Conditions: Psoriasis
Keywords: Psoriasis Ustekinumab STELARA
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 44
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the efficacy and safety of ustekinumab in pediatric participants aged greater than or equal to (\>=) 6 through less than (\<) 12 years with moderate to severe chronic plaque psoriasis

Detailed description:
This is an open label (identity of study drug will be known to participant and study staff) and multicenter (when more than one hospital or medical school team work on a medical research study) study. The participant population will be comprised of boys and girls who have had a diagnosis of plaque psoriasis for at least 6 months prior to first study drug administration and who have moderate to severe disease defined by Psoriasis Area and Severity Index score (PASI) \>=12, Physician's Global Assessment (PGA) \>=3, and Body Surface Area (BSA) \>=10 percent (%). The study consists of Screening Phase (up to 10 weeks before administration of the study drug), Treatment Period (Week 0 up to Week 52) and Safety follow up (Week 56). Participants will be primarily evaluated for efficacy, pharmacokinetics (PK) and safety. Following completion of the Week 52 visit, participants who have had a beneficial response from ustekinumab treatment as determined by the investigator, and who have not yet reached the age of 12 years or older in countries where marketing authorization for ustekinumab has been granted for the treatment of psoriasis in adolescent participants (12-17 years), and are willing to continue ustekinumab treatment, may enter the long-term extension period (from Week 56 through Week 264) of the study.

Arms:
arm 1: Participants will receive 1 of the following dose levels depending on their weight: participants weighing less than (\<) 60 kg will receive Ustekinumab 0.75 milligram per kilogram (mg/kg); participants weighing greater than or equal to (\>=) 60 kg to less than or equal to (\<=) 100 kg will receive ustekinumab 45 mg; participants weighing \>100 kg will receive ustekinumab 90 mg, at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants who enter the long-term extension (LTE) period will continue receiving ustekinumab every 12 weeks (q12w) beginning at Week 56 up to Week 248.

Interventions: intervention 1: Ustekinumab 0.75 mg/kg intervention 2: Ustekinumab 45 mg intervention 3: Ustekinumab 90 mg
Intervention descriptions: intervention 1: Participants weighing less than (\<) 60 kilograms will receive ustekinumab 0.75 milligram per kilogram (mg/kg) at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 0.75 mg/kg up to Week 248. intervention 2: Participants weighing greater than or equal to (\>=) 60 kg to less than or equal to (\<=) 100 kg will receive ustekinumab 45 mg at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 45 mg up to Week 248. intervention 3: Participants weighing \>100 kg will receive ustekinumab 90 mg at Weeks 0 and 4 followed by every 12 weeks dosing with the last dose at Week 40. Eligible participants for LTE period will continue to receive ustekinumab 90 mg up to Week 248.

Protocol document:
Prot_002.pdf: 
1
Status: Approved, Date: 18 May 2017
Janssen Research & Development *
Clinical Protocol
A Phase 3 Open-label Study to Assess the Efficacy, Safety, and Pharmacokinetics of 
Subcutaneously Administered Ustekinumab in the Treatment of Moderate to Severe 
Chronic Plaque Psoriasis in Pediatric Subjects ≥6 to <12 Years of Age
Protocol CNTO1275PSO3013; Phase 3
AMENDMENT 1
STELARA® (ustekinumab)
*Janssen Research & Development is a global organization that operates through different legal entities in 
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development 
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen 
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Infectious Diseases BVBA; Janssen 
Sciences Ireland UC; or Janssen Research & Development, LLC. The term “sponsor” is used throughout 
the protocol to represent these various legal entities; the sponsor is identified on the Contact Information 
page that accompanies the protocol.  
EudraCT NUMBER:  2016-000121-40
Status:
Approved
Date:
18 May 2017
Prepared by:
Janssen Research & Development, LLC  
EDMS number:
EDMS-ERI-96462988
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT02698475


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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
PROTOCOL AMENDMENTS....................................................................................................................... 5
SYNOPSIS.................................................................................................................................................... 9
TIME AND EVENTS SCHEDULE .............................................................................................................. 14
ABBREVIATIONS AND DEFINITIONS OF TERMS.................................................................................. 17
1.
INTRODUCTION................................................................................................................................ 18
1.1.
Background .................................................................................................................................... 18
1.2.
Overall Rationale for the Study...................................................................................................... 19
1.3.
Clinical Studies............................................................................................................................... 19
1.3.1.
Efficacy and Safety in Adult Psoriasis Studies ........................................................................... 19
1.3.2.
Efficacy and Safety in Pediatric Psoriasis Subjects ≥12 to <18 Years of Age ........................... 20
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 22
2.1.
Objectives ...................................................................................................................................... 22
2.2.
Hypothesis ..................................................................................................................................... 22
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 23
3.1.
Overview of Study Design.............................................................................................................. 23
3.2.
Study Design Rationale.................................................................................................................. 25
4.
SUBJECT POPULATION.................................................................................................................. 27
4.1.
Inclusion Criteria ............................................................................................................................ 27
4.2.
Exclusion Criteria ........................................................................................................................... 30
4.3.
Prohibitions and Restrictions ......................................................................................................... 33
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 34
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 34
7.
TREATMENT COMPLIANCE............................................................................................................ 35
8.
PRESTUDY AND CONCOMITANT THERAPY ................................................................................ 35
8.1.
Topical Therapies for Psoriasis...................................................................................................... 35
8.2.
Phototherapy or Systemic Therapies for Psoriasis........................................................................ 36
8.3.
Concomitant Therapies for Conditions Other Than Psoriasis........................................................ 36
9.
STUDY EVALUATIONS .................................................................................................................... 37
9.1.
Study Procedures........................................................................................................................... 37
9.1.1.
Overview..................................................................................................................................... 37
9.1.2.
Screening Phase ........................................................................................................................ 38
9.1.3.
Open-Label Treatment Period (Week 0 to Week 52)................................................................. 38
9.1.4.
Safety Follow-up (Week 52 to Week 56).................................................................................... 39
9.1.5.
Long-term Extension (Week 56 to Week 264)............................................................................ 39
9.2.
Efficacy........................................................................................................................................... 39
9.2.1.
Blinded Efficacy Evaluator.......................................................................................................... 39
9.2.2.
Physician’s Global Assessment.................................................................................................. 40
9.2.3.
Psoriasis Area and Severity Index.............................................................................................. 40
9.2.4.
Children’s Dermatology Life Quality Index ................................................................................. 40


STELARA® (ustekinumab)
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9.2.5.
Endpoints.................................................................................................................................... 41
9.3.
Pharmacokinetics and Immunogenicity ......................................................................................... 41
9.3.1.
Evaluations ................................................................................................................................. 42
9.3.2.
Analytical Procedures................................................................................................................. 42
9.3.3.
Immunogenicity Assessments (Antibodies to Ustekinumab)...................................................... 42
9.4.
Biomarker Evaluations ................................................................................................................... 43
9.5.
Pharmacogenomic (DNA) Evaluations .......................................................................................... 43
9.6.
Safety Evaluations ......................................................................................................................... 43
9.7.
Sample Collection and Handling.................................................................................................... 45
10.
SUBJECT COMPLETION/WITHDRAWAL....................................................................................... 46
10.1.
Completion of Main Study.............................................................................................................. 46
10.2.
Completion of Long-term Extension............................................................................................... 46
10.3.
Discontinuation of Study Treatment............................................................................................... 46
10.4.
Withdrawal From the Study............................................................................................................ 47
11.
STATISTICAL METHODS................................................................................................................. 48
11.1.
Subject Information ........................................................................................................................ 48
11.2.
Sample Size Determination ........................................................................................................... 48
11.3.
Efficacy Analyses ........................................................................................................................... 49
11.3.1.
Data-Handling Rules................................................................................................................... 50
11.4.
Pharmacokinetic Analyses............................................................................................................. 50
11.5.
Pharmacokinetic/Pharmacodynamic Analyses.............................................................................. 51
11.6.
Immunogenicity Analyses .............................................................................................................. 51
11.7.
Biomarker Analyses ....................................................................................................................... 51
11.8.
Pharmacogenomic Analyses ......................................................................................................... 51
11.9.
Safety Analyses ............................................................................................................................. 51
11.10.
Data Monitoring Committee ........................................................................................................... 52
12.
ADVERSE EVENT REPORTING ...................................................................................................... 52
12.1.
Definitions ...................................................................................................................................... 53
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 53
12.1.2.
Attribution Definitions.................................................................................................................. 54
12.1.3.
Severity Criteria .......................................................................................................................... 54
12.2.
Special Reporting Situations.......................................................................................................... 55
12.3.
Procedures..................................................................................................................................... 55
12.3.1.
All Adverse Events...................................................................................................................... 55
12.3.2.
Serious Adverse Events ............................................................................................................. 56
12.3.3.
Pregnancy................................................................................................................................... 57
12.3.4.
Events of Special Interest........................................................................................................... 57
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 58
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 58
13.1.
Procedures..................................................................................................................................... 58
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 58
14.
STUDY DRUG INFORMATION......................................................................................................... 58
14.1.
Physical Description of Study Drug(s) ........................................................................................... 58
14.2.
Packaging ...................................................................................................................................... 58
14.3.
Labeling.......................................................................................................................................... 59
14.4.
Preparation, Handling, and Storage............................................................................................... 59
14.5.
Drug Accountability ........................................................................................................................ 59
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 60
16.
ETHICAL ASPECTS ......................................................................................................................... 60
16.1.
Study-Specific Design Considerations........................................................................................... 60
16.2.
Regulatory Ethics Compliance....................................................................................................... 61
16.2.1.
Investigator Responsibilities ....................................................................................................... 61


STELARA® (ustekinumab)
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16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 61
16.2.3.
Informed Consent ....................................................................................................................... 62
16.2.4.
Privacy of Personal Data ............................................................................................................ 64
16.2.5.
Long-Term Retention of Samples for Additional Future Research ............................................ 64
16.2.6.
Country Selection ....................................................................................................................... 65
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 65
17.1.
Protocol Amendments.................................................................................................................... 65
17.2.
Regulatory Documentation ............................................................................................................ 65
17.2.1.
Regulatory Approval/Notification ................................................................................................ 65
17.2.2.
Required Prestudy Documentation............................................................................................. 65
17.3.
Subject Identification, Enrollment, and Screening Logs ................................................................ 66
17.4.
Source Documentation................................................................................................................... 67
17.5.
Case Report Form Completion ...................................................................................................... 67
17.6.
Data Quality Assurance/Quality Control ........................................................................................ 68
17.7.
Record Retention ........................................................................................................................... 68
17.8.
Monitoring ...................................................................................................................................... 69
17.9.
Study Completion/Termination....................................................................................................... 70
17.9.1.
Study Completion ....................................................................................................................... 70
17.9.2.
Study Termination....................................................................................................................... 70
17.10.
On-Site Audits ................................................................................................................................ 70
17.11.
Use of Information and Publication................................................................................................ 71
REFERENCES............................................................................................................................................ 73
INVESTIGATOR AGREEMENT ................................................................................................................. 81
LIST OF ATTACHMENTS
Attachment 1:
QuantiFERON®-TB Gold Testing ............................................................................... 75
Attachment 2:
Tuberculin Skin Testing.............................................................................................. 77
Attachment 3:
Physician’s Global Assessment ................................................................................. 78
Attachment 4:
Psoriasis Area and Severity Index ............................................................................. 79
Attachment 5:
Children’s Dermatology Life Quality Index ................................................................. 80
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Time and Events Schedule for the Main Study (Week 0 to Week 56) ..................................... 14
Table 2:
Time and Events Schedule for the LTE Phase (Week 56 to Week 264).................................. 16
Table 3:
Volume of Blood to be Collected From Each Subject in the Main Study.................................. 37
FIGURES
Figure 1:
Study Schema for the Main Study (Week 0 through Week 56)................................................ 24


STELARA® (ustekinumab)
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PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
22 January 2016
Amendment 1
18 May 2017
Amendments below are listed beginning with the most recent amendment.
Amendment 1 (17 May 2017)
This amendment is considered 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.
The overall reason for the amendment: The overall reason for this amendment is to allow pediatric subjects who 
have demonstrated clinical benefit through Week 52 of the main study to continue receiving ustekinumab. 
Additionally, longer-term safety and efficacy data in this patient population will be collected.
Applicable Section(s)
Description of Change(s)
Rationale: Update the study design and other applicable sections to add a long-term extension (LTE) to the study. 
Synopsis;
3.1. Overview of 
Study Design;
Long-term Extension: 
Week 56 through 
Week 264
Main Study: Week 0 through Week 56
A database lock (DBL) will occur at end of the main study (Week 56; Section 17.9.1).
Long -term Extension: Week 56 through Week 264
Following completion of the Week 52 visit, subjects who have had a beneficial response 
from ustekinumab treatment as determined by the investigator, and who have not yet 
reached the age of 12 years or older in countries where marketing authorization for 
ustekinumab has been granted for the treatment of psoriasis in adolescent patients 
(12-17 years), and are willing to continue ustekinumab treatment, may enter the LTE of the 
study. For these subjects, the safety follow-up for the main study and the first ustekinumab 
administration of the LTE will be completed at the Week 56 visit.
At the Week 52 visit, subjects who have not had a beneficial response from ustekinumab 
treatment as determined by the investigator, or who have reached the age of 12 years or 
older in countries where marketing authorization for ustekinumab has been granted for the 
treatment of psoriasis in adolescent patients (12-17 years), will not enter the LTE of the 
study. The Week 56 safety-follow-up will be the end of study participation.
Subjects may continue to participate in the LTE until they reach Week 264 or one of the 
following occurs:

The subject turns 12 years of age and resides in a country where marketing 
authorization has been granted for ustekinumab treatment of psoriasis in adolescent 
patients 
Marketing authorization is obtained for ustekinumab for treatment of plaque 
psoriasis for patients ≥6 to <12 years of age in the subject’s country of residence
Marketing authorization is denied for ustekinumab for the treatment of plaque 
psoriasis for patients ≥6 to <12 years of age in the subject’s country of residence
A company decision is made to no longer pursue an indication in plaque psoriasis in 
the pediatric population (≥6 to <12 years of age) in the subject’s country of 
residence


STELARA® (ustekinumab)
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Approved, Date: 18 May 2017
Applicable Section(s)
Description of Change(s)
All assessments will be performed per the Time and Events Schedule (see Table 2).
During the LTE, consideration should be given to discontinue ustekinumab treatment in 
subjects who are non-responders (defined by PGA >3 at 2 consecutive visits). A DBL will 
occur at end of the LTE (Week 264; Section 17.9.1). Additional DBLs may occur at the 
Sponsor’s discretion.
Rationale: The overall reason for this amendment is to allow pediatric subjects who have demonstrated clinical 
benefit through Week 52 of the main study to continue receiving ustekinumab. Additionally, longer-term safety and 
efficacy data in this patient population will be collected.
3.2 Study Design 
Rationale; Study 
Phases
The addition of the LTE is to allow pediatric subjects who have demonstrated clinical 
benefit through Week 52 of the main study to continue receiving ustekinumab. 
Additionally, longer-term safety and efficacy data in this patient population will be 
collected.
Rationale: Table 2 has been added to the Time and Events Schedule to summarize the frequency and timing of 
study drug administration, ongoing subject reviews, and safety and efficacy assessments in subjects who enter the
LTE starting at the Week 56 study visit.
Time and Events 
Schedule; Table 2: 
Time and Events 
Schedule for the LTE 
Phase (Week 56 to 
Week 264)
(new table)
Table 2 has been added to the Time and Events Schedule and includes the following 
parameters to be completed during the LTE:
Study drug administration/site visit every 12 weeks
Body weight measured every 12 weeks
A urine pregnancy test for female subjects performed every 12 weeks
Adverse events and concomitant medications collected every 12 weeks
Subject vital signs to be taken every 12 weeks
Efficacy evaluation (PGA only) every 6 months
A complete physical examination once per year
Height measured once per year
Full chemistry and hematology test results obtained once per year
Rationale: To update the footnotes from the main study (Table 1) to accommodate instructions for the LTE 
(Table 2), for details related to subjects who enter the LTE of the study and receive ustekinumab treatment.
Time and Events 
Schedule; Table 2: 
Time and Events 
Schedule for the LTE 
Phase (Week 56 to 
Week 264); 
Footnotes a, d, f, and
g
a All procedures and evaluations are to be completed prior to study drug injection. For 
subjects in the LTE who decide to withdraw from study participation, or who discontinue 
treatment, the assessments (excluding study drug injection) for the Week 248 study visit 
will be performed.
d Efficacy assessments (PGA) should be performed by the investigator or any qualified 
healthcare provider at the study site.
f Subjects who discontinue study drug but do not terminate study participation will continue 
to return for protocol-specified procedures and evaluations for approximately 16 weeks 
(4 months) following the last dose of study drug. At the subject’s last study visit for the 
LTE prior to Week 248, the procedures and evaluations (excluding study drug injection) 
for Week 248 will be followed. If a subject discontinues study drug and terminates study 
participation, the procedures and evaluations (excluding study drug injection) for 
Week 248 will be performed at the current visit.
g Final LTE visit. The Week 264 visit is a follow-up safety visit that will be handled as a 
phone call.


STELARA® (ustekinumab)
Clinical Protocol CNTO1275PSO3013 Amendment 1
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Approved, Date: 18 May 2017
Applicable Section(s)
Description of Change(s)
Rationale: To update the dosing and administration of ustekinumab to subject during the LTE of the study.
6 Dosage and 
Administration
All subjects enrolled in the study will receive ustekinumab at Weeks 0 and 4 followed by 
q12w dosing. Subjects who enter the LTE will receive ustekinumab q12w beginning at 
Week 56 and continue according to criteria defined in Section 3.1.
Rationale: Update rules for use of topical medications as concomitant medication for psoriasis treatment during the 
LTE.
8.3 Concomitant 
Therapies for 
Conditions Other 
Than Psoriasis
During the LTE, the medication rules outlined above still apply except that all topical
therapies, with the exception of ultra-high potency corticosteroids are permitted for 
treatment of psoriasis.
Rationale: To update total blood volume collected from subjects during the LTE.
9.1.1 Overview
For subjects participating in the LTE, a maximum of 4 additional hematology samples and 
4 additional serum chemistry samples (2 mL per hematology sample and 2.5 mL per serum 
chemistry sample; total blood volume of 18 mL) will be collected.
9.1.1 Overview: 
Table 3: Volume of 
Blood to be Collected 
From Each Subject in 
the Main Study
Table 2 has been renumbered to Table 3 with the addition of the new Time and Events 
Schedule for the LTE (new Table 2). Additionally, the table title has been updated to 
reflect that the table covers blood volumes collected during the main study.
Rationale: Update study design and other applicable sections to add an LTE to the study.
9.1.5 Open-label 
Long-term Extension 
(Week 56 to 
Week 264)
(new section)
Following completion of the Week 52 visit, subjects who have had a beneficial response 
from ustekinumab treatment as determined by the investigator, and who have not yet 
reached the age of 12 years or older in countries where marketing authorization for 
ustekinumab has been granted for the treatment of psoriasis in adolescent patients 
(12-17 years), and are willing to continue ustekinumab treatment, may enter the LTE of the 
study. For these subjects, the safety follow up for the main study and the first ustekinumab 
administration of the LTE will be completed at the Week 56 visit.
Subjects may continue to participate in the LTE until they reach Week 264 or one of the 
following occurs:

The subject turns 12 years of age and resides in a country where marketing 
authorization has been granted for ustekinumab treatment of psoriasis in adolescent 
patients 

Marketing authorization is obtained for ustekinumab for treatment of plaque 
psoriasis for patients ≥6 to <12 years of age in the subject’s country of residence

Marketing authorization is denied for ustekinumab for the treatment of plaque 
psoriasis for patients ≥6 to <12 years of age in the subject’s country of residence

A company decision is made to no longer pursue an indication in plaque psoriasis 
in the pediatric population (≥6 to <12 years of age) in the subject’s country of 
residence
During the LTE, consideration should be given to discontinue ustekinumab treatment in 
any subjects who are non-responders (defined by PGA >3 at 2 consecutive visits). A DBL 
will occur at end of the LTE (Week 264; Section 17.9.1). Additional DBLs may occur at 
the Sponsor’s discretion.).
Rationale: To update performance of PGA assessments during the LTE.
9.2.1 Blinded 
Efficacy Evaluation
During the LTE, PGA assessments should be performed by the investigator or any 
qualified healthcare provider at the study site. When possible, all PGA assessments for a 
subject should be performed by the same assessor.


STELARA® (ustekinumab)
Clinical Protocol CNTO1275PSO3013 Amendment 1
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Approved, Date: 18 May 2017
Applicable Section(s)
Description of Change(s)
Rationale: To add the determination of study completion/withdrawal and discontinuation of study treatment for 
subjects who received ustekinumab during the LTE of the study.
10.2 Completion of 
Long-term Extension 
(new section)
A subject will be considered to have completed the LTE if he or she has completed all 
assessments up through Week 264. For subjects in the LTE who decide to withdraw from 
study participation, who discontinue treatment for any reason, or who become ineligible to 
continue to receive study drug (ie, due to the occurrence of one of the criteria listed in 
Section 3.1), the assessments (excluding study drug injection) for the Week 248 study visit 
will be performed.
10.3 Discontinuation 
of Study Treatment; 
Long-term extension 
(new section)
During the LTE, subjects who discontinue study drug but do not terminate study 
participation will continue to return for protocol-specified procedures and evaluations for 
approximately 16 weeks (4 months) following the last dose of study drug.  At the subject’s 
last study visit for the LTE, the procedures and evaluations (excluding study drug 
injection) for Week 248 will be followed. If a subject discontinues study drug and 
terminates study participation, the procedures and evaluations for Week 248 will be 
performed at the current visit.
During the LTE, consideration should also be given to discontinue ustekinumab treatment 
in any subjects who are non-responders (ie, defined by PGA >3 at 2 consecutive visits).
Rationale: To update the assessments that should be obtained for subjects who withdraw or discontinue early and
received ustekinumab during the LTE of the study.
10.4 
Withdrawal 
from Study
If a subject withdraws from the study prior to Week 52, the Week 52 assessments will be 
obtained. If a subject withdraws from the study before the end of the LTE, the Week 248 
assessments (excluding study drug injection) will be performed.
Rationale: To update the data handling rules regarding treatment failures or missing data for PGA scores after 
Week 52.
11.3.1 Data-Handling 
Rules
After Week 52, treatment failure rules or missing data imputations will not be applied for 
PGA scores.
Rationale: To update the volume of blood collected during the study phases.
16.1 Study-Specific 
Design 
Considerations
The total blood volume to be collected during the main study will be approximately 69.5 mL 
and during the LTE will be approximately 18 mL, which is considered to be within the 
normal range allowed for the pediatric population.
Rationale: To update the determination of study completion for subjects who entered the LTE of the study and 
received ustekinumab treatment.
17.9.1. Study 
Completion

The main study is considered completed when the safety follow-up for the last subject 
is completed at Week 56. 

The LTE is considered completed when all subjects have either terminated 
participation according to Section 3.1 or completed their follow-up at Week 264. 
Rationale: Minor errors were noted.
Throughout the 
protocol
Minor grammatical, formatting, or spelling changes were made.


STELARA® (ustekinumab)
Clinical Protocol CNTO1275PSO3013 Amendment 1
9
Approved, Date: 18 May 2017
SYNOPSIS
A Phase 3 Open-label Study to Assess the Efficacy, Safety, and Pharmacokinetics of Subcutaneously 
Administered Ustekinumab in the Treatment of Moderate to Severe Chronic Plaque Psoriasis in Pediatric 
Subjects ≥6 to <12 Years of Age
STELARA® (ustekinumab) is a fully human immunoglobulin G1 kappa monoclonal antibody (mAb) that 
binds both human interleukin (IL)-12 and IL-23 via a common IL-12/23p40 subunit. Ustekinumab 
neutralizes the activities of IL-12 and IL-23 by preventing these cytokines from binding to the IL-12 
receptor beta-1 receptor protein, which is expressed on the surface of immune cells.  The first approval of 
ustekinumab for the treatment of adult patients with chronic moderate to severe plaque psoriasis occurred 
in Canada (12 December 2008) and was based primarily on data from 2 global Phase 3 pivotal studies
(C0743T08 [PHOENIX 1] and C0743T09 [PHOENIX 2]), comprising 1,996 subjects. Both studies had 
long-term extensions for up to 5 years. Ustekinumab was subsequently approved in numerous other 
countries in North America, Europe, South America, and the Asia-Pacific region, for the treatment of 
adult patients with chronic moderate to severe plaque psoriasis and/or psoriatic arthritis (PsA). 
Ustekinumab has also been approved for the treatment of pediatric moderate to severe psoriasis in 
patients ≥12 years to <18 years in Europe and other countries, based primarily on data from the completed 
Phase 3 CADMUS study. Extensive postmarketing experience also supports the favorable safety profile 
of ustekinumab established to date.
OBJECTIVES AND HYPOTHESIS
The primary and major secondary objectives of this study are:
Primary Objective

To evaluate the efficacy and safety of ustekinumab in pediatric subjects aged ≥6 through <12 years 
with moderate to severe chronic plaque psoriasis.
Major Secondary Objectives

To evaluate the pharmacokinetics (PK) of ustekinumab in pediatric subjects aged ≥6 through 
<12 years with moderate to severe chronic plaque psoriasis.

Evaluate the effect of ustekinumab on the dermatologic health-related quality of life in pediatric 
subjects aged ≥6 through <12 years with moderate to severe chronic plaque psoriasis.

Evaluate the immunogenicity of ustekinumab in pediatric subjects aged ≥6 through <12 years with 
moderate to severe chronic plaque psoriasis.
Hypothesis
There will be no formal hypothesis testing performed. Efficacy and safety of ustekinumab in pediatric 
subjects ≥6 through <12 years of age with moderate to severe chronic plaque psoriasis will be evaluated 
using descriptive statistics. The PK of ustekinumab in pediatric subjects will also be evaluated using 
descriptive statistics of serum ustekinumab concentration and population PK analyses. 
OVERVIEW OF STUDY DESIGN
Main Study 
This is an open-label multicenter study of ustekinumab in pediatric subjects ≥6 to <12 years of age with 
moderate to severe chronic plaque psoriasis. At least 40 subjects will receive a weight-based dose of 
ustekinumab administered subcutaneously at Weeks 0 and 4 followed by dose administrations every 
12 weeks (q12w) through Week 40. Subject weight will be measured at each visit and the dose of 


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ustekinumab will be adjusted accordingly. Visits will be every 4 weeks (q4w) through Week 16, then 
q12w through Week 52. Efficacy assessments will be collected through Week 52. Subjects will have a 
final safety telephone follow-up at Week 56. A single database lock (DBL) will occur at Week 56.
All assessments will be performed according to the Time and Events Schedule. Unblinded safety data will 
be routinely evaluated by the study medical monitor.
Long -term Extension
Following completion of the Week 52 visit, subjects who have had a beneficial response from 
ustekinumab treatment as determined by the investigator, and who have not yet reached the age of 
12 years or older in countries where marketing authorization for ustekinumab has been granted for the 
treatment of psoriasis in adolescent patients (12-17 years), and are willing to continue ustekinumab 
treatment, may enter the LTE of the study. For these subjects, the safety follow up for the main study and 
the first ustekinumab administration of the LTE will be completed at the Week 56 visit.
At the Week 52 visit, subjects who have not had a beneficial response from ustekinumab treatment as 
determined by the investigator, or who have reached the age of 12 years or older in countries where 
marketing authorization for ustekinumab has been granted for the treatment of psoriasis in adolescent 
patients (12-17 years), will not enter the LTE of the study. The Week 56 safety-follow-up will be the end 
of study participation.
Subjects may continue to participate in the LTE until they reach Week 264 or one of the following occurs:

The subject turns 12 years of age and resides in a country where marketing authorization has been 
granted for ustekinumab treatment of psoriasis in adolescent patients  

Marketing authorization is obtained for ustekinumab for treatment of plaque psoriasis for patients ≥6 
to <12 years of age in the subject’s country of residence

Marketing authorization is denied for ustekinumab for the treatment of plaque psoriasis for patients 
≥6 to <12 years of age in the subject’s country of residence

A company decision is made to no longer pursue an indication in plaque psoriasis in the pediatric 
population (≥6 to <12 years of age) in the subject’s country of residence 
All assessments will be performed per the Time and Events Schedule (see Table 2).
During the LTE, consideration should be given to discontinue ustekinumab treatment in subjects who are 
non-responders (defined by PGA >3 at 2 consecutive visits). A DBL will occur at end of the LTE 
(Week 264; Section 17.9.1). Additional DBLs may occur at the Sponsor’s discretion.
SUBJECT POPULATION
The subject population will comprise boys and girls ≥6 to <12 years of age with moderate to severe 
chronic plaque psoriasis. Subjects must have had a diagnosis of plaque psoriasis for at least 6 months 
prior to first study drug administration and have moderate to severe disease defined by Psoriasis Area and 
Severity Index score (PASI) ≥12, Physician’s Global Assessment (PGA) ≥3, and body surface area (BSA)
≥10%.


