A Multicentre, Randomised, Dose-confirmation, Factorial Phase II Study to Evaluate the Optimal Dose of 68Ga-OPS202 as a PET Imaging Agent in Subjects With Gastroenteropancreatic Neuroendocrine Tumour (GEP-NET)
Phase: PHASE2
Conditions: Gastro-Enteropancreatic Neuroendocrine Tumor
Sponsor: Ipsen



IPSEN GROUP 
D-FR-01070-002 
 
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COORDINATING INVESTIGATOR’S AGREEMENT 
 
Coordinating Investigator Agreement and Signature: 
I have read and agree to Protocol D-FR-01070-002 entitled “A multicentre, randomised, 
dose-confirmation, factorial phase II study to evaluate the optimal dose of 68Ga-OPS202 as a 
PET imaging agent in subjects with gastroenteropancreatic neuroendocrine tumour 
(GEP-NET)”. I am aware of my responsibilities as a coordinating investigator under the 
guidelines of Good Clinical Practice (GCP), local regulations and the study protocol. I agree to 
conduct the study according to these guidelines and to appropriately direct and assist the staff 
under my control, who will be involved in the study. 
   
NAME:  
 
TITLE: COORDINATING 
SIGNATURE: 
 
INVESTIGATOR 
   
   
DATE: 
OFFICE: 
UCLA Nuclear Medicine 
 
200 Medical Plaza, Suite B114 
 
Los Angeles, CA 90095 
 
USA 
 
 
 
PPD

IPSEN GROUP 
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SUMMARY OF CHANGES 
The current version of the protocol was released on 20 May 2019 and includes Amendment 3.0. 
For all protocol amendments, amendment forms were prepared and are provided in the 
Appendices listed in Table 1. All modifications (except minor changes) are presented in the 
appendices.  
Table 1 List of Protocol Amendments 
Amendment 
Release date 
Amendment form 
Original (Version 2.0) 
30 March 2017 
Appendix 2 
1.0 (Version 3.0) 
16 June 2017 
Appendix 3 
2.0 (Version 4.0) 
03 May 2018 
Appendix 4 
3.0 (Version 5.0) 
20 May 2019 
Appendix 5 
 

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SYNOPSIS  
 
Name of sponsor/company: IPSEN  
Name of finished product: 68Ga-OPS202 - 68Ga-satoreotide trizoxetan 
Name of active ingredient(s): 68Ga-OPS202 - INN for OPS202 is satoreotide trizoxetan 
Title of study: A multicentre, randomised, dose-confirmation, factorial phase II study to 
evaluate the optimal dose of 68Ga-OPS202 as a PET imaging agent in subjects with 
gastroenteropancreatic neuroendocrine tumour (GEP-NET) 
Study number: D-FR-01070-002 
Number of planned centres: Six specialised centres in the United States and Europe  
Planned study period: 
FPI: June 2017 - LPO: September 2019 
Phase of development: Phase II 
Objectives: 
Primary Study Objective:  
• 
To define the optimal dose range for peptide mass and radioactivity of 68Ga-OPS202 
based on detected lesions in adult subjects with somatostatin receptor 2 
(sstr2)-positive gastroenteropancreatic neuroendocrine tumour (GEP-NET). 
Secondary Study Objectives: 
• 
To further refine the optimal dose range for peptide mass and radioactivity of 
68Ga-OPS202 based on quantitative maximum standardized uptake value (SUVmax) 
and other quality parameters.  
• 
To describe the safety and tolerability of diagnostic 68Ga-OPS202 in subjects with 
sstr2-positive GEP-NET. 
• 
To characterize the pharmacokinetics (PK) of OPS202 in subjects with GEP-NET. 
Exploratory Objective: 
• 
To provide preliminary estimates of the sensitivity of 68Ga-OPS202 positron 
emission tomography/computed tomography (PET/CT) scan imaging, as well as 
SUV ratio (SUVmax lesion/ SUVmean reference tissue) and signal-to-noise ratios 
(SNR). 

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Duration of participation for a subject  
Subject participation in the study is estimated to last approximately 7 weeks and will 
include: 
• 
Visit 1: A screening period up to 2 weeks 
• 
Visit 2: A single i.v. injection of the first peptide/radioactivity dose of 68Ga-OPS202 
on Day 1 followed by PET/CT scan imaging 1 hour post dosing (up to 80 min) 
• 
Visit 3: A single i.v. injection of the second peptide/radioactivity dose of 
68Ga-OPS202 followed by PET/CT scan imaging 1 hour post dosing (up to 80 min), 
after a 15- to 21-day time interval from the first administration (Visit 2) 
• 
Visit 4: A 2-week follow-up period for evaluation of safety. 
 
Study Design and Subject Allocation 
Assessments 
At the Screening Visit (Visit 1) performed within 2 weeks prior to the first 68Ga-OPS202 
administration, the investigator will collect all the information required to check the 
eligibility of the subject to participate in the study including medical and surgical history, 
physical examination, laboratory tests (including haematology, blood chemistry and 
urinalysis) and tumour histopathology. Results from a somatostatin receptor positive scan 
within 6 months prior to the first 68Ga-OPS202 administration will be collected and sent to 
the ICL for assessment of quality and admissibility.  
Subjects’ eligibility will be re-checked by the investigator at Baseline/Day 1 (Visit 2) 
before randomisation. If the eligibility is confirmed, the subject will be randomly allocated 
to one of the three study arms to receive the first dose of 68Ga-OPS202 with PET/CT 
imaging, then discharged the day after. Intravenous iodinated CT contrast is required and 
will be injected according to the site standard procedure. This procedure will be repeated 
after 15 to 21 days at Visit 3 (Day 16 to 22) with the appropriate peptide/radioactivity dose 
range combinations of 68Ga-OPS202 as indicated by the subject’s randomisation. The 
PET/CT scanner must be the same for the two scans per subject and for all subjects at the 
same study site. Subjects may be hospitalised overnight at the discretion of the investigator. 

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For OPS202 PK, blood samples of 2 mL will be collected at the following timepoints: 
Baseline pre-dose (T0), 5 min, 15 to 45 min, 1h, 2h, 3h and 6h after the 68Ga-OPS202 i.v. 
administration at the corresponding visits (Visit 2 and Visit 3). Urine will also be collected 
during the first 6 hours in two separate samples: 0h to 3h and 3h to 6h after the 
68Ga-OPS202 i.v. administration. 
An End of Study Visit (Visit 4) will take place 2 weeks after the second PET/CT scan, 
during which the investigator will collect the safety information required by the study 
protocol (See Criteria of Safety Evaluation below). At the end of Visit 4, the subject’s 
participation in the study will end. For any adverse event (AE) emerging or worsening 
during the study that persists beyond Visit 4, the investigator will monitor the subject until 
the AE is resolved or considered stabilized. 
Comparative methods and blinding 
This is an open-label study. Independent readers will evaluate 68Ga-OPS202 PET/CT 
images and will be blinded to the investigator site and clinical status of the subject, 
including pathology, laboratory, and history/physical exam findings. Furthermore, the 
independent readers will be blinded to peptide mass dose, radioactivity dose, and the 
temporal sequence of dosing. 
Independent readers are specialized radiologists and/or nuclear medicine physicians who 
are experienced in reading 68Ga-radiolabeled agent PET/CT scans. To minimize inter- and 
intra-reader variability in results, the readers will be specifically trained for this protocol. 
Number of subjects planned:  
A total of 24 evaluable subjects with GEP-NET and two 68Ga-OPS202 PET/CT scans 
completed are required (8 subjects in each of the three study arms). A total of at least 25 
subjects will be enrolled in the study to ensure the 48 PET/CT scans for the analysis (see 
below Sample size and power considerations) 
Diagnosis and criteria for inclusion: 
Following a screening period of up to 2 weeks, eligible subjects will be enrolled in the 
study if they meet all the following inclusion criteria, and none of the following exclusion 
criteria:  
Inclusion criteria: 
1) Men or women aged 18 years or older  
2) Subjects 
with 
pathologically 
confirmed, 
well-differentiated 
functioning 
or 
nonfunctioning metastatic GEP-NET (Grade I and II as per World Health Organization 
(WHO) classification 2010)  
3) Subjects with a confirmed presence of somatostatin receptors (type 2) on technically 
evaluable tumour lesions documented by a positive somatostatin receptor scan within 
6 months prior to screening (Visit 1) and showing a minimum of two lesions in at least 
one of the key organs namely liver, lymph nodes, bone or lungs; these images shall be 
available to be sent to the ICL electronically to ascertain quality and admissibility 
4) Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 
5) Subjects with body weight between 50 kg (110 lb) and 110 kg (243 lb), inclusive 
6) Adequate bone marrow, liver and renal function, with: 
• 
Calculated glomerular filtration rate (GFR): ≥ 45 mL/min  

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• 
Albumin: > 30 g/L 
• 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (AP): ≤ 5 times ULN (upper limit of normal) 
• 
Bilirubin: ≤ 3 times ULN (3 × 1.1 mg/dL) 
• 
Leukocytes: ≥ 3*109/L and neutrophils ≥ 1*109/L 
• 
Erythrocytes: ≥ 3.5*1012/L 
• 
Platelets: ≥ 90*109/L 
7) Signed written informed consent prior to any study-related procedures 
Exclusion criteria: 
1) Subjects with fewer than five lesions in total and more than 25 lesions/organ detected 
by the somatostatin receptor positive scan in key organs: liver, lymph nodes, bone or 
lung 
2) Subjects who have received treatment of any somatostatin analogue, including 
Somatuline® Autogel® /Depot®, Sandostatin® LAR within 28 days, and Sandostatin® 
within 24 hours prior to first 68Ga-OPS202 administration 
3) Presence of active infection at screening or history of serious infection within the 
previous 6 weeks prior to the first 68Ga-OPS202 administration 
4) Prior or planned administration of a radiopharmaceutical within 8 half-lives of the 
radionuclide  
5) Clinically relevant trauma within 2 weeks prior to first 68Ga-OPS202 administration 
6) Known 
hypersensitivity 
to 
radiolabeled 
1,4,7-triazacyclononane,1-glutaric 
acid-4,7-acetic acid (NODAGA), to Gallium-68, to somatostatin analog peptide JR11 
(JR11) or to any of the excipients of 68Ga-OPS202 
7) History of, or current active allergic or autoimmune disease, including asthma or any 
condition requiring long-term use of systemic corticosteroids 
8) Known human immunodeficiency virus (HIV) or positive serology for HIV, hepatitis B 
or C 
9) Any condition that precludes the proper performance of PET and/or CT scan: 
• 
Subjects who are not able to tolerate the CT contrast agent,  
• 
Subjects with metal implants or arthroplasty, or any other objects that might interfere 
with the PET and/or CT analysis 
• 
Subjects unable to raise arms for prolonged imaging purposes  
• 
Subjects unable to lie still for the entire imaging time 
• 
Subjects weighing greater than 110 kg (243 lb) 
10) Administration of another investigational medicinal product within 30 days prior to first 
68Ga-OPS202 administration 
11) Female subjects who are pregnant, breast feeding or of childbearing potential not 
willing to practice effective contraceptive techniques during the study treatment period 
and for 30 days after the last dose of 68Ga-OPS202 administration; pregnancy test must 
be performed at the start of the study and prior to each 68Ga-OPS202 administration 
12) Subjects who have any severe and/or uncontrolled medical conditions or other 
conditions that could affect their participation in the study, including any mental 

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condition rendering the subject unable to understand the nature, scope, and possible 
consequences of the study, and/or evidence of an uncooperative attitude 
13) Subject who experienced a previous cancer (except basocellular carcinoma of the skin 
and/or in situ carcinoma of the cervix/uterus and/or subjects treated with curative intent 
and free from disease for more than 5 years) other than NET. 
Test product, dose, mode of administration: 
68Ga-OPS202 is a diagnostic medicinal product with 3 main components, namely: 
• 
68Ga, a positron emitter radionuclide with a half-life of 68 min  
• 
NODAGA, a chemical chelator group, and 
• 
JR11, an antagonist somatostatin analogue that binds to sst2 receptors 
OPS202 (cold kit) is available for clinical trials in a 50 μg peptide mass dose vial and is 
radiolabeled using a 68Ge/68Ga-generator. The radiolabelled OPS202 (68Ga-OPS202) 
consists of 50 μg of peptide in a total volume of 6 mL (8.33 μg/mL).  Sampling of 0.5 mL 
for quality control yields 5.5 mL solution from which the volume to be injected into the 
subject is withdrawn. This volume is calculated to obtain the target peptide mass dose and 
the desired radioactivity dose. 
The calculation of the volume takes into account the different components that determine 
the final radioactivity dose. The subject will be exposed to, in particular:  
• 
The amount of 68Ga eluted from the generator, which depends on the latter’s half-life 
• 
The time elapsed between OPS202 (cold kit) radiolabelling and the injection of 
68Ga-OPS202 to the subject (decay of 68Ga), the variation of which is a tool to adjust 
the final peptide/radioactivity dose to be injected 
• 
The required peptide mass dose and radioactivity dose of 68Ga-OPS202 to be 
injected. 
The actual peptide mass dose administered to the subject (injected dose) will be estimated 
using the following equation: 
Injected dose (μg) = [Volume injected (mL) / Volume used for 68Ga-OPS202 preparation 
(mL)] x Peptide dosage in the vial (μg) = [Injected Volume/6mL] x 50μg  
The radioactivity in the syringe is measured immediately before the administration of 
68Ga-OPS202 to the subject and immediately after; the difference between these two 
measurements (in MBq) constitutes the radioactivity dose injected to the subject. 
68Ga-OPS202 will be administered twice during the study for each subject by i.v. injection 
over one minute prior to PET/CT scan. The PET/CT scanner settings should be the same 
for the two scans per subject and for all subjects at the same study site, as described in the 
Imaging Review Charter (IRC). 
Duration of treatment: 68Ga-OPS202 will be administered i.v. twice: at Baseline/Day 1 
(Visit 2), and at Visit 3, which will be 15 to 21 days after the first injection. 

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Reference therapy, dose and mode of administration:  
Comparator compound/placebo: 
In this study, there is no comparison with a placebo or reference-imaging product. The 
statistical analyses will describe the differences between the different combinations of 
peptide mass dose range and radioactivity dose range.  
Other treatments: Any medication and/or therapy taken or received by the subject during 
the study, other than the study investigational compound (68Ga-OPS202), will be 
considered concomitant medication whether or not it is targeting the studied GEP-NET. 
Concomitant treatments are to be prescribed, modified, or discontinued at the investigator 
discretion.  Subjects must be withdrawn from the study, but followed-up when possible for 
further data collection, if at least one of the protocol-prohibited medications/therapies (see 
above-mentioned eligibility criteria) is received by the subjects during the study period up 
to the end of the second PET/CT scan (at Visit 3). 
Any addition, change, or discontinuation of concomitant medications should be 
documented as defined in the study protocol. 
Criteria for evaluation: 
Efficacy: 
All the primary and secondary imaging endpoints are read by third-party independent 
readers. Most of the reading will be conducted in blinded manner. Primary and secondary 
endpoints will be measured in key organs: liver, lymph nodes, bone and lungs. 
Primary Endpoint and Evaluation: 
• 
For each combination of injected peptide/radioactivity dose ranges, differences in 
relative lesion counts derived from a 2 × 3 factorial analysis measuring the ratio of 
the number of lesions detected by 68Ga-OPS202 to the number of lesions assessed 
by standard-of-truth (descriptive analyses). 
The standard-of-truth in the present study is the CT scan images acquired at Visit 2 and 
Visit 3.  
Secondary endpoints and evaluations: 
Key secondary endpoint: 
• 
For each combination of injected peptide/radioactivity dose ranges, differences in 
image quality derived from a 2 × 3 factorial analysis measuring the 
tumour-to-background ratio in each of the major anatomic sites (descriptive analyses 
for liver, lymph nodes, bone and lungs)  
A qualitative analysis of the image assessed by the independent blinded readers will be 
performed to back up the quantitative quality measured by tumour-to-background analysis.  
Other secondary endpoints: 
• 
Differences in lesion SUVmax between the two peptide mass dose ranges and the 
three radioactivity dose ranges measured in the most avid lesions (descriptive 
analyses for up to a maximum of five lesions per organ in liver, lymph nodes, bone 
and lungs) 
• 
Differences of absolute number of lesions between the two peptide mass dose ranges 
and the three radioactivity dose ranges detected in each of the following anatomic 
sites:  

