Conditions: Prostate Cancer
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 49
Healthy volunteers: no

Brief summary:
This will be an open-labelled, single centre study in the UK. The study group will include 60 patients with three groups of patients being studied. Group A will consist of 20 patients who have been newly diagnosed with primary high risk prostate cancer and are scheduled for radical prostatectomy surgery. Group B will consist of 20 patients with a diagnosis of BCR with previous radical prostatectomy, and are being considered for radical salvage therapy. Group C will consist of 20 patients with a diagnosis of BCR with previous radical radiotherapy (but no surgery), and are being considered for radical salvage therapy.

Detailed description:

Arms:
arm 1: Single intravenous administration of Gallium-68 THP-PSMA

Interventions: intervention 1: Gallium-68 THP-PSMA
Intervention descriptions: intervention 1: Subjects will undergo a Gallium-68 THP-PSMA scan in addition to standard of care monitoring. The results of this scan may influence the patient management plan.

Protocol document:
Prot_001.pdf: 
Protocol version: 2.0 (29 October 2018) Theragnostics Ltd Protocol number: THERAG0001 
Page 9 of 51 
1 
Synopsis 
Study Title 
A Phase II, Open-label Study to Assess Safety and Clinical Utility of 
68Ga-THP-PSMA PET/CT in Patients with High-risk Primary Prostate 
Cancer or Biochemical Recurrence after Radical treatment 
Short Title 
68Ga-THP-PSMA PET/CT imaging in high-risk primary prostate cancer or 
biochemical recurrence of prostate cancer. 
Study Design 
This is a Phase II, open-label study to evaluate the safety and clinical utility of 
gallium 68-trishydroxypyridinone-prostate-specific membrane antigen 
(68Ga-THP-PSMA) Positron Emission Tomography (PET)/Computed 
Tomography (CT) in patients with high-risk primary prostate cancer (PCa) or 
with biochemical recurrence (BCR) of PCa. 
Study Patients 
 Group A: Patients who have been diagnosed with high-risk primary PCa and 
indicated for primary radical curative therapy; 
 Group B: Patients with BCR being considered for radical salvage treatment 
(with curative intent), having had primary radical curative prostatectomy 
performed at least 3 months before enrolment; 
 Group C: Patients with BCR being considered for radical salvage treatment 
(with curative intent), having had primary radical curative radiotherapy (but 
no surgery) performed at least 3 months before enrolment. 
Planned Sample 
Size 
Recruitment of approximately 60 patients. 
Planned Study 
Period 
Patient recruitment is planned to start: June 2018 
Last patient in: End December 2018 
 
Objectives 
Endpoints 
Primary 
Evaluation of 68Ga-PSMA PET impact 
on the management of patients with 
PCa cancer in the setting of: 
1. BCR in patients treated with 
radical prostatectomy 
2. BCR in patients treated with 
radiotherapy 
3. newly diagnosed high-risk PCa
Change in-patient management as a 
result of 68Ga-PSMA PET 
documented after scan, compared with 
pre-scan management plan 
Secondary 
Evaluation of safety of 68Ga-PSMA in 
patients with PCa 
Adverse events: Clinically significant 
changes in heart rate, blood pressure, 
electrocardiogram, urinalysis and 
baseline serum haematology and 
biochemistry profile 
Tertiary 
(exploratory) 
Evaluation of technical feasibility of 
68Ga-PSMA in patients with PCa 
Technical success/failure of study, 
artefacts, pitfalls in interpretation 
Correlation of PSMA on imaging and 
PSMA within tumour 
Correlation of degree of uptake on 
PET/CT with histopathological 
staining of PSMA as per standard of 
care where histology is available 
 
 

SAP_000.pdf: 
 
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STATISTICAL ANALYSIS PLAN 
 
A Phase II, Open-label Study to Assess Safety and Clinical 
Utility of 68Ga-THP-PSMA PET/CT in Patients with High Risk 
Primary Prostate Cancer or Biochemical Recurrence after 
Radical treatment  
 
 
 
Date:   
 
24 June 2019 
Version: 
 
2.1 
Protocol Version: 
2.0 
Protocol Date:  
29 October 2018 
SAP Approvals:  
 
 
____________________________________ 
 
_________________ 
Greg Mullen 
 
 
 
 
 
 
Date 
Chief Executive Officer, Theragnostics 
 
 
 
 
 
 
 
 