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DOSAGE AND ADMINISTRATION
All subjects enrolled in the study will receive ustekinumab at Weeks 0 and 4 followed by q12w dosing 
with the last dose at Week 40. Subject weight will be measured at each visit and the dose of ustekinumab 
will be adjusted accordingly. Subjects will receive 1 of the following dose levels:

Weight <60 kg:  0.75 mg/kg

Weight ≥60 kg to ≤100 kg:  45 mg

Weight >100 kg:  90 mg
EFFICACY EVALUATIONS/ENDPOINTS
Efficacy evaluations chosen for this study are consistent with applicable US and EU regulatory guidance
and precedent established in previous studies of therapeutic biologic agents for the treatment of psoriasis.
Patient-reported outcomes (PROs) chosen for this study are also consistent with clinically relevant
measurements that are accepted in the medical literature for other studies in psoriasis and applicable 
US/EU regulatory guidance documents. Psoriasis response evaluations include:

Physician’s Global Assessment (PGA)

Psoriasis Area and Severity Index (PASI)

Children’s Dermatology Life Quality Index (CDLQI; PRO)
Given the open-label study design, PASI and PGA assessments will be performed by a blinded evaluator.
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Venous blood samples will be collected for the measurement of serum ustekinumab concentrations and 
detection of antibodies to ustekinumab at the timepoints presented in the Time and Events Schedule. 
Serum samples will also be collected at the final visit from subjects who terminate study participation 
early.
BIOMARKER EVALUATIONS
Biomarker assessments will include the evaluation of relevant serum markers.
PHARMACOGENOMIC (DNA) EVALUATIONS
A one-time swab collection for genetic and epigenetic analyses will be collected from those subjects (or 
their legally acceptable guardian) who sign a separate consent form to participate in the 
pharmacogenomics assessment.
SAFETY EVALUATION
Safety and tolerability will be assessed by monitoring AEs, clinical laboratory tests, vital signs, physical 
examinations, concomitant medication review, injection site evaluations, observations for allergic 
reactions, and assessments for early detection of active tuberculosis.
STATISTICAL METHODS
No formal hypothesis testing will be conducted. Data will be summarized using descriptive statistics. 
Continuous variables will be summarized using the number of observations, mean, standard deviation 
(SD), median, range, and interquartile range as appropriate. Categorical values will be summarized using 
the number of observations and percentages as appropriate. Graphical data displays may also be used to 
summarize the data.


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Subject baseline data, demographic and baseline clinical disease characteristics will be summarized. The 
baseline measurement is defined as the closest measurement taken at or before Week 0.
Safety and efficacy analysis will include enrolled subjects who receive at least 1 dose administration of
ustekinumab.
Sample Size Determination
The sample size of 40 was determined based on both efficacy and PK assessments. The primary objective 
is to evaluate the efficacy and safety of ustekinumab for pediatric subjects aged ≥6 to <12 years with 
moderate to severe chronic plaque psoriasis and 1 of the major secondary objective is to evaluate the 
pharmacokinetics of ustekinumab for this population. To support these objectives, a sample size of 40 
subjects was chosen. For the efficacy assessment, no formal hypothesis testing will be performed. 
However, the observed response rates and its 95% confidence interval of PGA of cleared (0) or minimal 
(1) at Week 12 will be provided. A sample size of 40 will provide a 95% confidence interval (50%, 80%), 
if the observed response rate is 65%.
To assess the pharmacokinetics of ustekinumab in this pediatric population, the sample size evaluation 
was based on simulations with a population PK model developed from Studies C0743T08, C0743T09, 
and CADMUS. The PK in pediatric subjects was simulated using the body weight distribution sampled 
with replacement from the National Health and Nutrition Examination Survey (NHANES) III growth 
database. A total of 300 replicates of the planned study design, including the PK sampling scheme shown 
in the Time and Events Schedule, were simulated and subsequently the population PK parameters were 
re-estimated for each replicate. The precisions to estimate the CL/F and V/F were calculated. The 
precisions of CL/F estimates with 30 and 40 subjects were 9.4% and 8.1%, respectively, which are lower 
than 20% and generally considered appropriate. The precisions of V/F estimates with 30 and 40 subjects 
were 10.4% and 9.2%, respectively. Considering potentially higher variability in pediatric subjects ≥6 to 
<12 years of age than the adolescent and adult populations, at least 40 subjects are planned to be enrolled 
to provide adequate data to characterize PK of ustekinumab in the planned study population.
Efficacy Analyses 
Efficacy results will be summarized for all subjects enrolled in the study and 95% confidence intervals 
will be calculated for the primary and major secondary efficacy endpoints.
Primary Endpoints

The proportion of subjects with a PGA of cleared (0) or minimal (1) at Week 12.
Major Secondary Endpoints

Serum ustekinumab concentrations will be summarized over time to assess the PK of ustekinumab.

The proportions of subjects who achieve a ≥75% improvement in PASI from baseline at Week 12. 

The change in CDLQI from baseline at Week 12.

The proportions of subjects who achieve a ≥90% improvement in PASI from baseline at Week 12. 
Other Endpoints
In addition to the primary and major secondary endpoint analyses, the following efficacy endpoints will 
be summarized:

The proportions of subjects achieving a PGA score of cleared (0), the proportion of subjects 
achieving a PGA score of cleared (0) or minimal (1), and the proportion of subjects achieving a PGA 
score of mild or better (≤2) over time.


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
The proportions of subjects who achieve PASI 50, PASI 75, PASI 90, and PASI 100 responses over 
time.

The percent improvement from baseline in PASI over time.

The change from baseline in CDLQI over time.

The proportion of subjects with CDLQI = 0 or 1 over time.
Other Analyses
The incidence and titers of antibodies to ustekinumab will be summarized by treatment group over time. 
Safety Analyses
Safety will be assessed by analyses of rates and type of adverse events (AEs), serious AEs, reasonably 
related AEs, injection-site reactions, infections, and AEs of psoriasis. Safety assessments will also include 
analyses of laboratory parameters and change from baseline in laboratory parameters (hematology and 
chemistry) and rates of markedly abnormal laboratory parameters (hematology and chemistry).


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TIME AND EVENTS SCHEDULE 
Table 1:
Time and Events Schedule for the Main Study (Week 0 to Week 56)
Screening
Treatment Periodk
Safety   
Follow 
up
Week
≤10 Weeks
0
4
8
12
16
28
40
52
56a
Study Procedures
Screening/Administrative
Informed consent/assent
X
Demographics
X
Medical History
X
Inclusion/exclusion criteriab
X
X
Body surface area (BSA)% psoriasis 
skin involvement
X
X
Study Drug Administration
Study drug administrationc
X
X
X
X
X
Safety Assessments
Physical examination
X
X
Vital signs
X
X
X
X
X
X
X
X
X
Height
X
X
X
X
X
Weight
X
X
X
X
X
X
QuantiFERON-TB® Gold testingd
X
Tuberculosis Intradermal Skin Testd
X
Urine pregnancy test, qualitativee
X
X
X
X
X
X
Full chemistry
X
X
X
X
X
Hematology
X
X
X
X
X
Serum varicella and measles antibody 
titers
X
Hep B Surf Ab (HBsAb)
X
Hepatitis B Core Antibody (HBcAb)
X
Hepatitis C Antibody (HCVAb)
X
HIV
X
Ongoing Subject Review
Concomitant medication review
X
X
X
X
X
X
X
X
X
X
Adverse event (AE) reviewf
X
X
X
X
X
X
X
X
X
X
Efficacy Assessments
Physician’s Global Assessment (PGA)g
X
X
X
X
X
X
X
X
X
Psoriasis Area and Severity Index 
(PASI)g
X
X
X
X
X
X
X
X
X
Children’s Dermatology Life Quality 
Index (CDLQI)h
X
X
X
X
X
Pharmacokinetics/Immunogenicityi
Serum ustekinumab concentration
X
X
X
X
X
X
X
Antibodies to ustekinumab
X
X
X
X
Biomarkers
Serum sample (eg, for IL-17 
quantification)
X
X
X


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Table 1:
Time and Events Schedule for the Main Study (Week 0 to Week 56)
Screening
Treatment Periodk
Safety   
Follow 
up
Week
≤10 Weeks
0
4
8
12
16
28
40
52
56a
Study Procedures
Pharmacogenomics (DNA)j
Buccal swab sample collection
X
a Telephone follow-up (only for subjects who will not enter the LTE phase).
b Minimum criteria for the availability of documentation supporting the eligibility criteria are described in Section 17.4, 
Source Documentation. 
c All procedures and evaluations are to be completed prior to study drug injection. For subjects who withdraw from study 
participation, every effort should be made to conduct final efficacy and safety assessments at Week 52.
d All subjects will receive QuantiFERON-TB® Gold testing and those subjects who are positive or have 2 indeterminate 
results will be excluded from the study. In countries where QuantiFERON-TB Gold test is not registered/approved, 
tuberculin skin testing will also be required.
e Urine pregnancy test to be conducted for girls of childbearing potential.
f Includes TB evaluation. Refer to the Early Detection Of Active Tuberculosis text in Section 9.6 for a complete 
description of this TB evaluation and the subsequent actions required based upon the results of this evaluation.
g PASI and PGA to be performed by a blinded efficacy evaluator.
h Performed prior to any tests, procedures, or other consultations (PASI, PGA) for that visit.
i All blood samples must be collected before study drug administration at visits when a study drug administration is 
scheduled. Details will be provided in the Laboratory Manual.
j Buccal swab for pharmacogenomics or epigenomics analysis will be collected only from subjects from whom separate
informed consent indicating willingness to participate in this optional component of the study has been obtained.
k Subjects who discontinue study drug but do not terminate study participation will continue to return for protocol-
specified procedures and evaluations for approximately 16 weeks (4 months) following the last dose of study drug. At the 
subject’s last study visit prior to Week 52, the procedures and evaluations for Week 52 should be followed. If a subject 
discontinues study drug and terminates study participation prior to Week 52, the procedures and evaluations for Week 52 
should be performed at the last visit.


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Table 2:
Time and Events Schedule for the Long-term Extension (Week 56 to Week 264)
Long-term Extensionf
Week
56
68
80
92
104
116
128
140
152
164
176
188
200
212
224
236
248
264g
Study Procedures
Study Drug Administration
Study drug administrationa
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety Assessments
Physical examination
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
X
X
X
Weight
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine pregnancy test, qualitativeb
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Full chemistrye
X
X
X
X
Hematologye
X
X
X
X
Ongoing Subject Review
Concomitant medication review
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse event (AE) reviewc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Efficacy Assessments
Physician’s Global Assessment (PGA)d
X
X
X
X
X
X
X
X
a All procedures and evaluations are to be completed prior to study drug injection. For subjects in the LTE who decide to withdraw from study participation, or who discontinue treatment, the 
assessments (excluding study drug injection) for the Week 248 study visit will be performed.
b Urine pregnancy test to be conducted for girls of childbearing potential.
c Includes TB evaluation. Refer to the Early Detection Of Active Tuberculosis text in Section 9.6.
d Efficacy assessments (PGA) should be performed by the investigator or any qualified healthcare provider at the study site.
e All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled. Details will be provided in the Laboratory Manual.
f Subjects who discontinue study drug but do not terminate study participation will continue to return for protocol-specified procedures and evaluations for approximately 16 weeks (4 months) 
following the last dose of study drug. At the subject’s last study visit for the LTE prior to Week 248, the procedures and evaluations (excluding study drug injection) for Week 248 will be followed. If 
a subject discontinues study drug and terminates study participation, the procedures and evaluations (excluding study drug injection) for Week 248 will be performed at the current visit.
g Final LTE visit. The Week 264 visit is a follow-up safety visit that will be handled as a phone call.


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ABBREVIATIONS AND DEFINITIONS OF TERMS
AE
adverse event
ALT
alanine aminotransferase
AST
aspartate aminotransferase
BCG
bacille Calmette-Guerin vaccine
BQL
below the lowest quantifiable sample concentration of the assay
BSA
body surface area
CADMUS
A Phase 3 Multicenter, Randomized, Double-Blind, Placebo-controlled Study Evaluating the 
Efficacy and Safety of Ustekinumab in the Treatment of ADolescent Subjects with Moderate to 
Severe Plaque-type psoriasis
CDLQI
Children’s Dermatology Life Quality Index
CL/F
apparent clearance
CRF
case report form
eDC
electronic data capture
EudraCT
European Clinical Trials Database
FVP
final vialed product
GCP
Good Clinical Practice
HBsAg
HBV surface antigen
HBV
hepatitis B virus
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IgG1k
immunoglobulin G1 kappa
IL
interleukin
IL-12Rb1
interleukin-12 receptor beta 1
IM
intramuscular
IRB
Institutional Review Board
IV
intravenous
IWRS
interactive web response system
LTE
Long-term extension
mAb
monoclonal antibody
MTX
methotrexate
NAbs
neutralizing antibodies 
PASI
Psoriasis Area and Severity Index
PD
pharmacodynamics(s)
PGA
Physician’s Global Assessment
PHOENIX 1
A Phase 3, multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy 
and safety of CNTO 1275 in the treatment of subjects with moderate to severe plaque-type 
psoriasis followed by long-term extension
PHOENIX 2
A Phase 3 multicenter, randomized, double-blind, placebo-controlled trial evaluating the efficacy 
and safety of CNTO 1275 in the treatment of subjects with moderate to severe plaque-type 
psoriasis followed by long-term extension 2
PK
pharmacokinetic(s)
PO
by mouth (per OS)
PQC
product quality compliant
PRO
patient-reported outcome(s)
PsA
psoriatic arthritis
q12w
every 12 weeks
SAE
serious adverse event
SC
subcutaneous
SD
standard deviation
TB
tuberculosis
V/F
apparent volume of distribution


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1.
INTRODUCTION
STELARA® (ustekinumab) is a fully human immunoglobulin G1 kappa (IgG1) monoclonal 
antibody (mAb) that binds both human interleukin (IL)-12 and IL-23 via a common IL-12/23p40 
subunit. Ustekinumab neutralizes the activities of IL-12 and IL-23 by preventing these cytokines 
from binding to the IL-12 receptor beta-1 receptor protein, which is expressed on the surface of 
immune cells. Abnormal regulation of IL-12 and IL-23 has been associated with multiple 
immune-mediated diseases, including psoriasis, and binding the shared IL-12/23p40 subunit may 
provide effective therapy in psoriasis. Ustekinumab is being developed by Janssen Research & 
Development.
The first approval of ustekinumab for the treatment of adult patients with chronic moderate to 
severe plaque psoriasis occurred in Canada (12 December 2008) and was based primarily on data 
from 2 global Phase 3 pivotal studies (C0743T08 [PHOENIX 1] and C0743T09 [PHOENIX 2]), 
comprising 1,996 subjects. Both studies had long-term extensions for up to 5 years. Ustekinumab 
was subsequently approved in numerous other countries in North America, Europe, South 
America, and the Asia-Pacific region, for the treatment of adult patients with chronic moderate to 
severe plaque psoriasis and/or psoriatic arthritis (PsA). Extensive postmarketing experience also 
supports the favorable benefit-risk profile of ustekinumab established to date. Ustekinumab is 
also approved for the treatment of pediatric psoriasis in patients ≥12 years to <18 years in Europe 
and other countries based on the CNTO1275PSO3006 (CADMUS) study in 110 subjects. 
For the most accurate and current information regarding the efficacy and safety of ustekinumab, 
refer to the latest version of the Investigator's Brochure for ustekinumab.
The term "Sponsor" used throughout this document refers to the entities listed in the Contact 
Information page(s), which will be provided as a separate document.
1.1.
Background
Psoriasis is a common chronic skin disease, characterized by the infiltration of inflammatory 
cells into the skin and excessive keratinocyte cellular proliferation, producing raised, 
well-demarcated erythematous lesions/plaques that significantly impacts patient quality of 
life.6,16 The pathogenesis of psoriasis involves environmental factors and immune dysregulation 
in genetically-predisposed individuals.10 The proinflammatory IL-12/T-helper (Th)1 and IL-23/ 
Th17 pathways are upregulated in psoriatic lesions.20,13 Ustekinumab is a fully human 
immunoglobulin G1 kappa monoclonal antibody to human IL-12/23p40 that binds with 
specificity to human IL-12 and IL-23 and neutralizes their bioactivity by preventing these 
cytokines from binding to specific receptors expressed on the surface of immune cells. 
Ustekinumab has been shown to be an effective treatment and has a favorable benefit risk profile 
for adult11,15and pediatric psoriasis patients age 12 and older.9
To assess potential risks in pediatric patients, toxicity studies in juvenile cynomolgus monkeys 
and developmental toxicity studies using pregnant monkeys have been performed. Ustekinumab
was well tolerated in these studies following weekly intravenous (IV) injection or twice weekly 
SC injection at doses up to 45 mg/kg. No ustekinumab related adverse effects were noted in 


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clinical pathology and histopathology evaluations and no evidence of immunotoxicity was 
observed. Additionally, there was no evidence of teratogenicity or developmental toxicity in 
fetuses or newborn monkeys who were exposed to ustekinumab as a result of ustekinumab 
administration in utero.
1.2.
Overall Rationale for the Study
Ustekinumab has been approved for the treatment of adult psoriasis in numerous countries 
beginning in 2008, and was recently approved for use in adolescent psoriasis patients age 12 and 
older in the EU and Canada based primarily on the results from the completed CADMUS study. 
The objectives of this clinical study are to evaluate the efficacy and safety of ustekinumab in 
pediatric subjects aged ≥6 to <12 years, and to determine if the weight based standard dosage 
being studied provides appropriate ustekinumab exposure in this age group. Determining that 
pediatric patients aged ≥6 to <12 receiving a weight based standard dosage are exposed to 
comparable levels of ustekinumab as adults is important for extrapolating the extensive and 
longer term safety data already available from the adult ustekinumab clinical experience to this 
pediatric population.
Clinical studies of adult and adolescent patients with moderate to severe psoriasis completed to 
date have demonstrated consistently low and predictable placebo response rates, suggesting that 
the efficacy of ustekinumab can be accurately assessed in the absence of a placebo control group. 
Therefore, this clinical study will utilize an open-label design. This approach accomplishes the 
scientific objectives of assessing ustekinumab efficacy, safety and pharmacokinetics (PK) in the 
population of interest, while also allowing all subjects to benefit from active treatment for the 
entire 52-week planned treatment duration. To help improve objectivity, given the open-label 
design, efficacy assessments will be performed by a blinded evaluator.
1.3.
Clinical Studies
As of 31 December 2014, a total of 30 clinical interventional studies of ustekinumab have been 
completed or are ongoing in the following indications, psoriasis, PsA, Crohn’s disease, 
rheumatoid arthritis, multiple sclerosis, sarcoidosis, primary biliary cirrhosis, axial 
spondyloarthritis, ulcerative colitis, systemic lupus erythematosus as well as in healthy subjects.
The development in rheumatoid arthritis, multiple sclerosis, sarcoidosis, and primary biliary 
cirrhosis are no longer being pursued due to a lack of efficacy.
The details of completed clinical studies or ongoing blinded clinical studies of ustekinumab can 
be found in the latest version of the Investigator's Brochure for ustekinumab.
1.3.1.
Efficacy and Safety in Adult Psoriasis Studies
Two placebo controlled Phase 3 studies, PHOENIX 1 (C0743T08)11 and PHOENIX 2 
(C0743T09)15 evaluated the efficacy of 2 dosages for the treatment of moderate to severe 
psoriasis:

45 mg at Week 0 and Week 4, followed by every 12 weeks (q12w) dosing;

90 mg at Week 0 and Week 4, followed by q12w dosing.


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These dosages led to a statistically significant, rapid onset of efficacy. High proportions of 
subjects (66.4% to 75.7% across ustekinumab groups in each study) achieved a Psoriasis Area 
and Severity Index (PASI) 75 response at Week 12 (the primary endpoint). With maintenance 
dosing, response rates continued to improve with consistent results across both studies at 
Week 28. While the 45 mg and 90 mg regimens both resulted in high levels of efficacy, the 
90 mg dosing regimen achieved approximately 8% to 10% higher PASI 75 response rates than 
the 45 mg dosing regimen by Week 28, which generally persisted over time.  
In both PHOENIX 1 and PHOENIX 2, subjects were followed in an open-label long-term 
extension for up to 5 years. In the overall population, PASI 50, PASI 75, and PASI 90 response 
rates were generally stable from Week 76 (PHOENIX 1) and Week 52 (PHOENIX 2) through 
Week 244 in both dose groups. Results suggested that with continuous maintenance treatment 
(ie, q12w or q8w), clinical response is sustained through the final treatment visit in the overall 
population treated with ustekinumab.
In both studies, ustekinumab was generally well tolerated. Through Week 12, adverse event (AE)
rates, AE profiles, and rates of AEs leading to study drug discontinuation in each of the 
ustekinumab treatment groups were generally comparable to those observed in the placebo 
group. Through the controlled and uncontrolled portions of the study, ustekinumab continued to 
be generally well tolerated with no apparent dose effect on safety evident between the 45 mg 
group and the 90 mg group.
Analyses of the 5-Year Psoriasis Safety Experience showed that follow-up-adjusted rates of 
serious infections, malignancies (nonmelanoma skin cancer [NMSC] and malignancies other 
than NMSC), and major adverse cardiovascular event (MACE) did not appear to increase over
time in the by-year analysis. The rates of these events were also lower than or consistent with
what would be expected from the general US population and/or the psoriasis population. These 
observations suggest that rates of these targeted AEs remain stable over time, and do not reveal 
evidence of risks associated with increasing duration of ustekinumab exposure.
1.3.2.
Efficacy and Safety in Pediatric Psoriasis Subjects ≥12 to <18 Years 
of Age
The first of 2 planned Phase 3 clinical studies of ustekinumab in pediatric psoriasis 
(CNTO1275PSO3006, [CADMUS]) has been completed. The CADMUS study was a 
randomized, double-blind, placebo-controlled, parallel group, multicenter 3-arm study conducted 
at sites in Europe and Canada. Subjects were randomized 2:2:1:1 to receive SC injections of the 
ustekinumab half-standard dosage, the ustekinumab standard dosage, or placebo and received 
their assigned treatment at Week 0 and Week 4 followed by q12w doses with the last dose at 
Week 40. Subjects in the placebo group were randomized at baseline to later crossover to either 
ustekinumab half-standard dosage or ustekinumab standard dosage at Weeks 12 and 16 followed 
by q12w dosing with the last dose at Week 40. The subject population was comprised of 
110 adolescent subjects ≥12 to <18 years of age who had a diagnosis of plaque-type psoriasis for 
at least 6 months prior to first study drug administration and who had moderate to severe disease 


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defined by PASI ≥12, Physician’s Global Assessment (PGA) ≥3, and body surface area (BSA) 
involvement ≥10%.
CADMUS studied 2 distinct weight-based ustekinumab dosages: a “standard dosage”, and a 
“half-standard dosage”. For the “standard dosage”, fixed doses of 45 mg for pediatric subjects 
weighing >60 kg to ≤100 kg and 90 mg for those weighing >100 kg, identical to adults, were 
utilized. For subjects weighing ≤60 kg, a weight adjusted dose of 0.75 mg/kg (obtained by 
adjusting the 45 mg adult dose by a body weight of 60 kg [45/60 = 0.75]) was utilized. 
Additionally, a “half-standard” dosage (ie, weight-based dose of 0.375 mg/kg for subjects 
weighing ≤60 kg, fixed dose of 22.5 mg for those weighing >60 kg to ≤100 kg, and a fixed dose 
of 45 mg for those weighing >100 kg) was also included, to allow for a more robust 
characterization of the dose-response relationship of ustekinumab in pediatric subjects and 
identification of an appropriate dosage for pediatric use.
Baseline demographics and disease characteristics were well-balanced across the CADMUS 
treatment groups. Mean age at baseline was 15 years and mean body weight was 65 kg. All of 
the CADMUS primary and major secondary efficacy endpoints were met. Significantly greater 
proportions of subjects in the half-standard and standard dosage groups achieved PGA scores of 
cleared (0) or minimal (1) at Week 12 (67.6% and 69.4%, respectively) compared with subjects 
in the placebo group (5.4%; p<0.001 for both ustekinumab dosage groups versus placebo).9
Significantly greater proportions of subjects in each of the ustekinumab dosage groups achieved 
PASI 75 and PASI 90 response, as well as a meaningful improvement in the Children’s 
Dermatology Life Quality Index (CDLQI) at Week 12. During the 12-week placebo controlled 
period, outcomes were generally comparable between the ustekinumab half-standard and 
standard dosage groups, and each ustekinumab dosage group was significantly better than 
placebo. However, differences in responses between the 2 ustekinumab dosage groups, favoring 
the standard dosage, were observed with more stringent efficacy criteria, including PGA scores 
of 0 and PASI 90 response at Week 12. Through Week 52, efficacy results were generally better 
with the standard dosage group relative to the half standard dosage group across most endpoints. 
Responses were better sustained through Week 52 over the 12-week dose interval in the standard 
dosage group whereas, a modest loss of efficacy was more frequently observed toward the end of 
the dose interval in the half-standard dosage group.  
Overall, dose-proportionality in serum ustekinumab concentration was observed when 
comparing mean or median serum ustekinumab concentrations through Week 52 between the 
half-standard dosage and standard dosage groups. A higher proportion of subjects with trough 
serum ustekinumab concentrations below the lowest quantifiable sample concentration of the 
assay (BQL; <0.1688 μg/mL) was observed in the half-standard dosage group (range: 21.7% to 
54.2%) compared with the standard dosage group (range: 6.3% to 16.1%). In addition, the 
standard dosage of ustekinumab in pediatric subjects produced comparable systemic drug 
exposure to that in adult subjects with body weight ≤100 kg who received the approved 45 mg 
fixed dose, whereas pediatric subjects treated with half-standard dosage had generally lower 
systemic exposure than adults. The comparability of exposure and efficacy responses between 


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the standard dosage in pediatric subjects and the approved adult dosage in adults confirms the 
similarity in the exposure-response relationship of ustekinumab in the 2 populations. 
Relative to the safety profile observed in the adult psoriasis and PsA populations treated with
ustekinumab, no new safety issues were identified in the adolescent subjects studied in 
CADMUS. The proportions of treated subjects reporting AEs and the AE terms were similar 
across the ustekinumab dosage groups and the placebo group through Week 12. No subject 
discontinued study drug due to an AE during the 12-week placebo-controlled period. The 
proportions of treated subjects reporting serious adverse event (SAEs) were low in all treatment 
groups during the placebo-controlled period; there was 1 SAE of worsening of psoriasis in a 
subject in the half-standard dosage group. Through Week 60, 6 SAEs were reported (including 
leukopenia, injury, psoriasis, pyelonephritis, dermatitis contact, ear infection), 5 were in the 
half-standard dosage group. Two of the SAEs (1 each in the half-standard dosage group and the 
standard dosage group) were considered infections. There was 1 death associated with injuries 
sustained in a motor vehicle accident. There were no cases of tuberculosis (TB), opportunistic 
infection, malignancy or major adverse cardiovascular events reported through Week 60. In 
addition, the safety profile of ustekinumab at the standard and half-standard dosages in pediatric 
subjects ≥12 years of age was comparable with that shown for adults, and there were no 
demonstrable differences in safety or tolerability between the 2 pediatric dosages studied.
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
Primary Objective
The primary objective of this study is:

To evaluate the efficacy and safety of ustekinumab in pediatric subjects aged ≥6 through 
<12 years with moderate to severe chronic plaque psoriasis.
Secondary Objectives
The secondary objectives of this study are:

To evaluate the pharmacokinetics of ustekinumab in pediatric subjects aged ≥6 through 
<12 years with moderate to severe chronic plaque psoriasis.

