A Randomized, Double-Blind, Multicentric, Parallel Group Therapeutic Equivalence Study Comparing Efficacy, Safety and Immunogenicity of Subcutaneous DMB-3115 and Stelara® in Patients With Moderate to Severe Chronic Plaque Psoriasis
Phase: PHASE3
Conditions: Moderate to Severe Chronic Plaque Psoriasis
Sponsor: Dong-A ST Co., Ltd.

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Protocol DMB-3115-2 - Protocol Amendment 01 
 
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TITLE PAGE 
Protocol Title:  
A Randomized, Double-Blind, Multicentric, Parallel Group Therapeutic Equivalence Study Comparing 
Efficacy, Safety and Immunogenicity of Subcutaneous DMB-3115 and EU Sourced Stelara® in Patients 
with Moderate to Severe Chronic Plaque Psoriasis. 
Protocol Number: DMB-3115-2 
Amendment Number: 01 
Product: Ustekinumab 
Short Title:  
Efficacy, Safety, and Immunogenicity of Subcutaneous DMB-3115 Versus EU Sourced Stelara® in Patients 
with Moderate to Severe Chronic Plaque Psoriasis. 
Study Phase: Phase III 
Sponsor Name: Dong-A ST Co. Ltd., Republic of Korea  
Legal Registered Address:  
64 Cheonho-daero, Dongdaemun-gu, Seoul, 02587, Republic of Korea 
Regulatory Agency Identifying Number(s):  
IND Number: 
 
EudraCT number: 
 
Date of Protocol: 04 June 2021 (Final) 
 
 
 

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Protocol DMB-3115-2 - Protocol Amendment 01 
 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Table A 
Document History 
Document 
Date 
Substantial 
Region 
Amendment 01 
04-Jun-2021 
Yes 
Global 
Original Protocol 
07-Dec-2020 
 
Global 
 
Amendment 01  
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment: 
The overall rationale for this amendment is to implement changes following regulatory authorities/ethic 
committees’ recommendations/feedback. Additional clarifications and corrections are added. Details on 
the changes and rationale are provided in Table B 
Description of Changes in Amendment.  
 
Table B 
Description of Changes in Amendment 
Section # and Name 
Description of Change 
Brief Rationale 
Section 1.1: Synopsis 
Section 1.3: Schedule of 
Activities  
Section 3.0: Objectives and 
Endpoints 
The pharmacokinetic endpoint was 
updated to include ‘post dose for 
24 hours’ timepoint. 
Wording updated to clarify 
timepoints. 
Section 1.1: Synopsis 
1.3: Schedule of Activities  
Section 4.1: Overall design  
Section 7.1: Discontinuation of 
Study Treatment  
Overall design (Period 1) has been 
updated to include:  
Patients who do not achieve Psoriasis 
Area and Severity Index (PASI) 50 
response by Week 12 will be 
discontinued from the study treatment 
with ustekinumab (either DMB-3115 or 
Stelara). 
To implement Food and Drug 
Administration (FDA) 
recommendation “Only patients 
who achieve at least PASI 50 at 
Week 12 be eligible for continued 
treatment”. 
Section 1.1: Synopsis 
1.3: Schedule of Activities  
Checking (✓) mark for Non-responder 
evaluation Week 12 Visit 8.  
Added in line with new 
discontinuation criteria PASI 50 
at Week 12. 
Section 1.1: Synopsis  
Section 4.1: Overall Design 
In Period 2, the text has been added 
regarding the re-stratification of the 
patients based on the body weight at 
Week 28 (≤100 kg or >100 kg). 
 
The following text has also been added 
to Period 2:  
The doses at re-randomization 
To clarify process in line with 
Interactive Response Technology 
(IRT) system specifications. 
 

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Protocol DMB-3115-2 - Protocol Amendment 01 
 
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Section # and Name 
Description of Change 
Brief Rationale 
(Week 28) for both DMB-3115 and 
Stelara would be re-assigned based on 
the body weight at Week 28 (≤100 kg or 
>100 kg). Patients receiving DMB-3115 
will continue to receive DMB-3115 up 
to Week 40 but they will also follow the 
re-randomization procedure in order to 
maintain blinding. 
Section 1.1: Synopsis 
Number of Investigators and Study Sites 
updated from 90 to 124. 
The change was made to be in 
alignment with an actual plan. 
Section 1.3: Schedule of 
Activities 
Appendix 3: Clinical Laboratory 
Tests 
Laboratory blood tests row was revised 
to include the erythrocytes 
sedimentation rate (ESR), which will be 
done locally with the kits provided by 
the central laboratory. 
Correction of original protocol 
wording due to error. 
Glucose updated to Glucose (fasting 
status not mandatory). 
In alignment with the Schedule of 
Activities and Informed Consent. 
‘Direct bilirubin’ has been included in 
the Chemistry panel. 
Added as per the inclusion 
criteria 10 and as per central 
laboratory set-up. 
Section 5.2: Exclusion Criteria 
Notes added for Exclusion criteria #5 
and #6. 
To clarify the wash-out period for 
the treatments that falls under 
Exclusion criteria #4, #5, and #6. 
Exclusion criteria number 19 has been 
revised to exclude active malignancy 
patients. 
To clarify that current malignancy 
is also to be excluded. 
Exclusion criteria number 24 has been 
clarified for patients with evidence of 
latent infection (at baseline positive TB 
test but negative chest X-ray). 
To implement FDA 
recommendation “Screening all 
subjects for TB at baseline. 
Subjects with a positive TB test 
should be evaluated for presence 
of active TB. Subjects with a 
baseline positive TB test but 
negative chest X-ray may be 
enrolled into the trial following 
initiation of appropriate treatment 
for latent tuberculosis.” 
Section 6.1.2: Drug Delivery 
Device Component 
 
