Clinical trial NCT04376827
Conditions: Lupus Nephritis
Sponsor: Janssen Research & Development, LLC
Start date: 2020-09-15; Completion date: 2023-02-01
Enrollment: 33 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy of guselkumab in participants with active lupus nephritis (LN).

Detailed description:
Guselkumab is a monoclonal antibody (mAb) that binds to human interleukin (IL)-23 with high affinity and blocks binding of extracellular IL-23 to cell surface IL-23 receptor, inhibiting IL 23 specific intracellular signaling and subsequent activation and cytokine production. It is used in treatment of plaque psoriasis, psoriatic arthritis, generalized pustular psoriasis, erythrodermic psoriasis. Lupus is a heterogeneous autoimmune disease with lesions confined to skin (cutaneous lupus erythematosus \[CLE\]) to others that involve 1 or more vital internal organs (systemic lupus erythematosus \[SLE\]). Renal involvement due to SLE is termed lupus nephritis (LN). There is a high unmet need for new treatment options in LN that are safe and effective, especially new therapies that can provide improved long-term efficacy over currently available therapies. This study will evaluate safety and efficacy of guselkumab added to standard-of-care compared to placebo added to standard-of-care. Total duration of study is up to 68 weeks: a less than or equal to 8 week screening period, a 48 week double-blind treatment period, a 12 week safety follow-up period after last dose. Participants who complete the assessments at Week 52 and have achieved complete renal response (CRR) may have the option to participate in the long-term extension (LTE) of study through Week 152 and the 12-week safety follow-up visit. Hypothesis of this study is that guselkumab plus standard-of-care is superior to placebo plus standard-of-care in participants with active LN as measured by the proportion of participants inducing at least a 50 percentage reduction of proteinuria with protocol specified steroid tapering regimen at Week 24. Safety assessments include Adverse events (AEs), clinical laboratory tests (hematology and chemistry), systolic and diastolic blood pressures over time, monitoring for hypersensitivity reactions, AEs temporally associated with infusion, injection-site reactions, suicidality assessment, and early detection of active tuberculosis (TB).

Arms: arm 1: Participants will receive guselkumab Dose 1 intravenously (IV) at Weeks 0, 4 and 8 and guselkumab Dose 2 subcutaneous (SC) every 4 weeks (q4w) from Week 12 through Week 48 along with standard-of-care treatment of mycophenolate mofetil (MMF)/mycophenolic acid (MPA) and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the long-term extension (LTE). arm 2: Participants will receive placebo IV at Weeks 0, 4 and 8 and placebo SC q4w from Week 12 through Week 48 along with standard-of-care treatment of MMF/MPA and glucocorticoids. Participants who achieved complete renal response (CRR) at Week 48 and 52 and have completed the Week 52 assessment may have the option to participate in the LTE of the study.
Interventions: intervention 1: Guselkumab Dose 1 intervention 2: Placebo intervention 3: Guselkumab Dose 2 intervention 4: Standard-of-care treatment
Intervention descriptions: intervention 1: Participants will receive guselkumab Dose 1 via IV administration. intervention 2: Participants will receive placebo IV at Weeks 0, 4 and 8 (that is, 3 IV doses) and placebo SC q4w from Week 12 through Week 48. intervention 3: Participants will receive guselkumab Dose 2 via SC route. intervention 4: Participants will receive standard of care treatment including MMF/MPA and glucocorticoids from Week 12 through Week 48.

Protocol documents:
Prot_002.pdf: 
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
1
Status: Approved, Date: 24 May 2022
*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 Pharmaceutica NV; Janssen
Sciences Ireland UC; Janssen Biopharma Inc.; 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.
United States (US)sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
Regulatory Agency Identifier Number(s):
IND: p140547
EudraCT NUMBER: 2018-003155-38
Janssen Research & Development *
Clinical Protocol
Protocol Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of
Guselkumab in Subjects with Active Lupus Nephritis
ORCHID-LN
Short Title
A Study of the Efficacy and Safety of Guselkumab in Participants with Active Lupus
Nephritis
Protocol CNTO1959LUN2001; Phase 2
Amendment 4
CNTO 1959  (guselkumab)
Status: 
Approved
Date: 
24 May 2022
Prepared by: Janssen Research & Development, LLC
EDMS number: 
EDMS-ERI-166768011, 5.0
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.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
2
Status: Approved, Date: 24 May 2022
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE
DOCUMENT HISTORY
Document 
Date
Amendment 4  
24 May 2022
Amendment 3 
29 March 2022
Amendment 2 
20 May 2021
Amendment 1 
07 May 2020
Original Protocol 
18 February 2020
Amendment 4 [24 May 2022]
Overall Rationale for the Amendment: To revise the protocol to reflect the sponsor’s decision to stop
screening of new participants and terminate the study early, as a result of enrollment challenges.
The changes made to the clinical protocol CNTO1959LUN2001 as part of Protocol Amendment 4 are listed
below, including the rationale of each change and a list of all applicable sections. Changes made in previous
protocol amendments are listed in Section 10.13 Appendix 13.
Section Number 
and Name
Description of Change 
Brief Rationale
1.1 Synopsis;
3 Objectives and Endpoints.
Added text that not all Objectives and
Endpoints described may be reported in the
CSR.
Due to enrollment challenges,
the sponsor made the decision to
stop screening of new
participants and terminate the
study early. The changes in this
amendment describe study
conduct for currently screened
and randomized participants in
the context of the plan for early
study termination.
1.1 Synopsis;
9 Statistical Considerations.
Added text that not all statistical analyses
described may be performed.
1.1 Synopsis;
4.1 Overall Design;
6.3 Measures to Minimize
Bias: Randomization and
Blinding.
Updated details for planned database locks.
1.1 Synopsis;
2.1 Study Rationale;
4.1.1 Main Study;
7.1 Discontinuation of Study
Intervention;
9.2 Sample Size
Determination.
Updated details of number of participants to
be enrolled in the study.
9.3 Populations for Analysis
Sets.
Defined additional populations for analysis.
1.1 Synopsis;
4.1.2 Long-Term Extension;
6.1.1 Long-Term Extension;
6.3 Measures to Minimize
Bias: Randomization and
Blinding.
Updated information regarding blinding
during the study.
1.3 Schedule of Activities
(SoA).
Defined the timing for final efficacy and
safety visits for participants prior to, and after,
early study termination notification.
1.1 Synopsis;
4.1 Overall Design;
4.4 End of Study Definition;
6.1 Study Interventions
Administered;
6.1.1 Long-Term Extension.
Defined the end of study.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
3
Status: Approved, Date: 24 May 2022
Section Number
and Name
Description of Change 
Brief Rationale
1.1 Synopsis;
4.1 Overall Design.
Updated information regarding study
termination and administration of study
intervention.
1.1 Synopsis;
4.1.2 Long-Term Extension;
6.1.1 Long-term Extension;
9.4.8 Long-Term Extension.
Updated description ofend of LTE. 
5.4 Screen Failures. 
Updated information regarding rescreening of
participants.
6.3 Measures to Minimize 
Bias: Randomization and 
Blinding.
Specified when randomization codes will be
disclosed fully.
3 Objectives and Endpoints. 
Corrected the units for eGFR in the CRR
definition.
Corrected typo.
Throughout the protocol. 
Minor grammatical, formatting, or spelling
changes were made.
Minor errors were noted.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
4
Status: Approved, Date: 24 May 2022
TABLE OF CONTENTS
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ............................................................... 2
TABLE OF CONTENTS ............................................................................................................................... 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 8
1. 
PROTOCOL SUMMARY..................................................................................................................... 9
1.1. 
Synopsis........................................................................................................................................... 9
1.2. 
Schema.......................................................................................................................................... 17
1.3. 
Schedule of Activities (SoA)........................................................................................................... 18
2. 
INTRODUCTION................................................................................................................................ 33
2.1. 
Study Rationale.............................................................................................................................. 33
2.1.1. 
Unmet Need in Lupus Nephritis.................................................................................................. 34
2.1.2. 
Rationale for Targeting IL-23 in Lupus Nephritis........................................................................ 34
2.2. 
Background.................................................................................................................................... 35
2.2.1. 
Nonclinical Studies ..................................................................................................................... 35
2.2.2. 
Clinical Studies ........................................................................................................................... 36
2.3. 
Benefit-Risk Assessment............................................................................................................... 37
2.3.1. 
Risks for Study Participation....................................................................................................... 37
2.3.2. 
Benefits for Study Participation .................................................................................................. 40
2.3.3. 
Benefit-Risk Assessment for Study Participation ....................................................................... 41
3. 
OBJECTIVES AND ENDPOINTS ..................................................................................................... 42
4. 
STUDY DESIGN ................................................................................................................................ 45
4.1. 
Overall Design................................................................................................................................ 45
4.1.1. 
Main Study.................................................................................................................................. 45
4.1.2. 
Long-Term Extension ................................................................................................................. 46
4.1.3. 
End of Study............................................................................................................................... 47
4.2. 
Scientific Rationale for Study Design............................................................................................. 47
4.2.1. 
Blinding, Control, Study Phase/Periods, Intervention Groups.................................................... 48
4.2.2. 
DNA and Biomarker Collection................................................................................................... 48
4.2.3. 
Participant Input Into Design ...................................................................................................... 49
4.2.4. 
Study-Specific Ethical Design Considerations ........................................................................... 49
4.3. 
Justification for Dose...................................................................................................................... 49
4.4. 
End of Study Definition................................................................................................................... 51
5. 
STUDY POPULATION ...................................................................................................................... 51
5.1. 
Main Study Inclusion Criteria......................................................................................................... 52
5.1.1. 
Long-Term Extension Inclusion Criteria..................................................................................... 55
5.2. 
Main Study Exclusion Criteria........................................................................................................ 56
5.2.1. 
Long-Term Extension Exclusion Criteria.................................................................................... 63
5.3. 
Lifestyle Considerations................................................................................................................. 63
5.4. 
Screen Failures.............................................................................................................................. 64
6. 
STUDY INTERVENTION................................................................................................................... 65
6.1. 
Study Interventions Administered .................................................................................................. 65
6.1.1. 
Long-Term Extension ................................................................................................................. 66
6.1.2. 
Combination Products ................................................................................................................ 66
6.2. 
Preparation/Handling/Storage/Accountability ................................................................................ 66
6.3. 
Measures to Minimize Bias: Randomization and Blinding............................................................. 68
6.4. 
Study Intervention Compliance...................................................................................................... 69
6.5. 
Concomitant Therapy..................................................................................................................... 69
6.5.1. 
Antimalarial Medications............................................................................................................. 72
6.5.2. 
Glucocorticoid Therapy............................................................................................................... 73
6.5.3. 
Nonsteroidal Anti-inflammatory Drugs........................................................................................ 74
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
5
Status: Approved, Date: 24 May 2022
6.5.4. 
Anti-hypertensive Medications.................................................................................................... 75
6.5.5. 
Non-biologic Immunomodulators................................................................................................ 75
6.5.6. 
Topical Medications.................................................................................................................... 75
6.5.7. 
Prohibited Therapies................................................................................................................... 75
6.5.8. 
Rescue Medication ..................................................................................................................... 77
6.5.9. 
Vaccinations (including COVID-19)............................................................................................ 77
6.6. 
Dose Modification........................................................................................................................... 77
6.7. 
Continued Access to Study Intervention After the End of the Study ............................................. 77
7.
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL............................................................................................... 78
7.1. 
Discontinuation of Study Intervention ............................................................................................ 78
7.1.1. 
Long-Term Extension ................................................................................................................. 80
7.2. 
Participant Discontinuation/Withdrawal From the Study................................................................ 80
7.2.1. 
Withdrawal From the Use of Research Samples ....................................................................... 81
7.3. 
Lost to Follow-up............................................................................................................................ 81
8.
STUDY ASSESSMENTS AND PROCEDURES ............................................................................... 82
8.1. 
Efficacy Assessments .................................................................................................................... 84
8.1.1. 
SLE Disease Activity Index 2000................................................................................................ 85
8.1.2. 
Physician's Global Assessment of Disease Activity................................................................... 85
8.1.3. 
Joint Count Assessments ........................................................................................................... 85
8.1.4. 
Cutaneous Lupus Erythematosus Disease Area and Severity Index......................................... 86
8.1.5. 
FACIT-Fatigue ............................................................................................................................ 86
8.1.6. 
Patient Global Impression of Change......................................................................................... 86
8.1.7. 
Lupus Symptoms........................................................................................................................ 86
8.1.8. 
Lupus Quality of Life Questionnaire ........................................................................................... 87
8.2. 
Safety Assessments....................................................................................................................... 87
8.2.1. 
Physical Examinations................................................................................................................ 87
8.2.2. 
Vital Signs................................................................................................................................... 88
8.2.3. 
Electrocardiograms..................................................................................................................... 88
8.2.4. 
Clinical Safety Laboratory Assessments .................................................................................... 88
8.2.5. 
Electronic Columbia-Suicide Severity Rating Scale................................................................... 89
8.2.6. 
Concomitant Medication Review ................................................................................................ 91
8.2.7. 
Injection-Site Reactions.............................................................................................................. 91
8.2.8. 
Hypersensitivity Reactions.......................................................................................................... 91
8.2.9. 
Adverse Events Temporally Associated with Infusion................................................................ 91
8.2.10. 
Infections .................................................................................................................................... 92
8.2.11. 
Tuberculosis Evaluations............................................................................................................ 92
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting ....................................... 93
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious Adverse Event
Information.................................................................................................................................. 94
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events .......................................... 94
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events ....................................................... 95
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events ............................................. 95
8.3.5. 
Pregnancy................................................................................................................................... 95
8.3.6. 
Disease-Related Events and Disease-Related Outcomes Not Qualifying as Adverse
Events or Serious Adverse Events............................................................................................. 96
8.3.7. 
Adverse Events of Special Interest............................................................................................. 96
8.4. 
Treatment of Overdose .................................................................................................................. 96
8.5. 
Pharmacokinetics........................................................................................................................... 97
8.5.1. 
Evaluations ................................................................................................................................. 97
8.5.2. 
Analytical Procedures................................................................................................................. 97
8.5.3. 
Pharmacokinetic Parameters and Evaluations........................................................................... 97
8.6. 
Pharmacodynamics........................................................................................................................ 98
8.7. 
Genetics......................................................................................................................................... 98
8.8. 
Biomarkers..................................................................................................................................... 98
8.8.1. 
Serum-based Biomarkers........................................................................................................... 98
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
6
Status: Approved, Date: 24 May 2022
8.8.2. 
Whole Blood-based Biomarkers................................................................................................. 98
8.8.3. 
RNA Expression Research of a Subset of RNA Species........................................................... 99
8.8.4. 
Stopping Analysis ....................................................................................................................... 99
8.9. 
Immunogenicity Assessments ....................................................................................................... 99
8.10. 
Medical Resource Utilization and Health Economics .................................................................. 100
9. 
STATISTICAL CONSIDERATIONS................................................................................................ 100
9.1. 
Statistical Hypotheses.................................................................................................................. 100
9.2. 
Sample Size Determination ......................................................................................................... 100
9.3. 
Populations for Analysis Sets ...................................................................................................... 101
9.4. 
Statistical Analyses ...................................................................................................................... 101
9.4.1. 
General Considerations............................................................................................................ 101
9.4.2. 
Primary Endpoint(s).................................................................................................................. 102
9.4.3. 
Secondary Endpoint(s)............................................................................................................. 102
9.4.4. 
Tertiary/Exploratory Endpoint(s)............................................................................................... 103
9.4.5. 
Long-Term Extension Exploratory Endpoints........................................................................... 103
9.4.6. 
Safety Analyses........................................................................................................................ 104
9.4.7. 
Other Analyses ......................................................................................................................... 105
9.4.8. 
Long-Term Extension ............................................................................................................... 106
9.5. 
Data Monitoring Committee or Other Review Board ................................................................... 107
10. SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS.......................... 108
10.1. 
Appendix 1: Abbreviations ........................................................................................................... 109
10.2. 
Appendix 2: 2019 EULAR/ACR Classification Criteria................................................................ 111
10.3. 
Appendix 3: Tuberculin Skin Testing ........................................................................................... 112
10.4. 
Appendix 4: Hepatitis B Virus (HBV) Screening with HBV DNA Testing..................................... 113
10.5. 
Appendix 5: Contraceptive and Barrier Guidance and Collection of Pregnancy Information...... 114
10.6. 
Appendix 6: CLASI....................................................................................................................... 117
10.7. 
Appendix 7: Glucocorticoid Taper................................................................................................ 118
10.8. 
Appendix 8: Clinical Laboratory Tests ......................................................................................... 119
10.9. 
Appendix 9: Regulatory, Ethical, and Study Oversight Considerations....................................... 121
10.9.1. 
Regulatory and Ethical Considerations .................................................................................... 121
10.9.2. 
Financial Disclosure.................................................................................................................. 124
10.9.3. 
Informed Consent Process ....................................................................................................... 124
10.9.4. 
Data Protection ......................................................................................................................... 125
10.9.5. 
Long-Term Retention of Samples for Additional Future Research .......................................... 126
10.9.6. 
Committees Structure............................................................................................................... 126
10.9.7. 
Publication Policy/Dissemination of Clinical Study Data.......................................................... 126
10.9.8. 
Data Quality Assurance............................................................................................................ 128
10.9.9. 
Case Report Form Completion................................................................................................. 128
10.9.10. Source Documents ................................................................................................................... 129
10.9.11. Monitoring ................................................................................................................................. 130
10.9.12. On-Site Audits........................................................................................................................... 130
10.9.13. Record Retention...................................................................................................................... 131
10.9.14. Study and Site Start and Closure ............................................................................................. 131
10.10. Appendix 10: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting............................................................................................................................... 133
10.10.1. Adverse Event Definitions and Classifications ......................................................................... 133
10.10.2. Attribution Definitions................................................................................................................ 134
10.10.3. Severity Criteria........................................................................................................................ 134
10.10.4. Special Reporting Situations .................................................................................................... 135
10.10.5. Procedures ............................................................................................................................... 135
10.10.6. Product Quality Complaint Handling......................................................................................... 137
10.10.7. Contacting Sponsor Regarding Safety, Including Product Quality........................................... 137
10.11. Appendix 11: Liver Safety: Suggested Actions and Follow-up Assessments.............................. 138
10.11.1. Stopping Algorithm ................................................................................................................... 138
10.11.2. Follow-up Assessments............................................................................................................ 139
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
7
Status: Approved, Date: 24 May 2022
10.12. Appendix 12: Guidance on Study Conduct during the COVID -19 Pandemic............................. 142
10.13. Appendix 13: Protocol Amendment History................................................................................. 144
11. REFERENCES................................................................................................................................. 154
INVESTIGATOR AGREEMENT............................................................................................................... 157
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
8
Status: Approved, Date: 24 May 2022
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)........................................ 18
Table 2: 
Schedule of Activities –Long-term Extension for Eligible Participants (through
Week 104)................................................................................................................................. 26
Table 3: 
Schedule of Activities –Long-term Extension for Eligible Participants
(Weeks 108to 160)................................................................................................................... 30
Table 4: 
Guselkumab Predicted Exposure Margins ............................................................................... 50
Table 5: 
Permitted Concomitant Medications for SLE and LN, the Minimum Stabilization Period
before Randomization, and the Maximum Allowed Doses at Study Randomization ............... 71
Table 6: 
Blinded Study Period - Protocol Requirements for Permitted Concomitant SLE or LN
Medications............................................................................................................................... 72
Table 7: 
Power to Detect Difference in Proportions of Participants with ≥50% Decrease in
Proteinuria Between the Guselkumab and Placebo Intervention Groups at Week 24........... 101
FIGURES
Figure 1: Schematic Overview of the Study............................................................................................. 17
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
9
Status: Approved, Date: 24 May 2022
1. 
PROTOCOL SUMMARY
1.1. 
Synopsis
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of Guselkumab in
Subjects with Active Lupus Nephritis
Guselkumab (CNTO 1959) is a fully human immunoglobulin G1 lambda monoclonal antibody (mAb) that
binds to human interleukin (IL)-23 with high affinity. The binding of guselkumab to IL-23 blocks the
binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting IL-23-specific intracellular
signaling and subsequent activation and cytokine production. In this manner, guselkumab inhibits the
biological activity of IL-23 in all in vitro assays examined.
EudraCT Number: 2018-003155-38
IND Number: p140547
OBJECTIVES AND ENDPOINTS
Due to the Sponsor’s decision to terminate the study early, only the primary endpoint, major secondary
endpoints and safety endpoints may be reported in the clinical study report. Details will be described in the
statistical analysis plan (SAP).
For informational purposes, the below table outlines the objectives and endpoints originally planned for the
study.
Objectives 
Endpoints
Primary
 
To evaluate the efficacy of 
guselkumab in participants with 
active lupus nephritis (LN)
 
Primary endpoint: Proportion of participants achieving at
least 50% decrease in proteinuria from baseline at Week 24
 
Major secondary endpoints to include:
 
Proportion of participants achieving complete renal
response (CRR) at Week 24
 
Proportion of participants achieving a sustained reduction
in steroid dose ≤10 mg/day of prednisone or equivalent
from Week 16 to Week 24
 
Proportion of participants achieving at least 50% decrease
in proteinuria from baseline at Week 52
 
Proportion of participants achieving CRR at Week 52
 
Proportion of participants with Urine Protein to Creatinine
Ratio (UPCR) <0.5 mg/mg at Week 24
 
Proportion of participants with UPCR <0.75 mg/mg at
Week 24
 
Time to achievement of CRR
 
Time to treatment failure (TF)
Secondary
 
To evaluate the safety and 
tolerability of guselkumab in 
participants with active LN  
 
Frequency and type of adverse events (AEs), serious
adverse events (SAEs), reasonably related AEs, AEs
leading to discontinuation of study intervention, infections,
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
10
Status: Approved, Date: 24 May 2022
Objectives 
Endpoints
serious infections, and infections requiring oral or
parenteral antimicrobial treatment, AEs temporally
associated with an infusion, and injection-site reactions
 
Laboratory parameters and change from baseline in
laboratory parameters (hematology and chemistry)
 
Summary of maximum Common Terminology Criteria for
Adverse Events (CTCAE) toxicity grade for postbaseline
laboratory values (hematology and chemistry)
 
Systolic and diastolic blood pressures over time
 
To 
evaluate 
the 
pharmacokinetics 
(PK) 
and
immunogenicity in participants
with active LN
 
Serum guselkumab levels over time
 
Serum anti-guselkumab antibodies through Week 24,
through Week 60, end of long-term extension (LTE), and in
participants discontinuing study intervention early
Tertiary/Exploratory
 
To evaluate the efficacy of
guselkumab in participants with
active LN over an extended
period
 
Proportion of participants maintaining CRR at Week 152
 
To evaluate the efficacy of
guselkumab in extrarenal lupus
manifestations
 
Proportion of participants with ≥4 points improvement at
Week 24 in systemic lupus erythematosus disease activity
index 2000 (SLEDAI-2K) modified to exclude renal items
 
Proportion of participants with baseline arthritis (with at
least 4 active joints at baseline) who have ≥50% reduction
in active joints at Week 24
 
Proportion 
of participants 
with 
baseline 
active
mucocutaneous lupus manifestations (Cutaneous Lupus
Erythematosus Disease Area and Severity Index [CLASI]
score ≥8) and ≥50% reduction in CLASI scores at Week 24
 
To evaluate the impact of
guselkumab on Health-Related
Quality of Life (HRQoL) and
fatigue in participants with
active LN
 
Change from baseline in Lupus Quality of Life (LupusQoL)
individual domains at Week 24
 
Change from baseline in Functional Assessment of Chronic
Illness Therapy (FACIT)-Fatigue score at Week 24
 
Change from baseline in lupus symptoms (joint pain, joint
stiffness, rash, and swelling [peripheral edema]) at Week 24
 
Patient Global Impression of Change [PGIC] - Change in
LN (health condition) at Week 24 and Week 52
 
Changes in PRO assessments including LupusQOL,
FACIT-Fatigue, lupus symptoms, and PGIC over time
during the long-term extension
 
To evaluate biomarkers of LN,
pharmacodynamic (PD) effects
of guselkumab, and to identify
participants most likely to
 
Serum biomarkers including IL-23, IL-17A, IL-17F, IL-22,
complement (C)3, C4, C1q, or autoantibodies, eg,
anti-double-stranded deoxyribonucleic acid (dsDNA)
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
11
Status: Approved, Date: 24 May 2022
Objectives 
Endpoints
benefit from treatment with 
guselkumab 
 
Cellular (urine and peripheral blood mononuclear cell
[PBMC]) and whole blood gene expression
 
Urine biomarkers (protein and /or nucleic acids)
 
Perform analyses of pre- and
post-treatment renal biopsies
(optional)
 
Histopathology of glomeruli and tubulointerstitial tissue,
immunohistochemistry for resident and infiltrating cell
types and inflammatory mediators (including IL-23, IL-17,
IL-21, interferon [IFN]-gamma, chemokines), and/or tissue
gene expression
Hypothesis
The primary hypothesis of this study is that guselkumab plus standard-of-care is superior to placebo plus
standard-of-care in participants with active LN as measured by the proportion of participants achieving at
least a 50% reduction of proteinuria with protocol specified steroid tapering regimen at Week 24.
OVERALL DESIGN
Main Study
This is a randomized, double-blind, placebo-controlled, parallel, multicenter, interventional Phase 2 study
in participants aged 18 to 75 (inclusive) with active LN. The total duration of the original study was up to
68 weeks: a ≤8-week screening period (rescreening is permitted once per participant), a 48-week double-
blind treatment period, and a 12-week safety follow-up period after the last dose (8 weeks after the final
efficacy visit). Participants starting mycophenolate mofetil (MMF)/mycophenolic acid (MPA)at/or within
2 weeks of screening may extend screening for up to 4 additional weeks.
Unscheduled visits are permitted for reasons such as safety events or worsening of LN.
The original study design included a target of approximately 60 participants to be randomly assigned with
approximately 30 participants planned per intervention group. Due to the sponsor’s decision to stop
screening of new participants as a result of enrollment challenges, fewer than 60 participants will be
enrolled in the study. After all enrolled participants have completed the Week 20 visit, no additional study
intervention will be administered. For further details, see End of Study Section of this synopsis.
A placebo comparator (in addition to standard-of-care background therapy) will be used in this study
through Week 48 to allow for blinded, placebo-controlled evaluation of the long-term efficacy and safety
ofguselkumab in participants with LN. Participants will be stratified by geographic region and UPCR level.
Efficacy, safety, PK, immunogenicity, and biomarkers (where local regulations permit) will be assessed
according to the Schedule of Activities. An optional pharmacogenomic blood sample will be collected from
participants who consent to the collection of these samples (where local regulations permit).
The primary efficacy analysis will be performed after all participants have completed Week 24 efficacy
assessments (or discontinued). Additional secondary endpoints will be completed at Week 24 and Week 52.
Every reasonable effort should be made to keep concomitant medications stable as defined in the protocol.
Beginning at the screening visit, all concomitant therapies and all changes in concomitant therapies should
be recorded throughout the study. Participants who experience an LN flare during the main study will be
discontinued from study intervention.
Key safety assessments include AEs, clinical laboratory tests (hematology and chemistry), systolic and
diastolic blood pressures over time, monitoring for hypersensitivity reactions, AEs temporally associated
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
12
Status: Approved, Date: 24 May 2022
with infusion, injection-site reactions, suicidality assessment, and early detection of active tuberculosis
(TB).
Long-Term Extension
Participants who achieve complete renal response (CRR) at Week 48 and complete the Week 52
assessments may have the option to participate in the long-term extension (LTE) of the study. The LTE
begins after the assessments have been completed at Week 52. The objective of the LTE is to evaluate the
efficacy and safety of long-term guselkumab treatment.
During the LTE, all participants will be assessed for safety and efficacy. Participants who experience an
LN flare during the LTE will be discontinued from study intervention and will be required to complete the
final efficacy/safety follow-up visits.
All study evaluations that should be performed during the LTE are listed in the SoA.
The study blind will be maintained throughout the study (including the LTE).
An external, independent Data Monitoring Committee (DMC) will be commissioned for this study. The
DMC will review unblinded data on a periodic basis to ensure the safety of participants enrolled in the
study. The main focus of the DMC will be on reviewing interim unblinded safety data, but the DMC may
also review efficacy data needed to ensure the full benefit:risk profile for guselkumab. The DMC
responsibilities, authorities, and procedures will be documented in a separate DMC charter.
End of Study
The end of study will occur after all enrolled participants have completed the Week 20 visit or discontinued
study intervention prior to Week 24, and all participants have completedtheir final efficacy and safety visits
per the Schedule of Activities (Section 1.3).
One database lock is planned at the end of study.
NUMBER OF PARTICIPANTS
An original target of approximately 60 participants were to be randomly assigned in this study  with
approximately 30 participants planned per intervention group. Due to the sponsor’s decision to stop
screening of new participants as a result of enrollment challenges, fewer than 60 participants will be
enrolled in the study.
INTERVENTION GROUPS AND DURATION
Participants in the study will maintain their standard-of-care treatment of mycophenolate mofetil
(MMF)/mycophenolic acid (MPA) and background glucocorticoid. Participants’ glucocorticoid dose will
be tapered.
In addition to remaining on the SOC noted above, participants will be randomized to 1 of 2 treatment groups
as described below:
 
Guselkumab: Participants will receive guselkumab 400 mg intravenously (IV)at Weeks 0, 4 and 8 (ie,
3 IV doses) and guselkumab 200 mg subcutaneous (SC) every 4 weeks (q4w) from Week 12 through
Week 48.
 