To evaluate the effect of ustekinumab on the dermatologic health-related quality of life in 
pediatric subjects aged ≥6 through <12 years with moderate to severe chronic plaque 
psoriasis. 

To evaluate the immunogenicity of ustekinumab in pediatric subjects aged ≥6 through 
<12 years with moderate to severe chronic plaque psoriasis.
2.2.
Hypothesis
There will be no formal hypothesis testing performed. Efficacy and safety of ustekinumab in 
pediatric subjects ≥6 through <12 years of age with moderate to severe chronic plaque psoriasis 
will be evaluated using descriptive statistics. The PK of ustekinumab in pediatric subjects will 


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also be evaluated using descriptive statistics of serum ustekinumab concentration and population 
PK analyses. 
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
Main Study: Week 0 through Week 56
This is an open label multicenter study of ustekinumab in pediatric subjects ≥6 to <12 years of 
age with moderate to severe chronic plaque psoriasis. The subject population will be comprised 
of boys and girls who have had a diagnosis of plaque-type psoriasis for at least 6 months prior to 
first study drug administration and who have moderate to severe disease defined by PASI ≥12, 
PGA ≥3, and BSA ≥10%.
At least 40 subjects will receive ustekinumab administered subcutaneously at weight-based doses 
at Weeks 0 and 4 followed by dose administrations every 12 weeks (q12w) through Week 40. 
Subject weight will be measured at each visit and the dose of ustekinumab will be adjusted 
accordingly. Expected duration of exposure to study drug during the active treatment period is 52 
weeks. Visits will be every 4 weeks (q4w) through Week 16, then q12w through Week 52. 
Efficacy assessments will be collected through Week 52. Subjects will have a final safety 
follow-up at Week 56. A database lock (DBL) will occur at the end of the main study (Week 56; 
Section 17.9.1).
Efficacy assessments (PGA, PASI, and CDLQI) will be performed per the Time and Events 
Schedule (see Table 1). Serum samples for PK and immunogenicity analyses will be collected at 
the timepoints shown in the Time and Events Schedule. Buccal swab samples for 
pharmacogenomic analysis will be collected at Week 0 from all subjects who consent separately 
to this component of the study (where local regulations permit). Subject participation in 
pharmacogenomic research is optional.
Safety and tolerability will be assessed by monitoring AEs, SAEs, clinical laboratory tests, vital 
signs, physical examinations, concomitant medication review, injection site evaluations, 
observations for allergic reactions, immunogenicity, and assessments for early detection of TB.  
All assessments will be performed per the Time and Events Schedule (see Table 1). The study 
schema is presented in Figure 1.


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Figure 1:
Study Schema for the Main Study (Week 0 through Week 56)
At the Week 52 visit, subjects who have not had a beneficial response from ustekinumab
treatment as determined by the investigator, or who have reached the age of 12 years or older in 
countries where marketing authorization for ustekinumab has been granted for the treatment of 
psoriasis in adolescent patients (12-17 years), will not enter the LTE of the study. The Week 56 
safety follow-up will be the end of study participation.
Long -term Extension: Week 56 through Week 264
Following completion of the Week 52 visit, subjects who have had a beneficial response from 
ustekinumab treatment as determined by the investigator, and who have not yet reached the age 
of 12 years or older in countries where marketing authorization for ustekinumab has been 
granted for the treatment of psoriasis in adolescent patients (12-17 years), and are willing to 
continue ustekinumab treatment, may enter the LTE of the study. For these subjects, the safety 
follow up for the main study and the first ustekinumab administration of the LTE will be 
completed at the Week 56 visit.
Subjects may continue to participate in the LTE until they reach Week 264 or one of the 
following occurs:

The subject turns 12 years of age and resides in a country where marketing authorization has 
been granted for ustekinumab treatment of psoriasis in adolescent patients  

Marketing authorization is obtained for ustekinumab for treatment of plaque psoriasis for 
patients ≥6 to <12 years of age in the subject’s country of residence

Marketing authorization is denied for ustekinumab for the treatment of plaque psoriasis for 
patients ≥6 to <12 years of age in the subject’s country of residence

A company decision is made to no longer pursue an indication in plaque psoriasis in the 
pediatric population (≥6 to <12 years of age) in the subject’s country of residence


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All assessments will be performed per the Time and Events Schedule for the LTE (see Table 2).
During the LTE, consideration should be given to discontinue ustekinumab treatment in subjects 
who are non-responders (defined by PGA >3 at 2 consecutive visits). A DBL will occur at end of 
the LTE (Week 264; Section 17.9.1). Additional DBLs may occur at the Sponsor’s discretion.
3.2.
Study Design Rationale
Dosing Rationale 
In the completed CADMUS study, the standard dosage group was demonstrated to be the more 
effective dose through Week 52 and had a similar safety profile as the half-standard dosage 
(Section 1.3.2). 
In addition, as noted in Section 1.3.2, results for CADMUS demonstrated that the PK of 
ustekinumab in children ≥12 to <18 years of age receiving a body weight adjusted dosage 
(0.75 mg/kg for subjects weighing ≤60 kg, 45 mg for subjects weighing >60 kg to ≤100 kg, and 
90 mg for subjects weighing >100 kg) was comparable to that of adults receiving the standard 
ustekinumab psoriasis dosage (45 mg for subjects weighing ≤100 kg and 90 mg for subjects 
weighing >100 kg). The safety and tolerability in pediatric subjects was no different from that 
extensively established in adults with psoriasis. Moreover, efficacy observed for psoriasis with 
this dosing approach in pediatric subjects from ≥12 to <18 years of age was also comparable to 
adults, suggesting that the exposure-response relationship of ustekinumab for psoriasis is similar 
between adult subjects and pediatric subjects ≥12 to <18 years of age.
Therefore, a body weight adjusted dosing approach identical to the standard dose shown to be 
safe and effective for pediatric subjects ≥12 to <18 years of age in CADMUS will be utilized in 
this clinical study of subjects ≥6 and <12 years of age.
Study Phases
The screening phase of up to 10 weeks will allow for sufficient time to perform screening study 
evaluations and determine study eligibility. Open label active treatment will continue through 
Week 52 (last ustekinumab injection at Week 40) and safety evaluations through Week 56 will 
provide adequate time to demonstrate the efficacy and safety of ustekinumab as maintenance 
therapy for psoriasis.
The addition of the LTE is to allow pediatric subjects who have demonstrated clinical benefit 
through Week 52 of the main study to continue receiving ustekinumab. Additionally, longer-term 
safety and efficacy data in this patient population will be collected.
Efficacy evaluations chosen for this study are consistent with applicable US and EU regulatory 
guidance and precedent established in previous studies of therapeutic agents for the treatment of 
psoriasis.  


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Patient reported outcomes (PROs) chosen for this study are consistent with clinically relevant 
measurements that are accepted in the medical literature for other studies in psoriasis and 
applicable US/EU regulatory guidance documents. Health-related quality of life impairment in 
dermatologic diseases like psoriasis has been shown to be as or even more burdensome than 
other chronic diseases like diabetes and asthma in the pediatric population.1 Skin disease in the
pediatric population specifically impacts physical, social, and emotional health with the potential 
for school functioning.18 Effective treatment of psoriasis may allow for improvements in 
physical, social, emotional, and school functioning and health. Data collected directly from the 
subject can best capture these concepts.
Psoriasis response evaluations include:

PGA

PASI

CDLQI
To help improve objectivity, given the open-label design, clinical efficacy assessments (PGA and 
PASI) will be performed by a blinded evaluator.
Pharmacokinetic Evaluations
To assess the pharmacokinetics of ustekinumab in pediatric subjects ≥6 and <12 years of age 
with psoriasis, serum samples will be collected at selected visits in this study.
Immunogenicity Evaluations
Serum samples for immunogenicity assessment will be collected at selected visits in this study.  
Samples that test positive for antibodies to ustekinumab will be further characterized to 
determine if antibodies to ustekinumab could neutralize the biological effects of ustekinumab in 
vitro (ie, neutralizing antibodies [NAbs] to ustekinumab).
Biomarker Evaluations
Serum samples for biomarker analyses will be collected to evaluate the mechanism of action of 
ustekinumab or help to explain inter-individual variability in clinical outcomes or help to identify 
population subgroups that respond differently to ustekinumab. The goal of the biomarker 
analyses is to evaluate the pharmacodynamics of ustekinumab by measuring levels of IL-17 and 
other inflammatory cytokines and aid in evaluating the pharmacodynamic-clinical response 
relationship. There is currently no accepted laboratory biomarker used to diagnose or monitor 
psoriasis therapy. However, emerging evidence from the literature and from our own research 
group suggest that IL-17 proteins, a family of effector cytokines partly downstream of IL-23, are 
increased in lesional skin and blood of patients with psoriasis7,8,21 and respond to IL-23 targeted 
therapies.17 Accumulating data from sensitive IL-17 assays utilized in previous psoriasis clinical 
studies of IL-23 directed therapies demonstrate that serum levels of IL-17A and IL-17F correlate 
with psoriasis severity based on PASI score (Zhang et al, 2010; unpublished data).22 Therefore,
assessment of IL-17 serum levels will be performed and will be used as an additional biomarker 
of ustekinumab response. 


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Pharmacogenomic (DNA) Evaluations
It is recognized that genetic variation can be an important contributory factor to interindividual 
differences in drug distribution and response and can also serve as a marker for disease 
susceptibility and prognosis. Pharmacogenomic research may help to explain interindividual 
variability in clinical outcomes and may help to identify population subgroups that respond 
differently to a drug. The goal of the pharmacogenomic component is to collect deoxyribonucleic 
acid (DNA)
to allow the identification of genetic factors that may influence the 
pharmacokinetics, pharmacodynamics, efficacy, safety, or tolerability of ustekinumab and to 
identify genetic factors associated with psoriasis.
Two buccal swab samples will be collected for pharmacogenomic assessments at Week 0 from 
subjects who consent separately to this component of the study (where local regulations permit). 
Subject participation in pharmacogenomic research is optional.
4.
SUBJECT POPULATION
Screening for eligible subjects must be performed within a maximum of 10 weeks before 
administration of the study drug can occur.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator should consult with the appropriate sponsor representative and resolve any issues 
before enrolling a subject in the study.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study. 
1.
Subject must be a boy or girl ≥6 and <12 years of age.
2.
Have a diagnosis of plaque-type psoriasis with or without PsA for at least 6 months 
prior to first administration of study drug, with widespread lesions defined by PASI 
≥12, PGA ≥3, and involved BSA ≥10%.
3.
Are candidates for phototherapy or systemic treatment of psoriasis (either naive or 
history of previous treatment) or have psoriasis considered by the investigator as poorly 
controlled with topical therapy after an adequate dose and duration of therapy.  


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4.
Before enrollment, a girl must be either:
a.
Not of childbearing potential: premenarchal; permanently sterilized (eg, bilateral 
tubal occlusion [which includes tubal ligation procedures as consistent with local 
regulations], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or 
otherwise be incapable of pregnancy,
b. Of childbearing potential and practicing a highly effective method of birth control 
consistent with local regulations regarding the use of birth control methods for 
subjects participating in clinical studies: eg, true abstinence (when this is in line with 
the preferred and usual lifestyle of the subject); established use of oral, injected or 
implanted hormonal methods of contraception; placement of an intrauterine device 
(IUD) or intrauterine system (IUS); barrier methods: condom with spermicidal 
foam/gel/film/cream/suppository or occlusive cap (diaphragm or cervical/vault caps) 
with spermicidal foam/gel/film/cream/suppository; male partner sterilization (the 
vasectomized partner should be the sole partner for that subject).
Note: If the childbearing potential changes after start of the study (eg, girl who is 
not heterosexually active becomes active, premenarchal girl experiences menarche) 
a girl must begin a highly effective method of birth control, as described above.  
5.
A girl of childbearing potential must have a negative urine pregnancy test at screening 
and at all visits when study drug is to be administered. 
6.
A boy who is sexually active with a female of childbearing potential must agree to use a 
barrier 
method 
of 
birth 
control
eg, 
either 
condom 
with 
spermicidal 
foam/gel/film/cream/suppository or partner with occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.
7.
Are considered eligible according to the following TB screening criteria:

Have no history of latent or active TB prior to screening.

Have no signs or symptoms suggestive of active TB upon medical history 
and/or physical examination.

Have had no recent close contact with a person with active TB. 

Within 10 weeks prior to the first administration of study drug, have a negative 
QuantiFERON®-TB Gold test result (see Attachment 1). Within 10 weeks, a 
negative tuberculin skin test prior to the first administration of study drug is 
additionally 
required 
if 
the 
QuantiFERON®-TB 
Gold 
test 
is 
not 
approved/registered in that country or the tuberculin skin test is mandated by 
local health authorities. 

Indeterminate results should be handled as outlined in Section 9.1.2.


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8.
Must have positive protective antibody titers to varicella and measles prior to the first 
administration of study drug. In the absence of positive protective antibody titers, the 
subject must have documentation of age-appropriate vaccination for varicella and/or
measles (that includes both doses of each vaccine) or verification of past varicella 
and/or measles infection documented by a health care provider.
9.
Must agree not to receive a live virus or live bacterial vaccination at least 2 weeks (or 
longer as indicated in the package insert of the relevant vaccine) prior to the first 
administration of study drug, during the study, or within 15 weeks after the last 
administration of study drug.  
10.
Must agree not to receive a bacille Calmette-Guérin (BCG) vaccination within 
12 months of screening, during the study, or within 12 months after the last 
administration of study drug.
11.
Must avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet 
light sources during study.
12.
Have screening laboratory test results within the following parameters:

Hemoglobin
≥10 g/dL (SI:  ≥100 g/L)

White blood cells
≥3.0 x 103 cells/µL (SI: ≥3.0 x 109cells/L)

Neutrophils
≥1.5 x 103 cells/µL (SI:  ≥1.5 x 109 cells/L)

Platelets
≥150 x 109/L 

Serum creatinine 
≤0.7 mg/dL (SI:  62 µmol/L; 6 to 10 years of age)

≤1.0 mg/dL (SI:  88 µmol/L; 11 to 12 years of age)

Aspartate aminotransferase (AST) ≤72 IU/L (girls and boys, 2 to 11 years of 
age)

Alanine aminotransferase (ALT)
≤54 IU/L (girls and boys, 2 to 18 years of 
age)
13.
Subject must be willing and able to adhere to the prohibitions and restrictions specified 
in this protocol.
14.
Each subject (or their legally acceptable representative) must sign an informed consent 
form (ICF) indicating that he or she understands the purpose of and procedures required 
for the study and are willing to participate in the study. Assent is also required of 
children capable of understanding the nature of the study (typically 7 years of age and 
older) as described in Section 16.2.3, Informed Consent.


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4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study. 
Disease Characteristics:
1.
Currently have nonplaque forms of psoriasis (eg, erythrodermic, guttate, or pustular).
2. 
Have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of 
psoriasis from beta blockers, calcium channel blockers, or lithium).
Concomitant or previous medical therapies received:
3.
Have used any therapeutic agent targeted at reducing IL-12 or IL-23, including but not 
limited to ustekinumab, guselkumab, and tildrakizumab.
4.
Have used topical medications/treatments that could affect psoriasis or PASI evaluation 
(including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D 
derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens, picrolimus, 
tacrolimus) within 2 weeks of the first administration of study drug.  
5.
Have received phototherapy or any systemic medications/treatments that could affect 
psoriasis or PASI evaluation (including, but not limited to, oral or injectable 
corticosteroids, retinoids, 1,25-dihydroxy vitamin D3 and analogues, psoralens, 
sulfasalazine, hydroxyurea, or fumaric acid derivatives) within 4 weeks of the first 
administration of study drug.
6.
Have received any systemic immunosuppressants (eg, methotrexate [MTX], 
azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, 
hydroxyurea, and tacrolimus) within 4 weeks of the first administration of study drug.
7.
Have received any biologic agent (eg, ENBREL®, HUMIRA®) within the previous 
3 months or 5 times the t1/2 of the agent, whichever is longer.
8.
Have received natalizumab, efalizumab, or agents that deplete B or T cells (eg, 
rituximab, alemtuzumab, abatacept, or visilizumab) within 12 months of screening, or, 
if after receiving these agents, evidence is available at screening of persistent depletion 
of the targeted lymphocyte population.
9.
Are currently receiving lithium, antimalarials, or intramuscular (IM) gold, or have 
received lithium, antimalarials, or IM gold within 4 weeks of the first administration of 
study drug.
10.
Have used a topical investigational agent within 4 weeks or 5 times the t1/2 of the 
investigational agent, whichever is longer, before the planned start of treatment or are 
currently enrolled in a study of a topical agent.


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11.
Have used a non-topical investigational drug within 3 months or 5 times the t1/2 of the 
investigational agent, whichever is longer, before the planned start of treatment or are 
currently enrolled in a study of a non-topical investigational agent.
12.
Have received, or are expected to receive, any live virus or bacterial vaccination at least 
2 weeks (or longer as indicated in the package insert of the relevant vaccine) prior to the 
first administration of study drug, during the study, or within 15 weeks after the last 
administration of study drug.
13.
Have had a BCG vaccination within 12 months of screening.
Infections or predispositions to infections:
14.
Have a history of chronic or recurrent infectious disease, including but not limited to 
chronic renal infection, chronic chest infection (eg, bronchiectasis), recurrent urinary 
tract infection (recurrent pyelonephritis or chronic nonremitting cystitis), or open, 
draining, or infected skin wounds or ulcers.
15.
Have had a serious infection (eg, hepatitis, pneumonia, or pyelonephritis), have been 
hospitalized for an infection, or have been treated with IV antibiotics for an infection 
within 2 months prior to first administration of study drug or have had multiple (≥2) 
serious infections requiring hospitalization or treatment with parenteral antibiotics 
within the past year. Less serious infections (eg, acute upper respiratory tract infection, 
simple urinary tract infection) need not be considered exclusionary at the discretion of 
the investigator.
16.
Have a history of latent or active granulomatous infection, including TB, 
histoplasmosis, or coccidioidomycosis, prior to screening.
17.
Have ever had a nontuberculous mycobacterial infection or systemic opportunistic 
infection (eg, cytomegalovirus, pneumocystosis, aspergillosis).
18.
Is infected with human immunodeficiency virus (HIV; positive serology for HIV 
antibody).
19.
Tests positive for antibodies to hepatitis C virus (HCV) at screening.
20.
Subjects must undergo screening for hepatitis B virus (HBV). At a minimum, this 
includes testing for HBsAg (HBV surface antigen), anti-HBs (HBV surface antibody), 
and anti-HBc (HBV core antibody total):


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a.
Subjects who test positive for surface antigen (HBsAg+) are not eligible for 
this study, regardless of the results of other hepatitis B tests.
b.
Subjects who test negative for surface antigen (HBsAg-) and test positive for 
core antibody (anti-HBc+) and surface antibody (anti-HBs+) are eligible for 
this study.
c.
Subjects who test positive only for surface antibody (anti-HBs+) are eligible
for this study.
d.
Subjects who test positive only for core antibody (anti-HBc+) must undergo 
further testing for hepatitis B deoxyribonucleic acid (HBV DNA test). If the 
HBV DNA test is positive, the subject is not eligible for this study. If the HBV 
DNA test is negative, the subject is eligible for this study. In the event the 
HBV DNA test cannot be performed, the subject is not eligible for this study.
Note: For subjects who are not eligible for this study due to HBV test results, 
consultation with a physician with expertise in the treatment of hepatitis B virus 
infection is recommended.
21.
Have a documented history of immune deficiency syndrome (eg, severe combined 
immunodeficiency syndrome, T cell deficiency syndromes, B cell deficiency syndromes 
and chronic granulomatous disease).
Malignancy or increased potential or malignancy:
22.
Have any known malignancy or have a history of malignancy.
23.
Have a known history of lymphoproliferative disease, including lymphoma, or signs and 
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy 
and/or splenomegaly.
Coexisting medical conditions or past medical history
24.
Have a history of or current signs or symptoms of moderate or severe progressive or 
uncontrolled liver or renal insufficiency; or significant cardiac, vascular, pulmonary, 
gastrointestinal, endocrine, neurologic, hematologic, psychiatric, or metabolic 
disturbances.
25.
Have shown a previous immediate hypersensitivity response, including anaphylaxis, to 
an immunoglobulin product (eg, plasma derived or recombinant mAb).
26.
Known allergies, hypersensitivity, or intolerance to ustekinumab or its excipients.
27.
Have a transplanted organ (with exception of a corneal transplant >3 months prior to the 
first administration of study drug).


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28.
Is currently undergoing or has previously undergone allergy immunotherapy for a 
history of anaphylactic reactions.
29.
Have been hospitalized in the past 1 year for asthma, ever required intubation for 
treatment of asthma, currently require oral corticosteroids for the treatment of asthma, 
or required more than one short-term (≤2 weeks) course of oral corticosteroids for 
asthma within the previous year. 
30.
Be known to have had a substance abuse (drug or alcohol) problem.
31.
Are pregnant, or nursing.
Other
32.
Are unable or unwilling to undergo multiple venipunctures because of poor tolerability 
or lack of easy access to veins.
33.
Are participating in another interventional study using an investigational agent or 
procedure during participation in the study.
34.
Subject has any condition for which, in the opinion of the investigator, participation 
would not be in the best interest of the subject (eg, compromise the well-being) or that 
could prevent, limit, or confound the protocol-specified assessments
35.
Subject is an employee of the investigator or study site, with direct involvement in the 
proposed study or other studies under the direction of that investigator or study site, as 
well as family members of the employees or the investigator.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
Investigators are encouraged to enroll subjects as soon as they become eligible and should not 
wait for the maximum of the 10-week screening period. If a subject's status changes (including 
laboratory results or receipt of additional medical records) after screening but before the first 
dose of study drug is given such that he or she no longer meets all eligibility criteria, then the 
subject should be excluded from participation in the study. Section 17.4, Source Documentation, 
describes the required documentation to support meeting the enrollment criteria.
4.3.
Prohibitions and Restrictions 
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the study to be eligible for participation.  
1.
Must not receive a live virus or live bacterial vaccination during the study or within 
15 weeks after the last administration of study drug.
2.
Must not receive a BCG vaccination during the study or within 12 months after the last 
administration of study drug.


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3.
Must agree not to plan a pregnancy or father a child within 6 months following the last 
administration of study drug.
4.
If sexually active, girls must remain on a highly effective method of birth control during 
the study and for 6 months after receiving the last administration of study drug.
5.
Refer to Section 8 (PRESTUDY AND CONCOMITANT THERAPY) for details
regarding prohibited and restricted therapy during the study.
6.
Agree to follow the contraceptive requirements as noted in the inclusion criteria.
7.
Subjects must avoid prolonged sun exposure and avoid use of tanning booths or other 
UV light sources during the study.
5.
TREATMENT ALLOCATION AND BLINDING
Treatment Allocation
Randomization will not be used in this study. All subjects will be assigned to receive active 
study drug (ustekinumab). 
Blinding
As this is an open-label study, blinding of study drug is not applicable. However, a blinded 
efficacy evaluator will be used to assess efficacy as described in Section 9.2.1.
6.
DOSAGE AND ADMINISTRATION
The ustekinumab for this study will be supplied as final vialed product (FVP), single-use 2 mL 
Schott Type I glass vial closed with a Daikyo D777-1 FluroTec®-coated stopper and a West 
13 mm aluminum seal and plastic light green flip-off button. The FVP formulation is composed 
of 90 mg/mL ustekinumab with excipient concentrations of 6.7 mM L-histidine, 7.6% (w/v) 
sucrose, and 0.004% (w/v) polysorbate 80, pH 6.0. There is 1 dose strength (ie, 45 mg in 0.5 mL 
volume). No preservatives are present. 
All subjects enrolled in the study will receive ustekinumab at Weeks 0 and 4 followed by q12w 
dosing. Eligible subjects who enter the LTE will receive ustekinumab q12w beginning at 
Week 56 and continue treatment according to criteria defined in Section 3.1. At each dosing 
visit, subject weight will be measured and the dose of ustekinumab will be adjusted accordingly. 
Subjects will receive 1 of the following dose levels depending on their weight:

Weight <60 kg:  0.75 mg/kg

Weight ≥60 kg to ≤100 kg:  45 mg

Weight >100 kg:  90 mg


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7.
TREATMENT COMPLIANCE
Compliance with the treatment schedule and study visit is strongly encouraged, although it is 
acknowledged that treatment may need to be interrupted for various reasons. The following visit 
windows must be adhered to: ±1 week for the Week 4, Week 8 and Week 12 (primary endpoint) 
visits and ±2 weeks for all visits after Week 12. For any reason, if the subject deviates from the 
scheduled visits, the rescheduled visit should occur as soon as possible, preferably within 
2 weeks. The subject should then resume the normal study schedule relative to the baseline visit 
(Week 0). The Sponsor must be contacted for any significant deviation in a visit or dosing.
All subject case report forms (CRFs) will be monitored by a site monitor designated by the 
sponsor.  During these monitoring visits, all procedures will be evaluated for compliance with 
the protocol.  Subject charts will be reviewed and compared with the data entries on the CRFs to 
ensure accuracy.
8.
PRESTUDY AND CONCOMITANT THERAPY
All concomitant therapies must be recorded throughout the study beginning when the first dose 
of study drug is administered.
All therapies (prescriptions or over-the-counter medications, including vitamins and herbal 
supplements) different from the study drug must be recorded in the concomitant therapy section 
of the CRF. Modification of an effective preexisting therapy should not be made for the explicit 
purpose of entering a subject into the study.
The Sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
8.1.
Topical Therapies for Psoriasis
The use of any topical corticosteroid preparations for the treatment of psoriasis is prohibited 
within 2 weeks prior to the first study drug administration and during the first 12 weeks of the 
study period.
After the Week 12 evaluation, low potency topical corticosteroids may be used on the face and 
groin only. Acceptable low potency corticosteroids include 2.5% concentration or less of 
hydrocortisone cream or equivalent.  
Other non-corticosteroid topical therapies that could affect psoriasis or the PASI evaluation, such 
as tar, anthralin, calcipotriene, tazarotene, methoxsalen, picrolimus, or tacrolimus, are prohibited 
through Week 52 of the study.
Through Week 52, shampoos (containing tar or salicylic acid only) and topical moisturizers are 
allowed. Subjects should not use these topical agents during the morning prior to a study visit. 
Nonmedicated shampoos may be used on the day of a visit.