Section 8.3.7: Medical Device 
Deficiencies  
The following text has been added:  
The regulatory considerations regarding 
the device component are governed by 
applicable directives and regulations 
and/or country legislation. The pre-filled 
syringe (PFS) does not fall under the 
current definition of a medical device in 
the European Union (EU). 
To clarify that PFS is not a 
medical device in the EU. As per 
medical devices and in vitro 
diagnostic medical devices 
Regulations (EU) 2017/745 and 
(EU) 2017/746. 
Section 6.3: Measures to 
Minimize Bias: Randomization 
and Blinding 
Assignment of 6-digit number as Subject 
Number or Subject ID at screening visit, 
has been added to delete ‘randomization 
number’ assigned on screening visits. 
Updated in line with other study 
documents. 
 

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Section # and Name 
Description of Change 
Brief Rationale 
Following text has been updated: 
Patients who achieve at least PASI 50 
response by Week 12 and PASI 75 
response at Week 28 will continue on 
the study. 
Updated the text to be consistent 
with the new added criteria of 
‘discontinuation criteria PASI 50 
at Week 12’ 
Section 6.5: Concomitant 
Therapy 
The concomitant therapy has been 
updated to include following points: 
 
This includes topical products such as 
moisturizing creams, emollients, and 
dressings as part of wound care with an 
exception of salicylic acid, lactic acid, 
urea, alpha-hydroxy or fruit acids. 
Text added to clarify that topical 
products as part of wound care 
are allowed during the study, 
following questions from the 
ethics committees/regulatory 
authorities. 
Text has been added to include the 
COVID-19 vaccines. 
Text added to clarify on the use 
of the COVID-19 vaccines.  
Section 7.1: Discontinuation of 
Study Treatment 
Discontinuation criteria has been 
updated to include ‘any female patient 
who becomes pregnant while 
participating in the study’. 
Added in alignment with 
Appendix 6. 
Section 7.1: Discontinuation of 
Study Treatment 
 
Section 8.2.5: Tuberculosis 
Evaluation 
Discontinuation criteria has been 
updated to include, ‘the patient 
diagnosed with active TB during study 
participation’. 
Added clarification following 
FDA recommendation. 
Section 7.1: Discontinuation of 
Study Treatment  
Section 2.3 Benefit/Risk 
Assessment Table 2 
Word ‘treatment’ has been added at the 
end of the sentence (Study treatment) in 
criteria 9i in the list of ‘Patients who will 
be removed from the study treatment by 
the Investigator’. 
Text updated to clarify that the 
patient will be discontinued from 
the study treatment only and will 
not be discontinued from the 
study. 
Section 7.1: Discontinuation of 
Study Treatment 
List of ‘Patients who can be removed 
from the study treatment by the 
Investigator’, has been updated to 
include, ‘the patient diagnosed with 
latent TB during the study participation’.  
Text updated in line with 
Section 8.2.5. 
Section 8.2.1: Physical 
Examinations 
Assessment of ‘dermatology’ has been 
included in complete physical 
examination. 
Added as per the eCRF set-up. 
Section 8.3.6: Adverse Events of 
Special Interest 
Modification to the hepatic injury:  
An elevation of AST and/or 
ALT≥3-fold upper limit of normal 
(ULN) combined with an elevation of 
total bilirubin ≥2-fold ULN measured in 
the same blood draw sample 
Following hepatic injury criteria has 
been added: 
An elevation of AST and/or 
ALT ≥3 fold ULN combined with an 
To maintain the consistency 
between the Section 8.3.6 and 
Appendix 3. 
 

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Section # and Name 
Description of Change 
Brief Rationale 
elevation of international normalized 
ratio (INR) >1.5, if INR measured, 
Section 8.3.7: Medical Device 
Deficiencies 
Updated the form name ‘Medical Device 
Deficiency Report form’. 
The Medical Device Deficiency 
Report Form is not the form 
included in the CRF, so the name 
was revised. 
Section 8.3.7.3: Prompt 
Reporting of Medical Device 
Deficiencies to Sponsor 
The timeline was updated for the prompt 
reporting of Medical Device 
Deficiencies.  
 
3rd point has been added to apply the 
timeline specified in original 1st point to 
the device malfunction/deficiency 
associated with an SAE. 
 