 
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TABLE OF CONTENTS 
1. 
STUDY OBJECTIVES ....................................................................................... 6 
1.1 
Primary Objectives ..................................................................................... 6 
1.2 
Secondary Objectives ................................................................................ 6 
1.3 
Tertiary Objectives ..................................................................................... 6 
2. 
Study Design ..................................................................................................... 6 
2.1 
Overall Study Design ................................................................................. 6 
2.2 
Methods of Assigning Patients to Groups ................................................... 7 
2.2.1 
Procedures for Randomization ............................................................ 7 
3. 
ENDPOINTS ..................................................................................................... 7 
3.1 
Primary Clinical Utility Endpoint .................................................................. 7 
3.1.1 
Change in Management Plan Rate (CMPR) ........................................ 7 
3.2 
Safety and Tolerability ................................................................................ 9 
3.2.1 
Safety Endpoints ................................................................................. 9 
3.2.1.1 
General Considerations for Safety Assessments .......................... 9 
4. 
Analysis Populations ....................................................................................... 10 
4.1 
Safety Population ..................................................................................... 10 
4.2 
Full Analysis Set ...................................................................................... 10 
4.3 
Per Protocol Set ....................................................................................... 10 
4.4 
Histopathology Set ................................................................................... 10 
4.5 
Summary of Analysis Populations ............................................................ 10 
5. 
Protocol Deviations.......................................................................................... 11 
5.1 
Major Deviations ...................................................................................... 11 
5.2 
Important Deviations ................................................................................ 12 
6. 
General Statistical Considerations ................................................................... 13 
6.1 
Sample Size Estimation ........................................................................... 14 
6.1.1 
Sample Size Re-estimation ............................................................... 14 


 
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6.2 
Adjustments for Covariates ...................................................................... 14 
6.3 
Handling of Dropouts or Missing Data ...................................................... 14 
6.4 
Monitoring and Interim Analyses .............................................................. 15 
6.4.1 
Monitoring ......................................................................................... 15 
6.4.2 
Interim Analysis ................................................................................. 15 
6.4.2.1 
Purpose of Interim Analyses ....................................................... 15 
6.4.2.2 
Planned Schedule of Interim Analyses ........................................ 15 
6.5 
Multiple Testing Strategy .......................................................................... 15 
6.6 
Examination of Subgroups ....................................................................... 15 
6.7 
Stratification Factors ................................................................................ 15 
7. 
Methods of Analysis ........................................................................................ 15 
7.1 
Change in Management Plan Rate (CMPR) ............................................. 15 
7.2 
Assessment of Safety and Tolerability ...................................................... 16 
7.2.1 
Assessment of Adverse Events ......................................................... 16 
7.2.2 
Assessment of Safety ....................................................................... 17 
7.3 
Disposition of Patients .............................................................................. 17 
7.4 
Demographics and Baseline Characteristics ............................................ 17 
7.5 
Primary Diagnosis Information ................................................................. 18 
7.6 
PSA At Diagnosis and After Radical Treatment (Groups B and C only) .... 18 
7.7 
Prior Cancer Therapy ............................................................................... 18 
7.8 
Medical History and Prior and Concomitant Medications .......................... 18 
7.9 
Treatment Management Plan Details ....................................................... 18 
7.10 
Prior Imaging Assessments ...................................................................... 18 
8. 
Changes from the Protocol .............................................................................. 19 
9. 
Programming Considerations .......................................................................... 19 
10. LIST OF TABLES, FIGURES AND LISTINGS ................................................. 20 
10.1 
Tables ...................................................................................................... 20 


 
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10.2 
Listings ..................................................................................................... 21 
10.3 
Figures ..................................................................................................... 22 
 
 


 
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LIST OF ABBREVIATIONS 
AE 
Adverse Event 
AST 
Aspartate aminotransferase 
BCR 
Biochemical Recurrence 
CMPR 
Change in Management Plan Rate 
CRF 
Case Report Form 
CT 
Computed Tomography 
CTC 
Common Toxicity Criteria 
DCO 
Data cut-off 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eGFR 
estimated Glomerular Filtration Rate 
FAS 
Full Analysis Set 
68Ga 
68Gallium 
HP 
Histopathology 
IMP 
Investigational Medicinal Product 
MedDRA 
Medical Dictionary for Regulatory Activities 
MRI 
Magnetic Resonance Imaging 
NCI 
National Cancer Institute 
PCa 
Prostate Cancer 
PET 
Positron Emission Tomography 
PP 
Per Protocol 
PSA 
Prostate Specific Antigen 
PSMA 
Prostate Specific Membrane Antigen 
PT 
Preferred Term 
RP 
Revised Plan 
SAP 
Statistical Analysis Plan 
SOC 
System Organ Class 
 
 
 


 
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1. 
STUDY OBJECTIVES 
1.1 
Primary Objectives 
The primary study objective is to evaluate the impact of 68Ga-THP-PSMA PET on the 
management of patients with prostate cancer (PCa) in the setting of: 
 
• 
Biochemical recurrence (BCR) in patients treated with radical prostatectomy 
• 
BCR in patients treated with radiotherapy  
• 
Newly diagnosed high risk prostate cancer 
 