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• 
Primary site of GEP-NET  
• 
Lymph nodes  
• 
Liver  
• 
Axial/appendicular skeleton  
• 
Lungs 
The primary and secondary endpoints will also be evaluated on a radioactivity dose/kg of 
body weight. 
Exploratory endpoints: 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of GEP-NETs by both 
subject-based and lesion-based analysis compared to standard-of-truth 
• 
Comparison to sstr2 agonist results will be computed for sensitivity analysis 
• 
Differences in SUVmax ratios between the two peptide mass dose ranges and three 
radioactivity dose ranges for lesions 
• 
SNR calculated from lesion-free volume of interest (VOI) in the liver: 
SUVmean/SUVSD between the three radioactivity doses. 
For further details on efficacy endpoints, refer to the core study protocol and IRC. 
Safety: 
The investigator will report the occurrence of any AE throughout the study, including 
clinically significant abnormalities in laboratory tests (serum chemistry, haematology, and 
urinalysis), vital signs (blood pressure and heart rate) measurements, physical examination 
findings and body weight measurements at each visit: Screening Visit (Visit 1), Baseline 
Visit (Visit 2; Day 1), Visit 3 (Day 16 to Day 22), and End of Study/ Early Withdrawal 
Visit (Visit 4; Day 30 to Day 36). The electrocardiogram (ECG) findings are to be recorded 
at Screening Visit and End of Study/ Early Withdrawal (Visit 4; Day 30 to Day 36). 
Concomitant medications/therapies will also be recorded throughout the study. 
The following safety endpoints will be evaluated: 
• 
Proportion of subjects experiencing at least one AE of any grade according to 
NCI-CTCAE v5.0), including any SAEs and suspected unexpected serious adverse 
reactions (SUSARs); all AEs will be coded using Medical Dictionary for Regulatory 
Activities (MedDRA) system organ class (SOC) and preferred term (PT) (as per most 
recent version) 
• 
Proportion of subjects experiencing at least one AE of grade ≥3 according to 
NCI-CTCAE   
• 
Clinically significant changes in physical examination, vital signs, ECG and 
laboratory findings, which will be recorded by the investigator as AEs. 
Pharmacokinetics: 
• 
Characterization of the PK of OPS202: 
OPS202 blood and urine PK sampling will be performed for all subjects participating in 
the study. Blood samples for measurement of OPS202 plasma levels will be collected at 
different time points at Visit 2 and Visit 3 (see Study Design – Assessments section). 
OPS202 plasma concentrations will be measured using a validated analytical method. 
Remaining plasma from the PK samples may be used to control the presence of potential 
major metabolites of OPS202. Urine collection to determine renal excretion of OPS202 

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• 
All the 48 scans will serve for the primary and key secondary 2 × 3 factorial analysis 
endpoints 
• 
24 sets for each of the two peptide mass dose ranges regardless of the radioactivity 
dose which will be analysed to describe the difference between these two dose ranges 
• 
16 sets for each radioactivity dose range regardless of peptide mass dose, which will 
be analysed to describe the differences between these three dose ranges. 
The analysis will be descriptive and no formal statistical tests are planned for the primary 
and secondary endpoints. Mean, standard deviation, median and ranges will be estimated. 
The primary endpoint and secondary tumour-to-background ratio and SUVmax endpoints’ 
analyses will be performed following the 2 × 3 factorial distribution of the imaging sets per 
combination of peptide/radioactivity dose ranges.  
Overall differences among the three radioactivity doses, overall difference among the two 
peptide mass doses, and interaction between the peptide mass doses and radioactivity doses 
will be analysed. 
Interim Analysis 
An interim analysis will be performed when a minimum of 12 subjects have fully completed 
the study. The study will continue while the interim analysis is performed and the study 
may be stopped per sponsor’s decision based on expert review of the data. The interim 
statistical analysis plan will provide further details of the statistical analyses.  
 

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TABLE OF CONTENTS 
INVESTIGATOR’S AGREEMENT ...................................................................................... 2 
TABLE OF CONTENTS ....................................................................................................... 15 
LIST OF ABBREVIATIONS ................................................................................................ 20 
1 
BACKGROUND INFORMATION ............................................................................ 23 
1.1 
Introduction ................................................................................................................... 23 
1.2 
Rationale to Conduct the Trial .................................................................................... 25 
1.3 
Population to Be Studied .............................................................................................. 25 
1.4 
Peptide Mass Dose Rationale ....................................................................................... 25 
1.5 
Radioactivity Dose Rationale ....................................................................................... 26 
2 
PURPOSE OF THE STUDY AND STUDY OBJECTIVES ..................................... 27 
2.1 
Purpose of the Study ..................................................................................................... 27 
2.2 
Study Objectives ........................................................................................................... 27 
3 
STUDY DESIGN ........................................................................................................... 28 
3.1 
General Design and Study Schema ............................................................................. 28 
3.2 
Primary and Secondary Endpoints and Evaluations ................................................ 29 
3.2.1 
Primary Efficacy Endpoint and Evaluation .............................................. 29 
3.2.2 
Secondary Efficacy Endpoints and Evaluations ........................................ 29 
3.2.3 
Safety Endpoints and Evaluations ............................................................. 30 
3.2.4 
Pharmacokinetic Endpoints ....................................................................... 31 
3.3 
Randomisation and Blinding ....................................................................................... 31 
3.4 
Study Imaging Product and Dosage ............................................................................ 32 
3.5 
Study Duration .............................................................................................................. 33 
3.6 
Stopping Rules and Discontinuation Criteria ............................................................ 33 
3.7 
Investigational Imaging Product Preparation, Storage and Accountability ........... 34 
3.7.1 
Investigational Imaging Product Storage and Security ............................ 34 
3.7.2 
Investigational Imaging Product Preparation ........................................... 34 
3.7.3 
Investigational Imaging Product Accountability ....................................... 34 
3.8 
Maintenance of Randomisation and Blinding ............................................................ 34 
3.9 
Source Data Recorded on the Case Report Form ...................................................... 34 
4 
SELECTION AND WITHDRAWAL OF SUBJECTS ............................................. 36 
4.1 
Inclusion Criteria .......................................................................................................... 36 
4.2 
Exclusion Criteria ......................................................................................................... 36 
4.3 
Subject Withdrawal Criteria and Procedures ........................................................... 37 
5 
STUDY PROCEDURES .............................................................................................. 38 
5.1 
Study Schedule .............................................................................................................. 38 
5.2 
Study Visits .................................................................................................................... 39 
5.2.1 
Procedures for Screening and Enrolment (Visit 1) ................................... 39 

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5.2.2 
Procedures Before Study IIP administration (Baseline/Visit 2 and Visit 
3 Predose) .................................................................................................... 40 
5.2.3 
Procedures During Study Treatment (Visit 2 and Visit 3 - Postdose) ....... 41 
5.2.4 
Procedures After Study Imaging Agent Administration ........................... 41 
5.2.4.1 
End of Study Visit (Visit 4) or Early Withdrawal Visit ................................ 41 
6 
DIAGNOSTIC IMAGING OF SUBJECTS ............................................................... 43 
6.1 
Study Imaging Product ................................................................................................ 43 
6.1.1 
68Ga-OPS202 ............................................................................................... 43 
6.1.1.1 
Spillage ........................................................................................................ 44 
6.1.2 
Other Investigational Medicinal Products ................................................. 44 
6.1.3 
Other Study Drugs ...................................................................................... 44 
6.2 
Concomitant Medication/Therapy .............................................................................. 45 
6.3 
Procedures for Monitoring Subject Compliance ....................................................... 45 
7 
ASSESSMENT OF EFFICACY .................................................................................. 46 
7.1 
Primary Efficacy Endpoint and Evaluation ............................................................... 46 
7.2 
Secondary Efficacy Endpoints and Evaluations ........................................................ 46 
7.3 
Methods and Timing of Assessing, Recording, and Analysing Efficacy Data ......... 47 
8 
ASSESSMENT OF SAFETY ....................................................................................... 49 
8.1 
Adverse Events .............................................................................................................. 49 
8.1.1 
Categorisation of Adverse Events ............................................................... 49 
8.1.1.1 
Intensity Classification ................................................................................. 49 
8.1.1.2 
Causality Classification ............................................................................... 50 
8.1.1.3 
Assessment of Expectedness ......................................................................... 50 
8.1.1.4 
Laboratory Test Abnormalities .................................................................... 50 
8.1.1.5 
Abnormal Physical Examination Findings .................................................. 50 
8.1.1.6 
Other Investigation Abnormal Findings ...................................................... 50 
8.1.2 
Recording and Follow up of Adverse Events ............................................. 50 
8.1.3 
Reporting of Serious Adverse Events ......................................................... 51 
8.1.4 
Pregnancy .................................................................................................... 52 
8.1.5 
Deaths .......................................................................................................... 53 
8.1.6 
Discontinuation/Withdrawal due to Adverse Events/Serious Adverse 
Events .......................................................................................................... 53 
8.2 
Clinical Laboratory Tests ............................................................................................ 53 
8.2.1 
Haematology ................................................................................................ 54 
8.2.2 
Blood Biochemistry ..................................................................................... 54 
8.2.3 
Urinalysis ..................................................................................................... 54 
8.2.4 
Pregnancy Test ............................................................................................ 54 
8.2.5 
Putative Antibody Testing ........................................................................... 54 
8.2.6 
Other Clinical Laboratory Tests ................................................................. 54 
8.3 
Physical Examination ................................................................................................... 54 

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8.4 
Vital Signs ...................................................................................................................... 55 
8.5 
Electrocardiography ..................................................................................................... 55 
9 
ASSESSMENTS OF PHARMACOKINETICS/PHARMACODYNAMICS .......... 56 
9.1 
Pharmacokinetics .......................................................................................................... 56 
9.1.1 
Sample Collection ....................................................................................... 56 
9.1.2 
Analytical Procedures ................................................................................. 56 
9.1.3 
Data Analysis ............................................................................................... 56 
10 
STATISTICS ................................................................................................................. 58 
10.1 Analysis Populations ..................................................................................................... 58 
10.1.1 
Populations Analysed .................................................................................. 58 
10.1.2 
Subject Allocation and Reasons for Exclusion from the Analyses ........... 58 
10.2 Sample Size Determination .......................................................................................... 58 
10.3 Significance Testing and Estimations ......................................................................... 59 
10.4 Statistical/Analytical Methods ..................................................................................... 59 
10.4.1 
Demographic and Other Baseline Characteristics .................................... 59 
10.4.2 
Homogeneity of Treatment Groups ............................................................ 59 
10.4.3 
Subject Disposition and Withdrawals ......................................................... 59 
10.4.4 
Pharmacokinetic Data ................................................................................ 59 
10.4.5 
Efficacy Evaluation ..................................................................................... 59 
10.4.6 
Adjustment for Country/Centre Effect ....................................................... 60 
10.4.7 
Safety Evaluation ........................................................................................ 60 
10.5 Subgroup Analyses ....................................................................................................... 61 
10.6 Interim Analyses ........................................................................................................... 61 
11 
DIRECT ACCESS TO SOURCE DATA AND DOCUMENTS ............................... 62 
12 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................... 63 
12.1 Protocol Amendments and Protocol Deviations and Violations ............................... 63 
12.1.1 
Protocol Amendments ................................................................................. 63 
12.1.2 
Protocol Deviations, Violations, and Exceptions ....................................... 63 
12.2 Information to Study Personnel .................................................................................. 63 
12.3 Study Monitoring .......................................................................................................... 63 
12.4 Audit and Inspection .................................................................................................... 64 
13 
ETHICS ......................................................................................................................... 65 
13.1 Compliance with Good Clinical Practice and Ethical Considerations .................... 65 
13.2 Informed Consent ......................................................................................................... 65 
13.3 Health Authorities and Independent Ethics Committees/Institutional Review 
Boards ............................................................................................................................ 66 
13.4 Confidentiality Regarding Study Subjects ................................................................. 66 
14 
DATA HANDLING AND RECORD KEEPING ....................................................... 67 
14.1 Data Recording of Study Data ..................................................................................... 67 

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14.2 Data Management ......................................................................................................... 67 
14.3 Record Archiving and Retention ................................................................................. 68 
15 
FINANCING AND INSURANCE ............................................................................... 69 
15.1 Contractual and Financial Details ............................................................................... 69 
15.2 Insurance, Indemnity and Compensation .................................................................. 69 
16 
REPORTING AND PUBLICATIONS OF RESULTS ............................................. 70 
16.1 Publication Policy ......................................................................................................... 70 
16.2 Clinical Study Report ................................................................................................... 70 
17 
REFERENCES .............................................................................................................. 71 
18 
LIST OF APPENDICES .............................................................................................. 72 
 

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LIST OF TABLES 
Table 1 List of Protocol Amendments .................................................................................... 4 
Table 2 Radiochemical Characteristics of 68Ga ................................................................... 24 
Table 3 Combinations of Studied Peptide Mass dose Ranges and Radioactivity Dose 
Ranges ................................................................................................................... 28 
Table 4 Sequences of Peptide Mass Doses and Radioactivity Doses .................................. 31 
Table 5 Study Procedures and Assessments ........................................................................ 38 
 
LIST OF FIGURES 
Figure 1 
Study Design and Subjects Allocation ............................................................... 28 
 

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LIST OF ABBREVIATIONS 
ABBREVIATION 
Wording Definition  
Ae 
Cumulative amount of unchanged drug excreted into the 
urine 
AE 
Adverse event 
ALARA 
As low as reasonably achievable 
ALT 
Alanine aminotransferase 
AP 
Alkaline phosphatase 
AST 
Aspartate aminotransferase 
AUC 
Area under the [plasma/serum/whole blood] concentration 
time curve  
AUClast 
area under the plasma concentration time curve from time 0 
to the time of the last quantifiable concentration 
AUC0-∞ 
Area under the [plasma/serum/whole blood] concentration 
time curve from time 0 to infinity 
BMI 
Body mass index 
CA 
Competent Authorities 
CFR 
Code of Federal Regulations  
CL 
Total plasma clearance 
Cmax 
Maximum observed [plasma/serum/whole blood] drug 
concentration 
CRO 
Contract research organisation 
CT 
Computed tomography 
D 
Day 
DICOM 
Digital Imaging and Communications in Medicine 
ECG 
Electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EDC 
Electronic data capture 
eCRF 
Electronic case report form 
EU 
European Union 
 
EU-GMP 
European Union Good Manufacturing Practices  
FDA 
Food and Drug Administration 
FDG 
Fluorodeoxyglucose 
68Ga 
Gallium – 68 
68Ga-DOTA-TATE  NETSPOT® 

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ABBREVIATION 
Wording Definition  
68Ga-DOTA-TOC 
Somakit-TOC 
GCP 
Good Clinical Practice 
GEP 
Gastroenteropancreatic 
GFR 
Glomerular filtration rate 
GGT 
Gamma-glutamyl transferase 
GI 
Gastrointestinal 
GMP 
Good Manufacturing Practice 
GRPP  
Good Radiopharmaceutical Practice 
EANM 
European Association of Nuclear Medicine 
HCG 
Human chorionic gonadotropin 
HIV 
Human immunodeficiency virus 
ICH 
International Conference on Harmonisation 
ICL 
Imaging core lab 
IEC 
Independent ethics committee 
IIP 
Investigational Imaging Product 
IND 
Investigational New Drug 
IRB 
Institutional review board 
IRC 
Imaging review charter 
i.v. 
Intravenous 
LC-MS/MS 
Liquid chromatography-tandem mass spectrometry  
max 
Maximum 
MBq 
Megabecquerel 
MCH 
Mean corpuscular haemoglobin 
MCHC 
Mean corpuscular haemoglobin concentration 
MCV 
Mean corpuscular volume 
MedDRA 
Medical Dictionary for Regulatory Activities 
MeV 
Mega electron-volt 
min 
Minimum 
MRI 
Magnetic resonance imaging 
NCI-CTCAE 
National Cancer Institute - Common Terminology Criteria 
for Adverse Events 
NEC 
Neuroendocrine carcinoma 

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ABBREVIATION 
Wording Definition  
NET 
Neuroendocrine tumour 
NOAEL 
No observable adverse effect level 
NODAGA 
1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid  
NOS 
Not otherwise specified 
PDM 
Pharmacokinetics, Dynamics and Metabolism 
PP 
Per protocol 
PET 
Positron emission tomography 
PK 
Pharmacokinetics 
PT 
Preferred Term 
QC 
Quality control 
RAP 
Reporting and analysis plan 
RBC 
Red blood cell(s) 
SAE 
Serious adverse event 
SAS® 
Statistical Analysis System® 
SD 
Standard deviation 
SNR 
Signal-to-noise ratio 
SOC 
System organ class 
SOP 
Standard operating procedure 
SPECT 
Single-photon emission computed tomography 
SSA 
Somatostatin analogues 
sstr 
Somatostatin receptors 
SUSAR 
Suspected unexpected serious adverse reaction 
SUV 
Standardised uptake value 
T½ 
Elimination half life 
ULN 
Upper limit of normal range 
US(A) 
United States (of America) 
V 
Volume of distribution 
VOI 
Volume of interest 
WBC 
White blood cell(s) 
WHO 
World Health Organisation 
WHO-DD 
World Health Organization (WHO) Drug Dictionary 

