Cupriks DJ, Havens JJ, Nguyen ML, Hilf R. A regulatory role for 
porphobilinogen deaminase (pbgd) in delta-aminolaevulinic acid (delta-ala)-induced 
photosensitization? Br J Cancer. 1998;77:235-242 
63. 
Yang X, Palasuberniam P, Kraus D, Chen B. Aminolevulinic acid-based tumor detection 
and therapy: Molecular mechanisms and strategies for enhancement. International 
Journal of Molecular Sciences. 2015;16:25865-25880 
64. 
Pourzand CK, E; Tyrrell, R; Reelfs, O. The iron regulatory protein can determine the 
effectiveness of 5-aminolevulinic acid in inducing protoporphyrin ix in human primary 
skin fibroblasts. Journal of Investigative Dermatology. 1999;112:419-425 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 115 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
65. 
Krieg RC, Fickweiler S, Wolfbeis OS, Knuechel R. Cell-type specific protoporphyrin ix 
metabolism in human bladder cancer in vitro. Photochem Photobiol. 2000;72:226-233 
66. 
Abels C, Heil P, Dellian M, Kuhnle GE, Baumgartner R, Goetz AE. In vivo kinetics and 
spectra of 5-aminolaevulinic acid-induced fluorescence in an amelanotic melanoma of the 
hamster. Br J Cancer. 1994;70:826-833 
67. 
Giuliano AE, Edge SB, Hortobagyi GN. Eighth edition of the ajcc cancer staging manual: 
Breast cancer. Ann Surg Oncol. 2018;25:1783-1785 
68. 
Mamounas EP. New issues in breast cancer surgical management. In: Bonadonna GH, 
Gabriel N;  Valagussa, Pinuccia, ed. Textbook of breast cancer: A clinical guide to 
therapy. Boca Raton, Florida: Taylor & Francis Group; 2006:115-162. 
69. 
Services USDoHaH. Common terminology criteria for adverse events (ctcae) v5.0. 2017 
70. 
Jaeschke R, Singer J, Guyatt GH. Measurement of health status. Ascertaining the 
minimal clinically important difference. Control Clin Trials. 1989;10:407-415 
71. 
Cano SJ, Klassen AF, Scott A, Alderman A, Pusic AL. Interpreting clinical differences in 
breast-q scores: Minimal important difference. Plast Reconstr Surg. 2014;134:173e-175e 
72. 
Clough KB, Benyahi D, Nos C, Charles C, Sarfati I. Oncoplastic surgery: Pushing the 
limits of breast-conserving surgery. Breast J. 2015;21:140-146 
73. 
Houssami N, Macaskill P, Luke Marinovich M, Morrow M. The association of surgical 
margins and local recurrence in women with early-stage invasive breast cancer treated 
with breast-conserving therapy: A meta-analysis. Annals of Surgical Oncology. 
2014;21:717-730 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 116 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
21. Appendices  
Appendix 1. 
Synopsis 
Protocol Title: A prospective multi-center clinical study evaluating the use of PD G 506 A and 
the Eagle V1.2 Imaging System for the visualization of carcinoma during breast conserving 
surgery 
 
Short Title: Fluorescence imaging of carcinoma during breast conserving surgery 
 
Rationale: Breast conserving surgery (BCS) is performed on patients with breast cancer to resect 
and completely remove carcinoma while conserving as much of the surrounding healthy tissue as 
possible. Current methods do not allow surgeons to determine the adequacy of surgical resection 
in real-time during the index surgical procedure. This often results in the need for a second 
surgical procedure (re-excision), or in some cases more than two surgical procedures in order to 
establish appropriate surgical margins after histopathological examination is complete, which 
typically takes approximately two weeks from the time of the index surgery.  
 
Re-excisions increase poor cosmesis, complications, discomfort, stress, adjuvant delay, medical 
costs and risk of local recurrence4, 8, 10-18, 72, 73. Reducing positive margin rates can be achieved 
through optimizing surgical procedures19. Thus, it is desirable for surgeons to have new methods 
to visualize carcinoma in real-time during surgery in order to assess the surgical cavity and margins 
of excised specimen(s) during the index BCS procedure.  
 
 
5-aminolevulinic acid hydrochloride (ALA HCl) is a prodrug that is metabolized intracellularly to 
form the fluorescent molecule protoporphyrin IX (PpIX). The exogenous application of ALA HCl 
leads to a highly selective accumulation of PpIX in malignant tissues. Visualization of breast 
carcinoma based on the imaging of ALA HCl-induced PpIX fluorescence has been demonstrated 
in an investigator-initiated trial in Canada, using a prototype handheld fluorescence imaging device 
called PRODIGI (Phase 2 Study #10-0633; clinicaltrials.gov identifier: NCT01837225). Protocol 
SBI-CIP 20-002 is a pivotal Phase 3 trial designed to evaluate the efficacy and safety of PD G 506 
A to aid in the visualization of carcinoma during BCS. The Eagle V1.2 Imaging System will be 
used in this trial to visualize red PpIX fluorescence. 
 
Objectives: This Phase 3 study will evaluate the safety and patient-level clinical usefulness, as 
well as patient and orientation-level diagnostic performance of PD G 506 A (ALA HCl granules 
for oral solution)-induced fluorescence for the real-time detection of carcinoma during standard of 
care (SoC) BCS.  Orientation-level analyses are based on the fluorescence and carcinoma status 
of the primary specimen, cavity shave specimens removed during resection, and the fluorescence 
status of the final cavity after FGR.  
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 117 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Overall Design: Protocol SBI-CIP 20-002 is a 2-part, double -blind [pathologist(s) & patients -
blinded] randomized placebo-controlled trial (Arm 1: SoC BCS, Arm 2: SoC BCS + Eagle V1.2 
Imaging System + PD G 506 A) to evaluate the safety and patient-level clinical usefulness, as well 
as patient- and orientation-level diagnostic performance of PD G 506 A-induced fluorescence for 
the real-time visualization of malignant tissue(s) during SoC lumpectomy for breast cancer.  Part 
A is an open-label training phase of the study to optimize workflow and Part B of the study is 
randomized and double-blind and will serve as the pivotal portion of the study.   
The Eagle V1.2 Imaging System will be used for the visualization of fluorescence. Data from the 
SoC arm will not be used for statistical analysis of the primary and key secondary efficacy 
endpoints. The purpose of the SoC arm is to compare patient reported cosmetic outcomes between 
study arms as well as to minimize bias introduced into the SoC procedure if the study surgeon is 
aware that they have an opportunity to revise the margins further after SoC is completed.  
 
     Number of Patients:  The sample size of Part A has been chosen on pragmatic grounds to be 
approximately 75 patients. Part A will include 75 patients assigned to receive PD G 506 A and 
undergo SoC BCS followed by FGR. The sample size for Part B will be determined based on the 
results of the first 30 Part A patients’ data.  
 
In Part B of the study, patients will be randomized in a ratio of 1:6 (Arm 1: N=72; Arm 2: N=428) 
in up to 20 sites in Canada and the United States. A total of 525 patients would be required, 
accounting for a 5% loss to follow-up. The primary efficacy analysis will be based on the mITT 
population, which includes all Part B patients randomized to Arm 2 who undergo surgery and have 
recorded surgical histopathology data. 
  
Treatment Groups and Duration: 
Part A will include up to 75 subjects and will not be randomized; all patients in Part A will receive 
PD G 506 A. 
 
In Part B, study patients will be randomized 1:6 to: 
● Arm 1 (SoC): placebo + conventional BCS (data from this arm will not be analyzed for 
the primary or secondary efficacy endpoints) 
● Arm 2 (experimental): PD G 506 A (20 mg/kg) + conventional BCS + Eagle V1.2 
Imaging System intraoperative assessment 
Patients in both arms will be enrolled at the time their index BCS procedure is scheduled and 
followed until the first post-operative follow-up, approximately 2 weeks (10 - 14 days) after their 
surgical procedure. A 3-month, 6-month and 1-year follow-up will also be performed.  
 
Investigational Drug: PD G 506 A for oral solution (aminolevulinic acid [ALA] hydrochloride 
[HCl] granules for oral solution) will be administered as a single dose (20 mg/kg body weight) 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 118 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
approximately 3 hours (min 2 hours, max 4 hours) prior to anesthesia. PD G 506 A is an optical 
imaging agent for real-time visualization of carcinoma.  
 
Investigational Device: The Eagle V1.2 Imaging System consists of a handheld, wireless, battery-
powered, imaging camera (Handheld Fluorescence Camera) and related accessories. The 
Handheld Fluorescence Camera  has 405 nm and white light illumination light sources and dual 
imaging sensors with optical filters for imaging of PD G 506 A-induced red PpIX fluorescence 
and standard full spectrum visible light, respectively.  
 
Study Population: Study patients will be adult female surgical patients with breast cancer 
undergoing breast conserving surgery. 
 
