Conditions: Moderate to Severe Chronic Plaque Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 598
Healthy volunteers: no

Brief summary:
This study is designed to evaluate efficacy, safety, pharmacokinetics (PK) and immunogenicity of subcutaneously administered DMB-3115 in comparison with Stelara for treatment of moderate to severe chronic plaque psoriasis.

Detailed description:

Arms:
arm 1: Patients randomized to receive DMB-3115 at the beginning of the study will continue to receive the same treatment arm 2: Patients randomized to receive Stelara at the beginning of the study will be re-randomized at Week 28 in a 1:1 ratio to either continue on Stelara or will be transitioned to receive DMB-3115

Interventions: intervention 1: DMB-3115 intervention 2: Stelara
Intervention descriptions: intervention 1: 45mg or 90mg dose subcutaneous administration intervention 2: 45mg or 90mg dose subcutaneous administration

Protocol document:
Prot_000.pdf: 
CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
1 
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) 
 
 
 




CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
3 
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. 
 


CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
4 
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. 
 


CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
5 
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. 
 


CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
6 
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. 
 
 
 


CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
7 
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 
 


CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
8 
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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Protocol DMB-3115-2 - Protocol Amendment 01 
 
9 
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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Protocol DMB-3115-2 - Protocol Amendment 01 
10 
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 
 


CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
11 
TABLE OF FIGURES 
Figure 1 
Treatment design schematic .............................................................................19 
 
 




CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
13 
• 
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 
 


CONFIDENTIAL 
Protocol DMB-3115-2 - Protocol Amendment 01 
 
14 
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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Protocol DMB-3115-2 - Protocol Amendment 01 
 
15 
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. 
 


CONFIDENTIAL 
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 
✓
✓
✓
✓
✓
✓
✓
✓
✓
✓
 
 


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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.
 
 

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Statistical Analysis Plan 
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 STATISTICAL ANALYSIS PLAN 
 
DMB-3115-2  
 
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. 
 
 
 
AUTHOR:  
 
 
VERSION NUMBER AND DATE: V1.0 21APR2022 
 
 
 




 
 
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Modification History 
Unique Identifier for this 
Version 
Date 
of 
the 
Document 
Version 
Author 
Significant 
Changes 
from  
Previous Authorized Version 
V1.0 
21APR2022 
 
 
 
 
Not Applicable 
 
 


 
 
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TABLE OF CONTENTS 
1. 
INTRODUCTION ................................................................................................................................ 9 
2. 
STUDY OBJECTIVES ........................................................................................................................ 9 
2.1. Primary Objective ............................................................................................................................................................................ 9 
2.2. Secondary Objectives ....................................................................................................................................................................... 9 
2.3. Exploratory Objectives .................................................................................................................................................................... 9 
3. 
STUDY DESIGN .................................................................................................................................. 9 
3.1. General Description ......................................................................................................................................................................... 9 
3.2. Schedule of Events ......................................................................................................................................................................... 11 
3.3. Changes to analysis from Protocol ............................................................................................................................................... 12 
4. 
PLANNED ANALYSIS ..................................................................................................................... 12 
4.1. Interim analysis .............................................................................................................................................................................. 12 
4.2. Final analysis .................................................................................................................................................................................. 12 
5. 
ANALYSIS SETS ............................................................................................................................... 12 
5.1. Screened Set (SCR) ........................................................................................................................................................................ 13 
5.2. Intent-to-Treat Set (ITT) ............................................................................................................................................................... 13 
5.3. Safety Set (SAF) ............................................................................................................................................................................. 13 
5.4. Per Protocol Analysis Set (PPS-EMA) ......................................................................................................................................... 13 
5.5. Per Protocol Analysis Set (PPS-US FDA) .................................................................................................................................... 14 
5.6. Pharmakokinetic Set (PK Set) ...................................................................................................................................................... 14 
6. 
GENERAL CONSIDERATIONS ..................................................................................................... 14 


 
 
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6.1. Reference Start Date and Study Day ............................................................................................................................................ 15 
6.2. Baseline ........................................................................................................................................................................................... 15 
6.3. Retests, Unscheduled Visits and Early Termination Data.......................................................................................................... 15 
6.4. Statistical Tests ............................................................................................................................................................................... 16 
6.5. Common Calculations ................................................................................................................................................................... 16 
6.6. Software Version ............................................................................................................................................................................ 16 
7. 
STATISTICAL CONSIDERATIONS ............................................................................................. 16 
7.1. Adjustments for Covariates and Factors to be Included in Analyses ........................................................................................ 17 
7.2. Missing data .................................................................................................................................................................................... 17 
7.3. Multiple Comparisons/ Multiplicity ............................................................................................................................................. 17 
8. 
DISPOSITION AND WITHDRAWALS ......................................................................................... 17 
8.1. Disposition ...................................................................................................................................................................................... 18 
9. 
DERIVATIONS .................................................................................................................................. 18 
10. 
PROTOCOL DEVIATIONS ............................................................................................................. 19 
11. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ........................................ 19 
12. 
MEDICAL HISTORY AND CONCOMITANT ILLNESS ........................................................... 20 
13. 
MEDICATIONS ................................................................................................................................. 21 
14. 
STUDY MEDICATION EXPOSURE .............................................................................................. 21 
15. 
STUDY MEDICATION COMPLIANCE ........................................................................................ 21 
16. 
ESTIMANDS ...................................................................................................................................... 23 


 
 
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17. 
EFFICACY OUTCOMES ................................................................................................................. 24 
17.1. 
Primary Efficacy ...................................................................................................................................................................... 24 
17.1.1. 
Primary Efficacy Variable(s) ............................................................................................................................................... 24 
17.1.2. 
Missing Data Methods for Primary Efficacy Variable(s) ..................................................................................................... 24 
17.1.3. 
Primary Analysis of Primary Efficacy Variable(s) .............................................................................................................. 24 
17.2. 
Secondary Efficacy .................................................................................................................................................................. 27 
17.2.1 Secondary Efficacy Variables  The secondary efficacy analyses will be performed for the ITT.............................................. 27 
17.2.1.1. 
Percentage of patients with a PASI 50 (a 50% reduction in the PASI score) response at Weeks 4, 8, 12, 16, 28, 40, 
and 52. 
27 
17.2.1.2. 
Percentage of patients with a PASI 75 (a 75% reduction in the PASI score) response at Weeks 4, 8, 12, 16, 28, 40, 
and 52. 
27 
17.2.1.3. 
Percentage of patients with a PASI 90 (a 90% reduction in the PASI score) response at Weeks 4, 8, 12, 16, 28, 40, 
and 52. 
27 
17.2.1.4. 
Percentage of patients with a PASI 100 (a 100% reduction in the PASI score) response at Weeks 4, 8, 12, 16, 28, 40, 
and 52. 
27 
17.2.1.5. 
Percentage change in AUEC for the PASI score from baseline at Weeks 4, 8, 12, 16, 28, 40, and 52. ....................... 27 
17.2.1.6. 
Percent change in the PASI score from baseline at Weeks 4, 8, 12, 16, 28, 40, and 52. .............................................. 27 
17.2.1.7. 
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. ............................................................................................................................................................................ 27 
17.2.1.8. 
Change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 4, 8, 12, 16, 28, 40, and 52. ................. 27 
17.2.2. 
Analysis of Secondary Efficacy Variables ........................................................................................................................... 27 
17.2.2.1. 
Analysis of Secondary Efficacy Endpoint- Psoriasis Area and Severity Index (PASI) Response ............................... 27 
17.2.2.2. 
Analysis of Secondary Efficacy Endpoint- Area under effect curve (AUEC) for Psoriasis Area and Severity Index 
(PASI) score ..................................................................................................................................................................................... 28 
17.2.2.3. 
Analysis of Secondory Efficacy Endpoint -Psoriasis Area and Severity Index (PASI) Score ..................................... 28 
17.2.2.4. 
Analysis of Secondory Efficacy Endpoint- Physicians Global Assessment (PGA) . ................................................... 28 
17.2.2.5. 
Analysis of Secondory Efficacy Endpoint- Dermatology Life Quality Index (DLQI) . .............................................. 29 
17.2.3. 
Sensitivity Analysis of Primary efficacy variables .............................................................................................................. 29 
17.2.4. 
Sensitivity Analysis of Primary Variables for subjects impacted by COVID-19 ................................................................ 29 
17.2.5. 
Supportive Analysis  to Secondary Endpoint For Period2 ................................................................................................... 30 
17.2.6. 
Examination of Subgroups ................................................................................................................................................... 31 
18. 
SAFETY OUTCOMES ...................................................................................................................... 31 
18.1. 
Adverse Events ......................................................................................................................................................................... 31 
18.1.1. 
All TEAEs ............................................................................................................................................................................ 32 
18.1.1.1. 
Intensity ........................................................................................................................................................................ 32 
18.1.1.2. 
Relationship to Study Medication ................................................................................................................................ 32 
18.1.2. 
TEAEs Leading to Discontinuation of Study Medication .................................................................................................... 33 
18.1.3. 
TEAEs Leading to Withdrawal of Patients from Study ....................................................................................................... 33 
18.1.4. 
Serious Adverse Events ....................................................................................................................................................... 33 
18.1.5. 
Adverse Events Leading to Death ........................................................................................................................................ 33 
18.1.6. 
Adverse Events related to COVID-19 .................................................................................................................................. 34 
18.1.7. 
Adverse Events related to Devices deficiency ..................................................................................................................... 34 
18.1.8. 
Adverse Events Of Special Interest ...................................................................................................................................... 34 