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1 
BACKGROUND INFORMATION 
1.1 
Introduction 
Neuroendocrine tumours are rare neoplasms [1, 2] with more than 50% of cases originating in 
the gastrointestinal (GI) system or pancreas [1]. Gastroenteropancreatic neuroendocrine 
tumours (GEP-NETs) constitute a heterogeneous group of tumours with their origin in 
neuroendocrine cells of the embryological gut. Most commonly, the primary lesion is located 
in the gastric mucosa, the small and large intestine, the rectum or pancreas. The crude incidence 
has notably increased over the last decade and is estimated to be 5.25/100 000/year. The 
prevalence has recently been calculated to 35/100 000/year [3]. Importantly, approximately 
80% of newly diagnosed patients present with metastasis, requiring an effective systemic 
treatment to prolong survival. The 5-year survival rate for this population is approximately 40% 
[4]. The latest World Health Organization (WHO) classification presented in 2010 defines the 
entire group of tumours as neuroendocrine neoplasms and divides the tumours into well 
differentiated NET G1, NET G2 and poorly differentiated neuroendocrine carcinoma (NEC G3) 
[5]. 
Most GEP-NETs overexpress somatostatin receptors (sstr), located on their cell surfaces [6]. 
To date a family of five different G protein-coupled sstr has been defined (sstr1–sstr5). The five 
subtypes share approximately half of the amino acid sequence, and have been shown to display 
different tumour tissue expression levels and biological functions.  sstr2 is the most commonly 
expressed sstr in GEP-NETs (80-90%) [7].  
The high expression level of sstr2 across the majority of tumours has led to the recommendation 
that for the clinical management, the initial disease staging should, whenever possible, include 
sstr scintigraphy which can nowadays be replaced by 68Gallium-labelled agent positron 
emission tomography (PET) with very high spatial resolution and quantification. PET is 
recommended to be complemented with computed tomography (CT) or magnetic resonance 
imaging (MRI) depending on the tumour location [3].  
Somatostatin-based radiolabeled agonistic peptides have been successfully introduced into the 
clinic for targeted imaging of sstr-positive NETs, especially of the clinically most relevant 
subtype sstr2. Currently three somatostatin-based radiolabeled peptide analogues are approved 
(or in Regulatory Authority review) in the US and/or Europe: namely, 111In pentetreotide 
(Octreoscan™), which is based on gamma rays, visualizing sstr-positive tumours in whole body 
single-photon 
emission 
computed 
tomography 
(SPECT) 
[8]; 
68Ga-DOTA-TATE  
(NETSPOT®) and 68Ga-DOTA-TOC (Somakit-TOC) used with PET imaging that provides 
several advantages over SPECT such as temporal and spatial resolution, reduced radiation 
burden and diminished examination time [9, 10]. In addition, on site cyclotron technology is 
not required for 68Gallium-labelled agents. 
OPS202 is a new generation somatostatin analogue (antagonist) compound with potential 
superior tumour detection as a consequence of the availability of more binding sites, both active 
and inactive sstr2. It consists of the small somatostatin analogue JR11 conjugated to the strong 
cyclical chelating agent 1,4,7-triazacyclononane,1-glutaric acid-4,7-acetic acid (NODAGA), 
which is radiolabelled with the radioactive isotope 68Gallium to produce 68Ga-OPS202. This 
complex (68Ga-OPS202) is being developed as a PET imaging agent for the detection of 
GEP-NETs in patients. 
68Gallium is a short-lived (half-life 68 min) positron-emitting isotope generated from decay of 
the parent isotope 68Germanium (half-life: 271 days). In the clinic, it can be created using a 
68Ga-generator. One of the main advantages of 68Ga is its cyclotron-independent availability, 

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Six out of 12 subjects (50.0%) experienced 11 adverse events (AEs), all of which were assessed 
by the investigator as being nonserious. Most of the AEs were mild in intensity and were 
considered by the investigator as unlikely or not related to the Investigational Imaging Product 
(IIP). Three AEs in two subjects were assessed as possibly related to 68Ga-OPS202: 
eosinophilia, rash and diarrhoea. The most frequently reported AEs were urinary tract infection 
(n=2) and fatigue (n=2); these AEs were considered unlikely or not related to the IIP. 
The study also showed promising preliminary efficacy results, with the most frequently 
identified lesions being malignant lesions in the liver. In all scans (somatostatin receptor 1-hour 
scan performed within 6 months before start of the study [pre-baseline] and the two 
68Ga-OPS202 dose 1-hour scans), malignant liver lesions were detected in nine subjects. 
Malignant lymph node lesions were identified in seven subjects in the pre-baseline somatostatin 
receptor 1-hour scan and eight subjects in the 68Ga-OPS202 1-hour scans. 
The detection rate of malignant lesions considering all organs/tissues (total) was significantly 
higher in the 68Ga-OPS202 1-hour scans than in the pre-baseline somatostatin receptor 1-hour 
scan (p≤0.016). This was based on the significantly higher number of liver lesions detected in 
the 68Ga-OPS202 1-hour scans compared to the somatostatin receptor 1-hour scan (p≤0.012). 
No significant difference was seen between the pre-baseline somatostatin receptor 1-hour scan 
and the 68Ga-OPS202 1-hour scans with regard to the detection rate of malignant lymph node 
lesions. 
1.2 
Rationale to Conduct the Trial 
The potential higher diagnostic accuracy of 68Ga-OPS202 (satoreotide trizoxetan) PET/CT 
compared to pre-baseline somatostatin receptor scan warrants the progression of the compound 
into a phase II study to confirm the optimal dose, particularly as the analysis of the safety data 
of Study OPS-B-001 did not raise any concern. 
The present dose-confirmation phase II study aims to define the optimal dose range for peptide 
mass and radioactivity based on detected number of lesions and tumour-to-background ratio in 
subjects with sstr2-positive GEP-NET. The study will also expand the evaluation of 
68Ga-OPS202 safety. 
1.3 
Population to Be Studied 
The study will enrol adult subjects with sstr2-positive GEP-NET. 
1.4 
Peptide Mass Dose Rationale 
In order to study the influence of specific activity (defined as radioactivity over peptide mass) 
on PET/CT image quality in the phase I/II clinical trial, two different peptide doses of 15 ± 5 μg 
and 50 ± 15 μg OPS202 (with 68Ga activity of 125 to 195 MBq) were administered to the same 
patient at the first and the second visit, respectively, allowing intra-patient comparison and 
resulting in a range of specific activity of 3 to 13 MBq/μg. In the proposed phase II study, the 
peptide ranges are designed to cover the lowest achievable peptide dose (5 μg to 20 μg; close 
to the 15 ± 5 μg of the phase I/II) and the upper range, within the capability of the kit (30 μg to 
45 μg; close to the 50 ±15 μg of the phase I/II). 
The internationally recognized procedure guidelines for PET/CT tumour imaging with 
68Ga-DOTA-conjugated peptides: 68Ga-DOTATOC, 68Ga-DOTANOC and 68Ga-DOTATATE, 
published by the European Association of Nuclear Medicine (EANM), which are based on the 
clinical experience with the known 68Ga-labeled somatostatin receptor agonists, proposes use 
of less than 50 μg of (injected) peptide as this amount would be expected not to have 
clinically-significant pharmacological effect [12]. The present OPS202 kit-formulation is 50 μg 

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to ensure reliable radiolabeling with a 68Ga radionuclide incorporation greater than 97%; the 
upper recommended limit of 50 μg was selected to compensate for the presence of potential 
metal contaminants (potential breakthrough of the parent radionuclide is possible [13] from the 
68Ge/68Ga generator elution and to provide a margin for robust radiolabeling. In the formulation 
given to patients, approximately 0.01-0.04% of OPS202 is complexed to 68Ga, whereas the 
remaining is unlabelled. 
The OPS202 kit supplied to the investigator sites will have a total of 50 μg of peptide to be 
made up into a 6 mL solution with 68Ga. A minimum of 0.5 mL or 4.2 μg of peptide will need 
to be withdrawn for quality control, leaving 5.5 mL or 45 μg of peptide available for injection. 
Based on this information, two peptide dose ranges were selected to be further evaluated in the 
phase II study: 5 μg to 20 μg and 30 μg to 45 μg, the latter value being the highest achievable 
from a 50 μg kit dose, as described above, and the lower dose is the lowest achievable that 
allows to adhere to the “as low as reasonably achievable” (ALARA) principle. 
It is anticipated that a range of injected peptide mass doses provides greater flexibility for 
radioactivity dosing. It is of note that this flexibility is important in clinical practice since the 
radioactivity dose is influenced by the age of the gallium generator. Other factors like PET 
scanner characteristics and subject’s body mass index (BMI) have to be accommodated by the 
flexibility in radioactivity dosing. 
1.5 
Radioactivity Dose Rationale 
Three radioactivity dose ranges are proposed: 
• 
40 - 80 MBq 
• 
100-140 MBq 
• 
160-200 MBq 
This phase II study will evaluate the radioactivity dose across a range that will be in the same 
order as the earlier phase I/II study with lower radioactivity doses also being evaluated to adhere 
to the ALARA principle. It is anticipated that to obtain good quality images with 68Ga-OPS202 
across a range of subject BMI and PET scanners, a radioactivity dose in the range of 100 MBq 
to 200 MBq will be required. To adhere to the ALARA principle and to identify a “near optimal 
dose” this phase II study will also evaluate a lower radioactivity dose range (40-80 MBq). It is 
anticipated that the lower radioactivity dose will be near optimal or below optimal for some 
subjects, particularly those who have a high BMI. 
Therefore, the aim of this phase II study is to demonstrate that over the range of injected 
radioactivity dose of 100 MBq to 200 MBq there is a clear diagnostic signal, regardless of the 
injected peptide dose used. One can consider the peptide as the “68Ga-carrier” that targets sstr2 
receptors, and hence the peptide dose within the micro-dosing range selected should not be a 
factor in diagnostic efficacy, but adjusted to ensure optimal radioactivity dose reaches the target 
lesions. 

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2 
PURPOSE OF THE STUDY AND STUDY OBJECTIVES 
2.1 
Purpose of the Study 
OPS202, an sstr2 antagonist compound, has demonstrated improved receptor binding, due to 
its capacity to bind both active and inactive sstr2, relative to sstr2 agonists. Therefore, the 
radiolabelled OPS202 potentially has an improved diagnostic performance as a PET imaging 
agent compared to ssrt2 agonists. Initial safety data have not raised any concerns. While the 
initial studies demonstrated good diagnostic performance in a single centre setting, the 
requirement to confirm both the peptide and radioactivity dose ranges in a multicentre setting 
was stipulated by the US Food and Drug Administration (FDA).  This study will therefore be 
conducted to evaluate the optimal combination of peptide mass dose and radioactivity dose 
ranges to provide optimal diagnostic efficacy of 68Ga-OPS202 for PET imaging in subjects with 
GEP-NET.  
2.2 
Study Objectives 
The primary objective of the study is: 
• 
To define the optimal dose range for peptide mass and radioactivity of 68Ga-OPS202 
based on detected lesions in adult subjects with sstr2-positive GEP-NET. 
The secondary objectives of the study are as follows: 
• 
To further refine the optimal dose range for peptide mass and radioactivity based on 
quantitative maximum standardised uptake value (SUVmax) and other image quality 
parameters  
• 
To describe the safety and tolerability of diagnostic 68Ga-OPS202 in subjects with 
sstr2-positive GEP-NET 
• 
To characterize the pharmacokinetics (PK) of OPS202 in subjects with GEP-NET. 
The exploratory objective of the study is: 
• 
To provide preliminary estimates of the sensitivity of 68Ga-OPS202 PET/CT scan 
imaging, as well as SUV ratio (SUVmax lesion/ SUVmean reference tissue), signal-to-noise 
ratios (SNR). 
 
 
 

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Subject participation in the study is estimated to last approximately 7 weeks and will include: 
• 
Visit 1: A screening period up to 2 weeks 
• 
Visit 2: A single intravenous (i.v.) injection of the first peptide/radioactivity dose of 
68Ga-OPS202 on Day 1 followed by PET/CT scan imaging 1 hour post dosing (up to 80 
min) 
• 
Visit 3: A single i.v. injection of the second peptide/radioactivity dose of  68Ga-OPS202 
followed by PET/CT scan imaging 1 hour post dosing (up to 80 min). This visit is 
scheduled 15 to 21days after the first 68Ga-OPS202 administration (Visit 2) 
• 
Visit 4: A 2-week follow-up period for evaluation of safety. 
Screening Procedures (Visit 1) 
During the Screening period (Visit 1) the investigator will select the candidate subjects and 
invite them to take part in the study. He or she will explain the study as indicated in Section 13.2 
and obtain written informed consent before conducting any study procedure. 
Randomisation and IIP Administration (Visit 2 and 3) 
At Visit 2, eligible subjects will be randomised to one of the three study arms, to receive a single 
i.v. injection of 68Ga-OPS202 with a peptide mass dose range of 5-20 μg and one of the 
radioactivity dose ranges (40-80 MBq, 100-140 MBq and 160-200 MBq activity of 68Ga). After 
a time interval of 15 to 21 days (Visit 3), another single i.v. injection of 68Ga-OPS202 will be 
administered to the subject with a peptide mass dose range of 30-45 μg and one of the 
radioactivity dose ranges (40-80 MBq, 100-140 MBq and 160-200 MBq activity of 68Ga) 
according to the study scheme (Figure 1). Specific details of the dosage arms are given in 
Section 6.  
Post Baseline Procedures (Visit 4) 
Subjects who complete Visit 2 (first PET/CT scan) and Visit 3 (second PET/CT scan) will be 
considered to have completed the study for efficacy analysis.  
Subjects who complete the study will have final procedures and assessments performed at the 
End of Study/Early Withdrawal Visit (Visit 4). Subjects who withdraw from the study before 
the completion of the second PET/CT scan evaluation will have Visit 4 (End of Study/Early 
Withdrawal Visit [Visit 4]) or early termination procedures and assessments performed at their 
final visit. An End of Study/Early Withdrawal Visit (Visit 4) will take place 2 weeks after the 
second PET/CT scan. 
3.2 
Primary and Secondary Endpoints and Evaluations 
All the primary and secondary imaging endpoints are read by third party independent readers. 
Most of the reading will be conducted in a blinded manner. 
3.2.1 
Primary Efficacy Endpoint and Evaluation 
• 
For each combination of injected peptide/radioactivity dose range, differences in relative 
lesion counts derived from a 2 × 3 factorial analysis measuring the ratio of the number 
of lesions detected by 68Ga-OPS202 to the number of lesions assessed by standard-of-
truth (descriptive analyses). 
The standard-of-truth in this study is the CT scan images acquired at Visit 2 and Visit 3. 
3.2.2 
Secondary Efficacy Endpoints and Evaluations 
Key Secondary Endpoint: 

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• 
For each combination of injected peptide/radioactivity dose range, differences in image 
quality derived from a 2 × 3 factorial analysis measuring the tumour-to-background ratio 
in each of the major anatomic sites (descriptive analyses for liver, lymph nodes, bone 
and lungs)  
A qualitative analysis of the image assessed by the independent blinded readers will be 
performed to back up the quantitative quality measured by tumour-to-background analysis. 
Other Secondary Endpoints: 
• 
Differences in lesion SUVmax between the two peptide mass dose ranges and the three 
radioactivity dose ranges measured in the most avid lesions (descriptive analyses for up 
to a maximum of five lesions per organ in liver, lymph nodes, bone and lungs) 
• 
Differences of absolute number of lesions between the two peptide mass dose ranges and 
the three radioactivity dose ranges detected in each of the following anatomic sites:  
- 
Primary site of GEP-NET  
- 
Lymph nodes  
- 
Liver  
- 
Axial/appendicular skeleton  
- 
Lungs 
• 
The primary and secondary endpoints will also be evaluated on a radioactivity dose/kg 
of body weight. 
Exploratory Endpoints: 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of GEP-NETs by both 
subject-based and lesion-based analysis compared to standard-of-truth 
• 
Comparison to sstr2 agonist results will be computed for sensitivity analysis 
• 
Differences in SUVmax ratios between the two peptide mass dose ranges and three 
radioactivity dose ranges for lesions  
• 
SNR calculated from lesion-free volume of interest (VOI) in the liver: SUVmean/SUVSD 
between the three radioactivity doses. 
3.2.3 
Safety Endpoints and Evaluations 
The safety and tolerability of 68Ga-OPS202 will be assessed throughout the study by evaluating 
AEs, clinical laboratory test results (serum chemistry, haematology, and urinalysis), vital signs 
measurements (blood pressure, heart rate and respiratory rate), electrocardiograms (ECGs), 
physical examination results and concomitant medication usage. 
The following safety endpoints will be evaluated: 
• 
Proportion of subjects experiencing at least one AE of any grade according to National 
Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE 
version 5.0), including any serious adverse events (SAEs) and suspected unexpected 
serious adverse reactions (SUSARs) 
• 
Proportion of subjects experiencing at least one AE of grade ≥3 according to 
NCI-CTCAE (version 5.0). All AEs will be coded using Medical Dictionary for 
Regulatory Activities (MedDRA) system organ class (SOC) and preferred term (PT) (as 
per most recent version) 
• 
Clinically significant changes in physical examination, vital signs, ECG and laboratory 
findings, which will be recorded by the investigator as AEs. 