Inclusion criteria 
1. Female, 18 years or older 
2. Histologically or cytologically confirmed primary breast cancer (includes invasive 
lobular carcinoma, invasive ductal carcinoma, inflammatory breast cancer, papillary 
breast cancer, adenoid cystic carcinoma of the breast, mucinous breast cancer, 
metaplastic breast cancer, cribriform carcinoma and ductal carcinoma in situ, alone or 
in combination with invasive disease) 
3. Scheduled for a lumpectomy (including bilateral lumpectomy) of a breast malignancy 
[eligibility for breast conserving surgery/partial mastectomy based on clinical staging 
using TNM staging system (AJCC Cancer Staging Manual: Breast Cancer, 8th 
Edition67)]. 
4. Patient must have normal organ and bone marrow function and be an appropriate 
surgical candidate per site standard of care 
5. Women of child-bearing potential must agree to use adequate contraception (hormonal 
or barrier method of birth control, abstinence) starting the day entering the study, and 
for the duration of the study period (until the Week 2 visit) 
 
 Subject exclusion criteria 
 
Disease and SoC treatment: 
1. Currently on (neo)adjuvant therapy to treat another cancer 
2. Receiving or intended to receive neoadjuvant therapy to treat the primary breast cancer 
(including chemotherapy, endocrine therapy and radiotherapy)  
3. Stage 4 cancer, inclusive of metastatic disease  
4. Non-invasive diseases of the breast (includes phyllodes, Paget’s disease of the breast, 
lobular carcinoma in situ)  
5. Patients who have had the following procedures performed on the involved breast: 
a. Surgery for a benign lesion(s) within 1 year of the BCS date 
b. Breast implants inserted within 1 year of the BCS date 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 119 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
c. Breast reduction, surgery for malignant disease or mastectomy (at any time 
prior to the BCS date) 
d. Surgery for a benign lesion(s) or insertion of implants >1 year prior to the 
BCS date and who have signs of ongoing inflammation, active tissue healing 
and/or extensive scarring   
e. Radiation at anytime prior to the BCS date and who have signs of 
ongoing inflammation, active tissue healing and/or extensive scarring   
6. Patients for whom intraoperative frozen section analysis is planned 
 
Concomitant diseases: 
7. Patients who have not recovered from adverse events due to an investigational 
pharmaceutical or diagnostic agents administered more than 30 days prior to their 
scheduled surgical procedure 
8. History of hypersensitivity to ALA HCl or porphyrins 
9. Known or documented personal or family history of porphyria 
10. Patient has a recording of any parameter as defined below: 
Bilirubin: Above upper limit of normal 
AST (SGOT): > 2.5 X institutional upper limit of normal 
ALT (SGPT): > 2.5 X institutional upper limit of normal 
11. Patient has an estimated glomerular filtration rate (eGFR) < 60 mL/min, calculated 
using the MDRD (Modification of Diet in Renal Disease Study) equation for 
estimating GFR. 
12. Uncontrolled concurrent illness that in the opinion of the Investigator would prevent 
the patient from participation in the study, including but not limited to:  
a. Ongoing or active infection; 
b. Cardiovascular disease (e.g. symptomatic congestive heart failure, unstable 
angina pectoris, or cardiac arrhythmia). 
13. Patients who have the following collagen vascular diseases:  
a. Lupus  
b. Scleroderma 
c. Sjogren’s Syndrome 
 
Concomitant medications: 
14. Use of an investigational drug within 30 days of their scheduled surgical procedure  
15. Simultaneous use of other potentially phototoxic substances (such as St. John’s wort, 
griseofulvin, thiazide diuretics, sulfonylureas, phenothiazines, sulphonamides, 
quinolones and tetracyclines), and topical preparations containing ALA for 24 hours 
during the perioperative period. 
 
Consent/compliance/other: 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 120 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
16. Social or medical situations including uncontrolled psychiatric illnesses that would in 
the opinion of the Investigator limit compliance with study requirements (e.g. ability 
to travel for follow-up) 
17. Patients who are pregnant or become pregnant (it is unknown if ALA HCl is 
teratogenic or has abortifacient effects) 
18. Patients who are breastfeeding (there is an unknown but potential risk for adverse 
events in nursing infants secondary to treatment of the mother with ALA HCl, 
breastfeeding should be discontinued if the mother is treated with PD G 506 A) 
19. Inability to consent  
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 121 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Appendix 2. 
Study Workflow 
The following is a summary of steps to be performed as part of this clinical study. Refer to the 
referenced sections of the protocol for more details.  
 
Step 
Action 
Baseline Procedures (Section 12.2 & 12.3)
1
Pre-screen patient for eligibility 
2 
Perform informed consent procedure.  
If patient signs informed consent proceed to Step 3  
If patient requires more time to consider participation provide her with the ICF to 
take home.  
If patient refuses participation, do not approach again. 
3 
Complete screening for eligibility 
Bloodwork must be performed ≤ 7 days prior to Day 1 (day of surgery) 
Diagnostic imaging may be performed ≤ 90 days prior to Day 1 (day of surgery) 
Diagnostic histopathology may be performed ≤ 90 days prior to Day 1 (day of 
surgery)
4 
Enrol eligible participant once their surgery has been booked  
Note: Site must complete the Enrollment Form and submit to the sponsor a minimum 
of 2 business days prior to the planned breast conserving surgery.
5
Administer Breast-Q survey ≤ 30 days prior to Day 1 (day of surgery)
Day 1 Pre-operative Procedures (Section 12.4.1)
6 
Confirm participant weight and eligibility.  
Note: weight used for calculating the investigational drug administration volume 
(collected ≤ 7 days prior to surgery) must be provided to the 3rd party responsible for 
preparing and dispensing the investigational drug.
7
Measure baseline blood pressure and heart rate prior to administration. 
8 
Administer investigational drug (PD G 506 A) or placebo approximately 3 hours prior 
to anesthesia (min: 2 hours; max: 4 hours). 
Note: administration to be performed by a medically qualified individual (e.g. nurse) 
that is blinded to treatment allocation. Neither the surgeon nor surgeon’s assistant  
can administer the investigational drug/placebo.
9
Monitor participant for acute AEs (for 30 minutes post-dosing).
10 
Monitor and record blood pressure and heart rate immediately after dosing and 30 
minutes post-dosing.

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 122 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
11 
Monitor and record blood pressure and heart rate at least every hour following the 
initial 30-min observation period post-dosing. This should be done by appropriately 
trained medical staff (e.g. patient’s nursing staff). 
NOTE: Patients must have an IV line in place prior to study drug administration 
NOTE: The patient should receive instructions on reporting symptoms of hypotension, 
(e.g. light headedness, blurry vision, nausea, dizziness, weakness, blurry vision, etc.) 
after receiving the study drug. 
NOTE: During this period of medical supervision from the time of P DG 506 A dosing 
until the initiation of anesthesia, trained medical personnel and applicable therapies 
should be immediately available for the treatment of hypotension or any other 
hypersensitive reactions during administration of PD G506A and the post- 
administration monitoring period.
12 
Describe and provide participant with light-protection instructions (written) and list of 
other common photosensitizing medications which should be avoided (Appendix 3).
Day 1 Intraoperative Procedures (Sections 12.4.2 & 12.4.3)
13 
 
Surgeon performs SoC lumpectomy (as described in Section 12.4.2) up to the point 
of removing the primary specimen.  
Primary specimen is placed inside a black or opaque container and moved to the DIB 
 
NOTE 1: do not send the specimen out of the operating room and/or perform any SoC 
intraoperative imaging at this stage. 
NOTE 2: the primary specimen must be marked (e.g. sutured) for identification of the 
anatomical surfaces as per SoC; specimen inking cannot be performed at this stage
14 
Surgeon’s assistant places the excised primary specimen collected in Step 13 inside 
the DIB and acquires FL-video and FL-images of the 6 surfaces 
 
NOTE 1: In cases where a given anatomical surface of the excised tissue does not fit 
inside the field of view of the camera, multiple still images of each anatomical surface 
will be acquired to capture all anatomical surfaces of all margins 
NOTE 2: WL imaging of a particular surface is recommended when positive red PpIX 
fluorescence is observed. 
NOTE 3: if specimen inking is performed intraoperatively, it must be performed after 
FL-imaging of the primary specimen is complete. 
15a 
Surgeon performs SoC margin assessment including white light visualization and 
palpation and/or intraoperative ultrasound and/or specimen radiography. 
15b
If applicable, radiologist reports findings of specimen imaging to surgeon. 
16
Surgeon verbalizes response to 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 123 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
“Do you intend to revise a margin based on SoC margin assessment?” 
If ‘Yes’ – verbalize which margin(s) will be revised and which SoC margin 
assessment technique informed that decision, proceed to Step 17  
If ‘No’ – proceed to Step  21  
Record response on Intraoperative Data Collection Tool. 
17 
Surgeon revises margin(s) identified in Step 15a.  
SoC-driven cavity shave specimen(s) is placed in a black/opaque container and moved 
to the DIB. 
Note 1: all cavity shave specimens must be marked (e.g. sutured) for orientation 
purposes as per SoC. 
Note 2: all cavity shave specimens must be assigned an identifier that indicates from 
which margin they were resected and whether they are the 1st, 2nd, 3rd, etc. shave 
resected from that margin.  
The identifier should not indicate whether the shave specimen was SoC-driven or FL-
driven.
18 
Surgeon’s assistant acquires FL-video and FL-images of the outside surface and 
inside  of all (if any) SoC-driven cavity shave specimens collected in Step 15a using 
the DIB.  
 