The primary objective will be measured by the proportion of patients with a change in 
management plan following 68GA-THP-PSMA PET scan, compared to the pre-scan 
intended management plan 
1.2 
Secondary Objectives 
• 
Evaluation of the safety of 68Ga-PSMA in patients with PCa as assessed via 
adverse events (AEs), vital signs (including heart rate and blood presurre), 
ECGs, clinical laboratory assessments (haematology, ,biochemistry and 
urinalysis) 
1.3 
Tertiary Objectives 
• 
Evaluation of the technical feasibility of 68Ga-THP-PSMA  in patients with PCa, 
as measured by: 
o The technical success/failure of the scan 
o The need for a re-scan 
o The presence/absence of artefacts on the scan 
o The rate of scans reported to have interpretation limitations 
• 
Correlation of PSMA on imaging with PSMA within tumour 
Note: The final tertiary objective relating to tumour PSMA data will be reported outside 
of the main CSR, and is not covered by this SAP. 
2. 
Study Design 
2.1 
Overall Study Design 
The study is open-labelled, non-randomised trial conducted in the UK. The whole study 
group consists of three groups of patients being studied. The three studied groups are: 
• 
Group A: newly diagnosed with primary high-risk prostate cancer and are 
scheduled for radical prostatectomy surgery 
• 
Group B: participants with PCa and a diagnosis of BCR, previously treated with 
radical prostatectomy, being considered for radical salvage therapy (with 
curative intent). 


 
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• 
Group C: participants with PCa and a diagnosis of BCR, previously treated with 
radical radiotherapy, being considered for radical salvage therapy (with 
curative intent). 
The study will consist of measurements to be taken at four timepoints. These are: 
• 
Visit 1 - Pre-scan. At any point within 4 weeks of scan date 
• 
Visit 2 - Day of scan. Data collected both pre-scan and post scan 
• 
Visit 3 - Post scan. Via telephone, 24-72 hours post scan 
• 
Visit 4 - Post scan. Approximately 2 weeks post scan 
On the day of the scan (visit 2), the participant will be cannulated, and receive one 5 
mL dose of 68Ga-THP-PSMA. This will be injected via the cannula with arms down, 
and a slow push over 1 minute followed by ~ 10mL flush. The participant will be 
scanned in the supine position in the direction of mid-thigh to skull base, with the arms 
positioned overhead following the dose and flush. Patients who have an imaging 
technical failure will be injected and scanned again. 
2.2 
Methods of Assigning Patients to Groups 
This is an open label, non-randomised study.  For the purpose of reporting the study 
data, patients will be allocated to one of the three groups described in Section 2.1 
based on their disease status (newly diagnosed = Group A or BCR= Group B or C) 
and prior treatment received (radical prostatectomy = Group B, radical radiotherapy = 
Group C) .  
2.2.1 
Procedures for Randomization 
Not applicable. This is a non-randomized study. 
3. 
ENDPOINTS 
3.1 
Primary Clinical Utility Endpoint 
3.1.1 
Change in Management Plan Rate (CMPR) 
The primary endpoint is the percentage of patients in the full analysis set with a change 
in the revised management plan as a result of 68GA-THP-PSMA PET scan, 
documented after scan, compared with the pre-scan management plan. 
As per the study case report form (CRF), the management plan is recorded to indicate 
the specific types of interventions planned for the patient both pre-scan and post-scan.  
A list of the specific interventions captured is provided in Table 1. 


 
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Table 1 Treatment Categories 
CRF Intervention Name 
TRUS Biopsy 
Targeted Biopsy  
Template Biopsy 
Prostatectomy  
Prostatectomy with limited node dissection 
Prostatectomy with extended lymph node dissection (incl internal, external illiac and obturator 
nodes) 
Radiotherapy to Prostate/Prostate bed 
Radiotherapy to Prostate/Prostate bed with boost to areas guided by conventional imaging  
Radiotherapy to Prostate/Prostate bed and whole pelvis 
Radiotherapy to Prostate/Prostate bed and whole pelvis with boost to areas guided by 
conventional imaging  
Stereotactic body radiotherapy (SBRT)/cyberknife 
Brachytherapy 
Cryotherapy 
HIFU 
Hormone therapy with a combination of any of the above 
Hormone therapy alone  
Chemotherapy  
Radionucleide therapy 
Other, Specify 
 
For each patient, each management plan may include multiple interventions. 
In order to derive the primary endpoint, a binary endpoint will be created. A change 
status of ‘Yes’ will be assigned if there is any difference in treatment options between 
the intended and revised management plans. A change status of ‘No’ will be assigned 
if the intended and revised management plans are identical.  
For the analysis set of interest, the CMPR will be calculated as the proportion of 
patients with a change status of “yes”, taking as a denominator the number of patients 
in the analysis set. 
The primary analysis of CMPR will be based on the Full Analysis Set (FAS, Section 
4.2), thus the CMPR will be defined as: 
𝐶𝑀𝑃𝑅= 𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑖𝑛 𝑡ℎ𝑒 𝐹𝐴𝑆 𝑤𝑖𝑡ℎ 𝑎 𝐶ℎ𝑎𝑛𝑔𝑒 𝑆𝑡𝑎𝑡𝑢𝑠 𝑜𝑓 𝑌𝑒𝑠
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑃𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑖𝑛 𝑡ℎ𝑒 𝐹𝐴𝑆
 