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3.2.4 
Pharmacokinetic Endpoints 
OPS202 plasma concentration will be evaluated at the following timepoints: Baseline pre-dose 
(T0), 5 min, 15 to 45 min, 1h, 2h, 3h and 6h after the 68Ga-OPS202 i.v. administration at the 
corresponding visits (Visit 2 and Visit 3). Urine collection to determine renal excretion of 
OPS202 will be performed over the first 6 hours in two separate samples: 0h to 3h and 3h to 6h 
after the 68Ga-OPS202 i.v. administration at the corresponding visits (Visit 2 and Visit 3). 
OPS202 PK parameters include the following: 
• 
Maximum plasma concentration (Cmax) 
• 
Area under the plasma concentration time curve from time 0 to the time of the last 
quantifiable concentration (AUClast) 
• 
Area under the plasma concentration time curve extrapolated to infinity (AUC0-∞) 
• 
Elimination half-life (T1/2) 
• 
Total plasma clearance (CL) 
• 
Volume of distribution (V) 
• 
Excreted amount of OPS202 in the urine over each time interval (see Section 3.2.4) as 
well as the 6-hour cumulative amount of unchanged OPS202 excreted into the urine (Ae). 
3.3 
Randomisation and Blinding 
This is an open-label study and there is no blinding for the administration of the IIP nor for its 
doses (peptide mass dose as well as radioactivity dose).  
An independent statistician (the sponsor’s randomisation manager) will prepare the master list 
of randomisation numbers for this study. This list will be produced in blocks, on a balance ratio 
for the three sequences summarized in Table 4. 
Table 4 Sequences of Peptide Mass Doses and Radioactivity Doses  
 
 
Visit 2 (D1) 
Visit 3 (between D16-D22) 
Sequence A 
5-20μg / 40-80 MBq 
30-45μg / 100-140 MBq 
Sequence B 
5-20μg / 100-140 MBq 
30-45μg / 160-200 MBq 
Sequence C 
5-20μg / 160-200 MBq 
30-45μg / 40-80 MBq 
 
After eligibility is confirmed at Visit 2 (Day 1), subjects will be assigned to a randomisation 
number and to the associated sequence of study arm, in sequential order within each centre. 
Each subject will receive, at Visit 2 and Visit 3, the peptide mass dose and radioactivity dose 
associated to this randomisation number. The randomisation number and the dose ranges will 
be provided by the electronic case report form (eCRF), which will assign the subjects in a study 
arm according to the predefined randomisation list. The investigator will under no 
circumstances be able to change the randomisation number and the sequence of treatment arms 
allocated to the subject.  
Recruitment will stop once 24 evaluable subjects have been randomised and completed the 
study procedures. Each non-evaluable subject (see Section 3.6) will be replaced by a subject 
who will receive the same dose ranges sequence as the one assigned to the replaced subject. In 
this context, a mirror randomisation list will also be produced to randomise the replacement 
subjects. In this mirror randomisation list, only the replacement randomisation numbers of 
non-evaluable subjects will be considered. 

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The IIP packs and all vials will be labelled. Each label will be designed in accordance with 
Appendix 13 of the European Union Good Manufacturing Practices (EU-GMP) (see Appendix 
1) and in accordance with specific local requirements if any. After reconstitution and 
radiolabelling the vial will be included in a lead container. This lead container will be labelled 
according to Appendix 13 of EU GMPs (see Appendix 1) and according to specific local 
requirements if any.   
Final IIP reconstitution, radiolabelling, quality control (QC) and IIP release will be performed 
at the study site’s radiopharmacy facility. Labels for the final IIP and containers can be provided 
by the sponsor if required by the clinical site. 
The IIP (OPS202, cold precursor) will be packaged and delivered to the investigational 
sites/central or interim storage facilities. A sufficient quantity of IIP will be supplied as well as 
an acknowledgement of receipt form. No code break envelopes will be supplied as the double 
blinding relates to the independent central readers.  
The investigator, or designee, will only administer IIPs to subjects included in this study. Each 
subject will only be given the IIP carrying his/her number. The dispensing by the responsible 
pharmacist and the administration to each subject will be documented in the eCRF. 
The peptide mass dose ranges and the radioactivity dose ranges are summarized in Table 3, and 
their sequence of administration in Figure 1. 
3.5 
Study Duration 
This study will consist of up to a 2-week screening period, an approximately 3-week imaging 
period, and a 2-week follow-up period. Subjects are expected to participate in this study for a 
minimum of 6 weeks and up to 7 weeks.  
The subject’s participation in the study will be considered to have ended at the time of the last 
visit (Visit 4 or End of Study/Early Withdrawal Visit), which should occur approximately 
2 weeks after their last IIP administration. 
3.6 
Stopping Rules and Discontinuation Criteria 
There are no formal rules for early termination of this study. During the conduct of the study, 
SAEs will be reviewed (see Section 8.1.3) as they are reported from the study centres to identify 
safety concerns. The study may be terminated by the sponsor at any time. 
A subject may discontinue participation in the study at any time for any reason (e.g., withdrawal 
of consent, AE). The investigator and/or sponsor can withdraw a subject from the study at any 
time for any reason (e.g., protocol deviation as defined in Section 12.1.2, noncompliance with 
the protocol conditions or AE). 
If a subject’s Visit 2 68Ga-OPS202 PET/CT scan images are non-evaluable for whatever reason, 
the subject will be discontinued from the study. This study has a small number of subjects 
requiring two timepoints for image evaluation.   
Each non-evaluable subject will be replaced by a subject who will receive the same IIP sequence 
as the one assigned to the replaced subject (see Section 3.3). A non-evaluable subject is one for 
whom any of the following image sets are missing or of unacceptable quality for ICL: 
1) Visit 2 and/or Visit 3 
68Ga-OPS202 PET/CT scans, as these provide the 
“standard-of-truth” information and both are needed for the factorial design 
2) Previous somatostatin receptor scans, which confirm the presence of sstr2 in the tumour 

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3) All images will be reviewed and assessed by ICL to ensure there are no quality issues 
relating to artefacts that are detrimental to the study endpoints.  These primarily consist 
of the following: 
(a) 
Metal implants 
(b) 
Patient motion 
(c) 
Excessive breathing artefacts between the PET and CT scan images. 
  
3.7 
Investigational Imaging Product Preparation, Storage and Accountability 
3.7.1 
Investigational Imaging Product Storage and Security 
The investigator, or an approved representative (e.g., pharmacist), will ensure that all IIP and 
any other study related material is stored in a secured area, under recommended temperature 
monitored storage conditions, in accordance with applicable regulatory requirements. 
3.7.2 
Investigational Imaging Product Preparation 
The investigator, or an approved representative (e.g., pharmacist), will ensure that all IIP is 
reconstituted, radiolabelled and dispensed by qualified staff members in order to be 
administered to the subject. 
3.7.3 
Investigational Imaging Product Accountability 
All IIP and any other study related material is to be accounted for on the IIP accountability log 
provided by the sponsor. It is essential that all used and unused supplies are retained for 
verification (by the sponsor or sponsor’s representative). The investigator should ensure 
adequate records are maintained in the IIP accountability log. 
The destruction of used and unused study treatment should be carried out only after any 
discrepancies have been investigated and satisfactorily explained and the reconciliation has 
been accepted. The study treatment will be destroyed on site. 
3.8 
Maintenance of Randomisation and Blinding 
This is an open-label study; there is no blinding for the imaging product used nor for its doses 
(peptide mas dose as well as radioactivity dose). The scan images collected at Visit 2 and Visit 
3 are to be read centrally in a blinded manner. 
The images will be sent to a central imaging core lab ICL.  The ICL will ensure that the 
68Ga-OPS202 and CT images are initially presented to the readers in a blinded manner and 
randomised to temporal sequence. Blinding includes subject ID, site, type of scanner(s), peptide 
mass dose and radiation dose (and therefore visit number). Full details of this complex read will 
be provided in the Imaging Review Charter (IRC). 
3.9 
Source Data Recorded on the Case Report Form 
Data will be collected in the eCRF in compliance with FDA 21 Code of Federal Regulations 
(CFR) Part 11. As required by Good Clinical Practice (GCP), the sponsor assigned monitor will 
verify, by direct reference to the source documents, that the data required by the protocol are 
accurately reported on the eCRF.  
The source documents must, as a minimum, contain a statement that the subject is included in 
a clinical study, the date that informed consent was obtained prior to participation in the study, 
the identity of the study, diagnosis and eligibility criteria, visit dates (with subject status), IIP 
administration, and any AEs and associated concomitant medication. 

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As required by International Conference on Harmonisation (ICH GCP) Section 6.4.9, if some 
items are recorded directly on the eCRF and are considered as source data, the identification of 
these data must be documented and agreed between the investigator and the sponsor. 
Definition for source data and source documents are given below: 
• 
Source Data: All original records and certified copies of original records of clinical 
findings, observations, or other activities necessary for the reconstruction and evaluation 
of the study. Source data are contained in source documents (original records or certified 
copies). 
• 
Source Documents: Original documents, data and records (e.g. hospital records, clinical 
and office charts, laboratory notes, memoranda, subjects’ diaries or evaluation checklists, 
pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate copies, microfiches, 
photographic negatives, microfilm or magnetic media, x rays, subject files, and records 
kept at the pharmacy, at the laboratories and at medicotechnical departments involved in 
the clinical study). The results of the independent central read are also considered source 
documents. 
The subject must have consented to their medical records being viewed by the sponsor’s 
authorised personnel, and by local, and possibly foreign, competent authorities (CAs). This 
information is included in the informed consent. 

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4 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
All subjects must fulfil all the following criteria to be included in the study: 
1) 
Men or women aged 18 years or older  
2) 
Subjects 
with 
pathologically 
confirmed, 
well 
differentiated 
functioning 
or 
non-functioning metastatic GEP-NET (Grade I and II as per WHO classification 2010)  
3) 
Subjects with a confirmed presence of somatostatin receptors (type 2) on technically 
evaluable tumour lesions documented by a positive Somatostatin Receptor Scan acquired 
within 6 months prior to screening (Visit 1) and showing minimally two lesions in at 
least one of the key organs (liver, lymph nodes, bone and lungs); these images shall be 
available to be sent to the ICL electronically to ascertain quality and admissibility 
4) 
Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 
5) 
Subjects with body weight between 50 kg (110 lb) and 110 kg (243 lb), inclusive  
6) 
Adequate bone marrow, liver and renal function, with: 
• 
Calculated Glomerular filtration rate (GFR) ≥ 45 mL/min  
• 
Albumin: > 30 g/L 
• 
Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline 
phosphatase (AP): ≤ 5 times upper limit of normal (ULN)  
• 
Bilirubin: ≤ 3 times ULN (3 × 1.1 mg/dL) 
• 
Leukocytes: ≥ 3*109/L and neutrophils ≥ 1*109/L 
• 
Erythrocytes: ≥ 3.5*1012/L 
• 
Platelets: ≥ 90*109/L 
7) 
Signed written informed consent prior to any study-related procedures 
4.2 
Exclusion Criteria 
Subjects will not be eligible for inclusion in the study if they have any of the following: 
1) 
Subjects with fewer than five lesions in total and more than 25 lesions/organ detected by 
the somatostatin receptor positive scan in key organs: liver, lymph nodes, bone or lungs 
2) 
Subject who have received treatment of any somatostatin analogue, including 
Somatuline® Autogel® /Depot®, Sandostatin® LAR within 28 days, and Sandostatin® 
within 24 hours prior to first 68Ga-OPS202 administration. 
3) 
Presence of active infection at screening or history of serious infection within the 
previous 6 weeks prior to the first 68Ga-OPS202 administration 
4) 
Prior or planned administration of a radiopharmaceutical within 8 half-lives of the 
radionuclide  
5) 
Clinically relevant trauma within 2 weeks prior to first 68Ga-OPS202 administration 
6) 
Known hypersensitivity to NODAGA, to Gallium-68, to JR11 or to any of the excipients 
of 68Ga-OPS202 
7) 
History of, or current active allergic or autoimmune disease, including asthma or any 
condition requiring long-term use of systemic corticosteroids 
8) 
Known human immunodeficiency virus (HIV) or positive serology for HIV, hepatitis B 
and C 

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9) 
Any condition that precludes the proper performance of PET and/or CT scan: 
• 
Subjects who are not able to tolerate the CT contrast agent,  
• 
Subjects with metal implants or arthroplasty, or any other objects that might interfere 
with the PET and/or CT analysis 
• 
Subjects unable to raise arms for prolonged imaging purposes  
• 
Subjects unable to lie still for the entire imaging time 
• 
Subjects weighing greater than 110 kg (243 lb) 
10) 
Administration of another investigational medicinal product within 30 days prior to first 
68Ga-OPS202 administration 
11) 
Female subjects who are pregnant, breast feeding or of childbearing potential not willing 
to practice effective contraceptive techniques during the study treatment period and for 
30 days after the last dose of 68Ga-OPS202 administration; pregnancy test must be 
performed at the start of the study and prior to each 68Ga-OPS202 administration 
12) 
Subjects who have any severe and/or uncontrolled medical conditions or other conditions 
that could affect their participation in the study, including any mental condition rendering 
the subject unable to understand the nature, scope and possible consequences of the 
study, and/or evidence of an uncooperative attitude 
13) 
Subject who experienced a previous cancer (except basocellular carcinoma of the skin 
and/or in situ carcinoma of the cervix/uterus and/or subjects treated with curative intent 
and free from disease for more than 5 years) other than NET 
4.3 
Subject Withdrawal Criteria and Procedures 
In accordance with the Declaration of Helsinki (in accordance with the applicable country’s 
acceptance), each subject is free to withdraw from the study at any time. The investigator also 
has the right to withdraw a subject from the study in the event of concurrent illness, AEs, or 
other reasons concerning the health or wellbeing of the subject, or in the case of lack of 
cooperation. Any subject who becomes pregnant during the course of the study will be 
withdrawn (see Sections 8.1.4 and 8.2.4). In addition, a subject may be withdrawn from the 
study as described in Sections 3.6, 5.2.4.1, 6.2 and 8.1.6.  
Should a subject decide to withdraw from the study after administration of IIP, or should the 
investigator decide to withdraw the subject, all efforts will be made to complete and report the 
observations up to the time of withdrawal as thoroughly as possible. A complete final evaluation 
at the time of the subject’s withdrawal should be made (see Section 5.2.4.1) and an explanation 
given of why the subject is withdrawing or being withdrawn from the study. 
The reason for and date of withdrawal from the study must be recorded on the eCRF. If a subject 
withdraws consent, every attempt will be made to determine the reason. If the reason for 
withdrawal is an AE or a clinically significant laboratory test abnormality, monitoring will 
continue until the event has resolved or stabilised, until the subject is referred to the care of a 
local health care professional, or until a determination of a cause unrelated to the IIP or study 
procedure is made. The specific AE or test result(s) must be recorded on the eCRF. All 
evaluations should be performed, according to the protocol, on the last day the subject receives 
IIP, or as soon as possible thereafter.  