NOTE 1: In cases where a >1 SoC-driven cavity shave specimen is resected for a given 
anatomical surface (e.g. two lateral SoC-driven cavity shave specimens) FL-video and 
FL-images of both the inside and outside surface of all shaves for that orientation must 
be collected.
19 
Surgeon verbalizes completion of the SoC lumpectomy procedure  
*procedures unrelated to the resection of the primary tumor need not be completed at 
this stage.  
Record time of completion of SoC lumpectomy in the Intraoperative Data Collection 
Tool. 
20 
If Part A – Proceed to Step 21 
 
If Part B, open randomization envelope: 
Arm 1 (SoC): proceed to Step 29 
Arm 2 (SoC + PD G 506 A + Eagle V1.2 Imaging System): proceed to Step 21 
Record the time at which the envelope was opened on the Intraoperative Data 
Collection Tool.
21
Surgeon acquires FL-video and FL-images of all applicable surfaces of the final cavity

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 124 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
22 
The surgeon reviews all FL-video and FL-images acquired and assigns a FL-status to 
all tissue surfaces imaged, including the primary specimen (all anatomical surfaces), 
all SoC-driven cavity shave specimens (inside and outside surfaces), and the final 
cavity after SoC.  
 
The surgeon will verbalize their responses to the questions below and the surgeon’s 
assistant (or designated individual) will record the data in the Intraoperative Data 
Collection Tool. 
 
For the primary specimen, the surgeon verbalizes their response to: 
 
i. 
“While using the Eagle V1.2 Imaging System, do you (surgeon) see red 
fluorescence on the [insert specific anatomical location e.g. posterior] surface 
of the primary specimen   
If ‘Yes’ – the (posterior) margin of the primary specimen is classified as 
FL-positive  
If ‘No’– the final (posterior) margin of the primary specimen is classified 
as FL-negative  
 
Repeat for all surfaces (i.e., S, M, P, L, I, A) of the primary specimen. 
 
If SoC-driven cavity shave specimens were collected, the surgeon verbalizes their 
response to: 
 
ii. 
“While using the Eagle V1.2 Imaging System, do you (surgeon) see red 
fluorescence on the inside surface of the [insert specific anatomical location 
e.g. posterior] SoC-driven cavity shave specimen? 
If ‘Yes’ – the inside surface of the (posterior) SoC-driven cavity shave 
specimen of is classified as FL-positive  
If ‘No’– the inside surface of the (posterior) SoC-driven cavity shave 
specimen of is classified as FL-negative 
 
iii. 
While using the Eagle V1.2 Imaging System, do you (surgeon) see red 
fluorescence on the outside surface of the [insert specific anatomical location 
e.g. posterior] SoC-driven cavity shave specimen? 
If ‘Yes’ – the outside surface of the (posterior) SoC-driven cavity shave 
specimen is classified as FL-positive 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 125 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
If ‘No’– the outside surface of the (posterior) SoC-driven cavity shave 
specimen  is classified as FL-negative 
 
Repeat for all SoC-driven cavity shave specimen resected.  
 
iv. 
“While using the Eagle V1.2 Imaging System, do you (surgeon) see red 
fluorescence on the [insert specific anatomical location] surface of the final 
cavity after SoC? 
If ‘Yes’ – the (posterior) surface of the final cavity after SoC is classified 
as FL-positive  
If ‘No’– the (posterior) surface of the final cavity after SoC is classified as 
FL-negative 
 
Repeat for all surfaces of the final cavity after SoC. 
23 
The surgeon resects FL-driven cavity shave specimens based on the FL-status of the 
surfaces of the final cavity after SoC and final margins after SoC. 
 
Based on the FL status of the [insert specific anatomical location e.g. posterior] of the 
final cavity after SoC and final margin after SoC, perform the following:   
Cavity FL-positive/ Specimen FL-positive: resect a FL-guided cavity shave 
specimen of the (posterior) surface of the cavity,  
Cavity FL-positive/ Specimen FL-negative: resect a FL-guided cavity shave 
specimen the (posterior) surface of the cavity 
Cavity FL-negative/ Specimen FL-positive: resect a FL-guided cavity shave 
specimen of the (posterior) surface of the cavity 
Cavity FL-negative/ Specimen FL-negative: no cavity shave specimen 
 
NOTE 1: if it is not possible to resect a cavity shave specimen (e.g. the posterior 
margin is at the chest wall) the FL status of the specimen must will be noted,  however 
no additional tissue resection is required. 
NOTE 2: all cavity shave specimens must be marked (e.g. sutured) for orientation 
purposes as per SoC. 
NOTE 3: all cavity shave specimens must be assigned an identifier that indicates from 
which margin they were resected and whether they are the 1st, 2nd, 3rd, etc. shave 
resected from that margin (e.g., 1st lateral shave, 2nd lateral shave). The identifier 
should not indicate whether the shave was SoC-driven or FL-driven. 
 
 
24 
Repeat Steps 22-23 until all 6 anatomical orientations have been evaluated.  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 126 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
If no FL-guided cavity shave specimens are resected, proceed to Step 29.  
If ≥1 FL-guided cavity shave specimen is resected, proceed to Step 25. 
25 
Surgeon performs FL imaging of the outside and inside surface of all FL-driven cavity 
shave specimens resected in Step 23 and the corresponding surfaces of the surgical 
cavity . 
 
Record response to the following, for each anatomical location (i.e., S, M, P, L, I, A) 
where a FL-driven cavity shave specimen was collected: 
 
i. 
“While using the Eagle V1.2 Imaging System, do you (surgeon) see red 
fluorescence on the outside surface of the FL-driven cavity shave specimen? 
If ‘Yes’ – the outside margin of the FL-driven cavity shave specimen is 
classified as FL-positive. 
If ‘No’– the outside margin of the FL-driven cavity shave specimen is 
classified as FL-negative  
 
ii.  “While using the Eagle V1.2 Imaging System, do you (surgeon) see red 
fluorescence on the cavity surface corresponding to the location where the 
FL-driven cavity shave specimen was resected? 
If ‘Yes’ – the cavity surface is classified as FL-positive 
If ‘No’– the cavity surface is classified as FL-negative  
 
Record the FL-status of the outside surface of the FL-driven cavity shave specimen(s) 
and corresponding cavity surface(s) on the Intraoperative Data Collection Tool. 
26 
 
Based on the FL status of the outside surface of the FL-driven cavity shave 
specimen(s) and cavity surface determined in Step 25, surgeon performs the 
following, for each anatomical location (i.e., S, M, P, L, I, A):   
Cavity FL-positive/ Shave FL-positive: resect a FL-guided cavity shave specimen 
Cavity FL-positive/ Shave FL-negative: resect a FL-guided cavity shave specimen 
Cavity FL-negative/ Shave FL-positive: resect a FL-guided cavity shave specimen 
Cavity FL-negative/ Shave FL-negative: no cavity shave specimen 
27 
Repeat Steps 25-26 until no additional red PpIX fluorescence is observed on the 
outside surface of the last round of FL-driven cavity specimen(s) AND surgical cavity, 
or until no further tissue can be resected based on the surgeon’s best clinical 
judgement.

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 127 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
28 
Surgeon verbalises completion of Eagle V1.2 Imaging System assessment. 
 
If either the surgical cavity or final margin after FGR remain FL-positive and no 
further resection is performed, record the anatomical location(s) of residual 
fluorescence (i.e., S, M, P, L, I, A) and the reason for not performing further FGR. 
29 
Surgeon completes surgical procedure as per SoC (e.g., performs sentinel node 
procedure, if indicated, closes surgical cavity as per SoC) and all samples are sent to 
pathology. 
Peri-operative Procedures (Specimen Biopsy Collection Section 12.4.4.1; conducted in a subset 
of clinical sites)
30 
Bisect or serially section the primary specimen through the centre of the primary mass 
and place the sectioned specimen on the DIS with the tumor cross-section facing up. 
 