As a sensitivity analysis, the CMPR based on the Per Protocol Analysis Set (PP, 
section 4.3) will also be presented. The derivation of CMPR for the PP set will be 
analogous to the derivation shown above for the FAS, except the PP set will be used 
instead of the FAS for both the numerator and denominator. 


 
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3.2 
Safety and Tolerability 
3.2.1 
Safety Endpoints 
The assessment of safety of 68Ga-THP-PSMA PET in patients will be assessed 
using the following endpoints:  
 
• 
Adverse Events (AEs) 
• 
Vital Signs (blood pressure [systolic and diastolic] and heart rate) 
• 
Laboratory assessments (biochemistry chemistry, hematology and urinalysis) 
• 
Electrocardiogram (ECG) parameters: PR, QT, QTcB and QRS  
Adverse events will be coded by System Organ Class (SOC) and Preferred Term (PT) 
using the Medical Dictionary for Regulatory Activities (MedDRA 21) for concomitant 
diseases and AEs and WHO Drug for medications (WHO Drug Dictionary 2017). All 
AEs will be evaluated for severity according to NCI-CTCAE version 5.0 
Baseline will be defined as the last assessment prior to the administration of 68GA-
THP-PSMA. Therefore, if safety parameters were assessed at baseline Visit 1 
(screening) and pre-68GA-THP-PSMA administration at Visit 2, the Visit 2 values will 
be assumed to be the baseline value for the patient. For all endpoints that were not 
assessed at Visit 2, the Visit 1 value will be used as the baseline.  
Furthermore, if multiple assessments are performed at the same pre-treatment 
timepoint, for example triplicate ECG assessments, the mean of the values will be used 
as the baseline reading. 
Safety will be assessed in the Safety Set, Section 4.1. 
3.2.1.1 General Considerations for Safety Assessments 
Missing safety data will not be imputed. However, safety assessment values of the 
form of “< x” (i.e., below the lower limit of quantification) or > x (i.e., above the upper 
limit of quantification) will be imputed as “x” in the calculation of summary statistics but 
displayed as “< x” or “> x” in the listings.  
Furthermore, the following principles will apply to the presentation of safety data: 
• 
Listings should display all values for a patient, regardless of whether they were 
based on scheduled or unscheduled assessments. 
• 
Baseline will be defined as the last non-missing measurement prior to 68Ga-
THP -PSMA dosing. For the cardiovascular profile, and physical examination, 
any assessments made on day 1 will be considered pre-dose unless explicitly 
indicated otherwise. Where safety data are summarized over time, study day 
will be calculated in relation to date of the 68Ga-THP -PSMA dosing (which will 
be termed day 1). 


 
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4. 
Analysis Populations 
4.1 
Safety Population 
The safety population will consist of all those patients who received a 68Ga-THP -PSMA 
dose, regardless of whether they received the full intended dose, or proceeded to 
under-go the intended 68Ga-THP-PSMA PET/CT scan.  
 
All safety endpoints will be evaluated in the safety population.  
 
4.2 
Full Analysis Set 
The full analysis set (FAS)  is based on the intention-to-treat principle and includes the 
subset of the safety set who underwent the Visit 2 68Ga-THP-PSMA PET/CT scan, 
regardless of whether the scan was a technical success or failure.  
The FAS will be the primary analysis set used to address the primary outcome variable 
(Section 3.1.1) and all secondary clinical utility endpoints (Section Error! Reference s
ource not found.). 
4.3 
Per Protocol Set 
The per-protocol set is defined as the subset of the FAS with at least one technically 
successful post-baseline 68Ga-THP-PSMA PET/CT scan, and without any major 
protocol deviations as defined in Section 5.1. 
The PP set will be used to assess the sensitivity of the primary outcome variable to 
scan failures.   
4.4 
Histopathology Set 
The histopathology (HP) set is defined as the subset of the FAS with tumour 
histopathology data. 
The HP set will be used to assess the tertiary objectives only for information and 
relating to correlation between of PSMA on imaging with PSMA within tumour. The 
reporting of this data is beyond the scope of this SAP. 
4.5 
Summary of Analysis Populations 
A summary of the study outcome variables, and associated analysis sets is provided 
in Table 2. 