Placebo: Participants will receive placebo IV at Weeks 0, 4 and 8 (ie, 3 IV doses) and placebo SC q4w
from Week 12 through Week 48.
Participants will remain on their assigned treatment through Week 48. All participants will receive an IV
infusion at Weeks 0, 4, and 8 (either active or placebo) and 2 SC injections (either active or placebo) at
Week 12 through Week 48.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
13
Status: Approved, Date: 24 May 2022
If eligible for the LTE, participants will continue to receive the same study intervention that they were
assigned to receive through Week 48. The first dose in the LTE will be at Week 52, and the LTE will
continue for up to 2 years.
EFFICACY EVALUATIONS
Investigator assessments and patient-reported outcomes (PROs) of efficacy include the following:
 
SLEDAI-2K
 
Physician's Global Assessment of Disease Activity (PGA)
 
Joint count assessments
 
CLASI
 
PROs measures to assess: Lupus symptoms (Lupus Symptoms questionnaire), fatigue
(FACIT-Fatigue), health-related quality of life (LupusQoL), and changes in disease severity (Patient
Global Impression of Change –PGIC).
Efficacy evaluations also include laboratoryassessments related to kidney function that include the primary
endpoint and other key efficacy endpoints.
PHARMACOKINETIC EVALUATIONS
Serum samples will be used to evaluate the PK of guselkumab, as well as the immunogenicity of
guselkumab (antibodies to guselkumab).
In addition, 24-hour urine samples will be used to evaluate the potential renal excretion of guselkumab.
IMMUNOGENICITY EVALUATIONS
Antibodies to guselkumab will be evaluated in serum samples collected from all participants according to
the Schedule of Assessments (SoA). Additionally, serum samples should also be collected at the final visit
from participants who discontinued study intervention or were withdrawn from the study.
PHARMACODYNAMIC AND BIOMARKER EVALUATIONS
Pharmacodynamic markers will be evaluated using blood and urine samples collected at visits as indicated
in the SoA.
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment and/or LN, where local regulations permit.
Assessments will include the evaluation of relevant biomarkers in serum, whole blood, and urine collected
as specified in the SoA, where local regulations permit.
PHARMACOGENOMIC (DNA) EVALUATIONS
A pharmacogenomic blood sample will be collected from participants who consent separately to this
component of the study to allow for pharmacogenomic research, where local regulations permit.
Participation in pharmacogenomic research is optional.
SAFETY EVALUATIONS
Key safety assessments include AEs, clinical laboratory tests (hematology and chemistry), systolic and
diastolic blood pressures over time, monitoring for hypersensitivity reactions, AEs temporally associated
with infusion, injection-site reactions, suicidality assessment, and early detection of active TB.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
14
Status: Approved, Date: 24 May 2022
STATISTICAL METHODS
Due to the Sponsor’s decision to terminate the study early, some analyses described below may not be
performed.  The primary efficacy analysis and most secondary efficacy analyses will be performed.  All
safety analyses will be performed. Details will be described in the revised SAP.
For informational purposes, the below section outlines the original statistical plan.
Sample Size Determination
An original target of approximately 60 participants were planned to be enrolled into the study. Due to the
Sponsor’s decision to stop screening of new participants as a result ofenrollment challenges, fewer than 60
participants will be enrolled in the study.
The study will be considered a success if the 1-sided p-value from the difference in proportion of
participants with ≥50% decrease in proteinuria between the guselkumab and placebo intervention groups
from a logistic mixed effect repeat measurement (MMRM) longitudinal model is less than a 1-sided alpha
of 10%.
The table below shows the sensitivity of power to detect a difference in proportions of participants with
≥50% decrease in proteinuria between the guselkumab and placebo intervention groups at Week 24.
Power to Detect Difference in Proportions of Participants with ≥50% Decrease in Proteinuria Between the
Guselkumab and Placebo Intervention Groups at Week 24
Difference in proportion of participants with ≥50% 
decrease in proteinuria between the intervention
groups
Power (%)
20%  
56.34
25% 
79.61
30% 
89.84
35%  
96.08
Notes:
• Proportion of placebo participants with ≥50% decrease in proteinuria is assumed to be 49%.
• Power calculation is based on 1-sided α of 0.10.
• Total sample size is 60.
If the proportion of placebo participants with ≥50% decrease in proteinuria is 49%, and the difference in
proportion between the intervention groups is 30%, a total sample size of 60 with a 1-sided alpha of 10%
will provide approximately 90% power for success.
Primary Endpoint Analysis
Analyses of the primary efficacy endpoint (≥50% decrease in proteinuria from baseline at Week 24) will
include data from all randomized participants who received at least one administration of study intervention
based on their assigned intervention group, regardless of the actual intervention received and have baseline
data (Evaluable population).
Treatment Failure Criteria may include: initiation or increased use of a glucocorticoid or other
immunosuppressive agents, however these will be further defined in the SAP.
Participants who meet any of the TF criteria defined in the SAP will be assumed a non-responder, ie, did
not meet the ≥50% decrease in proteinuria criteria at Week 24.
The primary analysis will be based on the composite estimand where participants meeting TF criteria are
assumed non-achievers from the point of TF forward, and missing data are assumed as non-achievers as
well.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
15
Status: Approved, Date: 24 May 2022
The study will be considered a success if the 1-sided p-value from the difference in proportion of
participants with ≥50% decrease in proteinuria between the guselkumab and placebo intervention groups
from a logistic MMRM longitudinal model is less than a 1-sided alpha of 10%.
See the SAP for further details about the analysis of the primary endpoint, including sensitivity and
subgroup analyses.
Major Secondary Analyses
The major secondary endpoints are listed above. The Evaluable population will be used for analysis and
participants will be counted in the intervention group assigned, regardless of the study intervention
received.
Treatment failure and missing data will be included in the secondary endpoint estimands as non-achievers
or non-responders.
The details of the analysis of the major secondary endpoints will be included in the SAP.
Safety Analyses
The following analyses of AEs will be used to assess the safety of participants:
 
Frequency and type of AEs.
 
Frequency and type of SAEs.
 
Frequency and type of reasonably related AEs as assessed by the investigator.
 
Frequency and type of AEs leading to discontinuation of study intervention.
 
Frequency and type of infections, serious infections, and infections requiring oral or parenteral
antimicrobial treatment.
 
Frequency and type of AEs temporally associated with an infusion.
 
Frequency and type of injection-site reactions.
Summaries, listings, datasets, or participant narratives may be provided through Week 24 and Week 60, by
treatment intervention, for the above AEs, deaths, and severe AEs. Selected safety summaries will also be
performed for participants of the LTE.
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test over time, and by treatment intervention.
CTCAE toxicity grades (specified in the SAP) will be used in the summary of laboratory data. Descriptive
statistics will be calculated for each laboratory analyte at baseline and for observed values and changes
from baseline at each scheduled timepoint.
Vital Signs
Blood pressure (systolic and diastolic) will be summarized over time, using descriptive statistics and/or
graphically. The percentage of participants with values beyond clinically important limits will be
summarized.
Other Analyses
Pharmacokinetic Analyses
Serum guselkumab concentrations will be summarized over time for all participants who receive at least
1 dose of guselkumab. Descriptive statistics will be calculated at each sampling timepoint.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
16
Status: Approved, Date: 24 May 2022
Urine guselkumab concentrations will be summarized in a separate report.
Immunogenicity Analyses
The incidence of anti-guselkumab antibodies will be summarized for all participants who receive at least
1 dose of guselkumab and have appropriate samples for detection of antibodies to guselkumab (ie,
participants with at least 1 sample obtained after their first dose of guselkumab).
The incidence of neutralizing antibodies (NAbs) to guselkumab will be summarized for participants who
are positive for antibodies to guselkumab and have samples evaluable for NAbs to guselkumab.
Biomarkers Analyses
Changes in serum protein analytes may be summarized for the induction period and summarized by
treatment group for the maintenance period. Associations between baseline levels and changes from
baseline in select markers and response to treatment may be explored. Ribonucleic acid (RNA) analyses
from cells in blood or urine may be summarized in a separate technical report.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum concentrations of guselkumab and the efficacy measures and/or relevant
PD endpoints may be explored graphically when appropriate. If any visual trend is observed, additional
analysis may be conducted if deemed necessary, and will be described in a separate report if performed.
Pharmacogenomic Analyses
Genetic (deoxyribonucleic acid [DNA]) analyses will be conducted only in participants who sign the
consent form to participate in the pharmacogenomic sampling. These analyses are considered exploratory
and may be summarized in a separate technical report.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
17
Status: Approved, Date: 24 May 2022
1.2. 
Schema
Figure 1: 
Schematic Overview of the Study
Abbreviations: CRR complete renal response; DBL database lock; F/U follow up; LTE long term extension; IV intravenous; MSE major
secondary endpoint; N number of participants; PE primary endpoint, R randomization; SC subcutaneous; SOC standard of care.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
18
Status: Approved, Date: 24 May 2022
1.3. 
Schedule of Activities (SoA)
Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)
Phase 
Screeninga 
Double-blind Period  
Follow-up  
Notes
Weekb 
(≤8Weeks) 
0 
D2 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52/Final 
Efficacy 
Visitc,f 
60 or Final
Safety
Visitd,g
Study Procedure
Screening/Administrative
Informed consent
X
Must be signed before first study related
activity.
ICF for optional genetic
research samples
X
Demographics 
X
Review medical history
requirements
X
Review prestudy
therapy
X
Detailed information of prestudy topical and
systemic SLE and LN therapies including
dosage and frequency of administration must
be recorded for past history. Other prestudy
therapies administered at the time of
screening or up to 60 days before the first
dose of study intervention, whichever is
longer, must be recorded on the eCRF.
Inclusion/exclusion
criteria
X 
X
Minimum criteria for the availability of
documentation supporting the eligibility
criteria are described in Source Documents
section of Appendix 9, Regulatory, Ethical,
and Study Oversight Considerations. Check
clinical status again before first dose of study
intervention.
12 lead ECG  
X
QuantiFERON TB® test
X
All participants will undergo
QuantiFERON® TB testing. If the
QuantiFERON® TB test is not
approved/registered in the country in which
this protocol is being conducted or the
tuberculin skin test is mandated by local
health authorities, a negative tuberculin skin
test result is also required. In Ukraine, while
the QuantiFERON® TB test is not
approved/registered, it is accepted, and a
tuberculin skin test is not required.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
19
Status: Approved, Date: 24 May 2022
Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)
Phase 
Screeninga 
Double-blind Period  
Follow-up  
Notes
Weekb 
(≤8Weeks) 
0 
D2 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52/Final 
Efficacy 
Visitc,f 
60 or Final
Safety
Visitd,g
Study Procedure
Tuberculin skin test 
X 
Only required if QuantiFERON® TB is not
registered/approved or accepted locally or the
TST is mandated by local health authorities.
HBV and HCV testing 
X 
See Appendix 4 for details.
HIV test 
X
Chest x ray  
X
Chest x ray posterior/anterior and lateral
views (or per country regulations where
applicable) must be taken within 12 weeks
prior to randomization and read by a qualified
radiologist (or pulmonologist in accordance
with local regulations), with no evidence of
current, active TB or old, inactive TB. A
chest computed tomography (CT) scan,
obtained outside of the protocol, is also
acceptable instead of a chest radiograph.
SLE classification by 
2019 EULAR/ACR  
criteria
X 
The 2019 EULAR/ACR criteria are provided
in Appendix 2 (Section 10.2).
Renal biopsy Class 
III/IV Activity  
X
For participants not having a previous renal
biopsy (within the last 6 months prior to
screening), one must be performed during
screening. The pathology report documenting
renal biopsy Class III/IV (based on ISN/RPS
histology criteria)activity should be
submitted to the sponsor.
Tissue samples to assess for biomarker
analysis should be sought for all renal
biopsies for all participants who consent.
Study Intervention Administration
Randomization 
X
Study intervention 
infusion (at study site) 
X 
X 
X
Participants should remain for observation for
1 hr following the infusion.
Study intervention SC 
injection (at study site) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Participants should remain for observation for
30 minutes following the injections.
Efficacy Assessments
PROs 
Whenever possible, patient reported outcome
assessments should be conducted before any
tests, procedures, or other consultations for
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
20
Status: Approved, Date: 24 May 2022
Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)
Phase 
Screeninga 
Double-blind Period  
Follow-up  
Notes
Weekb 
(≤8Weeks) 
0 
D2 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52/Final 
Efficacy 
Visitc,f 
60 or Final
Safety
Visitd,g
Study Procedure
that visit to prevent influencing participants’
perceptions. It is recommended that PROs be
performed in the following sequence:
FACIT fatigue, PGIC, lupus symptoms
(assessment of joint pain, joint stiffness, rash,
and swelling), and LupusQoL.
FACIT Fatigue 
X 
X 
X 
X
PGIC  
X 
X
Lupus Symptoms 
X 
X 
X 
X 
X
LupusQol 
X 
X 
X
ClinROs 
ClinRO portion to be completed by the
investigator/designee at all sites.
SLEDAI 2K 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
PGA of Disease
Activity
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Joint count
assessment
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Cutaneous lupus
(CLASI)
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Repeat renal biopsy 
(optional) 
Xh 
The pathology report should be submitted to
the sponsor. Tissue samples to assess for
biomarker analysis should be sought for all
renal biopsies for all participants who
consent.
Safety Assessments
Full physical 
examination  
X 
X
A physical examination will be performed at
screening and the Week 60/Final safety
follow up visit. The head and neck, chest,
abdomen, and extremities should be
examined, as well as including examinations
based on the individual’s medical history and
manifestations of SLE and LN (edema, skin
manifestations, arthritis, etc.).
Targeted physical 
examination  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Targeted physical examination should also
include evaluation of signs or symptoms of
infection.
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Height 
X
Weight 
X 
X 
X 
X
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
21
Status: Approved, Date: 24 May 2022
Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)
Phase 
Screeninga 
Double-blind Period  
Follow-up  
Notes
Weekb 
(≤8Weeks) 
0 
D2 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52/Final 
Efficacy 
Visitc,f 
60 or Final
Safety
Visitd,g
Study Procedure
TB evaluation
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
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 (consistent with local
regulations), and QuantiFERON® TB test
should be performed. A TST is additionally
required if the QuantiFERON® TB test is not
registered/approved locally or the TST is
mandated by local health authorities.
Urine pregnancy test
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Females of childbearing potential only.
A serum pregnancy test may be conducted at
screening at the discretion of investigator or if
required by local regulations.
Review concomitant
therapy
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Glucocorticoid tapering
<Weeks 2 to 12>
See Section 6.5.2 and Appendix 7
(Section 10.7)for information on
glucocorticoid tapering.
Adverse events
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
AE review should include review and
documentation of medical history including
information about seeking medical attention
or hospitalizations that occur between study
visits.
eC SSRS
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
At the screening visit, the eC SSRS should be
completed as the first assessment after
signing informed consent and before any
other tests, procedures, or other consultations.
For subsequent visits, the eC SSRS should be
completed after all PROs and before any
other tests, procedures, or other consultations.
Infusion or injection
site reaction evaluation
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Participants should be monitored for the
occurrence of infusion or injection site
reactions for 60 or 30 minutes after the study
intervention administration, IV infusion or
SC injection, respectively.
NCT04376827


