Clinical trial NCT02349061
Conditions: Lupus Erythematosus, Systemic
Keywords: Systemic Lupus Erythematosus Ustekinumab
Sponsor: Janssen Research & Development, LLC
Start date: 2015-10-15; Completion date: 2019-03-13
Enrollment: 102 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief summary:
The purpose of this study is to evaluate the efficacy of ustekinumab as measured by a reduction in disease activity for subjects with active Active Systemic Lupus Erythematosus (SLE - chronic disorder of connective tissue in which there can be skin rash, arthritis, kidney problems, and anemia, among other problems).

Detailed description:
A multicenter (more than one medical research center involved in study), randomized (study drug assigned by chance), double-blind (neither the Investigator nor the participant know about the study drug), placebo-controlled, proof-of-concept study of ustekinumab in participants with active systemic lupus erythematosus. Participants will be screened to achieve all inclusion criteria and none exclusion criteria and will then receive either ustekinumab or placebo along with concomitant background medicine. Participants will be primarily assessed for response using the Systemic Lupus Erythematosus Response Index 2000 (SRI-4). Participants' safety will be assessed throughout the study.

Arms: arm 1: Participants will receive weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0 followed by ustekinumab 90 mg subcutaneously (SC) every 8 weeks (q8w) up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up. arm 2: Participants will receive placebo intravenously at Week 0 followed by placebo subcutaneously at Weeks 8 and 16. At week 24 participants will receive ustekinumab SC q8w up to Week 40. Participants who meet the study extension inclusion criteria will continue to receive ustekinumab 90 mg SC q8w starting at Week 48 or 56 through Week 104. Participants will continue stable concomitant treatment through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48. Participants who complete or discontinue study treatment will be evaluated for 16 additional Weeks of safety follow-up.
Interventions: intervention 1: Ustekinumab IV intervention 2: Placebo Infusion intervention 3: Placebo SC intervention 4: Ustekinumab SC intervention 5: Concomitant Medication
Intervention descriptions: intervention 1: Weight-range based dosing of approximately 6 mg/kg of ustekinumab intravenously at Week 0. intervention 2: Placebo intravenously at Week 0. intervention 3: Placebo subcutaneously at Weeks 8 and 16. intervention 4: Ustekinumab 90 mg subcutaneously every 8 weeks up to Week 40 and up to Week 104 in study extension (for eligible participants) intervention 5: Concomitant treatment (mycophenolate, azathioprine/6-mercaptopurine, methotrexate, hydroxychloroquine and/or chloroquine, oral corticosteroids, NSAIDs, antihypertensive medications, and topical medications) through Week 48, as well as through the study extension although tapering of corticosteroids is encouraged beyond Week 48.

Protocol documents:
Prot_000.pdf: 
Approved, 18 January 2017
Janssen Research & Development*
Clinical Protocol
A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of 
Ustekinumab in Subjects With Active Systemic Lupus Erythematosus
CNTO1275SLE2001; Phase 2a 
AMENDMENT 3
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 
R&D Ireland; 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. 
This study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
EudraCT NUMBER: 2014-005000-19
Status:
Approved
Date:
18 January 2017
Prepared by:
Janssen Research & Development, LLC  
EDMS number:
EDMS-ERI-89608352, 10.0
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.
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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 6
PROTOCOL AMENDMENTS....................................................................................................................... 7
SYNOPSIS.................................................................................................................................................. 28
TIME AND EVENTS SCHEDULE .............................................................................................................. 35
ABBREVIATIONS ...................................................................................................................................... 42
1.
INTRODUCTION................................................................................................................................ 44
1.1.
Background .................................................................................................................................... 45
1.2.
Overall Rationale for the Study...................................................................................................... 45
1.2.1.
Scientific Rationale for Use of Anti-IL-12/23p40 Therapy in Systemic Lupus 
Erythematosus............................................................................................................................ 45
1.2.1.1.
Subgroup of Subjects with Active Cutaneous Manifestations of Systemic Lupus 
Erythematosus......................................................................................................................... 46
1.3.
Justification for Dosing Regimen ................................................................................................... 46
2.
OBJECTIVES AND HYPOTHESIS ................................................................................................... 48
2.1.
Objectives ...................................................................................................................................... 48
2.2.
Hypothesis ..................................................................................................................................... 49
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 49
3.1.
Overview of Study Design.............................................................................................................. 49
3.2.
Study Design Rationale.................................................................................................................. 53
4.
SUBJECT POPULATION.................................................................................................................. 54
4.1.
Inclusion Criteria ............................................................................................................................ 55
4.1.1.
Inclusion Criteria Applicable to All Subjects ............................................................................... 55
4.1.2.
Additional Inclusion Criteria for the Cutaneous Lupus Substudy ............................................... 61
4.1.3.
Inclusion Criteria Applicable to All Subjects Entering into the Study Extension (Week 48 
or Week 56 visits) ....................................................................................................................... 61
4.2.
Exclusion Criteria ........................................................................................................................... 62
4.3.
Prohibitions and Restrictions ......................................................................................................... 66
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 67
5.1.
Procedures for Randomization ...................................................................................................... 67
5.2.
Blinding .......................................................................................................................................... 68
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 69
6.1.
IV administration ............................................................................................................................ 69
6.2.
SC administration........................................................................................................................... 69
7.
TREATMENT COMPLIANCE............................................................................................................ 70
8.
CONCOMITANT THERAPY.............................................................................................................. 71
8.1.
Immunomodulators ........................................................................................................................ 72
8.2.
Antimalarial Medications ................................................................................................................ 72
8.3.
Corticosteroid Therapy................................................................................................................... 72
8.4.
Nonsteroidal Anti-inflammatory Drugs ........................................................................................... 74
8.5.
Anti-hypertensive Medications ....................................................................................................... 74
8.6.
Topical Medications ....................................................................................................................... 74
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9.
STUDY EVALUATIONS .................................................................................................................... 75
9.1.
Study Procedures........................................................................................................................... 75
9.1.1.
Overview..................................................................................................................................... 75
9.1.2.
Screening Phase ........................................................................................................................ 75
9.1.2.1.
Screening Procedures ............................................................................................................. 75
9.1.2.2.
Retesting.................................................................................................................................. 76
9.1.2.3.
Rescreening............................................................................................................................. 77
9.1.3.
Double-Blind Treatment Phase .................................................................................................. 77
9.1.3.1.
Week 0/Day of Randomization................................................................................................ 77
9.1.3.2.
Placebo-controlled Treatment Period (Through Week 24)...................................................... 77
9.1.4.
Cross-over Treatment (Through Week 40)................................................................................. 77
9.1.5.
Study Extension (Week 48/Week 56 through Week 104) .......................................................... 77
9.1.6.
Subjects Withdrawing from Study Participation.......................................................................... 78
9.1.7.
Post-treatment Safety Follow-up ................................................................................................ 78
9.2.
Efficacy........................................................................................................................................... 78
9.2.1.
Evaluations ................................................................................................................................. 78
9.2.1.1.
SLEDAI-2K and S2K RI-50...................................................................................................... 78
9.2.1.2.
BILAG ...................................................................................................................................... 79
9.2.1.3.
CLASI ...................................................................................................................................... 79
9.2.1.4.
Physician Global Assessment of Disease Activity................................................................... 80
9.2.1.5.
Patient Global Assessments.................................................................................................... 80
9.2.1.5.1.
Patient Global Assessment of Disease Activity ................................................................... 80
9.2.1.5.2.
Patient Assessment of Pain ................................................................................................. 80
9.2.1.6.
Short-Form-36 ......................................................................................................................... 80
9.2.1.7.
Fatigue Severity Scale............................................................................................................. 81
9.2.2.
Definitions ................................................................................................................................... 81
9.2.2.1.
SRI-4........................................................................................................................................ 81
9.2.2.2.
BILAG-based Combined Lupus Assessment.......................................................................... 81
9.2.2.3.
Flares....................................................................................................................................... 82
9.2.2.4.
S2K RI-50 Response............................................................................................................... 82
9.2.2.5.
No Worsening in PGA ............................................................................................................. 82
9.2.3.
Endpoints.................................................................................................................................... 82
9.3.
Pharmacokinetics and Immunogenicity ......................................................................................... 83
9.3.1.
Serum Collection and Handling .................................................................................................. 84
9.3.2.
Analytical Procedures................................................................................................................. 84
9.3.3.
Immunogenicity Assessments .................................................................................................... 84
9.4.
Biomarkers ..................................................................................................................................... 84
9.5.
Pharmacogenomic Evaluations ..................................................................................................... 85
9.6.
Serologic Markers .......................................................................................................................... 85
9.7.
Cutaneous Lupus Substudy........................................................................................................... 85
9.8.
Safety Evaluations ......................................................................................................................... 86
9.9.
Sample Collection and Handling.................................................................................................... 88
10.
SUBJECT COMPLETION/WITHDRAWAL....................................................................................... 89
10.1.
Completion ..................................................................................................................................... 89
10.2.
Discontinuation of Study Treatment............................................................................................... 89
10.3.
Withdrawal from the Study............................................................................................................. 90
11.
STATISTICAL METHODS................................................................................................................. 91
11.1.
Subject Information ........................................................................................................................ 91
11.2.
Sample Size Determination ........................................................................................................... 91
11.3.
Efficacy Analyses ........................................................................................................................... 92
11.3.1.
Primary Endpoint Analysis.......................................................................................................... 92
11.3.2.
Major Secondary Analyses......................................................................................................... 93
11.3.3.
Other Planned Efficacy Analyses ............................................................................................... 94
11.3.4.
Efficacy Analyses in the Study Extension................................................................................... 94
11.4.
Interim Analyses............................................................................................................................. 94
11.5.
Pharmacokinetic Analyses............................................................................................................. 94
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11.6.
Immunogenicity Analyses .............................................................................................................. 94
11.7.
Biomarker Analyses ....................................................................................................................... 95
11.8.
Pharmacogenetics Analyses.......................................................................................................... 95
11.9.
Pharmacokinetic and Pharmacodynamic Analysis ........................................................................ 95
11.10.
Safety Analyses ............................................................................................................................. 95
11.11.
Data Monitoring Committee ........................................................................................................... 96
12.
ADVERSE EVENT REPORTING ...................................................................................................... 97
12.1.
Definitions ...................................................................................................................................... 97
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 97
12.1.2.
Attribution Definitions.................................................................................................................. 98
12.1.3.
Severity Criteria .......................................................................................................................... 99
12.2.
Special Reporting Situations.......................................................................................................... 99
12.3.
Procedures................................................................................................................................... 100
12.3.1.
All Adverse Events.................................................................................................................... 100
12.3.2.
Serious Adverse Events ........................................................................................................... 101
12.3.3.
Pregnancy................................................................................................................................. 101
12.4.
Contacting Sponsor Regarding Safety......................................................................................... 102
13.
PRODUCT QUALITY COMPLAINT HANDLING............................................................................ 102
13.1.
Procedures................................................................................................................................... 102
13.2.
Contacting Sponsor Regarding Product Quality .......................................................................... 102
14.
STUDY DRUG INFORMATION....................................................................................................... 102
14.1.
Physical Description of Study Drug.............................................................................................. 102
14.1.1.
IV administration....................................................................................................................... 102
14.1.2.
SC administration ..................................................................................................................... 103
14.2.
Packaging .................................................................................................................................... 103
14.3.
Labeling........................................................................................................................................ 103
14.4.
Preparation, Handling, and Storage............................................................................................. 103
14.5.
Drug Accountability ...................................................................................................................... 104
15.
STUDY-SPECIFIC MATERIALS..................................................................................................... 104
16.
ETHICAL ASPECTS ....................................................................................................................... 105
16.1.
Study-Specific Design Considerations......................................................................................... 105
16.2.
Regulatory Ethics Compliance..................................................................................................... 105
16.2.1.
Investigator Responsibilities ..................................................................................................... 105
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................. 105
16.2.3.
Informed Consent ..................................................................................................................... 107
16.2.4.
Privacy of Personal Data .......................................................................................................... 108
16.2.5.
Long-Term Retention of Samples for Additional Future Research .......................................... 108
16.2.6.
Country Selection ..................................................................................................................... 109
17.
ADMINISTRATIVE REQUIREMENTS ............................................................................................ 109
17.1.
Protocol Amendments.................................................................................................................. 109
17.2.
Regulatory Documentation .......................................................................................................... 109
17.2.1.
Regulatory Approval/Notification .............................................................................................. 109
17.2.2.
Required Prestudy Documentation........................................................................................... 109
17.3.
Subject Identification, Enrollment, and Screening Logs .............................................................. 110
17.4.
Source Documentation................................................................................................................. 111
17.5.
Case Report Form Completion .................................................................................................... 111
17.6.
Data Quality Assurance/Quality Control ...................................................................................... 112
17.7.
Record Retention ......................................................................................................................... 112
17.8.
Monitoring .................................................................................................................................... 113
17.9.
Study Completion/Termination..................................................................................................... 114
17.9.1.
Study Completion ..................................................................................................................... 114
17.9.2.
Study Termination..................................................................................................................... 114
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17.10.
On-Site Audits .............................................................................................................................. 114
17.11.
Use of Information and Publication.............................................................................................. 115
REFERENCES.......................................................................................................................................... 117
ATTACHMENT 1: EFFICACY EVALUATIONS AND ENDPOINTS........................................................ 120
ATTACHMENT 2:  QUANTIFERON-TB GOLD TESTING .................................................................... 122
ATTACHMENT 3:  TUBERCULIN SKIN TESTING ................................................................................. 124
ATTACHMENT 4:  HBV SCREENING AND MONITORING ................................................................... 125
ATTACHMENT 5: SLEDAI-2K/S2K RI-50 AT SCREENING VISIT......................................................... 126
ATTACHMENT 6: SLEDAI-2K / S2K RI-50 (BASELINE) ....................................................................... 129
ATTACHMENT 7: S2K RI-50 (FOLLOW-UP).......................................................................................... 133
ATTACHMENT 8: BILAG 2004................................................................................................................ 137
ATTACHMENT 9: CLASI ......................................................................................................................... 138
ATTACHMENT 10: PHYSICIAN GLOBAL ASSESSMENT OF DISEASE ACTIVITY............................ 139
ATTACHMENT 11: PATIENTS GLOBAL ASSESSMENTS OF DISEASE AND PAIN ACTIVITY ........ 140
ATTACHMENT 12: SF-36 ........................................................................................................................ 141
ATTACHMENT 13: FATIGUE SEVERITY SCALE.................................................................................. 147
INVESTIGATOR AGREEMENT ............................................................................................................... 148
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LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Time and Events Schedule for the Main Study Design (Screening through 8-Week/16-
Week Safety Follow-up)............................................................................................................ 35
Table 2:
Time and Events Schedule in the CNTO1275SLE2001 Study Extension (Week 48/56 
through Extension Safety Follow-up)........................................................................................ 39
Table 3:
Clinical and Immunological Criteria Used in the SLICC Classification Criteria*25 .................... 55
Table 4:
Power to Detect a Significant Treatment Difference in the Proportion of Subjects with 
SRI-4 Response at Week 24 .................................................................................................... 92
Figures
Figure 1:
Schematic Overview of the Main Study (Screening through 16-Week Safety Follow-
Up) ............................................................................................................................................ 52
Figure 2:
Schematic Overview Including the Study Extension ................................................................ 53
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PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
18 December 2014
Amendment 1
19 May 2015
Amendment 2
24 November 2015
Amendment 3
18 January 2017
Amendments below are listed beginning with the most recent amendment.
Amendment INT-3 (18 January 2017)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.
The overall reason for the amendment: The overall reason for the amendment is to further evaluate the safety and 
efficacy of long-term ustekinumab administration in subjects with Systemic Lupus Erythematosus (SLE) who are 
participating in the CNTO1275SLE2001 study extension.
Applicable Section(s)
Description of Change(s)
Rationale: The primary purpose of the amendment is to allow further evaluation of the safety and efficacy of long-
term ustekinumab administration in subjects with Systemic Lupus Erythematosus (SLE) who are participating in the 
CNTO1275SLE2001 study extension.
Synopsis
Exploratory 
Objectives

Safety and efficacy during long-term administration of ustekinumab.

Reduction in corticosteroid dosing during long-term administration of 
ustekinumab.
Synopsis
Overview of Study 
Design
Database locks (DBLs) will occur at Weeks 24 and 56 following the last subject’s Week 
56 visit, or the final subject’s Week 16 safety follow-up visit from the main study.
Synopsis
Overview of Study 
Design
The amended study design will continue to provide open-label ustekinumab 90 mg 
q8w SC administration through Week 104. Subjects will be eligible to continue study 
treatment through Week 104 if they meet the study inclusion criteria (Section 4.1.3) 
including:

must not have permanently discontinued study treatment on or before their 
Week 40 visit, and

are able to continue q8 week study treatment at approximately 8 weeks (±2
weeks) after their Week 40 visit
or

are able to resume study treatment with no more than 16 weeks (±2 weeks) since 
their Week 40 visit.
In addition to the DBL planned following the final subject’s Week 56 visit, or the last 
subject’s Week 16 safety follow-up visit from the main study, there will be an 
additional DBL at the end of the study extension (following Study Extension 16-week 
safety follow-up visit).
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
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Applicable Section(s)
Description of Change(s)
Synopsis
Dosage and 
Administration
Every reasonable effort should be made to keep concomitant medications stable at least 
through Week 28, with some adjustments allowed beyond Week 28 through Week 48 the 
8-Week Safety Follow-Up or study extension as defined in the protocol.
Subjects who are enrolled in the study extension will continue to receive ustekinumab 
90 mg SC administration every 8 weeks through Week 104. With the exception of 
corticosteroids, concomitant medications should be maintained at stable doses 
through the study extension.
After Week 40 to 16-Week Safety Follow-Up (Safety Follow-up Phase)
Groups 1 and 2: Subjects will who do not participate in the study extension are 
expected to return for safety follow-up visits at Weeks 44, 48, and 56 and for 8- and 16-
weeks safety follow up.
Study Extension (Week 48/Week 56 through Week 120)
Subjects who meet the study extension inclusion criteria (Section 4.1.3) will receive 
an additional 1 year of open label ustekinumab administration for the purpose of 
expanding the safety experience and maintenance of efficacy in lupus patients 
exposed to ustekinumab 90 mg q8w. Subjects who continue dosing in the extended 
study starting at Week 48 or at Week 56 will receive open-label ustekinumab SC 
dosing through Week 104. If the development of ustekinumab in SLE is terminated, 
then the study extension will also be discontinued.
Synopsis
Safety Evaluations
Subject diary cards will be used to capture medication changes that occur in between study 
visits during the main portion of this study.
Time and Events 
Schedule
Table 1: Time and Events Schedule for the Main Study Design (Screening through 8-
Week/16-Week Safety Follow-up)
Time and Events 
Schedule
Main Study Safety Follow-up Phase
8-Week Safety Follow-up 48b
16-Week Safety Follow-up/Final Visitb
Time and Events 
Schedule
b.
Subjects, who discontinue study agent administrations on or before the Week 40 
visit, must return approximately 8 and 16 weeks after last study agent administration for 
safety follow-up visits (analogous to assessments done at Week 48 and Week 56, 
respectively). The 8-week and/or 16-week safety follow-up visits are not required for 
subjects who continue treatment in the study extension within 8 (±2 weeks) or 16 (±2 
weeks) weeks, respectively, of their Week 40 visit (refer to Table 2).
Time and Events 
Schedule
c.
All assessments (except for injection-site evaluation) are to be completed prior 
to study agent administration, unless otherwise specified.
Time and Events 
Schedule
Table 2: Time and Events Schedule in the CNTO1275SLE2001 Study Extension
(Week 48/56 through Extension Safety Follow-up) added.
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Applicable Section(s)
Description of Change(s)
Section 1.3.
Justification for 
Dosing Regimen
Although the dosing rationale has not changed, some additional safety and efficacy 
information has become available from the ustekinumab Phase 3 CD (UNITI) studies 
which supports the treatment extension planned for this study. These results from the 
UNITI CD studies are summarized later in this section (Section 1.3).
In addition, there were also 3 Phase 3 studies in subjects with CD initiated in 2011
that have recently provided additional safety and efficacy data; UNITI-1, UNITI 2, 
and IM-UNITI. UNITI-1 and UNITI-2 were 8-week induction studies and were 
identical in design but studied distinct patient populations. UNITI-1 studied subjects 
who had failed or were intolerant to anti-TNF agents while UNITI-2 studied subjects 
who had not failed a TNF antagonist but who had failed conventional 
immunomodulator or steroid therapies. The IM-UNITI study evaluated maintenance 
treatment for patients enrolled from both UNITI-1 and UNITI-2 studies. The UNITI 
studies randomized 1,367 subjects to either placebo, 130 mg IV or approximately 6 
mg/kg IV. After Week 8 of therapy, subjects in both UNITI-1 and UNITI-2 studies 
could enter into IM-UNITI, which primarily evaluated two maintenance regimens of 
90 mg every 8 or 12 weeks compared to placebo in induction responders. While the 
IM-UNITI study is still ongoing in the long-term extension phase, the primary results 
of all 3 studies have been published,7 and the results supported the approval of 
ustekinumab in patients with active moderate to severe CD. The approved dose in 
induction is a single IV weight-based dose approximating 6 mg/kg and the approved 
maintenance dose is 90 mg either every 8 or 12 weeks depending on the approval 
region. 
The 
results 
of 
these 
studies 
are 
particularly 
relevant 
to 
the 
CNTO1275SLE2001 SLE study in that a similar dose is being evaluated. In addition, 
similar to the SLE population, about 1/3 of the CD patients enrolled into the UNITI 
studies were using concomitant immunomodulators (e.g MTX, AZA, 6-MP) and 
approximately 46% were on concomitant glucocorticoids. The results of these studies 
are reviewed in detail in the primary publication7 and the highlights are presented 
below:

In the 2 UNITI induction studies, the primary endpoint and all major secondary 
endpoints were met for both doses studied including the 6 mg/kg dose.

In the IM-UNITI maintenance study, both the 90 mg every 8 or every 12 week 
regimens were superior to placebo in maintaining response or achieving 
remission compared to placebo at Week 44.

Importantly, the safety profile of both maintenance doses were comparable to 
placebo over 44 weeks and no new safety signals were identified. The safety 
profile was similar to that seen in the psoriatic indications.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
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Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
In summary, these CD studies support the dosing regimen planned for this proof-of 
concept SLE study including body weight-range based IV loading dose approximating 
6 mg/kg followed by 90 mg SC q8w will be employed to ensure a high level of systemic 
exposure of ustekinumab to inhibit the actions of IL-12/23 in this proof-of-concept study 
in subjects with active SLE.
Open label 90 mg SC q8w ustekinumab dosing will be provided to subjects starting at 
Week 24 though Week 40. Per the amended study design, subjects who are able to 
continue q8w study treatment at approximately 8 weeks (±2 weeks) after their Week 
40 visit, or are able to resume study treatment with no more than 16 weeks (±2 
weeks) since their Week 40 visit will be eligible for continued 90 mg SC q8w 
ustekinumab treatment through Week 104, followed by an additional 16-week safety 
follow-up period.
2.1.
Objectives
Exploratory 
Objectives

Safety and efficacy during long-term administration of ustekinumab.

Reduction in corticosteroid dosing during long-term administration of 
ustekinumab.
3. Study Design and 
Rationale
A complete list describing all efficacy evaluations and endpoints, and which evaluations 
are included in the composite endpoints is provided in Attachment 1. The main study is 
defined from the original protocol as screening through the Main Study 8-week and 
16-week safety follow-up visits. Note that the Main Study 8-week and 16-week safety 
follow-up visits were previously described in the original protocol as the Week 48 and 
Week 56 visits. However, with this amendment, the Week 48 and Week 56 visits will 
only be used to describe treatment visits for those subjects who are participating in 
the study extension. The study extension (applicable to subjects meeting the inclusion 
criteria) is defined as the Week 48 or Week 56 visits through the Study Extension 16-
week safety follow-up visit.
3.1.
Overview of 
Study Design
Database locks (DBLs) will occur at Weeks 24 and 56 after the final subject’s Week 56 
visit or following the last subject’s 16-week safety follow-up visit from the main 
study.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
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Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
3.1.
Overview of 
Study Design
The amended study design will continue to provide open-label ustekinumab 90 mg 
q8w SC administration through Week 104 (study extension). Subjects will be eligible
to continue study treatment through Week 104 if they meet the study inclusion 
criteria (Section 4.1.3):

must not have permanently discontinued study treatment on or before their 
Week 40 visit, and

are able to continue q8 week study treatment at approximately 8 weeks 
(±2 weeks) after their Week 40 visit
or

are able to resume study treatment with no more than 16 weeks (±2 weeks) since 
their Week 40 visit
In addition to the DBL planned following the last subject’s Week 56 visit or the final 
16-week safety follow-up visit from the main study, there will be an additional DBL 
following the Extension 16-Week Safety Follow-up period.
A diagram of the main study design is provided below in Figure 1, and a diagram of the 
extended study is provided in Figure 2.
3.1.
Overview of 
Study Design
Figure 1:
Schematic Overview of the Main Study (Screening through 16-Week 
Safety Follow-Up)
3.1.
Overview of 
Study Design
Figure 1 updated
3.1.
Overview of 
Study Design
Figure 2:
Schematic Overview Including the Study Extension added.
4. Subject 
Population
The study extension population will be comprised of those subjects who have not 
permanently discontinued study treatment before or at the Week 40 dose and for 
whom the investigators judge that there is a potential benefit that outweighs the
potential risks to continued ustekinumab treatment.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
12
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
4.1.
Inclusion 
Criteria
4.1.3.
Inclusion Criteria Applicable to All Subjects Entering into the Study
Extension (Week 48 or Week 56 visits)
Any subjects who do not meet the inclusion criteria for the study extension must 
follow the Time and Events schedule for the main study design (Table 1), and have 
safety follow-up visits conducted at 8 and 16 weeks following their Week 40 or final 
study dose.
1.
Subjects must not have permanently discontinued study treatment on or before 
their Week 40 visit and are able to either continue q8w SC dosing at 
approximately 8 weeks (±2 weeks) after their Week 40 visit, or are able to resume 
dosing at Week 56 with no more than 16 weeks (±2 weeks) since their Week 40 
visit.
2.
In the judgment of the study investigator, the potential benefit of continuing 
ustekinumab long-term treatment outweighs the potential risks for the subject.
3.
Each subject must sign a revised informed consent indicating agreement to 
participate in the extended study.
4.3.
Prohibitions 
and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study (including the study extension) to be eligible 
for continued dosing in the study:
6.2.
Subcutaneous 
administration
After Week 40 to 16-week Safety Follow up (Safety Follow-up Phase)
Groups 1 and 2: Subjects will who do not participate in the study extension are 
expected to return for safety follow-up visits at Weeks 44, 48, and 56 and for 8- and 16-
weeks safety follow up.
Study Extension (Week 48/Week 56 through Week 120)
Subjects who meet the study extension inclusion criteria will receive open-label 
ustekinumab administration for the purpose of expanding the safety experience and 
maintenance of efficacy in lupus patients continuously exposed to ustekinumab 90 mg 
q8w. Subjects who continue dosing in the extended study starting at Week 48 or at 
Week 56 will receive open-label ustekinumab SC dosing through Week 104. If the 
development of ustekinumab in SLE is terminated, then the study extension will also 
be discontinued.
7.
Treatment 
Compliance.
Through the Week 32 visit, the visit and study agent administration should occur within 
± 7 days of the scheduled visit day (relative to Week 0). Following the Week 32 visit, the 
study agent administrations are allowed to occur within ±2 weeks of the scheduled 
visit day (relative to Week 0).
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
13
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
8.
Concomitant 
Therapy
Every reasonable effort should be made to keep concomitant medications stable at least 
through Week 28, and if possible also through Week 48 the main study 8-week safety 
follow-up or through the study extension (if applicable). With the exception of 
corticosteroids (see Section 8.3
regarding corticosteroid tapering), all other 
concomitant medications should be maintained at stable doses throughout the study.
8.
Concomitant 
Therapy
Subject diary cards will be used to capture changes in subject-administered medications 
that occur in between study visits during the main portion of this study, and these 
changes must also be recorded in the concomitant therapy section of the eCRF.
8.1.
Immunomodulators
Beyond Week 28, immunomodulators should remain as stable as possible through Week 
48 the 8-week safety follow-up or through the study extension (if applicable), 
however, dose adjustment is allowed for unacceptable side effects.
8.2
Antimalarial 
Medications
Stable treatment with hydroxychloroquine, chloroquine, or quinacrine is permitted through 
Week 48 the 8-week safety follow-up.
8.3.
Corticosteroid 
Therapy
Unnecessary dose changes are discouraged, and any dose adjustments should be made in 
increments. Changes in corticosteroids through Week 48 the 8-week safety follow-up or 
through the study extension (if applicable) are allowed for medical necessity, but the 
degree and timing of the adjustment should be carefully considered as this may have an 
impact on the study results, especially during the period between 12 and 28 weeks.
8.3.
Corticosteroid 
Therapy
Following Week 28, changes in corticosteroid dosing through Week 48 the 8-week safety 
follow-up is allowed for medical necessity, but the degree and timing of the adjustment 
should be carefully considered as this may have an impact on the study.
8.3.
Corticosteroid 
Therapy
Gradual tapering of oral corticosteroid dosing in the study extension (recommended 
reductions of no more than 10 to 20% of the original dose per week) is encouraged 
starting after the Week 48 dose at the discretion of the study investigator. Tapering 
to the lowest possible maintenance dose of corticosteroids is recommended, including 
complete weaning off of corticosteroids if possible. It is recommended that subjects 
should be educated and monitored by study staff for symptoms of steroid deficiency 
(eg, Addisonian symptoms) during periods of steroid tapering, as appropriate.
If subjects experience a worsening in their disease activity while tapering 
corticosteroids, further dose decreases may be suspended, and/or their oral 
corticosteroid dose may be temporarily increased if deemed necessary by the 
investigator. For subjects whose corticosteroid taper is interrupted, investigators are 
encouraged to resume tapering within 4 weeks.
In the event of increased corticosteroid dosing, it is recommended that the average 
dose should not be increased above the baseline dose unless medically necessary.  
Discretion should be used as any corticosteroid increases may render a subject to be 
considered a treatment or steroid tapering failure. Sustained oral corticosteroid doses 
of 40 mg/day or higher may result in discontinuation of study agent.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
14
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
8.3.
Corticosteroid 
Therapy
For subjects in the cutaneous lupus substudy, the initiation of, or an increase from baseline 
in, the use of potent topical corticosteroids, or intra-lesional corticosteroid injections, is not 
recommended allowed and should be avoided through Week 48 the 8-week safety follow-
up or the study extension.
8.4.
Nonsteroidal 
Anti-inflammatory 
Drugs
After Week 28 and through Week 48, A Minor adjustments in NSAID therapy are 
allowed after Week 28 although it is recommended that the use of any NSAIDS 
remain as stable as possible, and any notable changes should be recorded.
8.5.
Anti-
hypertensive 
medications
and would result in subject being classified at a treatment failure. Subjects should not 
initiate any new ARB or ACE inhibitor therapy between randomization and Week 
28.
8.6.
Topical 
Medications
Topical medications are permitted; however, topical compounds cannot include a 
prohibited medication. Topical ointments or creams of cyclosporine A are prohibited 
through Week 28; however ophthalmic use is permitted. Low potency topical steroids are 
allowed except on day of study visit. Medium to high potency topical corticosteroids are 
disallowed for all subjects through Week 48 the 8-week safety follow-up, and high 
potency topical corticosteroids are not allowed for subjects enrolled in the study 
extension. For subjects in the cutaneous lupus substudy, topical treatment of target lesions 
should remain stable during the cutaneous lupus substudy period. For 72 hours prior to 
study visit, topical medications should not be applied to lesions under evaluation.
9.1.
Study 
Procedures
9.1.1.
Overview
The total blood volume to be collected from each subject over the course of the main 
portion of the study will be approximately 640 mL. The total blood volume to be 
collected in the study extension between Weeks 48 and 120 will be approximately 
250 mL.
9.1.
Study 
Procedures
9.1.3.1. Week 0/Day 
of Randomization
Subject’s diary card which was distributed during screening will be reviewed at Week 0, 
and a new card will be provided at each study visit to record medication changes during 
the subsequent 4 weeks through the main portion of the study.
9.1.4.
Post-
treatment Phase 
(Follow-Up)
9.1.4 Post-treatment Phase (Follow-Up)
Post-treatment follow up visits will occur at 8 and 16 weeks following the last dose 
received at Week 40 (ie, through Week 56). Assessments will be performed as indicated in 
the Time and Events Schedule (Table 1). The final efficacy and safety assessments will be 
performed at Week 56.
9.1.5.
Study Extension (Week 48/Week 56 through Week 104)
Subjects who qualify for participation in the study extension through Week 104 will 
continue ustekinumab 90 mg q8w SC dosing at approximately 8 weeks (±2 weeks) 
after their Week 40 visit, or resume ustekinumab dosing at Week 56 with no more 
than 16 weeks (±2 weeks) since their Week 40 visit.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
15
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
9.1.4.2
Subjects 
Who Permanently 
Discontinue Study 
Agent before Week 
40
9.1.4.2
Subjects Who Permanently Discontinue Study Agent before Week 40
9.1.7
Safety Follow-up for Subjects Who Permanently Discontinue Study Agent at 
or before Week 104
Subjects who permanently discontinue study agent at or before Week 40, or permanently 
discontinue at or before Week 104 if they are participating in the study extension, but 
do not withdraw from study participation, should be followed for approximately 16 weeks 
(5 half-lives) after the last study agent administration according to the visit schedule and 
assessments indicated in the appropriate Time and Events Schedules (Table 1 and Table 
2). Follow-up visits should occur approximately 8 weeks and 16 weeks after the last study 
agent administration. Subjects who permanently discontinue study agent before or at 
Week 40 will not be eligible to participate in the study extension.
Telephone contact will be made to determine reasons for study discontinuation for up to 
16 weeks after the last dose of study drug, unless the subject has died, is lost to follow-up, 
or has withdrawn consent. If the information on reason for discontinuation is obtained via 
telephone contact, written documentation of the communication must be available for 
review in the source documents. If the subject has died, the date and cause of death will be 
collected and documented on the CRF.
9.2.3.
Endpoints
4.
 
 
 
5.
 