 
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Table 2 Summary of Outcome Variables and Analysis Populations 
Outcome Variable 
Analysis Population 
 (Sensitivity Analysis Population) 
Primary Endpoint 
 
CMPR 
FAS (PP) 
 
 
Secondary Endpoints 
 
 
 
Baseline Patient Characteristics 
 
Demography 
Safety Set 
Medical History 
Safety Set 
Concomitant Medications 
Safety Set 
 
 
Safety 
 
Adverse Events 
Safety Set 
Laboratory measurements 
Safety Set 
Vital Signs 
Safety Set 
ECG 
Safety Set 
 
 
Tertiary Objectives 
 
Histopathology data 
HP Set 
 
5. 
Protocol Deviations 
5.1 
Major Deviations 
Major protocol deviations, are defined as those deviations that have a profound impact 
on the assessment of the primary objective of the study. 
Patients who did not under-go the Visit 2 PET scan will be considered to have a major 
protocol deviation. 
Additionally, violations of any key inclusion/exclusion criteria pertinent to the intended 
disease or indication are also considered Major Protocol deviations. Thus, the 
following Major Protocol Deviations are defined by Patient Group. 
Group A 
• 
Patient did not have a histologically proven adenocarcinoma of the prostate 
gland.  
• 
 Patient did not have at least one of the following at screening: 
o Gleason score 4+3 and above 
• 
Patient was not considered to be suitable for surgical treatment as part of their 
standard of care management at screening.  
Group B 
• 
Patient did not have a previous diagnosis of PCa 


 
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• 
Patient has not undergone previous radical curative therapy completing at least 
3 month prior to enrolment 
• 
Patient did not have a diagnosis of BCR defined as: 
o 
Post RP: 2 consecutive rises in PSA and final PSA >0.l ng/mL or  
• 
The patient has had previous recurrences of PCa, i.e. this is not the first 
diagnosis of BCR.  
Group C 
• 
The patient did not have an original diagnosis of PCa 
• 
Patient has not undergone previous radical curative therapy at least 3 months 
before enrolment 
• 
The patient has had previous recurrences of PCa, i.e. this is not the first 
diagnosis of BCR.  
Note: If patients are found to have violated any of the above key inclusion criteria for 
their assigned patient group, but they do fulfil the inclusion criteria for another group, 
the patient will be retrospectively re-assigned to the appropriate group, rather than 
being classified as having a major deviation, and excluded from the PP analysis set. 
For example, if a patient in Group B had not had a prior prostatectomy, but did have 
prior radiotherapy and fulfilled the entry criteria for Group C, then they would be re-
assigned for Group C for the purpose of analysis and reporting.  
In addition, any other deviations which may significantly interfere with the study 
outcomes may also be declared a major deviation. 
Major protocol deviations will be listed.  
In addition to the programmatic determination of the major deviations, monitoring notes 
or summaries will be reviewed to determine any important post entry deviations that 
are not identifiable via programming, and to check that those identified via 
programming are correctly classified.  The final classification will be made prior to 
database lock.   
Note, failure of an inclusion/exclusion criteria will not automatically be classified as a 
major deviation.   
5.2 
Important Deviations 
In addition to the programmatic determination of the major deviations as described in 
Section 5.1, the following important deviations will be programmatically derived and 
listed and summarized: 
• 
Failure of any inclusion/exclusion criteria (with exception patients of those listed in 
Section 5.1 as major deviations) 
• 
Administration of a non-approved modified dose of 68Ga-THP -PSMA1 
 
1 Note: The term “approved” dose is used to describe either the protocol-defined dose-range, 
or lower doses that have been confirmed by site not to affect image quality. Instances of lower 


 
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Finally, monitoring notes or summaries will be reviewed to determine any important 
post entry deviations that are not identifiable via programming, and to check that those 
identified via programming are correctly classified.  The final classification will be made 
prior to database lock.   
All patients who failed any inclusion/exclusion criteria will be listed along with details 
of the failed criteria. This information will also be summarized in terms of the number 
(%) of patient failing any of the inclusion/exclusion criteria and will be based on the 
Safety Set. Note, failure of an inclusion/exclusion criteria will not automatically be 
classified as a major deviation.   
Other deviations may occur during the trial, which are considered minor and not 
believed to have any significant impact on the interpretation of the study results.  All of 
these deviations will be recorded by the study monitors but will not be listed or 
summarized as part of the CSR. 
Examples of minor deviations include: 
• 
Visits outside of protocol visit windows 
• 
Incomplete assessments 
This list is not exhaustive and other minor deviations may occur.  
6. 
General Statistical Considerations 
All statistical analyses will be performed by, or under the direct auspices of 
Theragnostics. 
For the purposes of this SAP, the end of the study is formally defined as the date of 
database lock (DBL), which is anticipated to occur within 6 weeks after the last patient 
has completed their final visit. The primary data analysis will be performed after the 
database has been locked. 
 