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
22
Status: Approved, Date: 24 May 2022
Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)
Phase 
Screeninga 
Double-blind Period  
Follow-up  
Notes
Weekb 
(≤8Weeks) 
0 
D2 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52/Final 
Efficacy 
Visitc,f 
60 or Final
Safety
Visitd,g
Study Procedure
Clinical Laboratory Tests
Chemistry  
Xe 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Cystatin C  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Lipid panel (fasting) 
X 
X 
X 
For fasting laboratory assessments, if the
participant has not fasted before the visit, the
visit may proceed, a note should be made in
the laboratory requisition form that the
participant had not fasted.
Hematology  
Xe 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Anti CCP/RF 
X
Flow cytometry  
X
Perform test clinical B cell flow cytometry
analyses at screening for participants
previously exposed to B cell depleting
therapies (eg, rituximab and obinutuzumab).
Coagulation  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
This refers to PT, PTT, and INR.
Antinuclear antibodies 
X 
X
Anti dsDNA, C3, C4  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Other autoantibodies 
X 
X 
X 
X
Other autoantibodies include testing for anti
Smith, SSA anti Ro, SSB anti La, anti RNP.
Anti phospholipid 
antibodies 
X 
X 
X 
X
This testing includes: anti cardiolipin IgG
and IgM, anti Beta2 glycoprotein IgG and
IgM, and lupus anticoagulant.
If an abnormal test result is not obtained at
Screening or Week 0, no additional follow up
testing is required. However, additional
testing may be performed if clinically
indicated.
Ig isotype profile 
X 
X 
X
Urine Analyses (spot urine)
Urinalysis (dipstick, all
participants)
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X
Urine sample for 
biomarkers (where local 
regulations permit) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xh
This urine sample will need to be processed
as per the procedure in the laboratory manual
including centrifugation, with the supernatant
frozen and the pellet cryopreserved.
Urine protein/creatinine 
ratio 
2Xe 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xh 
X
The UPCR must be collected on first morning
void specimens. Two urine specimen
containers should be provided prior to visits
for this collection.
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Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)
Phase 
Screeninga 
Double-blind Period  
Follow-up  
Notes
Weekb 
(≤8Weeks) 
0 
D2 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52/Final 
Efficacy 
Visitc,f 
60 or Final
Safety
Visitd,g
Study Procedure
Urine sediment analysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xh
24-hour urine analyses
Urine protein/creatinine 
ratio 
Give urine jug
for Wk0 
collection
X 
jug 
X 
jug 
Xh
Give urine jug during screening for Week 0
collection. Give urine jug at the Week 20 and
Week 48 visits for Week 24 and Week 52
collections.
24 hr urine for PK  
X 
X 
1. At Week 0 predose, the 24 hour PK urine
samples will be taken from the 24 hour
urine collection for urine protein and
creatinine.
2. A post dose sample will be taken starting
with the first void after the start of the first
infusion and ending with the last void
within 24 hours of the end ofthe first
infusion. The sample will be returned to
the study site at the Day 2 visit (+24 hour
window).
Pharmacokinetics/Immunogenicity
Serum guselkumab 
concentrations 
2X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
1.  At Week 0, 2 separate samples for serum
guselkumab concentrations (indicated by
“2X” in the SoA) will be collected
(1 sample will be collected prior to the IV
infusion and the other collected 1 hour
after the end of the infusion) for all
participants. For all other visits that
include study intervention administration,
only a predose serum guselkumab
concentration sample will be collected.
2. For visits with study intervention
administration, all blood samples for
assessing predose guselkumab
concentration and antibodies to
guselkumab MUST be collected BEFORE
the administration of the study
intervention.
3.  When both PK/ADA samples are
collected, one sample (instead of 2) will be
collected for both assays.
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Status: Approved, Date: 24 May 2022
Table 1: 
Schedule of Activities –Main Study (Screening Through Week 60)
Phase 
Screeninga 
Double-blind Period  
Follow-up  
Notes
Weekb 
(≤8Weeks) 
0 
D2 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52/Final 
Efficacy 
Visitc,f 
60 or Final
Safety
Visitd,g
Study Procedure
Population PK
X 
(Weeks 0 to 4)
X 
(Weeks 12
to 16)
These are additional study visits, at which a
venous blood sample for population PK
analysis will be collected from all
participants. This random sample collection
must occur on any day in each of the
2 designated time periods except on the days
of scheduled study visits. Additionally, this
blood sample must be collected at least
24 hours prior to or after the actual time of
study intervention administration. Note: This
random sample may not be drawn on the
Day 2 visit.
Antibodies to study
intervention 
X 
X 
X 
X 
X 
X 
X 
X
When both PK/ADA samples are collected,
one sample (instead of 2) will be collected for
both assays.
Pharmacogenomics (DNA)
Blood sample collection
(optional)
X 
X 
X
The pharmacogenomic (DNA) sample should
be collected at the specified timepoint,
however if necessary, it may be collected at a
later timepoint. The screening sample should
be collected no later than prior to
randomization.
Blood Biomarkers (where local regulations permit)
Serum biomarkers 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X
Whole blood (RNA) 
X 
X 
X 
X 
X 
X 
X 
X
PBMC (cellular 
analysis) 
X 
X 
X 
X 
X 
X
Whole blood will be collected and processed
for PBMC cryopreservation.
Abbreviations: ACR American College of Rheumatology; ADA anti drug antibodies; AE adverse events; anti CCP anti cyclic citrullinated peptide; anti RNP anti ribonucleoprotein; CLASI Cutaneous Lupus Erythematosus Disease Area and Severity Index;
ClinROs Clinical Reported Outcomes; DNA deoxyribonucleic acid; dsDNA double stranded DNA; ECG electrocardiogram; eCRF electronic case report form; eC SSRS electronic Columbia Suicide Severity Rating Scale; EULAR European League Against
Rheumatism; FACIT Functional Assessment of Chronic Illness Therapy; HBV hepatitis B virus; HCV hepatitis C virus; HIV human immunodeficiency virus; ICF informed consent form; Ig immunoglobulin; INR International Normalized Ratio;
ISN/RPS
International Society of Nephrology/Renal Pathology Society; IV intravenous; LN lupus nephritis; PBMC peripheral blood mononuclear cell; PGA Physician’s Global Assessment; PGIC Patient Global Impression of Change; PK pharmacokinetics;
PRO patient reported outcomes; PT prothrombin time; PTT partial thromboplastin time; RF rheumatoid factor; RNA ribonucleic acid; SC subcutaneous; SLE systemic lupus erythematosus; SLEDAI 2K SLE disease activity index 2000; SSA anti Ro anti
Sjögren's syndrome related antigen A; SSB anti La anti Sjögren’s syndrome related antigen B; TB tuberculosis; TST tuberculin skin test; UPCR  Urine Protein to Creatinine Ratio; Wk Week.
Footnotes:
a. 
Screening visit must be performed no more than 8 weeks prior to the randomization visit (Week 0). Screening may be extended by up to 4 additional weeks for participants who start MMF/MPA at or near (within
2 weeks before) the beginning of screening to allow for repeat of laboratory entry criteria after 8 weeks of mycophenolate mofetil (MMF)/ mycophenolic acid (MPA)treatment.
b. 
Administration of study intervention and visit window must be within ±7 days of the scheduled visit date. Unless otherwise specified, all assessments (except for infusion/injection-site evaluation) are to be completed
prior to study intervention administration.
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c. 
For participants who discontinue study intervention administrations, every effort should be made to conduct final efficacy and safety assessments. Participants who permanently discontinue study intervention, but do
not withdraw from study participation, should be followed at all subsequent study visits through Week 60. Week 52 may serve as the final safety follow-up visit if study medication was stopped on or before
Week 40, but a full physical exam should be performed at that visit (Week 52). Sites will be notified after all enrolled participants have completed the Week 20 visit or discontinued study intervention prior to
Week 24. Participants who are receiving study intervention will then complete a final efficacy visit approximately 4 weeks after the last administration of study intervention and the final safety follow-up visit
approximately 12 weeks after the last administration of study intervention.
d. 
Participants who discontinue study intervention administrations and do not wish to continue in the study should return 12 weeks after the last study intervention administration for a final safety follow-up visit and
complete assessment as indicated for Week 60.
e. 
Chemistry, hematology, and UPCR (x2) must be completed after the participant has received at least 8 weeks of MMF/MPA.
f. 
Refer to Table 2 for additional Week 52 assessments to be performed for participants who continue in the long-term extension (LTE).
g. 
These assessments will be performed for participants who complete their Week 52 visit, but do not enter the LTE.
h. 
Urinalysis assessments should not be done within 48 hours after biopsy to limit possible blood from biopsy in urine.
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Status: Approved, Date: 24 May 2022
2. 
INTRODUCTION
Guselkumab (CNTO 1959) is a fully human immunoglobulin G1 lambda monoclonal antibody
(mAb) that binds to human interleukin (IL)-23 with high affinity. The binding of guselkumab to
IL-23 blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor, inhibiting
IL-23-specific intracellular signaling and subsequent activation and cytokine production. In this
manner, guselkumab inhibits the biological activity of IL-23 in all in vitro assays examined.
Guselkumab has been approved for the treatment of adults with moderate to severe plaque
psoriasis in the United States (US), European Union (EU), Canada, Japan, and a number ofother
countries worldwide. In addition, guselkumab has been approved for the treatment of psoriatic
arthritis (PsA), generalized pustular psoriasis, erythrodermic psoriasis, and palmoplantar
pustulosis in Japan.
Guselkumab is currently being developed in other diseases including for the treatment of patients
with PsA, hidradenitis suppurativa (HS), familial adenomatous polyposis, Crohn’s disease, and
ulcerative colitis (UC). Phase 3 studies in PsA, a Phase 2/3 program in Crohn’s disease, a
Phase 2b/3 study in UC, and a Phase 2 study in HS are currently ongoing or planned globally.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator's Brochure (IB)for guselkumab.
The term “study intervention” throughout the protocol, refers to study drug, as defined in
Section 6.1, Study Interventions Administered.
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.
The term "participant" throughout the protocol refers to the common term "subject".
2.1. 
Study Rationale
Lupus is a heterogeneous autoimmune disease that includes a broad spectrum of clinical forms,
ranging from those with lesions confined to the skin (cutaneous lupus erythematosus [CLE]) to
others that involve 1 or more vital internal organs (systemic lupus erythematosus [SLE]). Renal
involvement due to SLE is termed lupus nephritis (LN).
Clinicopathologic Class III (focal proliferative) and Class IV (diffuse proliferative) LN per the
current classification system of International Society of Nephrology/Renal Pathology Society
(ISN/RPS) are considered more severe and have a poorer prognosis than Class I (minimal disease)
or Class II (mesangial proliferative). Both Class III and IV LN may have active (proliferative),
inactive (sclerosing), or combined active and inactive lesions.38 Approved therapies for active LN
are lacking, and patients with Class III or IV disease have a 50 to 75% risk of end-stage renal
disease requiring dialysis within 10 years.37 There is a high unmet need for new treatment options
in LN that are safe and effective, especially new therapies that can provide improved long-term
efficacy (ie, sustained remission) over currently available therapies (Section 2.1.1).
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The Phase 2 clinical development program for guselkumab for active Class III or IV LN will
evaluate the safety and efficacy of guselkumab added to standard-of-care compared to placebo
added to standard-of-care. This study was originally planned to enroll a target of approximately
60 participants with a total duration of up to approximately 68 weeks. Due to the sponsor’s decision
to stop screening of new participants as a result of enrollment challenges, fewer than 60
participants will be enrolled in the study  
.
An overview of the protocol design and supportive rationale is described in Section 4.
The clinical and scientific rationale in support of the overall development program is described in
Section 2.1.2.
Relevant background information on the nonclinical and clinical development of guselkumab is
summarized in Section 2.2.
2.1.1. 
Unmet Need in Lupus Nephritis
There are limited treatments approved to treat LN globally, although cyclophosphamide and some
glucocorticoids are approved to treat LN in the EU. However, the combination of a high-dose
glucocorticoid 
in 
combination 
with  cyclophosphamide or mycophenolate 
mofetil
(MMF)/mycophenolic acid (MPA) is an off-label treatment that has become standard-of-care in
more active forms of LN. Belimumab and voclosporin have been approved in the United States
for adults with active LN who are receiving standard background immunosuppressive therapy
regimens.3,20 Despite these treatments, there is still a high rate of treatment failures (TFs) and
progression to end-stage renal disease, highlighting the significant unmet medical need for more
effective therapies, especially over the longer term. 11,26,32
2.1.2. 
Rationale for Targeting IL-23 in Lupus Nephritis
Lupus nephritis is a manifestation of SLE affecting up to 60% of SLE patients at some point in
their disease course. The hallmark in the pathogenesis of LN is autoantibody production and an
immune complex formation with infiltration of inflammatory cells in renal tissue.42 Anti-double-
stranded deoxyribonucleic acid (dsDNA) antibodies and also antinucleosome antibodies are
specific to SLE and are more highly associated with incidence or flare of LN than with other organ
manifestations, both in human disease and in murine models.2,22,23,25,34,39 Remission of LN is
associated with decreases in anti-deoxyribonucleic acid (DNA)antibody levels.13,19
Interleukin-23 is important for the generation and maintenance of T-helper (Th)17 cells. There is
evidence which suggests that Th17 cells are involved in SLE and LN, including the detection of
IL-17+ T cells in the kidneys of SLE patients with nephritis.15,42 Additionally, IL-17+ T cells have
been reported in the spleen and kidney of lupus-prone mice, and these cells have a higher
expression of IL-23 receptors in the mice as they age and disease progresses.15 Studies have shown
that IL-23 is released from antigen presenting cells, which induces expansion of Th17 cells,
forming what is known as the IL-23/IL-17 axis.18,42 Additionally, other studies have shown high
serum levels of IL-23 in LN.4,40,42
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In a proof-of-concept preclinical mouse study, a mAb targeting IL-23 was given to lupus-prone
mice with nephritis. Control mice developed pyuria and proteinuria. Anti-IL-23 treated mice did
not develop pyuria, developed lower levels of proteinuria than the control treated mice, and
exhibited a decrease in IL-17 production.15 An IL-23 receptor deficiency has also been shown to
prevent development of nephritis in mice.16,42
A study completed in Polish patients with SLE showed correlation between elevated IL-23 and
patients having LN8; similar data was also shown in study in Chinese patients.41 In a 2015 clinical
study, 50 patients with active LN had biopsies taken at baseline and after treatment (eg,
cyclophosphamide, or MMF  + glucocorticoids). Those not responding to treatment (persistent
proteinuria >0.5 gram/day) were found to have higher levels of IL-23 than others after treatment,
while higher IL-17 at baseline was found in those with poor histological response (eg, persisting
active nephritis).
Taken together, these data support the scientific rationale for further evaluation of an IL-23
inhibitor in patients with LN. In this study, guselkumab, a human mAb directed against the p19
subunit of the IL-23, and thus inhibits IL-23, will be evaluated.
2.2. 
Background
2.2.1. 
Nonclinical Studies
A full nonclinical development program was conducted with guselkumab  to support the
development of guselkumab for psoriasis and other indications in accordance with International
Conference on Harmonisation (ICH) and other applicable guidelines. A comprehensive overview
of nonclinical data is presented in Section 3 of the guselkumab IB. Details on the nonclinical
studies supporting dosing is detailed in Section 4.3.
Nonclinical Pharmacology
Guselkumab has been shown to be pharmacologically active. Guselkumab prevents binding of
IL-23 to the IL-23 receptor and subsequent activation of intracellular signaling pathways. In vitro
studies have demonstrated that guselkumab inhibits the biological activity of human and
non-human primate IL-23.
Nonclinical Safety Pharmacology
In nonclinical toxicology assessments, no adverse effects of guselkumab were observed in safety
pharmacology evaluations following single or repeated dosing of cynomolgus monkeys via
intravenous (IV) and subcutaneous (SC) routes of administration at doses up to 50 mg/kg once
weekly for up to 6 months. Additionally, guselkumab was well-tolerated during a cardiovascular
(CV)safety pharmacology assessment in monkeys.
Nonclinical Pharmacokinetics
The pharmacokinetics (PK) of guselkumab was investigated in male cynomolgus monkeys
following a single IV or SC administration of guselkumab. Monkeys were treated with a single IV
dose of guselkumab at 50 mg/kg or a single SC dose of guselkumab at 1, 10, or 50 mg/kg. The
maximum observed concentration (Cmax) and area under the serum concentration versus time curve
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Status: Approved, Date: 24 May 2022
from time 0 to infinitywith extrapolation of the terminal phase (AUCinf), appeared to increase dose
proportionally from 10 to 50 mg/kg, but less than dose proportionally from 1 to 10 mg/kg. The
observed time to maximal concentration (Tmax) was 1 to 5 days after SC administration. The mean
elimination half-life (T1/2) after SC administration ranged from 7 to 10 days.
The PK of guselkumab was assessed as part of a 5-week (Phase 1) and 6-month (Phase 2)
toxicology study in cynomolgus monkeys. In Phase 1, the systemic exposure of guselkumab
increased in an approximately dose proportional manner over the dose range of 10 to 50 mg/kg
after SC administration. In Phase 2 of the study, the Cmax  and area under the curve (AUC) within
1 dose interval increased in an approximately dose proportional manner at steady-state following
weekly SC administration of guselkumab.
Nonclinical Toxicology
Administration of guselkumab was not associated with any toxicologically significant findings in
repeat dose toxicity studies in cynomolgus monkeys (once weekly) or guinea pigs (twice weekly);
these are the pharmacologically relevant species for the evaluation of the general and
developmental toxicity assessment of guselkumab. No evidence of CV effects was noted in
cynomolgus monkeys in a CV safety pharmacology assessment at IV doses of 10 and 50 mg/kg,
or during the 5-week (IV/SC)/24-week (SC) study at doses up to 50 mg/kg that included
assessments for CV liability. Guselkumab had no effects in pregnant cynomolgus monkeys or their
infants following once per week SC doses up to 50 mg/kg in an enhanced prenatal and postnatal
development study. Fertility and early embryo/fetal development were unaffected in the male and
female guinea pig following twice weekly SC administration of 25 and 100 mg/kg guselkumab.
2.2.2. 
Clinical Studies
Guselkumab has demonstrated efficacy in psoriasis and has received marketing approval in several
countries and regions globally for the treatment of adults with moderate to severe plaque psoriasis,
including in the US, Canada, EU, Latin America, and the Asia Pacific region. The approved
guselkumab dose for psoriasis is 100 mg by SC injection at Weeks 0, 4, and every 8 weeks (q8w)
thereafter. In addition, guselkumab has been approved for the treatment of PsA, GPP,
erythrodermic psoriasis, and palmoplantar pustulosis in Japan.
Guselkumab is also being studied in HS and familial adenomatous polyposis. A pediatric study in
participants with chronic plaque psoriasis aged ≥6 to <18 years old is also ongoing. Phase 3
development is ongoing globally in PsA, and a seamless global Phase 2/3 clinical program is
ongoing in Crohn’s disease. The Phase 2b study of the ongoing Phase 2/3 guselkumab Crohn’s
disease program, and Phase 2 HS studies evaluated the same induction dose regimens up to a
maximum dose of 1200 mg IV every 4 weeks (q4w)given 3 times, as well as a maintenance dose
range from 100 mg SC q8w to 200 mg SC q4w. The ongoing Phase 3 study of the Phase 2/3
guselkumab Crohn's disease program is evaluating an induction dose of 200 mg IV q4w given 3
times and a maintenance dose of 100 mg SC q8w or 200 mg SC q4w. In addition, a guselkumab
and golimumab combination Phase 2a proof-of-concept study in UC which includes a guselkumab
monotherapy arm (guselkumab 200 mg IV at Weeks 0, 4, and 8 followed by guselkumab 100 mg
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Status: Approved, Date: 24 May 2022
SC q8w) is currently ongoing. Details about these guselkumab clinical development programs
across various indications are provided in Section 4 of the latest version of the guselkumab IB.
Through the IB cutoff date of 12 July 2019, an estimated 203 healthy participants,
3,454 participants with psoriasis, 109 participants with rheumatoid arthritis (RA),
1,136 participants with PsA, 182 participants with palmoplantar pustulosis, 151 participants with
Crohn’s disease, 149 participants with HS, 29 participants with UC, and 3 participants with
familial adenomatous polyposis have been exposed to guselkumab. Overall, an estimated
5,416 participants have been exposed to guselkumab in the clinical development program.
The largest clinical experience to date with guselkumab has been in plaque psoriasis. The safety
profile of guselkumab in participants with moderate to severe plaque psoriasis is based on data
from the Phase 2 study CNTO1959PSO2001 and Phase 3 studies CNTO1959PSO3001,
CNTO1959PSO3002, and CNTO1959PSO3003. Of the 2,177 guselkumab treated participants,
1,748 participants were exposed for at least 1 year, 1,516 were exposed for at least 2 years, and
692 participants were exposed for 3 years. Long-term extensions of 2 of the studies
(CNTO1959PSO3001 and CNTO1959PSO3002) are ongoing and will continue through up to
5 years of follow-up.
2.3. 
Benefit-Risk Assessment
More detailed information about the known and expected benefits and risks of guselkumab may
be found in the guselkumab IB.
2.3.1. 
Risks for Study Participation
Potential Risks of Clinical 
Significance 
Summary of Data/
Rationale for Risk  
Mitigation Strategy
Clinical worsening of LN  
The benefit-risk of guselkumab in
treatment of LN has not been
established.
• During the study, participants
will be permitted to continue
treatment of LN with certain
standard-of-care medications
(Section 6.5).
• Participants may discontinue
study intervention if it is not in their
best interest or if they need to
initiate certain protocol-prohibited
medications including certain
biologics (Sections 6.5 and 7.1).
• Participants will be allowed to
use glucocorticoids as needed,
although this may trigger a TF if a
high enough dose is required as
detailed in Section 6.5.2.
Potential Risks Due to Study Intervention Guselkumab
Serious infections and reactivation 
of latent infections 
Available animal and human data 
suggest that blockade of IL-23 may 
be associated with an increased 
infection risk. 
• Participants with a history of, or
ongoing, chronic or recurrent
infectious disease, including human
immunodeficiency virus (HIV),
Hepatitis B or C virus (HBV,
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Infections have been identified as 
adverse reactions of guselkumab, 
including respiratory infections, 
herpes simplex and tinea infections. 
and gastroenteritis. 
HCV), will be excluded from the
study. Similarly, participants with
evidence of active or untreated
latent tuberculosis (TB) will be
excluded from the study
(Section 5.1.1).
• Participants who have received
a live viral or bacterial vaccination
within 12 weeks of baseline will be
excluded from the study. In
addition, participants must agree
not to receive a live viral or live
bacterial vaccination during the
study and for 12 weeks after
receiving the last dose of study
intervention (Section 5.1.1).
• Participants will be instructed to
seek medical attention if they
develop signs or symptoms
suggestive of an infection, and
investigators are instructed in the
protocol to monitor for signs or
symptoms of infections, including
TB (Sections 8.2.10 and 8.2.11).
• Discontinuation of a
participant’s study intervention
must be strongly considered if the
participant develops a serious
infection, including but not limited
to sepsis or pneumonia. In addition,
any serious infection should be
discussed with the medical monitor
or designee, and study intervention
should be withheld until the clinical
assessment is complete
(Section 7.1).
Hypersensitivity reactions, 
including serious hypersensitivity 
reactions. 
Serious hypersensitivity reactions 
including anaphylaxis have been 
reported in postmarketing 
experience with guselkumab in 
psoriasis patients. 
Hypersensitivity, including 
anaphylaxis, urticaria and rash have 
been identified as adverse drug 
reactions for guselkumab. 
• Participants with known allergy,
hypersensitivity, or intolerance to
guselkumab or its excipients will be
excluded from the study.
• Sites are instructed that before
any administration of study
intervention, appropriately trained
personnel and medications (eg,
injectable epinephrine) must be
available to treat hypersensitivity
reactions, including anaphylaxis. In
addition, all participants must be
observed carefully for signs and
symptoms of a hypersensitivity
reaction (eg, urticaria, pruritis,
angioedema, wheezing, dyspnea, or
hypotension) (Section 8.2.8).
• Any participant who develops a
serious hypersensitivity reaction
such as anaphylaxis must
discontinue study intervention
(Section 7.1).
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Malignancy  
The preponderance of preclinical 
data suggests that blockade of 
endogenous IL-23 would not be 
detrimental and may in fact be 
beneficial in tumor 
immunosurveillance and host 
protection; however, a risk of 
malignancy cannot be excluded. 
• Those participants who
currently have a malignancy or
have a history of malignancy within
5 years prior to screening (with
exceptions noted in Section 5.1.1)
will be excluded from the study.
Additionally, participants who have
a history of lymphoproliferative
disease, including lymphoma; a
history of monoclonal gammopathy
of undetermined significance or
signs and symptoms suggestive of
possible lymphoproliferative
disease, such as lymphadenopathy
or splenomegaly will be excluded
from the study (Section 5.1.1).
• During the conduct of the study,
participants will undergo regular
clinical monitoring including
routine safety labs to assess for any
changes in health status that may
indicate a possible malignancy.
• Participants who develop a
malignancy during the study (with
the exception ofno more than 2
localized basal cell skin cancers
that are treated with no evidence of
recurrence or residual disease) will
be discontinued from study
intervention (Section 7.1).
Liver injury  
A serious adverse event (SAE) of 
‘toxic hepatitis’ was reported in the 
ongoing Phase 2/3 guselkumab 
Crohn’s disease program in a 
participant who received 
guselkumab 1200 mg IV at Weeks 
0, 4, and 8, and 200 mg SC at 
Week 12. Based on the 
hepatocellular pattern of injury, 
temporal relationship of the event 
to guselkumab exposure, and the 
exclusion of alternative etiologies, 
this event may represent 
drug-induced liver injury possibly 
related to guselkumab. 
Transaminase increases have been 
identified as an adverse reaction of 
guselkumab. In PsA studies 
transaminase increases were 
observed with a higher incidence
with a maintenance dose of 100 mg
q4w compared to100 mg q8w.
• During the conduct of the study,
liver function tests will be
monitored at regular intervals in
accordance with regulatory
guidance.9 In addition, the
induction doses in this study will be
lower and will not exceed 400 mg
IV.
• Participants with marked liver
enzyme elevations or symptoms or
signs of liver dysfunction (eg,
jaundice), should undergo a
thorough investigation for possible
causes of liver injury. A participant
must have their study intervention
discontinued if the participant has
severe liver test abnormalities that
are not transient and are not
explained by other etiologies
(Section 7.1).
Immunosuppression 
Although guselkumab has been 
studied with other 
immunosuppressives in other 
diseases, there may be an increased 
risk of infection or malignancy. 
In order to minimize the theoretical
increased risk of infection or
malignancy with the combination
of guselkumab with
immunosuppressive therapy, the
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baseline dose of oral
glucocorticoids on study entry is
limited to a minimum prednisone
equivalent dose of 10 mg/day and
maximum 1 mg/kg/day or
≤60 mg/day, whichever is lower,
which must be tapered starting from
Week 2. Additionally, participants
are also excluded from the study if
they have received oral (PO)or IV
cyclophosphamide within 3 months
prior to randomization, received a
single B-cell targeting agent within
3 months prior to first study
intervention administration; or
received more than 1 previous
B-cell targeting therapy including
belimumab within 6 months prior to
first administration of the study
intervention; or received B-cell
depleting therapy (eg,
obinutuzumab) within 12 months
prior to first administration of the
study intervention or have evidence
of continued B-cell depletion
following such therapy: received
anti-tumor necrosis factor (TNF)
therapy, other biologic medications,
or experimental non-biologic
therapeutic agents within the past
90 day, or 5 half-lives prior to
screening, whichever is greater .
Further detail regarding
concomitant medications is
provided in Sections 5.1 and 5.1.1.
Risks Due to Study Procedures [if applicable]
Risks associated with renal biopsy 
include hematuria, hematoma, and 
pain. 
These risks are well recognized,
and the risk of serious
complications is rare.33
Trained and experienced physicians
will be performing the procedure
during this study.
2.3.2. 
Benefits for Study Participation
There is no established benefit to participants of receiving study intervention. Given the scientific
rationale for IL-23 blockade in the treatment of LN (Section 2.1.2), participants may experience
an improvement in disease status during treatment with guselkumab. Participants in the study will
also help in furthering development of this drug to treat LN and increased understanding of LN.
Thus, the knowledge gained from this study has the potential to benefit many more patients
suffering with LN, and thus offers potential public health benefits.
Participants may also experience some benefit from the participation in a clinical study irrespective
of receiving study treatment, due to regular visits and assessments monitoring their overall health.
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2.3.3. 
Benefit-Risk Assessment for Study Participation
Guselkumab has undergone extensive nonclinical and clinical development as summarized in the
latest version of the IB and described briefly in Section 2.2. The collective efficacy and safety
results of the Phase 1, Phase 2, and Phase 3 clinical studies in healthy volunteers and patients with
plaque psoriasis established a favorable benefit-risk profile for guselkumab in the treatment of
plaque psoriasis and regulatory approval for the plaque psoriasis indication. In Japan, guselkumab
has also been studied and received regulatory approval for the treatment of erythrodermic
psoriasis, generalized pustular psoriasis, and palmoplantar pustulosis. This clinical experience
provided support for the ongoing development of guselkumab in other inflammatory diseases such
as Crohn’s disease, UC, PsA, and HS.
Although at present there are no clinical results for guselkumab in the treatment of LN, animal and
human data suggests IL-23 plays an important role in the pathogenesis of LN (Section 2.1.2) and
inhibition of IL-23 cytokines will be helpful in controlling LN.
It is acknowledged that the proposed dose to be evaluated in induction (ie, 400 mg IV q4w given
3 times) and in maintenance (ie, 200 mg SC q4w)in this protocol is higher than the approved dose
regimen  of guselkumab in psoriasis. Based on the data from nonclinical toxicology studies
(Section 2.2.1), the predicted exposure margins during the induction and maintenance treatment
periods relative to the exposure at the no observed adverse effect level (NOAEL) identified in
cynomolgus monkey are adequate to support the proposed clinical doses (Section 4.3). The
Phase 2b study of the ongoing Phase 2/3 guselkumab Crohn’s disease program and the Phase 2
HS study evaluated induction dose regimens up to 1200 mg IV. The Phase 2b/3 UC study is
evaluating the same induction and maintenance dose regimens as this program. Excluding the
single patient with the report of “toxic hepatitis” noted above, no significant safety concerns have
been reported after treatment through up to 1 year (20 participants through 1 year and 184 through
6 months), although these Phase 2 studies evaluated a limited number of participants.
Potential risks of guselkumab, including those of serious infection and malignancy, are being
addressed via judicious inclusion/exclusion criteria, frequent study visits to allow for close
monitoring of patient safety, guidelines for participant management (including monitoring of
clinical laboratory tests and treatment discontinuation criteria), detailed description of allowed and
prohibited concomitant medications, and comprehensive medical monitoring of data by the
sponsor during the conduct of the studies. In addition, a comprehensive safety monitoring plan
with oversight from an external, independent Data Monitoring Committee (DMC) will be
implemented to ensure the safety of guselkumab in participants with moderately to severely active
LN (Section 9.5).
In summary, the collective preclinical and clinical evidence for the anti-IL-23 mechanism of action
in LN, and the benefit-risk profile of guselkumab established to date in psoriasis and other
immune-mediated diseases, provide a strong scientific and clinical rationale for pursuing
development of guselkumab in patients with active LN and for the investigation of guselkumab in
this Phase 2 program. Taking into account the measures taken to minimize risk to participants in
this study, the potential risks associated with guselkumab are justified by the potential benefits that
may be provided to participants with LN.
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3. 
OBJECTIVES AND ENDPOINTS
Due to the Sponsor’s decision to terminate the study early, only the primary endpoint, major secondary
endpoints and safety endpoints may be reported in the clinical study report. Details will be described in the
statistical analysis plan (SAP).
For informational purposes, the below table outlines the objectives and endpoints originally planned for the
study.
Objectives 
Endpoints
Primary
 
To evaluate the efficacy of 
guselkumab in participants with 
active LN
 
Primary endpoint: Proportion of participants achieving at
least 50% decrease in proteinuria from baseline at Week 24
 
Major secondary endpoints to include:
 
Proportion of participants achieving complete renal
response (CRR) at Week 24
 
Proportion of participants achieving a sustained reduction
in steroid dose ≤10 mg/day of prednisone or equivalent
from Week 16 to Week 24
 
Proportion of participants achieving at least 50% decrease
in proteinuria from baseline at Week 52
 
Proportion of participants achieving CRR at Week 52
 
Proportion of participants with Urine Protein to Creatinine
Ratio (UPCR) <0.5 mg/mg at Week 24
 
Proportion of participants with UPCR <0.75 mg/mg at
Week 24
 
Time to achievement of CRR
 
Time to TF
Secondary
 
To evaluate the safety and 
tolerability of guselkumab in 
participants with active LN  
 
Frequency and type of adverse events (AEs), serious
adverse events (SAEs), reasonably related AEs, AEs
leading to discontinuation of study intervention, infections,
serious infections, and infections requiring oral or
parenteral antimicrobial treatment, AEs temporally
associated with an infusion, and injection-site reactions
 
Laboratory parameters and change from baseline in
laboratory parameters (hematology and chemistry)
 
Summary of maximum Common Terminology Criteria for
Adverse Events (CTCAE) toxicity grade for postbaseline
laboratory values (hematology and chemistry)
 
Systolic and diastolic blood pressures over time
 
To 
evaluate 
the 
PK, 
immunogenicity, in participants
with active LN
 
Serum guselkumab levels over time
 
Serum anti-guselkumab antibodies through Week 24,
through Week 60, end of long-term extension (LTE), and in
participants discontinuing study intervention early
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Objectives 
Endpoints
Tertiary/Exploratory
 
To evaluate the efficacy of
guselkumab in participants with
active LN over an extended
period
 
Proportion of participants maintaining CRR at Week 152
 
To evaluate the efficacy of
guselkumab in extrarenal lupus
manifestations
 
Proportion of participants with ≥4 point improvement at
Week 24 in systemic lupus erythematosus disease activity
index 2000 (SLEDAI-2K)modified to exclude renal items
 
Proportion of participants with baseline arthritis (with at
least 4 active joints at baseline) who have ≥50% reduction
in active joints at Week 24
 
Proportion 
of participants 
with 
baseline 
active
mucocutaneous lupus manifestations (CLASI score ≥8) and
≥50% reduction in Cutaneous Lupus Erythematosus
Disease Area and Severity Index (CLASI) scores at
Week 24
 
To evaluate the impact of
guselkumab on Health-Related
Quality of Life (HRQoL) and
fatigue in participants with
active LN
 
Change from baseline in Lupus Quality of Life (LupusQoL)
individual domains at Week 24
 
Change from baseline in Functional Assessment of Chronic
Illness Therapy (FACIT)-Fatigue score at Week 24
 
Change from baseline in lupus symptoms (joint pain, joint
stiffness, rash, and swelling [peripheral edema]) at Week 24
 
Patient Global Impression of Change [PGIC] - Change in
LN (health condition) at Week 24 and Week 52
 
Changes in PRO assessments including LupusQOL,
FACIT-Fatigue, lupus symptoms, and PGIC over time
during the long-term extension
 
To evaluate biomarkers of LN,
pharmacodynamic (PD) effects
of guselkumab, and to identify
participants most likely to
benefit from treatment with
guselkumab
 
Serum biomarkers including IL-23, IL-17A, IL-17F, IL-22,
complement (C)3, C4, C1q, or autoantibodies, eg,
anti-dsDNA
 
Cellular (urine and peripheral blood mononuclear cell
[PBMC]) and whole blood gene expression
 
Urine biomarkers (protein and /or nucleic acids)
 
Perform analyses of pre- and
post-treatment renal biopsies
(optional)
 
Histopathology of glomeruli and tubulointerstitial tissue,
immunohistochemistry for resident and infiltrating cell
types and inflammatory mediators (including IL-23, IL-17,
IL-21, interferon [IFN]-gamma, chemokines), and/or tissue
gene expression
Refer to Section 8, Study Assessments and Procedures for evaluations related to endpoints.
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Definitions of Efficacy Endpoints:
 
At least 50% decrease in proteinuria from baseline
Participants who have a decrease in proteinuria of at least 50% from baseline based on UPCR.
 