4th point regarding the timelines of the 
other cases of medical device 
malfunction/deficiency has been added. 
To correct reporting timelines for 
device malfunction/deficiencies. 
Section 8.3.8:  Serious Adverse 
Device Effect Reporting 
The 1st point has been revised as follows: 
Any device malfunction/deficiency 
associated with an SAE should be 
reported to Sponsor or designee within 
24 hours after the Investigator 
determines that the event meets the 
protocol definition of a device 
deficiency. (In addition, eCRF must be 
completed within 24 hours of the 
Investigator being aware of the SAE). 
To add the timeline for the 
completion of the eCRF.  
Section 10: References 
Details of the references for Stelara EU 
Summary Product Characteristics and 
the product IB’s were updated in the 
reference list. 
Updated the reference list with 
latest available updated. 
Appendix 3 
Footnote ‘a’ to the Table 10 has been 
revised to include the following to 
Severe liver hepatic criteria: 
All events of (1) AST and/or ALT 
3 × ULN combined with total 
bilirubin 2 × ULN or (2) AST and/or 
ALT 3 × ULN combined with 
international normalized 
ratio (INR) >1.5, if INR measured and 
(3) Marked peak aminotransferase 
(ALT, and/or AST) elevations ≥10-fold 
ULN, which may indicate severe hepatic 
injury (possible Hy’s Law), must be 
reported as an SAE.  
To maintain consistency with 
Section 8.3.6. 
Throughout the document  
Minor editorial changes (e.g., deletion of 
duplicate sentence in Section 8.0). 
Minor changes. 
 
 
 

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TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ................................3 
TABLE OF TABLES .............................................................................................................10 
TABLE OF FIGURES ...........................................................................................................11 
1.0 
PROTOCOL SUMMARY ........................................................................................12 
1.1 
Synopsis ...........................................................................................................12 
1.2 
Schema ............................................................................................................19 
1.3 
Schedule of Activities .....................................................................................20 
2.0 
INTRODUCTION......................................................................................................23 
2.1 
Study Rationale ..............................................................................................23 
2.2 
Background ....................................................................................................23 
2.3 
Benefit/Risk Assessment ................................................................................25 
3.0 
OBJECTIVES AND ENDPOINTS ..........................................................................29 
4.0 
STUDY DESIGN ........................................................................................................31 
4.1 
Overall Design ................................................................................................31 
4.2 
Scientific Rationale for Study Design ...........................................................32 
4.3 
Justification for Dose .....................................................................................32 
4.4 
End of Study Definition .................................................................................33 
5.0 
STUDY POPULATION ............................................................................................34 
5.1 
Inclusion Criteria ...........................................................................................34 
5.2 
Exclusion Criteria ..........................................................................................35 
5.3 
Lifestyle Considerations ................................................................................37 
5.4 
Screen Failures ...............................................................................................37 
6.0 
STUDY TREATMENT .............................................................................................39 
6.1 
Study Treatments Administered ..................................................................39 
6.1.1 
Investigational Product ......................................................................39 
6.1.2 
Drug Delivery Device Component ....................................................40 
6.2 
Preparation/Handling/Storage/Accountability ...........................................40 
6.3 
Measures to Minimize Bias: Randomization and Blinding........................41 
6.4 
Study Treatment Compliance .......................................................................42 
6.5 
Concomitant Therapy ....................................................................................43 
6.6 
Dose Modification ..........................................................................................43 
6.7 
Treatment after the End of the Study ..........................................................44 
 

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7.0 
DISCONTINUATION OF STUDY TREATMENT AND PATIENT 
WITHDRAWAL ........................................................................................................45 
7.1 
Discontinuation of Study Treatment ............................................................45 
7.2 
Patient Withdrawal from the Study .............................................................46 
7.3 
Lost to Follow-up ...........................................................................................47 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ....................................................48 
8.1 
Efficacy Assessments .....................................................................................49 
8.1.1 
Psoriasis Area and Severity Index .....................................................49 
8.1.2 
Physician Global Assessment ............................................................49 
8.1.3 
Dermatology Life Quality Index .......................................................49 
8.2 
Safety Assessments .........................................................................................49 
8.2.1 
Physical Examinations .......................................................................49 
8.2.2 
Vital Signs .........................................................................................50 
8.2.3 
Electrocardiograms ............................................................................50 
8.2.4 
Chest X-ray ........................................................................................50 
8.2.5 
Tuberculosis Evaluation ....................................................................51 
8.2.6 
Clinical Safety Laboratory Assessments ...........................................51 
8.3 
Adverse Events ...............................................................................................52 
8.3.1 
Time Period and Frequency for Collecting Adverse Event 
and Serious Adverse Event Information ............................................52 
8.3.2 
Method of Detecting Adverse Events and Serious Adverse 
Events ................................................................................................53 
8.3.3 
Follow-up of Adverse Events and Serious Adverse Events ..............53 
8.3.4 
Regulatory Reporting Requirements for Serious Adverse 
Events ................................................................................................53 
8.3.5 
Pregnancy ..........................................................................................53 
8.3.6 
Adverse Events of Special Interest ....................................................54 
8.3.7 
Medical Device Deficiencies .............................................................55 
8.3.8 
Serious Adverse Device Effect Reporting .........................................57 
8.4 
Treatment of Overdose ..................................................................................57 
8.5 
Pharmacokinetics ...........................................................................................58 
8.6 
Immunogenicity..............................................................................................58 
8.7 
Genetics ...........................................................................................................59 
8.8 
Biomarkers .....................................................................................................59 
8.9 
Medical Resource Utilization and Health Economics.................................59 
9.0 
STATISTICAL CONSIDERATIONS .....................................................................60 
9.1 
Statistical Hypotheses ....................................................................................60 
9.2 
Sample Size Determination ...........................................................................60 
9.3 
Populations for Analyses ...............................................................................62 
9.4 
Statistical Analyses.........................................................................................62 
9.4.1 
Efficacy Analyses ..............................................................................63 
9.4.2 
Safety Analyses .................................................................................64 
9.4.3 
Other Analyses ..................................................................................67 
9.4.4 
Missing Data ......................................................................................67 
 