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5 
STUDY PROCEDURES 
5.1 
Study Schedule 
The schedule of procedures and assessments during the study is summarised in Table 5. 
Table 5 Study Procedures and Assessments 
Study Visits [1] 
Screening 
Visit 1 
Day 1 
Visit 2* 
Day 16-22 
Visit 3* 
End of 
Study/Early 
Withdrawal 
visit Day 30-36 
Visit 4 
Informed consent [2] 
X 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
Randomisation 
 
X 
 
 
Demographics [3] 
X 
 
 
 
Medical history [4] 
X 
 
 
 
Prior therapies [4] 
X 
 
 
 
Concomitant therapies [5] 
X 
X 
X 
X 
Physical examination [6] 
X 
X 
X 
X 
Vital signs [6] 
X 
X 
X  
X 
ECG [7] 
X 
 
 
X 
Haematology [8] 
X 
X 
X 
X 
Blood chemistry [9] 
X 
X 
X 
X 
Blood PK sampling [10] 
 
X 
X 
 
Urinalysis [11] 
X 
X 
X 
X 
Urine PK sampling [12] 
 
X 
X 
 
Pregnancy test [13] 
ßHCG 
(blood test) 
Urinary hCG 
Urinary hCG 
ßHCG 
(blood test) 
Somatostatin Receptor 
Scan [14] 
X 
 
 
 
68Ga-OPS202 PET/CT 
imaging [15] 
 
X 
X 
 
Adverse events [16] 
X 
X 
X 
X 
Compliance [17] 
 
X 
X 
 
[1] Study visits: Screening Visit up to 2 weeks; Visit 3 will occur between Day 16 and Day 22, Follow-up Visit 
to be performed 2 weeks after Visit 3. * The subjects may be hospitalised overnight at Visit 2 and Visit 3 at the 
discretion of the investigator. On Day 2 (prior to discharge if subject hospitalised), the subject should undergo the 
following examinations: review of AEs, new or changed concomitant medications, vital signs, physical 
examination, haematology, biochemistry, urinalysis. 
[2] Informed consent: Must be obtained prior to undergoing any study specific procedures and may occur prior 
to the 2-week screening period 
[3] Demographics: Age, sex and self-reported race/ethnicity 
[4] Medical history and prior therapies: To include clinically significant diseases, surgeries, cancer history 
(including prior NET Therapies) and all relevant medications 
[5] Concomitant medications: Dose and indication will be recorded from 3 months prior to the start of study 
treatment, at study entry and at each visit. Once the subject has withdrawn from the study, concomitant medications 
and treatments should be recorded until all study treatment-related toxicities have resolved; 
[6] Physical examination: Major body systems, body weight, height (screening visit only), vital signs 0.5, 1, 2 
and 4 hours post-injection (supine and standing systolic and diastolic blood pressure, heart rate), body temperature, 
respiratory rate 

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[7] ECG: Twelve-lead ECGs will be recorded at a paper speed of 25 mm/sec so that the different ECG intervals 
(RR, PR, QRS, QT) can be measured automatically as per study site usual practice. The ECG will be recorded 
with the subject in supine position after five minutes of rest until four regular consecutive complexes are available 
[8] Haematology: Red blood cell (RBC) count, haemoglobin, haematocrit, mean corpuscular volume (MCV), 
mean corpuscular haemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), white blood cell 
(WBC) absolute count (neutrophils, lymphocytes, monocytes, eosinophils, basophils, and others) and platelet 
count 
[9] Blood chemistry: urea, creatinine, chloride, bicarbonate, sodium, potassium, calcium, phosphate, total 
bilirubin, conjugated bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, 
gamma-glutamyl transferase, albumin, total protein, total cholesterol, triglycerides, fasting glucose 
[10] Blood PK Sampling: Blood samples of 2 mL will be collected at the following timepoints: Baseline pre-dose 
(T0), 5 min, 15 to 45 min, 1h, 2h, 3h and 6h after the 68Ga-OPS202 intravenous administration 
[11] Urinalysis: Dipstick for pH, protein, ketones, bilirubin, blood, urobilinogen, nitrites, leukocyte esterase, 
glucose and specific gravity 
[12] Urine OPS202 measurement: Urine collection during the 6 hours post-dosing: in two separate samples: 0h 
to 3h and 3h to 6h after the 68Ga-OPS202 i.v. administration at the corresponding visits (Visit 2 and Visit 3); 
subject will be asked to empty his/her bladder before dosing 
[13] Pregnancy test: A pregnancy test will be performed at each visit particularly before each 68Ga-OPS202 
administration. 
[14] Somatostatin Receptor Positive Scan: Results available in the preceding 6 months to the first administration 
of 68Ga-OPS202 PET. Anonymized Images to be sent to the Imaging Core Lab 
[15] 68Ga-OPS202 PET/CT imaging: Anonymized images to be sent to the Imaging Core Lab; i.v. iodinated CT 
contrast is required and will be injected according to the site standard procedure. 
[16] Adverse events: Subjects must be followed for AEs, regardless of relationship, from the time they signed the 
informed consent until at least 14 days after the last dose of investigational imaging product (IIP). Clinically 
significant changes in physical examination, vital signs, electrocardiogram and laboratory findings will be 
recorded as an adverse event 
[17] Compliance: The dose injected will be recorded at each visit. 
 
5.2 
Study Visits 
5.2.1 
Procedures for Screening and Enrolment (Visit 1) 
A signed and dated informed consent form will be obtained before screening procedures begin. 
Evaluations obtained as part of routine medical care and performed during the screening period 
may be used in place of the study-specific evaluations. Subjects will be asked to acknowledge 
and agree to the possible use of this information for the study by giving informed consent. 
After informed consent is obtained, subjects who are screened will be allocated a subject 
number. All screened subjects must be identifiable throughout the study. The investigator will 
maintain a list of subject numbers and names to enable records to be found at a later date if 
required. 
The Screening visit (Visit 1) will take place within the 2-week period prior to randomisation. 
The following assessments will be performed: 
• 
Eligibility check (inclusion/exclusion criteria) 
• 
Demographic data (date of birth/age, sex and race/ethnicity will be collected according 
to individual country regulations/requirements). The collection of these data is needed to 
establish whether or not there are potentially clinically important sex- and 
racial/ethnic-based differences in the anticipated effects of the studied product. 
• 
Medical history, including ongoing medical history 
• 
Physical examination 

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• 
Vital signs (supine and standing blood pressure, heart rate and respiratory rate) 
• 
ECG 
• 
Body temperature 
• 
Body weight 
• 
Body height 
• 
Laboratory safety tests (blood sampling for haematology and biochemistry, and 
urinalysis) 
• 
Beta human chorionic gonadotropin (ß-HCG) pregnancy test for women of childbearing 
potential 
• 
Prior and concomitant medications/therapies; please record the time period of 
concomitant medication(s) before subject begins the study 
• 
Prior and concomitant nondrug therapies and surgical procedures 
• 
Collection of AEs after signed informed consent has been obtained  
• 
Collection of previous somatostatin receptor scan and send to ICL. 
Each investigator will also maintain a record of all subjects screened into the study (i.e., who 
signed the informed consent form). Records up to the time of premature termination should be 
completed. In the event that the subject did not receive IIP, the primary reason will be recorded. 
5.2.2 
Procedures Before Study IIP administration (Baseline/Visit 2 and Visit 3 Predose) 
The following procedures will be performed at Baseline/Day 1 (Visit 2) and at Day 16-22 
(Visit 3) of the study, prior to the administration of IIP and information recorded (pre-dosing): 
• 
Eligibility confirmation, which applies that any test results needed for this check should 
be already available (some exams/tests may be repeated if not available from the 
Screening Visit or are clinically and medically needed before 
68Ga-OPS202 
administration) 
• 
Following confirmation of eligibility for the study, subjects will be given a randomisation 
allocation number and allocated to one of the three study arms specified in Section 6.1. 
• 
Review of AEs that may have occurred since informed consent form signature and before 
the first administration of the IIP (Visit 2) 
• 
Review of AEs that may have occurred before the second administration of the IIP 
(Visit 3) 
• 
Investigator will ensure that the subject can safely receive 68Ga-OPS202 and the PET 
scan can be performed. For women of potential childbearing age, the results of urinary 
pregnancy test (test strips provided by central laboratory) should be obtained before 
68Ga-OPS202 administration. 
• 
Pregnancy test on urine specimen (test strips provided by central laboratory) for women 
of childbearing potential. 
If the subject continues to meet all eligibility criteria at Visit 2, he/she will receive a single 
injection of 68Ga-OPS202 as per randomised allocation to one of the three study arms and will 
undergo PET/CT imaging. 
N.B. For Visit 2 and Visit 3, subjects may be required to be hospitalised overnight at the 
discretion of the investigator. 

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5.2.3 
Procedures During Study Treatment (Visit 2 and Visit 3 - Postdose) 
The following procedures will be performed at Visit 2 (Day 1), and Visit 3 (Day 16 to 22)]:  
• 
Review of AEs 
• 
New or changed concomitant medications 
• 
Vital signs at 0.5h, 1h, 2h and 4h post-injection 
• 
Whole body PET/CT images will be acquired 1 hour (static) after 68Ga-OPS202 injection 
(up to 80 min); i.v. iodinated CT contrast is required and will be injected according to 
the site standard procedure. 
• 
PK assessments of OPS202:  
• 
Blood sampling will be performed at Baseline pre-dose (T0), 5 min, 15 to 45 min, 
1h, 2h, 3h and 6h after the 68Ga-OPS202 i.v. administration for both doses at the 
corresponding visits (Visit 2 and Visit 3) 
• 
Urine collection to determine renal excretion of OPS202 will be performed over 
the first 6 hours in two separate samples: 0h to 3h and 3h to 6h. Subject will be 
asked to empty his/her bladder just before the 68Ga-OPS202 i.v. administration 
and then all urine voided during each of the above-mentioned time intervals will 
be collected and stored. 
The subject may be hospitalised overnight at the discretion of the investigator. On the next day 
(Day 2), the Investigator will evaluate if the subject is fit to be discharged home. Subjects who 
are not hospitalised have to return to the investigator site the next day (Day 2). Prior to 
discharge, the subject should undergo the following examinations, for which the results must 
be recorded on the eCRF: 
• 
Review of AEs 
• 
New or changed concomitant medications 
• 
Vital signs (supine and standing blood pressure, heart rate and respiratory rate) 
• 
Physical examination 
• 
Body weight 
• 
Clinical laboratory tests (blood sampling for haematology and biochemistry, and 
urinalysis) 
Upon discharge from hospital on Visit 2 (Day 2), the subject will be asked to return to study 
site in order to receive the next dose level (within 15 to 21 days). Upon discharge from the 
hospital on Visit 3 (Day 17 – Day 23), the subject will be asked to return to the study site in 
two weeks for safety follow-up. 
5.2.4 
Procedures After Study Imaging Agent Administration 
Two weeks after the second 68Ga-OPS202 PET/CT scan, the subject will come back to the study 
site for Visit 4 (End of Study/Early Withdrawal Visit). 
5.2.4.1 
End of Study Visit (Visit 4) or Early Withdrawal Visit 
Subjects who participate in the study in compliance with the protocol for the two IIP 
administrations (at Visit 2 and Visit 3) will be considered to have fully completed the study for 
efficacy analysis. Those who in addition attend End of Study Visit (Visit 4) will be considered 
to have fully completed the study (i.e., efficacy and safety). 
For subjects who complete the study, or for those who withdraw prematurely from the study 
(see Section 4.3), final evaluations will be performed approximately two weeks after the subject 

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receives the IIP. Subjects with ongoing AEs or clinically significant laboratory test 
abnormalities (as determined by the investigator) will be monitored as described in 
Section 8.1.2 and Section 8.1.1.4, respectively. 
The following procedures will be performed at the End of Study (Visit 4, Day 30 to Day 36), 
or Early Withdrawal Visit: 
• 
Review of AEs 
• 
New or changed concomitant medications 
• 
Physical examination 
• 
Vital signs (supine and standing blood pressure, heart rate and respiratory rate) 
• 
ECG 
• 
Body temperature 
• 
Body weight 
• 
Laboratory safety tests (blood sampling for haematology and biochemistry, and 
urinalysis) 
• 
ß-HCG pregnancy test for women of childbearing potential 

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6 
DIAGNOSTIC IMAGING OF SUBJECTS 
6.1 
Study Imaging Product  
6.1.1 
68Ga-OPS202 
At Screening, subjects will be allocated a subject number. Following confirmation of eligibility 
for the study, subjects will be randomised to one of the following sequence of 68Ga-OPS202 
peptide mass dose/ radioactivity dose ranges: 
• 
Arm A: 5-20 μg/ 40-80 MBq at Visit 2 and 30-45 μg/ 100-140 MBq at Visit 3 
or 
 
• 
Arm B: 5-20 μg/ 100-140 MBq at Visit 2 and 30-45 μg/ 160-200 MBq at Visit 3 
or 
• 
Arm C: 5-20 μg/ 160-200 MBq at Visit 2 and 30-45 μg/ 40-80 MBq at Visit 3 
68Ga-OPS202 is a diagnostic medicinal product with three main components, namely: 
• 
68Ga, a positron emitter radionuclide with a half-life of 68 min  
• 
NODAGA, a chemical chelator group, and 
• 
JR11, an antagonist somatostatin analogue that binds to sst2 receptors 
OPS202 (cold kit) is available for clinical trials in a 50 μg peptide dose vial, and is radiolabeled 
using a 68Ge/ 68Ga-generator. Due to the short half-life (68 min) of the 68Ga radioisotope, on-site 
generation of 68Ga-labeled radiopharmaceuticals is mandatory. The 68Ga is eluted initially from 
the generator with hydrochloric acid and the eluate combined with the reconstituted peptide kit 
preparation. The radiolabelling occurs at room temperature. The product then undergoes 
radiopharmaceutical quality control (see Preparation, Radiolabeling and QC manual).  
The radiolabelled OPS202 (68Ga-OPS202) consists of 50 μg of peptide in a total volume of 
6 mL (8.33 μg/mL).  Sampling of 0.5 mL for QC yields 5.5 mL solution from which the volume 
to be administered is withdrawn. This volume to be injected is calculated to obtain the target 
peptide mass dose and the desired radioactivity dose. 
The calculation of the volume takes into account the different components that determine the 
final radioactivity dose, the subject will be exposed to, in particular:  
• 
The amount of 68Ga eluted from the generator which depends on the latter half-life  
• 
The time elapsed between OPS202 (cold kit) radiolabelling and the injection of 
68Ga-OPS202 to the subject (decay of 68Ga), the variation of which is a tool to adjust the 
final peptide/radioactivity dose required to be injected 
• 
The required peptide mass dose and radioactivity dose of 68Ga-OPS202 to be injected. 
The actual peptide mass dose administered to the subject (injected dose) will be estimated using 
the following equation: 
Injected dose (μg) = [Volume injected (mL) / Volume used for 68Ga-OPS202 preparation (mL)] 
x Peptide dosage in the vial (μg) = [Injected Volume/6mL] x 50μg  
The radioactivity in the syringe is measured immediately before the injection of 68Ga-OPS202 
to the subject and immediately after; the difference between these two measurements (in MBq) 
constitutes the radioactivity dose injected to subject. 
68Ga-OPS202 will be administered twice during the study for each subject by i.v. injection over 
one minute. After injection is completed, any remaining imaging agent in the cannula is rinsed, 

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when appropriate, with 10 mL normal saline (0.9 % NaCl solution). The PET/CT scanner must 
be the same for the two scans per subject and for all subjects at the same study site. 
There are no fasting conditions, nor food restrictions that should apply when administering 
68Ga-OPS202 to the subject. N.B.: 
68Ga-OPS202 is labelled according to Good 
Radiopharmaceutical Practice (GRPP) per EANM guidelines and according to national 
regulations on radiopharmaceuticals. The radiopharmacy will receive training and specific 
written instructions on the labelling procedure.  
Radiation dose:  
According to data published for fluorodeoxyglucose (FDG) PET the effective dose was 
6.23 mSv [14]. Doses from FDG PET scanning to the gonads, uterus, and bladder were higher 
than to the other organs and were 5.0, 7.8, and 59.2 mSv, respectively. This is because of the 
final accumulation of 18F in the bladder. Other organ doses ranged from 2.5 to 4.8 mSv. The 
total effective doses of the combined PET/CT studies, calculated by summing the effective 
doses of CT and PET scanning ranged from 13.45 to 31.91 mSv for female patients and 13.65 
to 32.18 mSv for male patients taking various CT protocols into consideration [14]. Average 
contrast-enhanced CT of abdomen and pelvis dose is 20 mSv [15]. 
In the phase I/II study 68Ga-OPS202, the calculated effective dose for an injection of 150 MBq 
(4 mCi) of 68Ga-OPS202 was 3.6 mSv, which is lower than the radioactivity dose of the 
FDA- and EMA-approved OctreoscanTM.  
In this trial, each subject will get two PET/CT examinations with a 2- to 3-week interval 
between the two examinations. The total 68Ga-OPS202 in each 3-study arm will range from 
140 to 340 MBq (calculated by summing the doses at Visit 2 and Visit 3). Based on phase I/II 
study, the total dose for the study will range from approximately 3.6 mSv to 7.5 mSv. The dose 
of two CTs will depend on the imaging protocols and will not exceed 20 mSv for each CT 
examination. Thus, total cumulative dose for two PET/CT examinations will range from 
approximately 44 to 48 mSv. 
6.1.1.1 
Spillage 
All due precautions and site procedures should be implemented to prevent spillage or leakage 
of radiodiagnostics. Infusion bags, intravenous lines, venous access should all be secured and 
the connections thoroughly checked. The infusion line should be taped in a loop and taped to 
the subject to prevent direct tension between the line and the venous access. 
Despite precautions, if spillage or leakage should occur, then the site procedures must be 
implemented to protect the subject, staff and members of the public from radiation exposure. 
The subject should be moved from the area of the spillage or leakage while the area is 
decontaminated. Details of the spillage or leakage should be recorded (including how the 
incident happened, the time of the incident, an estimate (if possible) of the amount of substance 
lost) and the measures taken. In addition, the incident is to be reported in the same manner as 
an adverse event using the MedDRA PT Product Leakage and as appropriate PT Occupational 
exposure to radiation (if there is exposure to staff) and PT Exposure to radiation (if there is 
exposure to the subject or members of the public). 
6.1.2 
Other Investigational Medicinal Products 
There are no investigational products other than 68Ga-OPS202 in this study. 
6.1.3 
Other Study Drugs 
Not applicable.    