NOTE 1: this step may be performed at any time after completion of SoC lumpectomy 
procedure and Eagle V1.2 Imaging System assessment of the primary specimen  
NOTE 2: the tissue may be sectioned by any qualified individual (e.g. surgeon, 
surgeon’s assistant, pathologist, pathologist’s assistant) however interpretation of the 
fluorescence images must be performed by the surgeon or surgeon’s assistant. The 
individual grossing the specimen (e.g. pathologist’s assistant) must remain blind to 
the fluorescence imaging results collected by the surgeon and/or surgeon’s assistant. 
NOTE 3: the weight of all specimens must be recorded during grossing (as described 
in Steps 39-40), and should be performed prior to biopsy collection. 
31 
Capture FL and WL image(s) of the entire surface of the inside of the sectioned 
specimen:
32 
Surgeon or surgeon’s assistant makes determination of where red PpIX fluorescence 
(if any) is observed inside the sectioned specimen.  
Ink the area(s) where biopsies will be collected.  
Collect tissue biopsies while recording a fluorescence video in order to document the 
locations where biopsies were collected.  
 If both positive and negative fluorescence are observed, collect 1 fluorescence-
positive and 1 fluorescence-negative biopsy 
 If only positive fluorescence is observed, collect 1 fluorescence-positive biopsies 
 If only negative fluorescence is observed, collect 1 fluorescence-negative biopsies

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 128 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
Biopsies should be identified with an identifier that does not indicate the fluorescence 
status of the tissue.  
Record the fluorescence status of each of the collected biopsies  in the Intraoperative 
Data Collection Tool. 
Note 1: the location of collected biopsies should adhere to the procedure described in 
Section 12.4.4.1
Day 1 Peri-operative Procedures (Specimen Grossing, Section 12.4.4.2) 
33 
Receive research samples in clinical pathology laboratory for grossing and formalin 
fixation. 
34 
Weigh each individual tissue specimen (excluding biopsies) and record the mass on 
the Pathology Data Collection Tool.
35
Perform specimen grossing and inking as per standard of care. 
36
Fix tissue samples as per standard clinical pathology laboratory protocols.
Day 1 Post-operative Procedures (Section 12.4.5)
37 
Prior to discharge, collect and record participant’s blood pressure and heart rate as well 
as evaluate and record any adverse events and provide participants with sunscreen to 
take home. 
Post-operative Pathology Procedures  (Section 12.6)
38 
Block the primary specimen according to standard procedures. Block all cavity shave 
specimens in total. Block biopsies individually.  
 
Note 1: cavity shave specimens must be oriented such that histological sections can be 
made perpendicularly to the inked inside and outside surfaces 
Note 2: biopsies must be oriented such that histological sections can be made 
perpendicularly to the inked surface (i.e., imaged surface) 
 
Record the tissue block ID in the Pathology Data Collection Tool.
39 
Pathologist evaluates the primary specimen as per SoC.  
Record the status of all primary specimen anatomical surfaces (i.e., S, M, P, L, I, A) 
on the Pathology Data Collection Tool:  
i. 
Presence/absence of carcinoma at each inked surface 
ii. 
Presence/absence of carcinoma below each inked surface 
iii. 
Presence/absence of non-malignant abnormal cells (e.g. hyperplastic, 
dysplastic) at or below each inked surface  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 129 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
If carcinoma is present, record the following additional information of the Pathology 
Data Collection Tool: 
i. 
Type(s) of carcinoma (e.g. IDC, ILC, DCIS, if other specify) 
ii. 
Shortest distance from the inked surface to carcinoma 
 
If non-malignant abnormal cells are present, record the following additional 
information:  
i. 
Type(s) of abnormal cells (e.g. hyperplastic, dysplastic)
40 
Pathologist evaluates all cavity shave specimens and records the following on the 
Pathology Data Collection Tool:  
i. 
Presence/absence of carcinoma at or below the inked outside surface of all 
cavity shave specimens 
ii. 
Presence/absence of carcinoma at or below the inked inside surface of all 
cavity shave specimens 
iii. 
Presence/absence of non-malignant abnormal cells (e.g. hyperplastic, 
dysplastic) at or below the inked inside surface of all cavity shave 
specimens 
 
If carcinoma is present, record the following additional information on the Pathology 
Data Collection Tool:   
i. 
Type(s) of carcinoma (e.g. IDC, ILC, DCIS, if other specify) 
ii. 
Shortest distance from each inked surface (i.e., inside and outside surfaces) 
to carcinoma 
 
If non-malignant abnormal cells are present, record the following additional 
information:  
i. 
Type(s) of abnormal cells (e.g. hyperplastic, dysplastic)
41 
Pathologist evaluates all tissue biopsies and records the following on the Pathology 
Data Tool  
i. 
Presence/absence of carcinoma anywhere in a given biopsy 
ii. 
Presence/absence of non-malignant abnormal cells (e.g. hyperplastic, 
dysplastic) anywhere in a given biopsy 
 
If carcinoma is present, record the following additional information on the Pathology 
Data Collection Tool  
i. 
Type(s) of carcinoma (e.g. IDC, ILC, DCIS, if other specify ) 
ii. 
Shortest distance from the inked surface to carcinoma 
If non-malignant abnormal cells are present, record the following additional 
information: 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 130 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Step 
Action 
i. 
Type(s) of abnormal cells (e.g. hyperplastic, dysplastic)
Follow-up Procedures (Sections 12.5 & 12.7)
42 
Perform Day 2 follow-up within 24 hours (+24 hours) of the surgery. If participant has 
been discharged, follow-up may be performed via the telephone. 
Record any AEs in the EDC. 
43 
Perform Week 2 follow-up within 14 days (-4 days) of the surgery, including 
administration of the post-operative Breast-Q survey.   
Record any AEs in the EDC 
If no unresolved AE(s), this is the last in-person study visit.  
If unresolved AE(s) is present, follow for additional 7 days. 
If unresolved SAE(s) is present, follow for additional 30 days. 
Record any (S)AE(s) and outcome in the EDC. 
44 
Perform 3-month follow-up within 80 – 90 days of the surgery, including 
administration of the post-operative Breast-Q survey. If the patient is schedule to 
received adjuvant radiation therapy prior to 80 days post procedure, perform the 3-
month visit within 7 days prior to commencement of radiation therapy. 
AE, adverse event; DCIS ductal carcinoma in situ; DIB, Dark Imaging Box; DIS, Dark Imaging 
Sheet; EDC, electronic data capture; IDC, invasive ductal carcinoma; ILC, invasive lobular 
carcinoma; SoC, standard of care  
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 131 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Appendix 3. 
Sun Protection Instructions and List of Other 
Common Photosensitizing Medications Which Should be Avoided 
The following is an example of the information which should be provided to all study participants 
at the time of dosing. Formatting and non-critical information may be modified by sites to meet 
the requirements of their institution or REB/IRB of record. Modifications must be approved by the 
sponsor prior to implementation.  
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 132 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 133 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Appendix 4. 
Study Governance Considerations 
Regulatory and Ethical Considerations 
This trial will be conducted in compliance with the protocol, International Conference on 
Harmonization (IHC) of technical requirements for registration of pharmaceuticals for human use 
Good Clinical Research Practice (GCP) and all applicable regulatory requirement(s). 
 
This may include an inspection by SBI ALApharma Canada Inc. representatives and/or Health 
Canada representatives at any time. The investigator must agree to the inspection of study-related 
records by the Health Canada/SBI ALApharma Canada Inc. representatives, and must allow direct 
access to source documents to the Health Canada/SBI ALApharma Canada Inc. representatives. 
Health Canada approvals/authorizations/notifications, where required, will also be in place and 
fully documented prior to study start.  
 
The protocol, informed consent form(s), recruitment materials, and all participant materials will 
be submitted to the REB/IRB for review and approval. Approval of both the protocol and the 
consent form must be obtained before any participant is enrolled. Any amendment to the protocol 
will require review and approval by the REB/IRB before the changes are implemented to the study. 
All changes to the consent form will be REB/IRB approved; a determination will be made 
regarding whether previously consented participants need to be re-consented. 
Financial Disclosures and Conflict of Interest  
Investigators and sub-investigators will provide the sponsor with sufficient, accurate financial 
information as requested to allow the sponsor to submit complete and accurate financial 
certification or disclosure statements to the appropriate regulatory authorities. Investigators are 
responsible for providing information on financial interests during the course of the study and for 
1 year after completion of the study.  
 
Investigators, sub-investigators and study team members are required to declare in writing any 
actual, perceived or potential conflict of interest to SBI ALApharma Canada Inc. in advance of 
study start or their participation in the study (whichever comes first). Additionally, investigators, 
sub-investigators and study team members, will be required to comply with their institution’s 
conflict of interest policy as related to the conduct of this trial.  
Informed Consent Process 
(a) Consent and Other Informational Documents Provided to Participants 
 
Consent forms describing in detail the investigational drug, investigational device, study 
procedures, and risks are given to the participant and written documentation of informed consent 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 134 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
is required prior to starting intervention/administering study product. The following consent 
materials are submitted with this protocol: 
● Study Flyer 
● Informed Consent Form 
(b) Consent Procedures and Documentation 
Surgeon investigators will be responsible for confirming patient eligibility and a member of 
patient’s circle of care will introduce the patient to the study. If the patient expresses interest in the 
study, the investigator or study personnel (e.g. study coordinator) will be responsible for discussing 
the study with the patient, answering any questions and obtaining informed consent. The rights 
and welfare of the patient will be protected by emphasizing to them that the quality of their medical 
care will not be adversely affected if they decline to participate in this study. Patients will be 
provided information about the study and allowed appropriate time (minimum 24 hours if 
requested) to decide to volunteer for the study. Patients that request additional time to consider 
their participation may be provided a copy of the Informed Consent Form to take home and the 
research team will follow-up with them via telephone within 2-5 business days. All participants 
will be required to sign 2 copies of the Informed Consent Form, one of which they will keep and 
the other of which will be retained by the investigator.  
 