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8.2.
Phototherapy or Systemic Therapies for Psoriasis
The use of phototherapy (psoralen with ultraviolet light A [PUVA] and/or ultraviolet light B 
[UVB]), systemic antipsoriatic medications targeted for reducing tumor necrosis factor 
(including but not limited to etanercept or adalimumab), drugs targeted for reducing IL-12 or
IL-23 (including but not limited to guselkumab and tildrakizumab), alpha-4 integrin antagonists 
(including but not limited to natalizumab), any conventional systemic antipsoriatic therapy 
(including but not limited to MTX, cyclosporine, acitretin), and any other systemic agent that 
could affect psoriasis or the PASI evaluation are not allowed at any time during the study. 
Subjects taking these drugs must be discontinued from study drug and be followed for an 
additional 16 weeks.
8.3.
Concomitant Therapies for Conditions Other Than Psoriasis
Every effort should be made to keep subjects on stable concomitant medications. If the 
medication is temporarily discontinued because of abnormal laboratory values, side effects, 
concurrent illness, or the performance of a procedure, the change and reason for it should be 
clearly documented in the subject’s medical record.
The use of stable doses of nonsteroidal anti-inflammatory drugs (NSAIDs) is allowed. However, 
disease-modifying agents such as MTX, sulfasalazine, or IM gold must be discontinued within 
4 weeks of the first study drug administration and are prohibited during the study. Antimalarial 
agents, except for chloroquine, may be used after Week 12.
Corticosteroids should be used only as follows:

Topical Corticosteroids:  Topical corticosteroids for indications other than psoriasis should 
be limited to situations where, in the opinion of the treating physician, there are no adequate 
alternatives. They should be used on a short-term basis, preferably for 2 weeks.

Systemic Corticosteroids: (oral or IV only; IM steroids are prohibited):  Short term use 
(2 weeks) of oral or IV systemic corticosteroids for indications other than psoriasis should 
be limited to situations where, in the opinion of the treating physician, there are no adequate 
alternatives.  If feasible, the medical monitor or designee should be contacted prior to 
initiation.

Intralesional Corticosteroids:  Intralesional corticosteroids are not allowed for use in the 
treatment of psoriasis.  Intralesional corticosteroids for indications other than psoriasis 
should be limited to situations where, in the opinion of the treating physician, there are no 
adequate alternatives.  They should be used on a short-term basis.

Intra-articular Corticosteroids:  Subjects may receive no more than 2 intra-articular, 
tendon sheath, or bursal corticosteroid injections through Week 52 of the study.

Epidural Corticosteroids:  Epidural corticosteroids are prohibited through Week 52 of the 
study.  

Other Corticosteroids:  Inhaled, otic, ocular, nasal, or other routes of mucosal delivery of 
corticosteroids are allowed.


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During the LTE, the medication rules outlined above still apply except that all topical therapies, 
with the exception of ultra-high potency corticosteroids are permitted for treatment of psoriasis.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedule (Table 1 and Table 2) summarizes the frequency and timing of 
efficacy, pharmacokinetic,
immunogenicity,
biomarker, pharmacogenomic,
and safety 
measurements applicable to this study. The visit-specific CLDQI PRO assessment should be 
conducted/completed before any tests, procedures, or other consultations for that visit to prevent 
influencing subject perceptions.
Additional serum or urine pregnancy tests may be performed, as determined necessary by the 
investigator or required by local regulation, to establish the absence of pregnancy at any time 
during the subject's participation in the study.
The total blood volume to be collected from each subject will be 69.5 mL. Table 3 summarizes 
the estimated blood volume to be drawn during the study.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples.
Table 3:
Volume of Blood to be Collected From Each Subject in the Main Study
Type of Sample
Volume per 
Sample (mL)
No. of Samples 
per Subject
Total Volume of 
Blood (mL)a
Hematology
2
5
10
Serum chemistryb
2.5
5
12.5
Serology (HIV, hepatitis)
8.5
1
8.5
Pharmacokinetic onlyb
2.5
3
7.5
Pharmacokinetics and immunogenicityc
3.5
4
14
Serum antibody titers for varicella and measles
2.5
1
3.5
Biomarkersd
3.5
3
10.5
QuantiFERON®-TB Gold testing
3
1
3
Approximate Total
69.5
a
Calculated as number of samples multiplied by amount of blood per sample.
b
Blood samples collected for pharmacokinetics only evaluation (approximately 2.5 mL each): each serum sample 
will be split into 2 aliquots (approximately 0.5 mL each).
c
Blood samples collected for pharmacokinetic and immunogenicity evaluations (approximately 3.5 mL each): 
each serum sample will be split into 3 aliquots (approximately 0.5 mL each).
d
Blood samples collected for serum biomarkers (approximately 3.5 mL each): each serum sample will be split 
into 3 aliquots (approximately 0.5 mL each).
For subjects participating in the LTE, a maximum of 4 additional hematology samples and
4 additional serum chemistry samples (2 mL per hematology sample and 2.5 mL per serum 
chemistry sample; total blood volume of 18 ml), will be collected.


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9.1.2.
Screening Phase
After written informed consent has been obtained and within a maximum period of 10 weeks 
before enrollment into the study, all screening evaluations establishing subject eligibility must be 
performed. Subjects who meet all the inclusion and none of the exclusion criteria will be enrolled 
in the study as soon as practically possible. There is no need to wait for the maximum 10-week 
screening period. Every effort should be made to adhere to the study Time and Events Schedule 
for each subject (see Table 1).
Girls of childbearing potential must have a negative urine -human chorionic gonadotroptin 
(hCG) pregnancy test at screening and before enrollment. Girls and boys who are sexually 
active must consent to use a highly effective method of contraception and continue to use 
contraception for the duration of the study and for 6 months after the last dose of study drug. The 
method(s) of contraception used by each subject must be documented. 
Subjects must undergo testing for TB (see Attachment 1 and Attachment 2) and their medical 
history assessment must include specific questions about a history of TB or known occupational 
or other personal exposure to individuals with active TB. The subject should be asked about past 
testing for TB, including chest radiograph results and responses to tuberculin skin or other TB 
testing.
Subjects with a negative QuantiFERON®-TB Gold test result (and a negative tuberculin skin test 
result in countries in which the QuantiFERON-TB Gold test is not approved/registered or the 
tuberculin skin test is mandated by local health authorities) are eligible to continue with 
procedures.  Subjects with a newly identified positive QuantiFERON®-TB Gold (or tuberculin 
skin) test result must be excluded from the study.
A subject whose first QuantiFERON®-TB Gold test result is indeterminate should have the test 
repeated. In the event that the second QuantiFERON®-TB Gold test result is also indeterminate, 
the subject must be excluded from the study.
Subjects that do not have positive protective antibody titers to varicella and measles based on 
screening laboratory test results or appropriate documentation of prior immunization or 
documentation of prior infection from a health care provider can be immunized during the 
10-week screening period prior to receiving study drug. These subjects should receive both an 
initial immunization and a booster 4 weeks later. Also note that if a live attenuated viral vaccine 
is utilized, it is also necessary for 2 weeks to elapse between the booster shot and receipt of study 
drug.
9.1.3.
Open-Label Treatment Period (Week 0 to Week 52)
After screening, subjects will have clinic visits at Weeks 0, 4, 8, 12, and 16 then every 12 weeks 
through Week 52. The last injection of study drug will be administered at Week 40, the final 
efficacy assessments will be performed at Week 52.


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9.1.4.
Safety Follow-up (Week 52 to Week 56)
A final safety assessment at Week 56 will be obtained via telephone contact for those subjects 
not entering LTE.
9.1.5.
Long-term Extension (Week 56 to Week 264)
Following completion of the Week 52 visit, subjects who have had a beneficial response from 
ustekinumab treatment as determined by the investigator, and who have not yet reached the age 
of 12 years or older in countries where marketing authorization for ustekinumab has been 
granted for the treatment of psoriasis in adolescent patients (12-17 years), and are willing to 
continue ustekinumab treatment, may enter the LTE of the study. For these subjects, the safety 
follow up for the main study and the first ustekinumab administration of the LTE will be 
completed at the Week 56 visit.
Subjects may continue to participate in the LTE until they reach Week 264 or one of the 
following occurs:

The subject turns 12 years of age and resides in a country where marketing authorization has 
been granted for ustekinumab treatment of psoriasis in adolescent patients 

Marketing authorization is obtained for ustekinumab for treatment of plaque psoriasis for 
patients ≥6 to <12 years of age in the subject’s country of residence

Marketing authorization is denied for ustekinumab for the treatment of plaque psoriasis for 
patients ≥6 to <12 years of age in the subject’s country of residence

A company decision is made to no longer pursue an indication in plaque psoriasis in the 
pediatric population (≥6 to <12 years of age) in the subject’s country of residence 
All assessments will be performed per the Time and Events Schedule for the LTE (see Table 2).
During the LTE, consideration should be given to discontinue ustekinumab treatment in subjects 
who are non-responders (defined by PGA >3 at 2 consecutive visits). A DBL will occur at end of 
the LTE (Week 264; Section 17.9.1). Additional DBLs may occur at the Sponsor’s discretion.
9.2.
Efficacy 
Efficacy evaluations are consistent with those used to evaluate other therapies for psoriasis and 
will include the following:

PGA

PASI

CDLQI
9.2.1.
Blinded Efficacy Evaluator
During the main study, an independent, blinded efficacy evaluator, approved by the Sponsor, 
will be designated at each study site to perform all PASI and PGA efficacy assessments, 
including the screening visit. The blinded efficacy evaluator should have no contact with the 
subject during the study other than the efficacy assessments, should not discuss the subject’s 


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treatment with the subject, subject’s caregiver, or other site personnel at any time, and will not be 
permitted to review the subject’s medical records, questionnaires, or the electronic CRF prior to 
each assessment. The blinded efficacy evaluator should be documented in the source documents 
at each visit.
During the LTE, PGA assessments should be performed by the investigator or any qualified 
healthcare provider at the study site. When possible, all PGA assessments for a subject should be 
performed by the same assessor.
The Sponsor will provide PASI and PGA training for each site’s designated efficacy evaluator 
prior to the screening of the first subject at each site. If the efficacy evaluator was trained by the 
Sponsor in a previous clinical study within the last 3 years and there is adequate documentation 
of this training (certification), that training will be considered adequate for this study; however, 
repeat training prior to start of the study is encouraged. Training documentation of each efficacy 
evaluator should be maintained at the study site.   
All efficacy evaluators at a site must be listed on the Delegation Log at the study.
9.2.2.
Physician’s Global Assessment
The PGA is a static evaluation of the subject’s current psoriasis status based on a qualified 
healthcare provider’s assessment of the following categories:  induration, scaling, and erythema. 
A description of the PGA is provided in Attachment 3.
9.2.3.
Psoriasis Area and Severity Index
The PASI is a system used for assessing and grading the severity of psoriatic lesions and their 
response to therapy (Fredriksson and Pettersson, 1978).5 For the PASI assessment, the body is 
divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these 
areas is assessed separately for erythema, induration, and scaling, which are each rated on a scale 
of 0 to 4. The PASI produces a numeric score that can range from 0 to 72.  A PASI 50 response 
is defined as 50% improvement in PASI score from baseline; PASI 75 and PASI 90 are 
similarly defined. A description of the PASI is provided in Attachment 4.
9.2.4.
Children’s Dermatology Life Quality Index
The CDLQI is an adapted version of the DLQI for the pediatric population. The adaption and 
validation of the CDLQI was undertaken by the original developer of the DLQI to ensure it 
addressed the specific needs of the pediatric population.12 The CDLQI questionnaire is 
frequently used to assess the patient’s perspective on the impact of skin disorders on daily 
living.12,14 The development of the instrument included a wide variety of dermatologic 
conditions (Finlay and Khan, 1994).4 The content validity and other psychometric properties 
were further assessed in a subsequent study in patients with psoriasis.3 Additional validation 
work was completed on the children’s version.12 The CDLQI, a 10-item instrument, has 4 item 
response options and a recall period of 1 week. The instrument is designed for use in children (ie, 
subjects from 4 to 16 years of age), is self-explanatory and can be simply handed to the subject 


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who is asked to fill it in with the help of the child's parent or guardian. A sample CDLQI is 
provided in Attachment 5.
9.2.5.
Endpoints 
Primary Endpoint

The proportion of subjects with a PGA of cleared (0) or minimal (1) at Week 12.
PGA results will be summarized along with 95% confidence intervals for all subjects enrolled in 
the study.
Major Secondary Endpoints

Serum ustekinumab concentrations will be summarized over time to assess the PK of 
ustekinumab.

The proportions of subjects who achieve a ≥75% improvement in PASI from baseline at 
Week 12. 

The change in CDLQI from baseline at Week 12.

The proportions of subjects who achieve a ≥90% improvement in PASI from baseline at 
Week 12. 
The major secondary efficacy endpoints will be summarized along with 95% confidence 
intervals for all subjects enrolled in the study.
Applicable data handling rules for the efficacy endpoints are defined in Section 11.3.1.
Other Endpoints
In addition to the primary and major endpoint analyses, the following efficacy endpoints will be 
summarized:

The proportions of subjects achieving a PGA score of cleared (0), the proportion of subjects 
achieving a PGA score of cleared (0) or minimal (1), and the proportion of subjects 
achieving a PGA score of mild or better (≤2) over time

The proportions of subjects who achieve PASI 50, PASI 75, PASI 90, and PASI 100 
responses over time

The percent improvement from baseline in PASI over time 

The change from baseline in CDLQI over time.

The proportion of subjects with CDLQI = 0 or 1 over time
Safety data will be summarized using descriptive statistics
9.3.
Pharmacokinetics and Immunogenicity
Blood samples will be collected for the measurement of serum ustekinumab concentrations and 
evaluation of antibodies to ustekinumab at the timepoints presented in the Time and Events 


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Schedule (Table 1). Serum samples will also be collected at the final visit from subjects who 
terminate study participation early.
Serum ustekinumab concentrations will also be used for population PK modelling to characterize 
the PK of ustekinumab in this pediatric population and for exposure-response modeling and 
simulation analysis. These analyses will be presented in a separate technical report (see 
Section 11.5).
9.3.1.
Evaluations
Venous blood samples will be collected for measurement of serum ustekinumab concentrations 
and antibodies to ustekinumab at the timepoints shown in the Time and Events Schedule 
(Table 1). 
Venous blood samples of approximately 2.5 mL for pharmacokinetics only evaluations will be 
collected and each serum sample will be divided into 2 aliquots (1 for serum ustekinumab 
concentration and 1 for back-up). Venous blood samples of approximately 3.5 mL for both 
pharmacokinetics and immunogenicity evaluations will be collected and each serum sample will 
be divided into 3 aliquots (1 for serum ustekinumab concentration, 1 for antibodies to 
ustekinumab, and 1 for back-up). Samples collected for analyses of ustekinumab serum 
concentration and antibodies to ustekinumab may additionally be used to evaluate safety or 
efficacy aspects that address concerns arising during or after the study period, or for further 
characterization of immunogenicity. Samples must be collected before study drug administration 
at visits when a study drug administration is scheduled. The exact dates and times of blood 
sample collection must be recorded in the laboratory requisition form. See the Laboratory 
Manual for further information regarding collection, handling, and shipment of biological 
samples. Genetic analyses will not be performed on these serum samples. Subject confidentiality 
will be maintained.
9.3.2.
Analytical Procedures
Serum samples will be analyzed to determine serum ustekinumab concentrations using a 
validated, specific, and sensitive immunoassay method by the sponsor’s bioanalytical facility or 
under the supervision of the Sponsor. The Sponsor, or its designee, under conditions in which the 
subjects’ identity remains blinded, will assay these samples.
9.3.3.
Immunogenicity Assessments (Antibodies to Ustekinumab)
Antibodies to ustekinumab will be evaluated in serum samples collected from all subjects 
according to the Time and Events Schedule (Table 1). Additionally, serum samples should also 
be collected at the final visit from subjects who are discontinued from treatment or withdrawn
from the study. These samples will be tested by the Sponsor or Sponsor's designee.
Samples that test positive for antibodies to ustekinumab will be further characterized to 
determine if antibodies to ustekinumab could neutralize the biological effects of ustekinumab in 
vitro (ie, NAbs to ustekinumab). All samples will be tested by the Sponsor or Sponsor's 
designee.


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9.4.
Biomarker Evaluations 
Serum will be collected from all subjects for assay of IL-17 according to the Time and Events 
Schedule (Table 1). Serum may also be analyzed for levels of specific proteins including but not 
limited to
cytokines such as IL-12p40, IL-17, IL-21, IL-22, IL-23p19,
and other 
inflammation-related molecules.
9.5.
Pharmacogenomic (DNA) Evaluations 
Two buccal swab samples will be collected for pharmacogenomic assessments at Week 0 from 
subjects who consent separately to this component of the study (where local regulations permit). 
Subject participation in pharmacogenomic research is optional.
DNA samples will be used for research related to ustekinumab or psoriasis. They may also be 
used to develop tests/assays related to ustekinumab and psoriasis. Pharmacogenomic research 
may consist of the analysis of one or more candidate genes or of the analysis of genetic markers 
throughout the genome (as appropriate) in relation to ustekinumab or psoriasis clinical endpoints.
Subjects have the option to withdrawal consent from the phramcogenomic assessment or to 
withdraw their consent for their samples to be stored for research (refer to Sections 10.4 and 
16.2.5).
9.6.
Safety Evaluations
Any clinically relevant changes occurring during the study must be recorded on the AE section 
of the CRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will 
be followed by the investigator until resolution or until a clinically stable endpoint is reached. 
The study will include the following evaluations of safety and tolerability according to the time 
points provided in the Time and Events Schedule (Table 1):
Adverse Events
AEs will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject's legally acceptable representative) for the duration of the study. AEs will be followed by 
the investigator as specified in Section 12, Adverse Event Reporting.
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected. The investigator must 
review the laboratory report, document this review, and record any clinically relevant changes 
occurring during the study in the AE section of the CRF. The laboratory reports must be filed 
with the source documents. The following tests will be performed by the central laboratory. Use 
of local laboratories is only allowed in cases where safety follow-up is time-critical and the 
central laboratory results are not expected to be available if actions need to be taken for safety 
reasons. These laboratory results will not be entered in the CRF but should be retained with the 
source documents.


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
Hematology Panel
-hemoglobin
-neutrophils
-hematocrit
-bands
-red blood cell (RBC) count
-eosinophils
-white blood cell (WBC) count with differential
-basophils
-lymphocytes
-platelet count
-monocytes

Serum Chemistry Panel 
-blood urea nitrogen
-total bilirubin
-creatinine
-indirect bilirubin
-glucose
-albumin
-AST
-total protein
-ALT

Urine pregnancy testing for girls of childbearing potential only.

Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and hepatitis C virus 
antibody; serum antibody titers to varicella, measles)
During the study, all abnormal laboratory values will require further explanation from the 
investigator. Clinically significant abnormal laboratory values should be repeated until they 
return to normal or are otherwise explained by the investigator.  
Vital Signs 
Heart rate, respiratory rate, and blood pressure will be collected.
Physical Examination 
Physical examinations will be performed. Total body skin examination will be performed to 
evaluate for any suspected malignant skin lesions including basal cell carcinoma, squamous cell 
carcinoma, and melanoma. Height and weight will be collected.  
Concomitant Medication Review
Concomitant medications will be reviewed at each visit.  
Injection-site Reactions
A study drug injection-site reaction is any adverse reaction at an SC study drug injection site.  
The injection sites will be evaluated for reactions and any injection-site reactions will be 
recorded as an AE.
Allergic Reactions
All subjects must be observed carefully for symptoms of an allergic reaction (eg, urticaria, 
itching, hives) for at least 30 minutes after the injection.  If mild or moderate allergic reaction is 
observed, acetaminophen 650 mg by mouth (PO) or NSAIDs and diphenhydramine 25 mg PO or 
IV may be administered. 


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Subjects with reactions following an injection resulting in bronchospasm with wheezing 
and/or dyspnea requiring ventilatory support, or symptomatic hypotension with a decrease 
in systolic blood pressure greater than 40 mm mercury (Hg) will not be permitted to 
receive any additional study drug injections.  In the case of such reactions, appropriate 
medical treatment should be administered.
Early Detection of Active Tuberculosis 
To aid in the early detection of TB reactivation or new TB infection during study participation, 
subjects must be evaluated for signs and symptoms of active TB at each scheduled visit (refer to 
Time and Events Schedule) or by telephone contact approximately every 4 to 12 weeks.  The 
following series of questions is suggested for use during the evaluation: 

“Has your child had a new cough of > 14 days’ duration or a change in a chronic cough?”

“Has your child had any of the following symptoms:

Persistent fever?

Unintentional weight loss?

Night sweats?”

“Has your child had close contact with an individual with active TB?”  (If there is 
uncertainty as to whether a contact should be considered “close,” a physician specializing in 
TB should be consulted.)
Subjects who experience close contact with an individual with active TB during the conduct of 
the study must have a repeat QuantiFERON® TB Gold test, a repeat tuberculin skin test in 
countries in which the QuantiFERON®-TB Gold test is not approved/registered or the tuberculin 
skin test is mandated by local health authorities, and, if possible, referral to a physician 
specializing in TB to determine the subject’s risk of developing active TB and whether treatment 
for latent TB is warranted. If the QuantiFERON® TB Gold test result is indeterminate, the test 
should be repeated as outlined in Section 9.1.2.
If the evaluation raises suspicion that a subject may have TB reactivation or new TB infection, 
no additional study drug should be given, and an immediate and thorough investigation should 
be undertaken, including, where possible, consultation with a physician specializing in TB. 
Investigators should be aware that TB reactivation in immunocompromised subjects may present 
as disseminated disease or with extrapulmonary features. Subjects with evidence of active TB 
should be referred for appropriate treatment.
9.7.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the laboratory requisition 
form.
Refer to the Time and Events Schedule (Table 1) for the timing and frequency of all sample 
collections.


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Instructions for the collection, handling, storage, and shipment of samples are found in the 
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples 
must be under the specified, and where applicable, controlled temperature conditions as indicated 
in the laboratory manual.
10.
SUBJECT COMPLETION/WITHDRAWAL
10.1.
Completion of Main Study
A subject will be considered to have completed the main study if he or she has completed 
assessments at Week 56. Subjects who prematurely discontinue study treatment for any reason 
before completion of the main study will not be considered to have completed the study.
10.2.
Completion of Long-term Extension
A subject will be considered to have completed the LTE if he or she has completed all 
assessments up through Week 264. For subjects in the LTE who decide to withdraw from study 
participation, who discontinue treatment for any reason, or who become ineligible to continue to 
receive study drug (ie, due to the occurrence of one of criteria listed in Section 3.1), the 
assessments (excluding study drug injection) for the Week 248 study visit will be performed.
10.3.
Discontinuation of Study Treatment 
If a subject's study treatment must be discontinued before the end of the treatment regimen, this 
will not result in automatic withdrawal of the subject from the study. 
A subject's study treatment should be discontinued if any of the following occur:

The investigator or Sponsor’s medical monitor believes that for safety reasons (eg, AE) it is 
in the best interest of the subject to discontinue study treatment;

An AE temporally associated with study drug injection, resulting in bronchospasm with 
wheezing and/or dyspnea requiring ventilatory support, or symptomatic hypotension with a 
greater than 40 mm Hg decrease in systolic blood pressure;

The subject or their legally acceptable representative withdraws consent/assent for 
administration of study drug;

Pregnancy, or pregnancy planned within the study period or within 6 months after the last 
study drug injection;

The initiation of protocol-prohibited medications or treatments as outlined in Section 8;

Malignancy;

An opportunistic infection;

A recurrent or chronic serious infection;

A severe study drug injection-site reaction;


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
The subject is deemed ineligible according to the following TB screening criteria: 

A diagnosis of active TB is made.

A subject has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination, or has had recent close contact with a person 
with active TB.