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9.5 
Interim Analyses ............................................................................................67 
9.6 
Monitoring Committee ..................................................................................67 
10.0 
REFERENCES ...........................................................................................................69 
11.0 
APPENDICES ............................................................................................................71 
Appendix 1 
Abbreviations ...................................................................................71 
Appendix 2 
Regulatory, Ethical, and Study Oversight Considerations ..........74 
Regulatory and Ethical Considerations ............................................................74 
Financial Disclosure .........................................................................................74 
Insurance ..........................................................................................................75 
Data Protection.................................................................................................75 
Administrative Structure ..................................................................................76 
Medical Monitor ..............................................................................................76 
Dissemination of Clinical Study Data ..............................................................77 
Data Quality Assurance ...................................................................................77 
Source Documents ...........................................................................................77 
Study Closure and Study Site Closure .............................................................78 
Publication Policy ............................................................................................78 
Appendix 3 
Clinical Laboratory Tests ...............................................................80 
Appendix 4 
Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .....................................82 
Appendix 5 
Excluded Medications/Therapy .....................................................86 
Appendix 6 
Contraceptive Guidance and Collection of Pregnancy 
Information .....................................................................................................87 
Appendix 7 
Country-specific Requirements ......................................................91 
Appendix 8 
Signature of Investigator ................................................................92 
 
 

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TABLE OF TABLES 
Table A 
Document History ..............................................................................................3 
Table B 
Description of Changes in Amendment .............................................................3 
Table 1 
Schedule of Activities ......................................................................................20 
Table 2 
Summary of the Risk Assessment and Mitigation Strategies in the 
Context of COVID-19......................................................................................26 
Table 3 
Study Objectives and Endpoints ......................................................................29 
Table 4 
Study Treatment Details ..................................................................................39 
Table 5 
Percent Change in PASI in the PHOENIX 1 and PHOENIX 2 Pivotal 
Studies ..............................................................................................................60 
Table 6 
Sample Size scenarios based on parameters suggested by the US FDA 
and the EMA ....................................................................................................61 
Table 7 
Analysis Sets ....................................................................................................62 
Table 8 
Efficacy Analyses ............................................................................................63 
Table 9 
Study Administrative Structure ........................................................................76 
Table 10 
Protocol-required Safety Laboratory Assessments ..........................................80 
 

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TABLE OF FIGURES 
Figure 1 
Treatment design schematic .............................................................................19 
 
 

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• 
Percentage of patients with a Physician's Global 
Assessment (PGA) score of Cleared or Minimal at 
Weeks 4, 8, 12, 16, 28, 40, and 52. 
• 
Change from baseline in Dermatology Life Quality 
Index (DLQI) at Weeks 4, 8, 12, 16, 28, 40, and 52. 
Safety Endpoint: 
• 
Incidence of AEs, SAEs, including incidence of 
injection site reactions, changes in vital signs, 
laboratory abnormalities. 
Immunogenicity Endpoint:  
• 
Incidence of anti-drug antibodies (ADA) (binding 
and/or neutralizing). 
Pharmacokinetic Endpoint: 
• 
Drug concentrations at Weeks 0 (Pre dose and 
24 hours post dose [±12 hours]), 1, 2, 4, 8, 12, 16, 
28, 40, and 52. 
• 
Pharmacokinetic parameters after the first dose 
(maximum observed serum concentration [Cmax], 
time 
from 
dosing 
to 
maximum 
measured 
concentration 
[tmax], 
area 
under 
the 
concentration-time curve from Week 0 to Week 4 
[AUCw0-w4] 
and 
other 
PK 
parameter, 
as 
appropriate). 
Abbreviations: AE = adverse event; EMA = European Medicines Agency; EU = European Union; 
PK = pharmacokinetic; SAE = Serious Adverse Event; US FDA = United States Food and Drug Administration. 
Overall Design: 
This is a randomized, double-blind, multicentric, parallel group, and active controlled study comparing 
efficacy, safety and immunogenicity of SC administration of DMB-3115 and EU sourced Stelara in patients 
with moderate to severe chronic plaque psoriasis. 
After a screening period of up to 4 weeks, the eligible patients will be randomly assigned in a 1:1 ratio to 
receive treatment with either DMB-3115 or Stelara. Randomization will be stratified according to patient’s 
body weight at baseline (≤100 kg or >100 kg), geographic region (EU, US or Rest of the World [ROW]) 
and the number of previous systemic therapies for psoriasis (<3 or ≥3). 
The study will have 2 periods. 
Period 1: 
In the Period 1 (from Week 0 to Week 28), patients will receive the assigned treatment (either DMB-3115 
or Stelara) at Weeks 0, 4, and 16. 
Patients who do not achieve at least Psoriasis Area and Severity Index (PASI) 50 response by Week 12 will 
be discontinued from further treatment with ustekinumab (either DMB-3115 or Stelara). 
Period 2: 
In the Period 2 (from Week 28 to Week 52), patients randomized to receive DMB-3115 at the beginning of 
the study will continue to receive the same treatment up to Week 40 while patients randomized to receive 
Stelara at the beginning of the study will be re-randomized and re-stratified based on the body weight at 
Week 28 (≤100 kg or >100 kg) at Week 28 in a 1:1 ratio to either continue on Stelara or will be transitioned 
to receive DMB-3115 every 12 weeks up to Week 40 (i.e., 2 doses of investigational product [IP] after re-
randomization). The doses at re-randomization (Week 28) for both DMB-3115 and Stelara would be 
re-assigned based on the body weight at Week 28 (≤100 kg or >100 kg). Patients receiving DMB-3115 will 
 