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6.2 
Concomitant Medication/Therapy 
Any relevant prior or concomitant therapy or medication given to a subject within 3 months 
before IIP administration, during IIP administration and up to the end of the follow-up period 
will be indicated on the eCRF. Dose and generic name or tradename will be recorded. 
The following concomitant medications /therapies are not permitted during this study up to the 
second PET/CT scan and 48 hours post second OPS202 scan: 
• 
Administration of any radiopharmaceutical 
• 
On Visit 2 and Visit 3 parenteral amino acid solutions and any formulation of diuretics 
are not allowed. Stable adjusted diuretics such as for subjects with hypertension are 
permitted. 
Long acting SSAs, ie, Somatuline® Autogel® /Depot® (60, 90 or 120 mg) and Sandostatin® LAR 
(20 or 30 mg) will not be allowed within 28 days prior to the first 68Ga-OPS202 PET/CT exam 
(at Visit 2) and during the study up to Visit 3 after the second 68Ga-OPS202 PET/CT exam has 
been completed. Short acting Sandostatin® is allowed during the study with a washout period 
of 24 hours before each of the two 68Ga-OPS202 PET/CT (Visit 2 and Visit 3), to avoid possible 
interaction between the non-radioactive SSA and OPS202. 
Subjects on long acting SSA who need to continue such treatment for symptom control, should 
be switched to short acting SSA with a 24 hour wash out period before each of the two 
68Ga-OPS202 PET/CT (Visit 2 and Visit 3). Long acting SSAs can be resumed after Visit 3. 
Other concomitant medications are permitted during this study at the discretion of the 
investigator but they must be monitored closely and every effort should be made to keep their 
dose and dose regimen constant throughout the course of the study.  
6.3 
Procedures for Monitoring Subject Compliance 
The IIP is administered i.v. by the investigator or his/her delegate. Therefore, no specific 
procedure is required for monitoring subject compliance. The injected peptide mass dose and 
radioactivity dose will be recorded in the medical file and in the eCRF for each subject. 
The investigator will ensure that the subject did not and is not taking any of the prohibited 
medication listed in Section 6.2 during the study period. 

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7 
ASSESSMENT OF EFFICACY 
For the timing of efficacy assessments in this study, refer to the schedule in Table 5.  
The sets of images obtained at Visit 2 and Visit 3 for the primary endpoint and most of the 
secondary endpoint analyses will be sent to an ICL for centralised blinded reading by two 
independent experienced radiologists/nuclear medicine physicians, and a third for adjudication 
of discordances. The readers will be specifically trained for this protocol. Full details of the 
read design and conduct will be provided in the IRC. 
For the primary endpoint analysis, the number of lesions on each subject scan will be counted 
on a per organ basis by the two primary independent readers. Scans will be blinded to subject, 
site, peptide and radioactivity dose. In case of discrepancy, images will go to the adjudicator 
(third reader) for a final read and adjudication.  
After blinded reading, the readers will compare the paired scan for each subject and note which 
of the pair provides superior images based on overall image quality and lesion count. 
The primary endpoint is the mean number of lesions identified in each tabular cell (see Table 
3) as the ratio of the maximum number of lesions identified per organ per subject, removing 
individually differing absolute lesion numbers as a confounder and allowing the factorial design 
to be established to identify the optimum peptide mass and radioactivity dose. 
The sequence of image display and recording of results will be as follows on a per subject basis: 
1) Review of the two image sets of 68Ga-OPS202 scans in randomised step-wise fashion, 
without and with CT image fusion. The PET and CT images acquired at the same time 
will be used for co-registration. 
2) CT images for standard-of-truth assessments will be reviewed by two radiologists not 
involved in PET/CT images read. It is not anticipated that there will be a difference in 
the lesion counts between the two visits related to disease progression, due to slow 
development of GEP-NETs; however, there may be technical reasons for variations 
between the scans 
3) Review of the lesion-to-background ratios in each major anatomical site (liver, lymph 
nodes, bone and lungs) based on the evaluation of up to five most avid lesions per organ 
4) SUVmax calculations of the five most avid lesions per organ on PET scans (liver, lymph 
nodes, bone and lungs) 
5) For image quality, direct comparison of the two 68Ga-OPS202 scans with different 
peptide and radioactivity doses  
6) Evaluation of previously acquired ssrt2 receptor agonist positive scans. 
7.1 
Primary Efficacy Endpoint and Evaluation 
For each combination of injected peptide/radioactivity dose ranges, differences in relative 
lesion counts derived from a 2 × 3 factorial analysis measuring the ratio of the number of lesions 
detected by 68Ga-OPS202 to the number of lesions assessed by standard-of-truth:  blinded 
read-out (derived from above recording of results, points 1 and 2) with descriptive analyses. 
7.2 
Secondary Efficacy Endpoints and Evaluations 
Key Secondary Endpoint: 
• 
For each combination of injected peptide/radioactivity dose ranges, differences in image 
quality derived from a 2 × 3 factorial analysis measuring the tumour-to-background ratio 
in each of the major anatomic sites (descriptive analyses for liver, lymph nodes, bone 
and lungs) 

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A qualitative analysis of the image quality as assessed by the blinded readers will be performed 
to back up the quantitative quality measured by tumour-to-background analysis.  
For further details, refer to the IRC. 
Other Secondary Endpoints: 
• 
Differences of lesion SUVmax between the two peptide mass dose ranges and the three 
radioactivity dose ranges measured in the most avid lesions: descriptive analyses for up 
to a maximum of five lesions per organ (derived from above recording of results, point 
4), in liver, lymph nodes, bone and lungs 
• 
Differences of absolute number of lesions between the two peptide mass dose ranges and 
the three radioactivity dose ranges detected in each of the following anatomic sites, both 
as standalone and also compared to the standard-of-truth scans; blinded read-out (derived 
from above recording of results, points 1 and 2) with descriptive analyses:  
• 
Primary site of GEP-NET  
• 
Lymph nodes  
• 
Liver  
• 
Axial/appendicular skeleton  
• 
Lungs 
• 
The primary and secondary endpoints will also be evaluated on a radioactivity dose/kg 
of body weight. 
Exploratory Endpoints: 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of GEP-NETs by both 
subject-based and lesion-based analysis compared to standard-of-truth 
• 
Comparison to sstr2 agonist positive scan results will be computed for sensitivity analysis 
• 
Differences in SUVmax ratios between the two peptide mass dose ranges and three 
radioactivity dose ranges for lesions. 
• 
SNR calculated from lesion-free VOI in the liver: SUVmean/SUVSD between the three 
radioactivity doses. 
For further details on efficacy secondary endpoints assessment, refer to the IRC. 
7.3 
Methods and Timing of Assessing, Recording, and Analysing Efficacy Data 
Methods for assessing efficacy data are listed below and are described in further detail in the 
IRC. Timing of efficacy assessments are discussed in Section 5. Procedures for recording 
efficacy data are discussed in Section 14.1, and methods of analyses are discussed in 
Section 10.4.5. 
All images will be sent to a central ICL for QC and central read management.  This comprises 
the following images: 
• 
Prior sstr2 agonist positive PET scans (see Section 4.1) 
• 
All 68Ga-OPS202 PET/CT scans. 
The details of imaging set management and read design will be fully described in the IRC.  This 
will include the following: 
• 
Full acquisition guidelines for the site 
• 
Process for PET scanner quality control (phantom assessments and reporting) 
• 
Image transmission methodology 

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• 
Core lab QC methodology and management of the images 
• 
Read design for primary endpoint 
• 
Read design for secondary endpoint and process for calculating tumour-to-background 
ratio and SUVmax 
• 
Design of exploratory endpoints 
• 
Conduct of the read 
• 
Management, training and inter-reader evaluation 
• 
Data management 
• 
Data export overview 
• 
Archiving of images. 

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8 
ASSESSMENT OF SAFETY 
The safety and tolerability of 68Ga-OPS202 consists of evaluating: 
• 
AEs throughout the study 
• 
Clinical laboratory test results (serum chemistry, haematology, urinalysis) throughout 
the study 
• 
Vital signs measurements (blood pressure and heart rate) throughout the study  
• 
ECG at Visit 1 and 4 (End of treatment/ Early Withdrawal) 
• 
Physical examination results throughout the study 
• 
Concomitant medication usage throughout the study. 
8.1 
Adverse Events 
Adverse events will be monitored from the time that the subject gives informed consent and 
throughout the study (see Section 3.5 for a definition of the study duration) and will be elicited 
by direct, nonleading questioning or by spontaneous reports. Further details for AE reporting 
can be found in Section 8.1.1. 
Definition of an Adverse Event 
An AE is the development of an undesirable medical condition or the deterioration of a 
pre-existing medical condition following or during exposure to a pharmaceutical product, 
whether or not considered causally related to the product. An undesirable medical condition can 
be symptoms (e.g. nausea, chest pain), signs (e.g. tachycardia, enlarged liver) or the abnormal 
results of an investigation (e.g. laboratory findings, electrocardiogram). In clinical studies, an 
AE can include an undesirable medical condition occurring at any time, including run in or 
washout periods, even if no IIP has been administered.  
This definition includes events occurring from the time of the subject giving informed consent 
until the end of the study (as defined in Section 3.5). 
8.1.1 
Categorisation of Adverse Events 
8.1.1.1 
Intensity Classification 
Adverse events will be recorded and graded according to the current version of the NCI-CTCAE 
(version 5.0). In view of meta-analyses, and for conversion purposes, the following conversion 
mapping will apply if the NCI-CTCAE scale is not available for a given AE: 
• 
NCI-CTCAE Grade 1 corresponds to mild, 
• 
NCI-CTCAE Grade 2 corresponds to moderate, 
• 
NCI-CTCAE Grade 3 corresponds to severe, 
• 
NCI-CTCAE Grade 4 corresponds to life threatening/disabling, 
• 
NCI-CTCAE Grade 5 corresponds to death (related to AE). 
Where:  
• 
Mild: symptoms do not alter the subject’s normal functioning 
• 
Moderate: symptoms produce some degree of impairment to function, but are not 
hazardous, uncomfortable or embarrassing to the subject 
• 
Severe: symptoms definitely hazardous to wellbeing, significant impairment of function 
or incapacitation. 

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• 
Life threatening: any event that places the subject at immediate risk of death from the 
event as it occurred, i.e. it does not include a reaction that, had it occurred in a more 
severe form, might have caused death (also see Section 8.1.3). 
8.1.1.2 
Causality Classification 
The relationship of an AE to IIP administration will be classified according to the following: 
• 
Related: reports including good reasons and sufficient information (e.g. plausible time 
sequence, dose response relationship, pharmacology, positive dechallenge and/or 
rechallenge) to assume a causal relationship with IIP administration in the sense that it is 
plausible, conceivable or likely. 
• 
Not related: reports including good reasons and sufficient information (e.g. implausible 
time sequence and/or attributable to concurrent disease or other drugs) to rule out a causal 
relationship with IIP administration. 
8.1.1.3 
Assessment of Expectedness 
The expectedness of an AE shall be determined by the sponsor according to the IIP IB.  
The reference document for assessing expectedness of AEs/event in this study will be the 
current IB. 
8.1.1.4 
Laboratory Test Abnormalities 
All abnormalities in laboratory test values should only be reported as AEs if any of the 
following apply:  
• 
They result in a change in IIP schedule of administration (change in dosage, delay in 
administration, IIP discontinuation), 
• 
They require intervention or a diagnosis evaluation to assess the risk to the subject, 
• 
They are considered as clinically significant by the investigator, or the laboratory test 
abnormality suggests a disease and/or organ toxicity that is new or has worsened from 
baseline based on sponsor review. 
8.1.1.5 
Abnormal Physical Examination Findings  
Clinically significant changes, in the judgement of the investigator, in physical examination 
findings (abnormalities) will be recorded as AEs.  
8.1.1.6 
Other Investigation Abnormal Findings 
Abnormal test findings as judged by the investigator as clinically significant 
(e.g., electrocardiogram changes) that result in a change in IIP dosage or administration 
schedule, or in discontinuation of the IIP, or require intervention or diagnostic evaluation to 
assess the risk to the subject, should be recorded as AEs.  
8.1.2 
Recording and Follow up of Adverse Events 
At each visit, the subject should be asked a non-leading question such as: “How have you felt 
since the administration or last administration of the study compound.” 
All observed or volunteered AEs, regardless of study arm or suspected causal relationship to 
IIP, will be recorded on the AE page(s) of the eCRF. Events involving drug reactions, accidents, 
illnesses with onset during the treatment phase of the study, or exacerbations of pre-existing 
illnesses should be recorded according to NCI terminology. 
Any AEs already recorded and designated as ‘continuing’ should be reviewed at each 
subsequent assessment. 

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For all AEs, the investigator must pursue and obtain information adequate both to determine 
the outcome of the AE and to assess whether it meets the criteria for classification as a SAE 
requiring immediate notification to the sponsor or its designated representative. For all AEs, 
sufficient information should be obtained by the investigator to determine the causality of the 
AE (i.e. IIP or other illness). The investigator is required to assess causality and record that 
assessment on the eCRF. Follow-up of the AE, after the date of IIP discontinuation, is required 
if the AE or its sequelae persist. Follow-up is required until the event or its sequelae resolve or 
stabilise at a level acceptable to the investigator and the sponsor’s clinical monitor or his/her 
designated representative. 
8.1.3 
Reporting of Serious Adverse Events 
All SAEs (as defined below) regardless of study arm or suspected relationship to IIP must be 
reported immediately (within 24 hours of the investigator’s knowledge of the event) using the 
fax number specified at the beginning of this protocol. If the immediate report is submitted by 
telephone, this must be followed by detailed written reports using the SAE report form. 
A SAE is any AE that: 
1) 
Results in death, 
2) 
Is life threatening, that is any event that places the subject at immediate risk of death 
from the event as it occurred. It does not include an event that, had it occurred in a more 
severe form, might have caused death, 
3) 
Results in inpatient hospitalisation or prolongation of existing hospitalisation, excluding 
admission for social or administrative reasons (see further), 
4) 
Results in a persistent or significant disability/incapacity, where disability is a substantial 
disruption of a person's ability to conduct normal life functions, 
5) 
Results in congenital anomaly/birth defect in the offspring of a subject who received the 
IIP, 
6) 
Is an important medical event that may not result in death, be life threatening, or require 
hospitalisation when, based upon appropriate medical judgement, may jeopardise the 
subject and may require medical or surgical intervention to prevent one of the outcomes 
listed in this definition. Examples of such medical events include allergic bronchospasm 
requiring intensive treatment in an emergency room or at home, blood dyscrasias or 
convulsions that do not result in inpatient hospitalisation, or the development of drug 
dependency or drug abuse. 
In addition to the above criteria, any additional AE that the sponsor or an investigator considers 
serious should be immediately reported to the sponsor and included in the corporate SAEs 
database system. 
• 
Hospitalisation is defined as any inpatient admission (even if less than 24 hours). For 
chronic or long-term inpatients, inpatient admission also includes transfer within the 
hospital to an acute/intensive care inpatient unit. 
• 
Prolongation of hospitalisation is defined as any extension of an inpatient 
hospitalisation beyond the stay anticipated/required in relation to the original reason for 
the initial admission, as determined by the investigator or treating physician. For 
protocol-specified hospitalisation in clinical studies, prolongation is defined as any 
extension beyond the length of stay described in the protocol. Prolongation in the absence 
of a precipitating, treatment-emergent, clinical AE (i.e. not associated with the 
development of a new AE or worsening of a pre-existing condition) may meet criteria 

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for "seriousness" but is not an adverse experience and thus is not subject to immediate 
reporting to the sponsor.  
• 
Pre-planned or elective treatments/surgical procedures should be noted in the subject’s 
screening documentation. Hospitalisation for a pre-planned or elective treatment/surgical 
procedure should not be reported as an SAE unless there are complications or sequelae 
that meet the criteria for seriousness described above. 
Any SAE must be reported immediately (within 24 hours), to Ipsen Pharmacovigilance through 
the email (preferably) or fax number specified at the beginning of this protocol, independent of 
the circumstances or suspected cause, if it occurs or comes to the attention of the investigator 
at any time during the study period. 
Any AE/SAE with a suspected causal relationship to IIP administration occurring at any other 
time after completion of the study must be promptly reported. 
The following information is the minimum that must be provided to the sponsor within 24 hours 
for each SAE: 
• 
Study number 
• 
Centre number 
• 
Subject number 
• 
AE 
• 
Investigator's name and contact details 
The additional information included in the SAE form must be provided to the sponsor or 
representative as soon as it is available. The investigator should always provide an assessment 
of causality for each event reported to the sponsor. Upon receipt of the initial report, the sponsor 
will ask for the investigator's causality assessment if it was not provided with the initial report. 
The investigator should report a diagnosis or a syndrome rather than individual signs or 
symptoms. The investigator should also try to separate a primary AE considered as the foremost 
untoward medical occurrence from secondary AEs which occurred as complications. 
8.1.4 
Pregnancy 
Pregnancy itself is not regarded as an AE unless there is a suspicion that the IIP has interfered 
with a contraceptive method. If pregnancy occurs during the study, the outcome of the 
pregnancy will then need to be collected after the study and it may be necessary to discontinue 
administration of the IIP.  
Information regarding pregnancies must be collected on the AE page of the eCRF and reported 
to the sponsor as an SAE. The sponsor will request further information from the investigator as 
to the course and outcome of the pregnancy using the Standard Pregnancy Outcome Report 
Form.  
The investigator must instruct all subjects to inform them immediately should they or their 
female partner become pregnant during the study. In case the investigator becomes aware of 
pregnancy occurring in a subject (pregnancy test before each exposure to the IIP), the IIP 
administration should be stopped and the subject followed up until Visit 4 (End of the study). 
The investigator should counsel the subject, discuss the risks, if any, and the possible effects on 
the foetus. Monitoring of the subject (or female partner of a male subject) who becomes 
pregnant during the study after the administration of at least one of the two single IIP injections 
should continue until conclusion of the pregnancy, which may involve follow up after the 
subject’s involvement in the study has ended (as per Ipsen’s standard pharmacovigilance). 