Investigator will document the date and time that written consent was obtained as well as any 
questions/concerns discussed with the patient. Screening may not be performed in patients that 
have not provided written informed consent.  
Data Protection 
Participant confidentiality is strictly held in trust by the participating investigators, their staff, and 
SBI ALApharma Canada Inc. and their agents. This confidentiality is extended to cover testing of 
biological samples and clinical information relating to participants. Therefore, the study protocol, 
documentation, data, and all other information generated will be held in strict confidence. No 
information concerning the study or the data will be released to any unauthorized third party 
without prior written approval of SBI ALApharma Canada Inc..  
 
The study monitor, other authorized representatives of SBI ALApharma Canada Inc., 
representatives of the IRB/REB, regulatory authorities, investigational drug manufacturer and 
device manufacturer may inspect all documents and records required to be maintained by the 
investigator, including but not limited to, medical records (office, clinic, or hospital) and pharmacy 
records for the participants in this study. The clinical study site will permit access to such records.  
 
The study participant’s contact information will be securely stored at each clinical site for internal 
use during the study. At the end of the study, all records will continue to be kept in a secure location 
for as long a period as dictated by the governing IRB/REB, institutional regulations or governing 
regulatory body.  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 135 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
Study participant research data, which is for purposes of statistical analysis and scientific reporting, 
will be transmitted to and stored in the clinical study database. This will not include the 
participant’s contact or identifying information. Rather, individual participants and their research 
data will be identified by a unique study identification number. The study data entry and study 
management systems will be secured and password protected. At the end of the study, all study 
databases will be de-identified, archived and retained by SBI ALApharma Canada Inc. (the 
sponsor). 
Publication Policy 
The results of this study may not be published or presented at medical or scientific meetings 
without the expressed written permission of the sponsor. The study investigator agrees to submit 
all manuscripts or abstracts to the sponsor for review before submission. This allows the sponsor 
to protect proprietary information and to provide comments.  
 
The sponsor will comply with the requirements for publication of study results. SBI ALApharma 
Canada Inc. will register the trial in public registries (e.g. clinicaltrials.gov, Health Canada Clinical 
Trial Registry). In accordance with standard editorial and ethical practices, the results of this 
multicenter study will be reported in its entirety and not as individual site data. A coordinating 
investigator will be designated by mutual agreement. 
 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
Dissemination of Clinical Study Data 
The data generated by this study may be used for publication in peer-reviewed scientific journals, 
presented at conferences, used for commercial marketing, or submitted to regulatory authorities 
worldwide to support medical device and drug licenses.  
Data Quality Assurance 
● All participant data relating to the study will be recorded on an eCRF. The investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the CRF.  
● The investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF.  
● The investigator must permit study-related monitoring, audits, REB/IRB review, and 
regulatory agency inspections and provide direct access to source data documents.  
● The sponsor or designee is responsible for the data management of this study including 
quality checking of the data.  

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 136 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
● Quality control procedures will be implemented beginning with the data entry system and 
data quality control checks, that will be run on the database, will be generated. Any missing 
data or data anomalies will be communicated to the site(s) for clarification/resolution.  
● Study monitors will perform ongoing source data verification to confirm that data entered 
into the eCRF by authorized site personnel are accurate, complete, and verifiable from 
source documents; that the safety and rights of participants are being protected; and that 
the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements.  
● The site will provide direct access to all trial related source data/documents, and reports 
for the purpose of monitoring and auditing by or on behalf of SBI ALApharma Canada 
Inc., and inspection by local and regulatory authorities. 
● Records and documents, including signed ICFs, pertaining to the conduct of this study must 
be retained by the investigator for 5 years after study completion unless local regulations 
or institutional policies require a longer retention period. No records may be destroyed 
during the retention period without the written approval of the sponsor. No records may be 
transferred to another location or party without written notification to the sponsor.  
● All possible effort will be taken to ensure that the protocol is performed as accurately as 
possible and with all possible care by the clinical and research staff. All deviations from 
the protocol will be appropriately documented and reported as described in Section 17.1 
Source Documents 
● Source documents are filed at the investigator’s site. 
● Data reported entered in the eCRF that are transcribed from source documents must be 
consistent with the source documents or the discrepancies must be explained. The 
investigator may need to request previous medical records or transfer records, depending 
on the study. Also, current medical records must be available. 
● Definition of what constitutes source data can be found in the Data Management Plan. 
Study and Site Suspension and Closure 
All study sites will be closed upon study completion. A study site is considered closed when all 
required documents and study supplies have been collected and a study-site closure visit has been 
performed. Regulatory authorities will be notified of the completion of the study, as appropriate.  
 
The sponsor reserves the right to temporarily suspend or prematurely close a study site or study at 
any time for any reason at the sole discretion of the sponsor. The investigator may initiate study-
site closure at any time, provided there is reasonable cause and sufficient notice is given in advance 
of the intended termination. 
 
Reasons for the suspension or premature closure of a study site by the sponsor or investigator may 
include but are not limited to: 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 137 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
● Failure of the investigator to comply with the protocol, the requirements of the REB/IRB 
or local health authorities, the sponsor's procedures, or GCP guidelines 
● Inadequate recruitment of participants by the investigator 
● Data that are not sufficiently complete and/or evaluable  
Written notification, documenting the reason for study suspension or early closure, will be 
provided by SBI ALApharma Canada Inc. to the investigators and regulatory authorities will be 
notified, as appropriate. If the study is prematurely terminated or suspended, the PI will promptly 
inform the governing IRB/REB and will provide the reason(s) for the termination or suspension. 
 
If temporarily suspended, the study may resume once concerns about safety, protocol compliance 
and/or data quality are addressed and satisfy SBI ALApharma Canada Inc. and/or REB/IRB. 
 
Circumstances that may warrant termination or suspension of the trial include, but are not limited 
to:  
● Determination of unexpected, significant, or unacceptable risk to participants  
● Insufficient compliance to protocol requirements  
● Data that are not sufficiently complete and/or evaluable  
● Discontinuation of further study treatment development 
 
Written notification, documenting the reason for study site suspension or termination, will be 
provided by SBI ALApharma Canada Inc. to the investigator and regulatory authorities will be 
notified, as appropriate. If the study site is prematurely terminated or suspended, the PI will 
promptly inform the governing REB/IRB and will provide the reason(s) for the termination or 
suspension.  
 
The study may resume at a suspended site once concerns about safety, protocol compliance and/or 
data quality are addressed and satisfy SBI ALApharma Canada Inc. and/or REB/IRB. 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 138 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Appendix 5. 
Contraceptive Guidance and Collection of 
Pregnancy Information 
Definitions 
 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
● Documented hysterectomy 
● Documented bilateral salpingectomy 
● Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s: review of the participant’s 
medical records, medical examination, or medical history interview. 
3. Postmenopausal female 
● A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 12 
months of amenorrhea, a single FSH measurement is insufficient.  
● Females on HRT and whose menopausal status is in doubt will be required to use one 
of the non-hormonal highly effective contraception methods if they wish to continue 
their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception Guidance 
Female participants of childbearing potential are eligible to participate if they agree to use a highly 
effective method of contraception consistently and correctly as described in Appendix 5 Table 
5.1. 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 139 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Appendix 5 Table 5.1: Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependent a  
Failure rate of <1% per year when used consistently and correctly.
Combined (estrogen and progestogen containing) hormonal contraception associated with 
inhibition of ovulation 
● Oral  
● Intravaginal  
● Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
● Oral  
● Injectable 
Highly Effective Methods That Are User Independent a
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
● Intrauterine device (IUD) 
● Intrauterine hormone-releasing system (IUS) 
Bilateral tubal occlusion
Vasectomized partner  
A vasectomized partner is a highly effective contraception method provided that the partner is 
the sole male sexual partner of the WOCBP and the absence of sperm has been confirmed. If 
not, an additional highly effective method of contraception should be used. 
Sexual abstinence  
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study treatment. 
The reliability of sexual abstinence needs to be evaluated in relation to the duration of the 
study and the preferred and usual lifestyle of the participant. 
NOTES:  
a) Typical use failure rates may differ from those when used consistently and correctly. Use 
should be consistent with local regulations regarding the use of contraceptive methods for 
participants participating in clinical studies. 
 