 
16.
The proportion of subjects with meaningful changes in selected SLE medications 
from Week 12 through Week 48 Main Study 8-week Safety Follow-up Visit/Week 
48.
17.
Change in corticosteroid dose from Week 48 through Week 104 for subjects 
who participate in the study extension.
9.8.
Safety 
Evaluations
Refer to Section 4.1 for tuberculosis screening criteria. Subject diary cards will be used to 
capture medication changes that occur in between study visits through the main portion 
of this study.
9.8.
Safety 
Evaluations
The study will include the following evaluations of safety and tolerability according to the 
time points provided in Table 1 and Table 2 for the extended study.
9.8.
Safety 
Evaluations
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected according to the 
Time and Events Schedule (Table 1 and Table 2 for the extended study).
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
16
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
9.8.
Safety 
Evaluations
Physical Examination
A full body physical examination will be performed pre-treatment and during the study as 
shown in Table 1 and Table 2 for the extended study.
9.9.
Sample 
Collection and 
Handling
Refer to the Time and Events Schedule (Table 1 and Table 2 for the extended study) for 
the timing and frequency of all sample collections.
10.1.
Completion
A subject who does not enter into the study extension will be considered to have 
completed the main study if he or she has completed assessments through Week 56 16-
week safety follow-up of the main study. A subject who has enrolled into the study 
extension will be considered to have completed the main portion of this study if he or 
she has completed assessments through either the 8-week safety follow-up visit of the 
main study. Subjects who prematurely discontinue study treatment for any reason before 
Week 56 the Week 8 or Week 16 safety follow-up visits (from the main study), will not 
be considered to have completed the main portion of the study. A subject who has 
enrolled into the study extension will be considered to have completed the study 
extension if he or she has completed assessments through Week 120.
10.2.
Discontinuation of 
Study Treatment
If a subject's study treatment must be discontinued before or at Week 40 (for subjects 
who do not participate in the study extension) or before Week 104 (for subjects who 
do participate in the study extension), this will not result in automatic withdrawal of the 
subject from the study and follow-up assessments should be obtained approximately 8 and 
16 weeks following the last dose of study agent.
11.3.1.
Primary 
Endpoint Analyses

Initiation of new ARB or ACE inhibitor therapy after first dose of study agent and 
before Week 24. Subjects who were not receiving ARB or ACE inhibitor therapy 
who then initiated a new ARB or ACE inhibitor therapy between Week 12 and 
Week 24. Subjects who substitute an ARB or ACE inhibitor for a comparable 
medication would not be considered treatment failures.
11.3.4.
Efficacy 
Analyses in the 
Long-Term 
Extension
Long-term evaluations of efficacy including SRI-4, SLEDAI-2K, PGA, reduction in 
corticosteroid dosing, and evaluations of flare over time will also be performed for 
those subjects who participate in the study extension.
11.11.
Data 
Monitoring 
Committee
The DMC will no longer be active after the assessment of the primary endpoint in 
this study.
REFERENCES
7. 
Feagan, BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and 
Maintenance Therapy for Crohn's Disease. N Engl J Med. 2016;375(20):1946-
1960.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
17
Approved, 18 January 2017
Amendment INT-2 (24 November 2015)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union. 
The overall reason for the amendment: The overall reasons for the amendment are to provide clarification and 
additional detail regarding 1) subject eligibility and enrollment, 2) use of restricted and prohibited concomitant 
medications, 3) refine the definition of the primary endpoint, 4) specify conditions under which subjects may 
undergo retesting at screening, 5) elaborate on the statistical procedures to be used to conduct the interim and 
planned data analyses, and 6) provide additional information regarding the collection of samples during the Time 
and Events Schedule.
Applicable Section(s)
Description of Change(s)
Rationale: Clarifications in several sections in the Synopsis regarding: how the SLEDAI-2K scoring, and the 
BILAG A and BILAG B domain scores will be used to assess subject eligibility for randomization; increased 
medication use after randomization may result in assessment of the subject as a treatment failure; and evaluation of
photographs and/or biopsy samples in subjects who consent to participate in the cutaneous lupus substudy.
Synopsis
Overview of Study 
Design
Subjects must also demonstrate at least 1 British Isles Lupus Assessment Group 
(BILAG) A and/or 2 BILAG B domain scores observed during screening.. and/or 
Week 0 prior to first administration of study agent. In addition, subjects must have a 
clinical SLEDAI-2K score ≥4 (excluding laboratory results) at week 0, prior to 
randomization.
Synopsis
Subject Population
Screening for eligible subjects must be performed no more than 6 weeks prior to the 
randomization visit (Week 0).
Subjects must also have at least 1 BILAG A and/or 2 BILAG B domain scores 
observed during screening prior to first administration of study agent.
In addition, to be eligible for study participation, subjects must have a clinical 
SLEDAI-2K score 4 (excluding laboratory results) for clinical features at Week 0
(prior to randomization), and have received approval for study randomization 
following review and adjudication of screening lupus assessments by the Sponsor 
and/or Sponsor-selected independent reviewer(s).
SLE subjects enrolling into the main study with active cutaneous lupus (including subjects 
with discoid lupus erythematosus, subacute cutaneous lupus erythematosus, alopecia or 
SLE malar rash or other SLE skin lesions characterized by erythema and or scale) will be 
evaluated using CLASI scoring.
Synopsis
Dosage and 
Administration
If concomitant medications have been adjusted after randomization as allowed per 
protocol, every effort should be made to return subject back to the baseline (Week 0) dose 
level by the Week 12 visit; or increased medication use may render a subject to be 
considered a treatment failure.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
18
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
Synopsis
Cutaneous Lupus 
Substudy
Subjects who provide consent will be enrolled in the cutaneous lupus substudy evaluating 
the histology of cutaneous biopsies and/or skin photographs. Biopsy samples (2 samples, 4 
mm size) from consenting subjects will be collected prior to dosing at Week 0 and at 
Week 24 from a single lesion or area of active cutaneous disease. Photographs and skin 
biopsies can target a different area of active disease, but the follow-up photographs 
or biopsies should re-evaluate the same area of active disease as originally assessed at 
week 0.
Subjects with cutaneous lupus deemed unsuitable for biopsy (eg, malar rash or alopecia) 
can also be enrolled in the substudy, and may be evaluated by photography.
Rationale: Clarification and addition of explanatory footnotes for key data collection time points specified in the 
Time and Events Schedule.
TIME AND 
EVENTS 
SCHEDULE
Footnote a.
a. Screening visit must be performed no more than 6 weeks prior to the 
randomization visit (Week 0). To be eligible for study participation, subjects must 
have SLEDAI score ≥4 (excluding laboratory results) for clinical features at Week 
0 and have received approval for study randomization following review and 
adjudication of screening lupus assessments by the Sponsor and/or Sponsor-
selected independent reviewer(s).
Footnote j.
j. Subjects should be monitored for the occurrence of infusion or injection-site 
reactions for 30 minutes after administration of the infusion (IV administration) or 
injection.
Footnote q.
q. These tests will be performed on-site or at local lab(s).
Footnote w.
w. Biopsies are allowed to occur on the day of randomization or may occur 1 - 2 days 
prior to randomization and at the Week 24 visit.
Footnote x.
x. Photographs do not need to be taken at the same area of active disease as the 
biopsy; however, follow-up photographs or biopsies should re-evaluate the same 
area of active disease as originally assessed at week 0.
Rationale: Clarification of the Study Design with regard to use of the BILAG A and BILAG B domain scores at 
screening; conduct of 2 interim analyses with inclusion of the assessment of variations in placebo effect across 
regions.
3.1 Overview of 
Study Design
In addition, subjects must have at least 1 positive autoantibody test (ANA, anti-dsDNA 
antibodies, and/or anti-Smith antibodies) observed during screening, as well as a well-
documented positive autoantibody test in their medical history. Subjects must also 
demonstrate at least 1 BILAG A and/or 2 BILAG B domain scores observed during 
screening. and/or Week 0 prior to first administration of study agent. In addition, 
subjects must have a clinical SLEDAI-2K score ≥ 4 (excluding laboratory results) at 
week 0, prior to randomization.
Interim analyses (IA) will be conducted when approximately 1/3 and 2/3 of subjects reach 
Week 24. In the first IA, only an assessment of evidence for notable efficacy will be 
performedassessed. In the second IA, evidence for notable efficacy as well as treatment 
futility will be analyzed. Variations in placebo effect across regions will be 
incorporated into the interim analyses.
Rationale: Clarification regarding how the SLEDAI-2K score, and the BILAG A and BILAG B domain scores are
used to screen the Subject Population prior to randomization.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
19
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
4. Subject Population
Subjects must have at least 1 BILAG A and/or 2 BILAG B domain scores observed 
during screening. In addition, subjects must have at least 1 positive autoantibody test 
(ANA, anti dsDNA antibodies, and/or anti-Smith antibodies) observed during screening, 
as well as a well-documented positive autoantibody test in their medical history, and they 
must also have a clinical SLEDAI-2K score ≥4 (excluding laboratory results) prior to 
randomization at week 0. Subjects must be scored as having at least 1 BILAG A and/or 2 
BILAG B domain scores observed during screening.
Subjects with cutaneous lupus deemed unsuitable for biopsy (eg, malar rash or alopecia) 
can also be enrolled in the substudy, and may be evaluated by photography.
Rationale: Clarification of Inclusion Criteria and how the SLEDAI-2K scoring, and the BILAG A and BILAG B 
domain scores will be used to assess subject eligibility for randomization; clarifications regarding antimalarial
medications and immunodulatory drugs, and table formatting in the SLICC Classification criteria (leukopenia and 
lymphopenia).
4.1.1. Inclusion 
Criteria Applicable 
to All Subjects
Table 2, 10a, 10b
Criterion 3; bullet 3.
Criterion 4.
Criterion 7.
Criterion 8.
Table 2:
Clinical and Immunological Criteria Used in the SLICC Classification 
Criteria*23
10a. Leukopenia (<4000/mm3 at 
least once), or
10b. Lymphopenia (<1000/mm3 at 
least once)
In the absence of other known causes such as 
Felty’s, drugs, and portal hypertension
In the absence of other known causes such as 
corticosteroids, drugs, and infection
3. Bullet 3—At least 1 BILAG A and/or 2 BILAG B domain scores observed during
screening prior to first administration of study agent.
4. Demonstrate active disease based on SLEDAI-2K score ≥6 observed during screening
and assessed approximately 2 to 6 weeks prior to randomization. Must also have 
SLEDAI-2K ≥4 for clinical features (ie, SLEDAI excluding laboratory results) at Week 
0 prior to the first administration of study agent.
7.  If using antimalarials (eg, chloroquine, hydroxychloroquine, or quinacrine), subjects 
must have used the medication for ≥8 weeks and be on a stable dose for at least 6 
weeks prior to the first administration of study agent.
8. If using immunosuppressiveimmunomodulatory
drugs (mycophenolate mofetil 
[MMF]/mycophenolic acid [MPA] ≤2 g/day, azathioprine/6 mercaptopurine (AZA /6 
MP) ≤2 mg/kg/day and/or MTX ≤25 mg/wk with concomitant folic acid [recommend 
≥5 mg/wk]), subjects must be receiving a stable dose for at least 6 weeks prior to the 
first administration of study agent.
Rationale: Clarification of Additional Inclusion Criteria for subjects who may not be appropriate for biopsy 
sample collection in the cutaneous lupus substudy.
4.1.2. Additional 
Inclusion Criteria for 
the Cutaneous Lupus 
Substudy
Criterion 4.
4. Subjects with cutaneous lupus deemed unsuitable for biopsy (eg, malar rash or
alopecia) can also be enrolled in the substudy, and may be evaluated by photography.
Rationale: Clarification of Exclusion Criteria for subjects who have active Lyme disease; treatment with B cell
depletion therapy; status as an employee of the investigator; cross-reference to restriction on vaccination with BCG; 
have used or are using certain immunomodulatory therapies at screening; investigational drug or vaccine treatment; 
lives in an institution on court or authority order.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
20
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
4.2. Exclusion 
Criteria
Criterion 1.
1. Have other inflammatory diseases that might confound the evaluations of efficacy, 
including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), 
RA/lupus overlap, psoriasis or active Lyme disease.
Criterion 3.
3. Have received systemic or topical cream/ointment preparations of cyclosporine A 
or other systemic immunosuppressive immunomodulatory agents other than those 
described in the inclusion criteria within the past 3 months prior to first administration 
of study agent (Section 4.1). Corticosteroids are not included in this criterion; see 
Sections 4.3 and 8.3 regarding corticosteroids.
Criterion 4.
4. Have received a single B cell targeting agent within 3 months prior to first study 
agent administration; or received more than 1 previous B cell targeting therapy 
including belimumab or epratuzamab within 6 months prior to first administration of 
the study agent; or received B cell depleting therapy (eg, rituximab) within 12 months 
prior to first administration of the study agent or have evidence of continued B cell
depletion following such therapy.
Criterion 6.
6. Have received prior immunosuppressiveimmunomodulatory biologic therapy for lupus 
not described in Exclusion Criterion #4 including, but not limited to, tocilizumab, 
alefacept, efalizumab, natalizumab, abatacept, anakinra, brodalumab, secukinumab, 
ixekizumab, inhibitors of TNF, IL-1, IL-6, IL-17, or interferon pathways, less than 
5 half-lives or 3 months, whichever is longer, prior to first administration of the study 
agent.
Criterion 13.
13. Have received, or are expected to receive, any live virus or bacterial vaccination within 
3 months before the first administration of study agent, during the study, or within 3 
months after the last administration of study agent. For BCG vaccination criterion, 
see Exclusion Criterion 10 and Prohibition/Restriction Criterion 8.
Criterion 30.
30. Has received an investigational drug that is not previously defined in other 
exclusion criteria (including investigational vaccines or other medications specified 
in section 4.3, prohibition/restriction number 3) within 5 half-lives or 3 months, 
whichever is longer (eg, thalidomide and lenalidomide), or used an invasive 
investigational medical device within 3 months before the planned first dose of study 
drug, or is currently enrolled in an interventional study.
Criterion 36.
36. Subject is an employee of the investigator or study site (i.e. personnel to whom the 
investigator has delegated a role or responsibility for conducting the study), 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.
Criterion 37.
37. Lives in an institution on court or authority order, unless permitted by local 
regulations.
Rationale: Additions to the list of Prohibitions and Restrictions (medications) that must not be used by subjects 
during the study.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
21
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
4.3. Prohibitions and 
Restrictions
Prohibition and 
Restriction 3.
Bullet 11
Bullet 12
Bullet 14
Bullet 15
Bullet 16
3.  Use of additional immunosuppressants or immunomodulators, other than those 
explicitly allowed in the inclusion/exclusion criteria, are prohibited including but not 
limited to the following:
•
Cyclosporine A (oral or topical ointment/cream preparations)
•
Tacrolimus or picrolimus, oral or topical preparations
•
Thalidomide or lenalidomide
•
Dapsone
•
Adrenocorticotropic hormone (ACTH) by injection
Prohibition and 
Restriction 4.
4.  Use of cytotoxic drugs is prohibited including, but not limited to, cyclophosphamide, 
chlorambucil, nitrogen mustard, or other alkylating agents.
Prohibition and 
Restriction 5.
5. Multiple administrations of high doses of corticosteroids, and initiation of medium 
or high potency topical corticosteroids, are prohibited during the study as defined 
in Section 8.3.
Prohibition and 
Restriction 6.
6.   The initiation of a new permitted immunosuppressiveimmunomodulatory agent 
(MTX, azathioprine, 6-mercaptopurine, mycophenolate mofetil/mycophenolic 
acid) in addition to an ongoing immunosuppressiveimmunomodulatory therapy 
is prohibited.
Rationale: Clarification of Concomitant Therapy restrictions for subjects who may be receiving treatment with 
immunomodulators, antimalarials, or corticosteroids (topical or injection) during screening through specified study 
time points.
8. Concomitant 
Therapy
If concomitant medications have been adjusted after randomization as allowed per 
protocol, every effort should be made to return subject back to the baseline (Week 0) dose 
level by the Week 12 visit; or increased medication use (relative to baseline) may 
render a subject to be considered a treatment failure.
8.1. 
Immunomodulators
However, immunomodulator dose increases will generally not lead to the discontinuation 
of study agent administration or termination of study participation. Permanent 
discontinuation of the study treatment must be considered for subjects receiving an 
increase (relative to baseline) in their immunomodulator dose.
8.2. Antimalarial 
Medications
Stable treatment with hydroxychloroquine, chloroquine, or quinacrine is permitted 
through Week 48. Beyond Week 28, it is permitted to introduce or adjust dosing of 
antimalarials. Antimalarials produced by a licensed compounding pharmacy (eg, 
quinacrine) in the country of administration and using pharmacaceutical grade 
components are allowed.
8.3. Corticosteroid 
Therapy
Oral Corticosteriods*
*Rectal administration of corticosteroids, if necessary, should be short-term and 
using topical preparations.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
22
Approved, 18 January 2017
Applicable Section(s)
Description of Change(s)
Epidural, Intravenous, 
Intramuscular, Intra-
articular, and Intra-
lesional 
Corticosteroids
Epidural, IV, IM, IA, or intra-lesional administration of corticosteroids is strongly 
discouraged within 4 weeks prior to the first administration of study agent and is not 
allowed for the treatment of SLE through Week 28. Drugs that induce release of 
endogenous steroids such as ACTH administered by injection are not allowed within 
3 months prior to the first administration of study agent and throughout the study.
Corticosteroid Use in 
Cutaneous Lupus 
Substudy
For subjects in the cutaneous lupus substudy, initiation of medium to high potency 
topical corticosteroids, or an increase from baseline in the use of medium to high 
potency topical corticosteroids, or intra-lesional corticosteroid injections should be 
avoided through Week 48.
8.6 Topical 
Medications
Topical medications are permitted; however, topical compounds cannot include a 
prohibited medication. Topical ointments or creams of cyclosporine A are prohibited;
however, ophthalmic use is permitted.
Rationale: Clarification of conditions under which Retesting of subjects for screening laboratory test(s) will 
bepermitted, and further definition of the SLEDAI-2K score as a composite endpoint and the SRI-4 response 
endpoint based on various efficacy measures.
9.1.2.2. Retesting
If a subject has signed the ICF and failed to meet at least 1 entry requirement, a one-time 
retest of screening laboratory test(s) analyzed by the central laboratory will be allowed in 
the event of suspected error in sample collection or analysis performance, or a study entry 
procedure may be repeated once during the screening period if needed. A request to use a 
local test to replace a central lab test should be discussed with the medical monitor 
prior to retesting.
Exceptions to this are positive QuantiFERON®-TB Gold, hepatitis C or B, or HIV tests; 
unless there is a suspected error in sample collection or analysis performance, these 
tests may not be repeated to meet eligibility criteria.
Rationale: To incorporate the updated versions of the Attachments illustrating the SLEDAI-2K and S2K RI-50
scoring assessments; define values to be used in the assessment of the composite endpoint, SRI-4.
9.2.1.1. SLEDAI-2K 
and S2K RI-50
At screening (Attachment 5), features are scored by the assessing physician if present 
within the last 30 days with more severe features having higher scores, and then simply 
added to determine the total SLEDAI-2K score, which ranges from 0 to 105.31 At baseline 
(Attachment 6), the features assessed in the SLEDAI-2K are used for comparison to the 
S2K RI-50 index described below.
The SLEDAI-2K has been adapted and developed into the SLEDAI-2K Responder Index 
(S2K RI-50 [Follow-up], Attachment 7)33, a measure that can document partial 
improvement in the 24 disease features between SLEDAI-2K assessments.32
9.2.2.1. SRI-4
Systemic Lupus Erythematosus Disease Activity Index 2000 SRI-4 response is defined as 
a composite endpoint requiring at least a 4 point reduction in SLEDAI 2K score 
(Section 9.2.1.1), no worsening (˂10 mm increase) from baseline in the Physician’s 
Global Assessment of Disease Activity score (PGA) (Section 9.2.1.4), and no new 
BILAG Domain A and no more than 1 new BILAG Domain B scores (Section 
9.2.1.2).9 SRI-5 and SRI-6 are similarly defined with response requiring a ≥5 point 
reduction or ≥6 point reduction in SLEDAI 2K, respectively.
Rationale: Clarification of how and when photographs and biopsy samples should be collected for exploratory 
assessments and maintenance of subject confidentiality.
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Applicable Section(s)
Description of Change(s)
9.7 Cutaneous Lupus 
Substudy
Independent of cutaneous biopsy collection, subjects who participate in the cutaneous 
lupus substudy will be requested to provide consent for photographs to be collected from 
an identified cutaneous lesion or an area of active disease. Consenting subjects with 
cutaneous lupus unsuitable for biopsy (eg, malar rash or alopecia) may be evaluated by 
photography. The photographs are for exploratory purposes only. The photographs will be 
used to assist in a qualitative evaluation of clinical response. The photographs and skin 
biopsies can target a different area of active disease, but the follow-up photographs 
or biopsies should re-evaluate the same area of active disease as originally assessed at 
week 0. Confidentiality of the subjects involved in this study will be maintained; 
specifically photographs of subjects in this study will not be published or otherwise made 
public without blocking adequate portions of the subject’s face or body so that the 
individual cannot be identified.
Rationale: Clarification on when study treatment should be withheld or permanently discontinued depending on 
the type of infection a subject has developed and whether it resolves or not; clarification on urinalysis for laboratory 
tests.  Urine analyses will be required for all subjects, not only subjects with a history of nephritis or if the primary
investigator suspects nephritis may be present.
9.8 Safety 
Evaluations
Infections
Study agent should not be administered to a subject with a clinically important, active 
infection. Treatment with study agent should be withheld until serious and/or severe
infections are completely resolved. If a subject develops a serious or severe infection, 
including but not limited to sepsis or pneumonia, discontinuation of study treatment must 
be considered. Treatment must be permanently discontinued for subjects who develop 
an opportunistic infection. For active varicella-zoster infection or a significant exposure 
to varicella zoster infection in a subject without history of chickenpox, the subject should 
be evaluated for symptoms of infection and if the subject has received appropriate 
treatment and/or recovered or no symptoms of infection, may continue study 
administration after discussion with the study Sponsor.
Clinical Laboratory 
Tests
The investigator must review the laboratory report immediately upon availability, 
document this review, and record any clinically relevant changes occurring during the 
study in the AE section of the eCRF. Coomb’s direct test, urine dipstick, urine sediment 
microscopy and urine pregnancy test will be performed by site staff or the local 
laboratory.
Urine Analyses – Fresh spot urine
Urinalysis using urine dipstick. Urine sample will be further analyzed at  
Central laboratory.
Rationale: Clarification of specific criteria requiring permanent discontinuation of study treatment, as well as 
criteria whereby study treatment discontinuation must be considered.  
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Applicable Section(s)
Description of Change(s)
10.2. Discontinuation 
of Study Treatment
Criterion 3.
Criterion 4.
Criterion 9.
Concluding paragraph.
A subject's study treatment must be permanently discontinued if any of the following 
occur:
3. Pregnancy or planning to become pregnant within the study period or within 16 
weeks after the last study agent injection.
4. The initiation of prohibited medications or treatments (as per Sections 4.3).
9. Significant worsening of SLE disease activity from baseline or having high disease 
activity for 2 or more consecutive visits starting at Week 16 based on overall 
clinical assessments; or if a subject requires the addition of a new 
immunomodulator to the existing treatment regimen after Week 16.
In addition, permanent discontinuation of study agent treatment must be considered
for subjects who: 
•  Receive an increase (relative to baseline) in their immunomodulator dose.
• Develop any of the following adverse events that are reported as serious or 
severe: study agent infusion reaction, injection-site reaction, or infection.
Rationale: Clarification of the statistical procedures to be used for sample size determination, interim and planned 
data analyses of the primary and major secondary endpoints, and other efficacy analyses during the study.
11.2. Sample Size 
Determination
The sample size calculation is based upon the primary endpoint, proportion of SRI-4 
responders at Week 24. Approximately 60 subjects treated with ustekinumab and 
approximately 40 subjects with placebo is projected to give approximately 80% power to 
detect a significant difference in response rate compared with placebo (assume 35% and 
60% response rates in placebo and ustekinumab respectively, which translates to 25% 
absolute increase over placebo or an odds ratio of 2.79) with an alpha level of 0.1. The 
assumption of a 35% responder rate for placebo is based upon a previous study in which a 
similar SLE population was treated.34 Recent studies have shown very high placebo 
rates in certain regions, thus it is possible that the power for the study could be 
reduced depending on enrollment and patient assessments conducted in specific 
regions.14
11.3.1 Primary 
Endpoint Analysis
Subgroup analysis based on region will be performed. This is due to potential 
regional differences in evaluating efficacy, and high placebo response rates in certain 
regions. Subgroup analysis of the primary endpoint by other selected baseline 
characteristics will be presented. Details will be outlined in the SAP.
11.3.2. Major 
Secondary Analyses
• The proportion of subjects with BICLA response at Week 24.
The BICLA response will be analyzed as defined in the SAP.
Continuous responses will be analyzed using an analysis of covariance model with 
treatment group as a fixed factor and baseline stratifications (eg, regions) as a covariate.
11.3.3. Other 
Planned Efficacy 
Analyses
Continuous responses will be analyzed using an analysis of covariance model with 
treatment group as a fixed factor and baseline stratifications (eg, regions) as a covariate.
11.4. Interim 
Analyses
Interim analyses (IA) will be conducted when approximately 1/3 and 2/3 of subjects reach 
Week 24. In the first IA, only evidence for notable efficacy will be assessed. In the 
second IA, evidence for notable efficacy as well as treatment futility will be analyzed. 
Variations in placebo effect across regions will be incorporated into the interim 
analyses. Details concerning the IAs are described in the IA Statistical Analysis Plan.
Rationale: Clarification and inclusion of the revised definition of the SRI-4 as a composite endpoint based on 
other key efficacy measures.
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Applicable Section(s)
Description of Change(s)
ATTACHMENT 1: 
EFFICACY 
EVALUATIONS
AND ENDPOINTS
SRI-4
Composite endpoint requiring at least a 4 point reduction in SLEDAI 2K, no worsening 
(˂10 mm increase) from baseline in PGA and no new BILAG Domain A or B scores.
Composite endpoint requiring at least a 4 point reduction in SLEDAI 2K, no 
worsening (˂10 mm increase) from baseline in PGA and no new BILAG Domain A 
and no more than 1 new BILAG Domain B scores (see Section 9.2.2.1.).
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Amendment INT-1 (19 May 2015)
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union
The overall reason for the amendment: The overall reason for the amendment is to clarify the use of highly 
effective methods of contraception for subject inclusion and continuation in the study, and correction of minor 
errors and omissions.
Applicable Section(s)
Description of Change(s)
Rationale: Clarification of highly effective method of contraception
4.1.1. Inclusion 
Criterion #10.
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, established use of oral, injected or implanted hormonal 
methods of contraception associated with inhibition of ovulation; placement of an 
intrauterine device  or intrauterine system; 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); true abstinence (when this is in line 
with the preferred and usual lifestyle of the subject).  
Rationale: Clarification of highly effective method of contraception. Two methods of pregnancy prevention are not 
required for women using hormonal methods of birth control.
4.3. Prohibitions and 
Restrictions, #1.
If a woman is capable of pregnancy, she must remain on a highly effective method of birth 
control during the study and for 4 months after receiving the last study agent. If she is 
using hormonal contraceptives, she must use an additional non-hormonal birth control 
method. The exception to this restriction is if the subject or her male partner is sterilized; 
this situation does not require birth control. A woman must not donate eggs (ova, oocytes) 
for the purposes of assisted reproduction during the study and for 4 months after receiving 
the last dose of study agent.
Rationale: An additional exclusion criterion was added
4.2. Exclusion 
Criterion, #27.
Subject has a history of malignancy within 5 years before screening (exceptions are 
squamous and basal cell carcinomas of the skin that has been treated with no 
evidence of recurrence for at least 3 months before the first study agent 
administration and carcinoma in situ of the cervix that has been surgically cured).
Rationale: An additional exclusion criterion was added.
4.2. Exclusion 
Criterion, #36.
Lives in an institution on court or authority order.
Rationale: Changed number of categories for region to ‘approximately 4’.
5.1. Procedures for 
Randomization.
Dynamic central randomization targets to balance the distribution of subjects to achieve 
the randomization ratio (3:2) at the study level and within the levels of each individual 
stratification factor: skin biopsy (y/n, when n<16 for y), presence of lupus nephritis (y/n), 
baseline SLE medications and SLEDAI-2K score (combined factor)*, site, region 
(approximately 3 4 categories), and race (3 categories).
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Applicable Section(s)
Description of Change(s)
Rationale: Changed ‘should’ to ‘must’.
10.2. Discontinuation 
of Study Treatment.
A subject's study treatment should must be permanently discontinued if any of the 
following occur:
Rationale: Minor errors were noted
Throughout the 
protocol
Minor grammatical, formatting, or spelling corrections were made.
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SYNOPSIS
A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of 
Ustekinumab in Subjects with Active Systemic Lupus Erythematosus
STELARA® (ustekinumab) is a fully human G1 kappa monoclonal antibody that binds with high affinity 
and specificity to the shared p40 subunit of human interleukin (IL)-12 and IL-23 cytokines. The binding 
of ustekinumab to the IL-12/23p40 subunit blocks the binding of IL-12 or IL-23 to the IL-12R1 receptor 
on the surface of natural killer and CD4+ T cells, inhibiting IL-12- and IL-23-specific intracellular 
signaling and subsequent activation and cytokine production. Abnormal regulation of IL-12 and IL-23 has 
been associated with multiple immune-mediated diseases including Systemic Lupus Erythematosus 
(SLE). Therefore, inhibition of IL-12 and IL-23 has the potential to be effective in the treatment of SLE.
OBJECTIVE AND HYPOTHESIS
Primary Objective
The primary objective is to evaluate the efficacy of ustekinumab as measured by a reduction in disease 
activity for subjects with active SLE.
Secondary Objectives
The secondary objectives are to evaluate:

The safety and tolerability of ustekinumab in subjects with SLE.

The effect of ustekinumab administration on health-related quality of life in subjects with SLE.

The effects of ustekinumab on cutaneous manifestations of SLE.

Pharmacokinetics and immunogenicity of ustekinumab in subjects with SLE.
Exploratory Objective
The exploratory objectives are to evaluate:

Safety and efficacy during long-term administration of ustekinumab.

Reduction in corticosteroid dosing during long-term administration of ustekinumab.

Additional composite clinical endpoints or methods of calculation of clinical response with potential 
for greater sensitivity to improvement and/or worsening of SLE.

Biomarkers related to lupus disease (genetic, systemic, and skin-related).
Hypothesis
The hypothesis is that dosing with ustekinumab is significantly superior to placebo as measured by the 
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Responder Index (SRI-4) 
composite measure at Week 24.
OVERVIEW OF STUDY DESIGN
CNTO1275SLE2001 is a Phase 2a, proof-of-concept, multicenter, randomized, double-blind, placebo-
controlled study of the efficacy and safety of ustekinumab added to standard of care background in 
subjects with active SLE. Subjects to be enrolled must have SLE according to Systemic Lupus 
International Collaborating Clinics (SLICC) criteria and Systemic Lupus Erythematosus Disease Activity 
Index 2000 (SLEDAI-2K) score ≥6, despite conventional treatment (eg, immunomodulators, antimalarial 
drugs, corticosteroids, nonsteroidal anti-inflammatory drugs, anti-hypertensive drugs, and/or topical 
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medications). In addition, subjects must have at least 1 positive autoantibody test (antinuclear antibodies 
[ANA], anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies, and/or anti-Smith 
antibodies) observed during screening, as well as a well-documented positive autoantibody test in medical 
history. Subjects must also demonstrate at least 1 British Isles Lupus Assessment Group (BILAG) A 
and/or 2 BILAG B domain scores observed during screening. In addition, subjects must have a clinical 
SLEDAI-2K score ≥4 (excluding laboratory results) at week 0, prior to randomization.
Approximately 100 subjects will be randomly assigned in a 3:2 ratio to receive either ustekinumab or 
placebo through Week 24. Following randomization at Week 0, subjects will receive an initial body 
weight-range based IV dose approximating 6 mg/kg of ustekinumab (ustekinumab 260 mg [weight 
≥35 kg to ≤55 kg]; ustekinumab 390 mg [weight >55 kg and ≤85 kg]; ustekinumab 520 mg [weight 
>85 kg]) followed by 90 mg SC administered every 8 weeks (q8w).
At Week 24, subjects receiving placebo will cross-over and all subjects will receive ustekinumab 90 mg 
SC at Weeks 24, 32, and 40 followed by safety follow-up through Week 56 in a blinded fashion for 
16 weeks (ie, approximately 5 half-lives) after last study agent SC administration. 
A placebo comparator (added to standard of care background therapy) will be used through Week 24 for 
the evaluation of the efficacy and safety of ustekinumab in subjects with SLE. From Week 24 through 
Week 40, the placebo group will cross-over to receive ustekinumab 90 mg SC q8w. This cross-over 
design will permit placebo subjects to receive study agent and provide experience with ustekinumab 
90 mg SC without the IV loading dose in subjects with SLE. The 40-Week dosing period will be useful to 
understand the longer term safety and time course of potential clinical response of ustekinumab in the 
SLE population.
Every reasonable effort should be made to keep concomitant medications stable as defined in the 
protocol. All concomitant therapies must be recorded throughout the study beginning at entry into 
screening and any changes must be recorded throughout the study. 
All subjects with cutaneous disease will be evaluated using Cutaneous Lupus Erythematosus Disease 
Area and Severity Index (CLASI) scoring. Additionally, subjects with cutaneous disease who consent to 
participate in the cutaneous lupus substudy will have other assessments including collection of skin 
biopsies (optional consent) and/or photographs of a cutaneous lesion or area of active disease (optional 
consent). There will not be any restrictions on the number of subjects with cutaneous disease who can 
enroll into either the main study or the cutaneous lupus substudy. 
Interim analyses (IA) will be conducted when approximately 1/3 and 2/3 of subjects reach Week 24. In 
the first IA, only an assessment of notable efficacy will be performed. In the second IA, evidence for 
notable efficacy as well as treatment futility will be analyzed. Database locks (DBLs) will occur at Weeks 
24 and following the last subject’s Week 56 visit, or the final subject’s Week 16 safety follow-up visit 
from the main study. In addition, an independent data monitoring committee (DMC) will review interim 
safety data periodically including a formal review when approximately 1/3 and 2/3 of subjects reach 
Week 24, as well as at the Week 24 DBL. The DMC will make a recommendation to the Sponsor 
committee whether the study should be stopped for futility or for safety concerns or if data meet 
prespecified criteria demonstrating notable efficacy. The content of the summaries, the DMC role and 
responsibilities, and the general procedures (including communications) will be defined in the DMC 
charter.
The amended study design will continue to provide open-label ustekinumab 90 mg q8w SC 
administration through Week 104. Subjects will be eligible to continue study treatment through Week 104 
if they meet the study inclusion criteria (Section 4.1.3) including:

must not have permanently discontinued study treatment on or before their Week 40 visit, and
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
are able to continue q8 week study treatment at approximately 8 weeks (±2 weeks) after their 
Week 40 visit
or

are able to resume study treatment with no more than 16 weeks (±2 weeks) since their Week 40 visit.
In addition to the DBL planned after the final subject’s Week 56 visit, or after the last subject’s Week 16 
safety follow-up visit from the main study, there will be an additional DBL at the end of the study 
extension (following Study Extension 16-week safety follow-up visit).
SUBJECT POPULATION
Screening for eligible subjects must be performed no more than 6 weeks prior to the randomization visit 
(Week 0). The target study population is subjects with SLE according to SLICC criteria and SLEDAI-2K
score ≥6, despite conventional treatment (eg, immunomodulators, antimalarial drugs, corticosteroids,
nonsteroidal anti-inflammatory drugs, anti-hypertensive drugs, and/or topical medications). In addition, 
subjects must have at least 1 positive autoantibody test (ANA, anti-dsDNA antibodies, and/or anti-Smith 
antibodies) observed during screening, as well as a well-documented positive autoantibody test in medical 
history. Subjects must also have at least 1 BILAG A and/or 2 BILAG B domain scores observed during 
screening prior to first administration of study agent.
In addition, to be eligible for study participation, subjects must have a clinical SLEDAI-2K score 4 
(excluding laboratory results) for clinical features at Week 0 (prior to randomization) and have received 
approval for study randomization following review and adjudication of screening lupus assessments by 
the Sponsor and/or Sponsor-selected independent reviewer(s).
SLE subjects enrolling into the main study with active cutaneous lupus (including subjects with discoid 
lupus erythematosus, subacute cutaneous lupus erythematosus, alopecia or SLE malar rash or other SLE 
skin lesions characterized by erythema and or scale) will be evaluated using CLASI scoring. In addition, 
subjects who provide consent will be enrolled in the cutaneous lupus substudy evaluating the histology of 
cutaneous biopsies and/or skin photographs. Subjects participating in the cutaneous lupus substudy are 
not required to undergo biopsies, and may allow only photographs to document changes in an identified 
lesion or area of active disease.
DOSAGE AND ADMINISTRATION
All subjects will receive a body weight range-based IV administration of study agent (placebo or 
ustekinumab) at Week 0 and then SC administration of placebo or ustekinumab at Weeks 8 and 16, 
followed by all subjects receiving ustekinumab dosing at Weeks 24, 32, and 40. Every reasonable effort 
should be made to keep concomitant medications stable at least through Week 28, with some adjustments 
allowed beyond Week 28 through the 8-Week Safety Follow-Up or study extension as defined in the 
protocol. A concomitant medication may be reduced or medication temporarily discontinued because of 
abnormal laboratory values, side effects, concurrent illness, or the performance of a surgical procedure, 
but the change and reason for the medication change should be clearly documented in the subject’s 
medical record. If concomitant medications have been adjusted after randomization as allowed per 
protocol, every effort should be made to return subject back to the baseline (Week 0) dose level by the 
Week 12 visit; or increased medication use may render a subject to be considered a treatment failure.
Subjects who are enrolled in the study extension will continue to receive ustekinumab 90 mg SC 
administration every 8 weeks through Week 104. With the exception of corticosteroids, concomitant 
medications should be maintained at stable doses through the study extension.
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Week 0 up to Week 24 (Blinded Study Agent Administration Phase)
Group 1: Subjects will receive weight-range based IV dosing of approximately 6 mg/kg of ustekinumab at 
Week 0 followed by ustekinumab 90 mg SC administrations at Weeks 8 and 16. 
Group 2: Subjects will receive weight-range based IV dosing of placebo at Week 0 followed by placebo 
SC administrations at Weeks 8 and 16.
Week 24 to Week 40 (Cross-over Administration Phase)
Group 1: Subjects will receive an ustekinumab 90 mg SC administration at Week 24 followed by q8w 
administrations through Week 40. 
Group 2: Subjects in the placebo dosing group will cross-over to ustekinumab 90 mg SC administrations 
at Week 24 followed by q8w administrations through Week 40.
After Week 40 to 16-Week Safety Follow-Up (Safety Follow-up Phase)
Groups 1 and 2: Subjects who do not participate in the study extension are expected to return for safety 
follow-up visits at Week 44 and for 8- and 16-weeks safety follow up.
Study Extension (Week 48/Week 56 through Week 120)
Subjects who meet the study extension inclusion criteria (Section 4.1.3) will receive an 
additional 1 year of open label ustekinumab administration for the purpose of expanding the 
safety experience and maintenance of efficacy in lupus patients exposed to ustekinumab 90 mg 
q8w. Subjects who continue dosing in the extended study starting at Week 48 or at Week 56 will 
receive open-label ustekinumab SC dosing through Week 104. If the development of 
ustekinumab in SLE is terminated, then the study extension will also be discontinued.
EFFICACY EVALUATIONS
The primary efficacy endpoint of this study is to compare the proportion of subjects with a composite 
SRI-4 response at Week 24 for subjects receiving ustekinumab as compared to placebo treatment.
Efficacy evaluations and patient reported quality of life measures include:

SLEDAI-2K

S2K RI-50

BILAG

CLASI

Physician’s Global Assessment of Disease Activity

Patient’s Global Assessment of Disease Activity

Short-form 36 questionnaire

Fatigue Severity Scale

Patient’s Assessment of Pain
PHARMACOKINETIC AND IMMUNOGENICITY EVALUATIONS
Serum samples will be used to evaluate the pharmacokinetics of ustekinumab, as well as the 
immunogenicity of ustekinumab (antibodies to ustekinumab).
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 EVALUATIONS AND SEROLOGIC MARKERS
The collection, preparation, storage and shipment of skin biopsies, blood, serum and urine are detailed in 
the Laboratory Manual. Biomarkers may include, but are not limited to, inflammatory markers, 
ribonucleic acid (RNA), cell surface markers, autoantibodies, T cell and B cell repertoire, target specific 
markers, and other categories of biomarkers potentially involved in the development and the progression 
of lupus.
Serum Analyses
Serum will be analyzed for levels of specific proteins 
 
 
 
Skin Biopsy Analyses
Skin biopsies will be utilized for cellular, molecular, and gene expression analyses.
Whole Blood Gene Expression Analyses
Whole blood will be collected from all subjects for RNA, flow cytometry, T cell and B cell repertoire and 
epigenetics analysis (eg, deoxyribonucleic acid [DNA] methylation).
Serologic Markers
Autoantibodies (eg, ANA, anti-dsDNA, etc.), complement C3 and C4 will be collected as described in the 
Table of Events (Table 1).
PHARMACOGENOMIC (DNA) EVALUATIONS
DNA samples will be used for research related to this study (CNTO1275SLE2001). Specific genomic 
testing will be undertaken for consenting subjects (subjects participating in this portion of the study must 
sign a separate informed consent form. The procedure will involve taking a blood sample that may be 
analyzed for specific target genes that may play a role in lupus. Any genomic assessments will be 
performed in strict adherence to current subject confidentiality standards for genetic testing. Refusal to 
participate in genomics testing will not result in ineligibility for participation in the rest of the clinical 
study.
CUTANEOUS LUPUS SUBSTUDY
All subjects with cutaneous disease will be evaluated using CLASI scoring. Additionally subjects with 
cutaneous disease who consent to participate in the cutaneous lupus substudy will have other assessments 
including collection of skin biopsies (optional consent) and/or photographs of an identified cutaneous 
lesion or area of active disease (optional consent). There will not be any restrictions on the number of 
subjects with cutaneous disease who can enroll into either the main study or the cutaneous lupus 
substudy. 
Subjects who provide consent will be enrolled in the cutaneous lupus substudy evaluating the histology of 
cutaneous biopsies and/or skin photographs. Biopsy samples (2 samples, 4 mm size) from consenting 
subjects will be collected prior to dosing at Week 0 and at Week 24 from a single lesion or area of active 
cutaneous disease. Photographs and skin biopsies can target a different area of active disease, but the 
follow-up photographs or biopsies should re-evaluate the same area of active disease as originally 
assessed at week 0. Subjects participating in the cutaneous lupus substudy are not required to undergo 
biopsies, and may allow only photographs to document changes in an identified lesion or area of active 
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disease. Subjects with cutaneous lupus deemed unsuitable for biopsy (eg, malar rash or alopecia) can also 
be enrolled in the substudy, and may be evaluated by photography.
Independent of cutaneous biopsy collection, subjects who participate in the cutaneous lupus substudy will 
be requested to provide consent for photographs to be collected from an identified lesion or area of active 
disease. The photographs are for exploratory purposes only. The photographs will be used to assist in a 
qualitative evaluation of clinical response. Confidentiality of the subjects involved in this study will be 
maintained; specifically photographs of subjects in this study will not be published or otherwise made 
public without blocking adequate portions of the subject’s face or body so that the individual cannot be 
identified. 
SAFETY EVALUATIONS
Safety assessments include vital signs, general physical exam and skin evaluations, adverse events (AE), 
serious AEs, concomitant medication review, pregnancy testing, infusion reactions, chemistry and 
hematology laboratory tests, and antibodies to ustekinumab. Chest x-ray and tuberculosis, human 
immunodeficiency virus, hepatitis B, and hepatitis C testing will be required at time of screening. Any 
clinically significant abnormalities persisting at the end of the study will be followed by the investigator 
until resolution or until a clinically stable endpoint is reached. Subject diary cards will be used to capture 
medication changes that occur in between study visits during the main portion of this study. Safety data 
collected up to 16 weeks after the final administration of study agent will be evaluated.
STATISTICAL METHODS
Sample Size Determination
Approximately 100 subjects will be randomly assigned in a 3:2 ratio to receive either ustekinumab or 
placebo through Week 24. Approximately sixty subjects treated with ustekinumab and approximately 
40 subjects with placebo is projected to give approximately 80% power to detect a significant difference 
in response rate compared with placebo (assume 35% and 60% response rates in placebo and 
ustekinumab respectively, which translates to 25% absolute increase over placebo or an odds ratio of 
2.79) with an alpha level of 0.1.
Efficacy Analyses
The primary endpoint of this study is the proportion of subjects with a composite measure of SLE disease 
activity (SLE Responder Index [SRI]-4 response) at Week 24. The primary analysis will be based upon 
the primary endpoint and will be conducted on the modified intent-to-treat (mITT) population, which 
includes all randomized subjects who receive at least 1 dose of study agent, have at least 1 measurement 
prior to the administration, and have at least 1 post-baseline SRI-4 measurement. 
Last observation carried forward (LOCF) procedure will be used to impute the missing SRI-4 component 
if the subjects have data for at least 1 SRI-4 component at Week 24. If the subjects do not have data for 
any SRI components at Week 24, the subjects will be considered not to have achieved the SRI-4 response.
In addition, subjects who meet any of a variety of treatment failure criteria, such as receiving a dose of 
immunomodulator that is higher at Week 24 than at baseline, or initiated prohibited treatment (dose or
timing) with corticosteroids, or discontinued study agent due to a lack of efficacy will be considered to 
have not achieved the primary endpoint, SRI-4 response at Week 24.
Logistic regression, adjusting for baseline stratifications and baseline SLEDAI, will be used to analyze 
the primary endpoint. The baseline SLEDAI value is defined as the closest non-missing measurement 
taken prior to the Week 0 infusion. If significant non-normality is observed, appropriate nonparametric
tests will be used to evaluate the differences between treatments.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
28
Approved, 18 January 2017
The study will be considered positive if the primary analysis achieves statistical significance at a 
significance level of 0.1 (2-sided) and ustekinumab shows a positive treatment effect relative to placebo 
treatment.
Safety Analyses
Safety will be assessed by analyses of the incidence and type of AEs, SAEs, reasonably related AEs, 
infections, and infusion reactions.  Safety assessments will also include analyses of laboratory parameters 
and change from baseline in laboratory parameters (hematology and chemistry) and incidence of 
abnormal laboratory parameters (hematology and chemistry).
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
35
Approved, 18 January 2017
TIME AND EVENTS SCHEDULE
Table 1:
Time and Events Schedule for the Main Study Design (Screening through 8-Week/16-Week Safety Follow-up)
Blinded Study Agent Administration Phase
Cross-over Administration 
Phase
Safety Follow-up
Week
Screeninga
0
4
8
12
16
20
24
28
32
36
40
44
8-Week 
Safety 
Follow-
upb
16-
Week 
Safety 
Follow
-up/
Final 
visitb
Study Proceduresc
Screening/Administrative
Informed consent
X
Inclusion/exclusion criteria
X
Xa
Medical history and demographics
X
SLE classification by SLICC criteria
X
Study Drug Administration
Randomization
X
Study agent administration 
Xd
X
X
X
X
X
Diary card
Train on diary card and distribute
X
Collect, review and distribute diary cards
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety Assessments
Physical examination
X
X
X
X
HIV, HBV, and HCV
X
QuantiFERON®-TB Gold test
X
Tuberculin skin teste
X
TB evaluationf
X
X
X
X
X
X
X
X
X
Serum pregnancy testg
X
Urine pregnancy testh
X
X
X
X
X
X
X
X
Vital signs
X
X
X 
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
X
X
Chest x-rayi
X
Concomitant therapy
X
X
X 
X
X
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X 
X
X
X
X
X
X
X
X
X
X
X
X
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
36
Approved, 18 January 2017
Table 1:
Time and Events Schedule for the Main Study Design (Screening through 8-Week/16-Week Safety Follow-up)
Blinded Study Agent Administration Phase
Cross-over Administration 
Phase
Safety Follow-up
Week
Screeninga
0
4
8
12
16
20
24
28
32
36
40
44
8-Week 
Safety 
Follow-
upb
16-
Week 
Safety 
Follow
-up/
Final 
visitb
Study Proceduresc
Infusion or injection-site reaction 
  evaluationj
X
X
X
X
X
X
Cutaneous Lupus Substudy Assessmentsk
Skin biopsyw
X
X
Photograph lesion or area of active diseasex
X
X
X
X
X
X
Efficacy Assessmentsl
SLEDAI-2K (S2K RI-50 - Baseline)
X
Xm
S2K RI-50 (Follow-up)
X
X
X
X
X
X
X
X
X
X
X
X
X
CLASIn
X
X
X
X
X
X
X
X
X
X
X
X
X
X
BILAG
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s Global Assessment of Disease
  Activity
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s Global Assessments (Pain and 
  Disease Activity)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
SF-36
X
X
X
X
X
X
X
Fatigue Severity Scale
X
X
X
X
X
X
X
X
X
Clinical Laboratory Assessments
Hematologyo
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
C3, C4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Coombs direct testp,q
X
X
X
X
X 
X
X
X
X
X
X
X
X
X
X
Coagulation Labs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chemistry
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Anti-dsDNA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Other autoantibodiesr
X
X
X
X
Anti-phospholipid antibodiesp
X
X
X
X
Ig isotype profile
X
X
X
Urine Analyses (spot urine)
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
37
Approved, 18 January 2017
Table 1:
Time and Events Schedule for the Main Study Design (Screening through 8-Week/16-Week Safety Follow-up)
Blinded Study Agent Administration Phase
Cross-over Administration 
Phase
Safety Follow-up
Week
Screeninga
0
4
8
12
16
20
24
28
32
36
40
44
8-Week 
Safety 
Follow-
upb
16-
Week 
Safety 
Follow
-up/
Final 
visitb
Study Proceduresc
Urinalysis (dipstick, all study subjects)q
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Urine sample for biomarkers (all subjects) 
X
X
X
X
X
X
X
X
X
X
Protein/Creatinine ratios
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Microscopy of urine sedimentq
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Pharmacokinetics/Immunogenicity
Serum ustekinumab concentrationss,t
2Xv
X
X
X
X
X
X
X
X
X
X
Antibodies to study agents,t
X
X
X
X
X
X
X
X
Pharmacogenomics (DNA)u
Whole blood DNA
X
Biomarkers
Serum sample
X
X
X
X
X
X
X
X
X
X
X
Whole blood for RNA gene expression
X
X
X
X
X
X
X
X
X
T cell and B cell repertoire
X
X
X
X
Epigenetics
X
X
X
X
Flow cytometryv
X
X
X
X
a.
Screening visit must be performed no more than 6 weeks prior to the randomization visit (Week 0). To be eligible for study participation, subjects must have SLEDAI 
score 4 (excluding laboratory results) for clinical features at Week 0 and have received approval for study randomization following review and adjudication of 
screening lupus assessments by the Sponsor and/or Sponsor-selected independent reviewer(s).
b.
Subjects, who discontinue study agent administrations on or before the Week 40 visit, must return approximately 8 and 16 weeks after last study agent administration for 
safety follow-up visits. The 8-week and/or 16-week safety follow-up visits are not required for subjects who continue treatment in the study extension within 8 (±2 
weeks) or 16 (±2 weeks) weeks, respectively, of their Week 40 visit (refer to Table 2).
c.
All assessments (except for injection-site evaluation) are to be completed prior to study agent administration, unless otherwise specified.
d.
Intravenous administration of study agent at Week 0, all other doses will be SC.
e.
Only required if QuantiFERON®-TB is not registered/approved locally or the tuberculin skin test (TST) is mandated by local health authorities.
f.
If TB is suspected at any time during the study, a chest x-ray (local), and QuantiFERON®-TB Gold test should be performed. A TST is additionally required if the 
QuantiFERON®-TB Gold test is not registered/approved locally or the TST is mandated by local health authorities.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
38
Approved, 18 January 2017
Table 1:
Time and Events Schedule for the Main Study Design (Screening through 8-Week/16-Week Safety Follow-up)
Blinded Study Agent Administration Phase
Cross-over Administration 
Phase
Safety Follow-up
Week
Screeninga
0
4
8
12
16
20
24
28
32
36
40
44
8-Week 
Safety 
Follow-
upb
16-
Week 
Safety 
Follow
-up/
Final 
visitb
Study Proceduresc
g.
In addition to the screening evaluation, the pregnancy test may be repeated at any time at the discretion of investigator or subject.
h.
May conduct urine pregnancy test more frequently (eg, monthly basis) if required by local regulations.
i.
Posterior/anterior and lateral views must be taken within 3 months prior to the first administration of study agent for TB detection.
j.
Subjects should be monitored for the occurrence of infusion or injection-site reactions for 30 minutes after the infusion (IV administration) or injection.
k.
Only for subjects who consented to participate in the cutaneous lupus substudy for biopsy and/or photograph collection.
l.
All visit-specific patient reported outcome assessments should be conducted before any tests, procedures, or other consultations for that visit to prevent influencing 
subjects’ perceptions.
m. Complete SLEDAI-2K (Baseline) will be evaluated during screening and at Week 0, although at Week 0 only the clinical (non- laboratory) features will be considered to 
confirm eligibility for study enrollment. The photographs and skin biopsies can target a different location of active disease, but the follow-up photographs or biopsies 
should re-evaluate the same area of active disease as originally assessed at week 0.
n.
CLASI scoring will be obtained for all enrolled subjects with cutaneous lupus regardless of enrollment in the cutaneous lupus substudy.
o.
Also perform B cell analyses at screening for subjects previously exposed to B cell depleting therapies.
p.
If abnormal test result is not obtained at screening or at Week 0, no additional follow-up testing is required. However, additional testing may be performed if needed.
q.
These tests will be performed on-site or at local lab(s). 
r.
Anti-dsDNA should be analyzed at every specified visit.  If the other autoantibody tests are negative at both the screening and Week 0 visits, then those autoantibody 
tests need only be analyzed again at Weeks 24 and 48. However, if the other autoantibodies tests are positive at either screening or Week 0, then they should be analyzed 
at all visits.
s.
The same blood draw will be used for the measurement of ustekinumab concentration and detection of antibodies to ustekinumab. For visits with study agent 
administration, all blood samples for assessing pre-dose ustekinumab concentration and antibodies to ustekinumab MUST be collected BEFORE the administration of the 
study agent.
t.
At Week 0 visit, 2 separate samples for serum ustekinumab concentrations (indicated by “2X” in the Schedule above) will be collected (1 sample will be collected prior 
to IV infusion and the other collected 1 hour after the end of the infusion) for all subjects.
u.
Only for subjects who consent to allow genomic analyses.
v.
Flow cytometry samples will be analyzed from subjects at selected sites.
w.
Biopsies are allowed to occur 1 - 2 days prior to randomization and at the Week 24 visit.
x.
Photographs do not need to be taken at the same area of active disease as the biopsy; however, follow-up photographs or biopsies should re-evaluate the same area of 
active disease as originally assessed at week 0.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
39
Approved, 18 January 2017
Table 2:
Time and Events Schedule in the CNTO1275SLE2001 Study Extension (Week 48/56 through Extension Safety 
Follow-up)
Study Extension
Extension Safety Follow-upa
Week
Wk 
48
Wk 
56
Wk 
64
Wk 
72
Wk 
80 
Wk 
88
Wk 
96
Wk 
104
Extension 8-
Week Safety 
Follow-up
Extension 
16-Week
Safety 
Follow-
up/Final 
Visit
Study Proceduresb
Screening/Administrative
Informed consentc
X
X
Study Drug Administration
Study agent administration
Xc
Xc
X
X
X
X
X
X
Safety Assessments
Physical examination
X
X
X
X
X
X
TB evaluationd
X
X
X
X
X
X
X
X
X
X
Urine pregnancy teste
X
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
Adverse Events
X
X
X
X
X
X
X
X
X
X
Injection-site reaction evaluationf
X
X
X
X
X
X
X
X
Efficacy Assessmentsg
S2K RI-50
X
X
X
X
X
CLASIh
X
X
X
X
X
BILAG
X
X
X
X
X
Physician’s Global Assessment of 
Disease
  Activity
X
X
X
X
X
Patient’s Global Assessments (Pain and 
  Disease Activity)
X
X
X
X
X
SF-36
X
X
X
X
Fatigue Severity Scale
X
X
X
X
Clinical Laboratory Assessments
Hematologyi
X
X
X
X
X
X
X
X
X
X
C3, C4 
X
X
X
X
X
X
X
X
X
X
Coombs direct testj,k (as needed)
X
X
X
X
X
Coagulation Labs (as needed) i, j
X
X
X
X
X
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
40
Approved, 18 January 2017
Table 2:
Time and Events Schedule in the CNTO1275SLE2001 Study Extension (Week 48/56 through Extension Safety 
Follow-up)
Study Extension
Extension Safety Follow-upa
Week
Wk 
48
Wk 
56
Wk 
64
Wk 
72
Wk 
80 
Wk 
88
Wk 
96
Wk 
104
Extension 8-
Week Safety 
Follow-up
Extension 
16-Week
Safety 
Follow-
up/Final 
Visit
Study Proceduresb
Chemistryk
X
X
X
X
X
X
X
X
X
X
Anti-dsDNA
X
X
X
X
X
X
X
X
X
X
Other autoantibodiesl
X
Xl
X
Anti-phospholipid antibodiesj
X
X
X
Ig isotype profile
X
X
Urine Analyses (spot urine) i
Urinalysis (dipstick, all study subjects)i, 
m
X
X
X
X
X
X
X
X
X
X
Urine sample for biomarkers (all 
subjects) 
X
X
X
X
X
Protein/Creatinine ratioi
X
X
X
X
X
X
X
X
X
X
Microscopy of urine sedimentk,m
X
X
X
X
X
X
X
X
X
X
Pharmacokinetics/Immunogenicity
Serum ustekinumab concentrationsn
X
X
X
X
X
Antibodies to study agentn
X
X
X
X
X
Biomarkers
Serum sample
X
X
X
X
X
Whole blood for RNA gene expression
X
X
X
X
X
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
41
Approved, 18 January 2017
Table 2:
Time and Events Schedule in the CNTO1275SLE2001 Study Extension (Week 48/56 through Extension Safety 
Follow-up)
Study Extension
Extension Safety Follow-upa
Week
Wk 
48
Wk 
56
Wk 
64
Wk 
72
Wk 
80 
Wk 
88
Wk 
96
Wk 
104
Extension 8-
Week Safety 
Follow-up
Extension 
16-Week
Safety 
Follow-
up/Final 
Visit
Study Proceduresb
a.
Subjects, who complete all scheduled doses or discontinue study agent administration before the end of the study extension, must 
return at approximately 8 and 16 weeks after last study agent administration for safety follow-up visits.
b.
All assessments (except for injection-site evaluation) are to be completed prior to study agent administration.
c.
Prior to dosing in the study extension, subjects must sign a revised ICF indicating agreement to participate in the extended study. 
d.
TB evaluation includes an assessment of recent exposure or risk of TB including new or chronic cough, fever, night sweats, 
unintentional weight loss or recent contact with someone with active TB. If TB is suspected at any time during the study, a chest 
x-ray (local), and QuantiFERON®-TB Gold test should be performed. A TST is additionally required if the QuantiFERON®-TB 
Gold test is not registered/approved locally or the TST is mandated by local health authorities.
e.
In addition to scheduled urine dipstick testing, a serum or urine pregnancy test may be conducted at any time at the discretion of 
investigator or subject, or if required by local regulations.
f.
Subjects should be monitored for the occurrence of injection-site reactions for 30 minutes after the injection.
g.
All visit-specific patient reported outcome assessments should be conducted before any tests, procedures, or other consultations 
for that visit to prevent influencing subjects’ perceptions.
h.
CLASI scoring will be obtained for all enrolled subjects who have cutaneous lupus.
i.
If clinical concerns or abnormal results from prior visit observed in these assessments, then strong consideration should be given 
to more frequent testing (at least q4 week assessments) until normalized
j.
If history of abnormal test result was observed in main study, then follow scheduled assessments. Additional testing may be 
performed if needed.
k.
These tests will be performed on-site or at local lab(s).
l.
If the “other autoantibody” tests were routinely negative prior to Week 48, then those autoantibody tests need only be analyzed 
annually. However, if the other autoantibodies tests were positive at either screening or Week 0, then they should be analyzed 
every 6 months as shown.
m.
Urine sediment analyses to be performed at study site or local lab if possible. If necessary, with agreement from study sponsor, 
urine sediment analyses can be conducted at the Central Lab for specific sites that cannot arrange local analyses.
n.
The same blood draw will be used for the measurement of ustekinumab concentration and detection of antibodies to ustekinumab.
All blood samples collected for assessing pre-dose ustekinumab concentration and antibodies to ustekinumab MUST be collected 
BEFORE the administration of the study agent.
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
42
Approved, 18 January 2017
ABBREVIATIONS
ACE
angiotensin-converting enzyme
AE
adverse event
ANA
antinuclear antibodies
ANCOVA
analysis of covariance 
anti-dsDNA
anti-double stranded deoxyribonucleic acid
anti-HBc total 
HBV core antibody total
anti-HBs
HBV surface antibody
ARB
angiotensin II receptor blocker
AZA /6 MP
azathioprine/6-mercaptopurine
BAFF
B cell activating factor, also known as B lymphocyte stimulator (BLyS)
BCG
Bacille Calmette-Guérin
-hCG
-human chorionic gonadotropin
BICLA
BILAG-based Combined Lupus Assessment
BILAG
British Isles Lupus Assessment Group 
BLyS
B lymphocyte stimulator, also known as B cell activating factor (BAFF)
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CLE
cutaneous lupus erythematosus
CNS
central nervous system
COX-2
cyclooxygenase-2
CRF
case report form 
CD
Crohn’s disease
CTCAE
Common Terminology Criteria for Adverse Events 
CXCL10
C-X-C motif chemokine 10
DMC
data monitoring committee 
DNA
deoxyribonucleic acid
eCRF
electronic case report form
eDC
Electronic Data Capture 
EDTA
ethylenediaminetetraacetic acid
ELISA
enzyme-linked immunosorbent assay 
FSS
Fatigue Severity Scale 
FVP
Final Vialed Product
GCP
Good Clinical Practice 
HBsAg
HBV surface antigen
HBV
hepatitis B virus 
HCV
hepatitis C virus
HIV
human immunodeficiency virus 
IA
interim analyses
ICF
informed consent form
ICH
International Conference on Harmonisation 
IEC
Independent Ethics Committee
Ig
Immunoglobulin
IL
Interleukin
IM
Intramuscular
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
43
Approved, 18 January 2017
IP
Investigative Product 
IRB
Institutional Review Board 
IV
Intravenous
IWRS
interactive web response system 
JAK
janus kinase
mITT
modified intent-to-treat
MMF
mycophenolate mofetil 
MPA
mycophenolic acid 
MTX
Methotrexate
NAbs
neutralizing antibodies 
NSAIDs
nonsteroidal anti-inflammatory drugs 
PFS
prefilled syringe 
PGA
Physician’s Global Assessment of Disease Activity 
PK
Pharmacokinetic
PQC
product quality complaint 
PROs
patient reported outcomes
PsA
psoriatic arthritis
PtGA
Patient’s Global Assessment of Disease Activity 
q8w
every 8 weeks
RA
rheumatoid arthritis
RNA
ribonucleic acid
RNP
Ribonucleoprotein
S2K RI-50
SLEDAI-2K Responder Index
SAE
serious AE
SAP
statistical analysis plan
SC
Subcutaneous
SF
Short-form 
SLE
Systemic Lupus Erythematosus
SLEDAI
Systemic Lupus Erythematosus Disease Activity Index
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLICC
Systemic Lupus International Collaborating Clinics
SRI-4
SLE Responder Index
SSA
anti-Sjögren’s-syndrome-related antigen A
SSB
anti-Sjögren’s-syndrome-related antigen B
TB
Tuberculosis
Th
T helper
TNF
tumor necrosis factor alpha
ULN
upper limit of normal
VAS
visual analogue scale 
WBC
white blood cells 
NCT0239061


Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
44
Approved, 18 January 2017
1.
INTRODUCTION
STELARA® (ustekinumab) is a fully human G1 kappa monoclonal antibody that binds with high 
affinity and specificity to the shared p40 subunit of human interleukin (IL)-12 and IL-23 
cytokines. The binding of ustekinumab to the IL-12/23p40 subunit blocks the binding of IL-12 or 
IL-23 to the IL-12R1 receptor on the surface of natural killer and CD4+ T cells, inhibiting 
IL-12- and IL-23-specific intracellular signaling and subsequent activation and cytokine 
production. Abnormal regulation of IL-12 and IL-23 has been associated with multiple 
immune-mediated diseases including systemic lupus erythematosus (SLE). Therefore, inhibition 
of IL-12 and IL-23 has the potential to be effective in the treatment of SLE.
Systemic lupus erythematosus is a complex, chronic autoimmune disease of unknown etiology 
that can affect almost any organ system, and which follows a relapsing and remitting disease 
course. Systemic lupus erythematosus occurs much more often in women than in men, up to 
9 times more frequently in some studies, and often appears during the child-bearing years 
between 15 and 45. This disease is more prevalent in Afro-Caribbean, Asian, or Hispanic 
populations. In SLE, the immune system attacks the body's cells and tissue, resulting in 
inflammation and tissue damage which can harm the heart, joints, skin, lungs, blood vessels, 
liver, kidneys and nervous system. About half of the subjects diagnosed with SLE present with 
organ-threatening disease, but it can take several years to diagnose subjects who do not present 
with organ involvement. Some of the primary complaints of newly diagnosed lupus patients are 
arthralgia (62%) and cutaneous symptoms (new photosensitivity; 20%), followed by persistent 
fever and malaise.39 The estimated annual incidence of lupus varies from 1.8 to 7.6 cases per 
100,000 and the worldwide prevalence ranges from 14 to 172 cases per 100,000 people.39
Patients with mild disease have mostly skin rashes and joint pain and require little medication; 
regimens 
include 
nonsteroidal
anti-inflammatory 
drugs 
(NSAIDs), 
anti-malarials 
(eg, hydroxychloroquine, chloroquine, or quinacrine) and/or low dose corticosteroids. With more 
severe disease patients may experience a variety of serious conditions depending on the organ 
systems involved, including lupus nephritis with potential renal failure, endocarditis or 
myocarditis, pneumonitis, pregnancy problems, stroke, neurological complications, vasculitis 
and cytopenias with associated risks of bleeding or infection. Common treatments for more 
severe disease include immunomodulatory agents, such as methotrexate (MTX), azathioprine, 
cyclophosphamide, cyclosporine, high dose corticosteroids, biologic B cell cytotoxic agents or B 
cell modulators, and other immunomodulators. Patients with serious SLE have a shortening of 
life expectancy by 10 to 30 years, largely due to the complications of therapy and accelerated 
atherosclerosis, as well as experiencing a substantial impact of this disease on their quality of 
life. Existing therapies for SLE are generally either cytotoxic or immunomodulatory, and may 
have notable safety risks when used over long periods of time. Newer treatments for SLE have 
provided only modest benefits over standard of care therapy. Thus there is a large unmet need for 
new alternative treatments that can provide significant benefit in this disease without incurring a 
high safety risk.
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The long-term outcome for patients with lupus depends on a variety of factors including whether 
they have organ involvement, the presence of certain laboratory measures (such as 
anti-phospholipid antibodies), race, gender, age of consent, access to health care, adherence to 
treatment, education and other comorbidities. Only about 5% of patients who are diagnosed with 
SLE will demonstrate a spontaneous remission without treatment.  A variety of new therapeutic 
agents are being evaluated for the treatment of subjects with refractory lupus, however to date 
very few have demonstrated notable clinical efficacy beyond those medications currently 
considered standard of care for patients with this disease.  
In this study, the target population is subjects with SLE according to Systemic Lupus 
International Collaborating Clinics (SLICC) criteria and Systemic Lupus Erythematosus Disease 
Activity Index (SLEDAI)11 score ≥6, despite conventional treatment (eg, immunomodulators, 
antimalarial drugs, corticosteroids, NSAIDs, anti-hypertensive drugs, and/or topical 
medications). In addition, subjects must have at least 1 positive autoantibody test (antinuclear 
antibodies [ANA], anti-double stranded deoxyribonucleic acid [anti-dsDNA] antibodies, and/or 
anti-Smith antibodies) observed during screening, as well as a well-documented positive
autoantibody test in medical history. Subjects must also demonstrate at least 1 British Isles 
Lupus Assessment Group (BILAG)38 A and/or 2 BILAG B domain scores during screening. In 
addition, subjects must have a SLEDAI score ≥4 at Week 0 (prior to randomization) for clinical 
features (excluding laboratory results).This level of disease activity is consistent with prior 
studies that have investigated an experimental therapy for systemic lupus.36
For the most comprehensive nonclinical and clinical information regarding ustekinumab, refer to 
the latest version of the Investigator's Brochure and Addenda 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
To date, ustekinumab has received marketing approval globally, including countries in North 
America, Europe, South America, and the Asia-Pacific region, for the treatment of adult patients 
including those with chronic moderate to severe plaque psoriasis and/or active psoriatic arthritis. 
Ustekinumab is also being evaluated in a Phase 3 studies for Crohn’s disease (CD).
1.2.
Overall Rationale for the Study
1.2.1.
Scientific Rationale for Use of Anti-IL-12/23p40 Therapy in Systemic 
Lupus Erythematosus
Systemic lupus erythematosus is a complex, immune-mediated inflammatory disorder exhibiting 
dysregulated B lymphocytes that produce destructive autoantibodies. B cell targeted therapies 
(eg, belimumab) for SLE, however, have shown only modest clinical results beyond a limited 
standard of care control,22 suggesting that additional immune pathways play an important role in 
SLE pathogenesis. Chronic immune activation in SLE leads to the increased production of 
inflammatory cytokines that contribute actively to local inflammation and to processes that 
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mediate tissue damage. Many SLE patients, for example, have a characteristic type I interferon
signature observed in their blood cells.2 Interferon signatures have also been observed to occur 
more frequently in lupus families and may be a risk factor for development of SLE.23 Several 
studies have also reported an elevation of IL-12, IL-6, and IL-23 in both serum and tissues of 
patients,4,20,24,26,30,44 suggesting that the inflammatory environment in SLE is prone to induce 
T helper (Th)1 and Th17 cells. Increased levels of IL-17 in the serum have been observed in SLE 
patients,3,31,36,44,45,46 but the correlation of IL-17 levels to disease activity is not strong.37,46 No 
direct genetic links have been established in SLE to the IL-12/IL-23/Th17 pathway,18,28,29
although genome-wide association studies in SLE have identiﬁed STAT4, which mediates IL-12 
signaling, as a susceptibility gene in both the Caucasian and Asian populations.12,16  In patients 
with active SLE, messenger RNA levels of p19, p40, and p35 were significantly higher 
compared with those in the inactive SLE patients.14 Targeting IL-12/23p40 with ustekinumab has 
been shown in 3 separate case reports to be associated with a marked improvement of cutaneous 
lupus.5,6,43 Taken together, there is accumulating evidence to demonstrate the importance of the 
IL-12 and IL-23 cytokine pathways in SLE pathogenesis, warranting further clinical 
investigation of ustekinumab as an interventional therapy in this disease.
In addition, 2 disease-related groups, the Alliance for Lupus Research and Lupus Research 
Institute, independently commissioned a scientific review of a large set of commercially 
available lupus drug candidates, from which ustekinumab was recommended to be evaluated in 
SLE based on its molecular mechanism, which further supports the scientific rationale for a 
placebo-controlled clinical study to evaluate the efficacy and safety of ustekinumab in subjects 
with active SLE.
1.2.1.1.
Subgroup of Subjects with Active Cutaneous Manifestations of 
Systemic Lupus Erythematosus
The above mentioned case reports of patients with refractory cutaneous lupus responding to 
ustekinumab treatment prompts an evaluation of the effects of ustekinumab on cutaneous lesions. 
Given the relatively common occurrence of cutaneous manifestations in SLE, the feasibility of 
repeated punch biopsy and/or photographs of an identified lesion or area of active disease, and 
the availability of cutaneous lupus erythematosus (CLE)-specific disease assessment tools, this 
patient population may provide useful data regarding the effects of ustekinumab on SLE and the 
symptoms of cutaneous disease. All subjects with cutaneous disease will be evaluated using 
CLASI scoring. Additionally subjects with cutaneous disease who consent to participate in the 
cutaneous lupus substudy will be requested to provide potential collection of skin biopsies 
(optional consent) and/or photographs of an identified lesion or area of active disease (optional 
consent). There are no pre-specified numbers of subjects to be enrolled with cutaneous disease 
for either the main study or the cutaneous lupus substudy.
1.3.
Justification for Dosing Regimen
The dosing regimen for this study was selected based on experience with the use of ustekinumab 
in the treatment of subjects with moderately to severely active CD (C0743T26, 
CNTO1275CRD3001, and CNTO1275CRD3002). Both CD and SLE are immune-mediated 
inflammatory diseases, which are commonly treated with immunomodulators, such as 
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methotrexate (MTX), azathioprine and corticosteroids, and thus this indication serves as a useful 
model for risk assessment of ustekinumab in lupus. Although the dosing rationale has not 
changed, additional safety and efficacy information has become available from the ustekinumab 
Phase 3 CD (UNITI) studies which supports amending the protocol to further extend treatment 
with ustekinumab 90 mg SC q8w for an additional year. These results from the UNITI CD
studies are summarized later in this section.
Although the dosing rationale has not changed, some additional safety and efficacy information 
has become available from the ustekinumab Phase 3 CD (UNITI) studies which supports the 
treatment extension planned for this study. These results from the UNITI CD studies are 
summarized later in this section (Section 1.3).
In the Phase 2b dose ranging study C0743T26, a single IV ustekinumab dose of 6 mg/kg was the 
highest loading dose tested in subjects with CD. In this study, the 6 mg/kg IV dose was shown to 
be effective in inducing clinical response through Week 8 and was well tolerated with a safety 
profile generally comparable to the other treatment groups. Results from ustekinumab CD 
studies also suggest that an IV loading dose may provide a rapid onset of clinical response 
following IL-12 and IL-23 inhibition. In the Phase 3 studies CNTO1275CRD3001 and 
CNTO1275CRD3002, body weight-range dosing approach (ustekinumab 260 mg [weight 
≤55 kg]; ustekinumab 390 mg [weight >55 kg and ≤85 kg]; ustekinumab 520 mg [weight 
>85 kg]) was used to approximate the IV loading dose of 6 mg/kg. The body weight-range based 
dosing allows administration of complete vials to patients to simplify dose calculation and 
reduce the potential for errors in dosing. This weight range dosing is intended to achieve drug 
exposure similar to that observed with 6 mg/kg weight-adjusted dosing. Thus, in this study, a 
strategy of IV loading dose based on body weight range at Week 0 will be evaluated to assess the 
ability of the drug to rapidly reduce the disease activity of SLE without causing significant 
concern for increased safety risk based on data obtained from previous studies.
The ustekinumab maintenance dosing regimen of 90 mg SC every 8 weeks (q8w) was studied in 
subjects with CD (C0743T26). The results from C0743T26 study suggest that ustekinumab 
90 mg SC q8w was safe and effective in maintaining subjects in clinical remission. The q8w 
dosing frequency is selected to maintain sufficient ustekinumab exposure to determine if 
treatment with ustekinumab can provide sustained clinical response. In addition, SC 
administration is considered more convenient compared with IV administration. A 16-week 
follow-up period following last ustekinumab study dose was selected to allow more than 
5 half-lives for drug elimination and adequate safety follow-up.
In addition, there were also 3 Phase 3 studies in subjects with CD initiated in 2011 that have 
recently provided additional safety and efficacy data; UNITI-1, UNITI 2, and IM-UNITI. 
UNITI-1 and UNITI-2 were 8-week induction studies and were identical in design but studied 
distinct patient populations. UNITI-1 studied subjects who had failed or were intolerant to anti-
TNF agents while UNITI-2 studied subjects who had not failed a TNF antagonist but who had 
failed conventional immunomodulator or steroid therapies. The IM-UNITI study evaluated 
maintenance treatment for patients enrolled from both UNITI-1 and UNITI-2 studies. The UNITI 
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studies randomized 1,367 subjects to either placebo, 130 mg IV or approximately 6 mg/kg IV. 
After Week 8 of therapy, subjects in both UNITI-1 and UNITI-2 studies could enter into 
IM-UNITI, which primarily evaluated two maintenance regimens of 90 mg every 8 or 12 weeks 
compared to placebo in induction responders. While the IM-UNITI study is still ongoing in long-
term extension phase, the primary results of all 3 studies have been published,7 and the results 
supported the approval of ustekinumab in patients with active moderate to severe CD. The 
approved dose in induction is a single IV weight-based dose approximating 6 mg/kg and the 
approved maintenance dose is 90 mg either every 8 or 12 weeks depending on the approval 
region. The results of these studies are particularly relevant to the CNTO1275SLE2001 SLE 
study in that a similar dose is being evaluated. In addition, similar to the SLE population, about 
1/3 of the CD patients enrolled into the UNITI studies were using concomitant 
immunomodulators (e.g MTX, AZA, 6-MP) and approximately 46% were on concomitant 
glucocorticoids. The results of these studies are reviewed in detail. in the primary publication7
and the highlights are presented below:

In the 2 UNITI induction studies, the primary endpoint and all major secondary endpoints 
were met for both doses studied including the 6 mg/kg dose.

In the IM-UNITI maintenance study, both the 90 mg every 8 or every 12 week regimens 
were superior to placebo in maintaining response or achieving remission compared to 
placebo at Week 44.

Importantly, the safety profiles of both maintenance doses were comparable to placebo over 
44 weeks and no new safety signals were identified. The safety profile was similar to that 
seen in the psoriatic indications.
In summary, these CD studies support the dosing regimen planned for this proof-of concept SLE 
study including body weight-range based IV loading dose approximating 6 mg/kg followed by 
90 mg SC q8w to ensure a high level of systemic exposure of ustekinumab to inhibit the actions 
of IL-12/23.
Open label 90 mg SC q8w ustekinumab dosing will be provided to subjects starting at Week 24 
though Week 40. Per the amended study design, subjects who are able to continue q8w study 
treatment at approximately 8 weeks (±2 weeks) after their Week 40 visit, or are able to resume 
study treatment with no more than 16 weeks (±2 weeks) since their Week 40 visit will be eligible 
for continued 90 mg SC q8w ustekinumab treatment through Week 104, followed by an 
additional 16-week safety follow-up period.
2.
OBJECTIVES AND HYPOTHESIS
2.1.
Objectives
Primary Objective
The primary objective is to evaluate the efficacy of ustekinumab as measured by a reduction in 
disease activity for subjects with active SLE.
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Secondary Objectives
The secondary objectives are to evaluate:

The safety and tolerability of ustekinumab in subjects with SLE.

The effect of ustekinumab administration on health-related quality of life in subjects with
SLE.

The effects of ustekinumab on cutaneous manifestations of SLE.

Pharmacokinetics and immunogenicity of ustekinumab in subjects with SLE.
Exploratory Objectives
The exploratory objectives are to evaluate:

Safety and efficacy during long-term administration of ustekinumab.

Reduction in corticosteroid dosing during long-term administration of ustekinumab.

Additional composite clinical endpoints or methods for calculation of response with 
potential for greater sensitivity to improvement and/or worsening of SLE.

Biomarkers related to lupus disease (genetic, systemic, and skin-related).
2.2.
Hypothesis
The hypothesis is that ustekinumab is significantly superior to placebo as measured by the 
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Responder Index 
(SRI-4) composite measure at Week 24.
3.
STUDY DESIGN AND RATIONALE
A complete list describing all efficacy evaluations and endpoints, and which evaluations are 
included in the composite endpoints is provided in Attachment 1. The main study is defined from 
the original protocol as screening through the Main Study 8-week and 16-week safety follow-up 
visits. Note that the Main Study 8-week and 16-week safety follow-up visits were previously 
described in the original protocol as the Week 48 and Week 56 visits. However, with this 
amendment, the Week 48 and Week 56 visits will only be used to describe treatment visits for 
those subjects who are participating in the study extension. The study extension (applicable to 
subjects meeting the inclusion criteria) is defined as the Week 48 or Week 56 visits through the 
Study Extension 16-week safety follow-up visit.
3.1.
Overview of Study Design
CNTO1275SLE2001 is a Phase 2a, proof-of-concept, multicenter, randomized, double-blind, 
placebo-controlled study of the efficacy and safety of ustekinumab added to standard of care 
background therapy in subjects with active SLE. Subjects between 18 and 75 years of age must 
have SLE according to SLICC criteria and SLEDAI-2K score ≥6, despite conventional treatment 
(eg, immunomodulators, antimalarial drugs, corticosteroids, NSAIDs, anti-hypertensive drugs, 
and/or topical medications). In addition, subjects must have at least 1 positive autoantibody test 
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Stelara® (ustekinumab)
Clinical Protocol CNTO1275SLE2001 Amendment 3
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Approved, 18 January 2017
(ANA, anti-dsDNA antibodies, and/or anti-Smith antibodies) observed during screening, as well 
as a well-documented positive autoantibody test in their medical history. Subjects must also 
demonstrate at least 1 BILAG A and/or 2 BILAG B domain scores observed during screening.  
In addition, subjects must have a clinical SLEDAI-2K score ≥4 (excluding laboratory results) at 
week 0, prior to randomization.
Subject randomization will be stratified according to consent for skin biopsy collection (y/n), and 
other features (eg, presence of lupus nephritis [y/n], baseline SLE medications and SLEDAI 
score), site/region, and race, or concomitant medications as described in Section 8. 
Approximately 100 subjects will be randomly assigned by 3:2 ratio to receive either ustekinumab 
or placebo through Week 24. Following randomization at Week 0, subjects will receive an initial 
body weight-range based IV dose approximating 6 mg/kg of ustekinumab (ustekinumab 260 mg 
[weight ≥35 kg to ≤55 kg]; ustekinumab 390 mg [weight >55 kg and ≤85 kg]; ustekinumab 
520 mg [weight >85 kg]) followed by 90 mg SC administered q8w (Section 6). At Week 24, 
subjects receiving placebo will cross-over and all subjects will receive ustekinumab 90 mg SC at 
Weeks 24, 32, and 40 followed by safety follow-up through Week 56 in a blinded fashion for 
16 weeks (ie, approximately 5 half-lives) after last study agent SC administration.
A placebo comparator (added to standard of care background therapy) will be used through 
Week 24 for the evaluation of the efficacy and safety of ustekinumab in subjects with SLE. From 
Week 24 through Week 40, the placebo group will cross-over to ustekinumab 90 mg SC q8w. 
This cross-over design will permit placebo subjects to receive study agent and provide 
experience with ustekinumab 90 mg SC without the IV loading dose in subjects with SLE. The 
40-Week dosing period will be useful to understand the longer term safety and time course of 
potential clinical response of ustekinumab in the SLE population.
Every reasonable effort should be made to keep concomitant medications stable as defined in the 
protocol. All concomitant therapies must be recorded throughout the study beginning at entry 
into screening and any changes must be recorded throughout the study.
All subjects with cutaneous disease will be evaluated using CLASI scoring. Additionally,
subjects with cutaneous disease who consent to participate in the cutaneous lupus substudy will 
have other assessments including collection of skin biopsies (optional consent) and/or 
photographs of an identified cutaneous lesion or area of active disease (optional consent). There 
will not be any restrictions on the number of subjects with cutaneous disease who can enroll into 
either the main study or the cutaneous lupus substudy.
Interim analyses (IA) will be conducted when approximately 1/3 and 2/3 of subjects reach 
Week 24. In the first IA, only evidence for notable efficacy will be assessed. In the second IA, 
evidence for notable efficacy as well as treatment futility will be analyzed. Variations in placebo 
effect across regions will be incorporated into the interim analyses. Database locks (DBLs) will 
occur at Weeks 24 and after the final subject’s Week 56 visit or following the last subject’s 
16-week safety follow-up visit from the main study. In addition, an independent data monitoring 
committee (DMC) will review interim safety data periodically including a formal review when 
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approximately 1/3 and 2/3 of subjects reach Week 24, as well as at the Week 24 DBL. The DMC 
will make a recommendation to the Sponsor committee whether the study should be stopped for 
futility or for safety concerns or if data meet prespecified criteria demonstrating notable efficacy. 
The content of the summaries, the DMC role and responsibilities, and the general procedures 
(including communications) will be defined in the DMC charter.
The amended study design will continue to provide open-label ustekinumab 90 mg q8w SC 
administration through Week 104 (study extension). Subjects will be eligible to continue study 
treatment through Week 104 if they meet the study inclusion criteria (Section 4.1.3):

must not have permanently discontinued study treatment on or before their Week 40 visit, 
and

are able to continue q8 week study treatment at approximately 8 weeks (±2 weeks) after
their Week 40 visit
or

are able to resume study treatment with no more than 16 weeks (±2 weeks) since their 
Week 40 visit
In addition to the DBL planned following the last subject’s Week 56 visit or the final 16-week 
safety follow-up visit from the main study, there will be an additional DBL following the 
Extension 16-Week Safety Follow-up period.
A diagram of the main study design is provided below in Figure 1, and a diagram of the extended 
study is provided in Figure 2.
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Figure 1:
Schematic Overview of the Main Study (Screening through 16-Week Safety Follow-Up)
Abbreviations: DBL=database lock; FU=follow-up; IV=intravenous; PE=primary endpoint; PL=placebo; 
q8w=every 8 weeks; SC=subcutaneous; SLE=systemic lupus erythematosus; SRI=SLEDAI-2K Responder Index; 
Wks=weeks.
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Figure 2:
Schematic Overview Including the Study Extension
3.2.
Study Design Rationale
Blinding, Control, Study Phase/Periods, Treatment Groups
A placebo control will be used to establish the frequency and magnitude of changes in clinical 
endpoints that may occur in the absence of active treatment. Randomization will be used to 
minimize bias in the assignment of subjects to treatment groups, to increase the likelihood that 
known and unknown subject attributes (eg, demographic and baseline characteristics) are evenly 
balanced across treatment groups, and to enhance the validity of statistical comparisons across 
treatment groups. Blinded treatment will be used to reduce potential bias during data collection 
and evaluation of clinical endpoints.
DNA and Biomarker Collection
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 SLE.
Biomarker samples will be collected to evaluate the mechanism of action of ustekinumab or help 
to explain inter-individual variability in clinical outcomes or may help to identify population
subgroups that respond differently to a drug. The goal of the biomarker analyses is to evaluate 
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the pharmacodynamics of ustekinumab and aid in evaluating the drug-clinical response 
relationship.
DNA and Biomarker samples may be used to help address emerging issues and to enable the 
development of safer, more effective, and ultimately individualized therapies.
4.
SUBJECT POPULATION
The target study population is subjects with SLE according to SLICC criteria and SLEDAI-2K
score ≥6, despite conventional treatment (eg, immunomodulators, antimalarial drugs, 
corticosteroids, NSAIDs, anti-hypertensive drugs, and/or topical medications). Subjects must 
have at least 1 BILAG A and/or 2 BILAG B domain scores observed during screening. In 
addition, subjects must have at least 1 positive autoantibody test (ANA, anti-dsDNA antibodies, 
and/or anti-Smith antibodies) observed during screening, as well as a well-documented positive 
autoantibody test in their medical history, and they must also have a clinical SLEDAI-2K score 
≥4 (excluding laboratory results) prior to randomization at week 0.
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, the 
investigator should consult with the appropriate Sponsor representative before enrolling a subject 
in the study.
Subjects with SLE enrolling into the main study with active cutaneous lupus (including subjects 
with discoid lupus erythematosus, subacute cutaneous lupus erythematosus, or SLE malar rash or 
other SLE skin lesions characterized by erythema and/or scale) will be evaluated using CLASI 
scoring. In addition, subjects who provide consent will be enrolled in the cutaneous lupus 
substudy evaluating the histology of cutaneous biopsies and/or skin photographs. Biopsy samples 
(2 samples, 4 mm size) from consenting subjects will be collected prior to dosing at Week 0 and 
at Week 24 from a lesion demonstrating active cutaneous disease. Subjects participating in the 
cutaneous lupus substudy are not required to undergo biopsies, and may allow only photographs 
to document changes in an identified cutaneous lesion or area of active disease. Subjects with 
cutaneous lupus deemed unsuitable for biopsy (eg, malar rash or alopecia) can also be enrolled in 
the substudy, and may be evaluated by photography.
If a subject has failed screening and investigator wishes to rescreen the subject, this should be 
discussed with the study Sponsor and/or their designee. Only 1 rescreening is allowed per subject
(also see Section 9.1.2).
The study extension population will be comprised of those subjects who have not permanently 
discontinued study treatment before or at the Week 40 dose and for whom the investigators judge 
that there is a potential benefit that outweighs the potential risks to continued ustekinumab 
treatment.
For a discussion of the statistical considerations of subject selection, refer to Section 11.2,
Sample Size Determination.
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4.1.
Inclusion Criteria
4.1.1.
Inclusion Criteria Applicable to All Subjects
Each potential subject must satisfy all of the following criteria to be enrolled in the study. 
1.
Subject must be between 18 (or older as per local requirements) and 75 years of age, 
inclusive, and weigh at least 35 kg.
2.
Subjects must have documented medical history to meet SLICC classification criteria 
for SLE for a minimum of 3 months prior to first dose (Table 3).
Subjects eligible for enrollment in this study must qualify as having SLE by meeting the 
SLICC classification criteria for SLE25 based upon 1 or both of the following:

Meeting 4 criteria with at least 1 clinical criterion and at least 1 immunologic 
criterion, or 

A diagnosis of lupus nephritis with presence of at least 1 of the immunological 
variables
Table 3:
Clinical and Immunological Criteria Used in the SLICC Classification Criteria*25
Clinical Criteria
Specific Criteria
1.
Acute Cutaneous Lupus including 
lupus malar rash (do not count if malar 
discoid)

Bullous lupus

Toxic epidermal necrolysis variant of SLE

Maculopapular lupus rash

Photosensitive 
lupus 
rash 
(in 
absence 
of 
dermatomyositis)

Subacute cutaneous lupus (nonindurated psoriaform 
and/or annular polycyclic lesions that resolve 
without scarring, although occasionally 
with 
postinflammatory 
dyspigmentation 
or 
telangiectasias)
2.
Chronic cutaneous lupus including 
classical discoid rash

Localized (above the neck)

Generalized (above and below the neck)

Hypertrophic (verrucous) lupus

Lupus panniculitis (profundus)

Mucosal lupus

Lupus erythematosus tumidus

Chilblains lupus

Discoid lupus / lichen planus overlap
3.
Oral ulcers: palate

Buccal

Tongue

Nasal
In the absence of other causes such as vasculitis, 
Behcets, infection (herpes), inflammatory bowel disease, 
reactive arthritis, and acidic foods
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Table 3:
Clinical and Immunological Criteria Used in the SLICC Classification Criteria*25
4.
Non-scarring alopecia (diffuse thinning 
or hair fragility with visible broken 
hairs)
In the absence of other causes such as alopecia areata, 
drugs, iron deficiency and androgenic alopecia
5.
Synovitis involving two or more joints
Characterized by swelling or effusion OR tenderness in 
2 or more joints and thirty minutes or more of morning 
stiffness
6.
Serositis

Typical pleurisy for more than 1 day
o
Or pleural effusions
o
Or pleural rub

Typical pericardial pain (pain with recumbency 
improved by sitting forward) for more than 1 day
o
Or pericardial effusion
o
Or pericardial rub
o
Or pericarditis by EKG
In the absence of other causes such as infection, uremia 
and Dressler’s pericarditis
7.
Renal

Urine protein/creatinine (or 24 hour urine protein) 
representing 500 mg of protein/24 hour, or

Red blood cell casts
8.
Neurologic

Seizures

Psychosis

Mononeuritis multiplex (in the absence of other 
known causes such as primary vasculitis)

Myelitis

Peripheral or cranial neuropathy (in the absence of 
other known causes such as primary vasculitis, 
infection and diabetes mellitus)

Acute confusional state (in the absence of other 
causes including toxic-metabolic, uremia, drugs)
9.
Hemolytic anemia

Presence
10a. Leukopenia (<4000/mm3
at least 
once), or
10b. Lymphopenia (<1000/mm3 at least 
once)
In the absence of other known causes such as Felty’s,
drugs, and portal hypertension
In the absence of other known causes such as 
corticosteroids, drugs, and infection
11. Thrombocytopenia (<100,000/mm3 at 
least once)
In the absence of other known causes such as drugs, 
portal hypertension, and TTP
Immunological Criteria
Specific Criteria 
1.
ANA 
above laboratory reference range
2.
Anti-dsDNA
above laboratory reference range, except ELISA; twice 
above laboratory reference range
3.
Anti-Smith

Presence
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Table 3:
Clinical and Immunological Criteria Used in the SLICC Classification Criteria*25
4.
Anti-phospholipid
antibody 
(any 
shown to right)

Lupus anticoagulant

False-positive RPR

Medium or high titer anticardiolipin (IgA, IgG or 
IgM)

Anti-β2 glycoprotein 1 (IgA, IgG or IgM)
5.
Low Complement

Low C3

Low C4

Low CH50
6.
Direct Coombs test
In the absence of hemolytic anemia
*Criteria are cumulative and do not need to be present concurrently
3.
To be eligible for study enrollment, subjects must have:

At least 1 well-documented (subject file, referring physician letter, or laboratory
result) unequivocally positive, documented test for autoantibodies in medical history
including either of the following: ANA, and/or anti-dsDNA antibodies, and/or 
anti-Smith antibodies (Section 9.1.2).

At least 1 unequivocally positive autoantibody test including ANA and/or 
anti-dsDNA antibodies and/or anti-Smith antibodies (Section 9.1.2) detected during 
screening.

At least 1 BILAG A and/or 2 BILAG B domain scores observed during screening 
prior to first administration of study agent.
4.
Demonstrate active disease based on SLEDAI-2K score ≥6 observed during screening 
and assessed approximately 2 to 6 weeks prior to randomization. Must also have 
SLEDAI-2K ≥4 for clinical features (ie, SLEDAI excluding laboratory results) at Week 
0 prior to the first administration of study agent.
5.
Data from the SLICC, SLEDAI and BILAG evaluations will be reviewed and 
adjudicated by the Sponsor and/or the Sponsor-selected independent reviewer(s). For 
subjects to receive their first administration of study agent, approval must be received 
by the Sponsor and/or Sponsor-selected independent reviewers.  
6.
If using oral corticosteroids, subjects must be receiving this medication for at least 
6 weeks and on a stable dose equivalent to an average dose of ≤20 mg/day of 
prednisone for at least 4 weeks prior to the first administration of study agent. If 
currently not using corticosteroids, must have not received oral corticosteroids for at 
least 6 weeks prior to the first administration of study agent.
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7.
If using antimalarials (eg, chloroquine, hydroxychloroquine, or quinacrine), subjects 
must have used the medication for ≥8 weeks and be on a stable dose for at least 6 weeks 
prior to the first administration of study agent.
8.
If using immunomodulatory drugs (mycophenolate mofetil [MMF]/mycophenolic acid 
[MPA] ≤2 g/day, azathioprine/6 mercaptopurine (AZA /6 MP) ≤2 mg/kg/day and/or 
MTX ≤25 mg/wk with concomitant folic acid [recommend ≥5 mg/wk]), subjects must 
be receiving a stable dose for at least 6 weeks prior to the first administration of study 
agent.
9.
If receiving regular treatment with NSAIDs or other analgesics, subjects must be 
receiving stable dosing for at least 2 weeks prior to first administration of study agent.
10.
Before randomization, a woman must be either:
Not of childbearing potential: premenarchal; postmenopausal (>45 years of age with 
amenorrhea for at least 12 months); permanently sterilized (eg, tubal occlusion, 
hysterectomy, bilateral salpingectomy); or otherwise be incapable of pregnancy.
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, established use of oral, injected or implanted 
hormonal methods of contraception associated with inhibition of ovulation; placement 
of an intrauterine device  or intrauterine system; male partner sterilization (the 
vasectomized partner should be the sole partner for that subject); true abstinence (when 
this is in line with the preferred and usual lifestyle of the subject).  
Note: If the childbearing potential changes after start of the study (eg, woman who is 
not heterosexually active becomes active, premenarchal woman experiences menarche) 
a woman must begin a highly effective method of birth control, as described above.  
11.
A woman of childbearing potential must have a negative serum pregnancy test -human 
chorionic gonadotropin [-hCG]) at screening, and a negative urine pregnancy test at 
Week 0 before the first administration of study agent.
12.
Women of childbearing potential must be willing to remain on a highly effective 
method of birth control during the study and for 4 months after receiving the last study 
agent. Also, women of childbearing potential must agree to not donate eggs (ova, 
oocytes) for the purposes of assisted reproduction during the study and for 4 months 
after receiving the last dose of study agent. 
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13.
A man who is sexually active with a woman of childbearing potential and has not had a 
vasectomy 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, and all men 
must also not donate sperm during the study and for 4 months after receiving the last 
dose of study agent.
14.
Are considered eligible according to the following tuberculosis (TB) screening criteria:
a.
Have no history of latent or active TB prior to screening. An exception is made 
for subjects who have a history of latent TB and are currently receiving 
treatment for latent TB, will initiate treatment for latent TB prior to first 
administration of study agent, or have documentation of having completed 
appropriate treatment for latent TB within 3 years prior to the first 
administration of study agent. It is the responsibility of the investigator to verify 
the adequacy of previous anti-tuberculous treatment and provide appropriate 
documentation.  
b. Have no signs or symptoms suggestive of active TB upon medical history and/or 
physical examination.
c.
Have had no recent close contact with a person with active TB or, if there has 
been such contact, will be referred to a physician specializing in TB to undergo 
additional evaluation and, if warranted, receive appropriate treatment for latent 
TB prior to the first administration of study agent.
d. Within 6 weeks prior to the first administration of study agent, have a negative 
QuantiFERON®-TB Gold test result (Attachment 2), or have a newly identified 
positive QuantiFERON®-TB Gold test result in which active TB has been ruled 
out and for which appropriate treatment for latent TB has been initiated prior to 
the first administration of study agent.  Within 6 weeks prior to the first 
administration of study agent, a negative tuberculin skin test (Attachment 3), or 
a newly identified positive tuberculin skin test in which active TB has been ruled 
out and for which appropriate treatment for latent TB has been initiated prior to 
the first administration of study agent, 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.
i.
Subjects with persistently indeterminate QuantiFERON®-TB Gold test 
results may be enrolled without treatment for latent TB, if active TB is 
ruled out, their chest radiograph shows no abnormality suggestive of TB 
(active or old, inactive TB), and the subject has no additional risk factors 
for TB as determined by the investigator. This determination must be 
promptly reported to the Sponsor’s medical monitor and recorded in the 
subject's source documents and initialed by the investigator.
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ii.
The QuantiFERON®-TB Gold test and the tuberculin skin test are not 
required at screening for subjects with a history of latent TB and ongoing 
treatment for latent TB or documentation of having completed adequate 
treatment as described above; Subjects with documentation of having 
completed adequate treatment as described above are not required to 
initiate additional treatment for latent TB.  
e.
Subjects who test positive for TB by a TB test other than QuantiFERON®-TB 
Gold and TB skin test and who have no evidence of TB on chest radiograph will 
in the context of this protocol be considered latent TB positive and be required 
to undergo evaluation by a TB specialist and receive treatment for TB to be 
eligible for this study. 
f.
Have a chest radiograph (both posterior-anterior and lateral views) taken within 
3 months prior to the first administration of study agent and read by a qualified 
radiologist or pulmonologist, with no evidence of current, active TB or old, 
inactive TB.
15.
Have laboratory test results within the following parameters at screening: 
Hemoglobin
8.5 g/dL
(SI:  85 g/L)
Lymphocytes
≥0.5 x 103/L
(SI:  ≥0.5 GI/L)
Neutrophils
1.0 x 103/L
(SI:  1.0 GI/L)
Platelets
75 x 103/L
(SI:  75 GI/L)
Serum creatinine
1.8 mg/dL
(SI:  159 mol/L)
White blood cells
2.0 x 103/L
(SI:  2.0 GI/L)
The aspartate aminotransferase, alanine aminotransferase, and alkaline phosphatase 
levels must be within 2 x upper limit of normal (ULN) range for the laboratory 
conducting the test. For subjects within the range of 1.5 to 2 x ULN for transaminases, 
the subject may be included only if the investigator judges the abnormalities or 
deviations from normal to not be clinically significant or to be appropriate and 
reasonable for the population under study. This determination must be promptly 
reported to the Sponsor’s medical monitor and recorded in the subject's source 
documents and initialed by the investigator.
Subjects with other marked disease-associated laboratory abnormalities may be included 
only if the investigator judges the abnormalities or deviations from normal to be not 
clinically significant or to be appropriate and reasonable for the population under study. 
This determination must be promptly reported to the Sponsor’s medical monitor and 
recorded in the subject’s source documents and initialed by the investigator.
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16.
Subject must be willing and able to adhere to the prohibitions and restrictions specified 
in this protocol.
17.
Each subject 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. 
18.
Each subject must sign a separate informed consent form if he or she agrees to provide 
an optional DNA sample for research (where local regulations permit). Refusal to give 
consent for the optional DNA research sample does not exclude a subject from 
participation in the study.
4.1.2.
Additional Inclusion Criteria for the Cutaneous Lupus Substudy
To be enrolled in the cutaneous lupus substudy, an SLE subject must satisfy all previously listed 
inclusion criteria (Section 4.1.1) in addition to the criteria listed below: 
1.
Have diagnosis of active CLE at screening as well as documented cutaneous disease 
prior to study enrollment, including subjects with discoid lupus erythematosus, subacute 
cutaneous lupus erythematosus, or SLE malar rash or other SLE skin lesions including 
those characterized by erythema and/or scale.
2.
Subjects taking systemic, topical, or intra-lesional medications for CLE must be on a 
stable dose or treatment regimen for 4 weeks prior to first study agent administration.
3.
Subjects who consent to participate in the cutaneous lupus substudy will be asked to 
provide biopsies of an active CLE target lesion prior to dosing at Weeks 0 and 24. An 
active CLE lesion is characterized by scale and/or erythema, excluding previously 
scarred tissue. In addition, separate consent will be obtained to collect photographs of a 
cutaneous lesion or area of active disease according to the schedule defined in Table 1.
4.
Subjects with cutaneous lupus deemed unsuitable for biopsy (eg, malar rash or alopecia) 
can also be enrolled in the substudy, and may be evaluated by photography.
4.1.3.
Inclusion Criteria Applicable to All Subjects Entering into the Study 
Extension (Week 48 or Week 56 visits)
Any subjects who do not meet the inclusion criteria for the study extension must follow the Time 
and Events schedule for the main study design (Table 1), and have safety follow-up visits 
conducted at 8 and 16 weeks following their Week 40 or final study dose.
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1.
Subjects must not have permanently discontinued study treatment on or before their 
Week 40 visit, and are able to either continue q8w SC dosing at approximately 8 weeks 
(±2 weeks) after their Week 40 visit, or are able to resume dosing at Week 56 with no 
more than 16 weeks (±2 weeks) since their Week 40 visit.
2.
In the judgment of the study investigator, the potential benefit of continuing 
ustekinumab long-term treatment outweighs the potential risks for the subject.
3.
Each subject must sign a revised informed consent indicating agreement to participate in 
the extended study.
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study. 
1.
Have other inflammatory diseases that might confound the evaluations of efficacy, 
including but not limited to rheumatoid arthritis (RA), psoriatic arthritis (PsA), 
RA/lupus overlap, psoriasis, or active Lyme disease.
2.
Are pregnant, nursing, or planning a pregnancy or fathering a child while enrolled in the 
study or within 4 months after receiving the last administration of study agent.
3.
Have received systemic or topical cream/ointment preparations of cyclosporine A or 
other systemic immunomodulatory agents other than those described in inclusion 
criteria within the past 3 months prior to first administration of study agent 
(Section 4.1). Corticosteroids are not included in this criterion; see Sections 4.3 and 8.3
regarding corticosteroids.
4.
Have received a single B cell targeting agent within 3 months prior to first study agent 
administration; or received more than 1 previous B cell targeting therapy including 
belimumab or epratuzamab within 6 months prior to first administration of the study 
agent; or received B cell depleting therapy (eg, rituximab) within 12 months prior to 
first administration of the study agent or have evidence of continued B cell depletion 
following such therapy.
5.
Have ever received ustekinumab.
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6.
Have received prior immunomodulatory biologic therapy for lupus not described in 
Exclusion Criterion #4 including, but not limited to, tocilizumab, alefacept, efalizumab, 
natalizumab, abatacept, anakinra, brodalumab, secukinumab, ixekizumab, or inhibitors 
of TNF, IL-1, IL-6, IL-17, or interferon pathways, less than 5 half-lives or 3 months, 
whichever is longer, prior to first administration of the study agent.
7.
Have a known hypersensitivity to human immunoglobulin (Ig) proteins (eg, intravenous 
Ig).
8.
Have used oral cyclophosphamide within 90 days or IV cyclophosphamide within 
180 days of starting screening.
9.
Have a history of active granulomatous infection, including histoplasmosis, or 
coccidioidomycosis, prior to screening. Refer to inclusion criteria for information 
regarding eligibility with a history of latent TB.
10.
Have had a Bacille Calmette-Guérin (BCG) vaccination within 12 months of screening.
11.
Have a chest radiograph within 3 months prior to the first administration of study agent 
that shows an abnormality suggestive of a malignancy or current active infection, 
including TB. 
12.
Have had a nontuberculous mycobacterial infection or opportunistic infection 
(eg, cytomegalovirus, pneumocystosis, aspergillosis) within 6 months prior to screening.
13.
Have received, or are expected to receive, any live virus or bacterial vaccination within 
3 months before the first administration of study agent, during the study, or within 
3 months after the last administration of study agent. For BCG vaccination criterion, see 
Exclusion Criterion 10 and Prohibition/Restriction Criterion 8.
14.
Have had a serious infection (including but not limited to, hepatitis, pneumonia, sepsis, 
or pyelonephritis), or have been hospitalized for an infection, or have been treated with 
intravenous antibiotics for an infection within 2 months prior to first administration of 
study agent. Less serious infections (eg, acute upper respiratory tract infection, simple 
urinary tract infection) need not be considered exclusionary at the discretion of the 
investigator.
15.
Have a history of, or ongoing, chronic or recurrent infectious disease, including but not 
limited to, chronic renal infection, chronic chest infection (eg, bronchiectasis), sinusitis, 
recurrent urinary tract infection (eg, recurrent pyelonephritis), an open, draining, or 
infected skin wound, or an ulcer.
16.
Subject has a history of human immunodeficiency virus (HIV) antibody positive, or 
tests positive for HIV at screening.
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17.
Has a hepatitis B infection. Subjects must undergo screening for hepatitis B virus 
(HBV) (Attachment 4). At a minimum, this includes testing for HBsAg (HBV surface 
antigen), anti-HBs (HBV surface antibody), and anti-HBc total (HBV core antibody 
total).
18.
Subjects who are seropositive for antibodies to hepatitis C virus (HCV), unless they 
have 2 negative HCV RNA test results 6 months apart prior to screening and have a 
third negative HCV RNA test result at screening. 
19.
Subjects having experienced a recent single dermatomal herpes zoster eruption within 
the past 4 months are excluded. Those with multi-dermatomal herpes zoster or central 
nervous system (CNS) zoster within the past 5 years are excluded.
20.
Subjects with a history or suspected occurrence of drug-induced lupus. 
21.
Have urinary protein >4 g/day or protein/creatinine ratio >4.
22.
Have inherited complement deficiency or combined variable immunodeficiency.
23.
Have end-stage renal disease, or severe or rapidly progressive glomerulonephritis, 
including severe, active lupus nephritis reported in recent biopsy and/or other 
assessments such as active urinary sediment, rapidly increasing creatinine, or other 
factors that suggest severe or rapidly progressing nephritis (see also limits on serum 
creatinine in Inclusion Criterion #15).
24.
Have severe CNS lupus including but not limited to seizures, psychosis, transverse 
myelitis, CNS vasculitis and optic neuritis.
25.
Have severe, progressive, or uncontrolled hepatic, hematological, gastrointestinal, 
endocrine, pulmonary, cardiac, neurologic/ cerebral, or psychiatric disease, or current 
signs and symptoms thereof.
26.
Have a known history of lymphoproliferative disease, including lymphoma, or signs and 
symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy 
of unusual size or location, clinically significant splenomegaly, or history of monoclonal 
gammopathy of undetermined significance.
27.
Subject has a history of malignancy within 5 years before screening (exceptions are 
squamous and basal cell carcinomas of the skin that has been treated with no evidence 
of recurrence for at least 3 months before the first study agent administration and 
carcinoma in situ of the cervix that has been surgically cured).
28.
Has known allergies, hypersensitivity, or intolerance to ustekinumab, its excipients or 
latex (contained in the syringe needle cover, see Section 14.1) (refer to the ustekinumab 
Investigator’s Brochure).
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29.
Are currently receiving venom immunotherapy (honeybee, wasp, yellow jacket, hornet, 
or fire ant).
30.
Has received an investigational drug that is not previously defined in other exclusion 
criteria (including investigational vaccines or other medications specified in section 4.3, 
Prohibition/Restriction No. 3) within 5 half-lives or 3 months, whichever is longer, or 
used an invasive investigational medical device within 3 months before the planned first 
dose of study drug, or is currently enrolled in an interventional study.
31.
Has any condition for which, in the opinion of the investigator and/or Sponsor, 
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 
including a previous pattern of non-compliance with medical follow-up or being 
deemed unlikely to be compliant with a study visit schedule.
32.
Has had major surgery, (eg, requiring general anesthesia) within 1 month before 
screening, or will not have fully recovered from surgery, or has major surgery 
(eg, requiring general anesthesia) planned during the time the subject is expected to 
participate in the study or within 1 month after the last dose of study drug 
administration.
Note: Subjects with planned minor surgical procedures to be conducted under local 
anesthesia may participate.
33.
Have a transplanted organ (with the exception of a corneal transplant performed 
>3 months prior to first administration of study agent).
34.
Have or have had a substance abuse (drug or alcohol) problem within the previous 
3 years.
35.
Are unwilling or unable to undergo multiple venipunctures because of poor tolerability 
or lack of easy venous access.
36.
Subject is an employee of the investigator or study site (i.e. personnel to whom the 
investigator has delegated a role or responsibility for conducting the study), 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.
37.
Lives in an institution on court or authority order, unless permitted by local regulations.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
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 
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the enrollment criteria. Sponsor reserves the right to discontinue the subject for any operational 
or safety reasons.
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study (including the study extension) to be eligible for 
continued dosing in the study:
1.
If a woman is capable of pregnancy, she must remain on a highly effective method of 
birth control during the study and for 4 months after receiving the last study agent.  The 
exception to this restriction is if the subject or her male partner is sterilized; this situation 
does not require birth control. A woman must not donate eggs (ova, oocytes) for the 
purposes of assisted reproduction during the study and for 4 months after receiving the 
last dose of study agent.
2.
If a man, he is to use an effective method of birth control and not donate sperm during 
the study and for 4 months after receiving the last dose of study agent. The exception to 
this is if the subject or his female partner is sterilized; this situation does not require birth 
control.
3.
Use of additional immunosuppressants or immunomodulators, other than those explicitly 
allowed in the inclusion/exclusion criteria, are prohibited including but not limited to the 
following:

Biologic agents targeted at reducing TNF(including but not limited to infliximab, 
golimumab, certolizumab pegol, etanercept, yisaipu, CT-P13 [Remsima®] and 
adalimumab)

B cell depleting agents (anti-CD20 [eg, rituximab], anti-B cell activating factor 
[BAFF], also known as B lymphocyte stimulator [BLyS], [eg, belimumab], or
anti-CD22 [eg, epratuzumab])

Interleukin-1 inhibitors (eg, canakinumab)

Interferon inhibitors 

IL-1ra (eg, anakinra)

Tocilizumab or any other biologic targeting IL-6 or IL-6 receptor

Tofacitinib or any other janus kinase (JAK) inhibitor

Abatacept

Anti-IL-17 agents (eg, brodalumab, secukinumab, and ixekizumab) 

Leflunomide

Cyclosporine A (oral or topical ointment/cream preparations)

Tacrolimus or picrolimus, oral or topical preparations

Toll-like receptor inhibitors
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
Thalidomide or lenalidomide

Dapsone

Adrenocorticotropic hormone (ACTH) by injection
4.
Use of cytotoxic drugs is prohibited including, but not limited to, cyclophosphamide, 
chlorambucil, nitrogen mustard, or other alkylating agents.
5.
Multiple administrations of high doses of corticosteroids, and initiation of medium or 
high potency topical corticosteroids, are prohibited during the study as defined in Section 
8.3.
6.
The initiation of a new permitted immunomodulatory agent (MTX, azathioprine, 6-
mercaptopurine, mycophenolate mofetil/mycophenolic acid) in addition to an ongoing 
immunomodulatory therapy is prohibited.
7.
Initiation of new angiotensin II receptor blocker (ARB) or angiotensin-converting 
enzyme (ACE) inhibitor therapy after first dose of study agent is not permitted for the 
treatment of lupus-related disease through Week 28.
8.
Must agree not to receive a live virus or live bacterial vaccination during the study. 
Subjects must also agree not to receive BCG vaccination for 12 months after last dose of 
study agent, or any other live vaccine for 3 months after receiving the last administration 
of study agent.
9.
Must agree not to receive an investigational medical device or an investigational drug 
other than study agent for the duration of this study.
10.
The use of complementary therapies that may trigger activation of lupus or mitigate the 
symptoms 
of 
SLE, 
including 
but 
not 
limited 
to, 
traditional 
medicine 
(eg, herbal/alternative preparations [eg, Echinacea], Chinese, acupuncture, ayurvedic) is 
prohibited through Week 40.  
11.
Study subjects should avoid excessive sun exposure and may not participate in 
commercial ultraviolet tanning or ultraviolet phototherapy during the study.
12.
Skin concealers or topical tan preparations should be avoided due to their potential to 
obscure skin disease activity.
13.
Sulfa-based antibiotics, where reasonable, should generally be avoided.
5.
TREATMENT ALLOCATION AND BLINDING
5.1.
Procedures for Randomization
Dynamic central randomization will be implemented in conducting this study. Subjects will be 
assigned to 1 of 2 treatment groups based on a minimization randomization algorithm 
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implemented in the interactive web response system (IWRS) before the study. Dynamic central 
randomization targets to balance the distribution of subjects to achieve the randomization ratio 
(3:2) at the study level and within the levels of each individual stratification factor: skin biopsy 
(y/n, when n<16 for y), presence of lupus nephritis (y/n), baseline SLE medications and 
SLEDAI-2K score (combined factor)*, site, region (approximately 4 categories), and race 
(3 categories). Based on the algorithm, each subject will be assigned to the treatment group 
which will produce minimum total imbalance score with a high probability, where the total 
imbalance score is a weighted average of the imbalance scores for each stratification factor and 
for the whole study. The IWRS will the assign a unique treatment code, which will dictate the 
treatment assignment for the subject.
* The baseline SLE medications and SLEDAI-2K score will be calculated as a combined factor, 
including:

SLEDAI-2K score (<10 or ≥10) combined with

Baseline medications:

High medications defined as ≥15 mg/wk MTX, or ≥1.5 mg/kg/day AZA/6-MP, or 
≥1.5 g/day MMF/MPA, and/or ≥15 mg/day prednisone.

Low medications defined as ˂15 mg/wk MTX, or ˂1.5 mg/kg/day AZA/6-MP, or 
˂1.5 g/day MMF/MPA, and/or ˂15 mg/day prednisone.
5.2.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual subject.
Under normal circumstances, the blind should not be broken until all subjects have completed 
the study at Week 56 or terminated study participation, and the database is finalized. Otherwise, 
the blind should be broken only if specific emergency treatment/course of action would be
dictated by knowing the treatment status of the subject. In such cases, the investigator may in an 
emergency determine the identity of the treatment by contacting IWRS. It is recommended that 
the investigator contact the Sponsor or its designee if possible to discuss the particular situation, 
before breaking the blind. Telephone contact with the Sponsor or its designee will be available 
24 hours per day, 7 days per week. In the event the blind is broken, the Sponsor must be 
informed as soon as possible. The date and reason for the unblinding must be documented by the 
IWRS, in the appropriate section of the case report form (CRF), and in the source document. The 
documentation received from the IWRS indicating the code break must be retained with the 
subject's source documents in a secure manner.
Subjects who have had their treatment assignment unblinded may be discontinued from further 
administration of study agent and should return for safety follow-up.
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In general, randomization codes will be disclosed fully only if the study is completed and the 
clinical database is closed. The Sponsor will be blinded through the Week 24 evaluation and 
until the database is cleaned and finalized for planned analyses. The clinical site, subjects, 
investigators, and site personnel will remain blinded through the end of the study until Week 56 
data are finalized. Data that may potentially unblind the treatment assignment will be handled 
with special care. 
6.
DOSAGE AND ADMINISTRATION
Detailed instructions on the IV and SC administration of study agent are provided in the 
Investigative Product (IP) Manual.
6.1.
IV administration
For IV administration, the study agent will be administered to each subject over a period of not 
less than 1 hour. 
Ustekinumab 5 mg/mL Final Vialed Product (FVP) (IV) is supplied as a single-use, sterile 
solution in 30 mL vials with 1 dose strength (ie, 130 mg in 26 mL nominal volume). In addition 
to ustekinumab, the solution contains 10 mM L-histidine, 8.5% (w/v) sucrose, 0.04% (w/v) 
polysorbate 80, 0.4 mg/mL L-methionine, and 20 µg/mL ethylenediaminetetraacetic acid 
(EDTA) disodium salt dihydrate at pH 6.0. No preservatives are present.
Placebo for FVP (IV) is supplied as single-use, sterile solution in 30 mL vials with a 26 mL 
nominal volume. The composition of the placebo is 10 mM L-histidine, 8.5% (w/v) sucrose, 
0.04% (w/v) polysorbate 80, 0.4 mg/mL L-methionine, and 20 µg/mL EDTA disodium salt 
dihydrate at pH 6.0. No preservatives are present. 
Body weight-range based dosing will allow administration of complete vials to patients to 
simplify dose calculation and reduce the potential for errors in dosing. This body weight-range 
based IV dosing is intended to achieve drug exposure similar to that observed with weight 
adjusted 6 mg/kg dosing. Comparable numbers of vials will be administered to subjects receiving 
placebo based on their body weight-range. The body weight-range doses are based on the 
following:

Body weight ≥35 kg and ≤55 kg: 260 mg ustekinumab (2 vials)

Body weight ˃55 kg and ≤85 kg: 390 mg ustekinumab (3 vials)

Body weight ˃85 kg: 520 mg ustekinumab (4 vials)
6.2.
SC administration
Ustekinumab will also be supplied as a single-use latex-free prefilled syringe (PFS) in a strength 
of 90 mg in 1 mL nominal volume for SC administration. Each 1 mL of ustekinumab solution in 
the PFS contains 90 mg ustekinumab with nominal excipient concentrations of 6.7 mM 
L-histidine, 7.6% (w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0. No preservatives are
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present. The needle cover on the PFS contains dry natural rubber (a derivative of latex), which 
may cause allergic reactions in individuals sensitive to latex.
Placebo administrations will have the same appearance as the respective ustekinumab 
administrations. Liquid placebo will also be supplied in a 1 mL PFS, and have a composition 
10 mM L-histidine, 8.5% (w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0. No 
preservatives are present.  The needle cover on the PFS contains dry natural rubber (a derivative 
of latex), which may cause allergic reactions in individuals sensitive to latex.  
Week 0 up to Week 24 (Blinded Study Agent Administration Phase)
Group 1: Subjects will receive weight-range based IV dosing of approximately 6 mg/kg of 
ustekinumab at Week 0 followed by ustekinumab 90 mg SC administrations at Weeks 8 and 16.
Group 2: Subjects will receive weight-range based IV dosing of placebo at Week 0 followed by 
placebo SC administrations at Weeks 8 and 16.
Week 24 to Week 40 (Cross-over Administration Phase)
Group 1: Subjects will receive an ustekinumab 90 mg SC administration at Week 24 followed 
by q8w administrations through Week 40.
Group 2: Subjects will cross-over to ustekinumab 90 mg SC administrations at Week 24 
followed by q8w administrations through Week 40.
After Week 40 to 16-Week safety Follow-up (Safety Follow-up Phase)
Groups 1 and 2: Subjects who do not participate in the study extension are expected to return 
for safety follow-up visits at Weeks 44 and for 8- and 16-weeks safety follow-up.
Study Extension (Week 48/Week 56 through Week 120)
Subjects who meet the study extension inclusion criteria will receive open-label ustekinumab 
administration for the purpose of expanding the safety experience and maintenance of efficacy in 
lupus patients continuously exposed to ustekinumab 90 mg q8w. Subjects who continue dosing 
in the extended study starting at Week 48 or at Week 56 will receive open-label ustekinumab SC 
dosing through Week 104. If the development of ustekinumab in SLE is terminated, then the 
study extension will also be discontinued.
7.
TREATMENT COMPLIANCE
Study personnel will maintain a log of all study agent administrations. Study agent supplies for 
each subject will be inventoried and accounted for. All ongoing therapies administered at the 
time of screening must be recorded.
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Compliance with the treatment schedule is strongly encouraged.  It is understood that treatment 
may be interrupted for health-related or safety reasons. The Weeks 0, 24, and 48 visits are 
essential for assessing efficacy and safety of ustekinumab as therapy for active SLE.
Therefore, if for any reason a subject cannot receive a dose of study agent at the scheduled visits, 
the subjects must make every effort to come for scheduled assessments. Through the Week 32
visit, the visit and study agent administration should occur within ± 7 days of the scheduled visit
day (relative to Week 0). Following the Week 32 visit, the study agent administrations are 
allowed to occur within ±2 weeks of the scheduled visit day (relative to Week 0). The study 
agent administrations are scheduled to occur approximately 8 weeks apart, and cannot occur ˂14 
days apart. If there is a delay in treatment, the subject should resume the normal study schedule 
relative to the baseline visit (Week 0).
All subject’s electronic case report forms (eCRFs) 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 
eCRFs to ensure accuracy. The Sponsor must be contacted for any deviation to the timeframes 
above.
8.
CONCOMITANT THERAPY
All prestudy therapies administered up to 90 days before entry into screening must be recorded at 
screening. Modification of an effective preexisting therapy should not be made for the explicit 
purpose of entering a subject into the study. All concomitant therapies must be recorded 
throughout the study beginning at entry into screening and any changes must be recorded 
throughout the study.
Every reasonable effort should be made to keep concomitant medications stable at least through 
Week 28, and if possible also through the main study 8-week safety follow-up or through the 
study extension (if applicable). With the exception of corticosteroids (see Section 8.3 regarding 
corticosteroid tapering), all other concomitant medications should be maintained at stable doses 
throughout the study. A concomitant medication may be reduced or medication temporarily 
discontinued because of abnormal laboratory values, side effects, concurrent illness, or the 
performance of a surgical procedure, but the change and reason for the medication change should 
be clearly documented in the subject’s medical record. If concomitant medications have been 
adjusted after randomization as allowed per protocol, every effort should be made to return 
subject back to the baseline (Week 0) dose level by the Week 12 visit; or increased medication 
use (relative to baseline) may render a subject to be considered a treatment failure. Corticosteroid 
adjustments for cause are permitted as defined in Section 8.3.
The Sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
All pharmacologic therapies (prescription or over-the-counter medications, including vaccines, 
vitamins, herbal supplements) different from the study agent must be recorded in the 
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concomitant therapy section of the eCRF. Subject diary cards will be used to capture changes in 
subject-administered medications that occur in between study visits during the main portion of 
this study, and these changes must also be recorded in the concomitant therapy section of the 
eCRF.
8.1.
Immunomodulators  
If receiving immunomodulators, subjects should be receiving stable dosing from screening 
through 
Week 
28. 
Subjects 
can 
be 
receiving 
MMF/MPA 
(≤2
g/day), 
azathioprine/6-mercaptopurine (≤2 mg/kg/day) and/or MTX (≤25 mg/wk) with concomitant folic 
acid (recommend ≥5 mg/wk), during screening and through Week 28. A reduction in 
immunomodulators from Week 12 through Week 28 is allowed only if the subject develops 
unacceptable side effects, with the implication that this may affect interpretation of the subjects’ 
clinical data. A higher dose of an immunomodulator (relative to the baseline dose) or the 
addition of a new immunomodulator to the existing treatment regimen between the Week 12 and 
24 visit will cause subjects to be considered a treatment failure for the purposes of the primary 
endpoint analysis. Permanent discontinuation of the study treatment must be considered for 
subjects receiving an increase (relative to baseline) in their immunomodulator dose. Beyond
Week 28, immunomodulators should remain as stable as possible through the 8-week safety 
follow-up or through the study extension (if applicable); however, dose adjustment is allowed for 
unacceptable side effects.
8.2.
Antimalarial Medications
Stable treatment with hydroxychloroquine, chloroquine, or quinacrine is permitted through the 
8-week safety follow-up. Beyond Week 28, it is permitted to introduce or adjust dosing of 
antimalarials. Antimalarials produced by a licensed compounding pharmacy (eg, quinacrine) in 
the country of administration and using pharmacaceutical grade components are allowed.
8.3.
Corticosteroid Therapy
Unnecessary dose changes are discouraged, and any dose adjustments should be made in 
increments. Changes in corticosteroids through the 8-week safety follow-up or through the study 
extension (if applicable) are allowed for medical necessity, but the degree and timing of the 
adjustment should be carefully considered as this may have an impact on the study results,
especially during the period between 12 and 28 weeks.
Oral Corticosteroids*
If using oral corticosteroids, must be receiving this medication for at least 6 weeks and on a
stable dose equivalent to an average dose of ≤20 mg of prednisone/day for at least 4 weeks prior 
to the first administration of study agent. Corticosteroid dose adjustment (increase or decrease) 
of no more than 5 mg prednisone (equivalent/day) to a maximum dose of 25 mg/day is permitted 
through Week 6. From Week 6 through Week 12, no corticosteroid dose increases are permitted, 
and within this window only a gradual decrease of up to 5.0 mg prednisone (equivalent/day)
adjustment towards the baseline dose are allowed up to the Week 12 visit. No further 
adjustments in doses of corticosteroid for the treatment of SLE disease are permitted between 
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Weeks 12 and 28. Following Week 28, changes in corticosteroid dosing through the 8-week 
safety follow up is allowed for medical necessity, but the degree and timing of the adjustment 
should be carefully considered as this may have an impact on the study. Dose increases of oral 
corticosteroids of 40 mg/day or more should be discussed with the medical monitor and may 
result in discontinuation of study agent administration.
Subjects may receive short courses (2 weeks or less) of oral corticosteroids for reasons such as 
prophylactic therapy before surgery (stress-dose corticosteroids) or therapy for limited 
infections, exacerbation of asthma, or chronic obstructive pulmonary disease.
Subjects likely to require multiple courses of steroids for reasons other than SLE should be 
excluded from study participation.
Gradual tapering of oral corticosteroid dosing in the study extension (recommended reductions 
of no more than 10 to 20% of the original dose per week) is encouraged starting after the 
Week 48 dose at the discretion of the study investigator. Tapering to the lowest possible 
maintenance dose of corticosteroids is recommended, including complete weaning off of 
corticosteroids if possible. It is recommended that subjects should be educated and monitored by 
study staff for symptoms of steroid deficiency (eg, Addisonian symptoms) during periods of 
steroid tapering, as appropriate.
If subjects experience a worsening in their disease activity while tapering corticosteroids, further 
dose decreases may be suspended, and/or their oral corticosteroid dose may be temporarily 
increased if deemed necessary by the investigator. For subjects whose corticosteroid taper is 
interrupted, investigators are encouraged to resume tapering within 4 weeks.
In the event of increased corticosteroid dosing, it is recommended that the average dose should 
not be increased above the baseline dose unless medically necessary.  Discretion should be used 
as any corticosteroid increases may render a subject to be considered a treatment or steroid 
tapering failure. Sustained oral corticosteroid doses of 40 mg/day or higher may result in 
discontinuation of study agent.
*Rectal administration of corticosteroids, if necessary, should be short-term and using topical 
preparations.
Epidural, Intravenous, Intramuscular, Intra-articular, and Intra-lesional Corticosteroids
Epidural, IV, IM, IA, or intra-lesional administration of corticosteroids is strongly discouraged 
within 4 weeks prior to the first administration of study agent and is not allowed for the 
treatment of SLE through Week 28. Drugs that induce release of endogenous steroids such as 
ACTH administered by injection are not allowed within 3 months prior to the first administration 
of study agent and throughout the study. Short-term (≤2 weeks) epidural, IV, IM, IA, or intra-
lesional corticosteroid use for the treatment of indications other than SLE should be limited to 
situations where, in the opinion of the treating physician, there are no adequate alternatives. If 
clinically necessary, a total of 1 or 2 IA injections may be permitted up to the Week 16 dosing, 
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however this would render those joints unevaluable for subsequent assessments. For conditions 
other than SLE, corticosteroid therapy should be limited to situations in which, in the opinion of 
the treating physician, there are no adequate alternatives. Intravenous corticosteroids of >625 mg 
prednisone equivalent/day for 2 or more days total in the 24-week period will be evaluated for 
treatment failure as per the statistical analysis plan (SAP).
Inhalation Corticosteroids
Corticosteroids administered by bronchial or nasal inhalation for treatment of conditions other 
than SLE may be given as needed.
Corticosteroid Use in Cutaneous Lupus Substudy
For subjects in the cutaneous lupus substudy, the initiation of, or an increase from baseline in,
the use of potent topical corticosteroids, or intra-lesional corticosteroid injections, is not allowed
and should be avoided through the 8-week safety follow-up or in the study extension.
8.4.
Nonsteroidal Anti-inflammatory Drugs
Subjects 
treated 
with 
NSAIDs, 
including 
aspirin 
and 
selective 
cyclooxygenase-2 
(COX-2) inhibitors, and other analgesics should receive the usual marketed doses approved in 
the country in which the study is being conducted. Prescriptions of NSAIDs and other regularly 
administered analgesics should not be adjusted for at least 2 weeks prior to the first 
administration of the study drug and through Week 28, and may be changed only if the subject 
develops unacceptable side effects. After Week 16 and through Week 28 the addition of new 
NSAIDs to the treatment regimen is not permitted. Minor adjustments in NSAID therapy are 
allowed after Week 28 although it is recommended that the use of any NSAIDS remain as stable 
as possible, and any notable changes should be recorded.
8.5.
Anti-hypertensive Medications
Subjects are permitted to receive stable doses of ARB or ACE inhibitors for the treatment of 
hypertension and lupus. Initiation of new ARB or ACE inhibitor therapy after first dose of study 
agent is not permitted for the treatment of lupus-related disease through Week 28. Subjects 
should not initiate any new ARB or ACE inhibitor therapy between randomization and Week 28.
New or adjusted ARB or ACE inhibitor therapy is allowed beyond Week 28.
8.6.
Topical Medications
Topical medications are permitted; however, topical compounds cannot include a prohibited 
medication. Topical ointments or creams of cyclosporine A are prohibited through Week 28;
however ophthalmic use is permitted. Low potency topical steroids are allowed except on day of 
study visit. Medium to high potency topical corticosteroids are disallowed for all subjects 
through the 8-week safety follow-up, and high potency topical corticosteroids are not allowed 
during the study extension. For subjects in the cutaneous lupus substudy, topical treatment of 
target lesions should remain stable during the cutaneous lupus substudy period. For 72 hours 
prior to study visit, topical medications should not be applied to lesions under evaluation.
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9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedule summarizes the frequency and timing of efficacy, 
pharmacokinetics, 
antibodies 
to 
ustekinumab, 
pharmacodynamics, 
pharmacogenomics, 
health-related quality of life, safety, and other measurements applicable to this study.
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 over the course of the main portion of 
the study will be approximately 640 mL. The total blood volume to be collected in the study 
extension between Weeks 48 and 120 will be approximately 250 mL.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
collection or analysis of specific samples.
A blood sample will be collected from subjects who have consented to participate in the 
pharmacogenomics component of the study. In the event of DNA extraction failure, a 
replacement pharmacogenomics blood sample may be requested from the subject. A separate 
informed consent would not be required to obtain a replacement sample.
Subjects who have consented to participate in the cutaneous lupus substudy will be requested to 
allow collection of skin biopsy samples at Week 0 and at Week 24. In addition, photographs will 
be taken of a target cutaneous lesion or area of active disease as noted in the Time and Events
Schedule (Table 1). For additional detail regarding the cutaneous lupus substudy, refer to 
Section 9.7.
9.1.2.
Screening Phase
9.1.2.1.
Screening Procedures
Written informed consent must be obtained and reviewed by investigator before any screening 
data is collected.
Screening procedures will be performed as indicated in the Time and Events Schedule (Table 1).
The screening visit must be performed no more than 6 weeks prior to the randomization visit 
(Week 0). In addition, to be eligible for study participation, subjects must have SLEDAI score 
4 for clinical features at Week 0 and have received approval for study randomization following 
review and adjudication of screening lupus assessments by the Sponsor and/or Sponsor-selected 
independent reviewer(s).
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Subjects will be trained on how to complete the Diary cards. Diary cards will be distributed to 
subjects for completion during the screening period.
Women of childbearing potential must have a negative serum β-hCG pregnancy test at screening 
and a negative urine β-hCG pregnancy test before randomization. Women of childbearing
potential and men must consent to use highly effective methods of contraception (see inclusion 
criteria, Section 4.1) and continue to use contraception for the duration of the study and for 
4 months after the last study agent administration. The method(s) of contraception used by each 
subject must be documented.
All screening evaluations establishing subject eligibility will be performed and reviewed by 
investigator before subject can be randomized. Although the SLICC criteria may not have been 
formally assessed, to be eligible for enrollment subjects must have demonstrated symptoms 
(documented in subject file) of SLE sufficient to meet SLICC criteria for a minimum of 
3 months prior to first dose of study agent. Subjects eligible for enrollment in this study must 
qualify as having SLE by meeting the SLICC classification criteria for SLE based upon 1 or both 
of the following (as described in Inclusion Criterion #2):

Meeting 4 criteria with at least 1 clinical criterion and at least 1 immunologic criterion, or 

A diagnosis of lupus nephritis with presence of at least 1 of the immunological variables,
Subjects must also have 1 well-documented (subject file, referring physician letter, or laboratory
result) medical historical value for unequivocally positive ANA, anti-dsDNA antibodies, and/or 
anti-Smith antibodies. Medical historical documentation of a positive test of ANA (eg, ANA by 
HEp-2 titer, ANA by enzyme-linked immunosorbent assay) or anti-dsDNA (eg, anti-dsDNA by 
Farr assay or ELISA) must include the date and type of the test, the testing laboratory name, 
numerical reference range, and a key that explains that the values provided are positive versus 
negative/equivocal or borderline. Only unequivocally positive values as defined in the 
laboratory’s reference range are acceptable; borderline values will not be accepted.
In addition, in order to assess the stability of SLE disease activity, subjects must demonstrate 
SLEDAI-2K score ≥6, despite conventional treatment (eg, immunomodulators, antimalarial 
drugs, corticosteroids, NSAIDs, anti-hypertensive drugs, and/or topical medications). In 
addition, subjects must have at least 1 positive autoantibody test (ANA, anti-dsDNA antibodies, 
and/or anti-Smith antibodies) observed during screening. Subjects must also demonstrate at 
least 1 BILAG A and/or 2 BILAG B domain scores observed prior to first administration of 
study agent.
9.1.2.2.
Retesting
If a subject has signed the ICF and failed to meet at least 1 entry requirement, a one-time retest 
of screening laboratory test(s) will be allowed in the event of suspected error in sample 
collection or analysis performance, or a study entry procedure may be repeated once during the 
screening period if needed. A request to use a local test to replace the central lab test should be 
discussed with the medical monitor prior to retesting. This is inclusive of only 1 additional blood 
draw to be completed for retesting, regardless of whether an additional laboratory value is found 
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to be out of range. The goal of the retest procedure is to assess if the subject is eligible for 
randomization within the screening window or should be screen failed. Subjects that have 
laboratory values that do not meet entry criteria following the retest or do not meet disease 
activity criteria following the repeat procedure are to be deemed a screen failure. Exceptions to 
this are positive QuantiFERON®-TB Gold, hepatitis C or B, or HIV tests; unless there is a 
suspected error in sample collection or analysis performance, these tests may not be repeated to 
meet eligibility criteria.
9.1.2.3.
Rescreening
If a subject has failed screening and investigator wishes to rescreen the subject, this should be 
discussed with the study Sponsor and/or their designee. Only 1 rescreening is allowed per 
subject. Subjects who are rescreened will be assigned a new subject number, undergo the 
informed consent process, and then restart a new screening phase.
9.1.3.
Double-Blind Treatment Phase
9.1.3.1.
Week 0/Day of Randomization
At Week 0, eligible subjects will be randomly assigned by the IWRS in a 3:2 ratio to receive 
either ustekinumab or placebo in a blinded manner.  Assessments will be performed as indicated 
in the Time and Events Schedule (Table 1). Subjects participating in the cutaneous lupus 
substudy will have baseline, pre-treatment photographs and/or skin biopsies collected. Subject’s 
diary card which was distributed during screening will be reviewed at Week 0, and a new card 
will be provided at each study visit to record medication changes during the subsequent 4 weeks
through the main portion of the study.
9.1.3.2.
Placebo-controlled Treatment Period (Through Week 24)
After randomization and the first administration of study agent by IV infusion, subjects will have 
blinded study agent administrations SC q8w through the Week 24 visit. Assessments will be 
performed as indicated in the Time and Events Schedule (Table 1). 
9.1.4.
Cross-over Treatment (Through Week 40)
At Week 24, subjects in the placebo group will cross-over to receive ustekinumab dosing, and all 
subjects will continue to receive SC administrations q8w through Week 40. All subjects will 
continue to remain blinded to study treatment received during the placebo-controlled treatment 
period as described in Section 9.1.3.2.
9.1.5.
Study Extension (Week 48/Week 56 through Week 104)
Subjects who qualify for participation in the study extension through Week 104 will continue 
ustekinumab 90 mg q8w SC dosing at approximately 8 weeks (±2 weeks) after their Week 40 
visit, or resume ustekinumab dosing at Week 56 with no more than 16 weeks (±2 weeks) since 
their Week 40 visit.
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9.1.6.
Subjects Withdrawing from Study Participation
Subjects who withdraw from study participation will not be required to return for any follow-up 
assessments.
9.1.7.
Post-treatment Safety Follow-up
Subjects who permanently discontinue study agent at or before Week 40, or permanently 
discontinue at or before Week 104 if they are participating in the study extension, but do not 
withdraw from study participation, should be followed for approximately 16 weeks (5 half-lives) 
after the last study agent administration according to the visit schedule and assessments indicated 
in the appropriate Time and Events Schedules (Table 1 and Table 2). Follow-up visits should 
occur approximately 8 weeks and 16 weeks after the last study agent administration. Subjects 
who permanently discontinue study agent before or at Week 40 will not be eligible to participate 
in the study extension.
Telephone contact will be made to determine reasons for study discontinuation for up to 
16 weeks after the last dose of study drug, unless the subject is lost to follow-up, or has 
withdrawn consent. If the information on reason for discontinuation is obtained via telephone 
contact, written documentation of the communication must be available for review in the source 
documents. If the subject has died, the date and cause of death will be collected and documented 
on the CRF.
9.2.
Efficacy
All efficacy evaluations should be consistently performed by the study investigator or 
sub-investigator to achieve comparable measures over time. Independent adjudication by 
Sponsor or Sponsor-designated independent reviewer(s) will be performed for key lupus 
assessments (eg, SLEDAI, BILAG, and CLASI). These data will be reviewed at every visit that 
these data are collected and may require reconciliation of inconsistencies across assessments.
9.2.1.
Evaluations
A complete list describing all efficacy evaluations and endpoints, and which evaluations are 
included in the composite endpoints is provided in Attachment 1.
9.2.1.1.
SLEDAI-2K and S2K RI-50
The SLE disease activity index 2000 (SLEDAI-2K / S2K RI-50 [Baseline]) is an established, 
validated SLE activity index. It is based on the presence of 24 features in 9 organ systems and 
measures disease activity in SLE patients in the previous 30 days. It is weighted according to the 
feature. At screening (Attachment 5), features are scored by the assessing physician if present 
within the last 30 days with more severe features having higher scores, and then simply added to 
determine the total SLEDAI-2K score, which ranges from 0 to 105.33 At baseline (Attachment 
6), the features assessed in the SLEDAI-2K are used for comparison to the S2K RI-50 index 
described below.
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The SLEDAI-2K has been adapted and developed into the SLEDAI-2K Responder Index (S2K 
RI-50 [Follow-up], Attachment 7)35, a measure that can document partial improvement in the 
24 disease features between SLEDAI-2K assessments.34 A threshold of 50% improvement was 
judged to reflect clinically significant improvement and is scored as half the weight for the 
feature. “When a descriptor is recorded as present at the initial visit, 1 of 3 situations can follow: 
(1) the descriptor achieves complete remission at follow-up, in which case the score would be 
“0”; (2) the descriptor does not achieve a minimum of 50% improvement at follow-up, in which 
case the score would be identical to its corresponding SLEDAI-2K value; or (3) the descriptor 
improves by ≥50% (according to the S2K RI-50 definition) but has not achieved complete 
remission, in which case the score is evaluated as one-half the score that would be assigned for 
SLEDAI-2K.”32 The S2K RI-50 score is the sum of the 24 scored items, which ranges from 0 to 
105.
9.2.1.2.
BILAG
The BILAG13,17 index scores subjects based on the need for alterations or intensification of 
therapy (Attachment 8). The assessing physician will evaluate 97 items divided into the 
following 9 organ/systems domains.