 
 
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18.2. 
Deaths ....................................................................................................................................................................................... 36 
18.3. 
Laboratory Evaluations .......................................................................................................................................................... 36 
18.3.1. 
Laboratory Reference Ranges Criteria ................................................................................................................................. 37 
18.4. 
ECG Evaluations ..................................................................................................................................................................... 37 
18.4.1. 
ECG Markedly Abnormal Criteria ....................................................................................................................................... 38 
18.5. 
Vital Signs................................................................................................................................................................................. 38 
18.6. 
Physical Examination .............................................................................................................................................................. 39 
18.7. 
Other Safety Assessments ....................................................................................................................................................... 39 
19. 
IMMUNOGENICITY ANALYSIS .................................................................................................. 39 
20. 
PHARMACOKINETICS .................................................................................................................. 40 
20.1. 
Serum Concentrations ............................................................................................................................................................. 41 
20.2. 
Serum Parameters ................................................................................................................................................................... 42 
21. 
DATA NOT SUMMARIZED OR PRESENTED ............................................................................ 44 
22. 
REFERENCES ................................................................................................................................... 44 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS ...................................................... 45 
 .................................................................................................................................................................. 45 
Dates & Times ........................................................................................................................................................................................ 45 
Spelling Format ...................................................................................................................................................................................... 45 
Listings  ................................................................................................................................................................................................... 45 
Output Presentations ............................................................................................................................................................................. 45 
APPENDIX 2. PARTIAL DATE CONVENTIONS ...................................................................................... 46 
Algorithm for Treatment Emergence of Adverse Events: .................................................................................................................. 46 
Algorithm for Prior / Concomitant Medications: ............................................................................................................................... 47 


 
 
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APPENDIX 3. SAMPLE CODES ................................................................................................................... 50 
 
 


 
 
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1. INTRODUCTION 
This document describes the rules and conventions to be used in the presentation and analysis of safety, immunogenicity, 
pharmacokinetic (PK) data and efficacy data.  
Current SAP has been generated based on Protocol No (DMB-3115-2)-Amedment-01 dated 04JUN 2021. 
2. STUDY OBJECTIVES 
2.1. PRIMARY OBJECTIVE 
• 
To evaluate efficacy of DMB-3115 in comparison with Stelara sourced from the EU. 
2.2. SECONDARY OBJECTIVES 
• 
To evaluate safety, tolerability, PK, and immunogenicity of DMB-3115 in comparison with Stelara sourced from the EU. 
2.3. EXPLORATORY OBJECTIVES 
• 
Not Applicable. 
3. STUDY DESIGN 
3.1. GENERAL DESCRIPTION 
This is a randomized, double-blind, multicentric, parallel group, and active controlled study comparing efficacy, safety and 
immunogenicity of subcutaneous administration of DMB-3115 and EU sourced Stelara in patients with moderate to severe chronic 
plaque psoriasis.  
The study includes a screening period of up to 4 weeks followed by IP administration of up to Week 40 and last (EOS) assessment at 
Week 52. 
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). 


 
 
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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 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 reassigned based on 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 to ensure blinding. Blinding will be maintained throughout the study.  
 
Only those patients who achieve at least Psoriasis Area and Severity Index (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 will remain in the study and be followed up to Week 52 for safety monitoring, including 
immunogenicity. 
Safety will be evaluated through an assessment of AEs, vital signs, electrocardiograms, and immunogenicity, along with clinical 
laboratory testing. 
Number of Investigators and Study Sites: 
Approximately 124 Investigators and sites are expected to participate in this study.  
Number of Patients:  
For primary efficacy analysis, the US FDA sample size of 490 patients in total, or 245 patients per treatment group at baseline, is selected 


 
 
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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. 
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 EMA (N=100), 590 patients (a minimum of 400 completed patients) will 
be necessary in total.  
Thus, 590 patients (295 patients per treatment group) 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. 
 
 
Abbreviation: EMA = European Medicines Agency; US FDA = United States Food and Drug Administration; w = weeks 
3.2. SCHEDULE OF EVENTS 
Schedule of events can be found in Section 1.3 of the protocol. 


 
 
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3.3. CHANGES TO ANALYSIS FROM PROTOCOL 
There will be additional sensitivity analysis conducted for COVID-19 affected subjects for which protocol will not be updated. COVID-
19 analysis: As the pandemic started at the time of recruitment and as per regulatory requirement sensitivity analysis e.g. extended 
window, is planned for COVID-19 patients, if any. 
Definition of Per Protocol set (EMA and USFDA) has been modified to indicate impact on primary efficacy analysis. Additional reasons 
which may impact primary endpoint has been added. Modifications for the same can be found in section 5.3 and 5.4.  
Subgroup analyses of treatment group differences for assessing Percent change in PASI will be presented for the primary endpoint 
based on imputed data. 
 
4. PLANNED ANALYSIS  
4.1. INTERIM ANALYSIS 
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 using the analysis methods described in this plan and an interim 
clinical study report will be generated for submission to the regulatory agencies. A limited number of identified individuals of the 
Sponsor or CRO will be unblinded for the interim analysis. However, patients, Investigators, and other study personnel will remain 
blinded throughout the entire study period. 
4.2. FINAL ANALYSIS 
Final analysis will be performed when all active patients complete the Week 52 assessment visit. The efficacy endpoints up to week 52 
and all available safety, ADA and PK data will be analyzed using the methods described in the analysis plan and a final CSR report will 
be generated for submission to the regulatory agencies. 
5. ANALYSIS SETS 
Agreement and authorization of subjects included/excluded from each analysis set will be conducted prior to the unblinding of the study.  


