An Open Label, Multicenter, Retrospective, Pivotal Trial to Evaluate the Efficacy of Clinical Decision Support System-mPDia for Neurodegenerative Parkinsonism Using MRI Images
Conditions: Diagnoses Disease
Sponsor: Heuron Inc.

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Clinical Trial Protocol 
 
 
 
 
An Open Label, Multicenter, Retrospective, Pivotal 
Trial to Evaluate the Efficacy of Clinical Decision 
Support System-mPDia for Neurodegenerative 
Parkinsonism using MRI images 
NCT04334902 
 
 
 
 
Protocol Number 
: 
HR-MPD-01 
Version (Date of Preparation) 
: 
3.4 (2020.10.06) 
 
 
CONFIDENTIAL 
 
All information in this protocol is provided for the principle investigator, related personnel of the study, 
institutional review board, and authority. No information can be released to a third party without prior written 
consent from Heuron Co.,Ltd except for receiving written consent about test participation from people to be 
applied with the investigational device. 

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◈ Summary of Protocol 
Title 
An Open Label, Multicenter, Retrospective, Pivotal Trial to Evaluate the 
Efficacy of Clinical Decision Support System-mPDia for 
Neurodegenerative Parkinsonism using MRI images 
Institution 
10 hospitals consisting of Gachon University Gil hospital et. al 
(Gangnam Severance Hospital, Kyung Hee University Hospital, Korea 
University Guro Hospital, Korea University Ansan Hospital, Seoul St. 
Mary’s Hospital, Seoul Asan Hospital, Hallym University Dongtan 
Sacred Heart Hospital, Hallym University Pyeongchon Sacred Heart 
Hospital, CHA Bundang Medical center) 
Investigational 
Device 
Product name: mPDia 
Item Name: Clinical Decision Support System 
Manufacturer: Heuron Co.,Ltd 
Purpose 
This trial is to check if the diagnosis results of mPDia would meet the 
success criteria, which is the lower limit of the 95% confidence interval 
satisfying 88.2% sensitivity and 70% specificity, while using final clinical 
diagnosis results of medical specialist groups as a golden standard. 
When the success criteria of mPDia, which is established based on prior 
reported sensitivity and specificity of neurodegenerative Parkinsonism 
diagnosis research, is satisfied, it is determined to have efficacy in 
assisting diagnosis of Parkinsonism. 
Design 
Open label, Multicenter, Retrospective, Pivotal clinical trial 
Target case amount 
Total of 221 cases 
 
The sensitivity and specificity goal were set as 95% and 86%, 
respectively, and the lower limit of the 95% confidence interval, which 
is the success criteria of this study, was calculated as 88.2% and 70%, 
respectively. The necessary case (image) amount for calculation was 144 
people and 56 people. Considering the 10% dropout rate, 159 people 
for the patient group and 62 people for the normal group, which is 221 
people in total, was calculated.  
 
Clinical 
performance 
target 
(𝑷𝟏) 
Least clinical 
performance (= lower 
limit of 95% confidence 
interval) (𝑷𝟎) 
N 
+10% 
dropout 
rate 
Total 

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Sensitivity: 
0.950 
Sensitivity: 0.882 
144 
159 
221 
Specificity: 
0.860 
Specificity: 0.700 
56 
62 
 
Inclusion Criteria 
and Exclusion 
Criteria 
1. Inclusion Criteria 
Normal group 
1) Adult more than 19 years old 
2) Person with confirmed 3T nigrosome 1 MRI image 
3) Person with confirmed normal 18F FP-CIT PET/CT image 
4) Research participant who visited clinic with parkinsonian 
symptom as chief complaint that did not correspond to 
neurodegenerative parkinsonism or healthy participant. 
 
Patient group 
1) Adult more than 19 years old 
2) Person with confirmed 3T nigrosome 1 MRI image 
3) Person with confirmed abnormal 18F FP-CIT PET/CT image 
4) Person who visited clinic with parkinsonian symptom as chief 
complaint and was diagnosed as neurodegenerative 
parkinsonism (multiple system atrophy parkinsonian type, 
progressive supranuclear palsy).  
 
2. Exclusion Criteria 
1) 
Patient with encephalopathy besides parkinsonism. 
2) 
Person with anatomic abnormality confirmed by MRI etc. 
3) 
Person with other causative disease in advance. (ex: thyroid 
disease) 
4) 
Patient with lesion in basal ganglia such as in Vascular 
Parkinsonism, Hydrocephalus, Wilson’s disease. 
5) 
Other cases that the researcher determines to be unsuitable 
for this clinical trial. 
* Specific reason will be documented in the case report form 
 

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Data collecting 
method 
The following data will be collected retrospectively from person whose 
past 3T nigrosome 1 MRI image, 18F FP-CIT PET/CT image, image 
interpretation, and neurologic exam results are confirmed by medical 
records, and those whose diagnosis as neurodegenerative parkinsonism 
is confirmed.  
 