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continue to receive DMB-3115 up to Week 40 but they will also follow the re-randomization procedure in 
order to maintain blinding. Blinding will be maintained throughout the study. 
Only those patients who achieve at least PASI 75 response at Week 28 will be eligible for inclusion into 
the Period 2 of the study (Transition period: from Week 28 to Week 52). 
 
Patients who do not achieve at least PASI 50 response by Week 12 or PASI 75 response by Week 28 will 
be discontinued from further treatment with ustekinumab. These patients will remain in the study and be 
followed up to Week 52 for safety monitoring, including immunogenicity. For safety monitoring and 
immunogenicity in non-responders the following should be completed at follow-up visits: physical 
examination, vital signs, hematology and biochemistry laboratory tests, urine analysis, tuberculosis 
evaluation, anti-drug antibodies (ADA) blood sampling, electrocardiogram, pregnancy testing, and adverse 
events (AEs). All patients who discontinue treatment including non-responders as per Section 7.1 will 
remain in the study and be followed up to Week 52 for safety monitoring, including immunogenicity.  
Any patients who are prematurely withdrawn from the study at any time post IP administration at Visit 2, 
will be required to have an early termination (ET) visit. Early termination visit will be performed within 
12 weeks from the last IP administration. If ET visit occurs before 12 weeks, a phone call for safety 
follow-up will be performed at 12 weeks from the last IP administration.  
Efficacy, safety, and immunogenicity assessments will be done periodically.  
Blood samples for PK and ADA assessments will be collected prior to IP administration (in case a dose is 
scheduled for the same visit).  
Safety will be evaluated through an assessment of AEs, vital signs, electrocardiograms, and 
immunogenicity, along with clinical laboratory testing.  
The patients will visit the clinical site for screening and then at baseline (Week 0/Day 1), Week 0/Day 2, 
Week 1, Week 2, Week 4, and then every 4 weeks up to Week 16. Thereafter, the patients will visit the 
clinical site every 12 weeks up to Week 52. The last visit at Week 52 will be End of Study (EOS) visit. 
There are total 12 scheduled visits planned, including the screening and EOS visit. 
An Interim Analysis will be performed when all active patients complete the Week 28 assessment visit. 
The efficacy endpoints up to Week 28 and all available safety, ADA and PK data will be analyzed and an 
interim clinical study report will be generated for submission to the regulatory agencies. 
Number of Investigators and Study Sites: 
Approximately 124 Investigators and sites are expected to participate in this study. 
Number of Patients: 
Assuming a dropout rate of 20% in Period 1, 15% in Period 2, and considering the 1:1 re-randomization 
rate for Stelara arm in Period 2 and to meet the minimum requirement of safety analysis by European 
Medicines Agency (EMA) (N=100), 590 patients (a minimum of 400 completed patients) will be necessary 
in total.  
Thus, 590 patients (295 patients per treatment group at baseline) will be enrolled. 
Treatment Groups and Duration: 
Two treatment groups (DMB-3115, and Stelara) in Period 1 and 3 treatment groups (DMB-3115, Stelara, 
and Stelara switched to DMB-3115) for Period 2. 
Patients who weigh ≤100 kg will receive an initial dose of 45 mg ustekinumab administered subcutaneously 
(either DMB-3115 or Stelara as assigned), followed by another 45 mg dose 4 weeks later, and then every 
12 weeks thereafter (up to 40 weeks after randomization). Patients who weigh >100 kg will receive 90 mg 
doses as per same schedule. 
The doses at re-randomization (Week 28) would be assigned on the body weight at that time. 
The total duration of patient participation in the study will be up to 56 weeks.  
 