A subject undergoing evaluation has a positive QuantiFERON®-TB Gold test result 
and/or an indeterminate QuantiFERON®-TB Gold test result on repeat testing (refer to 
Section 9.1.2) and/or a positive tuberculin skin test result in countries in which the 
QuantiFERON®-TB Gold test is not approved/registered or the tuberculin skin test is 
mandated by local health authorities.
Main Study
Subjects who discontinue study drug but do not terminate study participation will continue to 
return for protocol-specified procedures and evaluations for approximately 16 weeks (4 months) 
following the last dose of study drug. In addition to the procedures and evaluations listed for the 
corresponding visit, the Week 52 visit assessments should also be performed 16 weeks after the 
last dose of study drug.
If a subject discontinues study drug and terminates study participation prior to week 52, the 
procedures and evaluations for the current study visit will be completed. In addition, the 
Week 52 visit assessments should be performed in the subject’s current (final) visit.
All procedures and evaluations must be conducted prior to a subject’s withdrawal of consent.
Long-term Extension
During the LTE, subjects who discontinue study drug but do not terminate study participation 
will continue to return for protocol-specified procedures and evaluations for approximately 
16 weeks (4 months) following the last dose of study drug. At the subject’s last study visit for the 
LTE, the procedures and evaluations (excluding study drug injection) for Week 248 will be 
followed. If a subject discontinues study drug and terminates study participation, the procedures 
and evaluations for Week 248 excluding study drug injection will be performed at the current 
visit.
During the LTE phase, consideration should also be given to discontinue ustekinumab treatment 
in any subjects who are non-responders (ie, defined by PGA >3 at 2 consecutive visits).
10.4.
Withdrawal From the Study
A subject will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

Death


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If a subject is lost to follow-up, every reasonable effort must be made by the study site personnel 
to contact the subject and determine the reason for discontinuation/withdrawal. The measures 
taken to follow up must be documented.
When a subject withdraws before completing the study, the reason for withdrawal is to be 
documented in the CRF and in the source document. Study drug assigned to the withdrawn 
subject may not be assigned to another subject. Subjects who withdraw will not be replaced. If a 
subject withdraws from the study prior to Week 52, the Week 52 assessments will be obtained. If 
a subject withdraws from the study before the end of the LTE, the Week 248 assessments
(excluding study drug injection) will be performed.
11.
STATISTICAL METHODS
Statistical analysis will be done by the Sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below.
No formal hypothesis testing will be conducted. Data will be summarized using descriptive 
statistics. Continuous variables will be summarized using the number of observations, mean, 
standard deviation (SD), median, range, and interquartile range appropriate. Categorical values 
will be summarized using the number of observations and percentages as appropriate. Graphical 
data displays may also be used to summarize the data.
Subject baseline data, demographic and baseline clinical disease characteristics will be 
summarized. The baseline measurement is defined as the closest measurement taken at or before 
Week 0.
Safety and efficacy analysis will include enrolled subjects who receive at least 1 dose 
administration of ustekinumab.
11.1.
Subject Information
For all subjects who receive at least 1 dose of study drug, descriptive statistics will be provided.
11.2.
Sample Size Determination
The sample size of 40 was determined based on both efficacy and PK assessments. The primary 
objective is to evaluate the efficacy and safety of ustekinumab for pediatric subjects aged ≥6 to 
<12 years with moderate to severe chronic plaque psoriasis and 1 of the major secondary 
objective is to evaluate the pharmacokinetics of ustekinumab for this population. To support 
these objectives, a sample size of 40 subjects was chosen. For the efficacy assessment, no formal 
hypothesis testing will be performed. However, the observed response rates and its 95% 
confidence interval of PGA of cleared (0) or minimal (1) at Week 12 will be provided. A sample 
size of 40 will provide a 95% confidence interval [50%, 80%], if the observed response rate is 
65%.
To assess the pharmacokinetics of ustekinumab in this pediatric population, the sample size 
evaluation was based on simulations with a population PK model developed from Studies 


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C0743T08, C0743T09, and CADMUS. The PK in pediatric subjects was simulated using the 
body weight distribution sampled with replacement from the National Health and Nutrition 
Examination Survey (NHANES) III growth database.2 A total of 300 replicates of the planned 
study design, including the PK sampling scheme shown in the Time and Events Schedule, were 
simulated and subsequently the population PK parameters were re-estimated for each replicate. 
The precisions to estimate the CL/F and V/F were calculated. The precisions of CL/F estimates 
with 30 and 40 subjects were 9.4% and 8.1%, respectively, which are lower than 20% and 
generally considered appropriate.19 The precisions of V/F estimates with 30 and 40 subjects were 
10.4% and 9.2%, respectively. Considering potentially higher variability in pediatric subjects ≥6 
to <12 years of age than the adolescent and adult populations, at least 40 subjects are planned to 
be enrolled to provide adequate data to characterize PK of ustekinumab in the planned study 
population.
11.3.
Efficacy Analyses 
Efficacy results will be summarized for all subjects enrolled in the study and 95% confidence 
intervals will be calculated for the primary and major secondary efficacy endpoints.
Primary Endpoints

The proportion of subjects with a PGA of cleared (0) or minimal (1) at Week 12.
Major Secondary Endpoints

Serum ustekinumab concentrations will be summarized over time to assess the PK of 
ustekinumab.

The proportions of subjects who achieve a ≥75% improvement in PASI from baseline at 
Week 12. 

The change in CDLQI from baseline at Week 12.

The proportions of subjects who achieve a ≥90% improvement in PASI from baseline at 
Week 12. 
Other Endpoints
In addition to the primary and major endpoint analyses, the following efficacy endpoints will be 
summarized:

The proportions of subjects achieving a PGA score of cleared (0), the proportion of subjects 
achieving a PGA score of cleared (0) or minimal (1), and the proportion of subjects 
achieving a PGA score of mild or better (≤2) over time

The proportions of subjects who achieve PASI 50, PASI 75, PASI 90, and PASI 100 
responses over time

The percent improvement from baseline in PASI over time 

The change from baseline in CDLQI over time.

The proportion of subjects with CDLQI = 0 or 1 over time


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11.3.1.
Data-Handling Rules
The following treatment failure rules and data-handling rules will be applied to the efficacy 
analyses through Week 52 in this study.
Treatment Failure Criteria and Rules

Subjects are considered as treatment failures if they discontinue study treatment due to lack 
of efficacy, an AE of worsening of psoriasis, or start a protocol-prohibited 
medication/therapy during the study that could affect their psoriasis. 
A subject who meets one or more treatment failure criteria specified above will be 
considered as a treatment failure from that point onward. The baseline values will be used 
for all directly measured endpoints regardless of the actual measurements. Zeros will be 
assigned to improvements and percent improvements, and nonresponder status will be 
assigned to binary response variables. 

For the most efficacy analyses (eg, over time summaries), after the treatment failures, no 
imputation will be performed for missing data (eg, lost to follow-up, missed study visit) and 
the values will remain as missing except for the following: 
The dichotomous endpoints at Week 12: 

PGA score of cleared (0), cleared (0) or minimal (1), and mild or better (≤ 2);

PASI 100, PASI 90, PASI 75, and PASI 50 responses; 

CDLQI of 0 or 1.
For these types of endpoints, subjects with missing PGA score, PASI score, PASI 
component, or CDLQI at Week 12 will be considered as not achieving the respective 
endpoints at Week 12. 
After Week 52, treatment failure rules or missing data imputations will not be applied for PGA 
scores.
11.4.
Pharmacokinetic Analyses
Serum ustekinumab concentrations over time will be summarized for treated subjects. 
Descriptive statistics, including arithmetic mean, SD, median, interquartile range, minimum, and 
maximum will be calculated at each nominal sampling timepoint. All BQL concentrations or 
missing data will be labeled as such in the concentration data listing or Statistical Analysis 
System (SAS) dataset. The BQL concentrations will be treated as zero in the summary statistics.
A population PK analysis with nonlinear mixed effects modeling (NONMEM) approach will be 
used to characterize the disposition characteristics of ustekinumab in the current study. Data may 
be combined with those of other selected studies to support a relevant structural model. The 
CL/F and V/F values will be estimated. The influence of important variables (such as body 
weight and antibodies to ustekinumab) on the population PK parameter estimates will be 
evaluated. Details will be given in a population PK analysis plan, and results of the population 
PK analysis may be presented in a separate technical report.


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11.5.
Pharmacokinetic/Pharmacodynamic Analyses
A suitable population PK/pharmacodynamic (PD) model will be developed to describe the 
exposure-response relationship. Data may be combined with those of other selected studies to 
support a relevant structural PK/PD model. Details will be given in a population PK/PD analysis 
plan, and results of the population PK/PD analysis may be presented in a separate technical 
report.
11.6.
Immunogenicity Analyses 
The incidence and titers of antibodies to ustekinumab will be summarized for all subjects who 
receive at least 1 dose of ustekinumab and have appropriate samples for detection of antibodies 
to ustekinumab (ie, subjects with at least 1 sample obtained after their first dose of ustekinumab).
A listing of subjects who are positive for antibodies to ustekinumab will be provided in the 
Clinical Study Report (CSR).
The incidence of NAbs to ustekinumab will be summarized for subjects who are positive for 
antibodies to ustekinumab and have samples evaluable for NAbs.
11.7.
Biomarker Analyses 
Results will be presented in a separate report.
11.8.
Pharmacogenomic Analyses 
Results will be presented in a separate report.
11.9.
Safety Analyses
All subjects who receive at least 1 administration of study drug will be included in the safety 
analyses.
Adverse Events
The verbatim terms used in the CRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities (MedDRA). Treatment-emergent AEs are AEs
with onset during the treatment phase or that are a consequence of a pre-existing condition that 
has worsened since baseline. All reported AEs will be included in the analysis. For each AE, the 
percentage of subjects who experience at least 1 occurrence of the given event will be 
summarized by treatment group. In addition, comparisons between treatment groups will be 
provided if appropriate.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, who discontinue treatment due to an AE, or who experience a severe or an 
SAE.


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The following analyses will be used to assess the safety of subjects in the study:

The incidence and type of AEs.

The incidence and type of SAEs.

The incidence and type of reasonably related AEs.

The incidence and type of injection site reactions.

The incidence of infections.

The incidence AEs of psoriasis.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. Markedly abnormal results will 
be used in the summary of laboratory data. Descriptive statistics will be calculated for each 
laboratory analyte and for observed values and changes from baseline at each scheduled time 
point. Frequency tabulations of the markedly abnormalities will be presented. A listing of 
subjects with any markedly abnormal laboratory results will also be provided.
Vital Signs
Descriptive statistics of heart rate, respiratory rate, and blood pressure (systolic and diastolic) 
values and changes from baseline will be summarized at each scheduled time point. 
11.10. Data Monitoring Committee
This is an open-label study. Therefore, the investigators, who have primary responsibility for 
monitoring the safety of individual subjects under their care, will know that all subjects are 
receiving a weight-adjusted standard dosage of active ustekinumab throughout the duration of 
the study. Moreover, the available aggregate unblinded safety data will be routinely evaluated by 
experienced clinical trial medical monitors while the study is ongoing. Therefore, an external 
Data Monitoring Committee will not be utilized.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, investigators, and the Sponsor, and are mandated by 
regulatory agencies worldwide. The Sponsor has established Standard Operating Procedures in 
conformity with regulatory requirements worldwide to ensure appropriate reporting of safety 
information; all clinical studies conducted by the sponsor or its affiliates will be conducted in 
accordance with those procedures.


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12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal 
relationship with the treatment. An AE can therefore be any unfavorable and unintended sign 
(including an abnormal finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational or non-investigational) product, whether or not related to that 
medicinal (investigational or non-investigational) product. (Definition per International 
Conference on Harmonisation [ICH]).
This includes any occurrence that is new in onset or aggravated in severity or frequency from the 
baseline condition, or abnormal results of diagnostic procedures, including laboratory test 
abnormalities.
Note: The sponsor collects AEs starting with the signing of the ICF (refer to Section 12.3.1, All 
Adverse Events, for time of last AE recording).
Serious Adverse Event
An SAE based on ICH and EU Guidelines on Pharmacovigilance for Medicinal Products for 
Human Use is any untoward medical occurrence that at any dose:

Results in death

Is life-threatening
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe).

Requires inpatient hospitalization or prolongation of existing hospitalization

Results in persistent or significant disability/incapacity

Is a congenital anomaly/birth defect

Is a suspected transmission of any infectious agent via a medicinal product

Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
also appropriate in other situations, such as important medical events that may not be 
immediately life threatening or result in death or hospitalization but may jeopardize the subject 
or may require intervention to prevent one of the other outcomes listed in the definition above. 
These should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal 
relationship between the study drug and the event (eg, death from anaphylaxis), the event must 


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be reported as a serious and unexpected suspected adverse reaction even if it is a component of 
the study endpoint (eg, all-cause mortality). 
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For ustekinumab, the expectedness of an AE will be 
determined by whether it is listed in the Investigator's Brochure. 
Adverse Event Associated With the Use of the Drug
An AE is considered associated with the use of the drug if the attribution is possible, probable, or 
very likely by the definitions listed in Section 12.1.2.
12.1.2.
Attribution Definitions
Not Related
An AE that is not related to the use of the drug.
Doubtful
An AE for which an alternative explanation is more likely, eg, concomitant drug(s), concomitant 
disease(s), or the relationship in time suggests that a causal relationship is unlikely.
Possible
An AE that might be due to the use of the drug. An alternative explanation, eg, concomitant 
drug(s), concomitant disease(s), is inconclusive. The relationship in time is reasonable; therefore, 
the causal relationship cannot be excluded.
Probable
An AE that might be due to the use of the drug. The relationship in time is suggestive 
(eg, confirmed by dechallenge). An alternative explanation is less likely, eg, concomitant 
drug(s), concomitant disease(s).
Very Likely
An AE that is listed as a possible adverse reaction and cannot be reasonably explained by an 
alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship in time 
is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
12.1.3.
Severity Criteria 
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.


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Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg, laboratory abnormalities).
Note that seriousness and severity should not be confused. A subject could experience a severe 
headache that would not qualify as an SAE, while another might experience a mild stroke that, 
while not severe, would be considered serious.
12.2.
Special Reporting Situations
Safety events of interest on a sponsor study drug that may require expedited reporting and/or 
safety evaluation include, but are not limited to:

Overdose of a sponsor study drug

Suspected abuse/misuse of a sponsor study drug

Inadvertent or accidental exposure to a sponsor study drug

Medication error involving a sponsor product (with or without subject/patient exposure to 
the sponsor study drug, eg, name confusion)
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the serious adverse event page of the CRF.
12.3.
Procedures
12.3.1.
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from 
the time a signed and dated ICF is obtained until completion of the subject's last study-related 
procedure (which may include contact for follow-up of safety). SAEs, including those 
spontaneously reported to the investigator within 30 days after the last dose of study drug, must 
be reported using the Serious Adverse Event Form. The sponsor will evaluate any safety 
information that is spontaneously reported by an investigator beyond the time frame specified in 
the protocol.
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether 
they are protocol-specific assessments.
All AEs, regardless of seriousness, severity, or presumed relationship to study drug, must be 
recorded using medical terminology in the source document and the CRF. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory 
infection"). Investigators must record in the CRF their opinion concerning the relationship of the 
AE to study therapy. All measures required for AE management must be recorded in the source 
document and reported according to sponsor instructions.


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The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities. 
The sponsor will also report to the investigator (and the head of the investigational institute 
where required) all suspected unexpected serious adverse reactions (SUSARs). The investigator 
(or sponsor where required) must report SUSARs to the appropriate Independent Ethics 
Committee/Institutional Review Board (IEC/IRB) that approved the protocol unless otherwise 
required and documented by the IEC/IRB.
For all studies with an outpatient phase, including open-label studies, the subject (or their 
designees, if appropriate) must be provided with a "wallet (study) card" and instructed to carry 
this card with them for the duration of the study indicating the following:

Study number

Statement, in the local language(s), that the subject is participating in a clinical study

Investigator's name and 24-hour contact telephone number

Local sponsor's name and 24-hour contact telephone number (for medical staff only)

Site number

Subject number
Adverse Events Associated with the Study Population
Worsening of psoriasis is considered common for the study population defined in this protocol 
and, when determined to be serious, should be reported by the investigator as described in 
Section 12.3.2. For safety reporting, single occurrences of the event, when serious, may be 
excluded from expedited reporting. If aggregate analyses of this event indicate that it occurs 
more frequently with study drug, an expedited safety report may be submitted. 
12.3.2.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person 
by study-site personnel within 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event 
Form, which must be completed and signed by a physician from the study site, and transmitted to 
the sponsor within 24 hours. The initial and follow-up reports of an SAE should be made by 
facsimile (fax).
All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject's participation in the study, must be followed until any of the 
following occurs:

The event resolves

The event stabilizes

The event returns to baseline, if a baseline value/status is available


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
The event can be attributed to agents other than the study drug or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject or health care 
practitioner refusal to provide additional information, lost to follow-up after demonstration 
of due diligence with follow-up efforts)
Suspected transmission of an infectious agent by a medicinal product will be reported as an SAE. 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the
subject's participation in a study must be reported as an SAE, except hospitalizations for the 
following:

Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as 
pending placement in long-term care facility)

Surgery or procedure planned before entry into the study (must be documented in the CRF). 
Note: Hospitalizations that were planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened, will not 
be considered SAEs. Any AE that results in a prolongation of the originally planned 
hospitalization is to be reported as a new SAE.
The cause of death of a subject in a study within 16 weeks of the last dose of study drug, whether
the event is expected or associated with the study drug, is considered a SAE.
12.3.3.
Pregnancy 
All initial reports of pregnancy in female subjects or partners of male subjects must be reported 
to the sponsor by the study-site personnel within 24 hours of their knowledge of the event using 
the appropriate pregnancy notification form and report it as AE in CRF. Abnormal pregnancy 
outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic 
pregnancy) are considered SAEs and must be reported using the Serious Adverse Event Form. 
Any subject who becomes pregnant during the study must discontinue further study treatment. 
Because the effect of the study drug on sperm is unknown, pregnancies in partners of male 
subjects included in the study will be reported by the study-site personnel within 24 hours of 
their knowledge of the event using the appropriate pregnancy notification form and report as 
partner pregnancy in CRF. 
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
12.3.4.
Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first administration of 
study drug(s) in subjects participating in this clinical study must be reported by the investigator 
according to procedures in Section 12.3.2.  Investigators are also advised that active TB is 
considered a reportable disease in most countries.  These events are to be considered serious only 
if they meet the definition of an SAE.


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12.4.
Contacting Sponsor Regarding Safety
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding safety issues or questions regarding the study are listed on the Contact Information 
page(s), which will be provided as a separate document.
13.
PRODUCT QUALITY COMPLAINT HANDLING
A product quality complaint (PQC) is defined as any suspicion of a product defect related to 
manufacturing, labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, 
durability, or reliability of a product, including its labeling or package integrity. A PQC may have 
an impact on the safety and efficacy of the product. Timely, accurate, and complete reporting and 
analysis of PQC information from studies are crucial for the protection of subjects, investigators, 
and the sponsor, and are mandated by regulatory agencies worldwide. The sponsor has 
established procedures in conformity with regulatory requirements worldwide to ensure 
appropriate reporting of PQC information; all studies conducted by the sponsor or its affiliates 
will be conducted in accordance with those procedures.
13.1.
Procedures
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after 
being made aware of the event.
If the defect is combined with an SAE, the study-site personnel must report the PQC to the 
sponsor according to the SAE reporting timelines (refer to Section 12.3.2, Serious Adverse 
Events). A sample of the suspected product should be maintained for further investigation if 
requested by the sponsor.
13.2.
Contacting Sponsor Regarding Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed on the Contact Information page(s), which will be 
provided as a separate document.
14.
STUDY DRUG INFORMATION
14.1.
Physical Description of Study Drug(s)
The ustekinumab for this study will be supplied as FVP, single-use 2 mL Schott Type I glass vial 
closed with a Daikyo D777-1 FluroTec®-coated stopper and a West 13 mm aluminum seal and 
plastic light green flip-off button. The FVP formulation is composed of 90 mg/mL ustekinumab 
with excipient concentrations of 6.7 mM L-histidine, 7.6% (w/v) sucrose, and 0.004% (w/v) 
polysorbate 80, pH 6.0. There is 1 dose strength (ie, 45 mg in 0.5 mL volume). No preservatives 
are present.
14.2.
Packaging
The investigational supplies will be uniquely packaged to assure that they are appropriately 
managed throughout the supply chain process.  


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14.3.
Labeling
Study drug labels will contain information to meet the applicable regulatory requirements.
14.4.
Preparation, Handling, and Storage 
All study drug must be stored at controlled temperatures ranging from 36°F to 46°F (2°C to 
8°C). The ustekinumab product should not be frozen and should be protected from light.  
Vigorous shaking of the ustekinumab product should be avoided. The formulation does not 
contain preservatives. Prior to administration, the drug product should be inspected visually for 
particulate matter and discoloration. If discoloration (other than a slight yellow color), visible 
opaque particles, or other foreign particles are observed in the solution, the product should not be 
used.  
Refer to the Site Investigational Product Procedures Manual for additional guidance on study 
drug preparation and handling.
14.5.
Drug Accountability
The investigator is responsible for ensuring that all study drug received at the site is inventoried 
and accounted for throughout the study. The study drug administered to the subject must be 
documented on the drug accountability form. All study drug will be stored and disposed of 
according to the sponsor's instructions. Study-site personnel must not combine contents of the 
study drug containers.
Study drug must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study drug must be available for verification by the sponsor's 
study site monitor during on-site monitoring visits. The return to the sponsor of unused study 
drug will be documented on the drug return form. When the study site is an authorized 
destruction unit and study drug supplies are destroyed on-site, this must also be documented on 
the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes. 
Study drug should be dispensed under the supervision of the investigator or a qualified member 
of the study-site personnel, or by a hospital/clinic pharmacist. Study drug will be supplied only 
to subjects participating in the study. Study drug may not be relabeled or reassigned for use by 
other subjects. The investigator agrees neither to dispense the study drug from, nor store it at, 
any site other than the study sites agreed upon with the sponsor.


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15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Site Investigational Product Procedures Manual

Online access to electronic CRFs and Electronic Data Capture (eDC) Manual

Trial Center File

Laboratory Manual

Interactive Web Response System (IWRS) Manual

Subject study participation card

STELARA (ustekinumab) IB

Sample ICF
The following assessments are included as attachments to the protocol;

Physician’s Global Assessment 

Psoriasis Area and Severity Index

Children’s Dermatology Life Quality Index
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during the 
study, subjects will be given any new information that may affect their decision to continue 
participation. They will be told that their consent to participate in the study is voluntary and may be 
withdrawn at any time with no reason given and without penalty or loss of benefits to which they 
would otherwise be entitled. Only subjects who are fully able to understand the risks, benefits, and 
potential AEs of the study, and provide their consent voluntarily will be enrolled.
When referring to the signing of the ICF, the terms legal guardian and legally acceptable 
representative refer to the legally appointed guardian of the child with authority to authorize 
participation in research. For each subject, his or her parent(s) (preferably both parents, if 
available) or a legally acceptable representative(s), as required by local regulations, must give 
written consent (permission) according to local requirements after the nature of the study has been 
fully explained and before the performance of any study-related assessments. Assent must be 
obtained from children (minors) capable of understanding the nature of the study, typically subjects 
7 years of age and older, depending on the institutional policies. For the purposes of this study, all 
references to subjects who have provided consent (and assent as applicable) refers to the subjects 
and his or her parent(s) or the subject's legal guardian(s) or legally acceptable representative(s) 
who have provided consent according to this process. Minors who assent to a study and later 
withdraw that assent should not be maintained in the study against their will, even if their parents
still want them to participate.


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The total blood volume to be collected during the main study will be approximately 69.5 mL and 
during the LTE will be approximately 18 mL, which is considered to be within the normal range 
allowed for the pediatric population.
16.2.
Regulatory Ethics Compliance
16.2.1.
Investigator Responsibilities
The investigator is responsible for ensuring that the study is performed in accordance with the 
protocol, current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and 
country-specific requirements.
Good Clinical Practice is an international ethical and scientific quality standard for designing, 
conducting, recording, and reporting studies that involve the participation of human subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
16.2.2.
Independent Ethics Committee or Institutional Review Board
Before the start of the study, the investigator (or sponsor where required) will provide the 
IEC/IRB with current and complete copies of the following documents (as required by local 
regulations):

Final protocol and, if applicable, amendments

Sponsor-approved ICF (and any other written materials to be provided to the subjects)

Investigator's Brochure (or equivalent information) and amendments/addenda

Sponsor-approved subject recruiting materials

Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable

Investigator's curriculum vitae or equivalent information (unless not required, as 
documented by the IEC/IRB)

Information regarding funding, name of the sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects

Any other documents that the IEC/IRB requests to fulfill its obligation
This study will be undertaken only after the IEC/IRB has given full approval of the final 
protocol, amendments (if any, excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the ICF, applicable recruiting materials, and 
subject compensation programs, and the sponsor has received a copy of this approval. This 
approval letter must be dated and must clearly identify the IEC/IRB and the documents being 
approved.


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Approval for the collection of optional samples for research and for the corresponding ICF must 
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this 
optional research component.
During the study the investigator (or sponsor where required) will send the following documents 
and updates to the IEC/IRB for their review and approval, where appropriate:

Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of AEs that are serious, unlisted/unexpected, and associated with the study drug

New information that may adversely affect the safety of the subjects or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator's care

Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
For all protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct), the amendment and applicable ICF revisions 
must be submitted promptly to the IEC/IRB for review and approval before implementation of 
the change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study. The 
reapproval should be documented in writing (excluding the ones that are purely administrative, 
with no consequences for subjects, data, or study conduct).
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB 
about the study completion.
16.2.3.
Informed Consent
Each subject (or a legally acceptable representative) must give written consent according to local 
requirements after the nature of the study has been fully explained. The ICF(s) must be signed 
before performance of any study-related activity. The ICF(s) and assent form that is/are used 


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must be approved by both the sponsor and by the reviewing IEC/IRB and be in a language that 
the subject can read and understand. The informed consent should be in accordance with 
principles that originated in the Declaration of Helsinki, current ICH and GCP guidelines, 
applicable regulatory requirements, and sponsor policy.
Before enrollment in the study, the investigator or an authorized member of the study-site 
personnel must explain to potential subjects or their legally acceptable representatives the aims, 
methods, reasonably anticipated benefits, and potential hazards of the study, and any discomfort 
participation in the study may entail. Subjects will be informed that their participation is 
voluntary and that they may withdraw consent to participate at any time. They will be informed 
that choosing not to participate will not affect the care the subject will receive for the treatment 
of his or her disease. Subjects will be told that alternative treatments are available if they refuse
to take part and that such refusal will not prejudice future treatment. Finally, they will be told 
that the investigator will maintain a subject identification register for the purposes of long-term 
follow up if needed and that their records may be accessed by health authorities and authorized 
sponsor personnel without violating the confidentiality of the subject, to the extent permitted by 
the applicable law(s) or regulations. By signing the ICF the subject or legally acceptable 
representative is authorizing such access, including permission to obtain information about his or 
her survival status, and agrees to allow his or her study physician to recontact the subject for the 
purpose of obtaining consent for additional safety evaluations, if needed, and subsequent disease-
related treatments, or to obtain information about his or her survival status.
The subject or legally acceptable representative will be given sufficient time to read the ICF and 
the opportunity to ask questions. After this explanation and before entry into the study, consent 
should be appropriately recorded by means of either the subject's or his or her legally acceptable 
representative's personally dated signature. After having obtained the consent, a copy of the ICF
must be given to the subject.
Subjects will be asked for consent to provide optional samples for research (where local 
regulations permit). After informed consent for the study is appropriately obtained, the subject or 
his or her legally acceptable representative will be asked to sign and personally date a separate 
ICF indicating agreement to participate in the optional research component. Refusal to 
participate in the optional research will not result in ineligibility for the study. A copy of this 
signed ICF will be given to the subject.
A separate ICF will be used for the optional DNA component of the study.
If the subject or legally acceptable representative is unable to read or write, an impartial witness 
should be present for the entire informed consent process (which includes reading and explaining 
all written information) and should personally date and sign the ICF after the oral consent of the 
subject or legally acceptable representative is obtained.
Children (minors) or subjects who are unable to comprehend the information provided can be 
enrolled only after obtaining consent of a legally acceptable representative. Assent must be 
obtained from children (minors) capable of understanding the nature of the study, typically 


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subjects 7 years of age and older, depending on the institutional policies. Written assent should 
be obtained from subjects who are able to write. A separate assent form written in language the 
subject can understand should be developed for adolescents. After having obtained the assent, a 
copy of the assent form must be given to the subject, and to the subject's parent and/or legally 
acceptable representative.
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from subjects enrolled in this study will be 
limited to those data that are necessary to fulfill the objectives of the study.
These data must be collected and processed with adequate precautions to ensure confidentiality 
and compliance with applicable data privacy protection laws and regulations. Appropriate 
technical and organizational measures to protect the personal data against unauthorized 
disclosures or access, accidental or unlawful destruction, or accidental loss or alteration must be 
put in place. Sponsor personnel whose responsibilities require access to personal data agree to 
keep the identity of subjects confidential.
The informed consent obtained from the subject (or his or her legally acceptable representative) 
includes explicit consent for the processing of personal data and for the investigator/institution to 
allow direct access to his or her original medical records (source data/documents) for study-
related monitoring, audit, IEC/IRB review, and regulatory inspection. This consent also 
addresses the transfer of the data to other entities and to other countries.
The subject has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps 
will be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
Exploratory DNA research is not conducted under standards appropriate for the return of data to 
subjects. In addition, the sponsor cannot make decisions as to the significance of any findings 
resulting from exploratory research. Therefore, exploratory research data will not be returned to 
subjects or investigators, unless required by law or local regulations. Privacy and confidentiality 
of data generated in the future on stored samples will be protected by the same standards 
applicable to all other clinical data.
16.2.5.
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local 
regulations) for additional research. Samples will only be used to understand ustekinumab, to 
understand psoriasis, to understand differential drug responders, and to develop tests/assays 
related to ustekinumab and psoriasis. The research may begin at any time during the study or the 
post-study storage period. 