Sustained reduction in steroid dose ≤10 mg/day of prednisone or equivalent
Participants who sustained a continuous reduction in steroid to ≤10 mg/day of prednisone or
equivalent for the time duration measured.
 
Complete renal response
 
Urine Protein to Creatinine Ratio (UPCR) <0.5 mg/mg.
AND
 
Estimated Glomerular Filtration Rate (eGFR) ≥60 mL/min/1.73m2 or no confirmed
decrease ≥20% from baseline.
AND
 
Prednisone dose ≤10 mg/d.
 
Time to achievement of complete renal response
Time to first observation of CRR from baseline.
 
Time to Treatment Failure
Time to first occurrence of TF from baseline (Section 9.4.2).
 
Four (4) points improvement in systemic lupus erythematosus disease activity index 2000
modified to exclude renal items
A 4-point improvement from baseline in total SLEDAI-2K score modified to exclude renal
items (i.e., urinary casts, hematuria, proteinuria, pyuria).
 
50% reduction in active joints
Participants with baseline arthritis (with at least 4 active joints at baseline) and a ≥50%
reduction in active joints from baseline, i.e., an active joint must demonstrate tenderness and
at least one additional sign of inflammation (eg, observed swelling such as edema or effusion)
on physical examination as determined by the joint assessor.
 
50% reduction in Cutaneous Lupus Erythematosus Disease Area and Severity Index
score
Participants with baseline active mucocutaneous lupus manifestations (CLASI ≥8) and ≥50%
reduction in CLASI score from baseline (CLASI Activity and CLASI Damage analyzed
independently).
HYPOTHESIS
The primary hypothesis of this study is that guselkumab plus standard-of-care is superior to
placebo plus standard-of-care in participants with active LN as measured by the proportion of
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participants achieving at least a 50% reduction of proteinuria with protocol specified steroid
tapering regimen at Week 24.
4. 
STUDY DESIGN
4.1. 
Overall Design
4.1.1. 
Main Study
This is a randomized, double-blind, placebo-controlled, parallel, multicenter, interventional
Phase 2 study in participants aged 18 to 75 (inclusive) with active LN. The total duration of the
original study was up to 68 weeks: a ≤8-week screening period (rescreening is permitted once per
participant), a 48-week double-blind treatment period, and a 12-week safety follow-up period after
the last dose (8 weeks after the final efficacy visit). Participants starting MMF/MPA at/or within 2
weeks of screening may extend screening for up to 4 additional weeks.
Unscheduled visits are permitted for reasons such as safety events or worsening of LN.
The original study design included a target of approximately 60 participants to be randomly
assigned with approximately 30 participants planned per intervention group. Due to the Sponsor’s
decision to stop screening of new participants as a result of enrollment challenges, fewer than 60
participants will be enrolled in the study. After all enrolled participants have completed the
Week 20 visit, no additional study intervention will be administered. For further details of end of
study, see Section 4.1.3.
A placebo comparator (in addition to standard-of-care background therapy) will be used in this
study through Week 48 to allow for blinded, placebo-controlled evaluation of the long-term
efficacy and safety of guselkumab in participants with LN. Participants will be stratified by
geographic region and UPCR level.
Efficacy, safety, PK, immunogenicity, and biomarkers (where local regulations permit) will be
assessed according to the Schedule of Activities (SoA; Section 1.3). An optional
pharmacogenomic blood sample will be collected from participants who consent to the collection
of these samples (where local regulations permit).
The primary efficacy analysis will be performed after all participants have completed Week 24
efficacy assessments (or discontinued). Additional secondary endpoints will be completed at
Week 24 and Week 52.
Every reasonable effort should be made to keep concomitant medications stable as defined in the
protocol (see Section 6.5.2 for information on glucocorticoid tapering). Beginning at the screening
visit, all concomitant therapies and all changes in concomitant therapies should be recorded
throughout the study.
Key safety assessments include AEs, clinical laboratory tests (hematology and chemistry), systolic
and diastolic blood pressures over time, monitoring for hypersensitivity reactions, AEs temporally
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associated with infusion, injection-site reactions, suicidality assessment, and early detection of
active tuberculosis (TB).
Participants who complete the Week 52 visit and achieve a complete renal response, may have the
option to participate in an LTE study; see Section 4.1.2 for further details.
Participants who experience an LN flare during the main study will be discontinued from study
intervention. An LN flare is defined as an increase in proteinuria and/or serum creatinine
concentration, abnormal urine sediment or a reduction in creatinine clearance rate as a result of
active disease requiring a change in an immunomodulatory medication for LN beyond that which
is outlined in Section 6.5.
An external, independent DMC will be commissioned for this study (Section 9.5). The DMC will
review unblinded data on a periodic basis to ensure the safety of participants enrolled in the study.
The main focus of the DMC will be on reviewing interim unblinded safety data, but the DMC may
also review efficacy data needed to ensure the full benefit:risk profile for guselkumab. The DMC
responsibilities, authorities, and procedures will be documented in a separate DMC charter.
A diagram of the study design is provided in Section 1.2, Schema.
4.1.2. 
Long-Term Extension
Participants who complete the assessments at the Week 52 visit and have achieved CRR may have
the option to participate in the LTE of the study. The LTE begins after the assessments have been
completed at Week 52. The objective of the LTE is to evaluate the efficacy and safety of long-term
guselkumab treatment.
If a participant has achieved CRR at Week 48, they will be considered potentially eligible for the
LTE. At Week 52, after the assessments per the SoA have been completed and informed consent
for the LTE has been confirmed, the participant will receive the study intervention that was
assigned at randomization. Participants will continue to receive the same study intervention
every 4 weeks during the LTE that they were assigned to receive through Week 48. The Week 52
assessments will be checked after this visit to confirm that the participant has still achieved CRR.
If the participant has not achieved CRR at Week 52, study intervention will be discontinued, and
the participant will be required to complete the final efficacy and safety visits approximately
12 weeks after their last study intervention administration.
At the discretion of the investigator and participant, and after appropriate and documented training,
participants may self-administer study intervention at home during the LTE for the visits specified
in the SoA. A caregiver may also be trained to administer study intervention. After receiving
training at Week 60, participants who are eligible for self- (or caregiver) administration of study
intervention will be supplied with study intervention for at-home administration and may have
their first at-home administration at Week 64. Participants will record all at-home study
intervention administrations on a diary card. Participants will also be instructed to contact the
investigator promptly in the event of any signs of an allergic reaction, infection, or malignancy.
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Finally, participants will continue to have study visits at the investigative sites approximately q8w
through Week 148 and assessments performed as outlined in Section 1.3.
Participants who are unable or unwilling to have study intervention administered away from the
investigative site will continue administration at the investigative site and will be required to return
to the site for administration of study intervention.
During the LTE, all participants will be assessed for safety and efficacy. Participants who
experience an LN flare during the LTE will be discontinued from study intervention and will be
required to complete the final efficacy/safety visits. An LN flare is defined as an increase in
proteinuria and/or serum creatinine concentration, abnormal urine sediment or a reduction in
creatinine clearance rate as a result of active disease requiring a change in an immunomodulatory
medication for LN beyond that which is outlined in Section 6.5. Every effort should be made to
continue to adhere to the requirements for concomitant and prohibited therapy as outlined in
Section 6.5 of the protocol with some exceptions for antimalarials, angiotensin-converting enzyme
(ACE) inhibitors/ angiotensin II receptor blockers (ARBs), and glucocorticoids; see Section 6.5
for further details.
All study evaluations that should be performed during the LTE are listed in the SoA (Table 2 and
Table 3).
The study blind will be maintained throughout the study (including the LTE).
One database lock (DBL)for the study will occur at the end of study.
4.1.3. 
End of Study
The end of study will occur after all enrolled participants have completed the Week 20 visit or
discontinued study intervention prior to Week 24, and all participants have completed their final
efficacy and safety visits per the Schedule of Activities (Section 1.3).
4.2. 
Scientific Rationale for Study Design
A double-blind, placebo-controlled study was selected where guselkumab or placebo would be
randomized in addition to standard-of-care background therapy. This study design was selected as
a true placebo comparator group is unethical for this serious disease condition. Therefore, placebo
and experimental treatments will be added to a standard-of-care regimen of MMF/MPA and
glucocorticoids.
With this standard-of-care regimen, participants will enter on glucocorticoids (at minimum
prednisone equivalent dose of 10 mg/day and not exceeding 1 mg/kg/day or 60 mg/day prednisone
or its equivalent, whichever is lower) and will be tapered fairly rapidly to 5 mg/day prednisone
equivalent by Week 12 to minimize confounding treatment effects of glucocorticoids on major
efficacy endpoints, as has occurred in several, negative LN studies.14 Similar glucocorticoid tapers
have been used in some recent LN studies.31
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For participants who will be treated with guselkumab, an IV induction dose of guselkumab initially
through Week 12 was chosen, followed by SC doses as this follows the typical
induction-maintenance treatment paradigm for Class III/IV LN. This ensures target inhibition of
IL-23 in the kidney in this proof-of-relevance study. This dose of guselkumab is also being
evaluated in a Phase 2b/3 study in UC. Additional details are described in Section 4.3.
A primary analysis at Week 24 will be conducted for proof-of-concept and to allow for Phase 3
LN program planning.
4.2.1. 
Blinding, Control, Study Phase/Periods, Intervention Groups
Randomization will be used to minimize bias in the assignment of participants to intervention
groups, to increase the likelihood that known and unknown participant attributes (eg, demographic
and baseline characteristics) are evenly balanced across intervention groups, and to enhance the
validity of statistical comparisons across intervention groups. Blinded intervention will be used to
reduce potential bias during data collection and evaluation of clinical endpoints.
4.2.2. 
DNA and Biomarker Collection
Biomarker samples (where local regulations permit) will be collected to evaluate the cellular and
molecular mechanism of action of guselkumab, or help to explain interindividual variability in
clinical outcomes, or to identify population subgroups that respond differently to an intervention.
Biomarkers will be analyzed from the serum, as well as urine, in participants from select sites to
assess PD markers associated with the IL-23 pathway, and with response to guselkumab. Whole
blood samples will be collected from participants to assess the effect of study intervention on
ribonucleic acid (RNA) expression profiles, where local regulations permit. The goal of the
biomarker analyses is to further define the mechanism of action of the selective blockade of IL-23
with guselkumab in LN  and aid in evaluating the intervention-clinical response relationship.
Biomarker samples may also be used to help address emerging issues and to enable the
development of safer, more effective, and ultimately individualized therapies for lupus.
Optional pharmacogenomic samples may be obtained. It is recognized that genetic variation can
be an important contributory factor to interindividual differences in intervention 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,
identify markers associated with disease susceptibility and prognosis, and may help to identify
population subgroups that respond differently  to an intervention. The goal of the
pharmacogenomic component is to collect DNA to allow for the identification of genetic factors
that may influence the PK, PD, efficacy, safety, or tolerability of guselkumab and to identify
genetic factors associated with LN or the response to guselkumab treatment. The focus of this
analysis will be the evaluation of genetic single nucleic polymorphisms (SNP) associated with LN
and response to treatment with guselkumab. No genetic research will be done on samples from
participants unless specific consent is provided by signing the optional genetic research informed
consent form (ICF). Additional pharmacogenomic samples will be collected after exposure to
guselkumab or placebo. Epigenetic data from these samples will be compared to baseline collected
samples to identify epigenetic changes that may associate with treatment or treatment response.
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Collection of biomarker samples, including samples from the optional pharmacogenomic
collection, will only occur where local regulations permit and may not occur at all clinical sites.
4.2.3. 
Participant Input Into Design
Two advisory boards of LN patients were consulted on the study design and conduct. Participants
provided insights on the protocol design, where they perceived barriers to participation, and how
the clinical study experience could be improved for patients. In particular, concerns were raised
about some of the inclusion/exclusion criteria (biopsy requirement, steroid tapering) and the SoA,
as some additional biomarker and actigraphy assessments were being considered at that time.
New recruitment strategies were identified, including: providing sites with tools to help identify
newly diagnosed patients in their referral network that could be a good fit for the study, providing
more information about the biopsy requirement to explain its significance to potential participants,
and providing more education to potential participants about the protocol design and the
protections in place for participants of clinical trials.
4.2.4. 
Study-Specific Ethical Design Considerations
Potential participants will be fully informed of the risks and requirements of the study and, during
the study, participants 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 participants who are fully able to understand the risks, benefits,
and potential AEs of the study, and provide their consent voluntarily will be enrolled.
The primary ethical concern is the medication has not been shown to have efficacy in humans and
response to medication is theoretical at this time.
The total blood volume to be collected from each participant in this study is less than the American
Red Cross standard limit for whole blood donation (approximately 475 mL q8w) and is, therefore,
considered an acceptable amount of blood to be collected over this time. For more details regarding
blood collection, see Blood Sample Collection in Section 8.
4.3. 
Justification for Dose
The guselkumab dose regimen was selected based on the objective of determining the maximum
efficacy of guselkumab possible for treatment of LN, the existing safety information from relevant
preclinical and clinical studies, the approved dose regimen for psoriasis, and the understanding of
similar dosing requirements for induction and maintenance therapy in LN (and SLE) and Crohn’s
disease.
As the objective of this study is to demonstrate proof-of-concept for efficacy of guselkumab in the
treatment of LN, the maximum practicable dose (400 mg IV at Week 0, 4, and 8 then followed by
200 mg SC q4w), is chosen to be evaluated.
Data from the ongoing guselkumab Phase 2/3 Crohn’s disease program were considered in the
selection of the guselkumab IV induction dose regimens in this Phase 2 LN study. In the Phase 2
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Crohn’s disease study, 3 guselkumab IV induction doses of 200 mg, 600 mg and 1200 mg IV q4w
were assessed. 
The safety of 200 mg and 600 mg IV regimens in the Phase 2b Crohn’s disease trial was acceptable.
A single case of potential drug-induced liver injury possibly related to guselkumab was reported
in a participant who received the guselkumab 1200 mg IV dose regimen. Compared to the
guselkumab 1200 mg IV dose, the guselkumab 400 mg IV dose would provide an approximately
3-fold lower exposure. In addition, the predicted exposure margin for 400 mg IV relative to the
NOAEL of 50 mg/kg/week in cynomolgus monkeys is approximately 10 to 13-fold (Table 4),
which is considered adequate to support the limited duration of IV dosing (ie, 3 doses over
12 weeks).
The proposed dose regimen is supported by safety margins from preclinical toxicology data as
well as clinical safety data of guselkumab in other disease populations such as psoriasis, PsA,
Crohn’s disease, UC, and HS. Guselkumab IV doses of up to 50 mg/kg weekly for 5 weeks, and
guselkumab SC doses of up to 50 mg/kg weekly for 24 weeks, were well-tolerated in cynomolgus
monkeys. The predicted human guselkumab exposures following the proposed IV and SC dosages
generate acceptable safety margins. Shown in  Table 4, the estimated safety margins are
approximately 10-to 13-fold for the 400 mg IV dosing and 30-to 40-fold for 200 mg SC q4w
dosing.
Table 4: 
Guselkumab Predicted Exposure Margins
Guselkumab Predicted Exposure Margins at 400 mg IV Induction Dosing
Parameters 
Mean Cmax 
(µg/mL) 
Mean AUC
(µg.day/mL)
Cynomolgus Monkey Exposure at the NOAEL (50 mg/kg/week)
Following 4 Weekly IV Doses
1432a 
4817b
Human Predicted IV Exposure 
109c 
497d
Predicted Exposure Margine 
13.1 
9.7
Guselkumab Predicted Exposure Margins at 200 mg SC Maintenance Dosing
Parameters 
Mean Cmax 
(µg/mL) 
Mean AUC
(µg.day/mL)
Cynomolgus Monkey Exposure at the NOAEL (50 mg/kg/week)
Following 24 Weekly SC Doses
993a 
5412b
Human Predicted SC Exposure 
30c 
134d
Predicted Exposure Margine 
33.1 
40.4
Abbreviations: AUC area under the curve; Cmax maximum serum concentration; IV intravenous; NOAEL no observed
adverse effect level; SC subcutaneous
a. Highest observed concentration following the fourth 50 mg/kg dose (IV) or the twenty fourth 50 mg/kg dose (SC)
b. For IV, AUC from Day 21 through 28 (1 week after the last 50 mg/kg dose); or for SC, AUC from Day 161 through 168
(1 week after the last 50 mg/kg dose).
c. Highest predicted concentration after the third 400 mg IV guselkumab dose, or at steady state following SC administration.
d. Predicted human AUC after the third 400 mg IV guselkumab dose (from Week 8 through Week 12), or at steady state
following 200 mg SC every 4 weeks administration. Each value was divided by 4 to obtain the AUC over one week, which in
CCI
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Table 4: 
Guselkumab Predicted Exposure Margins
Guselkumab Predicted Exposure Margins at 400 mg IV Induction Dosing
turn corresponds to the AUC interval for cynomolgus monkeys. Simulation of human PK exposure was based on a body weight
of 70 kg.
e. Exposure margins represent the ratio between guselkumab exposure metrics in the cynomolgus monkey compared with those
predicted in humans.
In study CNTO1275SLE2001 (ClinicalTrials.gov Identifier: NCT02349061), the studied Crohn's
disease dose regimen (~6 mg/kg IV followed by 90 mg SC q8w) for ustekinumab, an antibody
targeting at IL-12/IL-23, demonstrated efficacy in SLE participants. Similar ustekinumab  PK
exposures have been demonstrated in participants with SLE and participants with Crohn’s disease
following the same dosage.
The proposed induction dosing followed by maintenance paradigm is a characteristic for
management of LN, as well as Crohn’s disease and UC. Induction therapy is essential to control
and reduce renal damage and the maintenance therapy is important to prevent renal flares.5
Overall, with an acceptable NOAEL, available clinical safety data from other ongoing studies in
conjunction with other similarities between SLE and Crohn’s disease in the ustekinumab studies
(in terms of induction dosing, efficacy, and PK), make it reasonable to study LN, a severe
manifestation of SLE, with this regimen.
4.4. 
End of Study Definition
End of Study Definition
The end of the study is defined as the last follow-up assessment for the last participant in the study
(see Section 4.1.3 for further details). The final data from the study site will be sent to the sponsor
(or designee) after completion of the final participant visit at that study site, in the time frame
specified in the Clinical Trial Agreement.
Study Completion Definition
A participant will be considered to have completed the main study if he or she has completed
assessments through  Week 52 and the 12-week  safety follow-up  visit or has completed the
assessments through Week 52 and enters the LTE. A participant will be considered to have
completed the full study if he or she has completed assessments through Week 152 and the
12-week safety follow-up visit.
5. 
STUDY POPULATION
Screening for eligible participants will be performed within 8 weeks before administration of the
study intervention. Refer to Section 5.4, Screen Failures for conditions under which the repeat of
any screening procedures are allowed.
The inclusion and exclusion criteria for enrolling participants in this study are described below. If
there is a question about these criteria, the investigator must consult with the appropriate sponsor
representative and resolve any issues before enrolling a participant in the study. Waivers are not
allowed. The inclusion and exclusion criteria will be adjudicated prior to enrollment. The
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adjudicated assessment by the sponsor or designee will be the final determinant for allowing
enrollment.
For a discussion of the statistical considerations of participant selection, refer to Section 9.2,
Sample Size Determination.
5.1. 
Main Study Inclusion Criteria
Each potential participant must satisfy all of the following criteria to be enrolled in the study:
1. 
Male or female (according to their reproductive organs and functions assigned by
chromosomal complement).
2. 
18 to 75 years of age, inclusive.
3. 
Meets classification criteria for SLE by the 2019 European League Against Rheumatism
(EULAR)/ACR.
4. 
Criterion modified per Amendment 3.
4.1. Kidney biopsy documentation ofactive ISN/RPS proliferative nephritis: Class III-IV
(with or without class V membranous nephritis) withinthe last 6 months prior to screening
or performed during screening.
Concomitant or previous medical therapies received
5. 
Criterion modified per Amendment 3.
5.1. Must have received MMF or MPA for at least 8 weeks at the time of randomization,
and currently receiving MMF at a dose of ≤3 g/day or MPA at dose of ≤2.2 g/day.
Note: Screening may be extended by up to 4 additional weeks for participants who start
MMF/MPA at or near (within 2 weeks before) the beginning of screening to allow for
repeat of laboratory entry criteria after 8 weeks of MMF/MPA treatment.
6. 
Criterion modified per Amendment 3.
6.1. At screening and randomization, must be receiving oral glucocorticoids at minimum
prednisone equivalent dose of 10 mg/day and maximum 1 mg/kg/day or ≤60 mg/day,
whichever is lower. Treated for ≥6 weeks with stable dosing ≥2 weeks before
randomization.
7. 
If receiving angiotensin-converting enzyme (ACE) inhibitor/angiotensin II receptor
blockers (ARB), a stable dose for at least 2 weeks prior to randomization.
8. 
If using antimalarials, must have been treated for ≥12 weeks, and with stable dosing for
≥6 weeks at time of randomization. See Table 5 for permitted dosing levels.
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Screening laboratory tests
9. 
Criterion modified per Amendment 3.
9.1. Positive antinuclear antibody (ANA; ≥1:80 titer by central laboratory test) or
anti-dsDNA antibodies (≥30 IU/mL by central laboratory test) detected at screening.
10. 
UPCR ≥1.0 mg/mg assessed on 2 first morning urine void specimens during screening.
Note: These 2 specimens do not need to be on consecutive days, however, 2 samples must
be tested with UPCR ≥1.0 mg/mg in a row. The UPCR requirement must be met after at
least 8 weeks of MMF/MPA treatment, and after stable glucocorticoid dosing is achieved
at the dose intended at time of randomization.
Tuberculosis: The participant is considered eligible according to the following TB  screening
criteria in Inclusion #11 to 14:
11. 
Has no history of latent or active TB before screening. An exception is made for
participants who have a history of latent TB AND satisfy one of the following criteria:
a. are currently receiving treatment for latent TB
OR
b. will initiate treatment for latent TB before the first dose of study intervention
OR
c. have documentation of having completed appropriate treatment for latent TB
within 5 years before the first dose of study intervention. It is the responsibility
of the investigator to verify the adequacy of previous anti-tuberculous treatment
and provide appropriate documentation. Patients with a history and
documentation of having completed appropriate treatment for latent TB more
than 5 years before the first dose of study intervention are not eligible.
12. 
Has no signs or symptoms suggestive of active TB based on medical history and/or
physical examination.
13. 
Has 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 before the first dose of study
intervention.
14. 
Within 8 weeks prior to the first dose of study intervention, have a negative
QuantiFERON-TB® test result, or have a newly identified positive QuantiFERON-TB®
test in which active TB has been ruled out and for which appropriate treatment for latent
TB has been initiated prior to the first dose of study intervention (see Section 8.2.11).
Indeterminate or borderline results should have the test repeated as described in
Section 8.2.11.
Note: A negative tuberculin skin test result (see Appendix 3 [Section 10.3]) is
additionally required if the QuantiFERON-TB® test is not approved/registered in the
country in which this protocol is being conducted. In Ukraine, while the
QuantiFERON-TB® test is not approved/registered, it is acceptable, and an additional
tuberculin skin test is not required. The QuantiFERON-TB® test and the tuberculin
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skin test are not required at screening for participants with a history of latent TB, if
active TB has been ruled out, and if appropriate treatment has been
initiated/completed as described above in Inclusion Criterion #11.
Has a chest radiograph (both posterior-anterior and lateral views, or per country
regulations where applicable), taken within 12 weeks prior to randomizationand read
by a qualified radiologist (or pulmonologist in accordance with local regulations),
with  no evidence of current, active TB or old, inactive TB. A chest computed
tomography (CT) scan is also acceptable if obtained instead of a chest radiograph
outside of the protocol.
Contraception
Contraceptive (birth control) use by men or women should be consistent with local regulations
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should
be consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.
15. 
A woman of childbearing potential must have a negative urine pregnancy test at screening
and at Week 0.
16. 
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for 12 weeks after the last dose of study intervention.
17. 
Criterion modified per Amendment 2.
17.1. Before randomization, a woman must be (as defined in Appendix 5 [Section 10.5],
Contraceptive and Barrier Guidance and Collection of Pregnancy Information):
a. Not of childbearing potential
OR
b. Of childbearing potential and:
o 
If heterosexually active, practicing a highly effective method of
contraception (failure rate of <1% per year when used consistently and
correctly)and agrees to remain on a highly effective method while receiving
study intervention and until 12 weeks after last dose (ie, the end of relevant
systemic exposure). Examples of highly effective methods of contraception
are located in Appendix 5 (Section 10.5), Contraceptive and Barrier
Guidance and Collection of Pregnancy Information; however, the method
selected must meet local/regional regulations/guidelines for highly effective
contraception.
o 
If using oral hormonal contraceptives for birth control and receiving
MMF/MPA, a woman must, in addition to the oral hormonal contraceptive,
utilize a barrier method of birth control (eg, either an occlusive cap
[diaphragm 
or 
cervical/vault 
caps] 
plus 
spermicidal
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foam/gel/film/cream/suppository if available in their locale) or their partner
must 
agree 
to 
use 
a 
condom 
with 
spermicidal
foam/gel/film/cream/suppository if available in their locale, during the
study and for at least 30 days after receiving the last  administration of study
intervention.
Note: If a participant’s childbearing potential changes after start of the study (eg, a
premenarchal woman experiences menarche) or the risk of pregnancy changes (eg, a
woman who is not heterosexually active becomes active), a woman must begin using a
highly effective method of contraception, as described above.
18. 
A man who is sexually active with a woman of childbearing potential and who 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.
19. 
A male participant must agree not to donate sperm for the purpose of reproduction during
the study and for a minimum of 12 weeks after receiving the last dose of study
intervention.
General
20. 
Must sign an ICF indicating that he or she understands the purpose of, and procedures
required for, the study and is willing to participate in the study. (In regions where the legal
age of consent is older than 18 years, those under the legal age, must obtain signed
informed consent from both the participant and his or her legally acceptable
representative.)
21. 
Must sign a separate ICF if he or she agrees to provide optional DNA samples for research
where local regulations permit. In regions where the legal age of consent is older than
18 years, those under the legal age, must obtain signed informed consent from both the
participant and his or her legally acceptable representative.
Refusal to give consent for the optional DNA samples does not exclude a participant from
participation in the study.
22. 
Must be willing and able to adhere to all specified requirements, including but not limited
to completion of the required assessments, adherence to the visit schedule, and
compliance with the lifestyle restrictions as specified in this protocol.
23. 
Must be able to read and write.
5.1.1. 
Long-Term Extension Inclusion Criteria
Each potential participant must satisfy the following criteria to continue to receive study
intervention as part of the LTE:
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1. 
The participant has achieved CRR at Weeks 48 and 52 and has completed the Week 52
assessments per Table 2 of the SoA (Section 1.3).
2. 
Must sign an ICF indicating that he or she understands the purpose of, and procedures
required for, the LTE and is willing to participate in the LTE. (In regions where the legal
age of consent is older than 18 years, those under the legal age, must obtain signed
informed consent from both the participant and his or her legally acceptable
representative.)
3. 
In the judgement of the study Investigator, the participant must be suitable for inclusion
in the LTE portion of the study.
5.2. 
Main Study Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the study:
1. 
Current or history of, severe, progressive, or uncontrolled renal disease, with the
exception of active LN.
2. 
Current or history of, severe, progressive, or uncontrolled hepatic, hematological,
gastrointestinal, pulmonary, cardiac, or neurological disease, either related or unrelated
to SLE (or, in the investigator's opinion, any other concomitant medical condition that
places the participant at risk by participating in this study).
3. 
Anticipated to require dialysis within 6 months.
4. 
Transplanted organ (with the exception of a corneal transplant performed >12 weeks
before screening).
5. 
Comorbidities (other than LN, eg, asthma, chronic obstructive pulmonary disease)
which have required 3 or more courses of systemic glucocorticoids within the previous
12 months.
6. 
Has any unstable or progressive manifestation of SLE (eg, lupus cerebritis, optic
neuritis, transverse myelitis, psychosis, uncontrolled seizures, systemic vasculitis,
rapidly progressive glomerulonephritis, end-stage renal disease], pulmonary
hemorrhage, myocarditis) that is likely to warrant escalation in therapy beyond
permitted background medications. Participants requiring renal hemodialysis or
peritoneal dialysis are also excluded.
7. 
Criterion modified per Amendment 3.
7.1. Isolated or predominant Class V LN (ie, without coexistent Class III or IV
nephritis).
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8. 
Has other inflammatory diseases that might confound the evaluations of efficacy,
including but not limited to RA, PsA, RA/lupus overlap, psoriasis, Crohn’s disease, or
active Lyme disease.
9. 
Has a history or suspected occurrence of drug-induced lupus.
10. 
Has a history of catastrophic antiphospholipid syndrome (APS). Subjects with a history
of non-catastrophic APS must be adequately controlled with anticoagulation and/or
anti-platelet therapy in accordance with local guidelines. The suitability of the subject
to participate in the study must be discussed with the medical monitor and/or sponsor
before the subject is randomized.
11. 
Has inherited complement deficiency or combined variable immunodeficiency.
Screening laboratory tests
12. 
eGFR <30 ml/min per 1.73m2.
13. 
Absolute neutrophil count <1.0 ×109/L.
14. 
Platelet count <75 ×109/L.
15. 
Criterion modified per Amendment 1.
15.1 Hemoglobin <8.0 g/dL.
16. 
Liver function test (aspartate aminotransferase [AST], alanine aminotransferase [ALT])
results that are ≥3× the upper limit of normal [ULN]).
Concomitant or previous medical therapies received
17. 
Previously treated with anti-IL-23 or anti-IL-12/23 therapy.
18. 
Have received a single B-cell targeting agent within 3 months prior to randomization;
or received more than 1 previous B-cell targeting therapy including belimumab within
6 months prior to randomization; or received B-cell depleting therapy (eg, rituximab,
obinutuzumab) within 12 months prior to randomization or has evidence of continued
B-cell depletion following such therapy.
19. 
Criterion modified per Amendment 3.
19.1. Received PO or IV cyclophosphamide within 3 months prior to randomization.
20. 
Use of anti-TNF medication, other biologic medications (eg, tocilizumab, alefacept,
efalizumab, natalizumab, abatacept, anakinra, brodalumab, secukinumab, ixekizumab,
or agents whose mechanism of action targets IL-1, IL-2, IL-6, IL-17, or CTLA-4), or
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experimental non-biologic therapeutic agents within the past 90 days, or 5 half-lives
prior to screening, whichever is greater.
21. 
Intravenous immunoglobulin, plasmapheresis, or leukopheresis within 90 days of
screening.
22. 
Use of investigational biologic agent within 3 months or 5 half-lives prior to screening.
23. 
Criterion modified per Amendment 3.
23.1. Has received systemic immunomodulatory agents (eg, leflunomide, methotrexate
[MTX], tacrolimus, sirolimus, mizoribine, cyclosporine, voclosporin) other than those
described in inclusion criteria #5 to #8 within 3 months (2 months for azathioprine
[AZA]/6-mercaptopurine [6-MP]) prior to randomization (Section 6.5.7).
Glucocorticoids are not included in this criterion; see Section 6.5.2 regarding
glucocorticoid use.
24. 
Has received adrenocorticotropic hormone (ACTH) administered by injection within
1 month prior to randomization.
25. 
Has received topical cream/ointment preparations of cyclosporine A, high  potency
topical glucocorticoids (World Health Organization WHO Classification, Group I to
III), or other topical immunomodulatory agents (such as tacrolimus, pimecrolimus)
within 4 weeks prior to randomization covering a body surface area (BSA) of >20%.
26. 
Is currently receiving venom immunotherapy (honeybee, wasp, yellow jacket, hornet,
or fire ant).
27. 
Criterion modified per Amendment 3.
27.1. Has received epidural, IV, or IM administration of glucocorticoids at a prednisone
equivalent dose of >125 mg/day within 6 weeks prior to randomization.
28. 
Criterion modified per Amendment 3.
28.1. The participant is anticipated to receive >125 mg/day of intravenous prednisone
(or equivalent) during the screening period.
Note: This includes the extended screening period for participants starting MMF/MPA
at or near the beginning (within 2 weeks) of screening.
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29. 
Use of complementary therapies, including traditional/Chinese medicines, herbs,
ointments, or procedures (eg, acupuncture), that have the potential to activate
(eg, echinacea) or inhibit (eg, Tripterygium wilfordii Hook F) the immune system is
prohibited within 6 weeks of randomization. In addition, use of complementary
therapies, including traditional/Chinese medicines and herbs, that have the potential to
interact with antithrombotic agents (eg, St. John’s Wort) is prohibited within 6 weeks
of randomization in those taking antithrombotic agents. Any questions or concerns with
the use of these therapies should be discussed with the study sponsor and/or medical
monitor.
Infections or predisposition to infections
NOTE: For COVID-19-related exclusion, see exclusion criterion 56.
30. 
History of latent or active granulomatous infection, including histoplasmosis or
coccidioidomycosis, before screening. Refer to Inclusion Criteria #11 to 14 for
information regarding eligibility with a history of latent TB.
31. 
History of, or ongoing, chronic or recurrent infectious disease, including but not limited
to, recurrent sinopulmonary infections, bronchiectasis, recurrent renal/urinary tract
infection (eg, recurrent pyelonephritis, recurrent cystitis), an open, draining, or infected
skin wound, or an ulcer.
32. 
Chest radiograph within 12 weeks before randomization  that shows an abnormality
suggestive of a malignancy or current active infection, including TB.
33. 
History of being HIV antibody-positive, or tests positive for HIV at screening.
34. 
Is seropositive for antibodies to HCV, unless they satisfy 1 of the following conditions:
a. Has a history of successful treatment, defined as being negative for HCV RNA
at least 24 weeks after completing antiviral treatment, and has a negative HCV
RNA test result at screening,
OR
b. While seropositive, has a negative HCV RNA test result at least 24 weeks prior
to screening and a negative HCV RNA test at the screening.
35. 
Tests positive for HBV infection, see (Appendix 4 [Section 10.4]).
Note: For participants who are not eligible for this study due to HIV, HCV, and HBV
test results, consultation with a physician with expertise in the treatment of those
infections is recommended.
36. 
Bacille Calmette-guérin (BCG) vaccination within 12 months or any other live bacterial
or live viral vaccination within 12 weeks of randomization.
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37. 
Has or has had a nontuberculous mycobacterial infection or clinically significant
opportunistic infection (eg, cytomegalovirus colitis, pneumocystosis, invasive
aspergillosis).
38. 
Has a history of an infected joint prosthesis, or has ever received antibiotics for a
suspected infection of a joint prosthesis, if that prosthesis has not been removed or
replaced.
39. 
Has had a clinically significant infection (eg, hepatitis, sepsis, pneumonia,
pyelonephritis), has been hospitalized for an infection, or has been treated with
parenteral antibiotics for an infection within 2 months before randomization. Treated
and resolved infections not considered clinically significant at the discretion of the
investigator need not be exclusionary (eg, acute upper respiratory tract infection,
uncomplicated urinary tract infection).
40. 
Evidence of a herpes zoster infection within 8 weeks of randomization. Past history of
disseminated or central nervous system herpes zoster would be exclusionary.
Malignancy or increased potential for malignancy
41. 
Currently has a malignancy or has a history of malignancy within 5 years before
screening (with the exception of a nonmelanoma skin cancer that has been adequately
treated with no evidence of recurrence for at least 3 months [defined as a minimum of
12 weeks] before randomization or cervical carcinoma in situ that has been treated with
no evidence of recurrence for at least 3 months before randomization).
42. 
History of lymphoproliferative disease, including lymphoma; a history of monoclonal
gammopathy of undetermined significance; or signs and symptoms suggestive of
possible lymphoproliferative disease, such as lymphadenopathy or splenomegaly, or
other precancerous lesions (except those of the skin such as actinic keratosis).
Coexisting medical conditions or past medical history
43. 
Has unstable suicidal ideation or suicidal behavior in the last 6 months, that may be
defined as an electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) rating at
screening of:
 