Pregnancy Testing 
Pregnancy testing will be performed locally at each site at baseline and on the Day 1 (prior to 
administration of the investigational agent) to confirm eligibility.  
● 
WOCBP should only be included after a confirmed menstrual period and a negative highly 
sensitive blood or urine pregnancy test. 
Collection of Pregnancy Information 
The investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate form 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 140 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
and submitted to the sponsor within 24 hours of learning of a participant's pregnancy. The 
investigator will request written permission to follow the participant until the outcome of the 
pregnancy. The investigator will collect follow-up information on the participant and the neonate 
and the information will be forwarded to the sponsor. Generally, follow-up will not be required 
for longer than 6 to 8 weeks beyond the estimated delivery date. Any termination of pregnancy 
will be reported, regardless of fetal status (presence or absence of anomalies) or indication for the 
procedure. 
 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous abortion is 
always considered to be an SAE and will be reported as such. Any post-study pregnancy related 
SAE considered reasonably related to the study treatment by the investigator will be reported to 
the sponsor as described in Section 13. While the investigator is not obligated to actively seek this 
information in former study participants, they may learn of an SAE through spontaneous reporting.  
 
Any participant that becomes pregnant following consenting to participate and prior to receiving 
the investigational drug, will be terminated immediately. If a participant becomes aware that they 
are pregnant following administration of the investigational drug but prior to completing the study, 
they will complete the study according to the protocol. 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 141 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Appendix 6. 
Breast-Q Version 2.0 © - Breast Conserving Therapy 
Module  
 
 
BREAST-QTM - BREAST CANCER CORE SCALE 
(PREOPERATIVE) VERSION 2.0: 
SATISFACTION WITH BREASTS 
 
With your breast area in mind, in the past week, how satisfied or dissatisfied have you been with: 
 
Very
Dissatisfied
Somewhat 
Dissatisfied
Somewhat 
Satisfied 
Very
Satisfied 
a. How you look in the mirror clothed? 
1 
2 
3 
4 
b. How comfortably your bras fit? 
1 
2 
3 
4 
c. Being able to wear clothing that is more fitted? 
1 
2 
3 
4 
d. How you look in the mirror unclothed? 
1 
2 
3 
4 
BREAST-Q VERSION 2.0 © Memorial Sloan Kettering Cancer Center and The University of British Columbia, 
2017. All rights reserved. 
 
 
 
 
 
 
 
 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 142 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
BREAST-QTM – BCT MODULE (POSTOPERATIVE) 
VERSION 2.0:  
SATISFACTION WITH BREASTS 
 
The following questions are about your breasts and your breast cancer treatment (by treatment, we mean 
lumpectomy with or without radiation).  If you have had a lumpectomy and radiation of both breasts, 
answer these questions thinking of the breast on which the study procedure was performed. If you are 
unsure on which breast the study procedure was performed, ask your surgeon. With your breasts in 
mind, in the past week, how satisfied or dissatisfied have you been with: 
 
Very 
Dissatisfied 
Somewhat 
Dissatisfied 
Somewhat 
Satisfied 
Very  
Satisfied 
a. 
How you look in the mirror clothed? 
1 
2 
3 
4 
b. 
The shape of your lumpectomy breast when you are 
wearing a bra? 
1 
2 
3 
4 
c. 
How normal you feel in your clothes? 
1 
2 
3 
4 
d. 
Being able to wear clothing that is more fitted? 
1 
2 
3 
4 
e. 
How your lumpectomy breast sits/hangs? 
1 
2 
3 
4 
f. 
How smoothly shaped your lumpectomy breast 
looks?
1 
2 
3 
4 
g. 
The contour (outline) of your lumpectomy breast? 
1 
2 
3 
4 
h. 
How equal in size your breasts are to each other? 
1 
2 
3 
4 
i. 
How normal your lumpectomy breast looks? 
1 
2 
3 
4 
j. 
How much your breasts look the same? 
1 
2 
3 
4 
k. 
How you look in the mirror unclothed? 
1 
2 
3 
4 
BREAST-Q® VERSION 2.0 © Memorial Sloan Kettering Cancer Center and The University of British Columbia, 
2017. All rights reserved. 
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 143 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Appendix 7. 
Protocol Amendment History 
 
The Protocol Amendment Summary of Changes Table for the current amendment is located 
directly before the Table of Contents (TOC). A history of all amendments will be provided 
below.  
 
Amendment 7: (13-Nov-2023), Version 1.7 
 
Overall Rationale for Amendment: 
Inclusion of safety information as a response to review of SUSAR case 2023SBI00001 as per the 
Ad Hoc DSMB meeting on 26 Jul 2023. Patient to have IV in place prior to administration of study 
drug. Dosing to take place in a location where patient can remain under medical supervision from 
the time of drug administration to anesthesia. Add hourly monitoring of BP and HR after 30 
minutes post-administration measurement (as is currently required per protocol); given 2-4 hour 
window between study drug administration and anesthesia this will add 1-2 additional BP and HR 
readings. 
 
Inclusion of safety request from FDA in IND 147228 Sequence 0047 in regards to SUSAR case 
2023SBI00001. Revision to include necessity of increased monitoring of study patients by 
medical personnel following administration of study drug 
 
Summary of Changes 
Section 
Changes/rationale 
3.4 Contract Research 
Organisation  
3.8 Monitoring Information 
Updated CRO information from: 
Name :  
CATO SMS 
Contact : 
Aleksandra Trajkovic 
to: 
Name :  
Allucent 
Contact : 
Andrew Daleus 
In order to account for CRO change in name, and Project Manager
4 Synopsis 
8.1 Description of the Study 
Design 
13.5 Study Pausing Rules 
15.2 Sample Size Estimation 
 
Modified the language regarding the patients from Part A of the trial that will 
be used to confirm sample size for Part B from: 
The sample size for Part B will be determined based on the results of 
Part A patients’ data, but is currently expected to be approximately 
350 patients in approximately 20 different clinical sites in Canada 
and the USA 
to:  
The sample size for Part B will be determined based on the results of 
Part A patients’ data, but is currently expected to be approximately 
350 patients in approximately 20 different clinical sites in Canada 
and the USA.  Sample size estimation for Part B will occur after TP 
residual FL is found in an orientation following SOC in at least 3 
patients in Part A. 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 144 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Additionally, all note of the total patients in Part A of the trial has been 
clarified to state: 
Part A will include approximately 75 subjects 
5. Schedule of Activities (SOA) 
Modified Baseline screening from: 
≤ 30 to Day 0 before procedure 
to: 
≤ 90 to Day 0 before procedure 
In order to account for the inclusion of Biopsy and Imaging done as SoC 
more than 30 days prior to surgery as part of screening for the trial, as noted 
in previous protocol amendment 1.6. 
Updated Figure 5.1 Schematic of Study Visits and Procedures through Week 
2 Visit to note this change to -90 days for baseline screening.
12.1 Screening (Day -90 – Day 
0) 
 
Modified title of section 12.1 from: 
Screening (Day -30 – Day 0) 
to: 
Screening (Day -90 – Day 0) 
In order to account for the inclusion of Biopsy and Imaging done as SoC 
more than 30 days prior to surgery as part of screening for the trial, as noted 
in previous protocol amendment 1.6. 
 
Clarified language regarding the use of Standard Of Care blood and 
examination results within 7 days prior to signing of ICF as per NTF 007 
released on 15-Jun-2023. The following language has been included: 
Baseline blood work may be collected before obtaining informed 
consent if both of the following 
criteria are met: 
3. Baseline blood work required to confirm eligibility 
according to study protocol SBI-CIP 20-002 is performed 
as part of the site’s standard of care for all patients 
undergoing breast conserving surgery. 
4. Standard of care baseline blood work is collected ≤ 7 days 
prior to surgery 
 
Baseline blood work may NOT be collected before obtaining 
informed consent if the following criterion is met: 
2. Baseline blood work required to confirm eligibility 
according to study protocol SBI-CIP 20-002 is NOT 
performed as part of the site’s standard of care for all 
patients undergoing breast conserving surgery.
12.2 Enrolment and 
Randomization 
 
Added requirements for the patient to meet additional safety monitoring 
requirements for risk of hypotension as per NTF 008 released on 28-Jul-2023, 
and the Dear Doctor Letter released to sites on 23-Aug-2023 
Following language included:  
‘Continued monitoring of the patient at hourly intervals following 
the initial 30-min observation post-administration of the study drug 
can be done by trained medical personnel (e.g. the patient’s nursing 
staff).’ 
12.3.1 Pre-operative Procedures
Updated language from:

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 145 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
‘Baseline heart rate and blood pressure will be collected prior to 
administration and post-administration heart rate and blood 
pressure will be monitored and recorded immediately after and 30 
minutes after administration.  
 
The participant will be observed for 30 minutes following 
administration for any acute (S)AE(s). (S)AE monitoring will 
continue for the duration of the study period (until the Week 2 visit) 
as described in Section 13.3.’ 
to: 
‘Patients must have an IV line in place prior to study drug 
administration, and must be under medical supervision from the time 
of dosing until the initiation of anesthesia. Baseline heart rate and 
blood pressure will be collected prior to administration and post-
administration heart rate and blood pressure will be monitored and 
recorded immediately after and 30 minutes after administration. 
Post-administration heart rate and blood pressure will continue to 
be collected at least hourly following the measurement at 30-mins 
post dosing, until the initiation of anesthesia. The participant will be 
observed for 30 minutes following administration for any acute 
(S)AE(s). (S)AE monitoring will continue for the duration of the 
study period (until the Week 2 visit) as described in Section 13.3.  
Instructions will be provided to the patient to immediately report any 
possible symptoms of hypotension (e.g. light headedness, blurry 
vision, nausea, dizziness, weakness, blurry vision, etc.) after 
receiving the study drug.  
 