 
 
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5.1. SCREENED SET (SCR) 
Consists of all subjects who provide informed consent for this study 
5.2. INTENT-TO-TREAT SET (ITT) 
 All patients who have been randomized. 
5.3. SAFETY SET (SAF) 
Patients who randomize and receive at least one dose of the IP. The safety analysis will be conducted according to the treatment that a 
patient actually receives. 
5.4. PER PROTOCOL ANALYSIS SET (PPS-EMA) 
Patients who complete the study up to Week 8 and have no critical/major protocol deviations which may have a significant impact on 
primary endpoint analysis. All decisions related to exclusion of patients from the analysis set will be made prior to unblinding to the 
study. 
Below are critical/major protocol deviations which may have a significant impact on primary endpoint analysis which are mentioned 
below and is not limited to: 
• 
Missing PASI score (primary endpoint data) at Baseline or Week 8 
• 
Not receiving at least one dose of IP (Compliance issue) 
• 
Randomization error  
• 
Subject does not meet any of inclusion criteria 
• 
Subject meets any of the exclusion criteria 
• 
Use of Prohibited medication/vaccine  
• 
Other major protocol deviations which may have a significant impact on primary endpoint analysis 


 
 
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5.5. PER PROTOCOL ANALYSIS SET (PPS-US FDA) 
Patients who complete the study up to Week 12 and have no critical/major protocol deviations which may have a significant impact on 
primary endpoint analysis. All decisions related to exclusion of patients from the analysis set will be made prior to unblinding to the 
study. 
Below are critical/major protocol deviations which may have a significant impact on primary endpoint analysis which are mentioned 
below and is not limited to: 
• 
Missing PASI score (primary endpoint data) at Baseline or Week 12 
• 
Not receiving at least one dose of IP (Compliance issue) 
• 
Randomization error  
• 
Subject does not meet any of inclusion criteria 
• 
Subject meets any of the exclusion criteria 
• 
Use of Prohibited medication/vaccine  
• 
Other major protocol deviations which may have a significant impact on primary endpoint analysis 
5.6. PHARMAKOKINETIC SET (PK SET) 
Patients who receive at least one dose of IP, have at least 1 measured concentration at a scheduled post dose PK time point, and have no 
major protocol deviations/events that may significantly affect the PK assessment. Pharmacokinetic data will be summarized based on 
the treatment a patient actually receives. 
6. GENERAL CONSIDERATIONS 
The following descriptive statistics will be presented in summary tables for non-PK data: 
For continuous variables:  the number of contributing observations (n), mean, standard deviation (SD), median, minimum, and maximum. 
For categorical variables: the number and percentage of subjects in each category. 
If the original data has N decimal places, then the summary statistics will have the following decimal places: 
Minimum and maximum: N; 


 
 
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Mean, median, lower and upper bounds of two-sided CI: N + 1; 
Percentage of subjects in each category, SD: N + 2 
p-values will be presented with 4 decimal places 
See Section 20 for descriptive statistics of PK data. 
 
6.1. REFERENCE START DATE AND STUDY DAY 
Study Day will be calculated from the reference start date and will be used to show start/stop day of assessments and events.  
Reference start date is defined as the day of the first dose of study medication, (Day 1 is the day of the first dose of study medication) 
and will appear in every listing where an assessment date or event date appears. 
If the date of the event is on or after the reference start date, then:  
Study Day = (date of event – reference start date) + 1. 
If the date of the event is prior to the reference start date, then:  
Study Day = (date of event – reference start date). 
In the situation where the event date is partial or missing, study day, and any corresponding durations will appear partial or 
missing in the listings.  
6.2. BASELINE 
Unless otherwise specified, baseline is defined as the last non-missing measurement taken prior to reference start date (including 
unscheduled assessments). In the case where the last non-missing measurement and the reference start date/time coincide, that 
measurement will be considered pre-baseline, but Adverse Events (AEs) and medications commencing on the reference start date will 
be considered post-baseline. 
6.3. RETESTS, UNSCHEDULED VISITS AND EARLY TERMINATION DATA 
In general, for by-visit summaries, data recorded at the nominal visit will be presented. Unscheduled measurements will not be included 
in by-visit summaries.  


 
 
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In the case of a retest (same visit number assigned), the latest available measurement for that visit will be used for by-visit summaries.  
Early termination data will be mapped to the ET/End of Study Follow-Up visit for by-visit summaries. 
Listings will include scheduled, unscheduled, retest and early discontinuation data. 
6.4. STATISTICAL TESTS 
Primary efficacy endpoint will be analyzed using an Analysis of Covariance (ANCOVA) at Week 8 (for EMA) and Week 12 (for US 
FDA). 
Secondary efficacy endpoints will be analyzed using ANCOVA and logistic regression for protocol specified visits and supportive 
analysis to secondary efficacy endpoint for Period 2 will be performed using ANCOVA with Welch’s test. 
Primary and secondary efficacy endpoints will be analyzed with 95% CI (for EMA) and 90% CI (for US FDA). using ANCOVA and 
Logistic Regression. Confidence Interval, Standard Errors and P values will be provided based on ANCOVA Model Results. 
Sensitivity and supportive analyses will be analyzed with 95% CI (for EMA) and 90% CI (for US FDA). 
Subgroup analyses of treatment group differences for assessing Percent change in PASI will be analyzed using an ANCOVA for the 
primary endpoint at Week 8 (for EMA) and Week 12 (for US FDA). 
 
6.5. COMMON CALCULATIONS 
Unless otherwise specified, for quantitative measurements, change from baseline will be calculated as: 
Test Value at Visit X – Baseline Value  
6.6. SOFTWARE VERSION 
Non-compartmental PK parameter calculations will be performed using Phoenix® WinNonlin® Version 8.3 or higher (Certara L.P., 
Princeton, New Jersey, USA.  All other analyses will be conducted using SAS® software (version 9.4 or higher).  
7. STATISTICAL CONSIDERATIONS 
All data listings, summaries, and analyses will be performed under the guidance and approval of the Sponsor. Descriptive statistics will 


 
 
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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.   
7.1. ADJUSTMENTS FOR COVARIATES AND FACTORS TO BE INCLUDED IN 
ANALYSES 
The following stratification factors are used in the analysis. 
• 
Baseline body weight (≤100 kg or >100 kg).  
• 
Geographic regions (EU, US or ROW). 
• 
Number of previous systemic therapies for psoriasis (<3 or ≥3). 
The following covariates are used in the analysis. 
• 
Visit, and the treatment-by-visit interaction will be used as Fixed effects.  
• 
Baseline PASI Score, Baseline PGA Score, Baseline DLQI Score will be used as Covariates.  
For details of their inclusion in the models, see the specific analysis. 
7.2. MISSING DATA 
Missing values for primary efficacy variable and subgroup analysis (for Primary efficacy) in the ITT will be imputed by multiple 
imputation (MI) method. Additional details are provided under missing data methods for primary efficacy variables. Safety, missing PK 
or immunogenicity data will not be imputed. Missing PK concentrations will be handled as described in Section 20. 
7.3. MULTIPLE COMPARISONS/ MULTIPLICITY 
Not Applicable 
8. DISPOSITION AND WITHDRAWALS 
All subjects who provide informed consent will be accounted for in this study.  


 
 
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8.1. DISPOSITION 
Subject disposition including the number of subjects screened, randomized, treated, completed as well as the number of dropouts along 
with the reasons for discontinuation will be tabulated for Screened Set (SCR). 
A listing will be presented to describe date of screening, assigned treatment, completion or early withdrawal, and the reason for early 
discontinuation, if applicable, for each subject. 
A disposition plot in terms of flowchart would be presented to capture all information pertaining to disposition. 
9. DERIVATIONS 
• 
BMI (kg/ m2) = weight (kg)/ height (m)2 
• 
Percent change of PASI score (%) at visit x = (PASI score at visit baseline– PASI score at visit X)/ PASI score at baseline 
x* 100 
• 
Coefficient of Variation (%)= (SD/Mean)*100 
In case of baseline value equal to 0 and non-missing post-baseline value recorded, then the change is set to 0% for the 
corresponding visit. 
 