Continuous data will be summarized in terms of the mean, standard deviation, median, 
minimum, maximum and number of observations, unless otherwise stated. The 
minimum and maximum will be reported to the same number of decimal places as the 
raw data recorded in the database. The mean and median will be reported to one more 
decimal place than the raw data recorded in the database. The standard deviation will 
be reported to two more decimal places than the raw data recorded in the database. 
In general, the maximum number of decimal places reported shall be four for any 
summary statistic. 
Categorical data will be summarized in terms of the number of patients providing data 
at the relevant time point (n), frequency counts and percentages.  
 
doses being administered and approved are captured in the trial master file and will not be 
classified as important deviations.   


 
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Percentages will be presented to one decimal place. Percentages will not be presented 
for zero counts. Percentages will be calculated using “n” as the denominator. If sample 
sizes are small, the data displays will show the percentages, but any textual report will 
describe frequencies only.  
For the purpose of reporting, for each patient, Study Day 1 is defined as the date of 
68Ga-THP -PSMA IV dose. 
The study is recruiting three distinct patient groups (Groups A, B and C), and unless 
stated otherwise, the following reporting conventions will apply: 
• 
Data will be presented for Group A (Newly Diagnosed patients), Groups B + C 
(BCR Patients) and Overall (Groups A + B + C). 
 
6.1 
Sample Size Estimation 
The sample size was based on the degree of uncertainty in the estimation of the 
primary outcome, the percentage of patients with a change in management, as 
measured by the confidence interval. Due to the phase of the study, at this stage 
relatively wide confidence intervals are allowed. 
For Group A, previous literature suggests that approximately 25% of patients would 
change management. Assuming a 95% confidence level, it is calculated that 20 
patients would be sufficient to obtain an estimate of the primary outcome that is within 
±20% of the population figure.  
For Groups B+C, previous literature suggests that approximately 45% would change 
management. With a 95% confidence level, a sample size of 40 patients in the two 
groups combined would be enable the primary outcome to be estimated to 
approximately ±15% of the population value. 
6.1.1 
Sample Size Re-estimation 
There are no planned sample size re-estimations. 
6.2 
Adjustments for Covariates 
Not applicable. 
6.3 
Handling of Dropouts or Missing Data 
In general, missing data will remain missing and will not be included in analyses.   
Exceptions are described below.  
• 
Missing Baseline Data 
If a baseline (Day 1) value is not available and a screening value is available for the 
same parameter, then the last screening value will be used as baseline.   


 
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6.4 
Monitoring and Interim Analyses 
6.4.1 
Monitoring 
The study will be monitored to ensure that the study is conducted and documented 
properly according to the protocol, good clinical practice (GCP), and all applicable 
regulatory requirements. 
6.4.2 
Interim Analysis 
6.4.2.1 Purpose of Interim Analyses 
An interim analysis was planned in the protocol to provide some early indication of the 
study results, specifically for the primary outcome, CMPR.  
 
The interim analysis was not performed. 
6.4.2.2 Planned Schedule of Interim Analyses 
Details of the planned interim analysis can be found in the study protocol. This analysis 
did not take place. 
6.5 
Multiple Testing Strategy 
Not applicable, since there is no formal hypothesis testing. 
6.6 
Examination of Subgroups 
Unless stated otherwise, the following reporting conventions will apply: 
• 
Data will be presented for Group A (Newly Diagnosed patients) 
• 
Groups B + C (BCR Patients)  
• 
Overall (Groups A + B + C). 
No further study subgroups will be considered. 
6.7 
Stratification Factors 
Not applicable. 
7. 
Methods of Analysis  
7.1 
Change in Management Plan Rate (CMPR) 
The primary endpoint, CMPR, will be summarized based on the FAS to show the 
number and percentage of patients categorized with a change status of “yes” (Section 
3.1.1). The two-sided 95% Clopper Pearson exact confidence interval, and the two-
sided 80% Clopper Pearson exact confidence interval will also be presented for the 
CMPR.  