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Stored samples will be coded throughout the sample storage and analysis process and will not be 
labeled with personal identifiers. Subjects may withdraw their consent for their samples to be 
stored for research (refer to Section 10.4, Withdrawal From the Study (Withdrawal From the Use 
of Samples in Future Research).
16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product, unless explicitly addressed as a specific ethical 
consideration in Section 16.1, Study-Specific Design Considerations.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
Protocol Amendments
Neither the investigator nor the sponsor will modify this protocol without a formal amendment 
by the sponsor. All protocol amendments must be issued by the sponsor, and signed and dated by 
the investigator. Protocol amendments must not be implemented without prior IEC/IRB 
approval, or when the relevant competent authority has raised any grounds for non-acceptance, 
except when necessary to eliminate immediate hazards to the subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involves only logistic or administrative aspects of the study, the 
IRB (and IEC where required) only needs to be notified.
During the study, in situations where a departure from the protocol is unavoidable, the 
investigator or other physician in attendance will contact the appropriate sponsor representative 
(see Contact Information page(s) provided separately). Except in emergency situations, this 
contact should be made before implementing any departure from the protocol. In all cases, 
contact with the sponsor must be made as soon as possible to discuss the situation and agree on 
an appropriate course of action. The data recorded in the CRF and source documents will reflect 
any departure from the protocol, and the source documents will describe this departure and the 
circumstances requiring it.
17.2.
Regulatory Documentation
17.2.1.
Regulatory Approval/Notification
This protocol and any amendment(s) must be submitted to the appropriate regulatory authorities 
in each respective country, if applicable. A study may not be initiated until all local regulatory 
requirements are met.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study drug to the 
study site:


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
Protocol and amendment(s), if any, signed and dated by the principal investigator

A copy of the dated and signed (or sealed, where appropriate per local regulations), written 
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if 
applicable, subject compensation programs. This approval must clearly identify the specific 
protocol by title and number and must be signed (or sealed, where appropriate per local 
regulations) by the chairman or authorized designee.

Name and address of the IEC/IRB, including a current list of the IEC/IRB members and 
their function, with a statement that it is organized and operates according to GCP and the 
applicable laws and regulations. If accompanied by a letter of explanation, or equivalent, 
from the IEC/IRB, a general statement may be substituted for this list. If an investigator or a 
member of the study-site personnel is a member of the IEC/IRB, documentation must be 
obtained to state that this person did not participate in the deliberations or in the 
vote/opinion of the study.

Regulatory authority approval or notification, if applicable

Signed and dated statement of investigator (eg, Form Food and Drug Administration [FDA]
1572), if applicable

Documentation of investigator qualifications (eg, curriculum vitae)

Completed investigator financial disclosure form from the principal investigator, where 
required

Signed and dated clinical trial agreement, which includes the financial agreement

Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first subject:

Completed investigator financial disclosure forms from all subinvestigators

Documentation of subinvestigator qualifications (eg, curriculum vitae)

Name and address of any local laboratory conducting tests for the study, and a dated copy of 
current laboratory normal ranges for these tests, if applicable

Local 
laboratory 
documentation 
demonstrating 
competence 
and 
test 
reliability 
(eg, accreditation/license), if applicable
17.3.
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification
and date of birth. In cases where the subject is not randomized into the study, the date seen and 
date of birth will be used.


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The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study.
17.4.
Source Documentation
At a minimum, source documentation must be available for the following to confirm data 
collected in the CRF: subject identification, eligibility, and study identification; study discussion 
and date of signed informed consent; dates of visits; results of safety and efficacy parameters as 
required by the protocol; record of all AEs and follow-up of AEs; concomitant medication; drug 
receipt/dispensing/return records; study drug administration information; and date of study 
completion and reason for early discontinuation of study drug or withdrawal from the study, if 
applicable. 
In addition, the author of an entry in the source documents should be identifiable.
At a minimum, the type and level of detail of source data available for a subject should be 
consistent with that commonly recorded at the study site as a basis for standard medical care. 
Specific details required as source data for the study will be reviewed with the investigator 
before the study and will be described in the monitoring guidelines (or other equivalent 
document).
The minimum source documentation requirements for Section 4.1, Inclusion Criteria and 
Section 4.2, Exclusion Criteria that specify a need for documented medical history are as 
follows:

Previous vaccination (measles and varicella) history and previous infection history
(specifically for subjects in which the screening blood test results do not demonstrate 
positive protective antibody titers to varicella and measles)

Referral letter from treating physician

Complete history of medical notes at the site

Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a 
minimum by subject interview or other protocol required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
17.5.
Case Report Form Completion
Case report forms are provided for each subject in electronic format. 
Electric Data Capture will be used for this study. The study data will be transcribed by study-site
personnel from the source documents onto an electronic CRF, and transmitted in a secure 
manner to the sponsor within the timeframe agreed upon between the sponsor and the study site. 
The electronic file will be considered the CRF.


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Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any 
such worksheets will become part of the subject's source documentation. All data relating to the 
study must be recorded in CRFs prepared by the sponsor. Data must be entered into CRFs in 
English. Study site personnel must complete the CRF as soon as possible after a subject visit, and 
the forms should be available for review at the next scheduled monitoring visit.
All subjective measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual (ie, the blinded efficacy evaluator) who made the initial 
baseline determinations whenever possible. The investigator must verify that all data entries in 
the CRFs are accurate and correct.
All CRF entries, corrections, and alterations must be made by the investigator or other authorized 
study-site personnel. If necessary, queries will be generated in the eDC tool. The investigator or 
study-site personnel must adjust the CRF (if applicable) and complete the query. 
If corrections to a CRF are needed after the initial entry into the CRF, this can be done in 3 
different ways:

Study site personnel can make corrections in the eDC tool at their own initiative or as a 
response to an auto query (generated by the eDC tool).

Study site manager can generate a query for resolution by the study-site personnel.

Clinical data manager can generate a query for resolution by the study-site personnel.
17.6.
Data Quality Assurance/Quality Control
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified 
investigators and appropriate study sites, review of protocol procedures with the investigator and 
study-site personnel before the study, periodic monitoring visits by the sponsor, and direct 
transmission of clinical laboratory data from a central laboratory and the IWRS into the 
Sponsor's data base. Written instructions will be provided for collection, handling, storage, and 
shipment of samples. 
Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study.
The sponsor will review CRFs for accuracy and completeness during on-site monitoring visits 
and after transmission to the sponsor; any discrepancies will be resolved with the investigator or 
designee, as appropriate. After upload of the data into the study database they will be verified for 
accuracy and consistency with the data sources. 
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRFs 
and all source documents that support the data collected from each subject, as well as all study 
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a 
Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 


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The investigator/institution will take measures to prevent accidental or premature destruction of 
these documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing 
application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
17.8.
Monitoring
The sponsor will use a combination of monitoring techniques: central, remote, and/or on-site 
monitoring to monitor this study.
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will 
record dates of the visits in a study site visit log that will be kept at the study site. The first post-
initiation visit will be made as soon as possible after enrollment has begun. At these visits, the 
monitor will compare the data entered in the CRFs with the hospital or clinic records (source 
documents). The nature and location of all source documents will be identified to ensure that all 
sources of original data required to complete the CRF are known to the sponsor and study-site 
personnel and are accessible for verification by the sponsor study-site contact. If electronic 
records are maintained at the study site, the method of verification must be discussed with the 
study-site personnel. 
Direct access to source documentation (medical records) must be allowed for the purpose of 
verifying that the data recorded in the CRF are consistent with the original source data. Findings 
from this review of CRFs and source documents will be discussed with the study-site personnel. 
The sponsor expects that, during monitoring visits, the relevant study-site personnel will be 
available, the source documentation will be accessible, and a suitable environment will be 
provided for review of study-related documents. The monitor will meet with the investigator on a 
regular basis during the study to provide feedback on the study conduct.


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In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, study-site personnel will be available to provide an update on the progress 
of the study at the site. 
Central monitoring will take place for data identified by the sponsor as requiring central review.
17.9.
Study Completion/Termination
17.9.1.
Study Completion

The main study is considered completed when the last follow-up for the last subject 
participating is completed at Week 56. 

The LTE is considered completed when all subjects have either terminated participation 
according to Section 3.1 or completed their follow-up at Week 264.  
The final data from the study site will be sent to the sponsor (or designee) after completion of the 
final subject telephone follow-up at that study site, in the time frame specified in the Clinical 
Trial Agreement.
17.9.2.
Study Termination
The sponsor reserves the right to close the study site or terminate the study at any time for any 
reason at the sole discretion of the sponsor. Study sites will be closed upon study completion. A
study site is considered closed when all required documents and study supplies have been 
collected and a study-site closure visit has been performed.
The investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination.
Reasons for the early closure of a study site by the sponsor or investigator may include but are 
not limited to:

Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or 
local health authorities, the sponsor's procedures, or GCP guidelines

Inadequate recruitment of subjects by the investigator

Discontinuation of further study drug development
17.10. On-Site Audits
Representatives of the sponsor's clinical quality assurance department may visit the study site at 
any time during or after completion of the study to conduct an audit of the study in compliance 
with regulatory guidelines and company policy. These audits will require access to all study 
records, including source documents, for inspection and comparison with the CRFs. Subject 
privacy must, however, be respected. The investigator and study-site personnel are responsible 
for being present and available for consultation during routinely scheduled study-site audit visits 
conducted by the sponsor or its designees. 


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Similar auditing procedures may also be conducted by agents of any regulatory body, either as 
part of a national GCP compliance program or to review the results of this study in support of a 
regulatory submission. The investigator should immediately notify the sponsor if he or she has
been contacted by a regulatory agency concerning an upcoming inspection.
17.11. Use of Information and Publication
All information, including but not limited to information regarding ustekinumab or the sponsor's 
operations (eg, patent application, formulas, manufacturing processes, basic scientific data, prior 
clinical data, formulation information) supplied by the sponsor to the investigator and not 
previously published, and any data, including pharmacogenomic research data, generated as a 
result of this study, are considered confidential and remain the sole property of the sponsor. The 
investigator agrees to maintain this information in confidence and use this information only to 
accomplish this study, and will not use it for other purposes without the sponsor's prior written 
consent.
The investigator understands that the information developed in the study will be used by the 
sponsor in connection to the continued development of ustekinumab, and thus may be disclosed 
as required to other clinical investigators or regulatory agencies. To permit the information 
derived from the clinical studies to be used, the investigator is obligated to provide the sponsor 
with all data obtained in the study.
The results of the study will be reported in a CSR generated by the sponsor and will contain CRF 
data from all study sites that participated in the study, and direct transmission of clinical
laboratory data from a central laboratory into the sponsor's database. Recruitment performance or 
specific expertise related to the nature and the key assessment parameters of the study will be 
used to determine a coordinating investigator. Results of pharmacogenomic or exploratory 
biomarker analyses performed after the CSR has been issued will be reported in a separate report 
and will not require a revision of the CSR. Study subject identifiers will not be used in 
publication of results. Any work created in connection to performance of the study and contained 
in the data that can benefit from copyright protection (except any publication by the investigator 
as provided for below) shall be the property of the sponsor as author and owner of copyright in 
such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor shall have the right to publish such primary (multicenter) data 
and information without approval from the investigator. The investigator has the right to publish 
study site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow 
for filing of a patent application. If issues arise regarding scientific integrity or regulatory 
compliance, the sponsor will review these issues with the investigator. The sponsor will not 
mandate modifications to scientific content and does not have the right to suppress information.


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For multicenter study designs and substudy approaches, secondary results generally should not 
be published before the primary endpoints of a study have been published. Similarly, 
investigators will recognize the integrity of a multicenter study by not submitting for publication 
data derived from the individual study site until the combined results from the completed study
have been submitted for publication, within 12 months of the availability of the final data (tables, 
listings, graphs), or the sponsor confirms there will be no multicenter study publication. 
Authorship of publications resulting from this study will be based on the guidelines on 
authorship, such as those described in the Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical 
review of the paper, and given final approval of the final version.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and/or disclose the existence of and the results of clinical studies as 
required by law.


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REFERENCES
1.
Beattie PE, Lewis-Jones MS. A comparative study of impairment of quality of life in children with skin disease 
and children with other chronic childhood diseases. Br J Dermatol. 2006; 155(1):145-151.
2.
Centers for Disease Control and Prevention. National Health and Nutrition Examination Survey. 
http://www.cdc.gov/nchs/nhanes.htm. Accessed 6 January 2015. 
3.
Feldman SR, Gordon KB, Bala M, et al. Infliximab treatment results in significant improvement in the quality 
of life of patients with severe psoriasis: a double-blind placebo-controlled trial. Br J Dermatol. 2005; 152:954-
960. 
4.
Finlay AY, Khan GK. Dermatology Life Quality Index (DLQI)—a simple practical measure for routine 
clinical use. Clin Exp Dermatol. 1994; 19(3):210-216. 
5.
Fredriksson T, Pettersson U. Severe psoriasis—oral therapy with a new retinoid. Dermatologica. 1978;
157(4):238-244.
6.
Griffiths CE, Barker JN. Pathogenesis and clinical features of psoriasis. Lancet. 2007;370:263-271. 
7.
Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in 
psoriasis. J Invest Dermatol. 2010; 130:1373–1383.  
8.
Kryczek I, Bruce AT, Gudjonsson JE, et al. Induction of IL-17+ T cell trafficking and development by 
IFN-gamma: mechanism and pathological relevance in psoriasis. J Immunol. 2008; 181:4733–4741. 
9.
Landells I, Marano C, Hsu M-C, et al. Ustekinumab in adolescent patients age 12 to 17 years with moderate-
to-severe plaque psoriasis: results of the randomized Phase 3 CADMUS study. J Am Acad Dermatol. 2015; 
73(4):594–603. 
10.
Lara-Corrales I, Xi N, Pope E. Childhood psoriasis treatment: evidence published over the last 5 years. Rev 
Recent Clin Trials 2011;6:36-43.
11.
Leonardi CL, Kimball AB, Papp KA, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 
monoclonal antibody, in patients with psoriasis: 76-week results from a randomised, double-blind, placebo-
controlled trial (PHOENIX 1). Lancet. 2008; 371:1665-1674.  
12.
Lewis-Jones MS, Finlay AY. The Children's Dermatology Life Quality Index (CDLQI): initial validation and 
practical use. Br J Dermatol. 1995; 132(6):942-949.  
13.
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 2007;445:866-873.
14.
Paller AS, Siegfried EC, Langley RG, et al, for the Etanercept Pediatric Psoriasis Study Group. Etanercept 
treatment for children and adolescents with plaque psoriasis. N Engl J Med. 2008; 358(3):241-251.  
15.
Papp KA, Langley RG, Lebwohl M, et al. Efficacy and safety of ustekinumab, a human interleukin-12/23 
monoclonal antibody, in patients with psoriasis: 52-week results from a randomised, double-blind, placebo-
controlled trial (PHOENIX 2). Lancet. 2008; 371(9625):1675-1684.
16.
Rapp SR, Feldman SR, Exum ML, Fleischer AB Jr, Reboussin DM. Psoriasis causes as much disability as 
other major medical diseases. J Am Acad Dermatol. 1999;41(3 Pt 1):401-407.
17.
Sofen H, Smith S, Matheson RT, et al. Guselkumab (an IL-23-specific mAb) demonstrates clinical and 
molecular response in patients with moderate-to-severe psoriasis. J Allergy Clin Immunol. 2014; 133(4):1032-
1040. 
18.
Varni JW, Globe DR, Gandra SR, Harrison DJ, Hooper M, Baumgartner S. Health-related quality of life of 
pediatric patients with moderate to severe plaque psoriasis: comparisons to four common chronic diseases. Eur 
J Pediatr. 2012;171(3):485-492.  
19.
Wang Y, Jadhav PR, Lala M, Gobburu JV. Clarification on precision criteria to derive sample size when 
designing pediatric pharmacokinetic studies. J Clin Pharmacol. 2012; 52:1601-1606.  
20.
Yawalkar N, Tscharner GG, Hunger RE, Hassan AS. Increased expression of IL-12p70 and IL-23 by multiple 
dendritic cell and macrophage subsets in plaque psoriasis. J Dermatol Sci. 2009;54:99-105


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21.
Zaba LC, Cardinale I, Gilleaudeau P, et al. Amelioration of epidermal hyperplasia by TNF inhibition is 
associated with reduced Th17 responses. J Exp Med. 2007; 204:3183-3194.  
22.
Zhang L, Yang XQ, Cheng J, Hui R-S, Gao T-W. Increased Th17 cells are accompanied by FoxP3(+) Treg cell 
accumulation and correlated with psoriasis disease severity. Clin Immunol. 2010; 135:108-117. 


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Attachment 1: QuantiFERON®-TB Gold Testing
The QuantiFERON®-TB Gold test is one of the interferon-(IFN-) based blood assays for TB screening (Cellestis, 
2009).  It utilizes the recently identified M. tuberculosis-specific antigens ESAT-6 and CFP-10 in the standard 
format, as well as TB7.7 (p4) in the In-Tube format, to detect in vitro cell-mediated immune responses in infected 
individuals.  The QuantiFERON®-TB Gold assay measures the amount of IFN-produced by sensitized T-cells 
when stimulated with the synthetic M. tuberculosis-specific antigens.  In M. tuberculosis-infected persons, sensitized 
T lymphocytes will secrete IFN-in response to stimulation with the M. tuberculosis-specific antigens and, thus, the 
QuantiFERON®-TB Gold test should be positive.  Because the antigens used in the test are specific to M. 
tuberculosis and not found in BCG, the test is not confounded by BCG vaccination, unlike the tuberculin skin test.  
However, there is some cross-reactivity with the 3 Mycobacterium species, M. kansasii, M. marinum, and 
M. szulgai.  Thus, a positive test could be the result of infection with one of these 3 species of Mycobacterium, in 
the absence of M. tuberculosis infection.
In a study of the QuantiFERON®-TB Gold test (standard format) in subjects with active TB, sensitivity has been 
shown to be approximately 89% (Mori et al, 2004).  Specificity of the test in healthy BCG-vaccinated individuals 
has been demonstrated to be more than 98%.  In contrast, the sensitivity and specificity of the tuberculin skin test 
was noted to be only about 66% and 35% in a study of Japanese patients with active TB and healthy BCG-
vaccinated young adults, respectively.  However, sensitivity and specificity of the tuberculin skin test depend on the 
population being studied, and the tuberculin skin test performs best in healthy young adults who have not been 
BCG-vaccinated.
Data from a limited number of published studies examining the performance of the QuantiFERON®-TB Gold assay 
in immunosuppressed populations suggest that the sensitivity of the QuantiFERON®-TB Gold test is better than the 
tuberculin skin test even in immunosuppressed patients (Ferrara et al, 2005; Kobashi et al, 2007; Matulis et al, 
2008).  The ability of IFN--based tests to detect latent infection has been more difficult to study due to the lack of a 
gold standard diagnostic test; however, several TB outbreak studies have demonstrated that the tests correlated 
better than the tuberculin skin test with the degree of exposure that contacts had to the index TB case (Brock et al, 
2004; Ewer et al, 2003).  In addition, TB contact tracing studies have shown that patients who had a positive 
QuantiFERON®-TB Gold test result and were not treated for latent TB infection were much more likely to develop 
active TB during longitudinal follow-up than those who had a positive tuberculin skin test and a negative 
QuantiFERON®-TB Gold test result (Higuchi et al, 2007; Diel et al, 2008).
Although the performance of the new IFN--based blood tests for active or latent M. tuberculosis infection have not 
been well validated in the immunosuppressed population, experts believe these new tests will be at least as, if not 
more, sensitive, and definitely more specific, than the tuberculin skin test (Barnes, 2004; personal communication, 
April, 2008 TB Advisory Board).
Performing the QuantiFERON®-TB Gold Test
The QuantiFERON®-TB Gold test In-Tube format will be provided for this study.  The In-Tube format contains 1 
additional M. tuberculosis-specific antigen, TB7.7 (p4), which is thought to increase the specificity of the test.  
To perform the test using the In-Tube format, blood is drawn through standard venipuncture into supplied tubes that 
already contain the M. tuberculosis-specific antigens.  Approximately 3 tubes will be needed per subject, each 
requiring 1 mL of blood.  One tube contains the M. tuberculosis-specific antigens, while the remaining tubes contain 
positive and negative control reagents.  Thorough mixing of the blood with the antigens is necessary prior to 
incubation.  The blood is then incubated for 16 to 24 hours at 37C, after which tubes are centrifuged for 
approximately 15 minutes at 2000 to 3000 g.  Following centrifugation, plasma is harvested from each tube, frozen, 
and shipped on dry ice to the central laboratory.  The central laboratory will perform an ELISA to quantify the 
amount of IFN-present in the plasma using spectrophotometry and computer software analysis.
The central laboratory will analyze and report results for each subject, and sites will be informed of the results.  
Subjects who have an indeterminate result should have the test repeated.


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Adherence to Local Guidelines
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous 
treatment regimens for latent TB.  If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed.
In countries in which the QuantiFERON®-TB Gold test is not considered approved/registered, a tuberculin skin test 
is additionally required.
References
Barnes PF.  Diagnosing latent tuberculosis infection:  Turning glitter to gold [editorial].  Amer J Respir Crit Care 
Med. 2004;170:5-6.
Brock I, Weldingh K, Lillebaek T, et al.  Comparison of tuberculin skin test and new specific blood test in 
tuberculosis contacts.  Am J Respir Crit Care Med. 2004;170:65-69.
Cellestis.  QuantiFERON-TB Gold clinicians guide and QuantiFERON-TB Gold In-Tube Method package insert.  
Downloaded from www.cellestis.com, February 2009.
Diel R, Loddenkemper R, Meywald-Walter K, Niemann S, Nienhaus A.  Predictive value of a whole blood IFN-
assay for the development of active tuberculosis disease after recent infection with mycobacterium tuberculosis.  Am 
J Respir Crit Care Med. 2008;177:1164-1170.
Ewer K, Deeks J, Alvarez L, et al.  Comparison of T-cell-based assay with tuberculin skin test for diagnosis of 
Mycobacterium tuberculosis infection in a school tuberculosis outbreak.  Lancet. 2003;361:1168-73.
Ferrara G, Losi M, Meacci M, et al.  Routine hospital use of a new commercial whole blood interferon-assay for 
the diagnosis of tuberculosis infection.  Am J Respir Crit Care Med. 2005; 172:631-635.
Higuchi K, Nobuyuki H, Mori T, Sekiya Y.  Use of QuantiFERON-TB Gold to investigate tuberculosis contacts in a 
high school.  Respirology.  2007;12:88-92.
Kobashi Y, Mouri K, Obase Y, et al.  Clinical evaluation of QuantiFERON TB-2G test for immunocompromised 
patients.  Eur Respir J. 2007; 30:945-950.
Matulis G, Jüni P, Villiger PM, Gadola SD.  Detection of latent tuberculosis in immunosuppressed patients with 
autoimmune diseases: performance of a Mycobacterium tuberculosis antigen-specific interferon assay.  Ann 
Rheum Dis. 2008;67:84-90
Mori T, Sakatani M, Yamagishi F, et al.  Specific detection of tuberculosis infection:  An interferon--based assay 
using new antigens.  Am J Respir Crit Care Med. 2004;170:59-64.


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Attachment 2: Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis.  Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled.  
Tuberculin skin testing is both safe and reliable throughout the course of pregnancy.  The Mantoux tuberculin test is 
performed by placing an intradermal injection of 0.1 mL of tuberculin into the inner surface of the forearm.  The test 
must be performed with tuberculin that has at least the same strength as either 5 tuberculin units (TU) of standard 
purified protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Seruminstitut, as recommended by the World 
Health Organization.  PPD strengths of 1 TU or 250 TU are not acceptable (Menzies, 2000).  Using a disposable 
tuberculin syringe with the needle bevel facing upward, the injection should be made just beneath the surface of the 
skin.  This should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter.  To prevent 
needle-stick injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, 
or otherwise manipulated by hand.  After they are used, disposable needles and syringes should be placed in 
puncture-resistant containers for disposal.  Institutional guidelines regarding universal precautions for infection 
control (eg, the use of gloves) should be followed.  A trained health care worker, preferably the investigator, should 
read the reaction to the Mantoux test 48 to 72 hours after the injection.  Subjects should never be allowed to read 
their own tuberculin skin test results.  If a subject fails to show up for the scheduled reading, a positive reaction may 
still be measurable up to 1 week after testing.  However, if a subject who fails to return within 72 hours has a 
negative test, tuberculin testing should be repeated.  The area of induration (palpable raised hardened area) around 
the site of injection is the reaction to tuberculin.  For standardization, the diameter of the induration should be 
measured transversely (perpendicular) to the long axis of the forearm.  Erythema (redness) should not be measured.  
All reactions should be recorded in millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised patients, and this definition is to be applied in this study to maximize the 
likelihood of detecting latent TB, even though the subjects may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin skin test is 
considered to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be 
consulted for the interpretation of tuberculin skin test results.  If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed.
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous 
treatment regimens for latent TB.  If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed.
References
Centers for Disease Control and Prevention.  Core curriculum on tuberculosis:  What the clinician should know 
(Fourth Edition).  Atlanta, GA:  Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86. 
Menzies RI.  Tuberculin skin testing.  In:  Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach.  2nd ed.  New York, NY:  Marcel Dekker, Inc.; 2000:279-322.