• 
PASI50 at visit X: 
o 
Yes if percent change of PASI score at visit X ≥ 50 
o 
No if percent change of PASI score at visit X < 50 
 
• 
PASI75 at visit X: 
o 
Yes if percent change of PASI score at visit X ≥ 75 
o 
No if percent change of PASI score at visit X < 75 
 
• 
PASI90 at visit X: 
o 
Yes if percent change of PASI score at visit X ≥ 90 
o 
No if percent change of PASI score at visit X < 90 
 
• 
PASI100 at visit X: 
o 
Yes if percent change of PASI score at visit X = 100 


 
 
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o 
No if percent change of PASI score at visit X < 100 
 
10. PROTOCOL DEVIATIONS 
Protocol deviations are the deviations from the procedure outlined in the protocol. All the Protocol Deviations (PDs) will be summarized 
using the ITT analysis set as obtained from Clinical Trial Management System (CTMS) logs. PDs will be identified and discussed with 
the Investigator/Sponsor in PD review discussion to categorize them, and to finalize analysis set assignment. 
Any PDs will be categorized into critical, major and minor protocol deviations and will be summarized based on severity categories. 
Critical and Major protocol deviations having impact on primary analysis will be considered while finalizing the Per Protocol (PP) 
Analysis set. PDs log will be used for reporting purpose in tables. PDs will be summarized based on period 1 and period 2  
11. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic data and other baseline characteristics will be summarized using the ITT and per-protocol set (EMA and US FDA). 
No statistical testing will be carried out for demographic or other baseline characteristics. 
Summary statistics will be provided for: 
• 
Age (years) 
• 
Weight (kg) 
• 
Height (cm) 
• 
BMI (kg/m2) 
Frequency and percentages will be provided for: 
• 
Gender 
• 
Ethnicity 
• 
Race  
• 
Patients body weight at baseline [≤100 kg or >100 kg]  
• 
Geographic region [EU, US or ROW] 


 
 
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• 
Number of previous systemic therapies for psoriasis [<3 or ≥3] 
• 
Number of subjects with PGA Score of 3 or more [3 or 4] at Baseline 
Summary statistics under baseline characteristics will be provided for: 
• 
PASI Score 
• 
PGA Score  
• 
DLQI Score 
• 
Duration of plaque-type psoriasis (years) 
• 
Percentage of Body surface area (BSA) affected by plaque-type psoriasis 
 Similarly, count and percentages will be provided for:  
• 
HIV Status 
• 
Hepatitis B Surface Antigen, Hepatitis B Core Antibody, Hepatitis C Virus Antibody 
• 
Quantiferon Gold Test.  
• 
Diagnosed with active or latent tuberculosis 
Results collected at Baseline.  
A listing of subject demographic data and other baseline characteristics will be presented. 
12. MEDICAL HISTORY AND CONCOMITANT ILLNESS 
Medical History and concomitant illness information will be summarized using the ITT analysis set.  A listing of medical history and 
concomitant illness will be provided. 
• 
Medical History and concomitant illness will be coded using the latest version of MedDRA Dictionary, according to the Data 
Coding Guidelines.  
• 
Medical History conditions are defined as those conditions which stop prior to screening or at screening.  
• 
Concomitant conditions/illnesses are defined as any medical conditions/illnesses that started before screening and were 
ongoing at screening or ended after screening.  


 
 
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• 
Presented by SOC and PT.  
13. MEDICATIONS 
All medications will be coded using the latest version of WHODrug Global B3. Each medication will be classified as prior medication 
if it is stopped prior to the first dose of IP, or concomitant medications defined as started prior to, on or after the first dose of study drug 
and started before the end of study drug and ended on or after the date of first dose of study drug or were ongoing at the end of the study 
drug.  
Prior and concomitant medication will be summarized by Anatomical Therapeutic Chemical level 1 (ATC 1) and Anatomical 
Therapeutic Chemical level 2 (ATC 2) categories, and preferred name. Prior medications will be summarized using the ITT, and 
concomitant medications will be summarized using the SAF. 
See Appendix 2 for handling of partial dates for medications, in the case where it is not possible to define a medication as prior, or 
concomitant, the medication will be classified by the worst case; i.e. concomitant.  
14. STUDY MEDICATION EXPOSURE 
Treatment groups in study listed as below: 
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. 
Exposure to study medication will be summarized by body weight (≤100kg and >100kg) for duration exposure, average dose 
at week and cumulative average dose (mg) for all weeks for the SAF. A listing will also be provided. 
Duration of medication exposure (weeks)= (Date of last study medication administration – Date of first study medication 
administration+1)/7. 
Duration of exposure (days)=Date of last dose of study drug -Date of first dose of study drug +1. 
 
15. STUDY MEDICATION COMPLIANCE  
• 
Compliance with trial medication will be based on the eCRF page “IP Administration”. An administered injection is 
considered when the question “Was Dose administered?” is answered “Yes”. Study medication compliance will be based 
on SAF. 
• 
Compliance will be based on the comparison of actual administered injections and the planned usage. 
  
Compliance will include visits until treatment discontinuation. 
• 
‘Per visit’ compliance will be calculated as: 
Compliance at visit N = Yes if the question “Was Dose administered?” is answered “Yes”. 


 
 
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           No  
else 
 
 Per visit compliance (%) = (Number of administered injections at visit x) *100/ (Planned number of injections at visit x) 
• 
 Overall’ compliance will be calculated as follows: 
 Overall compliance (%) = (Total Number of administered injections) *100/ (Total Planned number of injections) 
 
 


 
 
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16. ESTIMANDS 
 
. 
Estimand Definition 
Attributes 
Population 
Variable/Endpoint 
Intercurrent event 
handling strategy 
Population-
level 
summary 
measure 
Primary 
DMB-
3115/Stelara 
Dose 
Population 1-Subjects 
who qualify under 
PPS Analysis set with 
Week 8 Assessments  
Regulatory Authority-
EMA 
 
Percent change in the 
Psoriasis Area and 
Severity 
Index (PASI) score 
from baseline to Week 
8 (For 
EMA). 
Not Applicable 
[For EMA] 
95% 
confidence 
interval of 
the 
difference 
(DMB-3115 
- Stelara) in 
percent 
change in 
PASI at 
Week 8. 
 
 
Primary 
DMB-
3115/Stelara 
Dose 
Population 1-Subjects 
who qualify under 
ITT Analysis set with 
Week 12 Assessments  
Regulatory Authority-
US FDA 
 
Percent change in the 
Psoriasis Area and 
Severity 
Index (PASI) score 
from baseline to Week 
12 (For US FDA). 
Missing outcome at 
Week 12 will be 
imputed, using the 
Multiple Imputation 
at Week 12 
[For US-
FDA] 90% 
confidence 
interval of 
the 
difference 
(DMB-3115 
- Stelara) in 
percent 
change in 
PASI at 
Week 12. 
 


 
 
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17. EFFICACY OUTCOMES  
17.1. 
PRIMARY EFFICACY 
To evaluate efficacy of DMB-3115 in comparison with Stelara sourced from the EU. 
17.1.1. 
PRIMARY EFFICACY VARIABLE(S)  
The primary efficacy variable is 
• 
Percent change in the Psoriasis Area and Severity Index (PASI) score from baseline to Week 8 (For EMA). 
• 
Percent change in the PASI score from baseline to Week 12 (For US FDA). 
17.1.2. 
MISSING DATA METHODS FOR PRIMARY EFFICACY VARIABLE(S) 
Missing efficacy data for the primary endpoint will be handled using a Multiple Imputation (MI) procedure as follows: 
Step 1- Creation of monotone missing data structure using 50 interactions (M), to ensure that the results do not suffer from a relative 
efficiency loss. 
Intermediate (non-monotone) missing data (where some subjects may have missing records) will be imputed using the Markov Chain 
Monte Carlo (MCMC) method including treatment arm, PASI_Baseline, PASI_Week4, PASI_Week8, PASI_Week12, and assuming 
that the joint distribution of these variables is multivariate normal and the pattern for missing data is arbitrary. For this step the SAS 
procedure PROC MI with the MCMC option will be used 
Step 2- Further imputations:  
The datasets, now with monotone missing data, will be imputed further, in a stepwise manner to impute each week’s PASI from Week 
1 to Week 12 using the regression method (assuming missing at random). The model for each week will include terms for all the previous 
weeks and follow the structure of the following model for each visit. 
17.1.3. 
PRIMARY ANALYSIS OF PRIMARY EFFICACY VARIABLE(S) 
The primary objective of this study is to test the hypothesis that 
H0:  |Treatment(DMB-3115) – Treatment(Stelara)| ≥ 𝛿 
Vs 


 
 
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H1:  |Treatment(DMB-3115) – Treatment(Stelara)| < 𝛿 
Whereas 𝛿 is an equivalence margin which is defined as for EMA regulatory submission as [-15%, 15%] and for US FDA consider as 
[-10%, 10%]. 
The primary efficacy analysis will be performed for the PPS and the ITT analysis set for both regulatory submission (EMA at 8 week 
and US FDA at 12 week). 
Primary Efficacy Analysis (for EMA)  
• 
Percent change in PASI at Week 8 will be analyzed with a 95% 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 95% CI of the mean difference is entirely contained within 
the pre-specified equivalence margin of (-15%, 15%). 
• 
Analysis will be performed in the ITT and PPS. The PPS is the primary efficacy analysis population. 
• 
Missing values for primary efficacy variable in the ITT will be imputed by MI method. 