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Pregnancies with a probable conception date within completion of the study (30 days after 
subject’s last dose of IIP) must also be reported to the investigator for onward reporting to the 
sponsor. 
If the investigator becomes aware of a pregnancy occurring in the partner of a subject 
participating in the study, this should be reported to the sponsor. After the partner has given 
written consent, she should be counselled and followed as described above. Monitoring of the 
partner should continue until the pregnancy comes to an end. 
8.1.5 
Deaths 
For AEs leading to death, NCI CTCAE Grade 5 is the only appropriate grade (see 
Section 8.1.1.1). Deaths that cannot be attributed to an NCI CTCAE term associated with Grade 
5 or that cannot be reported within an NCI CTCAE category as ‘Other’ have to be reported as 
one of these four AE options: 
• 
Death not otherwise specified (NOS), 
• 
Disease progression NOS, 
• 
Multi-organ failure, 
• 
Sudden death. 
The term “sudden death” should only be used for the occurrence of an abrupt and unexpected 
death due to presumed cardiac causes in a patient with or without pre-existing heart disease, 
within 1 hour of the onset of acute symptoms or, in the case of an unwitnessed death, within 24 
hours after the patient was last seen alive and stable. If the cause of death is unknown and 
cannot be ascertained at the time of reporting, “unexplained death” should be recorded on the 
Adverse Event eCRF. If the cause of death later becomes available (e.g. after autopsy), 
“unexplained death” should be replaced by the established cause of death.” 
8.1.6 
Discontinuation/Withdrawal due to Adverse Events/Serious Adverse Events 
Discontinuation/withdrawal 
due 
to 
AEs 
should 
be 
distinguished 
from 
discontinuation/withdrawal due to insufficient response to the IIP (see Section 4.3). 
If the second dose of IIP cannot be given due to a SAE following Visit 2 administration, it must 
be reported immediately to the sponsor’s designated representative (see Section 8.1.3). 
In all cases, the investigator must ensure the subject is adequately followed up (see 
Section 8.1.2). 
Reporting to Competent Authorities/IECs/IRBs/Other Investigators 
The sponsor will ensure that processes are in place for submission of reports of SUSARs 
occurring during the study to the CA, independent ethics committees (IECs) and other 
investigators concerned by the IIP. Reporting will be done in accordance with the applicable 
regulatory requirements. 
For study centres in the USA, Investigational New Drug (IND) application safety reports will 
be submitted directly to the investigators. It is the investigators’ responsibility to notify their 
institutional review board (IRB) in a timely manner. 
8.2 
Clinical Laboratory Tests 
Blood samples will be collected at all study visits (Screening Visit [Visit 1], Baseline/Day 1 
[Visit 2], Visit 3, and End of Study/Early Withdrawal [Visit 4]) (see schedule of assessment in 
Table 5) or the evaluation of haematology and serum chemistry. Urine samples will be collected 
only at Visit 2 and Visit 3 to determine the amount of renal excretion of OPS202.  

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The investigator will review the safety laboratory test results, document the review, and record 
any clinically relevant result occurring or observed during the study in the AE section of the 
eCRF (see Section 8.1.1.4 for abnormal laboratory tests that should be recorded as AEs). 
All clinically relevant abnormal laboratory tests occurring during the study will be repeated at 
appropriate intervals until they return to Baseline or to a level deemed acceptable by the 
investigator and the sponsor’s clinical monitor (or his/her designated representative) or until the 
abnormality is explained by an appropriate diagnosis.  
8.2.1 
Haematology 
Blood samples will be collected (in a potassium ethylenediaminetetraacetic acid [EDTA] tube) 
to assess the following parameters: red blood cell (RBC) count, haemoglobin, haematocrit, 
mean corpuscular volume (MCV), mean corpuscular haemoglobin (MCH), mean corpuscular 
haemoglobin concentration (MCHC), white blood cell (WBC) absolute count (neutrophils, 
lymphocytes, monocytes, eosinophils, basophils, and others) and platelet count. 
8.2.2 
Blood Biochemistry 
Blood samples will be collected to assess the following parameters: 
• 
urea, creatinine, total bilirubin, conjugated bilirubin 
• 
chloride, bicarbonate, sodium, potassium, calcium, phosphate 
• 
AP, AST, ALT, gamma-glutamyl transferase (GGT) 
• 
albumin, total protein, total cholesterol, triglycerides, fasting glucose 
8.2.3 
Urinalysis 
Fresh urine samples (at least 10 mL) will be collected to assess the following parameters: pH, 
protein, ketones, bilirubin, blood, urobilinogen, nitrites, leukocyte esterase, glucose and specific 
gravity by dipstick.  
Microscopy will be performed, if indicated, but results will not be collected in the eCRF. If in 
the opinion of the investigator there are any clinically significant abnormalities in microscopy, 
they will be recorded as an AE in the eCRF. 
8.2.4 
Pregnancy Test 
A ßHCG test will be performed for all female subjects of childbearing potential at Screening 
(Visit 1) and End of Study Visit (Visit 4). A urinary hCG test will be performed at Baseline 
Visit (Visit 2) before first IIP administration and at Visit 3 before second IIP administration and 
if clinically indicated. Any subject becoming pregnant during the study will be withdrawn. All 
pregnancies (including in female partners of male participants) that occur during the study are 
to be reported as described in Section 8.1.4. 
8.2.5 
Putative Antibody Testing 
Not applicable 
8.2.6 
Other Clinical Laboratory Tests 
Not applicable.  
8.3 
Physical Examination 
Physical examinations, including body weight, will be conducted at Screening, Baseline 
(Visit 2), Visit 3 and End of Study (Visit 4)/Early Withdrawal (see Table 5), and height will be 
measured at Screening. 

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Any clinically significant physical examination findings (abnormalities) observed during the 
study will be reported as AEs. Any physical examination findings (abnormalities) persisting at 
the end of the study will be followed by the investigator until resolution or until reaching a 
clinically stable endpoint. 
8.4 
Vital Signs 
Blood pressure and heart rate will be assessed with an automated device so that measurements 
are independent of the observer. Blood pressure and heart rate will be recorded after five 
minutes rest in sitting position and after one minute standing. Absolute values and change from 
Baseline will be analysed. 
Respiratory rate and temperature (tympanic/oral) will be recorded. 
8.5 
Electrocardiography 
An ECG analysis will be included as a safety evaluation/endpoint in this study. 
The ECGs will be recorded at Screening Visit, and End of Study/Early Withdrawal (Visit 4). 
Twelve-lead ECGs will be recorded at a paper speed of 25 mm/sec so that the different ECG 
intervals (RR, PR, QRS, QT) can be measured automatically as per study site usual practice. 
The ECG will be recorded with the subject in supine position after five minutes of rest until 
four regular consecutive complexes are available. ECG interval estimates will be measured as 
per study site usual practice, in this study. 
Any clinically significant abnormalities will be recorded as AEs. 

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9 
ASSESSMENTS OF PHARMACOKINETICS/PHARMACODYNAMICS 
9.1 
 Pharmacokinetics 
9.1.1 
Sample Collection 
Subjects randomized to each of the six dose range combinations of peptide mass and 
radioactivity will participate in the OPS202 PK sampling. 
Blood samples (2 mL each) for determination of OPS202 plasma concentrations will be 
collected preferably by venepuncture in low-binding tubes at the following timepoints: Baseline 
pre-dose (T0), 5 min, 15 to 45min, 1h, 2h, 3h and 6h after the 68Ga-OPS202 i.v. administration 
at the corresponding visits (Visit 2 and Visit 3).  
Urine collection in low-binding containers to determine renal excretion of OPS202 will be 
performed over the first 6 hours (0h to 3h and 3h to 6h after the 68Ga-OPS202 i.v. administration 
at the corresponding visits: Visit 2 and Visit 3). Subjects will be asked to empty his/her bladder 
just before the 68Ga-OPS202 i.v. administration and then all urine voided during the collection 
interval (0-6 hours post 68Ga-OPS202 i.v. administration) will be collected and stored. 
All details about sample collection, storage and shipment will be provided in the 
Pharmacokinetics, Dynamics and Metabolism (PDM) Sample Management Plan/Laboratory 
Manual. 
During the study, the nominal sample collection times may be changed, but the total number of 
samples will not increase. The exact dates and times of blood sample collection and study drug 
administration must be recorded in the eCRF. 
9.1.2 
Analytical Procedures 
Plasma samples will be analysed to determine concentrations of OPS202 using a validated, 
specific and sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method 
at Kymos Pharma Services, Barcelona, Spain. As an exploratory analysis, some of the 
additional plasma samples may be used to measure potential metabolites (identified during 
pre-clinical investigations) using a qualified LC-MS/MS method.  
Urine samples will be analysed to determine concentrations of OPS202 using a validated 
method. As an exploratory analysis, some of the urine samples might be used to explore 
potential metabolites. 
9.1.3 
Data Analysis 
Individual plasma and urine concentrations for OPS202 will be listed and summarised by 
timepoints and dose range combinations using descriptive statistics for continuous variables 
(number of available observations, mean, median, standard deviation, minimum, maximum, 
geometric mean, and geometric coefficient of variation assuming log-normally distributed 
data). Linear and semilogarithmics plots of individual and mean plasma concentration-time 
profiles as well as spaghetti plots will be reported. 
Analysis of plasma and urine PK data by non-compartmental approach using Phoenix 
WinNonLin Version 6.3 or higher will be documented in a separate analysis plan. The analysis 
of PK data will be performed by a CRO under Ipsen Clinical PK department’s supervision and 
if warranted by the data the following parameters, but not limited to, will be computed: 
• 
Cmax 
• 
AUClast 
• 
AUC∞ 

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• 
Elimination half-life (T1/2) 
• 
Total plasma clearance (CL) 
• 
Volume of distribution (V) 
• 
Excreted amount in the urine over each time interval (0h to 3h and 3h to 6h after the 
68Ga-OPS202 i.v. administration at the corresponding visits: Visit 2 and Visit 3), as well 
as the 6-hour Ae). 
Descriptive summary statistics (the number of observations [n], mean, median, standard 
deviation [SD] and range for continuous variables, and n and per cent [%] for 
categorical/nominal variables) will be presented for each PK parameter. 
Additional exploratory model-based analysis (population PK analysis) might also be conducted 
using NONMEM software.  

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randomisation numbers 
 will be included only in the safety analysis. 
Therefore, a total of at least 25 subjects will be enrolled in the study to ensure the 48 PET scans 
for the analysis. 
10.3 
Significance Testing and Estimations 
The analysis will be descriptive and no formal statistical tests are planned for the primary and 
secondary endpoints.  
10.4 
Statistical/Analytical Methods 
Statistical analyses will be performed by an external CRO, managed by the sponsor’s Biometry 
Department. 
A Reporting and Analysis Plan describing the planned statistical analysis in detail with tables, 
figures and listings templates will be developed as a separate document. 
Statistical evaluation will be performed using Statistical Analysis System (SAS)® (version 8 or 
higher). 
10.4.1 
Demographic and Other Baseline Characteristics 
Descriptive summary statistics (n, mean, SD, median, minimum, maximum) and frequency 
counts of demographic and baseline data (medical history, concomitant disease, predosing AEs 
and ongoing medical history, prior medications and therapies, baseline symptoms, etc.) will be 
presented by study arm and overall for the randomised and PP populations. 
10.4.2 
Homogeneity of Treatment Groups 
Not applicable. 
10.4.3 
Subject Disposition and Withdrawals 
The numbers and percentages of subjects enrolled and included in each of the randomised, PP 
and safety populations will be tabulated by arm. The reasons for subject exclusions from each 
of the populations will be listed and tabulated by arm. In addition, the numbers of subjects who 
were randomised, received IIP, discontinued and completed at each of the study periods (e.g. 
Visit 2 and Visit 3, active follow-up period) will be tabulated by arm. Primary reasons for 
discontinuation of study IIP will be listed and tabulated by arm. 
10.4.4 
Pharmacokinetic Data 
The pharmacokinetic data analysis will be performed independently by a CRO under Ipsen 
Clinical PK department’s supervision as described in Section 9.1.3. 
Individual listings and summary tables of OPS202 plasma concentrations and amount excreted 
in urine will be provided. 
10.4.5 
Efficacy Evaluation 
As indicated in Section 7.1, the primary efficacy variable is the differences in relative lesion 
counts derived from a 2 × 3 factorial analysis measuring the ratio of the number of lesions 
detected by 68Ga-OPS202 to the number of lesions assessed by standard-of-truth, for each 
combination of injected peptide/radioactivity dose ranges. Primary efficacy variable will be 
summarised by study arm and by each combination peptide/radioactivity dose range. 
As indicated in Section 7.2, the secondary efficacy variables are the below listed variables 
measured at Visit 2 and Visit 3 after the i.v. administration of the IIP: 
Key Secondary Endpoint: 
CCI

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• 
Differences in image quality derived from a 2 × 3 factorial analysis measuring, for each 
combination of injected peptide/radioactivity dose ranges, the tumour-to-background 
ratio in each of the major anatomic sites (descriptive analyses for liver, lymph nodes, 
bone and lungs). Key secondary efficacy variable will be summarised by study arm and 
by each combination peptide/radioactivity dose range. A qualitative analysis of the image 
assessed by the blinded readers will be performed to back up the quantitative quality 
measured by tumour-to-background analysis. 
Other Secondary Endpoints: 
• 
Differences of lesion SUVmax between the two peptide mass dose ranges and the three 
radioactivity dose ranges measured in the most avid lesions (descriptive analyses for up 
to a maximum of five lesions per organ), in liver, lymph nodes, bone and lungs 
• 
Differences of absolute number of lesions between the two peptide mass dose ranges and 
the three radioactivity dose ranges detected in each of the following anatomic sites:  
• 
Primary site of GEP-NET  
• 
Lymph nodes  
• 
Liver  
• 
Axial/appendicular skeleton  
• 
Lungs. 
Exploratory Endpoints: 
• 
Preliminary diagnostic sensitivity of 68Ga-OPS202 imaging of GEP-NETs by both 
subject-based and lesion-based analysis compared to standard-of-truth 
• 
Comparison to sstr2 agonist positive scan results will be computed for sensitivity analysis 
• 
Differences in SUVmax ratios between the two peptide mass dose ranges and three 
radioactivity dose ranges for lesions 
• 
SNR calculated from lesion-free VOI in the liver: SUVmean/SUVSD between the three 
radioactivity doses. 
10.4.6 
Adjustment for Country/Centre Effect 
It is not planned to perform a subgroup analysis on centres.  
10.4.7 
Safety Evaluation 
All AEs will be coded according to the MedDRA version (latest version in use) and will be 
classified by MedDRA SOC and PT. AEs, SAEs, AEs leading to discontinuation of study 
treatment, and AEs leading to death will be summarized and listed by subject, SOC class and 
PT. Adverse events reported by investigators using the NCI-CTCAE classification (version 5.0) 
will be coded using MedDRA dictionary (latest available version).  
Incidence of all reported AEs and SAEs will be tabulated by dosing arm and overall. In addition, 
summary tables will be presented by maximum intensity, drug relationship and AEs associated 
with premature withdrawal of study medication. 
Concomitant medication will be coded by using WHO Drug Dictionary (WHO-DD) (latest 
available version) and will be summarised by dosing arm and by overall. 
Summary statistics (mean, median, SD and range as appropriate) by IIP dose ranges 
combination and overall will be presented for vital signs, blood pressure, heart rate, ECG 
parameters, clinical laboratory tests etc. at each assessment with change from Baseline. For 
laboratory data, abnormal values will be flagged in the data listings and a list of clinically 

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significant abnormal values will be presented. Clinically significant ECG findings will also be 
flagged. Shift tables will be presented of the number and percentage of subjects with low, 
normal or high values and normal or abnormal exams. 
Summary incidence tables will be provided classified by SOC, PT, and associated NCI-CTCAE 
worst grade. In the event of multiple occurrences of the same AEs being reported by the same 
subject, the maximum intensity (Grade 5 > Grade 4 > Grade 3 > Grade 2 > Grade 1 > missing 
> not applicable) will be chosen.  
Haematological and biochemistry toxicities will be recorded and graded according to the 
NCI-CTCAE criteria. The NCI-CTCAE grade 3 and 4 haematology and biochemistry 
parameters by subject and by cycle will be listed.  
10.5 
Subgroup Analyses 
Not applicable. 
10.6 
Interim Analyses 
An interim analysis will be performed when a minimum of 12 subjects have fully completed 
the study. The study will continue while the interim analysis is performed and the study may 
be stopped per sponsor’s decision based on expert review of the data. The interim statistical 
analysis plan will provide further details of the statistical analyses. 