Constitutional

Mucocutaneous

Neuropsychiatric

Musculoskeletal

Cardiorespiratory

Gastrointestinal

Ophthalmic

Renal

Hematological
The assessing physician ought to consider each item as to its presence in the past 4 weeks, and 
answer 0=not present, 1=improving, 2=same, 3=worse, or 4=new as compared with a specified 
reference visit. Each organ/system domain is classified as BILAG A, B, C, D, or E based upon 
organ/system specific items and criteria specific to the domain.
9.2.1.3.
CLASI
Cutaneous lupus erythematosus disease activity will be measured by the CLASI. The CLASI is 
an instrument the assessing physician will use to assess the disease activity and damage caused 
to the skin for CLE patients with or without systemic involvement. The CLASI consists of 
2 scores; the first summarizes the activity of the disease while the second is a measure of the 
damage done by the disease (Attachment 9). Activity is scored on the basis of erythema, 
scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. 
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Damage is scored in terms of dyspigmentation and scarring, including scarring alopecia. The 
scores are calculated by simple addition based on the extent of the symptoms.1 Higher activity 
and damage scores indicate worse disease activity.
9.2.1.4.
Physician Global Assessment of Disease Activity
The physician must complete the Physician Global Assessment of Disease Activity8 independent 
of subjects’ assessment (Attachment 10). The assessments will be recorded on a visual analogue 
scale (VAS; 0 to 10 cm). The scale for the assessment ranges from “no Lupus activity” (0) to 
‘extremely active Lupus” (10).
The physician assessor should preferably be the same person at every study visit for a given 
subject.
9.2.1.5.
Patient Global Assessments
The subject must complete the Patient Global Assessment of Disease Activity and Patient’s 
Assessment of Pain independent of the Physician’s Global Assessment of Disease Activity.
9.2.1.5.1.
Patient Global Assessment of Disease Activity
The Global Assessment of Disease Activity will be recorded on a visual analogue scale (VAS; 0 
to 10 cm). The scale for the assessment ranges from “very well” (0) to “very poor” (10) (see 
Attachment 11).
9.2.1.5.2.
Patient Assessment of Pain
The Patient’s Assessment of Pain is used to assess the patient reported pain intensity. The 
patient's will be asked to assess their average pain during the past week on a visual analogue 
scale (VAS; 0 to 10 cm). The anchors of the instrument include 0 to represent ‘no pain’ and 10 to 
represent ‘the worst possible pain.’
9.2.1.6.
Short-Form-36 
The RAND short-form (SF)-36 questionnaire is a self-administered multi-domain scale with 
36 items. Eight health domains cover a range of functioning (Attachment 12):

Limitations in physical function

Limitations in usual role activities

Bodily pain

General mental health (psychological distress and well-being)

Vitality (energy and fatigue)

Limitations in social functioning due to physical or mental health problems

Limitations in usual role activities due to personal or emotional problems

General health perception
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The subscales are scored from 0 to 100. The scoring yields a Physical Component Summary 
score and a Mental Component Summary score, a total score, and subscale scores. Higher scores 
represent better outcomes. It is appropriate for persons over the age of 14 and may be completed 
in 5 to 10 minutes. Translations are available in most languages; the instrument has undergone 
extensive linguistic and cultural validation. Version 2 acute will be used in the study.
The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, 
allowing comparison of relative burden of different diseases and the benefit of different 
treatments.42 A change of 3 points in any of the subscales or 5 points for the component score is 
associated with clinically meaningful change.27,41,40 The SF-36 has been used extensively in 
clinical trials providing evidence of psychometric properties. Reliability estimates for physical 
and mental component summary scores exceeded 0.90 in early studies21 and have been further 
confirmed in later studies. Construct validation was established through comparison to several 
other generic health surveys.
9.2.1.7.
Fatigue Severity Scale
The Fatigue Severity Scale (FSS) is a 9-item questionnaire designed to assess the severity of 
fatigue and its impact on daily living using 7 response options (1=Completely Disagree, 
7=Completely Agree) during a recall period of the past week (Attachment 13). It can be 
completed within 5 minutes by the subject. Scores above 36 of the total possible score of 63 
reflect increasing severity of fatigue. The scale was developed for use in SLE.19 The scores on 
the scale correlate with patient reported pain, sleep, depression, and with each subscale of the 
SF-36. The FSS has shown a high internal consistency, and differentiates patients from controls 
in studies with SLE subjects. The instrument was translated from the original English version 
and is available in several languages.
9.2.2.
Definitions 
A complete list describing all efficacy evaluations and endpoints, and which evaluations are 
included in the composite endpoints is provided in Attachment 1.
9.2.2.1.
SRI-4
Systemic Lupus Erythematosus Disease Activity Index 2000 SRI-4 response is defined as a 
composite endpoint requiring at least a 4 point reduction in SLEDAI 2K score (Section 9.2.1.1), 
no worsening (˂10 mm increase) from baseline in the Physician’s Global Assessment of Disease 
Activity score (PGA) (Section 9.2.1.4), and no new BILAG Domain A and no more than 1 new 
BILAG Domain B scores (Section 9.2.1.2).9 SRI-5 and SRI-6 are similarly defined with response 
requiring a ≥5 point reduction or ≥6 point reduction in SLEDAI 2K, respectively.SRI-5 and SRI-
6 are similarly defined with response requiring a ≥5 point reduction or ≥6 point reduction in 
SLEDAI-2K, respectively.
9.2.2.2.
BILAG-based Combined Lupus Assessment 
The BILAG-based Combined Lupus Assessment (BICLA) requires patients to meet response 
criteria across 3 assessment tools: (1) the BILAG-2004 index (2) the SLEDAI index and (3) a 
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PGA. Patients are identified as responders or non-responders based upon the following 
requirements:39
Requirements for BICLA Response
BILAG
BILAG improvement classified as:

All BILAG A scores at baseline improved to either BILAG B,C or D

All BILAG B scores at baseline improved to either BILAG C or D

No worsening in disease activity defined as no new BILAG A scores 
and ≤1 new BILAG B score
SLEDAI-2K
No worsening of total SLEDAI-2K from baseline (change ≤0)
PGA
No significant deterioration (<10 mm increase) in 100 mm visual analogue 
PGA
Treatment Failure
No treatment failure (see SAP for definition of treatment failure)
9.2.2.3.
Flares
9.2.2.4.
S2K RI-50 Response
S2K RI-50 response is defined as a decrease of at least 6 points from baseline in the SLEDAI-2K 
score.
9.2.2.5.
No Worsening in PGA
No worsening in PGA is defined as less than a 10 mm increase on 100 mm VAS. 
9.2.3.
Endpoints
Primary Endpoint
The primary endpoint of this study is the proportion of subjects with a composite SRI-4 response 
at Week 24.
Major Secondary Endpoints
The major secondary endpoints are listed in order of importance as specified below:
1.
The change from baseline in SLEDAI-2K at Week 24.
2.
The change from baseline in PGA at Week 24.
3.
The proportion of subjects with BICLA response at Week 24.
Other Endpoints
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SLE Disease activity:
6.
The proportion of subjects with responses in SRI-4, SRI-5, SRI-6, S2K RI-50 response and 
BICLA over time.
7.
 
 
 
9.
The absolute change from baseline in SLEDAI-2K, S2K RI-50, PGA over time.
10. The percent change in serological activity (eg, ANA, anti-dsDNA, other autoantibodies, C3, 
C4) or SLEDAI feature measurements over time.
11.
 
 
 
 
Medications:
16. The proportion of subjects with meaningful changes in selected SLE medications from 
Week 12 through Main Study 8-week Safety Follow-up Visit/Week 48.
17. Change in corticosteroid dose from Week 48 through Week 104 for subjects who participate 
in the study extension.
Development and analyses of the new endpoint(s) will be included in a separated technical 
report.
9.3.
Pharmacokinetics and Immunogenicity
Serum samples will be used to evaluate the pharmacokinetics (PK) of ustekinumab, as well as 
the immunogenicity of ustekinumab (antibodies to ustekinumab). Serum collected for PK and 
immunogenicity analyses may additionally be used to evaluate safety or efficacy aspects that 
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address concerns arising during or after the study period. Genetic analyses will not be performed 
on these serum samples. Subject confidentiality will be maintained.
9.3.1.
Serum Collection and Handling
Venous blood samples will be collected at the time points shown in the Time and Events 
Schedule for the determination of serum ustekinumab concentrations and antibodies to 
ustekinumab. Serum samples will also be collected at the final visit from subjects who terminate 
study participation early. At visits where PK and immunogenicity will be evaluated, 1 blood 
draw of sufficient volume can be used. Each sample will be split into 3 aliquots (1 aliquot for 
serum ustekinumab concentration, 1 aliquot for antibodies to ustekinumab, and 1 aliquot as a 
back-up). Samples must be collected before study drug administration at visits when study drug 
administration is scheduled. The exact dates and times of blood sample collection must be 
recorded in the laboratory requisition form.
Additional information about the collection, handling, and shipment of biological samples can be 
found in the Laboratory Manual.
9.3.2.
Analytical Procedures
Serum samples will be analyzed to determine ustekinumab concentrations using a validated, 
specific, and sensitive immunoassay method by 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 will be detected using a validated immunoassay method in serum 
samples collected from all subjects. Serum 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). All samples will be tested by the Sponsor or Sponsor's designee.
9.4.
Biomarkers
The collection, preparation, storage and shipment of skin biopsies, blood, serum and urine are 
detailed in the Time and Events schedule (Table 1) and the Laboratory Manual. Biomarkers may 
include, but are not limited to, inflammatory markers, RNA, cell surface markers, 
auto-antibodies, T cell and B cell repertoire, target specific markers, and other categories of 
biomarkers potentially involved in the development and the progression of lupus.
Serum Analyses
Serum will be analyzed for levels of specific proteins 
 
 
 
.
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Urine Samples
Urine samples will be evaluated for excreted proteins or other markers believed to have 
relevance in SLE.
Skin Biopsy Analyses
Skin biopsies will be utilized for cellular, molecular, and gene expression analyses.
Whole Blood Gene Expression Analyses
Whole blood will be collected from all subjects for RNA, flow cytometry (samples from selected 
sites will be analyzed at central laboratory or other analytical laboratory), T cell and B cell
repertoire (nucleic acid analyses [RNA and DNA] for specific T and B cell receptors only) and 
epigenetics analysis (eg, DNA methylation).
9.5.
Pharmacogenomic Evaluations
The DNA samples will be used for research related to this study (CNTO1275SLE2001). Specific 
genomic testing will be undertaken for consenting subjects (subjects participating in this portion 
of the study must sign a separate ICF). The procedure will involve taking a blood sample that 
may be analyzed for specific target genes that may play a role in lupus. Any genomic 
assessments will be performed in strict adherence to current subject confidentiality standards for 
genetic testing. Refusal to participate in genomics testing will not result in ineligibility for 
participation in the rest of the clinical study.
9.6.
Serologic Markers
Sample for autoantibodies (including ANA, anti-dsDNA, anti-Smith), complement C3, C4, and 
other analytes will be collected as described in the Table of Events (Table 1) and Section 9.8
Safety Evaluations (Clinical Laboratory Tests).
9.7.
Cutaneous Lupus Substudy
Subjects with cutaneous disease will be evaluated using CLASI scoring. Additionally, subjects 
with cutaneous disease who consent to participate in the cutaneous lupus substudy will have 
additional assessments including collection of skin biopsies (optional consent) prior to study 
agent administration at Week 0 and at Week 24 and/or photographs of a cutaneous lesion or an 
area of active disease (optional consent) to be performed as shown in the Table of Events (Table 
1). There will not be any restrictions on the number of subjects with cutaneous disease who can 
enroll into either the main study or the cutaneous lupus substudy.
Subjects who consent to the optional biopsy collection will have 2 skin biopsies (4 mm) excised 
from an active target lesion at Week 0, followed by 2 additional biopsies of the same lesion 
(regardless of cutaneous disease activity) at Week 24 (Cutaneous Lupus Substudy Manual). Skin 
biopsies will be utilized for cellular, molecular, and gene expression analyses.
Independent of cutaneous biopsy collection, subjects who participate in the cutaneous lupus 
substudy will be requested to provide consent for photographs to be collected from an identified 
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cutaneous lesion or an area of active disease. Consenting subjects with cutaneous lupus 
unsuitable for biopsy (eg, malar rash or alopecia) may be evaluated by photography. The 
photographs are for exploratory purposes only. The photographs will be used to assist in a 
qualitative evaluation of clinical response. The photographs and skin biopsies can target a 
different area of active disease, but the follow-up photographs or biopsies should re-evaluate the 
same area of active disease as originally assessed at week 0. Confidentiality of the subjects 
involved in this study will be maintained; specifically photographs of subjects in this study will 
not be published or otherwise made public without blocking adequate portions of the subject’s 
face or body so that the individual cannot be identified.
9.8.
Safety Evaluations
Safety assessments include vital signs, general physical examinations and skin evaluations
(assessed during S2K RI-50 and CLASI evaluations), adverse events, concomitant medication 
review, pregnancy testing (refer to Section 12.3.3), administration reactions, chemistry and 
hematology laboratory tests, and antibodies to ustekinumab. Chest x-ray and TB, HIV, hepatitis 
B, and hepatitis C testing will be required at time of screening (Table 1). Refer to Section 4.1 for 
tuberculosis screening criteria. Subject diary cards will be used to capture medication changes 
that occur in between study visits through the main portion of the study.
Any clinically significant abnormalities persisting at the end of the study 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 Table 1 and Table 2 for the extended study.
Adverse Events
Adverse events (AE) will be reported by the subject (or, when appropriate, by a caregiver) for 
the duration of the study, and will be followed by the investigator.
Infections
Subjects will be provided an alert card of signs and symptoms for infections, and will be 
instructed to contact the site between scheduled visits should any signs and symptoms occur. At 
each site visit, investigators or other site personnel are required to evaluate subjects for any signs 
or symptoms of infection, and ask about symptoms of infection or other AEs that may have 
occurred in between site visits.
Study agent should not be administered to a subject with a clinically important, active infection. 
Treatment with study agent should be withheld until serious and/or severe infections are 
completely resolved. If a subject develops a serious or severe infection, including but not limited 
to sepsis or pneumonia, discontinuation of study treatment must be considered. Treatment must 
be permanently discontinued for subjects who develop an opportunistic infection. For active 
varicella-zoster infection or a significant exposure to varicella zoster infection in a subject 
without history of chickenpox, the subject should be evaluated for symptoms of infection and if 
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the subject has received appropriate treatment and/or recovered or no symptoms of infection, 
may continue study administration after discussion with the study Sponsor.
Clinical Laboratory Tests 
Blood samples for serum chemistry and hematology will be collected according to the Time and 
Events Schedule (Table 1 and Table 2 for the extended study). The investigator must review the 
laboratory report immediately upon availability, document this review, and record any clinically 
relevant changes occurring during the study in the AE section of the eCRF. Coomb’s direct test, 
urine dipstick, urine sediment microscopy and urine pregnancy test will be performed by site 
staff or the local laboratory. With the approval of the study Sponsor, the use of local laboratories 
may also be allowed in cases where initiation of treatment or safety follow-up is time-critical and 
the central laboratory results are not expected to be available before the need to provide study 
agent treatment or if actions need to be taken for safety reasons.
A one-time retest of screening laboratory test(s) analyzed by the central laboratory will be 
allowed in the event of suspected error in sample collection or analysis performance.

Hematology Panel
-hemoglobin
-hematocrit
-white blood cell (WBC) count with differential (basophils, eosinophils, lymphocytes, 
monocytes, neutrophils)
-platelet count
-CD 19 -cell analyses during screening only if needed for subjects previously 
exposed to cell depleting therapies (Section 4.1.3)
-Coomb’s direct test (local laboratories, if available)

Serology Laboratory
-Ig isotype profile (IgG, IgM, IgA levels)
-C3 and C4 Complement
-ANA
-anti-dsDNA 
-anti-phospholipid antibodies including lupus anticoagulant, anti-cardiolipin, and 
anti-β2-glycoprotein-I antibodies
-other autoantibodies including anti-Smith, anti-Sjögren’s-syndrome-related antigen 
A (SSA [anti-Ro], and B (SSB [anti-La]), anti-ribonucleoprotein (anti-RNP)

Coagulation Labs
-Prothrombin Time 
-Partial Thromboplastin Time 
-International Normalized Ratio 

Serum Chemistry Panel
-sodium
-alkaline phosphatase
-potassium
-calcium
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-chloride
-phosphorous
-bicarbonate
-albumin
-blood urea nitrogen 
-total protein
-creatinine
-creatinine kinase
-glucose 
-aspartate aminotransferase 
-aldolase (if creatine kinase is elevated at 
screening then aldolase test at Week 0 and 
follow-up as needed)
-alanine aminotransferase 
-total bilirubin, and if total bilirubin is 
abnormally elevated, then direct bilirubin, 
and indirect bilirubin

Urine Analyses – Fresh spot urine

Urinalysis using urine dipstick. Urine sample will be further analyzed at 
Central laboratory.

Urinary protein/creatinine ratio9 will be analyzed at the central laboratory
using an aliquot of spot urine collected from subjects.

Urine Sediment Microscopy (Local Laboratory Assessment using spot urine 
samples)
-Red blood cells
-WBC, with note if urinary tract infection is present/absent
-epithelial cells
-crystals
-Red blood cells, WBC, or heme-granular casts
-bacteria

Serum and urine pregnancy testing for women of childbearing potential only

Viral serology (HIV antibody, HBsAg, anti-HBs, anti-HBc total, and hepatitis C virus 
antibody)
Vital Signs
Weight and temperature will be assessed. Blood pressure and heart rate measurements will be 
assessed.
Physical Examination
A full body physical examination will be performed pre-treatment and during the study as shown 
in Table 1 and Table 2 for the extended study.
9.9.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded on the laboratory requisition 
form.
Refer to the Time and Events Schedule (Table 1 and Table 2 for the extended study) for the 
timing and frequency of all sample collections.
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Instructions for the collection, handling, and shipment of samples are found in the laboratory 
manual that will be provided for sample collection and handling.
10.
SUBJECT COMPLETION/WITHDRAWAL
10.1.
Completion
A subject who does not enter into the study extension will be considered to have completed the 
main study if he or she has completed assessments through 16-week safety follow-up of the main 
study. A subject who has enrolled into the study extension will be considered to have completed 
the main portion of this study if he or she has completed assessments through the 8-week safety 
follow-up visit of the main study. Subjects who prematurely discontinue study treatment for any 
reason before the Week 8 or Week 16 safety follow-up visits (from the main study), will not be 
considered to have completed the main portion of the study. A subject who has enrolled into the 
study extension will be considered to have completed the study extension if he or she has 
completed assessments through Week 120.
10.2.
Discontinuation of Study Treatment
If a subject's study treatment must be discontinued before or at Week 40 (for subjects who do not 
participate in the study extension) or before Week 104 (for subjects who do participate in the 
study extension), this will not result in automatic withdrawal of the subject from the study and 
follow-up assessments should be obtained approximately 8 and 16 weeks following the last dose 
of study agent.
A subject's study treatment must be permanently discontinued if any of the following occur:
1.
An AE temporally associated with study agent infusion or 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.
2.
The subject withdraws consent for administration of study agent.
3.
Pregnancy or planning to become pregnant within the study period or within 16 weeks after 
the last study agent injection.
4.
The initiation of prohibited medications or treatments (as per Section 4.3).
5.
Malignancy, with the exception of no more than 2 localized basal cell skin cancers that are 
treated with no evidence of recurrence or residual disease.
6.
An opportunistic infection.
7.
The investigator or Sponsor’s medical monitor deems it is in the subject’s best interest.
8.
The subject is deemed ineligible according to the following TB 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, and cannot or will not continue to undergo additional evaluation.
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
A subject undergoing continued screening has a chest radiograph with evidence of 
current active TB and/or a positive QuantiFERON®-TB Gold test and/or a positive 
tuberculin skin test result in countries in which the QuantiFERON®-TB Gold is not 
approved/registered result and/or an indeterminate QuantiFERON®-TB Gold test result 
on repeat testing, unless active TB can be ruled out and appropriate treatment for latent 
TB can be initiated either prior to or simultaneously with the next administration of 
study agent and continued to completion.

A subject receiving treatment for latent TB discontinues this treatment prematurely or is 
noncompliant with the therapy.
9.
Significant worsening of SLE disease activity from baseline or having high disease activity 
for 2 or more consecutive visits starting at Week 16 based on overall clinical assessments; or 
if a subject requires the addition of a new immunomodulator to the existing treatment 
regimen after Week 16.
In addition, permanent discontinuation of study agent treatment must be considered for subjects
who:

Receive an increase (relative to baseline) in their immunomodulator dose.

Develop any of the following adverse events that are reported as serious or severe: study 
agent infusion reaction, injection-site reaction, or infection.
10.3.
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
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 from this study will not 
be replaced.
A subject who withdraws from the study will have the following options regarding the optional
research samples:

The collected samples will be retained and used in accordance with the subject's original 
informed consent for optional research samples.

The subject may withdraw consent for optional research samples, in which case the samples
will be destroyed and no further testing will take place. To initiate the sample destruction 
process, the investigator must notify the Sponsor study site contact (or appropriate designee) 
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of withdrawal of consent for the optional research samples and to request sample 
destruction. The Sponsor study site contact will, in turn, contact the biomarker 
representative to execute sample destruction. If requested, the investigator will receive 
written confirmation from the Sponsor that the samples have been destroyed.
Withdrawal from the Optional Research Samples While Remaining in the Main Study
The subject may withdraw consent for optional research samples while remaining in the study. In 
such a case, the optional research samples will be destroyed. The sample destruction process will 
proceed as described above.
Withdrawal from the Use of Samples in Future Research
The subject may withdraw consent for use of samples for research (refer to Section 16.2.5, 
Long-Term Retention of Samples for Additional Future Research). In such a case, samples will 
be destroyed after they are no longer needed for the clinical study. Details of the sample 
retention for research are presented in the main ICF and in the separate ICF for optional research 
samples.
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. Specific details will be provided in the Statistical Analysis Plan.
11.1.
Subject Information
For all subjects who receive at least 1 dose of study drug descriptive statistics will be provided 
for demographic data and baseline characteristics, including prior and background SLE 
therapies. All subjects who are randomized and received at least 1 dose of study agent will be 
included in the efficacy analyses according to their assigned treatment group. The safety analysis 
population will include those subjects who received at least 1 dose of study agent, and will be 
analyzed according to the actual study agent received.
11.2.
Sample Size Determination
The sample size calculation is based upon the primary endpoint, proportion of SRI-4 responders 
at Week 24. Approximately 60 subjects treated with ustekinumab and approximately 40 subjects 
with placebo is projected to give approximately 80% power to detect a significant difference in 
response rate compared with placebo (assume 35% and 60% response rates in placebo and 
ustekinumab respectively, which translates to 25% absolute increase over placebo or an odds 
ratio of 2.79) with an alpha level of 0.1. The assumption of a 35% responder rate for placebo is 
based upon a previous study in which a similar SLE population was treated.36 Recent studies 
have shown very high placebo rates in certain regions, thus the power for the study could be 
reduced.14
The power to detect a significant treatment difference at α=0.1 (2-sided) is calculated under
various assumptions (see Table 4).
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Table 4:
Power to Detect a Significant Treatment Difference in the Proportion of Subjects with SRI-4 
Response at Week 24
Proportion of Placebo 
Group with Response (%)
Absolute Increase in 
Response (%)
Proportion of Ustekinumab 
Group with Response (%)
Odds Ratio
Power
20
20
40
2.67
70%
25
45
3.27
85%
30
50
4.00
94%
25
20
45
2.45
67%
25
50
3.00
82%
30
55
3.67
92%
30
20
50
2.33
64%
25
55
2.85
80%
30
60
3.50
91%
35
20
55
2.27
62%
25
60
2.79
79%
30
65
3.45
91%
40
20
60
2.25
62%
25
65
2.79
79%
30
70
3.50
91%
*Note:  SRI-4 response is defined as a ≥ 4 point reduction in SLEDAI-2K score, no new domain scores in either BILAG A or 
BILAG B  and no worsening (˂10 mm increase) from baseline in the PGA.10
11.3.
Efficacy Analyses 
All efficacy analyses will be performed on the modified intent-to-treat (mITT) analysis set. The 
mITT analysis set will include all subjects who are randomized and received at least 1 dose of 
study agent. The efficacy analyses will be calculated according to their assigned treatment group.
11.3.1.
Primary Endpoint Analysis
The primary endpoint of this study is the proportion of subjects with a composite measure of 
SLE disease activity (SRI-4 response) at Week 24 (Section 9.2.2.1). The primary analysis will be 
based upon the primary endpoint and will be conducted on the mITT population, which includes 
all randomized subjects who receive at least 1 dose of study agent, have at least 1 measurement 
prior to the administration, and have at least 1 post-baseline SRI-4 measurement.
Last observation carried forward procedure will be used to impute the missing SRI-4 component 
if the subjects have data for at least 1 SRI-4 component at Week 24. If the subjects do not have 
data for any SRI components at Week 24, the subjects will be considered not to have achieved 
the SRI-4 response. In addition, subjects who meet any 1 of the following criteria will be 
considered to have not achieved the primary endpoint, SRI-4 response at Week 24 (full details 
will be provided in the SAP):

Between the Week 12 visit and the Week 24 visit, either the dose of an immunomodulator is 
higher than at baseline, or a new immunomodulator has been added to the existing treatment 
regimen.

The addition of a new immunomodulator to the existing treatment regimen before Week 12 
and subject still was receiving that immunomodulator after Week 12.
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
Initiate treatment with disallowed dose or disallowed use of oral, IV or IM or other type of 
corticosteroid administration for SLE, or increase the dose of oral corticosteroids for SLE 
above baseline between the Week 12 and 24 visits.

Subjects who were not receiving ARB or ACE inhibitor therapy who then initiated a new 
ARB or ACE inhibitor therapy between Week 12 and Week 24. Subjects who substitute an 
ARB or ACE inhibitor for a comparable medication would not be considered treatment 
failures.

Discontinue study agent due to lack of efficacy for an AE of worsening of SLE prior to 
Week 24.
For subjects who use systemic corticosteroids for another indication, the efficacy measurement 
will be carried forward from the last observation prior to the initiation of the treatment, for the 
period of 2 weeks after initiation of the treatment. After the 2 week period, the subject’s 
calculated value will be as measured.
Other situations may confound the primary endpoint, such as a subject initiating NSAIDs after 
Week 16, or using epidural, IV, IM, IA, or intra-lesional, inhaled corticosteroids, and topical 
medication. Data handling rules will be specified in the Statistical Analysis Plan.
Logistic regression, adjusting for baseline stratifications and baseline SLEDAI, will be used to 
analyze the primary endpoint. The baseline SLEDAI value is defined as the closest non-missing 
measurement taken prior to the Week 0 infusion. If significant non-normality is observed, 
appropriate nonparametric tests will be used to evaluate the differences between treatments.
The study will be considered positive if the primary analysis achieves statistical significance at a 
significance level of 0.1 (2-sided) and ustekinumab shows a positive treatment effect relative to 
placebo treatment.
In addition to the primary analysis, sensitivity analyses will be performed to explore the effects 
with different data handling rules. If it is deemed necessary, the primary endpoint will be 
analyzed on the per protocol population. Details of the inclusion/exclusion rules for per protocol 
population will be provided in the SAP.
Subgroup analysis based on region will be performed. This is due to potential regional 
differences in evaluating efficacy, and high placebo response rates in certain regions. Subgroup 
analysis of the primary endpoint by other selected baseline characteristics will be presented. 
Details will be outlined in the SAP.
11.3.2.
Major Secondary Analyses

The change from baseline in SLEDAI-2K at Week 24.

The change from baseline in PGA at Week 24. 

The proportion of subjects with BICLA response at Week 24.
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Continuous responses will be analyzed using an analysis of covariance model with treatment 
group as a fixed factor and baseline stratifications (eg, regions) as a covariate. Nonparametric 
methods will be adopted when the normality assumption is violated. 
11.3.3.
Other Planned Efficacy Analyses
For the other efficacy endpoints listed in Section 9.2.3, the following statistical methods will be 
applied:
Binary data will be analyzed using the same statistical method as in the primary efficacy 
analysis. Continuous responses will be analyzed using an analysis of covariance model with 
treatment group as a fixed factor and baseline stratifications (eg, regions) as a covariate. 
Nonparametric methods will be adopted when the normality assumption is violated. Log-rank 
tests will be used to compare endpoints defined by time to an event.
11.3.4.
Efficacy Analyses in the Study Extension
Long-term evaluations of efficacy including SRI-4, SLEDAI-2K, PGA, reduction in 
corticosteroid dosing, and evaluations of flare over time will also be performed for those subjects 
who participate in the study extension.
11.4.
Interim Analyses
Interim analyses (IA) will be conducted when approximately 1/3 and 2/3 of subjects reach Week 
24. In the first IA, only evidence for notable efficacy will be assessed. In the second IA, evidence 
for notable efficacy as well as treatment futility will be analyzed. Variations in placebo effect 
across regions will be incorporated into the interim analyses. Details concerning the IAs are 
described in the IA Statistical Analysis Plan.
11.5.
Pharmacokinetic Analyses
Serum ustekinumab concentrations will be summarized for each treatment group over time. 
Descriptive statistics, including arithmetic mean, standard deviation, median, interquartile range, 
minimum, and maximum will be calculated at each sampling time point.
If feasible, a population PK analysis using nonlinear mixed effects modeling may be used to 
characterize the disposition characteristics of ustekinumab in the current study. The influence of 
important variables such as body weight and antibodies to ustekinumab status on the population 
PK parameter estimates may be evaluated. Details will be given in a population PK analysis 
plan, and results of the population PK analysis will be presented in a separate technical report.
11.6.
Immunogenicity Analyses
The incidence and titers of antibodies to ustekinumab will be summarized for subjects who 
received at least 1 administration 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).
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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
The following results from treated and untreated SLE subjects will be summarized:

The concentration of individual serum and urine markers.

Results from selected biomarkers in skin biopsy tissue by RNA-sequencing and 
immunohistochemistry.

Results from whole blood gene expression profiling, flow cytometry, T cell and B cell
repertoire, and epigenetics.