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Statistical methods: 
All data listings, summaries, and analyses will be performed under the guidance and approval of the 
Sponsor. 
Descriptive statistics will be used for all variables, as appropriate. Continuous variables will be summarized 
by the number of observations, mean, standard deviation (SD), median, minimum, and maximum. 
Categorical variables will be summarized by frequency counts and percentages for each category. Unless 
otherwise stated, percentages will be calculated out of the total population for each treatment group. 
Primary Efficacy Analysis (for European Medicines Agency [EMA]) 
• 
Percent change in PASI at Week 8 will be analyzed with a 95% confidence interval (CI) for the 
difference in means using estimates from an Analysis of Covariance (ANCOVA) model adjusted for 
baseline PASI score and the stratification factors (patient’s body weight at baseline [≤100 kg, or 
>100 kg], geographic region [EU, US or ROW] and the number of previous systemic therapies for 
psoriasis [<3 or ≥3]). 
• 
Equivalence between the 2 treatment groups will be declared if the 95% CI of the mean difference is 
entirely contained within the pre-specified equivalence margin of (-15%, 15%).  
• 
Analysis will be performed in the Intent-to-Treat (ITT) and Per Protocol Set (PPS). The PPS is the 
primary efficacy analysis population. 
• 
Missing values for primary efficacy variable in the ITT set will be imputed by multiple imputation 
(MI) method. 
Primary Efficacy Analysis (for United States Food and Drug Administration [US FDA]) 
• 
Percent change in PASI at Week 12 will be analyzed with a 90% CI for the difference in means using 
estimates from an ANCOVA model adjusted for baseline PASI score and the stratification factors 
(patient’s body weight at baseline [≤100 kg, or >100 kg], geographic region [EU, US, or ROW] and 
the number of previous systemic therapies for psoriasis [<3 or ≥3]). 
• 
Equivalence between the 2 treatment groups will be declared if the 90% CI of the mean difference is 
entirely contained within the pre-specified equivalence margin of (-10%, 10%).  
• 
Analysis will be performed in the ITT and PPS. The ITT is the primary efficacy analysis population. 
• 
Missing values for primary efficacy variable in ITT set will be imputed by MI method.  
Sensitivity Analysis 
Percent change in PASI will be analyzed for each PPS and ITT set (EMA and US FDA) using a mixed 
linear model with treatment group, baseline body weight (≤100 kg, or >100 kg), geographic region (EU, 
US or ROW), the number of previous systemic therapies for psoriasis (<3 or ≥3), visit, and the 
treatment-by-visit interaction as fixed effects and baseline PASI score as a covariate. The treatment mean 
difference at Week 8 (for EMA) and Week 12 (for US FDA), along with CI are calculated. The 
variance-covariance matrix of unstructured form is used to model the correlation within each patient. 
Secondary Efficacy Analysis 
Endpoints based on proportions will be analyzed using a logistic regression test with the baseline value, 
baseline body weight (≤100 kg, or >100 kg), geographic region (EU, US or ROW), and the number of 
previous systemic therapies for psoriasis (<3 or ≥3) as covariates. Percentage change from baseline will be 
analyzed using ANCOVA with baseline PASI score, body weight (≤100 kg, or >100 kg), geographic region 
(EU, US or ROW), and the number of previous systemic therapies for psoriasis (<3 or ≥3) as covariates. 
Change from baseline in Dermatology Life Quality Index (DLQI) will be analyzed using ANCOVA with 
baseline DLQI score, body weight (≤100 kg, or >100 kg), geographic region (EU, US or ROW), and the 
number of previous systemic therapies for psoriasis (<3 or ≥3) as covariates. All the secondary efficacy 
endpoints are summarized by the 90% CI (for US FDA) and 95% CI (for EMA). 
 

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Protocol DMB-3115-2 - Protocol Amendment 01 
 
16 
Supportive Analysis to Secondary Endpoint for Period 2 
Percentage change in PASI score from baseline to Weeks 40 and 52 will be analyzed using ANCOVA with 
Welch’s test with baseline PASI score, body weight (≤100 kg, or >100 kg), geographic region (EU, US, or 
ROW), and the number of previous systemic therapies for psoriasis (<3 or ≥3) as covariates. 
Safety Analysis 
The number and proportion of patients experiencing AEs and Serious Adverse Events will be tabulated and 
compared by treatment group. Adverse events will be coded according to the Medical Dictionary for 
Regulatory Activities (MedDRA).  
Vital signs and clinical laboratory parameters being monitored for safety will be summarized by treatment 
and scheduled time point using descriptive statistics of number of observations, mean, SD, minimum, 
median, and maximum. Data listings of clinically significant abnormalities/outliers will be presented.  
Immunogenicity Analyses  
The incidence of ADAs and neutralizing antibodies will be summarized by treatment group and visit and 
listed.  
Pharmacokinetic Analysis 
Pharmacokinetic data will be summarized descriptively. Pharmacokinetic parameters after the first dose 
(e.g., Cmax, tmax, area under the concentration-time curve from Week 0 to Week 4 [AUCw0-w4] and other PK 
parameters, as appropriate) will be determined using an appropriate analysis methodology. 
Additional details about the statistical methods including, but not limited, analysis sets, missing data 
strategies, etc. will be provided in the body of the protocol and the Statistical Analysis Plan (SAP) which 
will be prepared as a separate document prior to database lock. 
Statistical Hypotheses 
Statistical hypotheses and testing utilized will be defined in the SAP, including the null and alternative 
hypotheses. Primary and secondary endpoint analyses will be included in the SAP. 
Sample Size Determination 
The sample size required for the primary endpoint has been calculated based on the following assumptions; 
two-sided alpha of 0.05 (for EMA) or 0.10 (for US FDA), power of 90%, the difference between Stelara 
and DMB-3115 is 0, and the SD is 0.3. One to one (1:1) randomization rate of Period 1 is assumed. 
Equivalence margins of 15% and 10% were recommended by the EMA and US FDA, respectively. The SD 
assumption was derived from the observed SD of the mean improvement in PASI score in studies 
PHOENIX 1 and PHOENIX 2. Sample size was calculated using the Two one-sided t-tests (TOST) 
procedure as implemented in the R package power TOST. The overall sample size will be based on the 
larger sample size calculated through EMA and US FDA’s recommendation. 
 