Ideation level 4: Some intent to act, no plan; OR
 
Ideation level 5: Specific plan and intent; OR
 
Any of the following suicidal behaviors:
 
Actual suicide attempts
 
Interrupted attempts
 
Aborted attempts
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Preparatory actions
AND
is confirmed to be at risk by the investigator based on an evaluation by a mental health
professional. The final decision on excluding a participant will be made at the judgment
of the investigator.
44. 
Poor tolerability of venipuncture or lacks adequate venous access for required blood
sample collections during the study period.
45. 
History of drug or alcohol abuse according to the Diagnostic and Statistical Manual of
Mental Disorders, 5th edition , within 1 year before screening.
46. 
Known allergy, hypersensitivity, or intolerance to guselkumab or its excipients (refer
to the guselkumab IB).
47. 
Known intolerance to MMF or MPA.
48. 
Has shown a previous immediate hypersensitivity response, including anaphylaxis, to
mAbs.
49. 
Is a woman who is pregnant, or breastfeeding, or planning to become pregnant while
enrolled in this study or within 12 weeks after the last dose of study intervention.
50. 
Is a man who plans to father a child while enrolled in this study or within 12 weeks after
the last dose of study intervention.
51. 
Has had major surgery (eg, requiring general anesthesia and hospitalization) within
8 weeks before screening, or will not have fully recovered from such surgery, or has
such major surgery planned during the time the participant is expected to participate in
the study.
Note: Participants with planned surgical procedures to be conducted under local
anesthesia may participate.
52. 
Has undergone a splenectomy.
General
53. 
Lives in an institution on court or authority order.
54. 
Currently participating or intends to participate in any other study using an
investigational agent or procedure during the conduct of this study.
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55. 
Is an employee of the investigator or study site, with direct involvement in the proposed
study or other studies under the direction of that investigator or study site, as well as
family members of the employees or the investigator.
56. 
Criterion modified per Amendment 2.
56.1 A potential participant with the following features will be excluded from
participating in the study protocol:
 
During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-
CoV-2 (Coronavirus Disease 2019; COVID-19) infection (test positive), OR
(b) suspected SARS-CoV-2 infection (clinical features without documented
test results), OR (c) close contact with a person with known or suspected
SARS-CoV-2 infection
 Exception: may be included with a documented negative result for a
validated SARS-CoV-2 test
(i) obtained at least 2 weeks after conditions (a), (b), (c) above
(timed from resolution of key clinical features if present, eg,
fever, cough, dyspnea)
AND
(ii) with absence of ALL conditions (a), (b), (c) above during the
period between the negative test result and the baseline study
visit
 
NOTES on COVID-related exclusion:
1. The field of COVID-related testing (for presence of, and immunity to, the
SARS-CoV-2 virus) is rapidly evolving. Additional testing may be
performed as part of screening and/or during the study if deemed necessary
by the investigator and in accordance with current regulations/guidance
from authorities/standards ofcare.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening.
If a participant's clinical status changes (including any available laboratory results or receipt of
additional medical records) after screening but before the first dose of study intervention is given
such that he or she no longer meets all eligibility criteria, then the participant should be excluded
from participation in the study. Section 5.4, Screen Failures, describes options for retesting. The
required source documentation to support meeting the enrollment criteria are noted in Appendix 9,
[Section 10.9] Regulatory, Ethical, and Study Oversight Considerations. The sponsor’s or
designee’s decision, as determined by adjudication of inclusion and exclusion criteria, is the final
determinant for eligibility to participate in the study.
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5.2.1. 
Long-Term Extension Exclusion Criteria
Any potential participant who meets any of the following criteria will be excluded from
participating in the LTE. If there are questions, the site should contact the sponsor for clarification.
1. 
The participant experiences an LN flare as defined in Section 4.1.1.
2. 
The participant should not have permanently discontinued study intervention or met
criteria for discontinuation of study intervention.
5.3. 
Lifestyle Considerations
Potential participants must be willing and able to adhere to the following lifestyle restrictions
during the course of the study including the LTE to be eligible for participation:
1. 
Refer to Section 6.5, Concomitant Therapy  for details regarding prohibited and
restricted therapy during the study.
2. 
Agree to follow all requirements that must be met during the study as noted in the
inclusion and exclusion criteria (eg, contraceptive requirements).
3. 
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion
Criteria. Participants should continue using these contraceptive measures for 12 weeks
after last dose of study intervention.
4. 
Must agree not to receive a live virus or live bacterial vaccination during the study and
for 12 weeks after receiving the last dose of study intervention.
5. 
Must agree not to receive a BCG vaccination during the study and for 12 months after
receiving the last dose of study intervention.
6. 
Participants who require treatment for latent TB must complete the appropriate course
of TB therapy as described in Section 5.1, Inclusion Criteria.
7. 
Must not receive guselkumab outside of this protocol or participate in any other clinical
study with an investigational agent while in this study and must terminate study
participation if they do. A participant who intends to participate in any other clinical
study with an investigational agent should complete the appropriate visit(s) as described
in Section 1.3 before he or she terminates study participation.
8. 
Agree to avoid excess exposure to natural or artificial (tanning beds, phototherapy, etc)
sunlight. In addition, it is advised that subjects maintain their typical use of sun
protective measures (such as a hat, sunglasses, protective clothing, sunscreen). The time
period for this requirement is from the start of screening until the last dose of study
agent has been received.
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9. 
Participants who are entering the LTE and self-administering the study intervention at
home must be willing and able to complete a diary card to document clinical symptoms,
AEs, etc.
10. 
It is recommended participants be up-to-date on all age-appropriate vaccinations prior
to screening per routine local medical guidelines. For study participants who received
locally approved (including emergency use-authorized) COVID-19 vaccines recently
prior to study entry, follow applicable local vaccine labelling, guidelines, and standards
of care for patients receiving immune-targeted therapy when determining an appropriate
interval between vaccination and study enrollment (see also Section 6.5.9).
5.4. 
Screen Failures
Participant Identification, Enrollment, and Screening Logs
The investigator agrees to complete a participant identification and enrollment log to permit easy
identification of each participant during and after the study. This document will be reviewed by
the sponsor study site contact for completeness.
The participant identification and enrollment log will be treated as confidential and will be filed
by the investigator in the study file. To ensure participant confidentiality, no copy will be made.
All reports and communications relating to the study will identify participants by participant
identification and age at initial informed consent. In cases where the participant is not randomized
into the study, the date seen and age at initial informed consent will be used.
Individuals who do not meet the criteria for participation in this study (screen failure) may be
rescreened one time after discussion with the sponsor representative.
Rescreening
Rescreened participants will be assigned a new participant number, undergo the informed consent
process, and then start a new screening phase. Some assessments from screening (eg, hepatitis B
virus, hepatitis C virus, HIV, chest x-ray, ANA, flow cytometry) could be considered to be
complete without repeating for rescreening after discussion and written agreement by the sponsor
or sponsor representative.
Rescreening of participants after the sponsor’s decision to stop screening of new participants is
not permitted.
Retesting
Retesting of abnormal laboratory values that may lead to exclusion will be allowed once. Retesting
can occur at an unscheduled visit during the screening phase, as long as this is done within the
specified screening window of up to 8 weeks (with 4 additional weeks for those who qualify per
MMF start date as noted above). If a laboratory abnormality occurs, the site is encouraged to wait
for all laboratory tests to be completed to ensure other laboratory tests do not need to be repeated,
as only 1 retest of laboratory tests is allowed. A screening laboratory test(s) analyzed by the central
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laboratory may be repeated more than once in the event of suspected error in sample collection or
analysis as long as the result is obtained within the screening period. Retests should not be
completed for UPCR levels unless there is an error found with the test such that the test cannot be
completed by the laboratory or an error noted by the site that is conveyed to the sponsor prior to
the result being reported.
6. 
STUDY INTERVENTION
6.1. 
Study Interventions Administered
Participants in the study will maintain their standard-of-care treatment of MMF/MPA  and
background glucocorticoid (see also Section 5.1, Inclusion  Criterion #5 and Inclusion
Criterion #6). The glucocorticoid dose tapering is described in Section 6.5.2 and a tapering
schedule is provided in Appendix 7[Section 10.7].
In addition to remaining on the standard-of-care noted above, participants will be randomized to 1
of 2 treatment groups as described below:
 
Guselkumab: Participants will receive guselkumab 400 mg IV at Weeks 0, 4 and 8 (ie, 3 IV
doses) and guselkumab 200 mg SC q4w from Week 12 through Week 48.
 
Placebo: Participants will receive placebo IV at Weeks 0, 4 and 8 (ie, 3 IV doses) and placebo
SC q4w from Week 12 through Week 48.
Participants will remain on their assigned treatment through Week 48. All participants will receive
an IV infusion at Weeks 0, 4, and 8 (either active or placebo) and 2 SC injections (either active or
placebo) at Week 12 through Week 48.
Intravenous study intervention (including the flush) should be administered over a period of not
less than 1 hour, and not more than 2 hours. The infusion (including the flush) should be completed
within 6 hours of preparation.
Since multiple SC injections are administered at visits, each injection of study intervention should
be given at a different location of the body.
Study intervention administration must be captured in the source documents and the electronic
case report form (eCRF).
Guselkumab and placebo for guselkumab will be manufactured and provided under the
responsibility of the sponsor. Refer to the guselkumab IB for a list of excipients. Both guselkumab
and placebo are designated as Investigational Medicinal Product.
Detailed instructions on the administration of study intervention will be provided in the Site
Investigational Product Procedures Manual and Investigational Product Preparation and
Administration Instructions (IPPI).
For a definition of study intervention overdose, refer to Section 8.4, Treatment of Overdose.
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The end of study will occur after all enrolled participants have completed the Week 20 visit or
discontinued study intervention prior to Week 24, and all participants have completed their final
efficacy and safety visits per the Schedule of Activities (Section 1.3).
6.1.1. 
Long-Term Extension
During the LTE of the study, participants will continue to receive the same study intervention q4w
(placebo or guselkumab) that they were assigned to receive through Week 48. The first dose in the
LTE will be at Week 52.
The study intervention will remain blinded throughout the study (including the LTE).
Instructions for administration of the study intervention will be provided to participants (or
caregiver) who have been trained and would like to administer the study intervention at home.
The end of study will occur after all enrolled participants have completed the Week 20 visit or
discontinued study intervention prior to Week 24, and all participants have completed their final
efficacy and safety visits per the Schedule of Activities (Section 1.3).
6.1.2. 
Combination Products
 
For this protocol, the term combination product refers to the single integral drug-device
combination.
 
The sponsor-manufactured combination product for use in the main  study is the 1.0 mL
prefilled syringe (PFS)(100mg/mL)assembled in an UltraSafe Plus™ Passive Needle Guard
(PFS-U). Additional details on the PFS-U are provided in Section 6.2 and the guselkumab IB.
 
The sponsor-manufactured combination products provided for use in the LTE (Section 4.1.2)
are the 2.0 mL PFS  (200mg/2mL) with YpsoMate Autoinjector (PFS-Y) and the
1.0 mL PFS-U (100mg/mL). The YpsoMate device (Y) is manufactured by the medical device
manufacturer Ypsomed. The UltraSafe Plus device (U) is manufactured by medical device
manufacturer Becton-Dickinson. The sponsor manufactures the 100mg/mL and 200mg/2mL
guselkumab PFS. The sponsor also assembles the PFS with the devices to form the PFS-U
and PFS-Y combination products. Additional details on the PFS-U and PFS-Yare provided
in Section 6.2 and the guselkumab IB.
 