Additional exploratory analyses may be performed following evaluation of the data.
The samples collected from other ongoing clinical studies may also be included in the biomarker 
data analyses. Results of biomarker analyses may be presented in a separate report.
11.8.
Pharmacogenetics Analyses
The DNA research may consist of the analysis of 1 or more candidate genes or of the analysis of 
genetic markers throughout the genome (as appropriate) in relation to this study.
Results of genomic analyses will be presented in a separate report once the overall number of 
samples including those collected from other sources is appropriate.
11.9.
Pharmacokinetic and Pharmacodynamic Analysis
If data permit, the relationships between serum ustekinumab concentration and efficacy or 
pharmacodynamic measures may be analyzed graphically.
11.10. Safety Analyses
Safety analyses will be based on the population of subjects who received at least 1 dose of either 
study agent; subjects will be summarized by the treatment they actually received.
Adverse Events
The verbatim terms used in the CRF by investigators to identify AEs will be coded using the 
Medical Dictionary for Regulatory Activities. All reported AEs with onset during the treatment 
phase (ie, treatment-emergent AEs, and AEs that have worsened since baseline) 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. Routine safety evaluations will be 
performed. Adverse events, serious AEs (SAEs), reasonably related AEs, and AEs by severity 
will be summarized by treatment group.
The incidence and types of infections, infusion reaction, and inject site reactions will be analyzed 
for this study. An infusion reaction is defined as an AE that occurs during or within 1 hour 
following the infusion of study agent, with the exception of laboratory abnormalities.
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Special attention will be given to those subjects who died, or who discontinued treatment due to 
an adverse event, or who experienced a severe or a serious adverse event(eg, summaries, listings, 
and narrative preparation may be provided, as appropriate).
Clinical Laboratory Tests
Laboratory data will be summarized by the type of laboratory test. Reference ranges and 
Common Terminology Criteria for Adverse Events (CTCAE) will be used in the summary of 
laboratory data. Descriptive statistics will be calculated for each laboratory analyte at baseline 
and at each scheduled time point. Changes from baseline results will be presented in pre-versus 
post-treatment cross-tabulations (with classes for below, within, and above normal ranges based 
on laboratory reference ranges). The baseline is defined as the last measurement prior to the first 
dose of the randomized treatment. The number and percentage of subjects by Maximum CTCAE 
Grade will be summarized for each treatment group for each laboratory analyte. The laboratory 
parameters and change from baseline in selected laboratory parameters (hematology and 
chemistry), and the number of subjects with abnormal laboratory parameters (hematology and 
chemistry) based on CTCAE toxicity grading will be summarized treatment group. Listings of 
SAEs will also be provided. All safety analyses will be based on the population of subjects who 
received at least 1 dose of either study agent; subjects will be summarized by the treatment they 
actually received.
Urine protein and creatinine measurements will be used to calculate the urine protein to 
creatinine ratio. Descriptive statistics will be calculated for these ratios at baseline and at each 
scheduled time point.
Vital Signs
Vital sign measures at each scheduled time point and their changes from baseline will be 
summarized using descriptive statistics. The baseline is defined as the last measurement prior to 
the first dose of the randomized treatment.
11.11. Data Monitoring Committee
An independent DMC will be established to monitor data on an ongoing basis to ensure the 
continuing safety of the subjects enrolled in this study and to conduct interim efficacy analysis. 
The committee will meet at least twice to review interim data, including when 1/3 and 2/3 of 
subjects reach Week 24. After each review, the DMC will make a recommendation to the 
Sponsor committee whether the study should be stopped for safety concerns. In the first IA, 
Sponsor will also be notified for notable efficacy in order to advance to next trial. In the second 
IA, Sponsor will be notified for notable efficacy as well as futility. The details will be provided 
in a separate DMC charter and in the IA Statistical Plan.
The DMC will have 3 to 6 members who are independent of the Sponsor. The DMC will consist 
of at least 1 medical expert in the relevant therapeutic area and at least 1 statistician. The DMC 
responsibilities, authorities, and procedures will be documented in its charter.
The DMC will no longer be active after the assessment of the primary endpoint in this study.
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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.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event is any untoward medical occurrence in a clinical study subject administered a 
medicinal (investigational or non-investigational) product. An adverse event does not necessarily 
have a causal relationship with the treatment. An adverse event 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 adverse events starting with the signing of the ICF (refer to 
Section 12.3.1, All Adverse Events, for time of last adverse event recording).
Serious Adverse Event
A serious adverse event 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*
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*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 1 of the other outcomes listed in the definition above. 
These should usually be considered serious.
If a serious and unexpected adverse event occurs for which there is evidence suggesting a causal 
relationship between the study drug and the event (eg, death from anaphylaxis), the event must 
be reported as a serious and unexpected suspected adverse reaction.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An adverse event is considered unlisted if the nature or severity is not consistent with the 
applicable product reference safety information. For ustekinumab, the expectedness of an 
adverse event will be determined by whether or not it is listed in the Investigator's Brochure. For 
ustekinumab with a marketing authorization, the expectedness of an adverse event will be 
determined by whether or not it is listed in the Investigator’s Brochure.
Adverse Event Associated With the Use of the Drug
An adverse event is considered associated with the use of the drug if the attribution is possible, 
probable, or very likely by the definitions.
12.1.2.
Attribution Definitions
Not Related
An adverse event that is not related to the use of the drug.
Doubtful
An adverse event 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 adverse event 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 adverse event 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).
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Very Likely
An adverse event 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.
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).
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)

Adverse events of special interest: any newly identified malignancy, opportunistic infection 
(ie, infection by an organism that normally is not pathogenic or does not cause invasive 
infection in immunocompetent hosts), or case of active TB occurring after the first 
administration of study agent in subjects participating in this clinical trial must be reported 
by the investigator following procedures. 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.
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of a serious adverse event should be recorded on the serious adverse event page 
of the CRF.
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12.3.
Procedures
12.3.1.
All Adverse Events
All adverse events 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). Serious adverse 
events, including those spontaneously reported to the investigator within 16 weeks 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 a serious adverse event will be reported as serious adverse 
events, regardless of whether they are protocol-specific assessments.
All adverse events, 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 adverse event to study therapy. All measures required for adverse event 
management must be recorded in the source document and reported according to Sponsor
instructions.
The Sponsor assumes responsibility for appropriate reporting of adverse events to the regulatory 
authorities. The Sponsor will also report to the investigator (and the head of the investigational 
institute where required) all serious adverse events that are unlisted (unexpected) and associated 
with the use of the study drug. The investigator (or Sponsor where required) must report these 
events to the appropriate Independent Ethics Committee/Institutional Review Board (IEC/IRB) 
that approved the protocol unless otherwise required and documented by the IEC/IRB. 
The subject 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

Any other information that is required to do an emergency breaking of the blind
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12.3.2.
Serious Adverse Events
All serious adverse events 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 serious adverse events 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 a serious 
adverse event should be made by facsimile (fax).
All serious adverse events 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

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 a 
serious adverse event. Any event requiring hospitalization (or prolongation of hospitalization) 
that occurs during the course of a subject's participation in a study must be reported as a serious 
adverse event, except hospitalizations for the following:

Hospitalizations not intended to treat an acute illness or adverse event (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). 
The cause of death of a subject in a study within 16 weeks of the last dose of study drug, whether 
or not the event is expected or associated with the study drug, is considered a serious adverse 
event.
12.3.3.
Pregnancy
All initial reports of pregnancy 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. This includes subject report of a positive home over-the-counter pregnancy test. Abnormal 
pregnancy outcomes (eg, spontaneous abortion, stillbirth, and congenital anomaly) are 
considered serious adverse events and must be reported using the Serious Adverse Event Form. 
Any subject who becomes pregnant during the study must discontinue further study treatment, 
and followed for 4 months after last study dose.
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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.  
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
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 a serious adverse event, the study-site personnel must report the 
PQC to the Sponsor according to the serious adverse event 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
14.1.1.
IV administration
Ustekinumab 5 mg/mL FVP (IV) is supplied as a single-use, sterile solution in 30 mL vials with 
1 dose strength (ie, 130 mg in 26 mL nominal volume). In addition to ustekinumab, the solution 
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contains 10 mM L-histidine, 8.5% (w/v) sucrose, 0.04% (w/v) polysorbate 80, 0.4 mg/mL 
L-methionine, and 20 µg/mL EDTA disodium salt, dihydrate at pH 6.0. No preservatives are 
present.
Placebo for FVP (IV) is supplied as single-use, sterile solution in 30 mL vials with a 26 mL 
nominal volume. The composition of the placebo is 10 mM L-histidine, 8.5% (w/v) sucrose, 
0.04% (w/v) polysorbate 80, 0.4 mg/mL L-methionine, and 20 µg/mL EDTA disodium salt, 
dihydrate at pH 6.0. No preservatives are present.
14.1.2.
SC administration
Ustekinumab will also be supplied as a single-use latex-free PFS in a strength of 90 mg in 1 mL 
nominal volume for SC administration. Each 1 mL of ustekinumab solution in the PFS contains 
90 mg ustekinumab with nominal excipient concentrations of 6.7 mM L-histidine, 7.6% (w/v) 
sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0. No preservatives are present. The needle cover 
on the PFS contains dry natural rubber (a derivative of latex), which may cause allergic reactions 
in individuals sensitive to latex.
Placebo administrations will have the same appearance as the respective ustekinumab 
administrations. Liquid placebo will also be supplied in a 1 mL PFS, and have a composition 
10 mM L-histidine, 8.5% (w/v) sucrose, 0.004% (w/v) polysorbate 80, at pH 6.0. No 
preservatives are present. The needle cover on the PFS contains dry natural rubber (a derivative 
of latex), which may cause allergic reactions in individuals sensitive to latex. 
14.2.
Packaging
The investigational supplies will be uniquely packaged to assure that they are appropriately 
managed throughout the supply chain process.
14.3.
Labeling
Study drug labels will contain information to meet the applicable regulatory requirements. 
14.4.
Preparation, Handling, and Storage
All study agent must be stored at controlled temperatures ranging from 36°F to 46°F (2°C to 
8°C), not frozen, and protected from light. Vigorous shaking of the product should be avoided. 
Prior to administration, the 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.
Study agent in glass vials of PFS will be ready to use. The infusions will be prepared according 
to the subject’s treatment assignment and weight (for weight-range based infusions). The 
pharmacist (or designated personnel) will prepare the required volume of study agent to be 
infused using the appropriate number of vials.
Aseptic procedures must be used during the preparation and administration of the study material. 
Exposure to direct sunlight should be avoided during preparation and administration.
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Refer to the Investigational Product manual for additional guidance on study agent 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, and study drug returned by the subject, 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, or used returned study drug for destruction, 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 infusion bags, needles, syringes and vials 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. Returned study drug must not be dispensed again, even to 
the same subject. 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.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator Brochure 

Package Insert for Ustekinumab

Study site investigational product procedures manual

Central Laboratory manual

Cutaneous lupus substudy manual

Investigational Product manual

PRO questionnaires and efficacy worksheets

IWRS manual 
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
Sample ICF

Subject diary card
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 adverse events of the study, and provide their consent voluntarily will be 
enrolled.
The total blood volume to be collected will be approximately 640 mL per subject over the course 
of the study, which is approximately 1.5 times the amount of a typical blood donation.
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

Subject diary card

Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable
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
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.
Approval for the collection of optional pharmacogenetics samples and / or cutaneous skin 
biopsies 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 adverse events 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 
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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 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) that is/are used 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 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 is authorizing such access, 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 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 the subject'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 
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.
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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 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, pharmacodynamic, biomarker, PK and immunogenicity 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 for PK, immunogenicity and biomarker analyses 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 lupus, to understand differential drug 
responders, and to develop tests/assays related to ustekinumab and lupus. The research may 
begin at any time during the study or the post-study storage period. 
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 10.3, Withdrawal From the Study [Withdrawal From the Use 
of Samples in Future Research]).
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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 course of 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:

Protocol and amendment(s), if any, signed and dated by the principal investigator
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
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 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 adverse events and follow-up of adverse events; 
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 following data will be recorded directly into the CRF and will be considered source data: 

Race

History of smoking 

Blood pressure, temperature, and pulse/heart rate 

Height and weight
The minimum source documentation requirements for Section 4.1, Inclusion Criteria and 
Section 4.1.3, Exclusion Criteria that specify a need for documented medical history are as 
follows:

Referral letter from treating physician or

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]. 
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Electronic Data Capture (eDC) will be used for this study. The study data will be transcribed by 
study-site personnel from the source documents onto an electronic CRF (eCRF), 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 to be the eCRF.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the subject's source documentation. All data relating to the 
study must be recorded in eCRFs prepared by the Sponsor. Data must be entered into eCRFs in 
English. Study site personnel must complete the eCRF 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 who made the initial baseline determinations whenever 
possible. The investigator must verify that all data entries in the eCRFs are accurate and correct.
All eCRF 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 eCRF (if applicable) and complete the query. 
If corrections to the eCRF are needed after the initial entry into the eCRF, 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 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 
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Clinical Trial, and all study documents as specified by the applicable regulatory requirement(s). 
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.
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 into 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.
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. It is important that the study data be recorded promptly in order to 
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facilitate continuous remote monitoring of data, as well as to conduct interim assessments of 
study futility and/or notable efficacy.
Central monitoring will take place for data the identified by the Sponsor as requiring central 
review. 
17.9.
Study Completion/Termination
17.9.1.
Study Completion
The study is considered completed with the last visit for the last subject participating in the 
study. The final data from the study site will be sent to the Sponsor (or designee) after 
completion of the final subject visit 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. 
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.
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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 or exploratory biomarker 
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 with 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 Clinical Study Report 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 Clinical Study Report has been issued will 
be reported in a separate report and will not require a revision of the Clinical Study Report. 
Study subject identifiers will not be used in publication of results. Any work created in 
connection with 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. In the event that 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. 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, 
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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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Riquelme M, et al. Genome-wide association scan in women with systemic lupus erythematosus identifies 
susceptibility variants in ITGAM, PXK, KIAA1542 and other loci. Nat Genet. 2008;40(2):204-210.
17.
Isenberg DA, Rahman A, Allen E, et al. BILAG 2004. Development and initial validation of an updated 
version of the British Isles Lupus Assessment Group’s disease activity index for patients with systemic lupus 
erythematosus. Rheumatology. 2005;44:902-906.
18.
Kim HS, Kim I, Kim JO, Bae JS, Shin HD, Bae SC, No association between interleukin 23 receptor gene 
polymorphisms and systemic lupus erythematosus. Rheumatol Int. 2009;30: 33–38.
19.
Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale: application to patients with 
multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989;46(10);1121-1123.
20.
Linker-Israeli M, Deans RJ, Wallace DJ, et al. Elevated levels of endogenous IL-6 in systemic lupus 
erythematosus. A putative role in pathogenesis. J Immunol. 1991;147:117–123.
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21.
McHorney CA, Ware JE Jr, Lu JF, Sherbourne CD. The MOS 36-item Short-Form Health Survey (SF-36): III. 
Tests of data quality, scaling assumptions, and reliability across diverse patient groups. Med Care.
1994;32(1):40-66.
22.
Navarra SV, Guzmán RM, Gallacher AE, et al. Efficacy and safety of belimumab in patients with active 
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23.
Niewold TB, Hua J, Lehman TJA, Harley JB, Crow MK. High serum IFN-α activity is a heritable risk factor 
for systemic lupus erythematosus. Genes Immuno. 2007, 8(6):492-502.
24.
Oh SH, Roh HJ, Kwon JE, et al. Expression of interleukin-17 is correlated with interferon-α expression in 
cutaneous lesions of lupus erythematosus. Clin Exp Dermatol. 2011;36:512–520.
25.
Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International 
Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 
2012;64(8):2677-2686. 
26.
Qiu F, Song L, Yang N, Li X. Glucocorticoid downregulates expression of IL-12 family cytokines in systemic 
lupus erythematosus patients. Lupus. 2013;22(10):1011-1016.
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28.
Sánchez E, Rueda B, Callejas JL, et al. Analysis of interleukin-23 receptor (IL23R) gene polymorphisms in 
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29.
Sestak AL, Fürnrohr BG, Harley JB, Merrill JT, Namjou B. The genetics of systemic lupus erythematosus and 
implications for targeted therapy. Ann Rheum Dis. 2011;70(S1): i37–i43.
30.
Shah K, Lee WW, Lee SH, et al. Dysregulated balance of Th17 and Th1 cells in systemic lupus erythematosus. 
Arthritis Res Ther. 2010;12:R53.
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Tanasescu CE, Balanescu P, Balanescu R, et al. IL-17 in cutaneous lupus erythematosus. Eur J Intern Med. 
2010;21:202–207.
32.
Touma Z, Gladman DD, Ibanez D, Urowitz MB. Development and initial validation of the systemic lupus 
erythematosus disease activity index 2000 responder index 50. J Rheumatol. 2011; 38:2; 
doi:10.3899/jrheum.100724.
33.
Touma Z, Gladman DD, Urowitz MB. SLEDAI-2K for a 30 day window. Lupus. 2010a;19(1):49-51. Epub 
2009 Nov 12.
34.
Touma Z, Urowitz M, Ibañez D, Gladman D. SLEDAI-2K 10 days versus SLEDAI-2K 30 days in a 
cross-sectional and longitudinal evaluation. Lupus. The 9th International Congress on SLE June 24-27 2010c, 
Vancouver, Canada. Abstract PO2.D.6.
35.
Touma Z; Urowitz M, Gladman D. SLEDAI-2K Responder Index-50 (SRI-50).  Lupus.  The 9th International 
Congress on SLE June 24-27 2010b, Vancouver, Canada. Abstract PO2.D.7.
36.
Van Vollenhoven RF, Petri MA, Cervera R. et al. Belimumab in the treatment of systemic lupus 
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37.
Vincent FB, Northcott M, Hoi A, et al. Clinical associations of serum interleukin-17 in systemic lupus 
erythematosus. Arthritis Res Ther. 2013;15: R97.
38.
Wallace DJ, Strand D, Furie V, et al. Evaluation of Treatment Success in Systemic Lupus Erythematosus 
Clinical Trials: Development of the British Isles Lupus Assessment Group-based Composite Lupus 
Assessment Endpoint. Arthritis Rheum. 2011;63 (S10):S885.
39.
Wallace DJ. Lupus: The essential clinician’s guide. New York, NY: Oxford University Press, Inc; 2008.
40.
Ware JE. SF-36 Health Survey Update. Spine. 2000;25(24):3130-3139.
41.
Ware JE, Kosinski M, Keller SK. SF-36 Physical and Mental Health Summary Scales: A User’s Manual. 
Boston MA. The Health Institute, 1994.
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42.
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item selection. Med Care. 1992;30(6):473-483.
43.
Winchester D, Duffin KC, Hansen C. Response to ustekinumab in a patient with both severe psoriasis and 
hypertrophic cutaneous lupus. Lupus. 2012; 21:1007–1010.
44.
Wong CK, Lit LCW, Tam LS, et al.  Hyperproduction of IL-23 and IL-17 in patients with systemic lupus 
erythematosus: implications for Th17-mediated inflammation in auto-immunity. Clin Immunol. 2008;127: 
385–393.
45.
Yang X, Wang H, Zhao X, et al. Th22, but not Th17 might be a good index to predict the tissue involvement of 
systemic lupus erythematosus. J Clin Immunol. 2013; 33:767–774.
46.
Zhao XF, Pan HF, Yuan H, et al. Increased serum interleukin 17 in patients with systemic lupus 
erythematosus. Mol Biol Rep. 2010;37:81–85.
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ATTACHMENT 1: EFFICACY EVALUATIONS AND ENDPOINTS
Efficacy Evaluations
Description
Composed of Other 
Assessments
BILAG
British Isles Lupus Assessment 
Group
Measure of alterations to therapy consisting of 97 questions in 9 organ 
systems, each put into 1 of 5 categories (A,B,C,D,E) depending on 
presence of items.  Higher scores indicate more disease involvement.
BICLA
BILAG-based Combined Lupus 
Assessment
Composite requiring subjects to meet response criteria across the 
BILAG, PGA and SLEDAI-2K index.
BILAG
PGA
SLEDAI-2K
CLASI
Cutaneous Lupus Erythematosus 
Disease Area and Severity Index
Assesses the disease activity and damage caused to the skin for CLE 
patients.  Scored 0-70 for activity and 0-56 for damage with higher 
scores indicating extremely active Lupus.
 
 
 
FSS
Fatigue Severity Scale
A 9-item questionnaire designed to assess the severity of fatigue and its 
impact on daily living.  Each item scored from 1-7 with higher score 
indicating more severe impact.  Scored 9-63.
Pain VAS
Patients Numeric Rating Scale of 
Pain
Measures the patient’s assessment of pain on a visual analogue scale 
(VAS; 0 to 10 cm). The anchors of the instrument include 0 to represent 
‘no pain’ and 10 to represent ‘the worst pain.’
PGA
Physician’s Global Assessment of 
Disease Activity
Measures the PGA on a VAS scale. Each scored from 0-10 with higher 
scores indicating worse activity.
PtGA
Patient’s Global Assessment of 
Disease Activity
Measures the PtGA on a VAS scale. Each scored from 0-10 with higher 
scores indicating worse activity.
SF-36
RAND Short-Form-36 Health 
Survey
Measures 36 items within 8 health domains.  Scored 0-100 for each 
health concept with higher scores indicating an improved health state.  
In addition, health concepts can be combined into either a physical or 
mental component, also scored 0-100.
SLEDAI-2K
(Baseline)
Systemic Lupus Erythematosus 
Disease Activity Index 2000
Measures 24 features in 9 organ domains over the previous 30 days.  
Scored 0-105 with higher scores indicating more disease activity.
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S2K RI-50
(Follow-up)
SLEDAI-2K Responder Index 50
Measures clinically important 50% reduction in SLEDAI-2K score.
SLEDAI-2K
SRI-4
SLE Responder Index-4
Composite endpoint requiring at least a 4 point reduction in SLEDAI 
2K, no worsening (˂10 mm increase) from baseline in PGA and no new 
BILAG Domain A and no more than 1 new BILAG Domain B scores 
(see Section 9.2.2.1.).
SLEDAI-2K
PGA
BILAG
SRI-5 and SRI-6
SLEDAI 2-K SLE Responder 
Index-5 and SLEDAI 2-K SLE 
Responder Index-6
Same criteria as SRI-4 however the SRI-5 and SRI-6 require at least a 
5 point or 6 point reduction in SLEDAI-2K respectively.
SLEDAI-2K
PGA
BILAG
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ATTACHMENT 2:  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 In Tube 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 3000g.  Following centrifugation, 
plasma is harvested from each tube, frozen, and shipped on dry ice to the central laboratory.  The central 
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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.
Adherence to Local Guidelines
Local country guidelines for immunocompromised patients should be consulted for acceptable anti-
tuberculous 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 3:  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 anti-
tuberculous 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 4:  HBV SCREENING AND MONITORING
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 total 
(HBV core antibody total): 
1)
Subjects who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and 
anti-HBs-) are eligible for this study.
2)
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.
3)
Subjects who test positive only for surface antibody (anti-HBs+) are eligible for 
this study.
4)
Subjects who test positive for surface antigen (HBsAg+) are NOT eligible for this 
study, regardless of the results of other hepatitis B tests.
5)
Subjects who test positive only for core antibody (anti-HBc+) must undergo 
further testing for the presence of hepatitis B virus 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. 
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.  
Eligibility based on hepatitis B virus test results
Hepatitis B test result
Action
Hepatitis B 
surface antigen
(HBsAg)
Hepatitis B 
surface antibody
(anti-HBs)
Hepatitis B core 
antibody
(anti-HBc total)
Include
—
—
—
—
+
—
—
+
+
Exclude
+
— or +
— or +
Require testing for 
presence HBV DNA*
—
—
+
* If HBV DNA is detectable, exclude from the clinical study. If HBV DNA testing 
cannot be performed, or there is evidence of chronic liver disease, exclude from the 
clinical study.  
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ATTACHMENT 5: SLEDAI-2K/S2K RI-50 AT SCREENING VISIT
            
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ATTACHMENT 6: SLEDAI-2K / S2K RI-50 (BASELINE)
       
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ATTACHMENT 7: S2K RI-50 (FOLLOW-UP)
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ATTACHMENT 8: BILAG 2004
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ATTACHMENT 9: CLASI
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ATTACHMENT 10: PHYSICIAN GLOBAL ASSESSMENT OF DISEASE ACTIVITY
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ATTACHMENT 11: PATIENTS GLOBAL ASSESSMENTS OF DISEASE AND PAIN 
ACTIVITY
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ATTACHMENT 12: SF-36
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ATTACHMENT 13: FATIGUE SEVERITY SCALE
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INVESTIGATOR AGREEMENT
NCT0239061

SAP_001.pdf: 
1
Approved, Date: 22 March 2018
Janssen Research & Development 
Statistical Analysis Plan (Week 56 DBL)
A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of 
Ustekinumab in Subjects with Active Systemic Lupus Erythematosus
Protocol CNTO1275SLE2001; Phase 2a
STELARA® (ustekinumab)
Status:
Approved
Date:
22 March 2018
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-ERI-159968603
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.
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Statistical Analysis Plan CNTO1275SLE2001
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TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
AMENDMENT HISTORY.............................................................................................................................. 4
ABBREVIATIONS ........................................................................................................................................ 4
1.
INTRODUCTION.................................................................................................................................. 6
1.1.
Trial Objectives ................................................................................................................................ 6
1.2.
Trial Design ...................................................................................................................................... 6
1.3.
Statistical Hypotheses for Trial Objectives....................................................................................... 8
1.4.
Sample Size Justification ................................................................................................................. 8
1.5.
Randomization and Blinding ............................................................................................................ 8
2.
GENERAL ANALYSIS DEFINITIONS .............................................................................................. 10
2.1.
Visit Windows................................................................................................................................. 10
2.2.
Pooling Algorithm for Analysis Centers.......................................................................................... 10
2.3.
Analysis Sets.................................................................................................................................. 11
2.3.1.
Efficacy Analysis Set(s) .............................................................................................................. 11
2.3.1.1.
Primary Efficacy Analysis Set.................................................................................................. 11
2.3.2.
Safety Analysis Set..................................................................................................................... 11
2.3.3.
Pharmacokinetics Analysis Set(s) .............................................................................................. 11
2.3.4.
Immunogenicity Analysis Set...................................................................................................... 11
2.3.5.
Pharmacodynamics Analysis Set ............................................................................................... 11
2.4.
Definition of Subgroups.................................................................................................................. 11
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 12
4.
SUBJECT INFORMATION................................................................................................................ 12
4.1.
Demographics and Baseline Characteristics ................................................................................. 12
4.2.
Disposition Information................................................................................................................... 12
4.3.
Treatment Compliance................................................................................................................... 12
4.4.
Extent of Exposure......................................................................................................................... 13
4.5.
Protocol Deviations ........................................................................................................................ 13
4.6.
Prior and Concomitant Medications ............................................................................................... 13
5.
EFFICACY ......................................................................................................................................... 13
5.1.
Analysis Specifications................................................................................................................... 13
5.1.1.
Level of Significance................................................................................................................... 13
5.1.2.
Data Handling Rules................................................................................................................... 14
5.1.3.
General Analysis Methods.......................................................................................................... 14
5.1.4.
Treatment Failure Criteria........................................................................................................... 14
5.1.5.
Estimands ................................................................................................................................... 15
5.2.
Efficacy Variable(s) ........................................................................................................................ 16
5.2.1.
Definitions ................................................................................................................................... 17
5.2.2.
Analysis Methods........................................................................................................................ 21
6.
SAFETY............................................................................................................................................. 22
6.1.
Adverse Events .............................................................................................................................. 22
6.2.
Clinical Laboratory Tests................................................................................................................ 24
6.3.
Vital Signs and Physical Examination Findings ............................................................................. 24
6.4.
Electrocardiogram.......................................................................................................................... 25
7.
PHARMACOKINETICS/IMMUNOGENICITY/PHARMACODYNAMICS .......................................... 25
7.1.
Pharmacokinetics........................................................................................................................... 25
7.2.
Immunogenicity (Antibodies to ustekinumab) ................................................................................ 26
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7.3.
Pharmacodynamics........................................................................................................................ 26
7.4.
Pharmacokinetic/Pharmacodynamic Relationships....................................................................... 27
8.
HEALTH ECONOMICS ..................................................................................................................... 27
REFERENCES............................................................................................................................................ 28
APPROVALS.............................................................................................................................................. 29
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AMENDMENT HISTORY
SLEDAI 2K SRI-4:
Note that the definition of the primary endpoint, SRI-4 response, has been updated from the Week 24 
SAP.  The following changes were adopted:
Week 24 SRI-4 Response:  Defined as ≥ 4-point reduction from baseline in SLEDAI-2K score, no new 
domain scores in either BILAG A or BILAG B and no worsening from baseline in the physician’s 
global assessment of disease activity.2
Week 56 SRI-4 Response:  Defined as ≥ 4-point reduction from baseline in SLEDAI-2K score, no new 
BILAG A and no more than 1 new BILAG B domain scores, and no worsening from baseline in the 
physician’s global assessment of disease activity.2
All analyses at the Week 56 DBL are based upon the Week 56 SRI-4 definition.
Treatment Failure Rules:
Note that treatment failure rules were updated from the Week 24 SAP.  The following changes were 
adopted:
The Week 24 SAP did not allow for replacement immunomodulator therapy, similar to the allowance for 
replace of immunomodulators (i.e. dose equivalent replacement).  The Week 56 SAP has been updated to 
allow a replacement immunomodulator as long as the dose equivalent is the same or less than the current 
immunomodulator.
ABBREVIATIONS
ACE
angiotensin-converting enzyme
AE
adverse event
ALT
alanine aminotransferase
ANCOVA
Analysis of Covariance
APAC
Asia Pacific
ARB
Angiotensin II receptor blocker
AST
aspartate aminotransferase
ATC
Anatomical Therapeutic Chemical
AUC
area under the curve
AZA/6 MP
Azathioprine / 6-mercaptopurine
NSAIDS
nonsteroidal anti-inflammatory drugs
BICLA
BILAG-based Combined Lupus Assessment
BILAG
BMI
BP
CI
The British Isles Lupus Assessment Group 
body mass index
blood pressure
confidence interval
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CRF
case report form
DBL
database lock
DMC
Data Monitoring Committee
DPS
Data Presentation Specifications
eCRF
electronic case report form
EEU
Eastern European Union
FDA
Food and Drug Administration
FSS
Fatigue Severity Scale
HR
heart rate
IA
Interim Analysis
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IAC
Interim Analysis Committee
ICF
informed consent form
IQ
IV
IWRS
interquartile
intravenous
interactive web response system
LA
Latin America
 
LN
Lupus Nephritis
LOCF
last observation carried forward
mITT
modified intent to treat
MMF
mycophenolate mofetil
MPA
mycophenolic acid
MTX
methotrexate
NCI CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
NSAID
non-steroidal anti-inflammatory drug
P/C
protein/creatinine ratio
PBO
PD
PGA
RBC
S2K RI-50
SAE
SAP
placebo
pharmacodynamics 
Physicians Global Assessment
red blood cells
SLEDAI-2K Responder Index
Serious Adverse Event
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
SF-36
Short-form 36 questionnaire
SLE
Systemic lupus erythematosus
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
SLICC
Systemic Lupus International Collaborating Clinics
SRI
Systemic Lupus Erythematosus Responder Index
TEAE
treatment emergent adverse event
US
Unites States
VAS
Visual Analogue Scale
WBC
white blood cells
WEU
Western European Union
WHO
World Health Organization
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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, tolerability, pharmacokinetics (PK), 
pharmacodynamics (PD) and immunogenicity of ustekinumab.  This Week 56 SAP is specific to 
the Week 56 database lock (DBL) for the CNTO1275SLE2001 study.
The primary DBL for the CNTO1275SLE2001 study occurred at Week 24 and the details of the 
Week 24 analyses were included in a separate SAP.  The analyses for the Week 56 DBL are to 
evaluate safety and durability of effect through Week 56 (i.e. the end of the study).
1.1.
Trial Objectives
Primary Objectives
The primary objectives are:

To evaluate the efficacy of ustekinumab in the reduction of signs and symptoms of 
systemic lupus erythematosus (SLE) as measured by the SLE Responder Index (SRI-4) 
response rate at Week 24.
Secondary Objectives
The secondary objectives are to evaluate:

The safety and tolerability of ustekinumab in SLE.

The effect of ustekinumab administration on health-related quality of life in subjects with 
SLE.

Pharmacokinetics and immunogenicity of ustekinumab in subjects with active SLE.

The effects of ustekinumab on cutaneous manifestations of SLE.
Exploratory Objectives
The exploratory objectives are to evaluate:       

Biomarkers related to lupus disease (genetic, systemic, and skin-related).

Additional composite clinical endpoints or methods of calculation of clinical response 
with potential for greater sensitivity to improvement and/or worsening of SLE.
1.2.
Trial Design
CNTO1275SLE2001 is a Phase 2a, proof-of-concept, multicenter, randomized, double-blind, 
placebo-controlled study of the efficacy and safety of ustekinumab compared with placebo in 
subjects with active SLE. Enrolled subjects are expected to have active disease (SLICC 
classification criteria, SLEDAI score ≥6, ANA and/or anti-dsDNA positivity as well as 1 BILAG 
A and/or 2 BILAG B scores) despite conventional treatment with standard lupus therapy 
(corticosteroids, anti-malarial drugs, non-steroidal anti-inflammatory drugs (NSAIDs), and/or 
immunosuppressive drugs). 
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Approximately 100 subjects will be randomly assigned in a 3:2 ratio to receive either intravenous 
(IV) ustekinumab 6 mg/kg or IV placebo initially at Week 0 followed by continued treatment 
with subcutaneous (SC) ustekinumab 90 mg or placebo at Weeks 8 and 16.  Subjects with 
cutaneous disease who sign a separate informed consent form (ICF) will be enrolled in the 
cutaneous lupus sub-study for additional assessments including photographs of skin lesions 
(optional consent) and/or collection of skin biopsies (optional consent) to be performed prior to 
study agent administration at Week 0 and at Week 24.  There will not be any restrictions on the 
number of subjects with cutaneous disease who can enroll into either the main study or the 
cutaneous lupus sub study. Dynamic randomization will be utilized in this study to balance as 
best as possible the distribution of subjects to achieve the randomization ratio at both the study 
level and within each stratification factor: skin biopsy, presence of lupus nephritis, baseline SLE 
use and SLEDAI score (combined factor), site/region and race.  
At Week 24, subjects receiving placebo will crossover and all subjects will then receive SC 
ustekinumab 90 mg at Weeks 24, 32, and 40 in a blinded fashion followed by 16 weeks of safety 
follow-up through Week 56 (i.e. more than 5 half-lives) after last SC administration. 
Interim efficacy and safety analyses (IA) were conducted when approximately 1/3 and 2/3 of 
subjects reached Week 24. In the first IA, safety and an interim assessment of feasibility were 
assessed for the purpose of advising the study sponsor whether marked efficacy was observed, 
thus providing an early indicator to advance planning for a Phase 3 clinical trial in this 
indication. In the second IA, safety and evidence of marked efficacy as well as futility were
analyzed. Database locks (DBLs) were to occur at Weeks 24 and 56.
A diagram of the study design is provided in Figure 1.
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Figure 1:  Study Design Schema
1.3.
Statistical Hypotheses for Trial Objectives
The hypothesis is that ustekinumab is significantly superior to placebo as measured by the 
Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Responder Index 
(SRI-4) composite measure at Week 24.
There is no formal statistical hypothesis testing for the Week 56 DBL.  The data from the Week 
56 DBL are supportive to Week 24 and will evaluate longer term safety and durability of effect.
1.4.
Sample Size Justification
The overall study sample size calculation was based upon the proportion of SRI responders at 
Week 24.  To have approximately 80% power to detect a clinically significant odds ratio in the 
group proportions of 2.79, corresponding to a clinically significant increase in responders of 25% 
(35% placebo and 60% active) using a 2-sided Z-test at a 0.1 level of significance with pooled 
variance, 60 subjects with active treatment and 40 subjects with placebo are required. The 
assumption of a 35% responder rate for placebo is based upon a previous study in which a 
similar SLE population was treated.1
1.5.
Randomization and Blinding
Randomization
The study employed an adaptive design using continuous enrollment. Dynamic randomization
was used to randomize subjects to treatment group stratified by the following factors:  
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
collection of cutaneous skin biopsy (Y/N)

presence of Lupus Nephritis (Y/N)

composite of baseline SLE medications and SLEDAI score (high medications and 
SLEDAI ≥ 10, high medications and SLEDAI < 10, medium medications and SLEDAI ≥ 
10, medium medications and SLEDAI < 10)
o
High medications defined as ≥ 15 mg/wk MTX, or ≥ 1.5 mg/kg/day AZA/6-MP, 
or  ≥ 1.5 g/day MMF/MPA, and/or ≥ 15mg/day prednisolone or equivalent 
o
Medium medications defined as < 15 mg/wk MTX, or < 1.5 mg/kg/day AZA/6-
MP, or < 1.5 g/day MMF/MPA, and/or < 15 mg/day prednisolone or equivalent 