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Attachment 3: Physician’s Global Assessment
The PGA is used to determine the subject’s psoriasis lesions overall at a given time point.  
Overall lesions will be graded for induration, erythema, and scaling based on the scales below.  
The sum of the 3 scales will be divided by 3 to obtain a final PGA score.
Induration (I) (averaged over all lesions; use the National Psoriasis Foundation Reference card 
for measurement)
0 = no evidence of plaque elevation
1 = minimal plaque elevation, = 0.25 mm
2 = mild plaque elevation, = 0.5 mm
3 = moderate plaque elevation, = 0.75 mm
4 = marked plaque elevation, = 1 mm
5 = severe plaque elevation, = 1.25 mm or more
Erythema (E) (averaged over all lesions)
0 = no evidence of erythema, hyperpigmentation may be present
1 = faint erythema
2 = light red coloration
3 = moderate red coloration
4 = bright red coloration
5 = dusky to deep red coloration
Scaling (S) (averaged over all lesions)
0 = no evidence of scaling
1 = minimal; occasional fine scale over less than 5% of the lesion
2 = mild; fine scale dominates
3 = moderate; coarse scale predominates
4 = marked; thick, nontenacious scale dominates
5 = severe; very thick tenacious scale predominates
Add I + E + S = ______   / 3 = ________(Total Average)
Physician’s Static Global Assessment based upon above Total Average
0 = Cleared, except for residual discoloration
1 = Minimal - majority of lesions have individual scores for I + E + S / 3 that averages 1
2 = Mild - majority of lesions have individual scores for I + E + S / 3 that averages 2
3 = Moderate - majority of lesions have individual scores for I + E + S / 3 that averages 3
4 = Marked - majority of lesions have individual scores for I + E + S / 3 that averages 4
5 = Severe - majority of lesions have individual scores for I + E + S / 3 that averages 5
Note:  Scores should be rounded to the nearest whole number.  If total ≤1.49, score = 1; if total 
≥1.50, score = 2


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Attachment 4: Psoriasis Area and Severity Index
The Psoriasis Area and Severity Index or PASI is a system used for assessing and grading the 
severity of psoriatic lesions and their response to therapy.  The PASI produces a numeric score 
that can range from 0 to 72.  The severity of disease is calculated as follows.
In the PASI system, the body is divided into 4 regions:  the head (h), trunk (t), upper extremities 
(u), and lower extremities (l), which account for 10%, 30%, 20% and 40% of the total BSA, 
respectively.  Each of these areas is assessed separately for erythema, induration and scaling, 
which are each rated on a scale of 0 to 4.
The scoring system for the signs of the disease (erythema, induration, and scaling) are:  0 = none, 
1 = slight, 2 = moderate, 3 = severe, and 4 = very severe.
The scale for estimating the area of involvement for psoriatic lesions is outlined below.
0 = no involvement
1 = 1% to 9% involvement
2 = 10% to 29% involvement
3 = 30% to 49% involvement
4 = 50% to 69% involvement
5 = 70% to 89% involvement
6 = 90% to 100% involvement
To help with the area assessments, the following conventions should be noted:
a.
the neck is considered part of the head
b.
the axillae and groin are part of the trunk
c.
the buttocks are part of the lower extremities
The PASI formula is:
PASI = 0.1 (Eh + Ih + Sh) Ah + 0.3 (Et + It + St) At + 0.2 (Eu + Iu + Su) Au + 0.4 (El + Il + Sl) Al
where E = erythema, I = induration, S = scaling, and A = area


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Attachment 5: Children’s Dermatology Life Quality Index
1.    Over the last week, how itchy, “scratchy”, sore or painful has your skin been?    
Very much
Quite a lot
Only a little
Not at all




2.    Over the last week, how embarrassed or self conscious, upset or sad have you 
been
       because of your skin?
Very much
Quite a lot
Only a little
Not at all




3.    Over the last week, how much has your skin affected your friendships?
Very much
Quite a lot
Only a little
Not at all




4.    Over the last week, how much have you changed or worn different or special
       clothes/shoes because of your skin?
      
Very much
Quite a lot
Only a little
Not at all




5.    Over the last week, how much has your skin trouble affected going out, playing, 
or 
       doing hobbies?
Very much
Quite a lot
Only a little
Not at all




6.    Over the last week, how much have you avoided swimming, or other sports
because of 
       your skin trouble?
     
Very much
Quite a lot
Only a little
Not at all




7.    Last week,
                          was it
                     school time?                  
                                     OR
                         was it 
                    holiday time?
If school time:  Over the last week, how 
much did your skin problem affect your 
school work?
Prevented school
Very much
Quite a lot
Only a little
Not at all





If holiday time:  How much over the last 
week, has your skin problem interfered with 
your enjoyment of the holiday?
Very much
Quite a lot
Only a little
Not at all




8.    Over the last week, how much trouble have you had because of your skin with 
other
       people calling you names, teasing, bullying, asking questions or avoiding 
you?
Very much
Quite a lot
Only a little
Not at all




9.    Over the last week, how much has your sleep been affected by your skin problem?
Very much
Quite a lot
Only a little
Not at all




10.  Over the last week, how much of a problem has the treatment for your skin been?
Very much
Quite a lot
Only a little
Not at all






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INVESTIGATOR AGREEMENT
PPD
PPD

SAP_001.pdf: 
1
Approved, Date: 8 February 2018
Janssen Research & Development 
Statistical Analysis Plan
A Phase 3 Open-label Study to Assess the Efficacy, Safety, and Pharmacokinetics of
Subcutaneously Administered Ustekinumab in the Treatment of Moderate to Severe
Chronic Plaque Psoriasis in Pediatric Subjects ≥6 to <12 Years of Age
Protocol CNTO1275PSO3013; Phase 3
CNTO1275  (Ustekinumab)
Status:
Approved
Date:
8 February 2018
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-ERI-152425925
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
NCT02698475


CNTO1275  (Ustekinumab)
Statistical Analysis Plan CNTO1275PSO3013
2
Approved, Date: 8 February 2018
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
ABBREVIATIONS ........................................................................................................................................ 4
1.
INTRODUCTION.................................................................................................................................. 5
1.1.
Trial Objectives ................................................................................................................................ 5
1.2.
Trial Design ...................................................................................................................................... 5
1.3.
Statistical Hypotheses for Trial Objectives....................................................................................... 7
1.4.
Sample Size Justification ................................................................................................................. 7
1.5.
Randomization and Blinding ............................................................................................................ 8
2.
GENERAL ANALYSIS DEFINITIONS ................................................................................................ 8
2.1.
Imputation Rules for Partial or Missing AE Dates............................................................................ 8
2.2.
Visit Windows................................................................................................................................... 9
2.3.
Pooling Algorithm for Analysis Centers............................................................................................ 9
2.4.
Analysis Sets.................................................................................................................................... 9
2.4.1.
Efficacy Analysis Set(s) ................................................................................................................ 9
2.4.1.1.
Full Analysis Set ........................................................................................................................ 9
2.4.1.2.
Per Protocol Analysis Set.......................................................................................................... 9
2.4.2.
Safety Analysis Set..................................................................................................................... 11
2.4.3.
Pharmacokinetics Analysis Set .................................................................................................. 11
2.4.4.
Immunogenicity Analysis Set...................................................................................................... 11
2.5.
Definition of Subgroups.................................................................................................................. 11
2.6.
Study Day and Baseline Definition................................................................................................. 12
2.6.1.
Study Day ................................................................................................................................... 12
2.6.2.
Baseline ...................................................................................................................................... 12
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 12
4.
SUBJECT INFORMATION................................................................................................................ 12
4.1.
Demographics and Baseline Characteristics ................................................................................. 13
4.1.1.
Demographics............................................................................................................................. 13
4.1.2.
Baseline Characteristics ............................................................................................................. 13
4.2.
Disposition Information................................................................................................................... 13
4.3.
Treatment Compliance................................................................................................................... 14
4.4.
Extent of Exposure......................................................................................................................... 14
4.5.
Protocol Deviations ........................................................................................................................ 14
4.6.
Prior and Concomitant Medications ............................................................................................... 15
5.
EFFICACY ......................................................................................................................................... 15
5.1.
Analysis Specifications................................................................................................................... 15
5.1.1.
Level of Significance................................................................................................................... 15
5.1.2.
Definition of the Efficacy Endpoints and Calculation of the Efficacy Instruments ...................... 15
5.1.2.1.
Physician’s Global Assessment............................................................................................... 15
5.1.2.2.
Psoriasis Area and Severity Index .......................................................................................... 16
5.1.2.3.
Children Dermatology Life Quality Index................................................................................. 16
5.1.3.
Data Handling Rules................................................................................................................... 17
5.1.3.1.
Treatment Failure Criteria........................................................................................................ 17
5.1.3.2.
Treatment Failure Rules .......................................................................................................... 18
5.1.3.3.
Additional Data Handling Rules for Children Life Quality Index (CDLQI) ............................... 18
5.1.3.4.
Missing Data Imputation.......................................................................................................... 19
5.2.
Primary Efficacy Endpoint(s).......................................................................................................... 19
5.2.1.
Definition..................................................................................................................................... 19
5.2.2.
Estimand..................................................................................................................................... 19
5.2.3.
Analysis Methods........................................................................................................................ 19
5.2.4.
Data Handling ............................................................................................................................. 20
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5.3.
Major Secondary Endpoints........................................................................................................... 20
5.3.1.
Definition..................................................................................................................................... 20
5.3.2.
Analysis Methods........................................................................................................................ 20
5.3.3.
Data Handling ............................................................................................................................. 21
5.4.
Other Efficacy Variable(s) .............................................................................................................. 21
5.4.1.
Definition..................................................................................................................................... 21
5.4.2.
Analysis Methods........................................................................................................................ 21
5.4.2.1.
Analyses Related to PGA........................................................................................................ 22
5.4.2.2.
Analyses Related to PASI ....................................................................................................... 22
5.4.2.3.
Analyses Related to CDLQI..................................................................................................... 22
5.4.3.
Data Handling ............................................................................................................................. 22
6.
SAFETY............................................................................................................................................. 22
6.1.
Adverse Events .............................................................................................................................. 23
6.2.
Clinical Laboratory Tests................................................................................................................ 24
6.3.
Vital Signs and Physical Examination Findings ............................................................................. 25
6.4.
Other Safety Parameters ............................................................................................................... 26
7.
PHARMACOKINETICS/PHARMACODYNAMICS/IMMUNOGENICITY .......................................... 26
7.1.
Pharmacokinetics........................................................................................................................... 26
7.2.
Immunogenicity.............................................................................................................................. 27
7.3.
Pharmacokinetic/Pharmacodynamic Relationships....................................................................... 28
7.4.
Biomarker....................................................................................................................................... 28
7.5.
Pharmacogenomic (DNA) Evaluations .......................................................................................... 28
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ABBREVIATIONS
AE
adverse event
CDLQI
Children Dermatology Life Quality Index
CI
confidence interval
CL/F
apparent clearance
CRF
case report form
CSR
Clinical Study Report
DBL
database lock
DMC
Data Monitoring Committee
DPS
Data Presentation Specifications
eCRF
electronic case report form
FDA
Food and Drug Administration
IgG1λ
Immunoglobulin G1 lambda
IWRS
interactive web response system
LTE
long-term extension
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
MTX
methotrexate
NAb
neutralizing antibodies
PASI
Psoriasis Area and Severity Index
PD
pharmacodynamic
PGA
Physician’s Global Assessment
PK
pharmacokinetic(s)
PK/PD
pharmacokinetic/ pharmacodynamic 
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
V/F
apparent volume of distribution
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1.
INTRODUCTION
This statistical analysis plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical methods for the analysis of efficacy, safety and pharmacokinetics for the ustekinumab 
(CNTO 1275) clinical study CNTO1275PSO3013. Ustekinumab is a fully human 
immunoglobulin G1 lambda (IgG1κ) monoclonal antibody (mAb) that binds both human 
interleukin (IL)-12 and IL-23 via a common IL-12/23p40 subunit and has been approved for the 
treatment for the adult and adolescent subjects (12 years and older) with moderate to severe 
psoriasis in North America, Europe and other countries based on the CNTO1275PSO3006 
(CADMUS) study in 110 subjects. Study CNTO1275PSO3013 evaluates the efficacy, safety and 
pharmacokinetics of ustekinumab for the treatment of pediatric subjects aged ≥6 to <12 years old 
with moderate to severe psoriasis.  
1.1.
Trial Objectives
Primary Objective
The primary objective of this study is:

To evaluate the efficacy and safety of ustekinumab in pediatric subjects aged ≥6 through 
<12 years with moderate to severe chronic plaque psoriasis.
Secondary Objectives
The secondary objectives of this study are:

To evaluate the pharmacokinetics of ustekinumab in pediatric subjects aged ≥6 through 
<12 years with moderate to severe chronic plaque psoriasis.

To evaluate the effect of ustekinumab on the dermatologic health-related quality of life in 
pediatric subjects aged ≥6 through <12 years with moderate to severe chronic plaque 
psoriasis.

To evaluate the immunogenicity of ustekinumab in pediatric subjects aged ≥6 through 
<12 years with moderate to severe chronic plaque psoriasis.
1.2.
Trial Design
Main Study: Week 0 through Week 56
This is an open label multicenter study of ustekinumab in pediatric subjects ≥6 to <12 years of
age with moderate to severe chronic plaque psoriasis. The subject population will be comprised
of boys and girls who have had a diagnosis of plaque-type psoriasis for at least 6 months prior to
first study drug administration and who have moderate to severe disease defined by PASI ≥12,
PGA ≥3, and BSA ≥10%.
At least 40 subjects will receive ustekinumab administered subcutaneously at weight-based doses
at Weeks 0 and 4 followed by dose administrations every 12 weeks (q12w) through Week 40. 
Subject weight will be measured at each visit and the dose of ustekinumab will be adjusted 
accordingly. Expected duration of exposure to study drug during the active treatment period is 
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52 weeks. Visits will be every 4 weeks (q4w) through Week 16, then q12w through Week 52. 
Efficacy assessments will be collected through Week 52. Subjects will have a final safety follow-
up at Week 56. A database lock (DBL) will occur at the end of the main study (Week 56). 
The study schema is presented in Figure 1.
Figure 1:
Study Schema for the Main Study (Week 0 through Week 56)
For those subjects who do not meet the protocol defined criteria to enter the LTE of the study, 
Week 56 safety follow-up will be the end of study participation for these subjects.
Long-term Extension: Week 56 through Week 264
Following completion of the Week 52 visit, subjects who have had a beneficial response from
ustekinumab treatment as determined by the investigator, and who have not yet reached the age
of 12 years or older in countries where marketing authorization for ustekinumab has been
granted for the treatment of psoriasis in adolescent patients (12-17 years), and are willing to
continue ustekinumab treatment, may enter the LTE of the study. For these subjects, the safety
follows up for the main study and the first ustekinumab administration of the LTE will be at the 
Week 56.
Subjects may continue to participate in the LTE until they reach Week 264 or one of the
following occurs:

The subject turns 12 years of age and resides in a country where marketing authorization has
been granted for ustekinumab treatment of psoriasis in adolescent patients

Marketing authorization is obtained for ustekinumab for treatment of plaque psoriasis for
patients ≥6 to <12 years of age in the subject’s country of residence

Marketing authorization is denied for ustekinumab for the treatment of plaque psoriasis for
patients ≥6 to <12 years of age in the subject’s country of residence

A company decision is made to no longer pursue an indication in plaque psoriasis in the
pediatric population (≥6 to <12 years of age) in the subject’s country of residence
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All assessments will be performed per the Time and Events Schedule for the LTE in the 
protocol.
During the LTE, consideration should be given to discontinue ustekinumab treatment in subjects 
who are non-responders (defined by PGA >3 at 2 consecutive visits). A DBL will occur at end of 
the LTE. The LTE is considered completed when all subjects have either terminated participation 
according to the above criteria or completed their follow-up at Week 264. Additional DBLs may 
occur at the Sponsor’s discretion.
1.3.
Statistical Hypotheses for Trial Objectives
There will be no formal hypothesis testing performed. Efficacy and safety of ustekinumab in 
pediatric subjects ≥6 through <12 years of age with moderate to severe chronic plaque psoriasis 
will be evaluated using descriptive statistics. The PK of ustekinumab in pediatric subjects will 
also be evaluated using descriptive statistics of serum ustekinumab concentration and population 
PK analyses.
1.4.
Sample Size Justification
The sample size of 40 was determined based on both efficacy and PK assessments. The primary
objective is to evaluate the efficacy and safety of ustekinumab for pediatric subjects aged ≥6 to
<12 years with moderate to severe chronic plaque psoriasis and one of the major secondary 
objectives is to evaluate the pharmacokinetics of ustekinumab in this population. To support 
these objectives, a sample size of 40 subjects was chosen. For the efficacy assessment, no formal 
hypothesis testing will be performed. The observed response rates and its 95% confidence 
interval of PGA of cleared (0) or minimal (1) at Week 12 will be provided. A sample size of 40 
will provide a 95% confidence interval [50%, 80%], if the observed response rate is 65%.
To assess the pharmacokinetics of ustekinumab in this pediatric population, the sample size 
evaluation was based on simulations with a population PK model developed from adult Studies 
C0743T08, C0743T09, and adolescent study CNTO1275PSO3006. The PK in pediatric subjects 
≥6 to <12 years of age was simulated using the body weight distribution sampled with 
replacement from the National Health and Nutrition Examination Survey (NHANES) III growth 
database. A total of 300 replicates of the planned study, including the PK sampling scheme 
shown in the Time and Events Schedule, were simulated and subsequently the population PK 
parameters were re-estimated for each replicate. The precisions to estimate the CL/F and V/F 
were calculated. The precisions of CL/F estimates with 30 and 40 subjects were 9.4% and 8.1%, 
respectively, which are lower than 20% and generally considered appropriate. The precisions of 
V/F estimates with 30 and 40 subjects were 10.4% and 9.2%, respectively. Considering 
potentially higher variability in pediatric subjects ≥6 to <12 years of age than the adolescent and 
adult populations, at least 40 subjects are planned to be enrolled to provide adequate data to 
characterize PK of ustekinumab in the planned study population.
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1.5.
Randomization and Blinding
Treatment Allocation
This is an open label study. All subjects will be assigned to receive active study drug 
(ustekinumab).
Blinding
As this is an open-label study, blinding of study drug is not applicable. However, a blinded
efficacy evaluator will be used to assess efficacy during the main study.
2.
GENERAL ANALYSIS DEFINITIONS
This analysis plan provides the general analysis definitions and describes the planned subject
information, efficacy, safety, pharmacokinetics, and antibody analyses for the two planned
DBLs.
2.1.
Imputation Rules for Partial or Missing AE Dates
Partial AE onset dates will be imputed as follows:

If the onset date of an adverse event is missing day only, it will be set to:

First day of the month that the AE occurred, if month/year of the onset of AE is 
different than the month/year of the study agent start

The day of study agent start, if the month/year of the onset of AE is the same as 
month/year of the study agent start date and month/year of the AE resolution date is 
different

The day of study agent start or day of AE resolution date, whichever is the earliest, if 
month/year of the onset of AE and month/year of the study agent start date and 
month/year of the AE resolution date are same

If the onset date of an adverse event is missing both day and month, it will be set to the 
earliest of:

January 1 of the year of onset, as long as this date is on or after the study agent start 
date

Month and day of the study agent start date, if this date is in the same year that the AE 
occurred

Last day of the year if the year of the AE onset is prior to the year of the study agent 
start date,

The AE resolution date.

Completely missing onset dates will not be imputed.
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Partial AE resolution dates not marked as ongoing will be imputed as follows:

If the resolution date of an adverse event is missing day only, it will be set to the earliest of 
the last day of the month of occurrence of resolution or the date of death, if the death 
occurred in that month.

If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year.
Completely missing resolution dates will not be imputed.
2.2.
Visit Windows
There are no visit windows for analyses. Nominal visits will be used for all by-visit analyses in 
the study unless otherwise specified, regardless of the scheduled visit window. The study visits 
scheduled should occur at the times delineated in the Time and Events Schedule of the protocol.
2.3.
Pooling Algorithm for Analysis Centers
There is no pooling algorithm for analysis centers.
2.4.
Analysis Sets
2.4.1.
Efficacy Analysis Set(s)
2.4.1.1.
Full Analysis Set
In this study, the efficacy analyses will be performed on the full analysis set, which is defined as 
all enrolled and treated subjects who received at least 1 injection of ustekinumab (partial or 
complete) during the study. The full analysis set will be used for all primary and secondary 
efficacy analyses. 
In addition, the primary endpoint will also be performed using the per protocol analysis set as 
defined below.
2.4.1.2.
Per Protocol Analysis Set
The per protocol population includes subjects in full analysis set except those

who did not meet the inclusion criteria 2 in the protocol as listed below:

Have a PASI ≥12 at screening and at baseline.

Have an PGA ≥3 at screening and at baseline.

Have an involved BSA ≥10% at screening and at baseline.

who violated the exclusion diagnosis criteria 1 or 2:

Currently have nonplaque forms of psoriasis (eg, erythrodermic, guttate, or pustular).

Have current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of 
psoriasis from beta blockers, calcium channel blockers, or lithium).
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
who violated the concomitant or previous psoriasis medical therapies-related exclusion
criteria (from 3 through 11) as listed below:

Have used any therapeutic agent targeted at reducing IL-12 or IL-23, including but not 
limited to ustekinumab, guselkumab, and tildrakizumab.

Have used topical medications/treatments that could affect psoriasis or PASI evaluation 
(including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D
derivatives, 
retinoids, 
tazarotene, 
methoxsalen, 
trimethylpsoralens, 
picrolimus,tacrolimus) within 2 weeks of the first administration of study drug.

Have received phototherapy or any systemic medications/treatments that could affect
psoriasis or PASI evaluation (including, but not limited to, oral or injectable
corticosteroids, 
retinoids, 
1,25-dihydroxy 
vitamin 
D3 
and 
analogues, 
psoralens,sulfasalazine, hydroxyurea, or fumaric acid derivatives) within 4 weeks of the 
first administration of study drug.

Have received any systemic immunosuppressants (eg, methotrexate [MTX],
azathioprine, 
cyclosporine, 
6-thioguanine, 
mercaptopurine, 
mycophenolate 
mofetil,hydroxyurea, and tacrolimus) within 4 weeks of the first administration of study 
drug.

Have received any biologic agent (eg, ENBREL®, HUMIRA®) within the previous
3 months or 5 times the t1/2 of the agent, whichever is longer.

Have received natalizumab, efalizumab, or agents that deplete B or T cells (eg, 
rituximab, alemtuzumab, abatacept, or visilizumab) within 12 months of screening, or, 
if after receiving these agents, evidence is available at screening of persistent depletion 
of the targeted lymphocyte population.

Are currently receiving lithium, antimalarials, or intramuscular (IM) gold, or have 
received lithium, antimalarials, or IM gold within 4 weeks of the first administration of 
study drug.

Have used a topical investigational agent within 4 weeks or 5 times the t1/2 of the 
investigational agent, whichever is longer, before the planned start of treatment or are 
currently enrolled in a study of a topical agent.

Have used a non-topical investigational drug within 3 months or 5 times the t1/2 of the 
investigational agent, whichever is longer, before the planned start of treatment or are 
currently enrolled in a study of a non-topical investigational agent.

Subjects enrolled and received ustekinumab at Week 0 but did not receive all scheduled
ustekinumab administrations or receive an extra ustekinumab administration prior to 
Week 12.
However, among subjects who did not receive all scheduled ustekinumab administrations or 
received an extra ustekinumab administration prior to Week 12, those who discontinued the 
study agent due to unsatisfactory therapeutic effect or an adverse event (AE) of worsening of 
psoriasis, or started prohibited medications and continued receiving study agents prior to 
Week 12 will be included in the per protocol analysis and the treatment failure rules specified in 
Section 5.1.3.2 will apply.
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Subjects who were excluded from the per protocol analyses will also be summarized.
2.4.2.
Safety Analysis Set
Safety analysis set will be the same as the full analysis set, ie, enrolled subjects who received at 
least 1 injection of ustekinumab (partial or complete) during the study.
2.4.3.
Pharmacokinetics Analysis Set
The PK analysis set is defined as subjects who received at least one injection of ustekinumab and 
have at least one valid blood sample drawn for PK analysis.
2.4.4.
Immunogenicity Analysis Set
The immunogenicity analysis set is defined as all subjects who received at least one injection of 
ustekinumab and have at least one appropriate sample collected post ustekinumab administration 
for the detection of antibodies to ustekinumab.
2.5.
Definition of Subgroups
To evaluate the consistency of efficacy in the primary endpoint over demographic, baseline
disease characteristics, and psoriasis medication history, subgroup analyses will be performed
when the number of subjects in the subgroups permits.
Baseline demographics:

Sex (male, female)

Baseline Age (<10 years, ≥10 years)

Baseline weight (<60 kg, ≥60 to <100 kg, ≥100 kg)
Baseline disease characteristics:

Age at diagnosis (years) (< 6, ≥ 6)

Psoriasis disease duration (years) (< 3, ≥ 3)

Baseline PASI (<20, ≥20)

Baseline PGA (<4, ≥4)

Baseline BSA (<20%, ≥20%)

Baseline CDLQI (<10, ≥10)
Psoriasis medication history:

Phototherapy (Ultraviolet B light [UVB] or psoralen-ultraviolet-light [PUVA])

Never used

Ever used
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
Non-biologic
systemics (PUVA, MTX, cyclosporine, acitretin, apremilast, or 
tofacitinib)

Never used

Ever used

Biologics (etanercept, infliximab, alefacept, efalizumab, briakinumab, secukinumab, 
ixekizumab, brodalumab, or adalimumab)

Never used

Ever Used

Non-biologic systemics or biologics (as defined above)

Never used

Ever used
In these subgroup analyses, the proportion of subjects achieving a PGA score of cleared (0) or 
minimal (1) with corresponding 95% CIs will be presented by subgroup. In addition, the 
proportion of subjects achieving a PGA score of cleared (0) or minimal (1) at Week 12 will also
be summarized by investigational site. All above subgroup analyses will also be performed on 
the proportion of PASI 75 responders at Week 12.
2.6.
Study Day and Baseline Definition
2.6.1.
Study Day
Study Day 1 refers to the first study agent administration date. The study day for an event is 
defined as:

Event date - (date of Study Day 1) +1, if event date is ≥ date of Day 1

Event date - date of Day 1, if event date < date of Day 1 
2.6.2.
Baseline
In general, the baseline measurement is defined as the closest measurement taken prior to or at 
the time of the first study agent administration date unless otherwise specified.
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
No formal interim analysis is planned. There is no Data Monitoring Committee (DMC) for this 
study.
4.
SUBJECT INFORMATION
The full analysis set will be used for the subject information analyses as specified below unless 
otherwise noted. In addition, the distribution of subjects by country and site will be presented.
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Simple descriptive statistics, such as mean, median, standard deviation, interquartile range,
maximum, and minimum for continuous variables, and counts and percentages for discrete
variables will be used to summarize most data. In addition, subject listings will also be used to 
present the data.
4.1.
Demographics and Baseline Characteristics
4.1.1.
Demographics
Table 1 presents a list of the demographic variables that will be summarized for the full analysis 
set.  
Table 1:
Demographic Variables
Continuous Variables:
Summary Type
Age (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum], and IQ range).
Weight (kg)
Height (cm)
Categorical Variables:
Age (<10 years and ≥10 years)  
Frequency distribution with the 
number and percentage of 
subjects in each category.
Sex (male, female)
Weight (<60 kg, ≥60 to <100 kg, ≥100 kg)
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Other, 
Multiple, Unknown, Not reported)
Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Not 
Reported, Unknown)
BMI (Normal [<25], Overweight [25 -<30], Obese [≥30])
aIf multiple race categories are indicated, then Race is recorded as “Multiple.”
In addition, the histogram plots for the distributions of age at baseline will be provided.
4.1.2.
Baseline Characteristics
Psoriasis baseline disease characteristics (i.e., psoriasis disease duration [years], age at diagnosis 
[years], BSA [%], psoriatic arthritis, baseline PGA score, baseline PASI score [0-72], and 
baseline CDLQI) will be summarized for the full analysis set.
4.2.
Disposition Information
Screened subjects will be summarized overall.
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The number of subjects in the following disposition categories will be summarized:

Subjects enrolled and treated

Subjects who completed the study

Subjects who discontinued study agent

Reasons for discontinuation of study agent

Subjects who terminated study prematurely

Reasons for termination of study
The above categories will include summaries over the period of Week 56 and Week 264 if
appropriate.
Listings of subjects will be provided for the following categories:

Subjects who discontinued study agent

Subjects who terminated study prematurely
4.3.
Treatment Compliance
Study agent compliance will be summarized descriptively through Week 56 and through 
Week 248 for the full analysis set. 
4.4.
Extent of Exposure
The exposure data will be summarized through Week 56 and through Week 248. The number 
and percentage of subjects who receive study agent will be summarized for the safety analysis 
set. Descriptive statistics will be presented for the following parameters:

Number of administrations

Cumulative total dose
In addition, the study agent lots received will be summarized.
4.5.
Protocol Deviations
In general, the following list of major protocol deviations may have the potential to impact 
subjects’ rights, safety or well-being, or the integrity and/or results of the clinical trial. Subjects 
with major protocol deviations will be identified prior to database lock and will be summarized 
by category through Week 56 and through Week 264 for the full analysis set.