All combination product deficiencies (including failure, malfunction, improper or inadequate
design, manufacturer error, use error, and inadequate labeling) shall be documented and
reported by the investigator throughout the study. For studies using a combination product,
these deficiencies will be reported as product quality complaints (PQC) (see Section 10.10.6
Appendix 10: Adverse Events, Serious Adverse Events, Product Quality Complaints, and
Other Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up,
and Reporting)and appropriately managed by the sponsor.
6.2. 
Preparation/Handling/Storage/Accountability
Preparation/Handling/Storage
For IV administration, guselkumab will be supplied as a 100 mg/mL sterile liquid in a single dose
PFS assembled in an UltraSafe Plus™ Passive Needle Guard (PFS-U). For IV administration,
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placebo for guselkumab will be supplied as a 1 mL sterile liquid in a single dose PFS assembled
in a PFS-U. Study intervention will be prepared for IV administration based on the instructions
provided to clinical sites in the IPPI.
For SC administration during the main study, guselkumab will be supplied as a 100 mg/mL sterile
liquid in a single dose PFS-U. For SC administration, placebo for guselkumab will be supplied as
a 1 mL sterile liquid in a single dose PFS-U. For SC administration during the LTE, guselkumab
will be supplied as the 2.0 mL PFS-Y (200mg/2mL) or the 1.0 mL PFS-U (100mg/mL). Placebo
for guselkumab during the LTE will be supplied as a 1 mL sterile liquid in a single dose PFS-U or
2.0 mL PFS-Y.
Guselkumab and placebo for guselkumab should be clear and colorless to light yellow solution
that may contain small translucent particles. Do not use guselkumab or placebo for guselkumab if
the liquid is cloudy or discolored or has large particles. Protection from light is not required during
the preparation and administration of the study intervention material, but avoid direct exposure to
sunlight. Aseptic procedures must be used during the preparation and administration of the study
intervention material.
Refer to the site IPPI for additional guidance on study intervention preparation, handling, and
storage.
Accountability
The investigator is responsible for ensuring that all study intervention received at the site is
inventoried and accounted for throughout the study. All study intervention will be stored in its
original container and disposed of according to the sponsor's instructions.
Study intervention 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 intervention  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 intervention will be documented on the intervention return form. When the study site is an
authorized destruction unit and study intervention supplies are destroyed on-site, this must also be
documented on the intervention return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be
retained for intervention accountability purposes.
Study intervention 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 intervention will be
supplied only to participants participating in the study. Returned study intervention must not be
dispensed again, even  to the same participant. Study intervention may not be relabeled or
reassigned for use by other participants. The investigator agrees neither to dispense the study
intervention from, nor store it at, any site other than the study sites agreed upon with the sponsor.
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Further guidance and information for the final disposition of unused study interventions are
provided in the Site Investigational Product Procedures Manual.
6.3. 
Measures to Minimize Bias: Randomization and Blinding
Intervention Allocation
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Participants will be randomly assigned
to 1 of 2 intervention groups based on a computer-generated randomization schedule prepared
before the study by or under the supervision of the sponsor. The randomization will be balanced
by using randomly permuted blocks and will be stratified by geographic region and UPCR level.
The interactive web response system (IWRS) will assign a unique intervention code, which will
dictate the intervention assignment and matching study intervention kit for the participant. The
requestor must use his or her own user identification and personal identification number when
contacting the IWRS, and will then give the relevant participant details to uniquely identify the
participant.
Blinding
To maintain the study blind, the study intervention container will have a label containing the study
name, study intervention number, reference number, and storage conditions. The label will not
identify the study intervention in the container. However, if it is necessary for a participant's safety,
the study blind may be broken and the identity of the study intervention ascertained. The study
intervention number will be entered in the eCRF when the study intervention is administered. The
study interventions will be identical in appearance and will be packaged in identical containers.
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 participant.
Data that may potentially unblind the intervention  assignment (ie, study intervention  serum
concentrations, anti-guselkumab antibodies, study intervention preparation/accountability data,
intervention allocation, and biomarker or other specific laboratory data) will be handled with
special care to ensure that the integrity of the blind is 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 DBL and
unblinding.
Under normal circumstances, the blind should not be broken until all participants have completed
the main study and the database is finalized. The investigator may in an emergency determine the
identity of the intervention by contacting the IWRS. While the responsibility to break the
intervention code in emergency situations resides solely with the investigator, 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, 7days per week. In the event the blind is broken, the sponsor must be
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informed as soon as possible. The date and reason for the unblinding must be documented in the
appropriate section of the eCRF and in the source document. The documentation received from
the IWRS indicating the code break must be retained with the participant's source documents in a
secure manner.
Participants who have had their intervention assignment unblinded should continue to return for
scheduled evaluations.
Additionally, a given participant’s treatment assignment may be unblinded to the sponsor, the
Independent Ethics Committee/Institutional Review Board (IEC/IRB), and site personnel to fulfill
regulatory reporting requirements for suspected unexpected serious adverse reactions (SUSARs).
If a participant is unblinded by the site, the information must be entered in the appropriate section
of the eCRF and in the participant's source documents.
A separate code break procedure will be available for use by J&J Global Medical Safety group to
allow for unblinding of individual participants to comply with specific requests from regulatory or
health authorities.
In general, randomization codes will be disclosed fully at the end of study when the clinical
database is closed.
The study blind will be maintained throughout the study (including the LTE).
One DBL for the study will occur at the end of study.
6.4. 
Study Intervention Compliance
When study intervention is administered as an IV infusion or SC injection by qualified staff, the
details of each administration will be recorded in the eCRF. For IV infusions, this will include date
and start and stop times of the IV infusion and volume infused; for SC injections, this will include
date and time of SC injection.
Additional details may be provided in the site IPPI that is provided separately. Compliance with
the treatment schedule is strongly encouraged.
6.5. 
Concomitant Therapy
Detailed information of prestudy topical and systemic SLE and LN therapies including dosage and
frequency of administration must be recorded for past history  as well as any COVID-19
vaccinations and treatments (including authorized for emergency use) at any time in the past. Other
prestudy therapies administered at the time of screening or up to 60 days before first dose of study
intervention, whichever is longer, must be recorded at screening. For any therapies that were
discontinued, the reason for discontinuation (eg, non-response, loss of response, intolerance, safety
concern, etc) should be documented.
Concomitant SLE and LN therapies (and non-SLE, LN concomitant therapies) must be recorded
throughout the study beginning with screening to the final safety follow-up visit after the last dose
of study intervention. Concomitant therapies should also be recorded beyond the final safety
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follow-up visit only in conjunction with SAEs that meet the criteria outlined in Serious Adverse
Events in Section 8.3.1, Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal
supplements; non-pharmacologic therapies such as electrical stimulation, acupuncture, special
diets, exercise regimens, or other specific categories of interest) different from the study
intervention must be recorded in the eCRF. Recorded information will include a description of the
type of therapy, duration of use, dosing regimen, route of administration, and indication.
Modification of an effective preexisting therapy should not be made for the explicit purpose of
entering a participant into the study.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in
which prohibited therapies are administered.
Every reasonable effort should be made to keep concomitant medications stable to avoid
introducing non-protocol medications for SLE or LN disease activity through the final safety visit,
or as specified in the following sections. Dose stabilization of all concomitant medications is
required prior to randomization. All medications must meet study protocol guidelines (see
Sections 5.1 and 5.1.1, and Table 5 and Table 6, which outline permitted concomitant medication
use and dose stabilization requirements prior to randomization and during the blinded study
period). It is recommended that all other concomitant medications be maintained at stable doses
through the final safety visit, including for those discontinuing the study prematurely. If necessary,
a concomitant medication may be reduced or temporarily discontinued because of abnormal
laboratory values, safety and tolerability issues, concurrent illness, or the performance of a surgical
procedure, but the change and reason for the medication change should be clearly documented in
the participant’s medical record. Adjustments in concomitant therapies that do not comply with
the study protocol guidelines may cause a participant to be considered a TF for the primary and
secondary endpoints through Week 52.
During the entire study, Investigators should consider whether increases in permitted background
therapy due to increased SLE or LN disease activity warrant discontinuation of study intervention.
If protocol-prohibited immunosuppressants (such as cyclosporine, voclosporin, or tacrolimus),
biologics (such as belimumab or rituximab), cytotoxic agents (such as cyclophosphamide), IV
glucocorticoids, or average daily doses of oral glucocorticoids >60 mg (prednisone or equivalent)
are initiated for severe, progressive, or unstable SLE disease activity, the participant should be
considered for discontinuation from study intervention (see Section 7.1). This should be discussed
with the medical monitor and/or sponsor.
During the LTE, every effort should be made to continue to adhere to the requirements for
concomitant therapies with some exceptions as specified in the sections below.
Table 5 outlines permitted concomitant medication use and dose stabilization requirements prior
to randomization.
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In the main study and the LTE, treatment for an  LN flare, which is defined as an increase in
proteinuria and/or serum creatinine concentration, abnormal urine sediment or a reduction in
creatinine clearance rate as a result of active disease requiring a change in an immunomodulatory
medication for LN beyond that which is outlined in Table 5 and Table 6 will require
discontinuation of study medication.
Table 5: 
Permitted Concomitant Medications for SLE and LN, the Minimum Stabilization Period
before Randomization, and the Maximum Allowed Doses at Study Randomization
Permitted Concomitant 
Medications for SLE 
Stabilization Period Prior to 
Randomization
Maximum Allowable Dose
Antimalarials (chloroquine, 
hydroxychloroquine, or 
quinacrine) 
Treated for ≥12 weeks with  
stable dosing for ≥6 weeks 
≤250 mg/day chloroquine
(≤3 mg/kg/day)
≤400 mg/day hydroxychloroquine
≤100 mg/day quinacrine
Oral glucocorticoids 
Treated for ≥6 weeks with stable 
dosing ≥2 weeks before 
randomization. 
Must not have received epidural, 
IV, or IM administration of
glucocorticoids at a prednisone
equivalent dose of >125 mg/day
within 6 weeks prior to
randomization.
Equivalent to average daily dose of
1 mg/kg/day or ≤60 mg/day of
prednisone or its equivalent,
whichever is lower
NSAIDs and other analgesics 
At least 2 weeks 
No more than the usual marketed
doses approved in the country
where the study is being conducted
Anti-hypertensive medications 
(ARBs or ACE inhibitors) 
At least 2 weeks 
No more than the usual marketed
doses approved in the country
where the study is being conducted.
Non-biologic immunomodulators: 
MMF  
MPA  
Treated for ≥8 weeks at
randomization 
≤3 g/day
≤2.2 g/day
Abbreviations: ACE=angiotensin-converting enzyme; ARB=angiotensin II receptor blockers; IM=intramuscular;
IV=intravenous; LN=lupus nephritis; MMF=mycophenolate mofetil; MPA=mycophenolic acid;
NSAID=non-steroidal anti-inflammatory drug; SC=subcutaneous; SLE=systemic lupus erythematosus.
Table 6 summarizes the protocol requirements and any allowed changes in dosing for
study-permitted SLE and LN medications during the double-blind study period.
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Table 6: 
Blinded Study Period - Protocol Requirements for Permitted Concomitant SLE or LN
Medications
Permitted Concomitant 
Medications for SLEa 
Study Dose at Randomization 
Maximum Allowable Dose
During Study
Antimalarials (chloroquine, 
hydroxychloroquine, or 
quinacrine) 
≤250 mg/day chloroquine 
(≤3 mg/kg/day) 
≤400 mg/day hydroxychloroquine 
≤100 mg/day quinacrine 
Stable dosing through Week 52.
Initiation of new antimalarial
treatment is not permitted through
Week 52.
Oral glucocorticoidsb 
Stable oral glucocorticoids at 
minimum prednisone equivalent 
dose of 10 mg/day and maximum 
1 mg/kg/day or ≤60 mg/day, 
whichever is lower. 
Week 2 Through Week 12 -
tapering starting from Week 2 to
prednisone 5 mg equivalent PO
daily by Week 12 according to
schedule (Appendix 7
[Section 10.7])
Reason(s) for not tapering
glucocorticoids should be
documented
NSAIDs and other analgesics 
Stable dosing through Week 52 with no more than the usual marketed
doses approved in the country where the study is being conducted. Notable
changes in NSAID dosing to be recorded in concomitant medications. The
initiation of treatment with NSAIDs should be avoided unless other
analgesics are contraindicated.
Anti-hypertensive medications 
(ARBs or ACE inhibitors) 
No more than the usual marketed doses approved in the country where the
study is being conducted. The initiation of treatment with ARB or ACE
inhibitors should be avoided between randomization and Week 52 unless
other hypertensive treatments are contraindicated. Substitution of ACE
inhibitors for ARBs or ARBs for ACE inhibitors is permitted if medically
necessary.
Non-biologic immunomodulators: 
MMF  
MPA  
≤3 g/day  
≤2.2 g/day  
Stable dosing through Week 52.
Initiation of a new
immunomodulator is not permitted
through Week 52.
a 
Permitted concomitant medications are not supplied by the sponsor.
b 
Between Weeks 12 and 52, participants requiring average daily doses of glucocorticoids for SLE or LN
disease activity that exceed their baseline dose at Week 0 may be categorized as TFs. While these participants
will be permitted to remain in the study, the investigator must consider whether glucocorticoid dose increases
to an average daily dose ≥60 mg prednisone or equivalent for more than 7 consecutive days or whether a
requirement for multiple rescues with glucocorticoid therapy between Weeks 12 and 52 should result in
discontinuation of study intervention administration (see Section 7.1).
Abbreviations: ACE=angiotensin-converting enzyme; ARB=angiotensin II receptor blockers; IM=intramuscular;
IV=intravenous; LN=lupus nephritis; MMF=mycophenolate mofetil; MPA=mycophenolic acid;
NSAID=non-steroidal anti-inflammatory drug; PO=orally; SC=subcutaneous; SLE=systemic lupus
erythematosus.
6.5.1. 
Antimalarial Medications
Stable treatment with hydroxychloroquine, chloroquine, or quinacrine is permitted through
Week 52 as shown in Table 5 and Table 6. It is not permitted to introduce or adjust dosing of
antimalarials through Week 52; however, if necessary, one antimalarial may be substituted for
another at an equivalent or lower dose. Antimalarials produced by a licensed compounding
pharmacy (eg, quinacrine) in the country of administration and using pharmaceutical grade
components are allowed. It is recommended that participants receiving antimalarials receive
screening for retinal toxicity according to local guidelines.
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During the LTE, antimalarial doses or medications may be changed in order to treat other aspects
of SLE as needed, but should not be changed to treat LN.
6.5.2. 
Glucocorticoid Therapy
Participants likely to require multiple courses of systemic glucocorticoids for reasons other than
SLE or LN (eg, history of uncontrolled asthma, uncontrolled chronic obstructive pulmonary
disease, etc) should be excluded from study participation, including the LTE. However,
participants may receive short courses (10 days or less) of oral glucocorticoids for reasons such as
prophylactic therapy before surgery (stress-dose glucocorticoids), therapy for certain infections,
acute exacerbation of asthma or chronic obstructive pulmonary disease, or other condition (eg,
contact dermatitis) not related to increased SLE or LN disease activity. Dosage, duration, and
reason for glucocorticoid use in these instances must be documented.
Unnecessary changes in glucocorticoid dose are discouraged, and any dose adjustments are
recommended to be made in small amounts. Changes in glucocorticoid dosing other than those
described in this section of the protocol are allowed only for medical necessity. The degree and
timing of any unspecified glucocorticoid adjustments should be carefully considered as this may
have a significant impact on the study results and upon continuation of study intervention.
Oral Glucocorticoids
Participants must be receiving this medication at screening and be on a stable dose equivalent to
an average daily dose of 1 mg/kg/day or ≤60 mg/day prednisone (or equivalent), whichever is
lower for at least 2 weeks prior to the first study intervention dose. Participants are required to be
receiving at least 10 mg/day prednisone equivalent at screening and randomization.
A summary of allowed glucocorticoid dosing at randomization and changes during the study are
shown in Table 5 and in Table 6, respectively. A glucocorticoid tapering schedule starting from
Week 2 down to 5 mg po qd prednisone equivalent by Week 12 is provided in Appendix 7
[Section 10.7]. It is required that all participants adhere to this steroid tapering schedule as closely
as possible. Significant deviation from this tapering schedule should be discussed with the medical
monitor. Glucocorticoid doses should not be changed to start within one of the columns of the
tapering schedule. If a participant falls between the doses noted in 2 adjacent columns (eg, 55 mg
instead of 50 or 60 mg), the investigator should make a clinical decision as to which column they
should be tapered to (eg, 30 or 40 mg) then stay within that column for the rest of the taper. A
participant’s lowest glucocorticoid dose should be 5 mg po qd through Week 24 unless an AE
requires discontinuation. Reason(s) for not tapering glucocorticoids should be documented.
Additional considerations of oral glucocorticoid use during the study are as follows:
 
If a participant experiences worsening disease activity while tapering glucocorticoids from
Weeks 2 to 12, further dose decreases may be suspended, and/or their oral glucocorticoid dose
may be temporarily increased (ie, glucocorticoid rescue) if deemed necessary by the
investigator.
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 
Increases in average daily glucocorticoid dose that exceed the baseline dose may trigger TF
rules. If glucocorticoid tapering is interrupted, Investigators are encouraged to resume
tapering as soon as it is practical.
 
Increases above 10 mg/day prednisone equivalent after Week 12 will be considered a TF.
 
It is recommended that participants be educated about and monitored for symptoms of steroid
adrenal insufficiency/deficiency (eg, Addisonian symptoms such as fatigue, muscle weakness,
decreased appetite, nausea, vomiting, joint and muscle pain) by study staff during periods of
steroid tapering, as appropriate.
 
After Week 24, further tapering of glucocorticoids is permitted, however, the taper should not
exceed a decrease of 1 mg/day prednisone equivalent per month (eg, 5 mg/day to 4 mg/day
over a 1-month time period). Investigators should monitor these participants for signs and
symptoms of Addisonian crisis.
Epidural, Intravenous, Intramuscular, Intra-articular, Intrabursal injection, and
Intralesional Glucocorticoids
Epidural, IV, and IM glucocorticoids at a prednisone equivalent dose of >125 mg/day should not
be used during the study or within 6 weeks prior to randomization.
Intra-articular (IA), intrabursal, or intralesional administration of glucocorticoids is strongly
discouraged within 6 weeks prior to randomization. Use of an intrabursal or intralesional
glucocorticoid is highly discouraged but is allowed if no other treatments are available.
ACTH administered by injection is not allowed within 1 month prior to randomization and
throughout the study.
During the study, use of epidural, IV, IM glucocorticoid use may cause participants to be
considered TFs. If use of epidural, IV or IM glucocorticoids is planned for a participant, discussion
with the medical monitor is recommended.
If clinically necessary, a total of up to 2 IA injections may be permitted for SLE up to Week 12
and should be recorded as a medical procedure.
Rectal Administration
Rectal administration of glucocorticoids, if necessary, should be short-term and topical
preparations should be used.
Inhalation Glucocorticoids
Glucocorticoids administered by bronchial or nasal inhalation for treatment of conditions other
than SLE or LN may be given as needed.
6.5.3. 
Nonsteroidal Anti-inflammatory Drugs
Nonsteroidal anti-inflammatory drugs (NSAIDs) and other regularly administered analgesics
should not be adjusted for at least 2 weeks prior to the first administration of the study intervention
and through Week 52, and they may be changed only if the participant develops unacceptable side
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effects. Participants are permitted to receive the usual marketed doses approved in the country in
which the study is being conducted. NSAIDs, including aspirin or selective cyclooxygenase-2
inhibitors, and other analgesics (including injectable NSAIDs, analgesics or other pain-relieving
agents) that are used on an “as needed” basis would generally not be considered to constitute stable
dosing as noted is required in Table 5 and Table 6. The initiation of treatment with NSAIDs should
be avoided unless other analgesics are contraindicated. Participants using them in specific
situations (eg, prior to an activity) may be considered stable but these situations should be
discussed with the medical monitor or sponsor prior to enrollment into the study.
6.5.4. 
Anti-hypertensive Medications
Participants are permitted to receive stable doses of ARB or ACE inhibitors for the treatment of
hypertension, cardiovascular disease, kidney disease, and LN. If receiving regular treatment with
ACE inhibitors or ARBs, participants must be receiving stable dosing for at least 2 weeks prior to
randomization. If necessary, participants are permitted to switch between ARB and ACE inhibitors
or vice versa. Effort should be made to ensure that the effective doses of the switched drugs are
comparable. The initiation of treatment with ARB or ACE inhibitors should be avoided between
randomization and Week 52 unless other hypertensive treatments are contraindicated.
During the LTE, the dose of ACE inhibitors/ARBs may be changed or ACE inhibitors/ARBs may
be initiated, if needed to help with blood pressure control or because of specific medication
availability and/or convenience (eg, using combined ARB hydrochlorothiazide medications), but
medication changes to treat LN flares would require discontinuation from the LTE.
6.5.5. 
Non-biologic Immunomodulators
Stable dosing of MMF or MPA as described in Table 5 is required. No other immunomodulators
are permitted during the study. A reduction in immunomodulators is allowed only if the participant
develops unacceptable side effects, with the implication that this may affect interpretation of the
participant’s clinical data. There should be no additions of a new immunomodulator to the existing
treatment regimen.
For subjects who initiate MMF (or MPA) during screening or close to screening, the dose should
be titrated up during screening based on tolerability to a target dose of ≤3.0 grams/day MMF (or
equivalent MPA) and kept stable thereafter.
6.5.6. 
Topical Medications
Regular use of topical medications is permitted. “As needed” use of topical NSAIDs, analgesics,
or other pain-relieving agents such as capsaicin is permitted, but not within 48 hours prior to study
visit. “As needed” use of topical glucocorticoids is permitted if involving a limited BSA (≤20%),
but not within 48 hours prior to a study visit.
6.5.7. 
Prohibited Therapies
Use of additional immunosuppressants or immunomodulators, other than those explicitly allowed
in the inclusion/exclusion criteria (Section 5.1 and 5.1.1), are prohibited including, but not limited
to, the following:
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 
Agents targeted at reducing TNFα  (eg, infliximab, golimumab, certolizumab pegol,
etanercept, CT-P13, adalimumab)
 
B-cell targeted agents (anti-CD20 [eg, rituximab, obinutuzumab], anti-CD19 [eg, obexelimab
(XmAb5871)], anti-B-cell activating factor, also known as B lymphocyte stimulator [BLyS;
eg, belimumab], anti-CD22 [eg, inotuzumab, ozogamacin], or other B-cell targeted therapies,
such as tabalumab, atacicept, daratumumab)
 
IL-1 inhibitors (eg, canakinumab)
 
IL-2 inhibitors or exogenous IL-2 therapy
 
IFN inhibitors or exogenous IFN therapy
 
IL-1 receptor antagonists (eg, anakinra)
 
Tocilizumab or any other biologic targeting IL-6 or IL-6 receptor
 
Tofacitinib, baricitinib, upadacitinib, or any other janus kinase inhibitor
 
Abatacept
 
Anti-IL-17 agents (eg, brodalumab, secukinumab, or ixekizumab)
 
Leflunomide
 
Cyclosporine A except for topical use
 
Calcineurin inhibitors (eg, tacrolimus or pimecrolimus, voclosporin)
 
Sirolimus, everolimus
 
Immunomodulatory preparations (eg, MTX, AZA/6-MP, mizoribine)
 
Toll-like receptor inhibitors
 
Thalidomide or lenalidomide
 
Dapsone
 
ACTH by injection
 
Epidural, IV, and IM glucocorticoids (see Section 6.5.2)
 
Other investigational agents
Use of cytotoxic drugs is prohibited including, but not limited to, cyclophosphamide,
chlorambucil, nitrogen mustard, or other alkylating agents.
Multiple administrations of high doses of oral glucocorticoids (average daily dose ≥60 mg), or
initiation of high potency topical glucocorticoids (>20% BSA), are prohibited during the study as
defined in Section 6.5.2.
Sulfa-based antibiotics, where reasonable and necessary, are allowed but should generally be
avoided.
The use of complementary therapies (eg, herbs, ointments, traditional Chinese medicine,
acupuncture) that have the potential to activate or inhibit the immune system is prohibited (see
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Section 5.1.1). In addition, use of complementary therapies that have the potential to interact with
antithrombotic agents is prohibited in those taking antithrombotic agents.
The use of other complementary therapies is strongly discouraged; in individual cases, use may be
permitted following discussion with the study sponsor and/or medical monitor.
As these lists cannot be exhaustive, please consult the medical monitor to discuss prior to starting
any biologic or other advanced therapies.
6.5.8. 
Rescue Medication
Higher doses of steroids can be used as rescue medication, however this may trigger a TF (see
Section 6.5.2 for details on glucocorticoid therapy concomitant use).
Increases in doses of current medications or addition of new protocol permitted medications for
SLE or LN disease activity, such as NSAIDs, ACE inhibitors, ARBs, immunomodulators
(antimalarials) and, potentially, topically applied (>20% BSA) or locally injected therapies (if
clinically indicated) should be discussed with the medical monitor and/or sponsor.
Severe, progressive, or unstable worsening of SLE disease activity that requires escalation in
therapy, including biologics such as belimumab or rituximab, systemic immunomodulators such
as cyclosporine or tacrolimus, sustained high doses of oral glucocorticoids, use of IV
glucocorticoids, or use of cytotoxic agents such as cyclophosphamide may require discontinuation
from the study intervention (see Section 6.5 and Section 7.1).
6.5.9. 
Vaccinations (including COVID-19)
When considering use of locally approved vaccines (including emergency use authorized
COVID-19 vaccines) in study participants, follow applicable local vaccine labelling, guidelines,
and standards of care for patients receiving immune-targeted therapy.
For study participants receiving a locally-approved COVID-19 vaccine (including emergency use
authorized), in order to help identify acute reactions potentially related to COVID-19 vaccine, it is
recommended where possible that vaccine and study drug be administered on different days,
separated by as large an interval as is practical within the protocol.
6.6. 
Dose Modification
Not applicable.
6.7. 
Continued Access to Study Intervention After the End of the Study
Local regulations on continued access will always take precedence. Plans for continued access
stated in this protocol may change if new information on the benefit-risk profile of guselkumab
becomes available during the study or program.
At the end of their participation in the main study, participants who have completed the study and
are benefiting from the study intervention, as determined by meeting CRR at Weeks 48 and 52,
will be offered the opportunity to enter the LTE study.
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If a DMC  review performed prior to the first patient’s entry into the LTE or during the LTE
demonstrates unfavorable benefit:risk profile or safety concerns arise, the study (and LTE) may
be stopped.
7. 
DISCONTINUATION OF STUDY INTERVENTION AND PARTICIPANT
DISCONTINUATION/WITHDRAWAL
7.1. 
Discontinuation of Study Intervention
A participant's study intervention must be discontinued if:
 
The participant withdraws consent to receive study intervention.
 
The investigator believes that for safety reasons or tolerability reasons (eg, AEs) it is in the
best interest of the participant to discontinue study intervention.
 
The participant becomes pregnantwithin the study period. Refer to Appendix 5 [Section 10.5],
Contraceptive Guidance and Collection of Pregnancy Information.
 
The participant develops an opportunistic infection (this does not include candidiasis that is
limited to the mouth).
 
The participant is deemed ineligible according to the following TB screening criteria:
 
A diagnosis of active TB is made.
 
A participant 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.
 
A participant undergoing evaluation has a chest radiograph with evidence of current
active TB and/or a positive QuantiFERON-TB® test result (and/or a positive tuberculin
skin test result in countries in which the QuantiFERON-TB® test is not
approved/registered or the tuberculin skin test is mandated by local health authorities),
unless active TB can be ruled out and appropriate treatment for latent TB can be initiated
prior to the next study intervention administration and continued to completion (see also
Section 8.2.11 and Appendix 3 [Section 10.3]). Indeterminate QuantiFERON-TB® test
results should be handled as described in Section 8.2.11. Participants with persistently
indeterminate QuantiFERON-TB® test results may continue 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 participant has no additional risk factors for TB
as determined by the investigator. This determination must be promptly reported to the
medical monitor or designee and recorded in the participant's source documents and
initialed by the investigator.
 
Note: In Ukraine, while the QuantiFERON-TB® test is not approved/registered, it is
acceptable, and an additional tuberculin skin test is not required.
 
A participant receiving treatment for latent TB discontinues this treatment prematurely
or is noncompliant with the therapy.
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 
The participant has a serious adverse reaction that is related to an injection or an infusion
resulting in bronchospasm with wheezing and/or dyspnea that requires ventilatory support OR
that results in symptomatic hypotension with a decrease in systolic blood pressure >40 mm
Hg or blood pressure <90/60 mm Hg.
 
The participant has a reaction resulting in myalgia and/or arthralgia with fever and/or rash
(suggestive of serum sickness and not representative of signs and symptoms of other
recognized clinical syndromes) occurring 1 to 14 days after an injection of study intervention.
These may be accompanied by other events including pruritus, facial, hand, or lip edema,
dysphagia, urticaria, sore throat, and/or headache.
 
The participant has a malignancy including squamous cell skin cancer. Consideration may be
given to allowing participants who develop ≤2 basal cell skin cancers that are adequately
treated with no evidence of residual disease to continue to receive study intervention.
 
Participant requires dialysis.
 
Noncompliance with study drug administration defined as multiple episodes of missing the
window in which to receive study intervention.
 