site/region

race (white, black, not white or black)
Dynamic randomization was utilized to balance these features as best as possible and is 
described in detail in the Interactive Web Response System (IWRS) randomization specification 
documents.
Approximately 100 subjects were to be randomly assigned in a 3:2 ratio to receive either IV 
ustekinumab 6 mg/kg or IV placebo initially at Week 0 followed by continued treatment with SC 
ustekinumab 90 mg or placebo at Weeks 8 and 16.  The interactive web response system (IWRS) 
assigned a unique treatment code based upon the best possible balance of these stratification 
factors, which dictated the treatment assignment and matching study drug kit for the subject. The 
requestor used his or her own user identification and personal identification number when 
contacting the IWRS, and then gave the relevant subject details to uniquely identify the subject.
Blinding
Blinded treatment was used to reduce potential bias during data collection and evaluation of 
clinical endpoints as well as adverse events. Subjects received either ustekinumab (6 mg/kg IV 
followed by 90 mg SC) or its matching placebo through week 16 dosing, then all subjects 
received active treatment from week 24 through week 40.
The investigator was not provided with randomization codes. The codes were maintained within 
the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual subject.
Data that may potentially unblind the treatment assignment (i.e., study agent serum 
concentrations, study agent preparation/accountability data, treatment allocation, biomarker or 
other specific laboratory data) was handled with special care to ensure that the integrity of the 
blind was maintained and the potential for bias is minimized. This can include making special 
provisions, such as segregating the data in question from view by the investigators, clinical team, 
or others as appropriate until the time of end of study database lock (DBL) and unblinding.
Under normal circumstances and unless otherwise stated, the original treatment blind should not 
be broken until all subjects have completed the study at Week 56 or terminated study 
participation and the database is finalized. Otherwise, the blind should be broken only if specific 
emergency treatment/course of action would be dictated by knowing the treatment status of the 
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subject. In such cases, the investigator may in an emergency determine the identity of the 
treatment by contacting the IWRS. It is recommended that the investigator contact the sponsor or 
its designee if possible to discuss the particular situation, before breaking the blind. Telephone 
contact with the sponsor or its designee will be available 24 hours per day, 7 days per week. In 
the event the blind is broken, the sponsor must be informed as soon as possible. The date and 
reason for the unblinding must be documented by the IWRS, and/or in the appropriate section of 
the electronic case report form (eCRF). The documentation received from the IWRS indicating 
the code break must be retained with the subject's source documents in a secure manner.
The Data Monitoring Committee (DMC) and Statistical Support Group (SSG) may be unblinded 
to subject treatment groups.  The contents of the unblinded data to which the DMC and SSG 
have access should not be divulged, in any way, to members of the study team or to any 
members of the Sponsor Committee unless specifically requested by the Sponsor Committee 
Chairperson until the study has completed.
Subjects who have had their treatment assignment unblinded should continue to return for 
scheduled evaluations.
In general, randomization codes will be disclosed fully only if the study is completed and the 
clinical database is closed. For the specified interim analyses, the randomization codes and the 
translation of randomization codes into treatment and control groups will be disclosed to those 
authorized as detailed in the DMC Charter.  The Sponsor will be blinded through the Week 24 
evaluation and until the database is cleaned and finalized for Week 24 planned analyses.  The 
clinical site, subjects, investigators, and site personnel will remain blinded through the end of the 
study until Week 56 data are finalized.  
2.
GENERAL ANALYSIS DEFINITIONS
2.1.
Visit Windows
Nominal visits will be used for all by visit analyses. The study visits scheduled after 
randomization should occur at the times delineated in the Time and Events Schedule. 
2.2.
Pooling Algorithm for Analysis Centers
Data from all investigational centers/sites will be pooled for analyses since analyses will not be 
adjusted for investigator site.
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2.3.
Analysis Sets
2.3.1.
Efficacy Analysis Set(s)
2.3.1.1.
Primary Efficacy Analysis Set
The primary efficacy analysis set will be based upon the Full Analysis Set (FAS) defined as 
randomized subjects who receive at least 1 dose (partial or complete, IV or SC) of ustekinumab 
or placebo.  Subjects will be analyzed according to their randomized treatment group.
2.3.2.
Safety Analysis Set
The safety analysis set is defined as the set of all randomized subjects who have received at least 
1 dose (partial or complete, IV or SC) of ustekinumab or placebo.  Subjects will be analyzed 
according to the actual treatment received.  Randomized subjects confirmed not to have taken 
any study medication will not be included in the safety analysis set.
2.3.3.
Pharmacokinetics Analysis Set(s)
The PK analysis set is defined as all subjects who received at least 1 complete dose of 
ustekinumab and have at least one post initial dose sample collection with measureable 
concentrations.  Subjects will be analyzed according to the actual treatment received.
2.3.4.
Immunogenicity Analysis Set
The immunogenicity analysis set is defined as all subjects who received at least 1 dose (partial or 
complete) of ustekinumab and have at least one post initial dose sample collection.  Subjects will 
be analyzed according to the actual treatment received.
2.3.5.
Pharmacodynamics Analysis Set
The PD analysis set is defined as all subjects who received at least one dose (complete or partial, 
IV or SC) of study agent.  Subjects will be analyzed according to the actual treatment received.
2.4.
Definition of Subgroups
To evaluate the consistency of the proportion of subjects with SRI-4 composite response at Week 
48, subgroup analyses may be performed on the following subgroups of baseline characteristics:
1. Region (APAC, LA, EEU, WEU, US)
2. Race
3. Ethnicity (Hispanic or Latino, Not Hispanic or Latino)
4. SLEDAI-2K Score (< Median, ≥ Median)
5. PGA Score (< Median, ≥ Median)
6. Renal disease presence (Y, N)
7. P/C Ratio (< Median, ≥ Median)
8. SLE Medications (High dose, Medium dose)
9. Age (18-25, 26-55, Over 55)
10. Body Weight (≥ 35 and ≤ 55, > 55 and  ≤ 85, > 85)
11. Baseline OCS Use
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3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
Details of the Data Monitoring Committee safety reviews and interim analysis assessments are 
included in a separate DMC SAP.  The DMC SAP contains definitions of analysis sets, derived 
variables, scope and objects of the DMC, data-cutoff points, statistical methods and output to be 
produced for the safety reviews and interim analyses of efficacy as required by the DMC 
Charter.  Additionally, a dedicated DMC Data Presentation Specifications (DPS) document 
details output and programming specifications.
4.
SUBJECT INFORMATION
4.1.
Demographics and Baseline Characteristics
Demographics and baseline characteristics will be summarized based upon the randomized 
analysis set.  Descriptive statistics (mean, standard deviation, median, and range) will be 
provided for the subjects’ age and baseline factors including SLEDAI-2K score, PGA score, 
weight and height, Body Mass Index (BMI), Fatigue Severity Score (FSS), SF-36 physical and 
mental component summary, number of joints with pain and inflammation, number of joints with 
pain, number of joints with inflammation, CLASI damage and activity score, disease duration in 
months, BILAG index total, antinuclear antibodies, anti-double stranded DNA and SLE 
medications.  Subjects’ sex, race, ethnicity, region, baseline BILAG categories, baseline P/C 
ratio, number of subjects with serum creatinine above normal, number of subjects with Lupus 
Nephritis at baseline, Smith antibody presence and number of subjects with low complement will 
be summarized as frequency distributions by treatment group.  Prior and concomitant 
medications used at baseline will be listed.
Age will be calculated as (date of informed consent – date of birth + 1) / 365.25 in units of years.
BMI will be calculated as weight/height2 with units of kg/m2.
4.2.
Disposition Information
Disposition information will be summarized by treatment group in terms of numbers of subjects 
randomized, treated, and completing scheduled visits.  Disposition information will be based 
upon the randomized analysis set. The number of subjects who enrolled in the study extension 
will be summarized.  Additionally, the number of subjects who discontinued study agent and the 
reason for discontinuation as well as those who terminated the study and reason for termination 
will be summarized.
4.3.
Treatment Compliance
Study agent will be administered as an IV (initial dose) and SC injection by an authorized and 
qualitied staff and the details of each administration will be recorded in the electronic case report 
form (eCRF) including date, start and stop times for infusion and start time for injection.  
Compliance with the treatment assignments will be controlled by the study site personnel.
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4.4.
Extent of Exposure
The number of subjects exposed to study agent, the number of administrations of study agent, 
and cumulative dose of study agent will be summarized by actual treatment group.
4.5.
Protocol Deviations
Major protocol deviations will be tabulated by treatment group as defined in the following 
categories:

Subjects who entered but did not satisfy entry criteria

Subjects who received the wrong treatment of incorrect dose

Subjects who developed withdrawal criteria but were not withdrawn

Subjects who received a disallowed concomitant medication

Other deviations (e.g. study procedures out of window visit, missed visits for reasons 
other than AEs, unblinding error, actions deemed as major deviations by the study team)
4.6.
Prior and Concomitant Medications
Background medication use for active SLE will be summarized by treatment group.  Subjects 
initiating new or altering dose (increasing or decreasing) of medication for active SLE during the 
study will be summarized over time.  Subjects with increases in medication will be listed.
Prior and concomitant medications will be coded according to the World Health Organization 
(WHO) encoding dictionary, and the number and percent of subjects receiving each medication 
in each treatment group will be summarized by Level 3 Anatomical Therapeutic Chemical 
Classification (ATC) code (first four numbers in the code). 
5.
EFFICACY
5.1.
Analysis Specifications
5.1.1.
Level of Significance
Unless otherwise stated, statistical significance is set to 2 sided α-level of 0.10 as per protocol.  
Where appropriate, 90% confidence intervals will be provided.
Two interim analyses on the primary endpoint were performed when 1/3 (approximately 33 
subjects) and 2/3 (approximately 66 subjects) of the subjects reached their Week 24 visit. Per 
protocol, the study was not to be stopped for efficacy at interims.
At the Week 24 primary DBL, the primary and major secondary endpoints were tested 
sequentially according to the order specified in the protocol. If previous endpoint proved not 
statistically significant, subsequent endpoint(s) were not to be tested and nominal p-values were 
provided. 
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5.1.2.
Data Handling Rules
Missing Data Rules:  Unless otherwise specified, in situations with the presence of missing data 
(e.g. lost to follow-up, missed study visit) the following rules will apply:
Missing baseline value:  No imputation will be performed for missing baseline values.  
Subjects missing values for any subgroup parameters (defined in Section 2.4) at baseline will be 
excluded from the subgroup analysis.
Continuous endpoints:  

No imputation will be performed for missing post-baseline continuous values. Missing 
continuous endpoints tested at Week 24 will be adjusted for in the statistical model (i.e. 
Mixed effect Model Repeated Measures) 
Binary endpoints:   

For primary and major secondary composite binary endpoints (SRI, BICLA), non-
responder imputation will be performed for missing post-baseline response values.

For any other binary endpoints tested, missing data will be imputed using multiple 
imputation methods (MI).  If the missing data is not monotone, a Markov chain Monte 
Carlo (MCMC) method will be used first to effectively make the missing pattern 
monotone.  For monotone missing data, a serial logistic regression method will be used.  
The imputation models will include treatment group and baseline SLEDAI as a covariate.       
5.1.3.
General Analysis Methods
Descriptive statistics (e.g. mean, median, standard deviation, interquartile range, minimum, 
maximum) will be used to summarize continuous variables.  Counts and percentages will be used 
to summarize categorical variables.  Recurrence data will be summarized by mean as well as 
counts and percentages.  Median will be reported for time to event variables. Graphical displays 
will also be used to present the data.
5.1.4.
Treatment Failure Criteria
Treatment Failure Criteria:  Subjects who have 1 or more of the following events will be 
defined as treatment failures:
Non-biologic Immunomodulators (Mycophenolate mofetil [MMF], Mycophenolic acid [MPA], 
Azathioprine [AZA], 6-mercaptopurine [6-MP], Methotrexate [MTX])

Between the Week 12 and the Week 24 visit either; (a) the dose of an immunomodulator 
is higher than at baseline, or (b) a new immunomodulator (not present at randomization) 
has been added to the existing treatment regimen and this immunomodulator does NOT 
replace a current immunomodulator (i.e. dose equivalent is equal or less than current 
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dose) of similar mechanism of action (e.g. MMF substitution for MPA or vice versa, 
AZA substitution for 6-MP or vice versa)

There was addition of a new immunomodulator to the existing treatment regimen before 
Week 12 and the subject still was receiving that immunomodulator after Week 12 and 
this immunomodulator does NOT replace a current immunomodulator (i.e. dose 
equivalent is equal or less than current dose) of similar mechanism of action (e.g. MMF 
substitution for MPA or vice versa, AZA substitution for 6-MP or vice versa)
Antimalarials

Between the Week 12 and the Week 24 visit either; (a) the dose of an antimalarial is 
higher than at baseline, or (b) a new antimalarial (not present at randomization) has been 
added to the existing treatment regimen and this antimalarial does NOT replace a current 
antimalarial (i.e. dose equivalent is equal or less than current dose) 

There was addition of a new antimalarial to the existing treatment regimen before Week 
12 and the subject still was receiving that antimalarial after Week 12 and this antimalarial
does NOT replace a current antimalarial (i.e. dose equivalent is equal or less than current 
dose)
Glucocorticoids

Between the Week 12 and Week 24 visit, initiation of treatment with (a) disallowed dose 
or (b) disallowed use of oral, IV or IM or other type of corticosteroid, for SLE or (c) 
increased the dose of oral corticosteroids for SLE above baseline.
Angiotensin II Receptor Blocker or Angiotensin-Converting Enzyme

Initiation of new angiotensin II receptor blocker (ARB) or angiotensin-converting 
enzyme (ACE) inhibitor therapy after the first dose of study agent and before Week 24 
and this medication does NOT replace a current ARB or ACE respectively. 
Discontinuation

Discontinuation of study agent due to lack of efficacy or for an AE of worsening of SLE 
prior to Week 24
Treatment failure rules will NOT be applied after a subject discontinues study agent (i.e. after the 
date of discontinuation of study agent.)
5.1.5.
Estimands  
The Composite Estimand is defined by the following:

Population:  Subjects in the FAS with active SLE despite receiving one or more standard-
of-care treatments.

Variable:  Proportion of SRI-4 composite response

Intercurrent event:  The following intercurrent events to be taken into account:
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1. It a subject takes rescue medication or discontinues treatment (see treatment 
failure rules for details), assume non-response from the point of treatment failure 
onward
2. If a subject is lost to follow-up, assume non-response from the point of loss to 
follow-up onward

Population-level summary:  Proportion of subjects achieving SRI-4 composite response
The Hypothetical Estimand is defined by the following:

Population:  Subjects in the FAS with active SLE despite receiving one or more standard-
of-care treatments.

Variable:  Proportion of SRI-4 composite response

Intercurrent event:  The following intercurrent events to be taken into account:
1. It a subject takes rescue medication or discontinues treatment (see treatment 
failure rules for details), do not assume non-response and instead assume missing 
values
2. If a subject is lost to follow-up, do not assume non-response and instead assume 
missing 

Population-level summary:  Proportion of subjects achieving SRI-4 composite response
The Treatment Policy (deFacto) Estimand is defined by the following:

Population:  Subjects in the FAS with active SLE despite receiving one or more standard-
of-care treatments.

Variable:  Proportion of SRI-4 composite response

Intercurrent event:  The occurrence of an intercurrent event is irrelevant.  All observed 
values will be used regardless of occurrence of an intercurrent event.
1. All observed values will be used regardless of occurrence of an intercurrent event.
2. If a subject is lost to follow-up, no imputation is performed

Population-level summary:  Proportion of subjects achieving SRI-4 composite response.
5.2.
Efficacy Variable(s)

 
 
SLE Disease Activity:

The proportion of subjects with responses in SRI-4, SRI-5, SRI-6, SRI-7, SRI-8, S2K RI-
50 response and BICLA over time
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
 

The absolute change from baseline in SLEDAI-2K, S2K RI-50, PGA over time

The percent change from baseline in serological activity (eg, ANA, anti-dsDNA, other 
autoantibodies, C3, C4) or SLEDAI-2K feature measurements over time



The change from baseline in active, tender, and swollen joint counts in subjects with joint 
disease over time


  
   
 
 
 
Medications:

The proportion of subjects with meaningful changes in selected SLE medications over 
time
5.2.1.
Definitions
SLEDAI 2K SRI-4 (Modified): This version was used in the Week 24 DBL and will NOT be 
applied to Week 56 SRI analyses.  Defined as ≥ 4-point reduction from baseline in SLEDAI-2K 
score, no new domain scores in either BILAG A or BILAG B and no worsening from baseline 
in the physician’s global assessment of disease activity. (see Week 24 SAP) 
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SLEDAI 2K SRI-4: This version will be used in all Week 56 SRI analyses.  Defined as ≥ 4-point 
reduction from baseline in SLEDAI-2K score, no new BILAG A and no more than 1 new 
BILAG B domain scores, and no worsening from baseline in the physician’s global assessment 
of disease activity.2
Composite response is defined as subjects who achieve SRI-4 response and do not meet the 
treatment failure criteria prior to the analysis time point (e.g. prior to Week 24 for the primary 
endpoint)
SLEDAI-2K SRI-5, SRI-6, SRI-7 and SRI-8 are similarly defined as above with response 
requiring a ≥ 5-point, ≥ 6-point, ≥ 7-point or ≥ 8-point reduction from baseline in SLEDAI-2K 
score respectively. Subjects evaluable for SRI-5 through SRI-8 response will include subjects 
with a baseline SLEDAI score of at least 5 through 8 respectively.
SLEDAI-2K: The SLE disease activity index 2000 (SLEDAI-2K is an established, validated 
SLE activity index.  It is based on the presence of 24 features in 9 organ systems and measures 
disease activity in SLE patients in the previous 30 days. It is weighted according to the feature. 
Features are scored by the assessing physician if present within the last 30 days with more severe 
features having higher scores, and then simply added to determine the total SLEDAI 2K score, 
which ranges from 0 to 105.3 The baseline measurement for the SLEDAI is defined as the closest 
measurement taken prior to the initiation of the Week 0 administration, unless otherwise 
specified.
BILAG:  The BILAG4,5 index scores subjects based on the need for alterations or intensification 
of therapy.  The assessing physician will evaluate 97 items divided into 9 organ system domains.  
The physician considers presence of each item in the past 4 weeks and answers 0=not present, 
1=improving, 2=same, 3=worse, or 4=new.  Each organ/system domain is classified as BILAG 
A, B, C, D, or E based upon criteria specific to the domain.  The baseline measurement for the 
BILAG is defined as the worst (highest) measurement at any time prior to the initiation of the 
Week 0 administration, unless otherwise specified. The baseline measurement for the BILAG is 
defined as the closest measurement taken during the study prior to the initiation of the Week 0 
administration, unless otherwise specified.  
PGA: The Physician’s Global Assessment of Disease Activity6 independent of subjects’ 
assessment is recorded on a visual analogue scale (VAS; 0 to 10 cm). The scale for the 
assessments range for ‘no Lupus activity’ (0) to ‘extremely active Lupus’ (10). No worsening in 
PGA is defined as less than a 10 mm increase from baseline on 100 mm VAS.  The baseline 
measurement for the PGA is defined as the closest measurement taken prior to the initiation of 
the Week 0 administration, unless otherwise specified.
BICLA:  The BILAG-based Combined Lupus Assessment (BICLA) requires patients to meet 
response criteria across 3 assessment tools: (1) the BILAG-2004 index (2) the SLEDAI index 
and (3) a PGA. Patients are identified as responders or non-responders based upon the following 
requirements: 7
Table 2:  BICLA Response Criteria
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Requirements for BICLA Response (BILAG + SLEDAI-2K + PGA + Treatment Failure criteria must be 
met)
BILAG
BILAG improvement classified as:

All BILAG A scores at baseline improved to either BILAG B, C or D

All BILAG B scores at baseline improved to either BILAG C or D

No worsening in disease activity defined as no new BILAG A scores 
and ≤1 new BILAG B score
SLEDAI-2K
No worsening of total SLEDAI-2K from baseline (change ≤0)
PGA
No significant deterioration (<1 cm increase) in 10 cm visual analogue PGA
Treatment Failure
No treatment failure (see SAP for definition of treatment failure)
SLEDAI-2K RI-50 (S2K RI-50): The SLEDAI-2K has been adapted and developed into the 
SLEDAI-2K Responder Index (S2K RI-50)15, a measure that can document partial improvement 
in the 24 disease features between SLEDAI-2K assessments.16 A threshold of 50% improvement 
was judged to reflect clinically significant improvement and is scored as half the weight for the 
feature. “When a descriptor is recorded as present at the initial visit, 1 of 3 situations can follow: 
(1) the descriptor achieves complete remission at follow-up, in which case the score would be 
“0”; (2) the descriptor does not achieve a minimum of 50% improvement at follow-up, in which 
case the score would be identical to its corresponding SLEDAI-2K value; or (3) the descriptor 
improves by ≥50% (according to the S2K RI-50 definition) but has not achieved complete 
remission, in which case the score is evaluated as one-half the score that would be assigned for 
SLEDAI-2K.”17 The S2K RI-50 score is the sum of the 24 scored items, which ranges from 0 to 
105.  The S2K RI-50 post-baseline visits will be compared to baseline.

 
 
 
 
 
 
 
SLE SRI-4, SRI-5, SRI-6, SRI-7, SRI-8, S2K RI-50, BICLA, SLEDAI-2K, BILAG and PGA:  
These efficacy endpoints are defined in sections 5.2.1 and 5.3.1 above
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Patient’s Global Assessment (PtGA) of Disease Activity and Pain:  The PtGA of Disease 
Activity will be recorded by the patient on a visual analogue scale (VAS; 0 to 10 cm).  The scale 
for the assessments range from ‘very well’ (0) to ‘very poor’ (10).  The PtGA of Pain is used to 
assess the patient reported pain intensity.  The patient’s will be asked their average pain during 
the past week on a visual analogue scale (VAS; 0 to 10 cm).  The anchors of the instrument 
include 0 to represent ‘no pain’ and 10 to represent ‘the worst possible pain’.
CLASI:  The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) 
consists of 2 scores; the first summarizes the activity of the disease while the second is a measure 
of the damage done by the disease (CLASI Activity and CLASI Damage scores).  Activity is 
scored on the basis or erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair 
loss and non-scarring alopecia.  Damage is scored in terms of dyspigmentation and scarring, 
including scarring alopecia.  The scores are calculated by simple addition based on the extent of 
the symptoms.8 Higher activity and damage scores indicate worse disease activity.  CLASI 
scores range from 0-70 for activity and 0-56 for damage.
FSS:  The Fatigue Severity Scale (FSS) is a 9-item questionnaire designed to assess the severity 
of fatigue and its impact on daily living using 7 response options (1=Completely Disagree, 
7=Completely Agree) during a recall period of the past week.  It can be completed within 5 
minutes by the subject.  Scores above 36 of the total possible score of 63 reflect increasing 
severity of fatigue.  The scale was developed for use in SLE.9 The scores on the scale correlate 
with patient reported pain, sleep, depression, and with each subscale of the SF-36.  The FSS has 
shown a high internal consistency, and differentiates patients from controls in studies with SLE 
subjects.  The instrument was translated from the original English version and is available in 
several languages.
Clinically meaningful change in FSS defined as a change (decrease) that is ≥ ½ the baseline 
standard deviation of the pooled treatment groups.
SF-36:  The RAND short form (SF)-36 questionnaire is a self-administered multi-domain scale 
with 36 items. Eight health domains cover a range of functioning:  

Limitations in physical function

Limitations in usual role activities

Bodily pain

General mental health (psychological distress and well-being)

Vitality (energy and fatigue)

Limitations in social functioning due to physical or mental health problems

Limitations in usual role activities due to personal or emotional problems

General health perception 
The subscales are scored from 0 to 100. The scoring yields a Physical Component Summary
(PCS) score and a Mental Component Summary (MCS) score, a total score, and subscale scores. 
Higher scores represent better outcomes. It is appropriate for persons over the age of 14 and may 
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be completed in 5 to 10 minutes. Translations are available in most languages; the instrument has 
undergone extensive linguistic and cultural validation. Version 2 acute will be used in the study.
The concepts measured by the SF-36 are not specific to any age, disease, or treatment group, 
allowing comparison of relative burden of different diseases and the benefit of different 
treatments.10 A change of 3 points in any of the subscales or 5 points for the component score is 
associated with clinically meaningful change.11,12,13 The SF-36 has been used extensively in 
clinical trials providing evidence of psychometric properties.  Reliability estimates for physical 
and mental component summary scores exceeded 0.90 in early studies14 and have been further 
confirmed in later studies. Construct validation was established through comparison to several 
other generic health surveys.
 
 
 
 
 
 
 
 
 
Minimally clinical important difference in SF-36 defined as at least a 5-point improvement 
(increase) from baseline in SF-36 PCS or MCS score.
5.2.2.
Analysis Methods
For endpoints after Week 24:
SRI-4 response at Week 24 and Week 48 (8 Week Follow Up) in subjects that were randomized 
to placebo and crossed-over to receive ustekinumab at Weeks 24, 32 and 40 will be compared 
with appropriate methods (e.g. Kappa statistic or McNemar’s test of paired proportions).
In general, no statistical comparisons will be performed on endpoints occurring after the Week 
24 DBL.  Descriptive statistics (e.g. mean, median, standard deviation, interquartile range, 
minimum and maximum) will be used to summarize continuous variables.  Counts and 
percentages will be used to summarize categorical variables.  Recurrence data will be 
summarized by mean as well as counts and percentages.  Median will be reported for time to 
event variables. Graphical displays will also be used to present the data.
In general, analysis on SLEDAI-2K SRI and BICLA endpoints will be based on the Composite 
Estimand:  if subjects meet treatment failure criteria or are lost to follow-up, they are assumed to 
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be non-responders.  Sensitivity analyses may be performed using the Treatment Efficacy and 
DeFacto estimands.
In general, all other endpoints will be based upon the Treatment Efficacy estimand: if subjects 
meet treatment failure rules, their observations after meeting treatment failure criteria will be set 
to missing. Sensitivity analyses may be performed using the DeFacto estimand.
Subgroup Analyses:
Subgroup analyses of the SRI-4 response may be performed on the following: 

Region (APAC, LA, EEU, WEU, US)

Race

Ethnicity (Hispanic or Latino, Not Hispanic or Latino)

SLEDAI-2K Score (< Median, ≥ Median)

PGA Score (< Median, ≥ Median)

Renal disease presence (Y, N)

P/C Ratio (< Median, ≥ Median)

SLE Medications (High dose, Medium dose)

Age (18-25, 26-55, Over 55)

Body Weight (≥ 35 and ≤ 55, > 55 and  ≤ 85, > 85)

Baseline OCS Use
For subgroup analyses, the proportion of subjects who achieved composite SRI-4 response at 
Week 48 (8 Week Follow Up) will be presented by treatment sequence.  
6.
SAFETY
Unless otherwise stated, all safety analyses will be based upon the safety analysis set as 
described in Section 2.3.3 above.  No formal statistical comparison is planned.  
6.1.
Adverse Events
Adverse Event (AE) data will be collected at every study visit from screening through the end of 
the study.  Analyses of AEs will be performed on those events that are considered to be treatment 
emergent adverse events (TEAEs).  A TEAE is defined as any event that occurs at or after the 
initial administration of study agent.  AEs that occur prior to the administration of study agent 
but then increase in intensity after dosing are also considered to be treatment emergent.
Note that if the event occurs on the day of initial administration and either the event time or time 
of administration are missing, then the event will be assumed to be treatment emergent.
For the placebo group, AEs that occur before the first dose of ustekinumab (before crossing over) 
will be considered to have occurred while on placebo treatment.  For AEs that occur in the 
placebo group during or after the first dose of ustekinumab (after crossing over) will be 
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considered to have occurred while on ustekinumab treatment.  Summaries will clearly describe 
this separation (e.g. example heading below).  
Placebo – Ustekinumab
Placebo
(Up to Week 24)
Ustekinumab
(After Week 24 Crossover)
TEAEs will be tabulated by treatment group and Medical Dictionary for Regulatory Activities 
(MedDRA) System Organ Class (SOC) and be sorted in descending frequency of the Preferred 
Term (PT) within the SOC.  The following TEAEs will be summarized by treatment group:

All TEAEs

Serious TEAEs

TEAEs by severity (mild, moderate, severe)

TEAEs reasonably related to study agent

Treatment emergent infections

Treatment emergent infusion/injection reactions
In addition, the following will be listed by subject:

Serious TEAEs

TEAEs leading to discontinuation of study agent

Any deaths
A reasonably related AE is defined as any event with the relationship to study agent as ‘very 
likely’, ‘probable’, or ‘possible’ on the AE eCRF page or if the relationship to study agent is 
missing.
An infusion reaction is defined as an AE that occurs during or within 1 hour following the 
infusion of study agent AND the question on the AE eCRF page ‘Was this an infusion related 
reaction’ = ‘Yes’, with the exception of laboratory abnormalities.  If the AE onset time is missing 
and the AE onset date is the same as the date of infusion, an AE will be considered as an infusion 
reaction only if the question on the AE eCRF page ‘Was this an infusion related reaction’ = 
‘Yes’.
An injection site reaction is defined as an AE with the question on the AE eCRF page ‘Was this 
an injection site reaction’ = ‘Yes’.
An infection is defined as any AE that was characterized by the investigator as an infection on 
the eCRF.
Since safety should be assessed relative to exposure and follow-up, all AE summary tables will 
summarize the average weeks of follow-up and average exposure for each treatment group.
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6.2.
Clinical Laboratory Tests
Routine laboratory data from clinical chemistry, hematology, serology and urinalysis will be 
collected at screening and at Visits according to the time and events schedule in the study 
protocol.  The laboratory data to be summarized are as follows:
Clinical Blood Chemistry:  Chemistry panel including alanine aminotransferase (ALT), albumin, 
alkaline phosphatase, aspartate aminotransferase (AST), bicarbonate, calcium, chloride, 
creatinine, creatinine kinase, GFR, glucose, phosphate, potassium, protein/creatinine ration, 
sodium, total bilirubin, total protein and urea nitrogen.  If total bilirubin is abnormally elevated, 
both direct and indirect bilirubin will be assessed.
Hematology:  hemoglobin, hematocrit, platelet count, red blood cell (RBC) count, white blood 
cell (WBC) total and differential (basophils, eosinophils, lymphocytes, monocytes, neutrophils)
Urinalysis:  Dipstick (bilirubin, blood, glucose, ketones, leukocytes, nitrite, pH, specific gravity, 
and urobilinogen).  If dipstick is abnormal, flow cytometry will be used to measure sediment 
(bacteria, crystals, epithelial cells, granular casts, heme casts, RBC casts, WBC casts).
Additional lab data may be summarized as needed.
Descriptive statistics for each clinical laboratory analyte and for change from baseline at each 
scheduled post-baseline visit will be provided by treatment group.  The proportion of subjects 
with post-baseline values by maximum toxicity grade for clinical laboratory tests will be 
summarized by treatment group.  The National Cancer Institute’s Common Terminology Criteria 
for Adverse Events (NCI-CTCAE; version 4.0) will be used.  Subjects with toxicity grades ≥ 2 
will be listed.
For those labs without NCI toxicity grades, the incidence of markedly abnormal laboratory 
values will be presented by treatment group.  Additionally, the markedly abnormal laboratory 
values will be listed.  Markedly abnormal criteria will be defined in the Data Presentation 
Specifications (DPS) document.
6.3.
Vital Signs and Physical Examination Findings
Weight, height, blood pressure, temperature and heart rate will be assessed.  
Descriptive statistics of changes from baseline will be summarized by visit and treatment group.  
Abnormal findings will be summarized by treatment group.  In addition, a listing of subjects with 
abnormal vital signs will be presented.  Vital sign parameters will be considered abnormal using 
the criteria below:
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Vital Sign
Abnormally Low
Abnormally High
Systolic BP (mm Hg)
Absolute value < 90 mmHg and a 
decrease from baseline ≥ 20 mmHg
Absolute value > 180 mmHg and an 
increase from baseline ≥ 20 mmHg
Diastolic BP (mm Hg)
Absolute value < 50 mmHG and a 
decrease from baseline ≥ 15 mmHg
Absolute value > 105 and an 
increase from baseline ≥ 15 mmHg
Pulse Rate             
(beats/minute)
Absolute value < 50 bpm and a 
decrease from baseline ≥ 15 bpm
Absolute value > 120 bpm and an 
increase from baseline ≥ 15 bpm
Temperature (°C)
< 36°C
> 38°C
6.4.
Electrocardiogram
This section does not apply to this study.
7.
PHARMACOKINETICS/IMMUNOGENICITY/PHARMACODYNAMICS
7.1.
Pharmacokinetics
PK evaluations will be based on PK analysis set (section 2.3.4). No imputation for missing 
concentration data will be performed.
PK concentrations will be summarized by treatment group among PK evaluable subjects. 
Descriptive statistics, including arithmetic mean, SD, coefficient of variation, median, minimum, 
and maximum will be calculated for ustekinumab concentrations at each sampling time. 
Concentrations below the lowest quantifiable concentration in a sample will be treated as zero in 
the summary statistics.  All subjects excluded from the analysis will be clearly documented in the 
study report.  Once a subject meets one of the following dosing deviation criteria, the subject’s 
data will be excluded from the by-visit data analyses from that point onwards:
o
Discontinued ustekinumab administrations.
o
Skipped a ustekinumab administration.
o
Received an incomplete/ incorrect ustekinumab dose.
o
Received an incorrect study agent.
o
Received an additional ustekinumab dose.
o
Received an administration outside of visit windows (For PK analyses, the visit 
and the study agent administration should occur within +/- 7 days of the 
scheduled visit day relative to Week 0).
The definition of treatment group at Week 24 analysis is as follows:

Ustekinumab: Subjects who received ustekinumab from Week 0.  
The definition of treatment group at Week 56 analysis is as follows:
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
Ustekinumab: Subjects who received ustekinumab from Week 0.  

Placebo →Ustekinumab: Subjects who received placebo at Week 0 and then 
crossed-over at Week 24 to receive ustekinumab 
PK data may be displayed graphically.  Plots of mean (SD) or Median (IQ) serum concentrations 
of ustekinumab over time, using semi-logarithmic scales, may be provided. 
The relationship between PK and antibody to ustekinumab status may be assessed.
If feasible, a population PK analysis using nonlinear mixed effects modeling may be used to 
characterize the disposition characteristics of ustekinumab in the current study. The influence of 
important variables such as body weight and antibodies to ustekinumab status on the population 
PK parameter estimates may be evaluated. Results of the population PK analysis will be 
presented in a separate technical report.
7.2.
Immunogenicity (Antibodies to ustekinumab)
The incidence and titers of antibodies to ustekinumab will be summarized for all subjects who 
received at least one dose (complete or partial) of ustekinumab and had appropriate serum 
samples for antibody detection.  The incidence of NAbs to ustekinumab will be summarized for 
subjects who are positive for antibodies to ustekinumab and have samples evaluable for NAbs. A 
listing of subjects positive for antibodies to ustekinumab at any time will be provided.
The definition of treatment group at Week 24 analysis is as follows:

Ustekinumab: Subjects who received ustekinumab from Week 0.   
The definition of treatment group at Week 56 analysis is as follows:

Ustekinumab: Subjects who received ustekinumab from Week 0.  

Placebo →Ustekinumab: Subjects who received placebo at Week 0 and then 
crossed-over at Week 24 to receive ustekinumab 
7.3.
Pharmacodynamics
Anti-Smith, SS-A (Ro), SS-B (La) autoantibodies will be collected after Week 0 only in subjects 
who are positive for these autoantibodies at baseline.  Autoantibody levels and proportion of 
subjects with positive autoantibody over time will be summarized for those subjects positive at
baseline.
Changes in the concentration of individual pharmacodynamics markers from baseline to the 
selected post treatment time points will be summarized.  These include but are not limited to 
ANA, C3 and C4 complement, IgA, IgG, IgM, and SAA.  
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7.4.
Pharmacokinetic/Pharmacodynamic Relationships
If data permit, the relationships between serum ustekinumab concentration and efficacy or 
pharmacodynamic measures may be analyzed graphically.
8.
HEALTH ECONOMICS
Not applicable
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Touma Z, Urowitz M, Ibañez D, Gladman D. SLEDAI-2K 10 days versus SLEDAI-2K 30 days in a cross-
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Touma Z, Gladman DD, Ibanez D, Urowitz MB. Development and initial validation of the systemic lupus 
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NCT0239061


STELARA® (ustekinumab)  
Statistical Analysis Plan CNTO1275SLE2001
29
Approved, Date: 22 March 2018
APPROVALS
CNTO1275 SLE2001 Statistical Analysis Plan
A Multicenter, Randomized, Double-blind, Placebo-controlled, Proof-of-Concept Study of 
Ustekinumab (Stelara) in Subjects with Active Systemic Lupus Erythematosus 
Version 1.0: Dated 22Mar2018
Approved by:
, MD
Date (Day Month Year)
Director, Clinical Research, Immunology
Study Responsible Physician
, PhD
Date (Day Month Year)
Senior Director, Clinical Biostatistics
Immunology Therapeutic Area Statistical Head
NCT0239061