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11 
DIRECT ACCESS TO SOURCE DATA AND DOCUMENTS 
Authorised personnel from external CAs and sponsor-authorised Quality Assurance personnel 
may carry out inspections and audits. The purpose of an audit is to ensure that ethical, regulatory 
and quality requirements are fulfilled in all studies performed by the sponsor. 
Auditors and inspectors must have direct access to study documents and site facilities as 
specified in Section 12.4, and to any other locations used for the purpose of the study in question 
(e.g. laboratories). 
In the event of the site being notified directly of a regulatory inspection, the investigator must 
notify the sponsor’s representative as soon as possible, to assist with preparations for the 
inspection. 

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12 
QUALITY CONTROL AND QUALITY ASSURANCE 
12.1 
Protocol Amendments and Protocol Deviations and Violations 
12.1.1 
Protocol Amendments 
No changes from the final approved (signed) protocol will be initiated without the prior written 
approval or favourable opinion of a written amendment by the IEC/IRB, except when necessary 
to eliminate immediate safety concerns to the subjects or when the change involves only 
logistics or administration. The principal investigator and the sponsor will sign the protocol 
amendment. 
12.1.2 
Protocol Deviations, Violations, and Exceptions 
All protocol deviations will be identified and recorded by the sponsor or sponsor’s 
representative (see Section 10.1). 
A major protocol deviation is any significant divergence from the protocol, i.e. nonadherence 
on the part of the subject, the investigator, or the sponsor to protocol-specific 
inclusion/exclusion criteria, primary objective evaluation criteria, and/or GCP guidelines. 
Generally, a protocol deviation qualifies as major if: 
• 
The deviation has harmed or posed a significant or substantive risk of harm to the 
research subject 
• 
The deviation compromises the scientific integrity of the data collected for the study 
• 
The deviation is a willful or knowing breach of human subject protection regulations, 
policies, or procedures on the part of the investigator(s) 
• 
The deviation involves a serious or continuing noncompliance with any applicable 
human subject protection regulations, policies, or procedures 
• 
The deviation is inconsistent with Ipsen’s research, medical and ethical principles. 
See also Section 10.1.2 for details on the impact of major protocol deviations on the inclusion 
of subjects in each analysis population. 
A minor protocol deviation is any significant divergence from the protocol that does not impact 
the study results. 
12.2 
Information to Study Personnel 
The investigator is responsible for giving information about the study to all staff members 
involved in the study or in any element of subject management, both before starting any study 
procedures and during the course of the study (e.g. when new staff become involved, or new 
information becomes available). The investigator must assure that all study staff members are 
qualified by education, experience, and training to perform their specific responsibilities. These 
study staff members must be listed on the study centre authorisation form, which includes a 
clear description of each staff member’s responsibilities. This list must be updated throughout 
the study, as necessary. 
The study monitor is responsible for explaining the protocol to all study staff, including the 
investigator, and for ensuring their compliance with the protocol. Additional information will 
be made available during the study when new staff become involved in the study and as 
otherwise agreed upon with either the investigator or the study monitor. 
12.3 
Study Monitoring 
The investigator is responsible for the validity of all data collected at the site. 

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The sponsor is responsible for monitoring this data to verify that the rights and wellbeing of 
subjects are protected, that study data are accurate (complete and verifiable to source data) and 
that the study is conducted in compliance with the protocol, GCP and regulatory requirements. 
Sponsor assigned monitors will conduct regular site visits. The investigator will allow direct 
access to all relevant files (for all subjects) and clinical study supplies (dispensing and storage 
areas) for the purpose of verifying entries made in the eCRF, and assist with the monitor’s 
activities, if requested. Adequate time and space for monitoring visits should be made available 
by the investigator. 
The site must complete the eCRFs according to the sponsor monitoring manual, of the subject’s 
visit and on an ongoing basis to allow regular review by the study monitor, both remotely by 
the internet and during site visits. The central study monitor at the sponsor will use functions 
of the electronic data capture (EDC) system to address any queries raised while reviewing the 
data entered by the study site personnel in a timely manner. 
Whenever a subject name is revealed on a document required by the sponsor (e.g. laboratory 
printouts) the name must be blacked out permanently by the site personnel, leaving the initials 
visible, and annotated with the subject number as identification. 
12.4 
Audit and Inspection 
Authorised personnel from external CAs and the sponsor’s authorised Quality Assurance 
personnel may carry out inspections and audits (see Section 11). 
Data Quality Assurance 
Monitored eCRFs transferred from the investigational site to the assigned Data Management 
group will be reviewed (secondary monitoring) for completeness, consistency, legibility and 
protocol compliance. 
Reasons should be given on the relevant eCRF for any missing data and other protocol 
deviations. Any electronic queries and items not adequately explained will require additional 
electronic manual queries to be raised to the investigator by the monitor for 
clarification/correction. The investigator must ensure that queries are dealt with promptly. All 
data changes and clarifications can be viewed in the audit trail function of the eCRF. 

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13 
ETHICS 
13.1 
Compliance with Good Clinical Practice and Ethical Considerations 
This study will be conducted in compliance with IECs/IRBs, informed consent regulations, the 
Declaration of Helsinki and ICH GCP Guidelines (Section 1.1), and FDA, 21 CFR Part 11, 
Electronic Records, Electronic Signatures, and FDA, Guidance for Industry: Computerized 
Systems Used in Clinical Trials. 
In addition, this study will adhere to all local regulatory requirements.  
Before initiating a study, the investigator/institution should have written and dated 
approval/favourable opinion from the IEC/IRB for the study protocol/amendment(s), written 
informed consent form, any consent form updates, subject emergency study contact cards, 
subject recruitment procedures (e.g. advertisements), any written information to be provided to 
subjects and a statement from the IEC/IRB that they comply with GCP requirements. The 
IEC/IRB approval must identify the protocol version as well as the documents reviewed. 
After IEC/IRB approval, changes will require a formal amendment. Once the study has started, 
amendments should be made only in exceptional circumstances. Changes that do not affect 
subject safety or data integrity are classified as administrative changes and generally do not 
require ethical approval. If ethically relevant aspects are concerned, the IEC/IRB must be 
informed and, if necessary, approval sought prior to implementation. Ethical approval on 
administrative changes will be obtained if required by local/site IEC/IRB. 
13.2 
Informed Consent 
Prior to study entry, the investigator, or a person designated by the investigator, will explain 
the nature, purpose, benefits and risks of participation in the study to each subject, subject’s 
legally acceptable representative or impartial witness. Written informed consent must be 
obtained prior to the subject entering the study (before initiation of any study-related procedure 
and administration of the IIP). Sufficient time will be allowed to discuss any questions raised 
by the subject. 
The sponsor will provide a sample informed consent form. The final version-controlled form 
must be agreed to by the sponsor, and the IEC/IRB and must contain all elements included in 
the sample form, in language readily understood by the subject. Each subject’s original consent 
form, personally signed and dated by the subject or by the subject’s legally acceptable 
representative, and by the person who conducted the informed consent discussion, will be 
retained by the investigator. The investigator will supply subjects with a copy of their signed 
informed consent. 
The consent form may need to be revised during the study following a protocol amendment that 
includes important new information relevant to the safety of the subject. In this instance 
approval should always be given by the IEC/IRB. It is the investigator’s responsibility to ensure 
that all subjects subsequently entered into the study and those currently in the study sign the 
amended form. This is documented in the same way as previously described. Subjects who have 
completed the study should be informed of any new information that may impact on their 
welfare/wellbeing. 
The investigator should, with the consent of the subject, inform the subject’s primary physician 
about their participation in the clinical study. 

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13.3 
Health Authorities and Independent Ethics Committees/Institutional Review 
Boards 
As required by local regulations, the sponsor’s Regulatory Affairs group will ensure all legal 
regulatory aspects are covered, and obtain approval of the appropriate regulatory bodies, prior 
to study initiation in regions where an approval is required. 
13.4 
Confidentiality Regarding Study Subjects 
The investigator must assure that the privacy of the subjects, including their personal identity 
and all personal medical information, will be maintained at all times. In eCRFs and other 
documents or image material submitted to the sponsor, subjects will be identified not by their 
names, but by an identification code (e.g. initials and identification number). 
Personal medical information may be reviewed for the purpose of verifying data recorded on 
the eCRF. This review may be conducted by the study monitor, properly authorised persons on 
behalf of the sponsor, the quality assurance unit, or regulatory authorities. Personal medical 
information will always be treated as confidential. 

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14 
DATA HANDLING AND RECORD KEEPING 
14.1 
Data Recording of Study Data 
In compliance with GCP, the medical records/medical notes, etc, should be clearly marked and 
permit easy identification of a subject’s participation in the specified clinical study. 
The investigator must record all data relating to protocol procedures, IIP administration, 
laboratory data, safety data on the eCRFs provided for the study. The investigator, by 
completing the signature log, may formally designate authority to complete eCRFs to 
appropriately qualified staff having certified user access to the eCRF.  
The investigator must, as a minimum, provide an electronic signature (e-signature) to each case 
report book to attest to the accuracy and completeness of all the data. If any changes are made 
to the eCRF, after a form has been locked and electronically signed, the investigator will be 
required to perform an additional e-signature authorising agreement with any new information 
or changes to the eCRF. 
All corrections on the eCRF will be automatically tracked and a reason for change is always 
required. In the eCRF, the audit trail function will allow the changes made to be viewed on each 
item entered. 
14.2 
Data Management 
An EDC system will be utilised for collecting subject data. Each site is required to have a 
computer and internet connection available for site entry of clinical data. All entries in the eCRF 
will be done under the electronic signature of the person performing the action. This electronic 
signature consists of an individual and confidential username and password combination. It is 
declared to be the legally binding equivalent of the handwritten signature. Only sponsor 
authorised users will have access to the eCRF as appropriate to their study responsibilities. 
Users must have successfully undergone software application training prior to entering data into 
the eCRF. 
Data management will be conducted by a CRO, directed by the sponsor’s data management 
department. All data management procedures will be completed in accordance with the 
contracted CRO standard operating procedures (SOPs), unless otherwise specified. Prior to data 
being received in-house at the assigned CRO, it will be monitored at the investigator site, (for 
further details please see Section 12.3 Monitoring Procedures). The eCRF and other data 
documentation removed from the investigator site(s) will be tracked by the CRO and the 
monitor. 
The sponsor will ensure that an appropriate eCRF is developed to capture the data accurately, 
and suitable queries are raised to resolve any missing or inconsistent data. The investigator will 
receive their data, from the clinical study, in an electronic format (PDF files) which will be an 
exact copy of the eCRF, and will include the full audit trail, for archiving purposes and future 
reference. 
Any queries generated during the data management process will also be tracked by the 
contracted data management CRO/will be raised within the EDC system. It is the central study 
monitor’s responsibility to ensure that all queries are resolved by the relevant parties. 
The sponsor will also ensure that SAE data collected in the eCRF are consistent with 
information provided to the sponsor’s pharmacovigilance department (and vice versa).  
The coding of AEs, medical history, concomitant medication, procedure and non-drug therapy 
terms will be performed centrally by the specialised CRO, directed by the sponsor’s Biometry 
Group, and reviewed and approved by the sponsor. Concomitant medications will be coded 

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using WHO-DD (latest available version) and AEs/medical history terms will be coded using 
MedDRA (latest available version). 
14.3 
Record Archiving and Retention 
During the pre-study and initiation visits, the monitor must ensure the archiving facilities are 
adequate and archiving/retention responsibilities of the investigator have been discussed.  
Study documents should be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or planned marketing applications 
in an ICH region (that is at least 15 years) or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the product. However, these documents should be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. The investigator should take measures to prevent accidental or 
premature destruction of these documents. The final archiving arrangements will be confirmed by 
the monitor when closing out the site. The sponsor will inform the investigator, in writing, as to 
when these documents no longer need to be retained. 
If the principal investigator relocates or retires, or otherwise withdraws his/her responsibility 
for maintenance and retention of study documents, the sponsor must be notified (preferably in 
writing) so that adequate provision can be made for their future maintenance and retention. 

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15 
FINANCING AND INSURANCE 
15.1 
Contractual and Financial Details 
The investigator (and/or, as appropriate, the hospital administrative representative) and the 
sponsor will sign a clinical study agreement prior to the start of the study, outlining overall 
sponsor and investigator responsibilities in relation to the study. Financial remuneration will 
cover the cost per included subject, based on the calculated costs of performing the study 
assessments in accordance with the protocol, and the specified terms of payment will be 
described in the contract. The contract should describe whether costs for pharmacy, laboratory 
and other protocol-required services are being paid directly or indirectly. 
Financial Disclosure Statements will need to be completed, as requested by FDA 21 CFR 
Part 54. 
15.2 
Insurance, Indemnity and Compensation 
The sponsor will provide Product Liability insurance for all subjects included in the clinical 
study. Where required, a hospital-specific indemnity agreement will be used. 

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16 
REPORTING AND PUBLICATIONS OF RESULTS 
16.1 
Publication Policy 
The sponsor encourages acknowledgement of all individuals/organisations involved in the 
funding or conduct of the study, including medical writers or statisticians subject to the consent 
of each individual and entity concerned, including acknowledgement of the sponsor. 
The results of this study may be published or communicated to scientific meetings by the 
investigators involved in the study. For multicentre studies, a plan for scientific publication and 
presentation of the results may be agreed and implemented by the study investigators. The 
sponsor requires that reasonable opportunity be given to review the content and conclusions of 
any abstract, presentation, or paper before the material is submitted for publication or 
communicated. This condition also applies to any amendments that are subsequently requested 
by referees or journal editors. The sponsor will undertake to comment on the draft documents 
within the time period agreed in the contractual arrangements, including clinical trial 
agreements, governing the relationship between the sponsor and authors (or the author’s 
institution). Requested amendments will be incorporated by the author, provided they do not 
alter the scientific value of the material. 
If patentability would be adversely affected by publication, this will be delayed until (i) a patent 
application is filed for the content of the publication in accordance with applicable provisions 
of the clinical trial agreement concerned, (ii) the sponsor consents to the publication, or (iii) the 
time period as may be agreed in the contractual arrangements, including clinical trial 
agreements, governing the relationship between the sponsor and authors (or authors’ institution) 
after receipt of the proposed publication by the sponsor, whichever of (i), (ii) or (iii) occurs 
first. 
The author undertakes to reasonably consider the sponsor's request for delay to the proposed 
publication should the sponsor reasonably deem premature to publish the results obtained at 
this stage of the study. 
16.2 
Clinical Study Report 
A final clinical study report (CSR) will be prepared according to the ICH guideline on structure 
and contents of CSRs. A final CSR will be prepared where any subject has signed informed 
consent, regardless of whether the study is completed or prematurely terminated. Where 
appropriate an abbreviated report may be prepared. The CSR will be in compliance with any 
applicable regulatory requirements, national laws in force and will be in English. 

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17 
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