Entered but did not satisfy criteria

Developed withdrawal criteria but not withdrawn

Received a disallowed concomitant treatment
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
Received a wrong treatment or an incorrect dose

Other: to be defined in the major protocol deviation criteria document
Subjects with major protocol deviations will also be listed.
4.6.
Prior and Concomitant Medications
Subjects’ prior psoriasis medication history with topical agents, phototherapy, non-biologic 
systemic therapies, and biologic medications will be summarized. See Section 2.5 for lists of 
medications in each category. In addition, reasons for which subjects discontinued previous 
systemic therapies (contraindication, inadequate response, intolerance [ie, AEs], or other) will be 
summarized.
The number of subjects who received concomitant treatment with a moisturizer for psoriasis will 
be summarized.
Subjects who received concomitant corticosteroids for indications other than psoriasis will be 
listed.
5.
EFFICACY
In general, efficacy data summaries will be provided for the full analysis set. 
No formal hypothesis testing will be conducted. Descriptive statistics, such as mean, median, 
standard deviation, minimum and maximum, interquartile range for continuous variables, and 
counts and percentages for categorical variables will be used to summarize the data. Graphical 
data displays and subject listings may also be used to summarize the data.
5.1.
Analysis Specifications
5.1.1.
Level of Significance
No formal hypothesis testing will be conducted such that no p-values will be reported. Two-
sided exact 95% confidence intervals (CI) will be provided for the primary and major secondary
endpoints. The study is designed to provide reasonable precision on the estimation of response 
rates. 
5.1.2.
Definition of the Efficacy Endpoints and Calculation of the Efficacy 
Instruments
5.1.2.1.
Physician’s Global Assessment 
The Physician’s Global Assessment (PGA) is used to determine the subject’s psoriasis at a given 
time point. Overall lesions are graded for induration, erythema, and scaling. The patient’s 
psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), marked (4), or severe 
(5).
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Statistical Analysis Plan CNTO1275PSO3013
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Approved, Date: 8 February 2018
Efficacy endpoints related to the PGA score are defined below:
PGA cleared responder 
Subjects who achieve an PGA score of 0 will be considered PGA cleared responders.
PGA cleared or minimal responder
Subjects who achieve an PGA score of 0 or 1 will be considered PGA cleared or minimal 
responders.
PGA mild or better responder
Subjects who achieve an PGA score of 0, 1, or 2 will be considered PGA mild or better 
responders.
5.1.2.2.
Psoriasis Area and Severity Index 
The PASI is a system used for assessing and grading the severity of psoriatic lesions and their 
response to therapy. In the PASI system, the body is divided into 4 regions: the head, trunk, 
upper extremities, and lower extremities. Each of these areas is assessed separately for the 
percentage of the area involved, which translates to a numeric score that ranges from 0 (indicates 
no involvement) to 6 (90%-100% involvement), and for erythema, induration, and scaling, which 
are each rated on a scale of 0 to 4. The PASI produces a numeric score that can range from 0 (no 
psoriasis) to 72. A higher score indicates more severe disease.
Efficacy endpoints related to the PASI score are defined below:
PASI 50 Responder
Subjects with ≥50% improvement in PASI from baseline will be considered PASI 50 responders.
PASI 75 Responder
Subjects with ≥75% improvement in PASI from baseline will be considered PASI 75 responders.
PASI 90 Responder
Subjects with ≥90% improvement in PASI from baseline will be considered PASI 90 responders.
PASI 100 Responder
Subjects with 100% improvement in PASI from baseline (PASI score=0) will be considered 
PASI 100 responders.
5.1.2.3.
Children Dermatology Life Quality Index 
The Children Dermatology Life Quality Index (CDLQI) is a dermatology-specific quality of life 
instrument designed to assess the impact of the disease on a subject’s quality of life.  It is an 
adapted version of DLQI. The CDLQI, a 10-item questionnaire has a 4 item response option and 
a recall period of 1 week. In addition to evaluating overall quality of life, the CDLQI can be used 
to assess 6 different aspects that may affect quality of life:  symptoms and feelings, leisure, 
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Statistical Analysis Plan CNTO1275PSO3013
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school or holidays, personal relationships, sleep, and treatment. The scoring of each question is 
as follows:
Very much
Scored 3
Quite a lot
Scored 2
Only a little
Scored 1
Not at all
Scored 0
Question unanswered
Scored 0
Question 7: ”Prevented school”
Scored 3
The CDLQI is calculated by summing the score of each question resulting in a maximum of 30 
and a minimum of 0. A higher score indicates more severe disease. The 6 CDLQI components 
scores are calculated as follows:
Symptoms and feelings
Questions 1 and 2
Score maximum 6
Leisure
Questions 4, 5 and 6
Score maximum 9
School or holidays
Questions 7
Score maximum 3
Personal relationships
Questions 3 and 8
Score maximum 6
Sleep
Questions 9
Score maximum 3
Treatment
Questions 10
Score maximum 3
5.1.3.
Data Handling Rules
The following treatment failure rules and data handling rules will be applied to the PASI and 
PGA-related efficacy analyses in this study. 
5.1.3.1.
Treatment Failure Criteria
Subjects who discontinue study agent due to lack of efficacy or an adverse event (AE) of
worsening of psoriasis, or who started a protocol-prohibited medication/therapy during the study
that could affect their psoriasis are considered as treatment failures.
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The particular protocol-prohibited medications/therapies include:
Topical Therapies for the Treatment of Psoriasis:

Before Week 12, any topical corticosteroid used for treatment of psoriasis.

After Week 12 through Week 52, any topical corticosteroid used for treatment of psoriasis 
with the exception of low-potency corticosteroids used on the face and/or groin.

Non-corticosteroid topical therapies that could affect psoriasis or the PASI evaluation such
as tar, anthralin, calcipotriene, tazarotene, methoxsalen, pimecrolimus and tacrolimus
through Week 52 (with the exception of topical moisturizers and shampoos containing tar or 
salicylic acid only).
Note that in this study, shampoos (containing tar or salicylic acid only) and topical moisturizers 
are allowed.
Phototherapy or Systemic Therapies for the Treatment of Psoriasis:

Any systemic corticosteroid used for psoriasis with the exception of intra-articular 
corticosteroids.

Any other anti-psoriatic systemic therapy or biologic therapy.

Phototherapy of UVB or PUVA or any other phototherapy for psoriasis.
Concomitant Therapies for Conditions Other than Psoriasis: 

Any disease-modifying agents such as MTX, or sulfasalazine.

Any intramuscular corticosteroid for “Other” indications.
5.1.3.2.
Treatment Failure Rules
A subject who meets one or more treatment failure criterion specified in Section 5.1.3.1 will be 
considered a treatment failure from that point onward through Week 52. The baseline values will 
be used for all directly measured endpoints regardless of the actual measurements. Zero will be 
assigned to improvement and percent improvement, and non-responder status will be assigned to 
binary response variables. No treatment failure rules will be applied after Week 52.
Treatment failure is assumed to have occurred at the earlier of the following dates:  

Date of discontinuation (DC) of study treatment due to lack of efficacy or 

Date of discontinuation of study agent due to an AE of worsening of psoriasis or 

Start date of a protocol-prohibited medication/therapy during the study that could improve 
psoriasis
5.1.3.3.
Additional Data Handling Rules for Children Life Quality Index 
(CDLQI)
In addition to the data handling rules described in Section 5.1.3.1, the following data handling
rules also apply to all the secondary analyses related to Children Dermatology Life Quality Index 
(CDLQI) before applying the treatment failure rules.
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CNTO1275  (Ustekinumab)
Statistical Analysis Plan CNTO1275PSO3013
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For a partially answered questionnaire (eg, not all 10 answers in the CDLQI questionnaire were
available) or incorrectly completed questionnaire:

If one question is left unanswered, this question will be scored 0. The total score and each of 
the 6 component scores will then be calculated.

If two or more questions are left unanswered, the total score and the affected component 
scores will be set to missing.
If both parts of question 7 are completed, the higher of the two scores should be used.
5.1.3.4.
Missing Data Imputation
For the most efficacy analyses (eg, over time summaries), after the treatment failures, no
imputation will be performed for missing data (eg, lost to follow-up, missed study visit) and the 
values will remain as missing except for the following:
The dichotomous endpoints at Week 12:

PGA score of cleared (0), cleared (0) or minimal (1), and mild or better (≤ 2);

PASI 100, PASI 90, PASI 75, and PASI 50 responses;

CDLQI of 0 or 1.
For these types of endpoints, subjects with missing PGA score, PASI score, PASI component, or 
CDLQI at Week 12 will be considered as not achieving the respective endpoints at Week 12.
5.2.
Primary Efficacy Endpoint(s)
5.2.1.
Definition
The primary endpoint of the study is the proportion of subjects with a PGA of cleared (0) or 
minimal (1) at Week 12. The PGA documents the physician’s assessment of the subject’s 
psoriasis status according to the following categories: induration, scaling, and erythema.
5.2.2.
Estimand
Population:
subjects with moderate-to-severe plaque psoriasis who are treated with 
ustekinumab.
Endpoint: the proportion of subjects who achieve a PGA score of cleared (0) or minimal (1) at 
Week 12 and did not discontinue study agent due to lack of efficacy or AE of psoriasis, or 
initiate prohibited anti-psoriatic medication/therapy.
Intercurrent Events: defined through the endpoint description.
5.2.3.
Analysis Methods
In the primary analysis, the number and proportion of subjects achieving a PGA score of cleared 
(0) or minimal (1) at Week 12 will be summarized. Its two-sided exact 95% confidence intervals 
(CI) will be provided.
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To assess the robustness of the primary endpoint analysis result, the following two sensitivity
analyses will be conducted.
Sensitivity Analysis 1
For subject who have a missing PGA score at Week12, the score will not be imputed. That is, the 
analysis will be performed using observed data, after treatment failure rules (as defined in 
Section 5.1.3.2). Its two-sided exact 95% confidence intervals (CI) will be provided.
Sensitivity Analysis 2
The second sensitivity analysis will be performed by using multiple imputations (MI), after 
applying treatment failure rules (as defined in Section 5.1.3.2). The intermittent missing PGA 
score through Week 12 will be imputed using the Markov Chain Monte Carlo (MCMC) 
algorithm with 200 imputed data sets and seed = 123 to make the missing data pattern monotone. 
The PGA score of cleared (0) or minimal (1) responses will then be derived based on the
imputed scores at or before Week 12. The remaining missing data of the PGA score of cleared 
(0) or minimal (1) will be imputed with monotone logistic regression with baseline PGA score 
and PGA response status at each visit in the model with one imputed dataset and seed = 789 to
fill in the remaining missing items in each of the 200 copies of datasets. Its 95% CI will also be
provided under the normal approximation assumption.
5.2.4.
Data Handling
Subjects who meet treatment failure criteria specified in Section 5.1.3.1 prior to Week 12 will be 
considered not to have achieved an PGA score of cleared (0) or minimal (1). In addition, subjects 
with a missing PGA score at Week 12 or who do not return for evaluation at Week 12 will be 
considered not to have achieved the respective endpoint at Week 12.
5.3.
Major Secondary Endpoints
The sections below outline the major secondary analyses to be performed, as well as the analysis 
methods and the data imputation rules.
5.3.1.
Definition

The proportions of subjects who achieve a ≥75% improvement in PASI from baseline at 
Week 12.

The change in CDLQI from baseline at Week 12.

The proportions of subjects who achieve a ≥90% improvement in PASI from baseline at 
Week 12.
5.3.2.
Analysis Methods
Major secondary analyses for the number and proportion of subjects achieving a PASI 75 and a 
PASI 90 at Week 12 will be summarized, respectively. Their exact two-sided 95% confidence 
intervals based on the binomial distribution for the proportion of subjects with PASI 75 and 
PASI 90 will be provided, respectively. The similar sensitivity analyses with the same number of 
imputed datasets and the same seeds will be performed for these two endpoints.
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For the change from baseline in CDLQI at Week 12, the mean (95% confidence interval) will be 
computed. Its 95% confidence interval will be based on the normal approximation. A sensitivity 
analysis will be performed by using multiple imputations (MI), after applying treatment failure 
rules (as defined in Section 5.1.3.1). The intermittent missing CDLQI score through Week 12 
will be imputed using the Markov Chain Monte Carlo (MCMC) algorithm with 200 imputed data 
sets and seed = 123 to make the missing data pattern monotone. Once the missing pattern is 
monotone, the remaining missing data of the CDLQI score will be imputed with monotone 
regression with baseline CDLQI and CDLQI score at each visit in the model with one imputed 
dataset and seed = 789 to fill in the remaining missing data in each of the 200 copies of datasets. 
Its 95% CI will then be calculated.
5.3.3.
Data Handling
Data handling rules specified in Section 5.1.3 will be applied to the major secondary analyses.
5.4.
Other Efficacy Variable(s)
In addition to the primary and major endpoint analyses, the following efficacy endpoints will be 
summarized:

PGA

PASI

CDLQI 
The analyses of other secondary efficacy analyses outlined in the following sections in general 
will be carried out for 2 periods 

Analyses through Week 52:

Analyses at key time point: Week 12

Over time summaries: Through Week 52

Analyses through Week 248:

PGA responses over time summaries
5.4.1.
Definition
Refer to Section 5.1.2 for the definitions of the other efficacy endpoints described in the 
following section.
5.4.2.
Analysis Methods
Most of the other secondary efficacy analyses described in this section below will be based on 
the full analysis set.
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5.4.2.1.
Analyses Related to PGA

The proportions of subjects achieving a PGA score of cleared (0), the proportion of subjects 
achieving a PGA score of cleared (0) or minimal (1), and the proportion of subjects 
achieving a PGA score of mild or better (≤2) over time through Week 52 and through 
Week 248. Line plots will be provided displaying proportions and exact 95% CIs of subjects 
achieve a PGA score of cleared (0) or minimal (1) through Week 52 and Week 248.
5.4.2.2.
Analyses Related to PASI

The proportions of subjects who achieve PASI 50, PASI 75, PASI 90, and PASI 100 
responses over time through Week 52. Line plots will be provided displaying proportions 
and exact 95% CIs of PASI 75 responders and PASI 90 responders through Week 52.

The percent improvement from baseline in PASI over time through Week 52 will be 
provided.

The proportion of subjects who achieve 100% improvement, ≥90%, ≥75%, or ≥50% 
improvement from baseline in PASI component (induration, erythema, and scaling) and 
region component (head, trunk, upper extremities, and lower extremities) will be 
summarized at Week 12. 
5.4.2.3.
Analyses Related to CDLQI

The change from baseline in CDLQI over time through Week 52 will be provided.

The proportion of subjects with CDLQI = 0 or 1 at Week 12 with a baseline CDLQI score 
> 1.

The proportion of subjects with CDLQI = 0 or 1 over time through Week 52 with a baseline 
CDLQI score > 1 will be provided.

The change from baseline in CDLQI component scores at Week 12 will be provided.
5.4.3.
Data Handling
Data handling rules specified in Section 5.1.3 will be applied to all PGA, PASI, and CDLQI
related analyses. 
6.
SAFETY
Safety will be assessed by summarizing the incidence and type of AEs, and examining changes 
in laboratory parameters (hematology and chemistry), and summarizing vital signs, height, 
weight and BMI if appropriate.
In all the safety analysis, subjects who received at least 1 (partial or complete) dose of 
ustekinumab will be included. No formal hypothesis testing is planned.
Depending on the safety data categories, the cumulative safety data will be analyzed through 
different study periods which include through Week 56 for the main study and through 
Week 264 for the LTE of the study as appropriate.
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6.1.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Any AE starting at or after 
the initial administration of study agent through the end of the trial is considered to be treatment 
emergent. If the event occurs on the day of the initial administration of study agent, and either 
event time or time of administration are missing, then the event will be assumed to be treatment 
emergent. If the event date is recorded as partial or completely missing, then the event will be 
considered as treatment emergent unless it is known to be prior to the first administration of 
study agent based on partial onset date or resolution date. All reported treatment-emergent 
adverse events will be included in the analysis. For each adverse event, the number and 
percentage of subjects who experience at least 1 occurrence of the given event will be 
summarized. 
Summary tables will be provided for:

AEs

Serious AEs (SAEs)

AEs leading to discontinuation of study agent administration

AEs by severity

AEs by relationship to study agent

Infections

Serious infections

Infections treated with oral or parenteral antimicrobial treatment parenteral antibiotics

Injection-site reactions

AEs of psoriasis
In addition to the summary tables, listings will be provided for subjects who:

Had SAEs

Had AEs leading to discontinuation of study agent administration

Had AEs of severe intensity

Had serum sickness-like reactions or anaphylactic reactions

Had AE of psoriasis
Any unfavorable or unintended sign that occurs at the injection site is an injection site reaction 
and will be recorded as an injection site reaction by the investigator on the eCRF. An infection is 
defined as any AE that was recorded as an infection by the investigator on the eCRF.
The treatment-emergent adverse events of psoriasis include any event of erythrodermic psoriasis, 
pustular psoriasis, guttate psoriasis, and worsening or exacerbation of psoriasis.
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Since safety should be assessed relative to exposure and follow-up, most AE summary tables 
will include average weeks of follow-up and average number of study agent administrations for 
each treatment group.
6.2.
Clinical Laboratory Tests
All clinical laboratory reports will be displayed for the subjects included in the safety analysis 
set. The clinical laboratory parameters to be evaluated by the central laboratory include but are 
not limited to:

Hematology: hemoglobin, hematocrit, red blood cell (RBC) count, white blood cell (WBC) 
count, lymphocytes, monocytes, neutrophils, eosinophils, basophils, and platelets.

Chemistry: blood urea nitrogen/urea, glucose, creatinine, aspartate aminotransferase (AST), 
alanine aminotransferase (ALT), total bilirubin, indirect bilirubin, albumin, total protein.
Box plots of laboratory measurements and change from baseline will be provided for selected 
laboratory analytes. 
The proportion of subjects with any markedly abnormal post baseline laboratory values 
(hematology and chemistry) in selected laboratory measurements will be summarized. Similar to 
AEs, markedly abnormal clinical laboratory will be summarized through Week 56 for the main
study and Week 264 for the LTE of the study, respectively. Markedly abnormal post baseline 
laboratory values will also be presented in listings.
Markedly abnormal changes from baseline are defined in Table 2. For a laboratory value to be 
considered markedly abnormal, the corresponding laboratory criteria below must be met. For 
example, for a platelet value to be markedly abnormal, the platelet value must be <100 x109/L 
and must be at least 50% decrease from the baseline platelet value. If the baseline value is 
missing for a parameter, the determination of whether the laboratory value is markedly abnormal 
will be based solely on the actual value (ie, the criterion for a specific increase or decrease from 
baseline will not be utilized).
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Table 2:
Markedly Abnormal Criteria for Laboratory Parameters
Hematology Test
Criteria for Markedly Abnormal Status
Hemoglobin (g/L)
Decrease from baseline > 20 g/L 
& absolute value < 100 g/L
Hematocrit, fraction
absolute value < 0.3 fraction
WBC (x109/L)
Decrease absolute value < 3 x 109/L
Increase absolute value > 20 x 109/L
Neutrophils (x109/L)
Percent decrease from baseline ≥ 33% 
& absolute value < 1.5 x 109/L
Lymphocytes (x109/L)
Percent decrease from baseline ≥ 33% 
& absolute value < 1.5 x 109/L
Eosinophils (x109/L)
Percent increase from baseline ≥ 100 % 
& absolute value > 1.0 x 109/L
Platelets (x109/L)
Percent decrease from baseline ≥ 50% 
& absolute value < 100 x 109/L
Chemistry Test
ALT/SGPT (U/L)
Percent increase from baseline >= 100 
& absolute value > 100 U/L
AST/SGOT (U/L)
Percent increase from baseline >= 100 
& absolute value > 100 U/L
Total bilirubin (umol/L)
Percent increase from baseline >= 100 
& absolute value > 41.0 umol/L
Non-fasting glucose (mmol/L)
Percent decrease from baseline ≥ 33 
& absolute value < 3.05 mmol/L
Percent increase from baseline ≥ 50 
& value > 8.88 mmol/L
Creatinine (umol/L)
Percent increase from baseline >= 66 
& absolute value > 99 umol/L
Albumin (g/L)
Decrease from baseline >= 10 g/L 
& absolute value < 25 g/L
6.3.
Vital Signs and Physical Examination Findings
Box plots of the observed and change from baseline will be provided for the vital signs variables 
including heart rate, respiratory rate, and blood pressure (systolic and diastolic).
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Physical exam findings will not be analyzed except that they are captured as AEs and are
included in the analyses of AEs.
6.4.
Other Safety Parameters
Weight, height and BMI will be summarized at selected points.
7.
PHARMACOKINETICS/PHARMACODYNAMICS/IMMUNOGENICITY
7.1.
Pharmacokinetics
Blood samples for measuring serum ustekinumab concentrations (pre-injection if it is injection
visit) will be collected from all subjects at scheduled visits as indicated in the Time and Events
Schedule in the protocol.
The PK analysis will be based on subjects who received at least 1 administration of ustekinumab
and had at least one serum sample for ustekinumab concentration. No imputation of missing 
concentration data will be performed, that is, data summaries will be based on the observed data.
All concentrations below the lowest quantifiable sample concentration of the assay or missing 
data will be labeled as such in the concentration data listings or Statistical Analysis Software
dataset. All BQL serum ustekinumab concentrations below the lowest quantifiable sample 
concentration in of the assay will be treated as zero in the summary statistics. All subjects and 
samples excluded from the analysis will be clearly documented.
For analysis of serum ustekinumab concentrations, descriptive statistics, including arithmetic
mean, SD, median, interquartile range, minimum, and maximum will be calculated at each 
scheduled sampling time point for the ustekinumab group. The PK concentration data may be
displayed graphically.
Serum ustekinumab concentrations will be summarized at each scheduled visit from Week 0 
through Week 52. All summaries for serum ustekinumab concentration will exclude data 
collected after subjects (1) did not receive a scheduled ustekinumab administration within ± 14 
days of the protocol scheduled dosing date; (2) discontinued study agent administration; (3) 
received a partial, incorrect, or an additional ustekinumab administration (ie, subjects received 
more than 1 ustekinumab injection within the scheduled ustekinumab injection window); or 4) 
received an increased or decreased dose due to body weight change (eg, from the initial category 
of <60 kg to the category of ≥60 to ≤100 kg or vice versa) for the concentration summaries by 
baseline weight. Of note, serum ustekinumab concentrations prior to the first of such events will 
be included in the summaries.
In addition, invalid concentration data will be excluded from analysis. A concentration will be
considered invalid (1) if a pre-injection sample was actually taken after study agent 
administration (based on date/time); or (2) a concentration value fell outside the predefined 
statistical range of mean ± 10*SD of the concentration values obtained at the same protocol 
specified sampling timepoint (refer to SOP-07948-GXP, Version 2.1).
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If there were multiple samples collected prior to an injection, the closest sample before the 
injection will be used. If a sampling time or an injection time was missing, the date will be used. 
If sampling date was the same as the injection date, the sample will be included in the statistical 
summary.
Serum ustekinumab concentrations will be summarized as follows:

Summary of serum ustekinumab concentrations through Week 52 (note: the rule #4 shown 
above is not applicable to this table).

Summary of serum ustekinumab concentrations through Week 52 by baseline weight 
(<60 kg, ≥60 to ≤100 kg, and >100 kg). 

Number of subjects with serum ustekinumab concentrations below the lowest quantifiable 
sample concentration of the assay (<0.1688 micrograms/mL) through Week 52 (note: the 
rule #4 shown above is not applicable to this table).

Number of subjects with serum ustekinumab concentrations below the lowest quantifiable 
sample concentration of the assay (<0.1688 micrograms/mL) through Week 52 by baseline 
weight (<60 kg, ≥60 to ≤100 kg, and >100 kg).

Median (IQ range) serum ustekinumab concentrations over time plot.

Median (IQ range) serum ustekinumab concentrations over time plot by baseline weight 
(≤60 kg, ≥60 to ≤100 kg, and >100kg).
A population PK analysis using a nonlinear mixed-effects modeling approach will be used to 
characterize the disposition characteristics of ustekinumab in the current study. Data may be 
combined with those of other selected studies to support a relevant structural model. The CL/F 
and V/F values will be estimated. The influence of important variables (such as body weight and 
antibodies to ustekinumab) on the population PK parameter estimates will be evaluated. The 
results of the population PK analysis will be presented in a separate technical report.
7.2.
Immunogenicity
Blood samples will be collected for the detection of antibodies to ustekinumab at the specified
visits as shown in the Time and Events schedule in the protocol.
The antibodies to ustekinumab analysis will be based on subjects who receive at least 1 dose of
ustekinumab and have at least one samples collected post ustekinumab administration for the
detection of antibodies to ustekinumab. No imputation of missing data will be performed, that is,
data summaries will be based on the observed data.
The following analyses will be performed for ustekinumab group as appropriate:

Summary of antibodies to ustekinumab status (incidence of antibodies to ustekinumab and 
antibody titers)

List of subjects who are positive for antibodies to ustekinumab
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In addition, the incidence of neutralizing antibodies (NAbs) to ustekinumab will be summarized
for subjects who are positive for antibodies to ustekinumab and have samples evaluable for
NAbs.
The effect of antibodies to ustekinumab on PK, efficacy, and safety will be explored, if data 
permit.
7.3.
Pharmacokinetic/Pharmacodynamic Relationships
The relationships between serum ustekinumab concentration and efficacy will be analyzed 
graphically. A suitable pharmacokinetic/ pharmacodynamic (PK/PD) model will be developed to 
describe the exposure-response relationship. Data may be combined with those of other selected 
studies to support a relevant structural PK/PD model. The results of the population PK/PD 
analysis may be presented in a separate technical report.
7.4.
Biomarker
The goal of the biomarker analyses is to evaluate the pharmacodynamics of ustekinumab by 
measuring levels of IL-17 and other inflammatory cytokines and aid in evaluating the 
pharmacodynamic-clinical response relationship. Assessment of IL-17 serum levels will be 
performed and potential association with ustekinumab response will be explored. Biomarker 
analyses will be summarized in a separate technical report.
7.5.
Pharmacogenomic (DNA) Evaluations
The goal of the optional pharmacogenomic component is to collect deoxyribonucleic acid (DNA) 
to allow research on the identification of genetic factors that may influence the 
pharmacokinetics, pharmacodynamics, efficacy, safety, or tolerability of ustekinumab and to 
explore genetic factors associated with psoriasis. Genomic analyses will be summarized in a 
separate technical report.
NCT02698475