While the patient is under medical supervision from the time of P 
DG 506 A dosing until the initiation of anesthesia, trained medical 
personnel and applicable therapies should be immediately available 
for the treatment of hypotension or any other hypersensitive 
reactions during administration of PD G506A and the post- 
administration monitoring period.’
Appendix 1. Study Workflow 
Step 11 of the Study Workflow has been amended to include the following 
language: 
‘Monitor and record blood pressure and heart rate at least every 
hour following the initial 30-min observation period post-dosing. 
This should be done by appropriately trained medical staff (e.g. 
patient’s nursing staff). 
NOTE: Patients must have an IV line in place prior to study drug 
administration 
NOTE: The patient should receive instructions on reporting 
symptoms of hypotension, (e.g. light headedness, blurry vision, 
nausea, dizziness, weakness, blurry vision, etc.) after receiving the 
study drug. 
NOTE: During this period of medical supervision from the time of P 
DG 506 A dosing until the initiation of anesthesia, trained medical 
personnel and applicable therapies should be immediately available 
for the treatment of hypotension or any other hypersensitive

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 146 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
reactions during administration of PD G506A and the post- 
administration monitoring period.’ 
Numbering of steps following this included Step 11 has been updated 
accordingly.
 
 
Amendment 6: (04-Jan-2023), Version 1.6 
 
Overall Rationale for Amendment:  
Improve Day 1 logistics (in response to site feedback), define the scope of exclusion criteria 5 to 
align with rationale for excluding patients with prior surgery (i.e. to exclude patients with 
changes to the breast tissue that may affect efficacy of drug/device). 
 
Summary of Changes 
Section 
Changes/rationale 
5. Schedule of Activities 
Modified to improve day 1 logistics: 
 
Dosing to be based on weight of patient collected within 7 days prior 
to study drug administration 
Day of surgery weight will still be collected and recorded in EDC 
4 Synopsis 
9.3 Eligibility  
Modified  exclusion criterion 5 from: 
 
Patients who have had previous surgery on the involved breast including 
breast surgeries, mastectomies, breast reconstructions or implants  
to: 
Patients who have had the following procedures performed on the 
involved breast: 
a. 
Surgery for a benign lesion(s) within 1 year of the BCS date 
b. Breast implants inserted within 1 year of the BCS date 
c. 
Breast reduction, surgery for malignant disease or mastectomy (at any time 
prior to the BCS date) 
d. Surgery for a benign lesion(s) or insertion of implants >1 year prior to the 
BCS date who have signs of ongoing inflammation, active tissue healing 
and/or extensive scarring   
Radiation at any time prior to the BCS date and who have signs of 
ongoing inflammation, active tissue healing and/or extensive scarring  
6.2.3 Residual device risk and 
mitigation 
Added description of  residual burn risk and mitigation to match Section 3.4 
of Eagle V1.2 Imaging System Instructions for Use 
19.1 Data Collection and 
Management Responsibilities
Updated source document description to specify data collection tools may 
exist in either electronic or paper format 
n/a 
Corrected spelling of sponsor name from SBI ALAphama Canada, Inc. to SBI 
ALApharma Canada Inc. 
 
Removed  reference to Medical Monitoring contact details as 
pharmacovigilance, medical inquiries and medical review of eCRFs is 
performed by spmd, Inc.
Amendment 5: (24-Mar-2022), Version 1.5 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 147 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
Overall Rationale for Amendment:  
To address non-clinical hold feedback FDA provided on 27 November 2021 and further clarify 
and/or modify imaging data collection, study specific procedures related to blinding, 
randomization, training, and SoA. 
 
Summary of Changes 
Section 
Changes/rationale 
5. Schedule of Activities 
Modified to improve day 1 logistics: 
 
Blood pregnancy test permitted within 7 days prior to surgery 
 
Abbreviated physical examination permitted on Day 1 if full examination 
performed within 7 days prior to surgery 
 
Modified to allow patients with older diagnostic biopsies to participate:  
 
Baseline diagnostic tissue sample collection permitted up to 90 days prior 
to surgery 
Figure 5 updated to include Part A and B design
7.1 Primary Objectives and 
Endpoints 
Updated based on recommendation of FDA: 
 
Abbreviated description of primary endpoint P(1.1) updated to 
differentiate from conversion rate among all patients endpoint  
 
Changed primary endpoint P(1.3) from patient-level specificity “at the 
end of FGR” to “at the final assessment at the end of SoC” (specificity at 
the end of FGR moved to secondary endpoint 4)
7.2 Secondary Objectives and 
Endpoints 
Updated based on recommendation of FDA: 
 
Conversion rate among all patients elevated to secondary endpoint 1 
[P(2.1)] 
 
Orientation-level diagnostic performance of combined imaging (in vivo 
and ex vivo) at the end of FGR elevated from exploratory endpoint 20 to 
secondary endpoint 3 [P(2.3)] 
 
Clarified terminology e.g. replaced “FL- orientations” with FL-negative 
orientation” 
 
Updated abbreviated description of secondary endpoint 12: percentage of 
patients with true-negative fluorescence at the end of standard of care 
Updated to improve clarity 
 
Added sequential numbers to all endpoints [e.g. P(2.17a)]
7.3 Exploratory Objectives and 
Endpoints 
Updated based on recommendation of FDA: 
 
Corrected the parameter description for exploratory endpoints 28 & 29 to 
include SoC-guided shaves 
 
Removed exploratory endpoint 32 as it was a duplicate of exploratory 
endpoint 27 (diagnostic performance of PD G 506 A to detect cancer in 
the primary specimen)
8. Study Design 
Updated to allow for all participating sites to have opportunity to perform 
first procedures under training conditions: 
 
Added ~45 patients to Part A and description of training requirements for 
all surgeons and surgeon’s assistant’s participating in the trial
8.1 Description of the Study
Updated based on recommendation of FDA:

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 148 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
 
Added description of stratification at randomization and permuted block 
randomization
8.3 Minimizing Bias 
Updated to improve clarity: 
 
Clarified language to state that individual grossing the specimen (e.g. 
pathologist’s assistant) must remain blind to the fluorescence imaging 
data collection of the serially sectioned specimen 
 
Added that neither surgeon nor surgeon’s assistant can dose patient due 
to risk of unblinding
10.1.2.4 Dosing and 
Administration 
Updated to improve clarity: 
 
Added that dosing container must be amber, as described in Pharmacy 
Manual
10.1.3 Investigational Medical 
Device 
 
Updated description of system components to match Eagle V1.2 Imaging 
System IFU (Rev 1.4) 
10.1.3.1 
Handling/Storage/Accountability 
Updated to improve clarity: 
 
Added details about use of Device Accountability Log and Device 
Return/Repair/Destruction Log
10.3 Blinding  
Updated based on recommendation of FDA: 
 
Added description of surgeon being blinded to fluorescence imaging data 
collected during SoC and requirement that surgeon refrain for viewing 
the specimen tagging procedure performed by the surgeon’s assistant
12.2 Enrolment and 
Randomization 
Updated based on recommendation of FDA: 
 
Added description of preparation and dissemination of randomization 
envelope and unblinding of OR team after completion of SoC 
lumpectomy 
Updated to improve clarity: 
 
Added description of Enrolment Form
12.3.3. Study-specific 
Procedures 
Updated to improve clarity: 
 
 Added description of process in event of accidental unblinding in the 
operating room
12.3.3.1 Specimen Tagging 
 
Corrected error in flow chart regarding the number of sutures to be 
placed on a FL-driven shave specimen 
12.3.4 Perioperative Procedures 
Updated to improve perioperative logistics: 
 
modified to permit surgeon’s assistant (in addition to surgeon) to 
interpret fluorescence images collected of the serially sectioned specimen 
and direct location of biopsy collection 
Updated to improve clarity: 
 
Language in Table 12.1 updated to reflect the similarities in requirements 
for collecting biopsies from specimens with a palpable vs. non-palpable 
mass
12.6 Week 2 Visit 
Updated based on recommendation of FDA: 
 
Definition of clinically significant elevation of liver enzymes added. 
Definition based on CTCAE v5.0 definition of a grade 2 event 
15.2 Sample Size Estimation 
Updated based on recommendation of FDA: 
 
Null proportion for P(1.1) changed from 0 (0.01%) to 0.03 (3%) and 
updated sample size calculated using null variance (rather than sample 
variance) 
 
P(1.2) updated to reflect change to endpoint in Section 7 
 
Updated overall sample size due to change threshold for P(1.1)

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 149 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
15.4.5.3 End of FGR 
Updated based on recommendation of FDA: 
 
definition corrected to include the outside surfaces of the last SOC-
guided shave specimens (if no FL-guided shave specimens are taken for 
the particular orientation)
15.4 Analysis Populations  
 