Data collecting must be executed following the protocol 10.2 random 
collection. Only the verified researcher who is registered in this study 
will have access to medical records. Data collected for this study will be 
as follows: 
 
­ 
Demographic information 
­ 
Environmental factor and medical history/past history 
­ 
Family history 
­ 
MDS-UPDRS assessment results 
­ 
Check Red Flag signs suggestive of PD plus syndrome 
­ 
Non-motor symptom assessment scale results of Parkinson’s 
disease 
­ 
REM sleep behavior disorder screening results 
­ 
Check of any pain 
­ 
Cognitive function test (K-MMSE, K-MoCA) results 
­ 
S&E ADL test results 
­ 
Hoehn & Yahr stage test results 
­ 
18F FP-CIT PET/CT image and interpretation results 
­ 
Results of neurologic exam and decision of neurodegenerative 
parkinsonism 
­ 
Confirmed 3T nigrosome 1 MRI image 
 
Data used in this study have been collected by the 10 participating 
institutions from May 1st, 2018 to the starting period of the clinical trial. 
Data used for the education of the investigational device were collected 
from November 1st, 2014 to April 30th, 2018 by one institution (Gachon 
University Gil Hospital), making it mutually independent. 
 

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Study Method 
 
 
1. Image blinding 
The blinding coordinator will select 3T nigrosome 1 MRI image from 
data collected by the 10.1 data collection method and blind all non-
image information such as the belonging group or demographic 
information. 
 
2. Interpretation using mPDia 
The blinded image will be delivered to an independent interpreter and 
the interpreter will sequentially upload the image on mPDia according 
to the image number, check the result, and save it. The saved results 
will be printed to be used as source document. The results should be 
blinded, so the saved and printed results should have separate 
passwords or be in a locked space so that researchers other than the 
independent interpreter have no access. The independent interpreter 
should be a neurologist or radiologist of each site who is not 
participating in this study and should be educated of mPDia usage for 
this study. Interpretation using mPDia should be performed 
independently from golden standard creation, and an independent 
statistician of the sponsor collects the mPDia interpretation data. 
 
3. Golden Standard 
Professor Sung Yunghee, a neurologist of Gachon University Gil 
Hospital, Kim Eung Yup, a radiologist of Gachon University Gil Hospital, 
will check the collected medical records, provide final diagnosis to the 
registered candidate based on protocol 10.5.1 neurodegenerative 
parkinsonism diagnosis checklist and check on the following 

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neurodegenerative 
parkinsonism 
classification 
chart. 
Cases 
corresponding to Parkinson’s disease or atypical Parkinsonian 
syndromes are defined as neurodegenerative parkinsonism diagnosis. 
Besides such cases, it is defined not to be neurodegenerative 
parkinsonism. Only when corresponding to neurodegenerative 
parkinsonism can the positive response of mPDia regarding 
neurodegenerative parkinsonism be confirmed. The following diagnosis 
results will be used as a golden standard in this study. 
 
1) Positive in neurodegenerative parkinsonism 
2) Negative in neurodegenerative parkinsonism 
 
When opinions of two specialists are different, the two will discuss to 
reach a consensus and record it on the final diagnosis result. All 
discussed contents will be documented on the Note to file. Golden 
standard creation must be performed independently from mPDia 
interpretation, and the golden standard data will be collected by an 
independent statistician of the sponsor. 
 
4. Independent statistician 
The independent statistician of this study will be Doctor Lee Donghyuk 
of Heuron Co.,Inc. Without participating in this study, the independent 
statistician will collect mPDia interpretation results and golden standard 
and save them in a separate hardware which only the independent 
statistician can have access to. The independent statistician cannot open 
the interpretation results or golden standard before statistical analysis 
is finished. 
Study Period 
12 months from IRB approval date 
Endpoint 
1. Efficacy endpoint 
Sensitivity and specificity of mPDia for diagnosis of neurodegenerative 
parkinsonism using final diagnosis results of the specialist group as a 
golden standard 
 
2. Efficacy endpoint assessment method 

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With the following calculation methods, sensitivity and specificity are 
calculated, and the 95% confidence interval is provided and evaluated 
to assess whether the lower limit of the 95% confidence interval reaches 
88.2% sensitivity and 70% specificity, which is the success criteria of 
mPDia, in comparison to the golden standard, which is the final clinical 
diagnosis 
result 
of 
the 
specialist 
group 
for 
diagnosis 
of 
neurodegenerative parkinsonism. 
 
< Sensitivity and specificity calculation method > 
Results 
Golden standard 
Positive 
Negative 
Total 
Investigational 
Device 
(mPDia) 
Positive 
True positive 
(TP) 
False positive 
(FP) 
True positive 
+ False 
positive 
Negative 
False 
negative (FN) 
True negative 
(FN) 
False 
negative + 
True negative 
Total 
True positive 
+  
False 
negative 
False positive 
+  
True negative 
N 
 
­ 
Sensitivity: 100 x True positive (TP)/[True positive (TP) + False negative 
(FN)] (%) 
­ 
Specificity: 100 x True negative (TN)/[False positive (FP) + True negative 
(TN)] (%)