 
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A listing presenting each patient’s change status will also be presented.  
The primary analysis of CMPR will be based on the FAS. A sensitivity analysis based 
on the PP set will also be presented, as described above for the FAS, if the FAS and 
PP sets differ. 
7.2 
Assessment of Safety and Tolerability  
7.2.1 
Assessment of Adverse Events 
All safety data will be assessed for the Safety population.  
All AE data will be listed along with information regarding the onset date and study 
day, end date (or ongoing), CTC grade, SAE criteria fulfilled, causality assessment 
(yes/no), and action taken and outcome.  
Treatment emergent AEs (TEAEs) are defined as AEs with an onset date on or after 
the administration of the 68Ga-THP -PSMA IV dose. The following summaries will be 
produced for all TEAEs:  
• 
An overview table of the incidence of TEAEs, grade 3+ TEAEs, SAEs, TEAEs 
leading to discontinuation from the study and TEAEs leading to death. For each 
summary category, the results will be shown overall (regardless of causality), and 
for the incidence of causally related TEAEs. For example, the overall incidence of 
TEAEs will be presented, as well as the incidence of TEAEs related to 68Ga-THP -
PSMA will be presented.  
o Note: If an AE is reported more than once during the study for an individual 
patient, the greatest severity and the worst-case attribution will be 
presented in the above summary table. 
• 
Summary of TEAEs by system organ class (SOC) and preferred term: Both the 
number and percentage of patients in each category (patient-level summary) and 
the number of episodes (episode-level summary). 
o Note: For the patient-level summary, patients will only be counted once if 
they have multiple incidence of the same TEAE. For the episode-level 
summary, each individual episode will be counted. 
Additionally, the following will be listed if any TEAEs in these categories occur during 
the trial:  
• 
AEs with outcome of death along with the date of onset, study day, and 
investigator’s assessment of severity and causality, and primary cause of death  
• 
All SAEs along with the date of onset, study day, date of resolution (if AE is 
resolved), investigator’s assessment of severity and causality and SAE criteria 
fulfilled. 
Any AEs commencing >30 days after the administration of  68Ga-THP -PSMA will not 
be included in the tabulations of AE data.  


 
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7.2.2 
Assessment of Safety  
All clinical laboratory data (clinical chemistry, hematology and urinalysis data), vital 
signs and ECG data will be listed.  
In addition, hematology, blood biochemistry and vital signs data will be summarized 
descriptively (n, mean, std, median, min and max) by time point. 
Additionally, for the ECG assessments, the following data summaries will also be 
produced: 
• 
For time point, the number and percentage of patients with clinically significant 
abnormal ECG reading will be summarised. 
Furthermore, to provide a preliminary evaluation of the cardiac effects, the following 
categorical data summary table will be produced: 
• 
The proportion of patients obtaining treatment-emergent absolute QTcB values 
> 450 ms and ≤ 480 ms; > 480 ms and < 500 ms; and > 500 msec 
• 
The proportion of patients obtaining a QTcB increase from baseline values ≥30-
60 ms and ≥60 ms 
• 
The proportion of patients obtaining a QRS change from baseline > 25% 
resulting in QRS > 120 ms 
• 
The proportion of patients obtaining a PR interval change from baseline >25% 
reaching a value >220 ms 
• 
The proportion of patients obtaining a > 25% decrease from baseline in heart 
rate, resulting in a heart rate < 50 beats per minute (bpm) or a >25% increase 
from baseline in heart rate resulting in a heart rate > 100 bpm 
7.3 
Disposition of Patients 
A summary of the number of patients that reached the various stages of the study will 
be summarized, along with a supporting listings outlining each patient’s progression 
through the study. Reasons for non-participation and withdrawal will be summarized 
and listed.  
 
A flow diagram will also be provided, outlining both the flow of patients, and the 
exclusions from the analysis sets. 
7.4 
Demographics and Baseline Characteristics 
Demographic and baseline characteristic data will be presented based on the safety 
set.  
 
Baseline demographic data, including, but not limited to: 
• 
age 
• 
race (Asian, White, Black or Other) 


 
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• 
weight 
• 
height 
• 
BSA 
• 
ECOG Status 
 
will be listed and summarised using appropriate descriptive statistics. 
7.5 
Primary Diagnosis Information 
The following information relating to the patients’ primary diagnosis will be listed and 
summarised: 
• 
PSA at diagnosis 
• 
PSA after radical treatment (nadir) 
• 
PSA prior to scan 
• 
Initial Diagnosis Stage 
• 
Initial Gleason Score 
• 
Initial Diagnosis Stage: T, N and M staging will be summarized separately 
 
7.6 
PSA At Diagnosis and After Radical Treatment (Groups B and C only) 
For patients with BCR (Groups B and C), the date of radical treatment, the PSA at 
diagnosis and after radical treatment, and the date of BCR will be listed. 
Additionally PSA at diagnosis and after radical treatment will be summarized 
descriptively. 
7.7 
Prior Cancer Therapy 
Prior cancer therapies will be listed. 
7.8 
Medical History and Prior and Concomitant Medications  
Relevant medical history will be listed.  
 
All medications received from Study Day 1 onwards (including those that were ongoing 
prior to administration of 68Ga-THP -PSMA) will be listed.  
 
7.9 
Treatment Management Plan Details 
A listing indicating each patient’s intended, revised and agreed treatment management 
plan will be provided. 
7.10 Prior Imaging Assessments 
Imaging history data will be listed. 