 
 
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 Primary Efficacy Analysis (for 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 the ITT will be imputed by MI method. 
 
 


 
 
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17.2. 
SECONDARY EFFICACY 
17.2.1 SECONDARY EFFICACY VARIABLES  
THE SECONDARY EFFICACY ANALYSES WILL BE PERFORMED FOR THE ITT. 
17.2.1.1. 
Percentage of patients with a PASI 50 (a 50% reduction in the PASI score) response at Weeks 4, 8, 12, 
16, 28, 40, and 52. 
17.2.1.2. 
Percentage of patients with a PASI 75 (a 75% reduction in the PASI score) response at Weeks 4, 8, 12, 
16, 28, 40, and 52. 
17.2.1.3. 
 Percentage of patients with a PASI 90 (a 90% reduction in the PASI score) response at Weeks 4, 8, 12, 
16, 28, 40, and 52.  
17.2.1.4. 
Percentage of patients with a PASI 100 (a 100% reduction in the PASI score) response at Weeks 4, 8, 12, 
16, 28, 40, and 52. 
17.2.1.5. 
Percentage change in AUEC for the PASI score from baseline at Weeks 4, 8, 12, 16, 28, 40, and 52. 
17.2.1.6. 
Percent change in the PASI score from baseline at Weeks 4, 8, 12, 16, 28, 40, and 52. 
17.2.1.7. 
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. 
17.2.1.8. 
Change from baseline in Dermatology Life Quality Index (DLQI) at Weeks 4, 8, 12, 16, 28, 40, and 52. 
17.2.2. 
ANALYSIS OF SECONDARY EFFICACY VARIABLES 
For Period 1 (Weeks 4, 8, 12, 16 and 28), analysis will be performed as mentioned below sections. 
For Period 2 the descriptive statistics will be provided for each treatment group.   
17.2.2.1. 
Analysis of Secondary Efficacy Endpoint- Psoriasis Area and Severity Index (PASI) Response  
 
The analysis of secondary endpoint 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 


 
 
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(<3 or ≥3) as covariates. 
An estimate of odds ratio of achieving PASI response of treatment group comparisons corresponding p-value and 90% CI (for US FDA)  
95% CI (For EMA) for the odds ratio of treatment group comparisons will be given using Wald’s test. 
Then CI criteria is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA - 95% CI). 
17.2.2.2. 
Analysis of Secondary Efficacy Endpoint- Area under effect curve (AUEC) for Psoriasis Area and 
Severity Index (PASI) score  
Percentage change from baseline will be calculated at each timepoint based on PASI score and then below mentioned trapezoidal formula 
will be applied for AUEC calculation 
 AUEC=∑i=2 1/2 (Mi-1+Mi)*(ti-ti-1); where i=2, …, k, t1=0, and M1=0 
Each Trapezoidal value is added cumulatively and last observation at a given timepoint will be its AUEC value 
Percent change of PASI value (%) at visit x =  (PASI value at baseline – PASI score at visit X)/ PASI value at baseline x 100 
Where m is the percent change of PASI Score and t is the timepoints for PASI Score. As per the above formula (trapezoidal rule) 
calculate the trapezoidal values for each timepoint. 
The analysis of secondary endpoint will be analyzed using ANCOVA at Weeks 4, 8, 12, 16, 28, 40, and 52 with baseline PASI value, 
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. 
Then Confidence Interval criteria is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA 
- 95% CI). 
17.2.2.3. 
Analysis of Secondory Efficacy Endpoint -Psoriasis Area and Severity Index (PASI) Score  
The analysis of secondary endpoint based on percentage change from baseline will be analyzed using ANCOVA at Weeks 4, 8, 12, 16, 
28, 40, and 52 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. 
Then CI criteria is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA - 95% CI). 
17.2.2.4. 
Analysis of Secondory Efficacy Endpoint- Physicians Global Assessment (PGA) . 
Percentage of patients with a Physician's Global Assessment (PGA) score of Cleared or Minimal at Weeks 4, 8, 12, 16, 28, 40, and 
52will be analyzed based on proportions 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. 


 
 
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Then CI is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA - 95% CI). 
17.2.2.5. 
Analysis of Secondory Efficacy Endpoint- Dermatology Life Quality Index (DLQI) . 
Change from baseline in Dermatology Life Quality Index (DLQI) will be analyzed using ANCOVA at Weeks 4, 8, 12, 16, 28, 40, and 
52 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. 
 Then CI criteria is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA - 95% CI). 
17.2.3. 
SENSITIVITY ANALYSIS OF PRIMARY EFFICACY VARIABLES 
Percent change in PASI will be analyzed for each PPS and the ITT (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. 
If the Mixed Model with unstructured covariance fails to converge, a simpler covariance structure will be used selected by the AIC 
criterion. 
Then Confidence Interval criteria is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA 
- 95% CI). 
17.2.4. 
SENSITIVITY ANALYSIS OF PRIMARY VARIABLES FOR SUBJECTS IMPACTED BY COVID-
19 
Percent change in PASI for COVID-19 confirmed subjects till Week 8 (for EMA) and Week 12 ( For US FDA) and subjects identified 
under COVID-19 impact log whose visit till Week 8 (for EMA) and Week 12 (For US FDA) will be analysed for each PPS and the ITT 
with a 95% CI (for EMA) and 90% CI (for US FDA) 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)). 
Similar Analysis will be conducted for subjects excluding subjects impacted by COVID-19 
Confidence Interval criteria is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA - 95% 
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17.2.5. 
SUPPORTIVE ANALYSIS  TO SECONDARY ENDPOINT FOR PERIOD2 
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. 
Then Confidence Interval criteria is decided and calculated on the basis of regulatory submission (for US FDA-90% CI) and (for EMA 
- 95% CI). 
 
 


 
 
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17.2.6. 
EXAMINATION OF SUBGROUPS 
Subgroup analyses of treatment group differences for assessing Percent change in PASI will be presented for the primary endpoint 
based on imputed data. 
The following subgroups will be assessed for endpoints which are specified above: 
1. body weight at baseline (≤100 kg or >100 kg) 
2. geographic region (EU, US or Rest of the World [ROW]) 
3. number of previous systemic therapies for psoriasis (<3 or ≥3) 
Percent change in PASI will be analyzed for each PPS and ITT (EMA and US FDA).  
Percent change in PASI will be analyzed with a 95% CI (for EMA) at Week 8 and 90% CI (for US FDA) at Week 12 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]) except the subgroup factor being analyzed. 
18. SAFETY OUTCOMES 
There will be no statistical comparisons between the treatment groups for safety data, unless otherwise specified with the relevant section.  
18.1. 
ADVERSE EVENTS 
Adverse Events (AEs) will be coded using the latest version of MedDRA Dictionary. 
Treatment emergent adverse events (TEAEs) are defined as:  
• 
A new event that occurs during or after first dose of study treatment or,  
• 
Any event present at baseline that worsens in either intensity or frequency after first dose of study treatment. 
See Appendix 2 for handling of partial dates for AEs.  In the case where it is not possible to define an AE as treatment emergent or not, 
the AE will be classified by the worst case; i.e. treatment emergent.  
All Adverse Events started on the date of Week 28 dosing should be included in the Period 2. 
Only TEAEs will be summarized on Safety Analysis Set (SAF). 
An overall summary of number of subjects along with number of events within each of the categories described in the sub-section below, 
will be provided as specified in the templates.  