Updated based on recommendation of FDA: 
 
Modified definition of mITT 
Throughout protocol
Updated to improve clarity: 
 
Other surgical tools (besides scalpel) can be used for SOC BCS 
procedure 
 
Neither surgeon or surgeon’s assistant can be responsible for dosing 
patient (due to risk of accidental unblinding) 
 
Patient should be observe for 30 mins post dosing but blood pressure and 
heart are collected immediately after and 30 mins post dosing 
 
Only outside surface of first SoC-driven shave specimen must be imaged; 
inside and outside surface of subsequent SoC shaves must be collected in 
FL-video and FL-images 
 
WL imaging is recommended when PpIX fluorescence is observed on a 
tissue surface
 
Amendment 4: 01-Oct-2021: 
 
Overall Rationale for the Amendment: To address feedback Health Canada provided during 
the CTA review process 
 
Summary of Changes 
 
Section # and Name 
Description of Change 
Brief Rationale 
Synopsis & 9.3 Exclusion 
criteria, Exclusion criterion 
11 
Use eGRF as a method of 
measuring renal function instead 
of serum creatinine or creatinine 
clearance. Furthermore, the 
exclusion criterion applies to all 
patients, not just those whose 
creatinine levels exceed 
institutional normal. 
Required as per Health 
Canada feedback 
Synopsis & 9.3 Exclusion 
criteria, Exclusion criterion 
13: 
Add Sjogren’s Syndrome to the 
list of collagen vascular diseases 
that are an exclusion criterion 
Required as per Health 
Canada feedback 
Amendment 3: 14-Apr-2021 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 150 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Overall Rationale for the Amendment: Modifications to clarify the intraoperative data 
collected to ensure all data required for endpoint analysis is collected. Modifications to clarify 
communication between CATO-SMS (CRO) and spmd (PV) in relation to study pausing rule 
 
Summary of Changes 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 12 Study 
Procedures 
& Appendix 1 Study 
Workflow  
Updated to clarify FL-status for 
all tissue surfaces must be 
recorded 
FL-status of all tissue 
surfaces required for 
analysis of diagnostic 
performance endpoints 
Section 13.5 – Study 
Pausing Rules 
Updated to clarify that CATO-
SMS is responsible for providing 
AE listing to DSMB  
Required to clarify 
responsibilities and 
channel of communication 
between CRO and PV 
vendors.  New language 
aligns with DSMB Charter 
v1.1 
 
Amendment 2: 28-Mar-2021 
 
Overall Rationale for the Amendment: to address feedback from the FDA provided during the 
IND review 
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Section 5 SoA; 
Section 12.6 Week 2 Visit; 
Section 13.3 Time Periods 
and Frequency for Event 
Assessment and Follow-up 
 
Added language stipulating if 
liver enzymes are elevated at the 
week 2 visit, participant must be 
followed until levels return to 
baseline 
Required as per FDA 
safety feedback 
Section 5 SoA;  
Section 13.3 Time Periods 
and Frequency for Event 
Assessment and Follow-up
Added assessment for 
neurological adverse events (AEs) 
at each AE assessment time point 
Required as per FDA 
safety feedback 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 151 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Section 10.5 Concomitant 
Therapy; 
Section 10.6 Prophylactic 
Medications Treatments and 
Procedures; 
Section 10.7 Warnings and 
Precautions 
Changed duration of sun 
protection from 24 to 48 hours 
after PD G 506 A 
Required as per FDA 
safety feedback 
Section 5 SoA & 12.6 Week 
2 Visit 
 
Added assessment of phototoxic 
reactions to physical exam at 2 
week visit 
Required as per FDA 
safety feedback 
Section 13.5 Study Pausing 
Rules 
Added rule to suspend enrollment 
for safety review after any SAE; 
revised communication between 
sponsor and contract research 
organization and 
pharmacovigilance vendors (spmd 
and CATO) 
Required as per FDA 
safety feedback 
Entire protocol; 
Section 12 Study 
Procedures and Schedule  
Altered study design to include a 
2-part design where Part A is an 
open-label training phase of the 
study to optimize workflow and 
Part B of the study is randomized 
and single-blind and will serve as 
the pivotal portion of the study 
To formalize the plan for a 
what was previously 
identified as the “roll-in” 
phase of the study and 
what is now called Part A 
of the 2 part study.   
Section 2 Definitions 
Definitions have been revised and 
new definitions are provided 
Updated to use FDA 
terminology (e.g. 
orientation) per FDA 
clinical feedback 
Section 7 Endpoints 
This section has been entirely 
replaced from version 1.1. 
Endpoints have been revised in 
accordance with advice and 
recommendations received by 
FDA 
Updated study endpoints 
per FDA clinical feedback 
Section 15 Statistical 
Considerations 
Section has been entirely replaced 
from the previous version.  
Efficacy endpoints have been 
revised in accordance with advice 
Updated to reflect new 
study endpoints per FDA 
clinical feedback 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 152 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
and recommendations received by 
FDA and analyses are updated 
accordingly 
Section 12 Study 
Procedures and Schedule 
and Appendix 1 Study 
Workflow 
Updates have been made to 
clarify the pathology data 
collection requirements in 
accordance with the new efficacy 
endpoints (e.g., distance to 
presence of cancer in each 
specimen) 
Updated to reflect new 
study endpoints per FDA 
clinical feedback. 
 
Amendment 1: 6-Jan-2021 
 
Overall Rationale for the Amendment: to fulfill requirements of Advarra central IRB review  
 
 
Section # and Name 
Description of Change 
Brief Rationale 
Entire protocol 
Clarification throughout protocol that 
the study is placebo controlled 
Requested by Advarra IRB
Section 4 Synopsis; 
Section 9.2 
Inclusions Criteria 
Added clinical staging criteria using 
current tumor, nodes, metastases (TNM) 
staging system to assess eligible patients 
Clarification requested by 
Advarra IRB 
Section 12.6 Week 2 
Visit (Day 10 - 14) 
Clarification that final pathological 
tumor staging, pathological tumor 
features/characteristics and nodal 
involvement will be collected from the 
surgical pathology report
Clarification requested by 
Advarra IRB 
Section 12.8 
Extension Phase 
Added 3- and 6-month follow-up to 
match V1.1 of the template Informed 
Consent Form 
Updated as requested by 
Advarra IRB 
Country or site-specific amendments will be numbered as follows:  
Example of Numbering a country-specific Protocol Amendment 
Type of Protocol 
Amendment 
Numbering 
Type of changes 
Country-specific 
Amendment 3/USA-2 
Same changes specific to USA added to global 
Amendment 3 (no new changes for Canada)

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 153 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Global
Amendment 3
New changes for all
Country-specific 
Amendment 2/CAD-2 
Additional changes specific to Canada added to 
global Amendment 2
Country-specific 
Amendment 2/CAD-1 
Same changes specific to Canada added to global 
Amendment 2 (no new changes for Canada)
Global
Amendment 2
New changes for all
Country-specific 
Amendment 1/USA-1 
Same changes specific to USA added to global 
Amendment 1 (no new changes for USA)
Global
Amendment 1
New changes for all
Country-specific
Amendment USA-1
Changes specific to USA added to original protocol
 
 

 
SBI-CIP 
20-002 
Rev: 
v1.8 
A prospective multi-center clinical study evaluating the use of PD G 
506 A and the Eagle V1.2 Imaging System for the visualization of 
carcinoma during breast conserving surgery 
Page: 154 of 157 
This document contains confidential information that is proprietary to SBI ALApharma Canada Inc. Neither the document nor the 
information contained therein should be disclosed or reproduced in whole or in part, without expressed written consent of SBI 
ALApharma Canada Inc
 
Example of Numbering a Site-specific Protocol Amendment 
Type of Protocol 
Amendment 
Numbering 
Type of changes 
Site-specific 
Amendment 2/SS-1 <<Insert Site 
Number(s)>> 
Same changes specific to site(s) added to 
global Amendment 2 (no new changes for 
site[s])
Global
Amendment 2
New changes for all
Site-specific 
Amendment 1/SS-1 <<Insert Site 
Number(s)>>
Changes specific to site(s)  added to 
global amendment
Global
Amendment 1
New changes for all
 
Global, country- or site-specific amendments will be tracked in Document History Tables 
as follows:  
Example of Document History Table for Global and Country-specific Protocol Amendments 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 2/USA-1
1-Feb-2016
Amendment 2
1-Feb-2016
Amendment 1/USA-1
1-Jan-2015
Amendment 1
01-Dec-2015
Original Protocol
01-Oct-2015
 
Example of Document History Table for Site-specific Amendments to a Global Amendment 
DOCUMENT HISTORY 
Document 
Date of Issue 
Amendment 2/SS-1
1-Feb-2016
Amendment 2
1-Feb-2016
Amendment 1/SS-1
1-Jan-2015
Amendment 1
01-Dec-2015
Original Protocol
01-Oct-2015