The participant has severe liver test abnormalities that meet one of the conditions outlined in
Appendix 11 (Section 10.11; Liver Safety: Suggested Actions and Follow-up Assessments).
The sponsor may elect to terminate the study at any time, and if the sponsor decides not to continue
development for any reason, study medication/drug will no longer be provided to any participants,
including those in the LTE.
Discontinuation of a participant’s study intervention should be considered under the
following conditions:
1. Persistent inadequate response or worsening of LN based on worsening of renal function.
2. If the participant initiates treatment with prohibited therapies for SLE or LN, the medical
monitor or designee should be notified for possible discontinuation  of study intervention
(Section 6.5).
3. The participant develops a serious infection, including but not limited to sepsis or pneumonia.
Note: Any serious infection should be discussed with the medical monitor or designee, and
study intervention should be withheld until the clinical assessment is complete.
4. Discontinuation of study treatment should be considered for participants who report suicidal
Ideation level 4 (some intent to act, no plan), Ideation level 5 (specific plan and intent), or any
suicidal behavior (actual suicide attempts, interrupted attempts, aborted attempts, or
preparatory actions) on a postbaseline (after Week 0) eC-SSRS assessment. Discussion of
such subjects with the medical monitor or designee is required.
5. The participant develops a severe injection-site or infusion reaction, but not meeting criteria
specified above.
If a participant discontinues study intervention for any reason before the end of the double-blind
phase they may continue in the study. If the participant wishes to discontinue the study, then the
Final Efficacy Visit and final safety visit assessments should be obtained as specified in the SoA
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(Section 1.3, or as noted in Footnote c of the SoA). Study intervention assigned to the participant
who discontinued study intervention may not be assigned to another participant.
7.1.1. 
Long-Term Extension
Participants may withdraw consent and discontinue treatment during the LTE at any time. A
participant’s treatment must be discontinued in the LTE if any of the criteria in Section 7.1 above
are met. In addition, study intervention will be discontinued if the participant has an LN flare that
requires a change in medication during the LTE.
If a participant permanently discontinues study intervention for any reason before the end of the
LTE, assessments should be obtained as specified in SoA (Table 2 and Table 3).
7.2. 
Participant Discontinuation/Withdrawal From the Study
A participant will be withdrawn from the study for any of the following reasons:
 
Lost to follow-up
 
Withdrawal of consent
 
Death
 
Sponsor decision (eg, participating in any other clinical study with an investigational agent)
When a participant withdraws before study  completion, the reason for withdrawal is to be
documented in the eCRF and in the source document. Participants who terminate study
participation will not be required to return for any follow-up assessments; however, these
participants should complete the safety and efficacy evaluations specified in the SoA (Section 1.3)
at the time they terminate study participation. If the reason for withdrawal from the study is
withdrawal ofconsent then no additional assessments are allowed.
Withdrawal of Consent
A participant declining to return for scheduled visits does not necessarily constitute withdrawal of
consent. Alternate follow-up mechanisms that the participant agreed to when signing the consent
form apply as local regulations permit.
Prior to a participant withdrawing consent for follow-up, the investigator should offer the
participant an opportunity for one of the alternative reduced follow-up mechanisms described
below. Participants will not be allowed to continue to receive study intervention if reduced follow-
up is in place, but other study evaluations should continue as much as possible. Withdrawal of
consent should be an infrequent occurrence in clinical studies30, therefore, prior to the start of the
study the sponsor and the investigator should discuss and reach a clear understanding of what
constitutes withdrawal of consent in the context of the available reduced follow-up mechanisms
listed.
Circumstances for Reduced Follow-up
In the situation where a participant may be at risk for withdrawal of consent and is unable to return
for scheduled visits at the protocol-defined frequency, the investigator may consider options for
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reduced follow-up with consultation of the sponsor and/or medical monitor. These may include
(as local regulations permit):
 
Less frequent clinical visits
 
Telephone, email, letter, social media, fax, or other contact with:
 
participant
 
relatives of the participant
 
participant’s physicians (general or specialist)
 
Review of any available medical records
Details regarding these contacts must be properly documented in source records including
responses by participants.
7.2.1. 
Withdrawal From the Use of Research Samples
A participant 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 participant's original
separate informed consent for optional research samples.
 
The participant 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 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 participant 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 participant may withdraw consent for use of samples for research (refer to Long-Term
Retention of Samples for Additional Future Research in Appendix 9 [Section 10.9], Regulatory,
Ethical, and Study Oversight Considerations). 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.
7.3. 
Lost to Follow-up
To reduce the chances of a participant being deemed lost to follow-up, prior to randomization
attempts should be made to obtain contact information from each participant, eg, home, work, and
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mobile telephone numbers and email addresses for both the participant as well as appropriate
family members.
A participant will be considered lost to follow-up if he or she repeatedly fails to return for
scheduled visits and is unable to be contacted by the study site. A participant cannot be deemed
lost to follow-up until all reasonable efforts made by the study-site personnel to contact the
participant are deemed futile. The following actions must be taken if a participant fails to return to
the study site for a required study visit:
 
The study-site personnel must attempt to contact the participant to reschedule the missed visit
as soon as possible, to counsel the participant on the importance of maintaining the assigned
visit schedule, to ascertain whether the participant wishes to or should continue in the study.
 
Before a participant is deemed lost to follow-up, the investigator or designee must make every
reasonable effort to regain contact with the participant (where possible, 3 telephone calls,
e-mails, fax, and, if necessary, a certified letter to the participant’s last known mailing address,
or local equivalent methods). These contact attempts should be documented in the
participant’s medical records.
 
Should the participant continue to be unreachable, they will be considered to have withdrawn
from the study.
8. 
STUDY ASSESSMENTS AND PROCEDURES
Overview
The SoA summarizes the frequency and timing of efficacy, PK, immunogenicity, PD, biomarker,
pharmacogenomic, and safety measurements applicable to this study.
All patient-reported outcome (PROs) assessments should be completed before any tests,
procedures, or other consultations to prevent influencing participant perceptions. All PROs should
be completed independently by study participants. It is recommended that PROs be completed in
the following sequence: FACIT-Fatigue, PGIC, lupus symptoms (assessment of joint pain, joint
stiffness, rash, swelling), and LupusQoL. Clinician-reported outcome (ClinRo) procedures to be
performed include: SLEDAI-2K, Physician’s Global Assessment (PGA), joint count assessment,
CLASI. Clinician-reported outcome assessments should be performed by an adequately trained
assessor (see Section 8.1 for details).
Additional 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
participation in the study.
Spot urine will be used for UPCR related analyses (including the primary endpoint and various
other key efficacy endpoints). Analysis of the primary endpoint based on UPCR is discussed in
Section 9.4.2. Refer to the SoA (Section 1.3) for the timing and frequency of these sample
collections. Instructions on the sample collection and handling of urine samples are described in
the laboratory manual.
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Screening Phase
The screening phase is up to 8 weeks duration before randomization (with up to 4 additional weeks
for those starting MMF/MPA at or near the beginning of screening). After written informed
consent has been obtained, all screening evaluations (eg, laboratory test results, clinical data, and
concomitant medication data) that establish participant eligibility will be performed by the
principal investigator or designee to confirm that the participant satisfies all inclusion criteria and
does not violate any exclusion criteria. Participants who meet all of the inclusion and none of the
exclusion criteria can be enrolled in the study. Participants must meet criteria for UPCR,
hematology, and chemistry after at least 8 weeks of MMF/MPA. Every effort should be made
to adhere to the SoA (Section 1.3) for each participant. The collection of AEs will start at the time
informed consent is obtained.
Participants must undergo testing for TB and their medical history assessment must include
specific questions about a history of TB or known occupational or other personal exposure to
individuals with active TB (Section 8.2.11 and Appendix 3 [Section 10.3]).
Women of childbearing potential must have a negative urine pregnancy test result at screening and
at each visit and before any study intervention administration. Participants who are women of
childbearing potential must be reminded that they are required to use a highly effective method of
contraception during the study (as described in Section 5.1, Inclusion Criterion 17and Appendix 5
[Section 10.5]) and must continue taking such precautions for 12 weeks after receiving the last
dose of study intervention. The method(s) of contraception used by each participant must be
documented.
All screening evaluations establishing participant eligibility will be performed and reviewed by
the investigator before a participant can be randomized. Participants must have received approval
for study randomization following adjudication of inclusion and exclusion criteria.
A kidney biopsy is required if one has not been done within the last 6 months prior to screening to
confirm Class III/IV (ISN/RPS) proliferative nephritis (with or without class V [ISN/RPS]
membranous nephritis). A de-identified copy of the pathology report will be required to be
provided, tissue samples will be requested (where applicable or where local regulations permit)
for all kidney biopsies during screening or within the last 6 months. If the participant is undergoing
a kidney biopsy during screening, the participant should meet all other eligibility criteria prior to
a biopsy being performed.
Documentation (historical or local laboratory testing) of unequivocally positive values (as defined
in the laboratory’s reference range) should be provided for the following: ANA (eg, ANA by
human epithelial type 2 cells [HEp-2] titer, ANA by enzyme-linked immunosorbent assay
[ELISA]), or anti-dsDNA (eg, anti-dsDNA by Farr assay or ELISA), or anti-Smith. To establish
participant eligibility, these results must be confirmed through central laboratory testing.
Blood Sample Collection
During the main study, the total blood volume to be collected from each participant will be
approximately 720 mL for those at sites collecting biomarkers, and approximately 380 mL for
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those at sites not collecting biomarkers. During the LTE, the total blood volume to be collected
from each participant will be approximately 270 mL for those at sites collecting biomarkers, and
approximately 215 mL for those at sites not collecting biomarkers.
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the
samples.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory
requisition form.
Refer to the SoA (Section 1.3)for the timing and frequency of all sample collections.
Instructions for the collection, handling, storage, and shipment of samples are found in the
laboratory manual that will be provided. Collection, handling, storage, and shipment of samples
must be under the specified, and where applicable, controlled temperature conditions as indicated
in the laboratory manual.
Study-Specific Materials
The investigator will be provided with the following supplies:
 
Investigator Site File (includes protocol and IB)
 
IPPI
 
Laboratory Manual
 
eCRF completion instructions
 
Patient recruitment materials
 
Sample ICFs
 
IWRS Manual
 
ePRO equipment
 
Laboratory kits
 
Pharmacy manual/study site investigational product and procedures manual
 
PRO questionnaires
 
Participant Diary Card (LTE only)
8.1. 
Efficacy Assessments
Investigator assessments and PROs of efficacy are included in this section.
 
The PRO instrument will be provided in the local language in accordance with local
guidelines.
 
The PRO instrument must be available for regulators and for IRB/IEC submissions.
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 
The PRO and adverse event data will not be reconciled with one another.
8.1.1. 
SLE Disease Activity Index 2000
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; the index 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 105.35,36 The baseline measurement for the SLEDAI-2K is defined as the closest measurement
taken prior to the initiation of the Week 0 study intervention administration.
SLEDAI improvement is defined as a reduction from baseline in total SLEDAI-2K score. No
worsening of total SLEDAI-2K from baseline is defined as a change ≤0 in SLEDAI-2K score and
meaningful improvement is best defined as a reduction in SLEDAI-2 K of 4 or more.
8.1.2. 
Physician's Global Assessment of Disease Activity
The PGA27,28 independent of participants’ assessment is recorded on a 10-cm VAS with responses
ranging from 0-3, and verbal anchors “No disease activity” (0) on the far-left side of the scale and
“Severe disease activity” (3) on  the far right of the scale. Disease activity can range from 0
representing no disease activity, 1 representing mild disease activity, 2 representing moderate
disease activity, to 3 representing extremely active disease. The baseline measurement for the PGA
is defined as the closest measurement taken prior to the initiation of the Week 0 administration.
No worsening in PGA defined as no significant deterioration (<10% increase from baseline) using
a 10-cm visual analogue scale.10
8.1.3. 
Joint Count Assessments
Assessment of active joints (defined as joints demonstrating tenderness and signs of
inflammation), tender joints, and swollen joints will be performed at visits indicated in the SoA
(Section 1.3). To be considered an active joint, an affected joint must demonstrate tenderness and
at least one additional sign of inflammation (eg, observed swelling such as edema or effusion) on
physical examination as determined by the joint assessor. Each of 28 joints will be evaluated for
tenderness and swelling.
The joint assessment should be performed by an adequately trained joint assessor. Training on how
the joint count will be performed will be provided by the sponsor. An independent joint assessor
would be preferred but if not available at the site, is not mandatory. The joint assessor should
preferably be a rheumatologist, but if a rheumatologist is not available, it should be a health care
provider with at least 1 year of experience in performing joint assessments. A health care provider
with less than 1 year of experience may serve as a joint assessor based upon the approval of the
sponsor. It is strongly recommended that the same joint assessor perform these assessments at
every visit. It is recommended that the designated assessor identify an appropriate back-up joint
assessor in case the designated joint assessor is unavailable.
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The arthritis score on the SLEDAI-2K should be in agreement with the active joint count
assessment as calculated in the eCRF.
8.1.4. 
Cutaneous Lupus Erythematosus Disease Area and Severity Index
Cutaneous lupus disease activity and severity will be measured by the CLASI. The CLASI is an
instrument to assess the disease activity and damage caused to the skin for CLE patients with or
without systemic involvement.1 The CLASI consists of 2 scores; the first summarizes the activity
of the disease while the second is a measure of the damage caused by the disease (CLASI Activity
and CLASI Damage scores). Activity is scored by the investigator based on erythema,
scale/hyperkeratosis, mucous membrane involvement, acute hair loss, and nonscarring 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.1
CLASI scores range from 0-70 for activity and 0-56 for damage, with higher scores indicating
worse disease activity.
8.1.5. 
FACIT-Fatigue
The FACIT-Fatigue version 4.0 is a 13-item questionnaire formatted for self-administration that
assesses patient-reported fatigue and its impact upon daily activities and function over the past
7days. Participants will be asked to answer each question using a 5-point Likert-type scale (0 Not
at all; 1 A little bit; 2 Somewhat; 3 Quite a bit; and 4 Very Much). The interpretation of
FACIT-Fatigue scores is such that a higher score indicates less fatigue, with a range of possible
scores of 0-52, with 0 being the worst possible score and 52 the best.7,17
8.1.6. 
Patient Global Impression of Change
The Patient Global Impression of Change (PGIC) in LN is a 1-item questionnaire based on the
clinical global impressions assessment and is designed to assess a patient’s impression of the
change in their health condition subsequent to receiving study treatment.10
The PGIC uses a 7-point Likert Scale on which patients rate the change in their LN since baseline
by choosing one of the following response options: “Very much improved” (1);
“Much improved” (2); “Minimally improved” (3); "No change" (4); "Minimally worse" (5);
"Much worse"(6); "Very much worse" (7).
The PGIC will also serve as an anchor measure to explore clinically meaningful change thresholds
for the other patient-reported outcomes included in the study.
8.1.7. 
Lupus Symptoms
Participants will be asked to report the worst severity of their joint pain, joint stiffness, skin rash,
and swelling in legs and/or feet over the past 7 days on a 0 to 10 numeric rating scale, with the left
anchor indicating “No [specific symptom]” and the right anchor, “Severe [specific symptom]”.
The items are scored individually, with higher scores reflecting greater symptom severity. The
administration frequency is described in the SoA (Section 1.3).
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8.1.8. 
Lupus Quality of Life Questionnaire
The LupusQoL Questionnaire is a valid, lupus-specific assessment of HRQoL consisting of
34 items across 8 domains (Physical health, Emotional health, Body image, Pain, Planning,
Fatigue, Intimate relationships, and Burden to others)developed for self-administration. The final
LupusQoL has a 5-point Likert response format, where 0 all the time, 1 most of the time, 2 a
good bit of the time, 3 occasionally, and 4 never, and uses a 4-week recall period. The LupusQoL
is scored by domain, with a higher score reflecting better HRQoL.21
8.2. 
Safety Assessments
Details regarding the external, independent DMC are provided in Section 9.5.
Adverse events will be reported and followed by the investigator as specified in Section 8.3,
Adverse Events, Serious Adverse Events, and Other Safety Reporting, and Appendix 10
[Section 10.10], Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-Up, and
Reporting.
Any clinicallyrelevant changes occurring during the study must be recorded on the Adverse Event
section of the eCRF.
Any clinically significant abnormalities persisting at the end of the study/early withdrawal will be
followed by the investigator until resolution or until a clinically stable condition is reached.
The study will include the following evaluations of safety and tolerability according to the
timepoints provided in the SoA (Section 1.3).
Study participants who are trained to self-inject (or will have a trained caregiver to inject) study
intervention at home will be trained to perform self-evaluation for injection-site reactions and
reporting of AEs after administering study interventions at home. Study participants will be asked
to self-identify signs or symptoms related to certain events (eg, potential TB infection, pregnancy,
malignancy) before administering study interventions and will be asked to contact the study site
doctor before administration if a symptom is identified.
8.2.1. 
Physical Examinations
For screening and the final safety visit, a full physical examination will be performed including:
the head and neck, chest, abdomen, and extremities, as well as including examinations based on
the individual’s medical history and manifestations of SLE and LN (edema, skin manifestations,
arthritis, etc.).
Assessment of the participants for safety and efficacy requires some physical examination by an
investigator at all visits. Targeted physical examinations, height and weight, and evaluation of
signs and symptoms of infection, will be performed as specified in the SoA  (Section 1.3).
Participants will be instructed to remove shoes and outdoor apparel and gear prior to measurements
for height and weight.
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8.2.2. 
Vital Signs
Through Week 52, temperature, pulse/heart rate, respiratory rate, and blood pressure will be
assessed at each visit. Blood pressure and pulse/heart rate measurements will be assessed with a
completely automated device. Manual techniques will be used only if an automated device is not
available. If feasible, blood pressure and pulse/heart rate measurements should be preceded by at
least 5 minutes of rest in a quiet setting without distractions (eg, television, cell phones).
Through Week 52, at a study intervention administration visit, vital signs should be obtained
before, approximately every 30 minutes during, and twice (at approximately 30-minute intervals)
after completion of the IV infusion(s), or before and approximately 30 minutes after the SC
injection, or if the participant reports any symptoms.
After Week 52 (during the LTE), vital signs will only be assessed when study participants receive
study intervention administration at the study site and at the final safety visit. Vital signs will be
assessed at these visits as described above in the SoA.
8.2.3. 
Electrocardiograms
A 12-lead electrocardiogram (ECG)will be performed at screening.
During the collection of the ECG, participants should be in a quiet setting without distractions
(eg, television, cell phones). Participants should rest in a supine position for at least 5 minutes
before ECG collection and should refrain from talking or moving arms or legs. If blood sampling
or vital sign measurement is scheduled for the same timepoint as ECG recording, the procedures
should be performed in the following order: ECG(s), vital signs, blood draw.
8.2.4. 
Clinical Safety Laboratory Assessments
Blood samples for serum chemistry and hematology and urine samples for urinalysis will be
collected as noted in Section 1.3. The investigator must review the laboratory results, document
this review, and record any clinically relevant changes occurring during the study in the AE section
of the eCRF. The laboratory reports must be filed with the source documents.
The following tests will be performed by the central laboratory unless otherwise specified or
approved by the medical monitor or designee:
 
Hematology assessments will include but are not limited to the following: hemoglobin,
hematocrit, platelet count, total and differential White Blood Cell (WBC) count, B-cell
analysis.
 
Blood chemistry assessments will include but are not limited to the following: chemistry
panel (total and direct bilirubin, ALT, AST, alkaline phosphatase, albumin, total protein,
calcium, phosphate, sodium, potassium, chloride, blood urea nitrogen/urea, and creatinine).
A medical monitor or designee and the clinical site will be notified if pre-specified abnormal
laboratory values defined in the laboratory manual are identified in any participant during the
conduct of the study.
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 
Viral serology (HIV antibody, hepatitis B surface antigen [HBsAg], anti-HBs, Hepatitis B
core antibody total, and HCV antibody)
 
QuantiFERON® -TB test
 
TB skin test (where applicable; performed locally)
 
Urine Analyses- Fresh spot urine
 
Urinalysis using urine dipstick. Urine sample will be further analyzed.
 
Urinary protein/creatinine ratio will be analyzed using an aliquot of spot urine collected
from participants.
 
Urine sediment microscopy (assessment using spot urine samples), withfeatures analyzed
to include (SoA: Section 1.3):
o 
Red blood cells
o 
WBC
o 
Epithelial cells
o 
Crystals
o 
Red blood cells, WBC, or heme-granular casts
o 
Bacteria
 
Urine pregnancy testing for women of childbearing potential only (performed locally)
Dipstick and sediment analysis of the urine samples will be performed. Specific gravity, pH,
glucose, protein, blood, ketones, bilirubin, and urobilinogen will be determined using a dipstick.
8.2.5. 
Electronic Columbia-Suicide Severity Rating Scale
No signal of suicidal ideation and behavior has been observed in the clinical trials of guselkumab
to date. However, in light of reports concerning suicidal ideation and behavior in patients with
plaque psoriasis treated with an IL-17R antagonist (brodalumab),6 the eC-SSRS will be used as a
screening tool to prospectively evaluate suicidal ideation and behavior among study participants.
The eC-SSRS measures 5 possible levels of suicidal ideation and 4 possible suicidal behaviors, as
well as non-suicidal self-injurious behavior. The assessment is a fully-structured, subject self-
report eC-SSRS questionnaire, including standardized questions, follow-up prompts, error
handling routines, and scoring conventions.24,29 Two versions of the eC-SSRS will be used in this
study, the Lifetime version and the Since Last Contact version. The Lifetime version will be
conducted during the screening visit and the Since Last Contact version will be conducted at all
other visits.
Participants will complete the eC-SSRS questionnaire using the sponsor-provided electronic
device. Study site personnel will train the participants on how to use the electronic device. The
eC-SSRS will be provided in the local languages in accordance with local guidelines.
The eC-SSRS will be performed during each evaluation visit according to the SoA. During a visit,
participants will be directed to a private, quiet place with the electronic device to complete the
assessment. Participants who do not have suicidal behavior or ideation will answer a limited
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number of questions and will usually complete the assessment in about 3 minutes. Participants
with significant suicidal ideation and behavior may require up to 10 minutes to answer all relevant
questions. At the screening visit, the eC-SSRS should be completed as the first assessment after
signing informed consent and before any other tests, procedures, or other consultations. For
subsequent visits, the eC-SSRS should be completed after all PROs and before any other tests,
procedures, or other consultations.
At the conclusion of each assessment, the eC-SSRS Findings Report can be viewed electronically.
At screening (“In the last 6 months”) and Week 0, participants with an Ideation level (1-5) or any
suicidal behaviors or with a response of “YES” for non-suicidal, self-injurious behavior must be
determined to be not at risk by the investigator based on an evaluation by a mental health
professional in order to be randomized. Participants with an Ideation level (1-5) on the eC-SSRS
or any suicidal behaviors or with a response of “YES” for non-suicidal, self-injurious behavior at
any postbaseline visit will also be referred to an appropriate mental health professional for
evaluation. If a participant’s psychiatric disorder can be adequately treated with psychotherapy
and/or pharmacotherapy then the participant, at the discretion of the investigator, should be
continued with treatment. Ultimately, the determination of suicidality and risk is up to the
investigator’s clinical judgment following evaluation by a mental health professional
(eg, psychiatrist, psychologist, or appropriately trained social worker or nurse).
Positive reports are generated from the eC-SSRS vendor for ANY of the following findings:
 
Ideation level 4: Some intent to act, no plan
 
Ideation level 5: Specific plan and intent
 
Behaviors: Actual suicide attempts
 
Behaviors: Interrupted attempts
 
Behaviors: Aborted attempts
 
Behaviors: Preparatory actions.
Negative suicidality indication reports are generated from the eC-SSRS vendor when there are NO
indications of the above.
The participant should not leave the site at screening or be dosed at dosing visits before the
eC-SSRS Findings Report (both for negative and positive reports) is reviewed by the investigator
and the participant’s risk has been assessed and follow-up determined, as appropriate.
For each Ideation level and Behavior, the following actions and associated alerts will be generated,
if applicable:
 
No ideation with No Behaviors: No further action is needed.
 
Ideation Levels (1-5) or suicidal behavior: Participant risk assessed and referral to a mental
health professional.
 
Ideation level of a 1, 2, or 3 with No Behaviors: Negative findings report will be
generated.
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Ideation level of a 4 or 5 or any suicidal behavior: Positive findings report will be
generated. When the system reports that the participant has a positive suicidal indication
(including for an incomplete-positive assessment), the site can immediately see the
outcome via the electronic device.
 
Non-suicidal, self-injurious behavior  YES: Participant risk assessed and referral to a mental
health professional. Negative findings report will be generated.
Interruption or the discontinuation of study treatment should be considered for any participant who
reports suicidal Ideation level 4 (some intent to act, no plan), Ideation level 5 (specific plan and
intent), or any suicidal behavior (actual suicide attempts, interrupted attempts, aborted attempts,
or preparatory actions) on a postbaseline (after Week 0) eC-SSRS assessment and who is deemed
to be at risk by the investigator based upon evaluation by a mental health professional. Discussion
of such participants with the medical monitor or designee is required (see Section 7.1). The final
decision on suitability for continuing in the study will be made by the investigator.
Any eC-SSRS findings, which in the opinion of the investigator are new or considered to be a
worsening and clinically significant, should be reported on the AE eCRF (see Appendix 10
[Section 10.10], Adverse Events, Serious Adverse Events, Product Quality Complaints, and Other
Safety Reporting: Definitions and Procedures for Recording, Evaluating, Follow-up, and
Reporting).
8.2.6. 
Concomitant Medication Review
Concomitant medications will be reviewed at each visit.
8.2.7. 
Injection-Site Reactions
An injection-site reaction is any adverse reaction at a SC study intervention injection-site. Injection
sites will be evaluated for reactions and any injection-site reaction will be recorded as an AE.
8.2.8. 
Hypersensitivity Reactions
Before any administration of study intervention at the study site, appropriately trained personnel
and medications (eg, antihistamines, injectable epinephrine) must be available to treat
hypersensitivity reactions, including anaphylaxis. All participants must be observed carefully for
signs and symptoms of a hypersensitivity reaction (eg, urticaria, pruritis, angioedema, wheezing,
dyspnea, or hypotension).
8.2.9. 
Adverse Events Temporally Associated with Infusion
Any AE (except laboratory abnormalities) that occurs during or within 1 hour after the IV infusion
of study intervention will be carefully evaluated. Minor infusion-related AEs may be managed by
slowing the rate of the IV infusion and/or treating with antihistamines and/or acetaminophen
(paracetamol) as clinically indicated. If an IV infusion of study intervention is interrupted because
of an AE that, in the opinion of the investigator, is not severe or does not result in an SAE, the
infusion may be restarted with caution.
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8.2.10. 
Infections
Investigators are required to evaluate participants for any signs or symptoms of infection at
scheduled visits. Study intervention administration should not be given to a participant with a
clinically significant, active infection. If a participant develops a serious infection, including but
not limited to sepsis or pneumonia, discontinuation of study intervention must be strongly
considered (Section 7.1). Any serious infection should be discussed with the medical monitor or
designee, and study intervention should be withheld until the clinical assessment is complete.
8.2.11. 
Tuberculosis Evaluations
8.2.11.1. 
Initial Tuberculosis Evaluation
Participants must undergo testing for TB (refer to Appendix 3 [Section 10.3]) and their medical
history assessment must include specific questions about a history of TB or known occupational
or other personal exposure to individuals with active TB. The participant should be asked about
past testing for TB, including chest radiograph results and responses to tuberculin skin or other TB
testing. Investigators have the option to use both the QuantiFERON-TB® test and the tuberculin
skin test to screen for latent TB if they believe, based on their judgment, that the use of both tests
is clinically indicated to evaluate a participant who is high risk of having latent TB. If either the
QuantiFERON-TB® test or the tuberculin skin test is positive, the participant is considered to have
latent TB infection for the purposes of eligibility for this study.
Participants with a negative QuantiFERON-TB® test result (and a negative tuberculin skin test
result in countries in which the QuantiFERON-TB® test is not approved/registered or the
tuberculin skin is mandated by local health authorities) are eligible to continue with
pre-randomization procedures. Participants with a newly identified positive QuantiFERON-TB®
test result must undergo an evaluation to rule out active TB and initiate appropriate treatment for
latent TB. Appropriate treatment for latent TB is defined according to local country guidelines for
immunocompromised patients. If no local country guidelines for immunocompromised patients
exist, US guidelines should be followed, or the participant will be excluded from the study.
A participant whose first QuantiFERON-TB® test result is indeterminate should have the test
repeated. In the event that the second QuantiFERON-TB® test result is also indeterminate, the
participant 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 participant
has no additional risk factors for TB as determined by the investigator. This determination must
be promptly reported to the medical monitor or designee and recorded in the participant's source
documents and initialed by the investigator.
8.2.11.2. 
Ongoing Tuberculosis Evaluation
Early Detection of Active Tuberculosis
To aid in the early detection of TB reactivation or new TB infection during study participation,
participants must be evaluated for signs and symptoms of active TB at scheduled visits (refer to
the SoA in Section 1.3) or by telephone contact approximately every 8 to 12 weeks. The following
series of questions is suggested for use during the evaluation:
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 
“Have you had a new cough of >14 days’ duration or a change in a chronic cough?”
 