 
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8. 
Changes from the Protocol 
For the purpose of patient enrolment, 3 patient groups were defined in the protocol: 
• 
Group A: newly diagnosed with primary high-risk prostate cancer and are 
scheduled for radical prostatectomy surgery 
• 
Group B: BCR patients previously treated with radical prostatectomy 
• 
Group C: BCR patients previously treated with radical radiotherapyGroup A: 
The distinction between groups B and C in the protocol was to clearly define the two 
types of BCR patients eligible for inclusion in this study. 
For the purpose of reporting, groups B and C will be combined, to present the effects 
in BCR patients (regardless of prior treatment pathway). 
The protocol included an interim analysis to be performed when both of the following 
two criteria had been met: 
i. 
30 of the 60 patients from all groups combined to have completed the study 
ii. 
10 of the 20 patients from group B to have completed the study 
The interim analysis was not performed, and the study will be reported following the 
DCO for the primary data analysis (Section 6). 
9. 
Programming Considerations 
The data analysis will be performed using SAS version 9.4. Programs recording details 
of all data manipulation and data analyses will be produced and kept, so that the 
analyses can be externally inspected and, if necessary, re-run.  
   
 


 
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10. 
LIST OF TABLES, FIGURES AND LISTINGS 
10.1 Tables 
Table 
Number 
Table Title 
14.1.1 
Subject Disposition and Withdrawals – All Patients 
14.1.2 
Analysis Populations – All Patients 
14.1.3 
Major Protocol Deviations – Safety Set  
14.1.4 
Important Protocol Deviations – Safety Set  
14.1.5 
Demographic Characteristics – Safety Set 
14.1.6 
Primary Diagnosis Information – Safety Set  
14.2.1 
Change in Patient Management Plan –  Full Analysis Set 
14.2.2 
Sensitivity Analysis of Change in Patient Management Plan –  Per 
Protocol Set 
14.2.3 
68Ga-THP-PSMA PET Scan Performance Characteristics – Full 
Analysis Set 
14.3.1 
Overview of TEAEs – Safety Set 
14.3.2 
Incidence of TEAEs by System Organ Class and Preferred Term – 
Subject and Episode Level – Safety Set 
14.3.2.1 
Incidence of Causally Related TEAEs by System Organ Class and 
Preferred Term – Patient and Episode Level – Safety Set 
14.3.3 
Summary Statistics for Haematology Parameters – Safety Set 
14.3.4 
Summary Statistics for Clinical Chemistry Parameters – Safety Set 
14.3.5 
Summary Statistics for Urine pH – Safety Set 
14.3.6 
Summary Statistics for Vital Signs Parameters – Safety Set 
14.3.7 
Absolute Values and Change from Baseline for 12-Lead ECG 
Parameters – Safety Set 
14.3.8 
12-Lead ECG Overall Evaluation by Visit – Safety Set 
14.3.9 
Categorical ECG Data Summaries – Safety Set 
 


 
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10.2 Listings 
Listing 
Number 
Listing Title 
16.2.1.1 
Discontinuation Information – Safety Set 
16.2.1.2 
Inclusion/Exclusion Criteria Eligibility – All Subjects 
16.2.1.3 
Screening Failure Data – All Subjects 
16.2.1.4 
Patient Progress through Study – All Subjects 
16.2.2.1 
Major Protocol Deviations – Safety Set 
16.2.2.2 
Important Deviations – Safety Set 
16.2.3 
Analysis Populations – All Subjects 
16.2.4.1 
Demographic Characteristics – Safety Set 
16.2.4.2 
Primary Tumour Diagnosis – Safety Set 
16.2.4.3 
Previous Radical Treatment – Safety Set (Groups B & C) 
16.2.4.4 
Medical History – Safety Set 
16.2.4.5 
Prior Cancer Therapies – Safety Set 
16.2.4.6 
Imaging History – Safety Set 
16.2.4.7 
Concomitant Medications – Safety Set 
16.2.5.1 
68Ga-THP_PSMA Injection – Safety Set 
16.2.5.2 
68Ga-THP-PSMA PET/CT Imaging – Full Analysis Set 
16.2.6 
Patient Management Plans– Safety Set 
16.2.7.1 
Adverse Events – Safety Set 
16.2.7.2 
Serious Adverse Events – Safety Set 
16.2.7.3 
Adverse Events Leading to Death – Safety Set 
16.2.7.4 
Deaths – Safety Set 
16.2.8.1 
Haematology Parameters – Safety Set 
16.2.8.2 
Clinical Chemistry Parameters – Safety Set 


 
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Listing 
Number 
Listing Title 
16.2.8.3 
Urinalysis Parameters – Safety Set 
16.2.8.4 
Urine Microscopy Parameters – Safety Set 
16.2.8.5 
Vital Signs – Safety Set 
16.2.8.6 
ECG Assessment– Safety Set 
16.2.8.7 
Physical Examinations– Safety Set 
16.2.8.8 
ECOG Assessments – Safety Set 
 
10.3 Figures