 
 
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Listings will include TEAEs and Non-TEAEs. 
Adverse events will be presented for Period 1, Period 2 and Overall period (Week 0 ~Week 52) 
18.1.1. 
ALL TEAES 
Incidence of TEAEs will be presented by System Organ Class (SOC) and Preferred Term (PT) and broken down further by relationship 
to study medication. 
Incidence of Non-TEAEs will be presented by System Organ Class (SOC) and Preferred Term (PT) 
18.1.1.1. 
Intensity 
Intensity will be classified according to CTCAE Grading V5.0 as (Grade1-Grade5). 
If a subject report a TEAE more than once within that SOC/ PT, the AE with the worst-case severity will be used in the corresponding 
severity summaries. 
• Grade 1: Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. 
• Grade 2: Moderate; minimal, local or non-invasive intervention indicated; limiting age-appropriate instrumental activities of   
daily living (ADL). 
• Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; limiting self-care ADL. 
• Grade 4: Life-threatening consequences; urgent intervention indicated. 
• Grade 5: Death related to AE. 
Adverse Events falling under Grades 3 to 5 are considered as Severe Adverse events. 
 
18.1.1.2. 
Relationship to Study Medication 
 
Relationship as indicated by the Investigator, is classified as “Unrelated”, “Unlikely to be related”, “Possibly related”, “Probably related” 
or, “Not applicable”.  
Probably related and Possibly related are considered as Related to study medication, Unlikely and Unrelated are considered as  Unrelated 
to study medication. 
• 
“Unrelated” is used if there is not a reasonable possibility that the study treatment caused the AE. 
• 
“Unlikely to be related” suggests that only a remote connection exists between the study treatment and the AE. Other conditions, 
including chronic illness, progression or expression of the disease state or reaction to concomitant therapy, appear to explain the 
reported AE.  
• 
“Possibly related” suggests that the association of the AE with the study treatment is unknown. However, the AE is not reasonably 


 
 
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supported by other conditions. 
• 
“Probably related” conveys that there are facts, evidence, and/or arguments to suggest a causal relationship, rather than a relationship 
cannot be ruled out. 
All efforts should be made to classify the AE according to the above categories. 
• 
The category “not applicable” may be used for SAEs which happen prior to any procedures/dosing. 
If a subject report the same AE more than once within that SOC/ PT, the AE with the maximum intensity to study medication will be 
used in the corresponding relationship summaries.  
18.1.2. 
TEAES LEADING TO DISCONTINUATION OF STUDY MEDICATION 
For TEAEs leading to permanent discontinuation of study medication, summaries of incidence rates (frequencies and percentages) by 
SOC and PT will be prepared. 
TEAEs leading to permanent discontinuation of study medication will be identified by using the AE page (“Drug Withdrawn” chosen 
for “Action Taken with Study Treatment”) of the (e)CRF. 
18.1.3. 
TEAES LEADING TO WITHDRAWAL OF PATIENTS FROM STUDY 
For TEAEs leading to withdrawal from study, summaries of incidence rates (frequencies and percentages) by SOC and PT will be 
prepared. 
TEAEs leading to withdrawal of patients from study will be identified by using the AE page (“Drug Withdrawn” chosen for “Action 
Taken with Study Treatment”, at the same time, “Yes” chosen for “Caused Study Discontinuation”) of the (e)CRF. 
 
18.1.4. 
SERIOUS ADVERSE EVENTS 
Serious adverse events (SAEs) are those events recorded as” Serious” on the Adverse Events page of the (e)CRF. A summary of serious 
TEAEs by SOC and PT will be prepared. Listing for SAEs will also be provided. 
18.1.5. 
ADVERSE EVENTS LEADING TO DEATH 
TEAEs leading to death are those events which are recorded as ”Results in Death” on the Adverse Events page of the (e)CRF. A 
summary of TEAEs leading to death by SOC and PT will be prepared. Listing will also be provided. 


 
 
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18.1.6. 
ADVERSE EVENTS RELATED TO COVID-19 
Adverse events occurring due to COVID-19 will be summarized by system organ class and preferred term. Adverse events occurring 
for COVID-19 patients also will be summarized by system organ class and preferred term. 
AEs related to COVID-19: includes TEAEs, where the verbatim term contains key text “COVID”. TEAEs related to COVID-19 vaccine, 
where the verbatim term contains “disease related to COVID-19 vaccine” will not be included. Listing will also be provided. 
18.1.7. 
ADVERSE EVENTS RELATED TO DEVICES DEFICIENCY 
Adverse events occurring due to Device deficiency will be summarized based on relationship category recorded as the response to the 
question “Is this event associated/related with device(prefilled syringe) deficiency?” on the AE eCRF page, which is classified as 
Unrelated, Unlikely, Possible, Probable and Not applicable.  
Listing related to adverse events due to device deficiency will be provided. 
 
18.1.8. 
ADVERSE EVENTS OF SPECIAL INTEREST  
Adverse Events of Special Interest (AESIs) are to have “Yes” recorded as the response to the question “Is the AE an Adverse event of 
special interest (AESI)?” on the AE eCRF page. 
The following are considered as AESIs: 
• 
Acquired immunodeficiency syndrome; 
• 
Autoimmune disease; 
• 
Cerebrovascular accident; 
• 
Confirmed myocardial infarction; 
• 
Congestive heart failure; 
• 
Depression; 
• 
Erythrodermic psoriasis; 
• 
Facial palsy; 
• 
Hematologic events (e.g., pancytopenia, aplastic anemia, or agranulocytosis); 


 
 
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• 
Hepatic injury: A hepatic injury is defined by the following alterations of hepatic laboratory parameters: 
• 
An elevation of AST and/or ALT ≥3-fold ULN combined with an elevation of total bilirubin ≥2-fold ULN measured in the 
same blood draw sample, or 
• 
An elevation of AST and/or ALT ≥3-fold ULN combined with an elevation of international normalized ratio (INR) >1.5, if 
INR measured, or 
• 
Marked peak aminotransferase (ALT, and/or AST) elevations ≥10-fold ULN. 
• 
These laboratory findings constitute a hepatic injury alert and the patients showing these laboratory abnormalities need to be 
followed up. In case of clinical symptoms of hepatic injury (icterus, unexplained encephalopathy, unexplained coagulopathy, 
right upper quadrant abdominal pain, etc.) without laboratory results (ALT, AST, and total bilirubin) available, the Investigator 
should 
make 
sure 
these 
parameters 
are 
analyzed, 
if 
necessary, 
in 
an 
unscheduled 
blood 
test. 
Hypersensitivity reactions; 
• 
Injection Site Reactions: An injection site reaction is any unfavorable or unintended sign that occurs at the IP injection site. 
Any adverse reaction (e.g., pain, erythema, and/or induration) should be recorded on the AE page of the eCRF; 
• 
Malignancies; 
• 
Neurologic or demyelinating events (e.g., progressive multifocal leukoencephalopathy; peripheral demyelination; posterior 
reversible encephalopathy syndrome [reversible Posterior Leukoencephalopathy Syndrome, RPLS]); have been reported with 
the administration of Stelara. Reversible Posterior Leukoencephalopathy Syndrome is a neurological disorder, which is not 
caused by demyelination or a known infectious agent. Reversible Posterior Leukoencephalopathy Syndrome can present with 
headache, seizures, confusion and visual disturbances. Conditions with which it has been associated include preeclampsia, 
eclampsia, acute hypertension, cytotoxic agents, and immunosuppressive therapy. Fatal outcomes have been reported 
(Prescribing Information for Stelara). In case RPLS is suspected, the treatment with the IP should be discontinued and the 
patient should be referred to neurologist for full evaluation and appropriate treatment. 
• 
Opportunistic infections; 
• 
Pustular psoriasis; 
• 
Transient ischemic attack ; 
• 
Tuberculosis; 
• 
Unexpected reaction to a vaccine (e.g., active infection by live-attenuated vaccine) 
Summaries of Treatment emergent AESI incidence rates (number and percentage of patients) by AESI Category will be prepared. Listing 


 
 