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Protocol DMB-3115-2 - Protocol Amendment 01 
 
17 
Sample Size scenarios based on parameters suggested by the US FDA and the EMA 
 
US FDA 
EMA 
Test Significance Level, α (two-sided) 
0.1 
0.05 
Lower Equivalence Limit for µ₀-µ₁, Δ(L) 
-0.1 
-0.15 
Upper Equivalence Limit for µ₀-µ₁, Δ(U) 
0.1 
0.15 
Expected Difference, µ₀-µ₁ 
0 
0 
Common Standard Deviation, σ 
0.3 
0.3 
Power (%) 
90 
90 
Evaluable Sample Size per Group, n 
196 
105 
Total 
392 
210 
Total with Dropout 20% in Period 1 for Primary Efficacy Analysis 
490 
264 
Abbreviations: EMA = European Medicines Agency; n = evaluable sample size per group; US FDA = United 
States Food and Drug Administration. 
As shown in above table, for primary efficacy analysis, the US FDA sample size of 490 patients in total 
(245 patients per treatment group at baseline) is selected to achieve 392 evaluable patients to have a 90% CI 
for the difference in primary endpoint fall entirely within the 10% equivalence margin with more than 
90% power.  
On the other hand, for safety analysis, a minimum of 400 completed patients (at least 100 patients per 
treatment group for long-term data) will be necessary to meet the minimum requirement by EMA 
considering 1:1 re-randomization for Stelara arm. To achieve 400 completed patients, 590 patients 
(295 patients per treatment group at baseline) need to be enrolled assuming both dropout rate of 20% in 
Period 1 and 15% in Period 2. 
The total number of patients needed for the safety analysis is larger than that needed for the primary efficacy 
analysis. Thus, 590 patients (295 patients per treatment group) in total need to be enrolled (randomized). 
Populations for Analyses 
For the purpose of analysis, the analysis sets are defined.  
• 
Intent-to-Treat set: All patients who have been randomized.  
• 
Per protocol set (for EMA): Patients who complete the study up to Week 8 and have no major protocol 
deviations. All decisions to exclude the patients from the per protocol population dataset will be made 
prior to the unblinding of the study.  
• 
Per protocol set (for US FDA): Patients who complete the study up to Week 12 and have no major 
protocol deviations. All decisions to exclude patients from the per protocol population dataset will be 
made prior to the unblinding of the study.  
• 
Safety set: Patients who randomize and receive at least 1 dose of the IP. The safety analysis will be 
conducted according to the treatment that a patient actually receives. 
• 
PK analysis set: Patients who receive at least 1 dose of IP, have at least one measured concentration at 
a scheduled post dose PK time point, and have no major protocol deviations/events that may 
significantly affect the PK assessment.  
 
Data Monitoring Committee:  
An independent Data Safety Monitoring Board (DSMB) will be constituted by the study Sponsor to oversee 
the safety aspects of this study. The DSMB will include physicians with relevant clinical expertise, none of 
 

CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
18 
whom is affiliated with the Sponsor. The DSMB will operate as per a written charter. The DSMB would 
periodically examine the safety data emerging from the study and provide its recommendations to the 
Sponsor. Based on its review, the DSMB may advise for the study to be continued as is, or for the protocol 
to be modified, or for the study to be terminated. 
 

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Protocol DMB-3115-2 - Protocol Amendment 01 
 