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will also be provided. 
18.2. 
DEATHS 
If any subjects die during the study as recorded on the “deaths” page of the (e)CRF, the information will be presented in a summary 
table and a data listing.  
Following summaries will be generated. 
Number (%) of patients who died during study period (TEAE, on-study) and reasons for death summarized for the SAF by treatment 
received. 
Death in nonrandomized patients or randomized and not treated patients will be listed. 
18.3. 
LABORATORY EVALUATIONS 
Results from the central laboratory and local laboratory will be included in the reporting of this study for Hematology, Blood Chemistry, 
Coagulation and Urinalysis.  
Quantitative laboratory measurements reported as “< X”, i.e. below the lower limit of quantification (BLQ), or “> X”, i.e. above the 
upper limit of quantification (ULQ), will be converted to X for the purpose of quantitative summaries, but will be presented as recorded, 
i.e. as “< X” or “> X” in the listings. 
The following summaries and plot will be provided for laboratory data: 
• 
Actual and change from baseline by visit (for quantitative measurements) 
• 
Laboratory shift from Baseline 
• 
Boxplot for Actual and change from baseline by visit for Hematology, Biochemistry and Coagulation (for quantitative 
measurements) 
• 
Listing of subjects meeting clinically abnormal criteria 
• 
Spaghetti plot for Hepatic Injury (Liver Enzyme Profile) for Subjects with Treatment-Emergent Abnormalities. Treatment 
Emergent abnormalities for hepatic injury is defined as below: 
• 
An elevation of AST and/or ALT ≥3-fold ULN combined with an elevation of total bilirubin ≥2-fold ULN measured in the 
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• 
An elevation of AST and/or ALT ≥3-fold ULN combined with an elevation of international normalized ratio (INR) >1.5, if 
INR measured, or 
• 
Marked peak aminotransferase (ALT, and/or AST) elevations ≥10-fold ULN 
• 
eDish Plot for total bilirubin versus ALT will be presented for possible Hy’s Law cases.  
18.3.1. 
LABORATORY REFERENCE RANGES CRITERIA 
Quantitative laboratory measurements will be compared with the relevant laboratory reference ranges in SI units and categorized as: 
• 
Low: Below the lower limit of the laboratory reference range.  
• 
Normal: Within the laboratory reference range (upper and lower limit included). 
• 
High: Above the upper limit of the laboratory reference range. 
18.4. 
ECG EVALUATIONS 
Results from the central ECG (Electrocardiogram) Reading Centre will be included in the reporting of this study. Results for ECG will 
be presented under SAF. 
The following ECG parameters will be reported for this study: 
• 
PQ Interval (PR) (msec) 
• 
QRS Interval (msec) 
• 
QT Interval (msec) 
• 
QTc Interval (msec) 
• 
QTcF Interval (msec) [derived] 
• 
QTcB Interval (msec) [derived] 
• 
HR (bpm) 
• 
Overall assessment of ECG (Investigator’s judgment): 
• 
Normal 


 
 
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• 
Abnormal, Not Clinically Significant (NCS) 
• 
Abnormal, Clinically Significant (CS) 
• 
The following summaries will be provided for ECG data: 
• 
Actual and change from baseline by visit (for quantitative measurements) 
• 
Listing of subjects meeting markedly abnormal criteria 
18.4.1. 
ECG MARKEDLY ABNORMAL CRITERIA 
All ECG data results (normal/abnormal) will be summarized using frequency and percentages for discrete variables. 
Clinically significant abnormalities will be presented in by-patient listings. 
18.5. 
VITAL SIGNS 
Results for Vital Signs will be presented under SAF. The following Vital Signs measurements will be reported for this study: 
• 
Systolic Blood Pressure (mmHg) 
• 
Diastolic Blood Pressure (mmHg) 
• 
Pulse Rate (beats/min) 
• 
Body Temperature (°C) 
• 
Height (cm) 
• 
Weight (kg) 
• 
BMI (kg/m2) 
• 
Body temperature collected °F will be converted to °C as follows:  
• 
°C = (°F − 32) * 5/9 
The following summaries will be provided for vital signs data: 
• 
Actual and change from baseline by visit  
• 
Listing capturing vital signs of Patients. 


 
 
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18.6. 
PHYSICAL EXAMINATION  
Physical examination findings as collected in eCRF and associated abnormalities, along with clinical significance will be tabulated and 
presented in the listings on SAF. 
The following summaries will be provided for physical examination data: 
• 
Incidence of abnormalities by visit. 
• 
Shift from Baseline. 
18.7. 
OTHER SAFETY ASSESSMENTS 
Results for other safety assessments will be presented under SAF unless specified otherwise. 
A chest X-ray (both posterior-anterior and lateral views) is required unless available within 12 weeks prior to the first administration of 
IP and should be read by a qualified radiologist or pulmonologist to evaluate signs of active TB or history of TB. 
A summary table and listing of TB assessment will be presented, Similarly Listing for Chest X-Ray will also be provided. 
Listing of Injection site reaction indicating findings will be provided.  
A listing of COVID-19 Impact log will be provided to indicate the assessment procedure, visit, type of impact. Reason of Impact and 
any additional information due to which assessment was affected would be provided.  This listing will be based on ITT population. 
A listing will be provided for female subjects for Pregnancy Test. Details indicating test type (Serum/Urine) and Test results would be 
provided. 
19. IMMUNOGENICITY ANALYSIS 
Venous blood samples of approximately 50 mL will be collected during the study for measurement of ADA (binding and/or neutralizing). 
Each serum sample will be divided into 10 aliquots (5 for ADA, 3 for neutralizing antibodies and 2 back-up). A tiered approach will be 
followed for assessing antibody formation in response to ustekinumab administration. All samples will be screened for occurrence of 
binding antibodies to ustekinumab. 
Those samples that test positive will be subjected to a confirmatory assay. Samples that are positive on confirmatory assay will be further 
tested for neutralizing potential and subjected to titration analysis. 
Results for Immunogenicity analysis will be presented under SAF. The following analyses will be performed: Number and frequency 
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o 
Negative 
o 
Positive 
The incidence of ADAs and neutralizing antibodies will be summarized by treatment group and visit and listed. 
Descriptive statistics for Binding and Neutralizing antibody titer will be provided for all available parameters at protocol specified visits 
using Number of subjects available at each assessment visit, Arithmetic Mean, Median, Minimum Maximum, quartiles and Geometric 
Mean. Summaries for both Actual and change from baseline will be presented. For geometric mean, the mean and the 95% CIs will be 
calculated on Log10 (titers/data), with subsequent antilog transformations applied. 
Incidence of ADA and Nabs will be summarized based on Period 1, Period 2 and overall period (Week0 to Week 52). 
20. PHARMACOKINETICS 
Changes to the procedures or events which may impact the quality of the PK data will be considered important protocol deviations or 
events and will be described within the clinical study report body text. These changes or events will include any circumstances that will 
alter the evaluation of the PK. Examples of deviations/events for PK include but may not be limited to sample processing errors that 
lead to inaccurate bioanalytical results, use of disallowed medications affecting PK, and/or inaccurate or incomplete dosing. Important 
deviations/events may potentially affect as little as a single data record (e.g. sample processing error) or an entire concentration-time 
profile.  In the case of a significant protocol deviation or event with impact on PK, the affected PK data will be excluded from PK 
analysis and/or descriptive statistics, as appropriate. Other changes to the procedures or events which do not impact the quality of the 
PK data will not be considered important protocol deviations. A common example of a protocol deviation which is not considered to be 
important is a missed blood sample or deviations from blood collection times at a non-critical time in the profile; such deviations may 
sometimes be adjusted for in the analysis, if appropriate, but will not result in exclusion of data from analysis. 
 
All PK concentrations will be reported and analyzed with the same precision as the source data provided by the bioanalytical laboratory 
regardless of how many significant figures or decimals the data carry. Derived PK parameters will be rounded for reporting purposes in 
by-subject listings.  Summary statistics of derived PK parameters will be performed by using the unrounded values and the statistical 
results will be rounded for reporting purposes. 
For most derived PK parameters, 3 significant digits will be used as the standard rounding procedure for reporting, with the following 
exceptions: 
• 
Parameters directly derived from source data (e.g. Cmax) will be reported and analyzed with the same precision as the source 
data. 
• 
Parameters derived from actual elapsed sample collection times (e.g. tmax) will be reported with a precision of 2 decimal places.   


 
 
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For the reporting of descriptive statistics, the means and SD will be presented to one digit more precision than the source data. The 
minimum, median, and maximum will be presented to the same precision as the source data.  Coefficients of variation will always be 
reported to 1 decimal place. 
20.1. 
SERUM CONCENTRATIONS  
Subjects with partial data will be evaluated on a case-by-case basis to determine if sufficient data are available for reliable estimation of 
PK parameters. 
 
A listing of PK blood sample collection times as well as derived sampling time deviations will be provided. Plasma concentrations will 
be summarized for each treatment and measurement time using descriptive statistics including n, mean, SD, coefficient of variation 
(CV%), median, minimum, and maximum.  Concentration summaries by treatment and body weight category (Week 0 to Week 28 only) 
will also be provided. Concentration summaries by treatment and ADA status (binding and neutralizing) will also be provided. For these 
summaries, a subject’s ADA status will be classified 2 ways: (1) An Overall categorization will be used where a subject’s status will be 
classified as positive if they have a positive result at any time over 0- to 52-week measurement period; otherwise it will be classified as 
negative. (2) A by-time-point categorization will be used where a subject’s status will be classified at each time point based on whether 
they have a positive or negative result at that time point; if there is no antibody measurement at a time point or if the antibody result is 
missing or inconclusive, the last reliable result will be carried forward to this time point. 
Concentrations that are below the limit of quantitation (BLQ) will be treated as zero for the computation of descriptive statistics. Samples 
that are collected outside the protocol-specified windows (Table 1 of the protocol) will be excluded from descriptive statistics. A subject 
listing of all concentration-time data for each treatment will be presented.  For subjects who switch from Stelara to DMB-3115 treatment 
at Week 28, concentrations up to and including Week 28 will be summarized under Stelara treatment, but post-Week 28 concentrations 
will be listed and summarized separately. 
 
Figures of arithmetic mean concentration-time data (±SD on linear plot) will be presented for each treatment on linear and semi-
logarithmic scales for the 0- to 4-week period. Figures of arithmetic mean (±SD) concentration-time data will also be presented for each 
treatment on linear scale for the 0- to 52-week period (separate figures will show subjects who switched from Stelara to DMB-3115 at 
Week 28 either included or excluded for time points beyond Week 28). Similar figures will also be included which further subset these 
treatments by ADA status (binding and neutralizing). Arithmetic mean figures by treatment and body weight category (Week 0 to Week 
28) will also be provided. Individual subject concentration-time data will be graphically presented on linear and semi-logarithmic scales 
(0- to 4-week period) and linear scale (0- to 52-week period).  Individual concentrations which are BLQ will be displayed as zero in the 
graphic presentations on linear scale, but will not be plotted on semi-logarithmic scale.  Means which fall below the LLOQ will be 


 
 
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displayed as zero in the graphic presentations on linear scale, but will not be plotted on semi-logarithmic scale. 
Handling of the concentration-time profiles for statistical summaries with anomalous predose concentrations of greater than 5.00% of 
Cmax prior to the first dose will follow the handling conventions of the PK parameters as described in Section 20.2. 
20.2. 
SERUM PARAMETERS  
Pharmacokinetic parameters will be calculated for the first dose. For PK parameter calculations, predose samples that are BLQ or 
missing will be assigned a numerical value of zero.  Any other BLQ concentrations will be assigned a value of zero if they precede 
quantifiable samples in the initial portion of the profile.  A BLQ value that occurs between quantifiable data points, especially prior to 
Cmax, will be evaluated to determine if an assigned concentration of zero makes sense, or if exclusion of the data is warranted.  Following 
Cmax, BLQ values embedded between 2 quantifiable data points will be treated as missing when calculating PK parameters.  If a BLQ 
value occurs at the end of the collection interval (after the last quantifiable concentration), it will be treated as zero.  If consecutive BLQ 
concentrations are followed by quantifiable concentrations in the terminal portion of the concentration curve, these quantified values 
will be excluded from the PK analysis by setting them to missing, unless otherwise warranted by the concentration-time profile.  
Any anomalous concentration values observed prior to the first dose will be identified in the study report and used for the computation 
of PK parameters. If the anomalous concentration is greater than 5.00% of Cmax (when rounded to 3 significant digits), the PK parameters 
for the affected subject profile will be calculated and reported in the listing but excluded from statistical summaries and analyses.  
Similarly, PK concentrations for the affected profile will be excluded from statistical summaries. 
The following PK parameters will be estimated for the first dose (Week 0) by non-compartmental methods using actual elapsed time 
from dosing (rounded to 2 decimal places).  A minimum of 3 quantifiable concentration-time data points will be required for calculation 
of PK parameters). 
 
Cmax 
Maximum concentration, obtained directly from the observed concentration versus time data.  
tmax 
Time of maximum concentration, obtained directly from the observed concentration versus 
time data. 
AUC(w0-w4) 
Area under the concentration-time curve from Week 0 (predose) to Week 4, calculated by 
linear up/log down trapezoidal summation.  Actual elapsed time and associated concentration 
at Week 4 will be used for the calculation. If the Week-4 sample is collected outside the 
protocol-specified window (see Table 1 of protocol), the AUC(w0-w4) for the affected subject 
profile will be calculated and reported in the listing but excluded from statistical summaries 
and analyses. 


 
 
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Pharmacokinetic parameters except tmax will be summarized by treatment using descriptive statistics including n, mean, SD, CV%, 
median, minimum, maximum, geometric mean and geometric CV%.  For tmax, only n, median, minimum, and maximum will be 
presented.  Summaries by treatment and body weight category will also be provided. A subject listing of individual PK parameters for 
each treatment will be provided. 
Box plots of Cmax and AUC(w0-w4) versus treatment will be presented.  Figures by treatment and body weight category will also be 
provided. 
 
 


 
 
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21. DATA NOT SUMMARIZED OR PRESENTED 
The other variables and/or domains not summarized or presented are: 
• 
Comments 
• 
These domains and/or variables will not be summarized or presented, but will be available in the clinical study 
database, SDTM and/or ADaM datasets. 
22. REFERENCES  
• 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/WC500096793.pdf 
Little, R., & Yau, L. (1996). Intent-to-Treat Analysis for Longitudinal Studies with Drop-Outs. Biometrics , vol 52, 1324-1333. 
• 
UZA82634-DMB-3115-2_Protocol_Amendment_v1_4Jun21-0001 
• 
UZA82634_DMB-3115-2_CRF Finalt_V5.0. 
• 
(Van Buuren, 2012 cited by Patricia Berglund and Steven Heeringa in Multiple imputation using SAS 
2014.): 
 
 
 
 


 
 
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APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS 
 
 
   
DATES & TIMES 
Depending on data available, dates and times will take the DDMMMYYYY Thh:mm:ss. 
SPELLING FORMAT 
English US (or English UK)  
LISTINGS 
All listings will be ordered by the following (unless otherwise indicated in the template): 
• 
Center-subject ID,  
• 
Randomized treatment group (or treatment received if it’s a safety output)  
• 
Date (where applicable), 
• 
For listings where non-randomized subjects are included, these will appear in a category after the randomized treatment groups 
labeled ‘Not Randomized’. 
OUTPUT PRESENTATIONS 
The templates provided with this SAP describe the presentations for this study and therefore the format and content of the summary 
tables, figures and listings to be provided by 
 
All visit assessments will be presented according to the nominal visit name. 
 
 








 
 
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APPENDIX 3. SAMPLE CODES  
MULTIPLE IMPUTATIONS FOR DATASETS 
 
 
   
  
  
 
   
   
   
 
 
 
 
 
 
     
 
     
 
 
 
   
 
  
 
  
  
 
  
  
 
  
 
 
 
 
 
 


 
 
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SAMPLE CODES FOR PRIMARY EFFICACY(MULTIPLE IMPUTATIONS) 
 
 
 
 
     
  
 
     
 
     
   
     
  
 
    
 
 
 
 
 
      
 
      
 
            
 
 
      
 
      
 
      
 
      
 
 
 
 
      
 
      
 
       
 
 
      
 
      
 
      
 
      
 
 
 


 
 
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Sample codes mixed model