19 
1.2 
Schema 
Figure 1 
Treatment design schematic 
 
 
Abbreviation: EMA = European Medicines Agency; US FDA = United States Food and Drug Administration; 
w = weeks. 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Protocol DMB-3115-2 - Protocol Amendment 01 
21 
Abbreviations: ADA = Anti-Drug Antibody; DLQI = Dermatology Life Quality Index; ECG = Electrocardiogram; EOS = End of Study; ESR = Erythrocyte 
sedimentation rate; ET = Early Termination; HBcAb = Hepatitis B core antibody; HBsAg = Hepatitis B surface antigen; HCVAb = Hepatitis C virus antibody; 
HIV = human immunodeficiency virus; IP = Investigational Product; PASI = Psoriasis Area and Severity Index; PGA = Physician’s Global Assessment; PK = 
Pharmacokinetics; SAE = Serious Adverse Event; Wk = Week. 
a. Complete physical examination, including height and weight, will be performed at screening visit, Weeks 0, 28, and ET/EOS (height: at screening only); at other
visits only brief physical examination will be performed (see Section 8.2.1).
b. Chest X-ray (posterior-anterior and lateral view) is required unless available within 12 weeks prior to the first administration of IP (see Section 8.2.4 and
Section 5.4).
c. Vital signs include pulse rate, blood pressure and oral/axillary body temperature (see Section 8.2.2).
d. Tuberculosis evaluation and QuantiFERON Gold test will be performed as detailed in Section 8.2.5.
(Central lab; ESR locally 
with Central Lab Kits) 
Urinalysisf 
✓
✓
✓
✓
✓
✓
✓
✓
Pregnancy Testg 
✓
✓
✓
✓
✓
✓
✓
12-lead ECGh
✓
✓
✓
PK blood Samplingi 
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
ADA blood 
Samplingj 
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Randomizationk 
✓
✓
IP administrationk, l, 
m,n
✓
✓
✓
✓
✓
Injection site reaction 
examination 
✓
✓
✓
✓
✓
✓
✓
✓
✓
PASIo 
✓
✓
✓
✓
✓
✓
✓
✓
✓
PGAo 
✓
✓
✓
✓
✓
✓
✓
✓
✓
DLQIo 
✓
✓
✓
✓
✓
✓
✓
✓
Concomitant and 
previous 
medicationsp 
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
Adverse eventsq 
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
 
 

CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
22 
e. Laboratory blood tests: Hematology = hemoglobin, hemoglobin A1c, hematocrit, platelet count, Red Blood Cell (RBC) Count, white blood cell count (total and
differential), Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), and erythrocytes sedimentation rate (ESR). ESR test will be done locally
with kits provided by central laboratory.
Biochemistry = sodium, potassium, creatinine, glucose (fasting status not mandatory), calcium, phosphorus, total bilirubin, direct bilirubin, albumin, alanine
aminotransferase, aspartate aminotransferase, alkaline phosphatase, blood urea nitrogen, total protein, and C-reactive protein.  
Other = Follicle stimulating hormone (as needed in women of non‑childbearing potential only at screening visit), prothrombin time, activated partial 
thromboplastin time, and international normalized ratio (see Section 8.2.6 and Appendix 3). 
f. Urinalysis: Color, Clarity/Appearance, protein, blood, leucocytes, nitrite, glucose, ketone, pH, specific gravity, bilirubin, urobilinogen, microscopic examination
(if blood or protein is abnormal).
g. Serum pregnancy test must be performed at screening visit for all females of childbearing potential only. Thereafter, from randomization onwards, a urine
pregnancy test will be performed at Weeks 0, 4, 16, 28, 40, and 52 and should be negative before each IP administration. Pregnancy testing will be performed
whenever a menstrual cycle is missed or when pregnancy is otherwise suspected (see Appendix 6).
h. 12-lead ECG will be performed as detailed in Section 8.2.3.
i. Blood samples for PK analysis will be collected at Weeks 0 (Pre dose and 24 hours post dose [±12 hours]), 1, 2, 4, 8, 12, 16, 28, 40, and 52. At visits when IP is
to be administered, the PK sample will be collected prior to IP administration.
j. Blood samples for ADA analysis will be collected at Weeks 0 (Pre dose and 24 hours post dose [±12 hours]), 2, 4, 8, 12, 16, 28, 40, and 52. At visits when IP is
to be administered, the ADA sample will be collected prior to IP administration.
k. At Week 28, patients who achieved a PASI 75 response will enter the study transition period. Patients receiving Stelara will be re-randomized in a 1:1 ratio to
either continue to receive Stelara or be transitioned to DMB-3115. Patients receiving DMB-3115 will continue to receive DMB-3115 up to Week 40 but they
will also follow the re-randomization procedure in order to maintain blinding.
l. Patients who do not achieve at least PASI 50 response by Week 12 will be discontinued from further treatment with ustekinumab. These patients will remain in
the study and will be followed up to Week 52 for safety monitoring, including immunogenicity.
m. Patients who do not achieve at least PASI 75 response by Week 28 will be discontinued from further treatment with ustekinumab (either DMB-3115 or Stelara).
These patients will remain in the study and will be followed up to Week 52 for safety monitoring, including immunogenicity.
n. Appropriate medical personnel must be in attendance at the time of the injection and for at least 30 minutes after the SC injection.
o. The PASI, PGA, and DLQI assessments shall be completed using the electronic devices provide by the site.
p. Previous and concomitant medication at screening and concomitant medication only at visits from randomization onwards (see Section 6.5).
q. Safety data reporting period begins from the time of signing the informed consent (even if this is prior to randomization visit) until Week 52 (±7 days). Note:
Related SAEs should be collected irrespective of the time elapsed since the last dose of IP. For detailed instructions on safety reporting (see Appendix 4).
r. Patients who are prematurely withdrawn from the study at any time post Visit 2, will be required to have an ET visit. The ET visit will be performed within
12 weeks from the last IP administration. If ET visit occurs before 12 weeks, a phone call for safety follow-up will be performed at 12 weeks from the last IP
administration.