“Have you had any of the following symptoms:
 
Persistent fever?
 
Unintentional weight loss?
 
Night sweats?”
 
“Have you had close contact with an individual with active TB?” (If there is uncertainty as to
whether a contact should be considered “close,” a physician specializing in TB should be
consulted.)
If the evaluation raises suspicion that a participant may have TB reactivation or new TB infection,
an immediate and thorough investigation should be undertaken, including, where possible,
consultation with a physician specializing in TB.
Investigators should be aware that TB reactivation in immunocompromised participants may
present as disseminated disease or with extrapulmonary features. Participants with evidence of
active TB should be referred for appropriate treatment.
Participants who experience close contact with an individual with active TB during the conduct of
the study must have a repeat chest radiograph, a repeat QuantiFERON®-TB test, a repeat tuberculin
skin test in countries in which  the QuantiFERON®-TB test is not approved/registered or the
tuberculin skin test is mandated by local health authorities, and, if possible, referral to a physician
specializing in TB to determine the participant’s risk of developing active TB and whether
treatment is warranted. Study intervention administration should be interrupted during the
investigation. A positive QuantiFERON®-TB test or tuberculin skin test result should be
considered detection of latent TB. Participants with a newly identified positive
QuantiFERON-TB® test result must undergo an evaluation to rule out active TB and initiate
appropriate treatment for latent TB. Appropriate treatment for latent TB is defined according to
local country guidelines for immunocompromised patients. If no local country guidelines for
immunocompromised patients exist, US guidelines should be followed, or the participant will be
excluded from the study. If the QuantiFERON-TB® test result is indeterminate, the test should be
repeated. Participants should be encouraged to return for all subsequent scheduled study visits
according to the protocol. Participants who discontinue treatment for latent TB prematurely or who
are noncompliant with therapy must immediately discontinue further administration of study
intervention and be encouraged to return for all subsequent scheduled study visits according to the
SoA (Section 1.3).
8.3. 
Adverse Events, Serious Adverse Events, and Other Safety Reporting
Timely, accurate, and complete reporting and analysis of safety information, including AEs, SAEs,
and PQC, from clinical studies are crucial for the protection of participants, investigators, and the
sponsor, and are mandated by regulatory agencies worldwide. The sponsor has established
Standard Operating Procedures in conformity with regulatory requirements worldwide to ensure
appropriate reporting of safety information; all clinical studies conducted by the sponsor or its
affiliates will be conducted in accordance with those procedures.
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Adverse events will be reported by the participant (or, when appropriate, by a caregiver, surrogate,
or the participant's legally acceptable representative) for the duration of the study.
For study intervention that meets the definition of a combination product, malfunctions or
deficiencies of a device constituent will be reported as PQC.
Further details on AEs, SAEs, and PQC can be found in Appendix 10 [Section 10.10], Adverse
Events, Serious Adverse Events, Product Quality Complaints, and Other Safety Reporting:
Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting.
8.3.1. 
Time Period and Frequency for Collecting Adverse Event and Serious
Adverse Event Information
All Adverse Events
All AEs and special reporting situations, whether serious or non-serious, will be reported from the
time a signed and dated ICF is obtained until completion of the participant's last study-related
procedure, which may include contact for follow-up of safety.
Serious Adverse Events
All SAEs, as well as PQC, 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.
Serious adverse events, including those spontaneously reported to the investigator by the final
safety visit, must be reported using a 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.
A possible Hy’s Law case is defined by the occurrence of ALT or AST ≥ 3xULN together with
total bilirubin ≥ 2xULN or INR > 1.5 (if measured). Any possible Hy’s Law case is considered an
important medical event and should be reported to the sponsor in an expedited manner using the
Serious Adverse Event form, even before all other possible causes of liver injury have been
excluded.
Information regarding SAEs will be transmitted to the sponsor using the Serious Adverse Event
Form, which must be completed and signed by a physician from the study site, and transmitted to
the sponsor within 24 hours. The initial and follow-up reports of an  SAE should be made by
facsimile (fax). Telephone reporting should be the exception and the reporter should be asked to
complete the appropriate form(s) first.
8.3.2. 
Method of Detecting Adverse Events and Serious Adverse Events
Care will be taken not to introduce bias when detecting AEs or SAEs. Open-ended and nonleading
verbal questioning of the participant is the preferred method to inquire about AE occurrence.
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Solicited Adverse Events
Solicited AEs are predefined local at the injection site and systemic events for which the participant
is specifically questioned.
Unsolicited Adverse Events
Unsolicited AEs are all AEs for which the participant is not specifically questioned.
8.3.3. 
Follow-up of Adverse Events and Serious Adverse Events
The investigator is obligated to perform or arrange for the conduct of supplemental measurements
and evaluations as medically indicated to elucidate the nature and causality of the adverse event,
serious adverse event, or PQC as fully as possible. This may include additional laboratory tests or
investigations, histopathological examinations, or consultation with other health care
professionals.
Adverse events, including pregnancy, will be followed by the investigator as specified in
Appendix 10 [Section 10.10], Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
8.3.4. 
Regulatory Reporting Requirements for Serious Adverse Events
The sponsor assumes responsibility for appropriate reporting of AEs to the regulatory authorities.
The sponsor will also report to the investigator (and the head of the investigational institute where
required) all SUSARs. The investigator (or sponsor where required) must report SUSARs to the
appropriate IEC/IRB that approved the protocol unless otherwise required and documented by the
IEC/IRB. A SUSAR will be reported to regulatory authorities unblinded. Participating
investigators and IEC/IRB will receive a blinded SUSAR summary, unless otherwise specified.
8.3.5. 
Pregnancy
All initial reports of pregnancy in female participants or partners of male participants 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. Abnormal pregnancy outcomes
(eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered SAEs and must be reported using anSAE reporting form. Any participant who becomes
pregnant during the study must discontinue further study intervention.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required (see Appendix 5 [Section 10.5], Contraceptive and Barrier Guidance and
Collection of Pregnancy Information and Appendix 10 [Section 10.10, Adverse Events, Serious
Adverse Events, Product Quality Complaints, and Other Safety Reporting: Definitions and
Procedures for Recording, Evaluating, Follow-Up, and Reporting).
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8.3.6. 
Disease-Related Events and Disease-Related Outcomes Not
Qualifying as Adverse Events or Serious Adverse Events
Flares of lupus activity, including LN (defined as an increase in proteinuria and/or serum creatinine
concentration, abnormal urine sediment or a reduction in creatinine clearance rate as a result of
active disease requiring a change in an immunomodulatory medication for LN beyond that which
is outlined in Section 6.5), that meet the definition of an SAE will be reported to the sponsor but
will not be reported to the Heath Authorities during the trial so that blinding may be retained in
order to ensure study integrity.
8.3.7. 
Adverse Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first study intervention
administration(s) in participants in this clinical study must be reported by the investigator to the
sponsor or designee within 24 hours after being made aware of the event, according to the
procedures in Appendix 10 (Section 10.10), Adverse Events, Serious Adverse Events, Product
Quality Complaints, and Other Safety Reporting: Definitions and Procedures for Recording,
Evaluating, Follow-Up, and Reporting, for SAEs. 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.
8.4. 
Treatment of Overdose
For this study, any dose of study intervention greater than 10% above the highest dose at a single
dosing visit specified in this protocol will be considered an overdose. The sponsor does not
recommend specific intervention for an overdose.
In the event of an overdose, the investigator or treating physician should:
 
Contact the medical monitor immediately.
 
Closely monitor the participant for AE/SAE and laboratory abnormalities.
 
Document the quantity of the excess dose in the eCRF.
Decisions regarding dose interruptions or modifications will be made by the investigator in
consultation with the medical monitor based on the clinical evaluation of the participant.
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8.5. 
Pharmacokinetics
Serum samples will be used to evaluate the PK ofguselkumab, as well as the immunogenicity of
guselkumab (antibodies to guselkumab). Serum collected for PK may additionally be used to
evaluate safety or efficacy aspects that address concerns arising during or after the study period.
Genetic analyses will not be performed on these serum samples. In addition, 24-hoururine samples
will be used to evaluate the potential renal excretion of guselkumab. Participant confidentiality
will be maintained.
8.5.1. 
Evaluations
Venous blood samples of approximately  5 mL will be collected for measurement of serum
concentrations of guselkumab and antibodies to guselkumab at the timepoints shown in the SoA
(Section 1.3).
Urine samples will be collected for measurement of guselkumab according to the SoA
(Section 1.3).
Venous blood samples will be collected and each serum sample will be divided into 3 aliquots
(1 each for PK, anti-guselkumab  antibodies, and a back-up). Samples collected for analyses of
guselkumab serum concentration and antibody to guselkumab may additionally be used to evaluate
safety or efficacy aspects that address concerns arising during or after the study period, for further
characterization of immunogenicity or for the evaluation of relevant biomarkers. Genetic analyses
will not be performed on these serum samples. Participant confidentiality will be maintained.
Additional information about the collection, handling, and shipment of biological samples can be
found in the laboratory manual.
8.5.2. 
Analytical Procedures
Pharmacokinetics
Serum and urine samples will be analyzed to determine concentrations of guselkumab using a
validated, specific, and sensitive immunoassay method by or under the supervision of the sponsor.
The sponsor, or its designee, under conditions in which the participants’ identity remains blinded,
will assay these samples.
8.5.3. 
Pharmacokinetic Parameters and Evaluations
Parameters
Based on the individual plasma concentration-time data, using the actual dose taken and the actual
sampling times, PK parameters and exposure information of guselkumab will be derived using
population PK modeling if data permits. Baseline covariates (eg, body weight, age, sex, CrCL,
race) may be included in the model, if relevant.
Pharmacokinetic/Pharmacodynamic Evaluations
If data permit, the relationships between serum guselkumab concentration and selected efficacy or
PD measures may be analyzed graphically.
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8.6. 
Pharmacodynamics
Pharmacodynamic markers will be evaluated using blood and urine samples collected at visits as
indicated in the SoA (Section 1.3). Postbaseline PD test results will not be released to the
investigators by the central laboratory.
8.7. 
Genetics
A pharmacogenomic blood sample will be collected from participants who consent separately to
this component of the study to allow for pharmacogenomic research, where local regulations
permit. Participation in pharmacogenomic research is optional.
Genetic (DNA) variation may be an important contributory factor to interindividual variability in
drug response and associated clinical outcomes. Genetic factors may also serve as markers for
disease susceptibility and prognosis and may identify population subgroups that respond
differently to an intervention.
8.8. 
Biomarkers
Biomarker assessments will be made to examine the biologic response to treatment and to identify
biomarkers that are relevant to guselkumab treatment and/or LN, where local regulations permit.
Assessments (detailed below) will include the evaluation of relevant biomarkers in serum, whole
blood, and urine collected as specified in the SoA (Section 1.3), where local regulations permit.
Data collected from these samples will be used for exploratory research that will include the
following objectives:
1. To understand the molecular effects of guselkumab.
2. To understand LN pathogenesis.
3. To understand why individual participants may respond differently to guselkumab.
4. To understand the impact of treatment with guselkumab on kidney or systemic inflammation.
5. To develop diagnostic tests to identify LN or SLE populations that may be responsive or
non-responsive to treatment with guselkumab.
8.8.1. 
Serum-based Biomarkers
Blood samples for serum-based biomarker analyses will be collected from all participants, where
local regulations permit. Serum will be analyzed for levels of specific proteins, autoantibodies,
and other inflammation-related molecules and/or disease-associated serologies relevant to LN and
SLE pathogenesis and treatment and response to guselkumab.
8.8.2. 
Whole Blood-based Biomarkers
Whole blood will be collected by venipuncture from participants for RNA expression analysis,
where local regulations permit. Total RNA will be isolated and used for differential gene
expression analyses to identify gene expression patterns that are relevant to guselkumab treatment
and/or LN and SLE, and to evaluate markers that can predict clinical response. Transcriptome
studies will be conducted using microarray, and/or alternative equivalent technologies, which
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facilitates the simultaneous measurement of the relative abundances of multiple RNA species
resulting in a transcriptome profile for each blood sample. This will enable the evaluation of
changes in transcriptome profiles that may correlate with biological response relating to LN or
SLE and/or the action of guselkumab.
Whole blood will also be collected and processed for PBMC isolation and cryopreserved for later
analysis. Analysis may include but is not limited to flow cytometric assessment of cell populations,
single cell transcriptomics, or functional assessment of cells in response to guselkumab treatment.
8.8.3. 
RNA Expression Research of a Subset of RNA Species
Urine will be analyzed for soluble proteins that may enable the identification of markers related to
LN or SLE disease activity and markers associating with guselkumab treatment or response to
treatment (from select sites). Cells isolated from the urine sample will be cryopreserved and may
later be examined by single cell transcriptomics to identify signatures associating with LN or SLE
pathogenesis and signatures associating with guselkumab treatment or response to treatment.
8.8.4. 
Stopping Analysis
Biomarker analyses are dependent upon the availability of appropriate biomarker assays and
clinical response rates. Biomarker analysis may be deferred or not performed, if during or at the
end of the study, it becomes clear that the analysis will not have sufficient scientific value for
biomarker evaluation, or if there are not enough samples or responders to allow for adequate
biomarker evaluation. In the event the study is terminated early or shows poor clinical efficacy,
completion of biomarker assessments is based on justification and intended utility of the data.
8.9. 
Immunogenicity Assessments
Antibodies to guselkumab  will be evaluated in serum samples collected from all participants
according to the SoA. Additionally, serum samples should also be collected at the final visit from
participants who discontinued studyintervention or were withdrawn from the study. These samples
will be tested by the sponsor or sponsor's designee.
Serum samples will be screened for antibodies binding to guselkumab and the titer of confirmed
positive samples will be reported. Other analyses may be performed to verify the stability of
antibodies to guselkumab and/or further characterize the immunogenicity of guselkumab.
Serum samples will be used to evaluate the immunogenicity of anti-guselkumab antibodies.
Samples collected for immunogenicity analyses may additionally be used to evaluate safety or
efficacy aspects that address concerns arising during or after the study period. Genetic analyses
will not be performed on these serum samples. Participant confidentiality will be maintained.
Analytical Procedures
The detection and characterization of antibodies to guselkumab will be performed using a validated
assay method by or under the supervision of the sponsor. All samples collected for detection of
antibodies to guselkumab will also be evaluated for guselkumab serum concentration to enable
interpretation of the antibody data. Antibodies may be further characterized and/or evaluated for
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their ability to neutralize the activity of the study intervention(s). Samples may be stored up to
15 years (or according to local regulations) following the last participant’s last visit for the study
at a facility selected by the sponsor to enable further analysis of immune responses to guselkumab.
8.10. Medical Resource Utilization and Health Economics
Not applicable.
9. 
STATISTICAL CONSIDERATIONS
Due to the sponsor’s decision to terminate the study early, some analyses described below may
not be performed.  The primary efficacy analysis and most secondary efficacy analyses will be
performed.  All safety analyses will be performed.
For informational purposes, the below section outlines the original statistical plan.
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 revised SAP.
9.1. 
Statistical Hypotheses
The primary hypothesis of this study is that guselkumab plus standard-of-care is superior to
placebo plus standard-of-care in participants with active LN as measured by the proportion of
participants inducing at least a 50% reduction of proteinuria with protocol specified steroid
tapering regimen at Week 24.
9.2. 
Sample Size Determination
The original design of the study included a target of approximately 60 participants to be randomly
assigned, with approximately 30 participants planned per intervention group. Due to the sponsor’s
decision to stop screening of new participants as a result of enrollment challenges, fewer than 60
participants will be enrolled in the study.
It should be noted that the sample size determination below was calculated assuming
approximately 60 participants would be randomized in this study.
The study will be considered a success if the 1-sided p-value from the difference in proportion of
participants with ≥50% decrease in proteinuria between the guselkumab and placebo intervention
groups from a logistic mixed effect repeat measurement (MMRM)longitudinal model is less than
a 1-sided alpha of 10%.
Table 7 shows the sensitivity of power to detect a difference in proportions of participants with
≥50% decrease in proteinuria between the guselkumab and placebo intervention groups at
Week 24.
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Table 7: 
Power to Detect Difference in Proportions of Participants with ≥50% Decrease in Proteinuria
Between the Guselkumab and Placebo Intervention Groups at Week 24
Difference in proportion of participants with ≥50% 
decrease in proteinuria between the intervention
groups
Power (%)
20%  
56.34
25% 
79.61
30% 
89.84
35%  
96.08
Notes:
• Proportion of placebo participants with ≥50% decrease in proteinuria is assumed to be 49%.
• Power calculation is based on 1-sided α of 0.10.
• Total sample size is 60.
If the proportion of placebo participants with ≥50% decrease in proteinuria is 49%, and the
difference in proportion between the intervention groups is 30%, a total sample size of 60 with a
1-sided alpha of 10% will provide approximately 90% power for success.
9.3. 
Populations for Analysis Sets
For purposes of analysis, the following populations are defined:
Population 
Description
Enrolled 
All participants who signed the ICF.
Full Analyses 
Set (FAS) 
All participants who were randomized in the study and received at least one administration of
study intervention.
Full Analyses 
Set (FASC24) 
All participants who were randomized in the study and received at least one administration of
study intervention and have the opportunity to complete the Week 24 visit prior to study
termination.
Full Analyses 
Set (FASC52) 
All participants who were randomized in the study and received at least one administration of
study intervention and have the opportunity to complete the Week 52 visit prior to study
termination.
Evaluable 
All FAS participants with a baseline measurement.
Safety Analysis 
Set (SAS)
All participants who received at least one dose of study intervention.
Immunogenicity 
Analysis Set 
(IAS)
All participants who received at least 1 administration of guselkumab and have at least one
post-dose sample collection.
PK Analysis Set 
(PKAS) 
All participants who received at least 1 administration of guselkumab and have at least one
post-dose sample collection.
PD Analysis Set 
(PDAS) 
All participants who received at least 1 administration of study intervention and have at least
one post-dose sample collection.
9.4. 
Statistical Analyses
The SAP will include a more technical and detailed description of the statistical analyses described
in this section. This section is a summary of the planned statistical analyses of the more important
endpoints including primary and key secondary endpoints.
9.4.1. 
General Considerations
Data primarily will be summarized using descriptive statistics. Continuous variables will be
summarized using the number of observations, mean, standard deviation (SD), median,
interquartile range, minimum and maximum, as appropriate. Categorical values will be
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summarized using the number of observations and percentages as appropriate. Median time will
be reported for time to event variables. In addition, graphical data displays (eg, line plots) and
participant listings may also be used to summarize/present the data.
For continuous endpoints, MMRM (with the Huber-White sandwich estimator) and Analysis of
Covariance will be used for analysis. For binary endpoints, logistic regression (MMRM or
parametric longitudinal models) and/or the Cochran Mantel Haenszel test will be used to analyze
data. For time to event data, log-rank tests will be used to analyze the data.
In general, all statistical tests will be performed at a nominal 1-sided significance level of α 0.10.
No multiplicity adjustment will be made for the endpoints being tested.
9.4.2. 
Primary Endpoint(s)
The primary endpoint is the proportion of participants achieving at least a 50% decrease in
proteinuria from baseline at Week 24.
Primary endpoint analysis
Analyses of the primary efficacy endpoint (≥50% decrease in proteinuria from baseline at
Week 24) will include data from all randomized participants who received at least one
administration of study intervention based on their assigned intervention group, regardless of the
actual intervention received and have baseline data (Evaluable population).
Treatment Failure Criteria may include: initiation or increased use ofa glucocorticoid or other
immunosuppressive agents, however these will be further defined in the SAP.
Participants who meet any of the TF criteria defined in the SAP will be assumed a non-responder,
ie, did not meet the ≥50% decrease in proteinuria criteria at Week 24.
The primary analysis will be based on the composite estimand where participants meeting TF
criteria are assumed non-achievers from the point of TF forward, and missing data are assumed as
non-achievers as well.
The study will be considered a success if the 1-sided p-value from the difference in proportion of
participants with ≥50% decrease in proteinuria between the guselkumab and placebo intervention
groups from a logistic MMRM longitudinal model is less than a 1-sided alpha of 10%.
See the SAP for further details about the analysis of the primary endpoint, including sensitivity
and subgroup analyses.
9.4.3. 
Secondary Endpoint(s)
Major secondary endpoints include:
1. Proportion of participants achieving CRR at Week 24.
2. Proportion of participants achieving a sustained reduction in steroid dose ≤10 mg/day of
prednisone or equivalent from Week 16 to Week 24.
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3. Proportion of participants achieving at least 50% decrease in proteinuria from baseline at
Week 52.
4. Proportion of participants achieving CRR at Week 52.
5. Proportion of participants with UPCR <0.5 mg/mg at Week 24.
6. Proportion of participants with UPCR <0.75 mg/mg at Week 24.
7. Time to CRR.
8. Time to TF.
Secondary endpoint analyses
The Evaluable population will be used for analysis and participants will be counted in the
intervention group assigned, regardless of the study intervention received.
Treatment failure and missing data will be included in the secondary endpoint estimands as
non-achievers or non-responders.
The details of the analysis of the major secondary endpoints will be included in the SAP.
9.4.4. 
Tertiary/Exploratory Endpoint(s)
Tertiary Endpoints
Extra Renal Lupus Manifestations
1. Proportion of participants with ≥4-point improvement at Week 24 in SLEDAI-2K modified
to exclude renal items.
2. Proportion of participants with baseline arthritis (with at least 4 active joints at baseline)who
have ≥50% reduction in active joints at Week 24.
3. Proportion of participants with baseline active mucocutaneous lupus manifestations (CLASI
score ≥8) and ≥50% reduction in CLASI scores at Week 24.
Health-Related Quality of Life and Fatigue
1. Change from baseline in LupusQoL individual domains at Week 24.
2. Change from baseline in FACIT-Fatigue score at Week 24.
3. Change from baseline in lupus symptoms (joint pain, joint stiffness, rash, and swelling
[peripheral edema]) at Week 24.
4. PGIC - Change in LN (health condition) at Week 24 and Week 52.
Further details of tertiary and exploratory endpoints analyses will be provided in the SAP.
9.4.5. 
Long-Term Extension Exploratory Endpoints
1. Proportion of participants maintaining CRR at Week 152.
2. Changes in PRO assessments including LupusQOL, FACIT-Fatigue, lupus symptoms, and
PGIC over time during the long-term extension.
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9.4.6. 
Safety Analyses
All safety analyses will be analyzed using the SAS population (refer to Section 9.3 for definition).
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using the
Medical Dictionary for Regulatory Activities. Any AE occurring at or after the initial
administration of study intervention  is considered to be treatment-emergent. All reported
treatment-emergent AEs will be included in the analysis. For each AE, the percentage of
participants who experience at least 1 occurrence of the given event will be summarized by
intervention group. In addition, comparisons between intervention  groups will be provided if
appropriate.
The following analyses of AEs will be used to assess the safety of participants:
 
Frequency and type of AEs.
 
Frequency and type of SAEs.
 
Frequency and type of reasonably related AEs as assessed by the investigator.
 
Frequency and type of AEs leading to discontinuation of study intervention.
 
Frequency and type of infections, serious infections, and infections requiring oral orparenteral
antimicrobial treatment.
 
Frequency and type of AEs temporally associated with an infusion.
 
Frequency and type of injection-site reactions.
Summaries, listings, datasets, or participant narratives may be provided through Week 24 and
Week 60 by treatment intervention, for the above AEs, deaths, and severe AEs. Selected safety
summaries will also be performed for participants of the LTE (Section 9.4.8).
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test over time, and by treatment
intervention. CTCAE toxicity grades (specified in the SAP) will be used in the summary of
laboratory data. Descriptive statistics will be calculated for each laboratory analyte at baseline and
for observed values and changes from baseline at each scheduled timepoint.
The following summaries of clinical laboratory tests will be used to assess participant safety:
 
Laboratory parameters and change from baseline in laboratory parameters (hematology and
chemistry).
 
Summary of maximum CTCAE toxicity grade for postbaseline laboratory values (hematology
and chemistry).
Listings of participants with any abnormal postbaseline laboratory values of CTCAE Grade ≥2
will also be provided.
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Vital Signs
Blood pressure (systolic and diastolic) will be summarized over time, using descriptive statistics
and/or graphically. The percentage of participants with values beyond clinically important limits
will be summarized.
9.4.7. 
Other Analyses
Pharmacokinetic Analyses
Data will be listed for all participants with available serum concentrations. Participants will be
excluded from the PK analysis if their data do not allow for accurate assessment of the PK (eg,
incomplete administration of the study intervention; missing information of dosing and sampling
times; concentration data not sufficient for PK parameter calculation).
All concentrations below the lowest quantifiable concentration or missing data will be labeled as
such in the concentration database. All participants and samples excluded from the analysis will
be clearly documented in the study report.
Serum guselkumab concentrations will be summarized over time for all participants who receive
at least 1 dose of guselkumab. Descriptive statistics will be calculated at each sampling timepoint.
Urine guselkumab concentrations 24-hrs prior to and after the first IV administration of
guselkumab will be summarized in a separate report.
If feasible, population PK analysis of serum concentration-time data of guselkumab  may be
performed using nonlinear mixed-effects modeling. Data may be combined with those of other
selected studies to support a relevant structural model. Available baseline participant
characteristics (demographics, laboratory variables, genotypes, race, etc.) will be tested as
potential covariates affecting PK parameters. Details will be given in a population PK analysis
plan and the results of the population PK analysis will be presented in a separate report.
Immunogenicity Analyses
The incidence of anti-guselkumab antibodies will be summarized for all participants who receive
at least 1 dose of guselkumab  and have appropriate samples for detection of antibodies to
guselkumab (ie, participants with at least 1 sample obtained after their first dose of guselkumab).
A listing of participants who are positive for antibodies to guselkumab  will be provided. The
maximum titers of antibodies to guselkumab will be summarized for participants who are positive
for antibodies to guselkumab.
The incidence of neutralizing antibodies (NAbs) to guselkumab  will be summarized for
participants who are positive for antibodies to guselkumab and have samples evaluable for NAbs
to guselkumab.
Other immunogenicity analyses may be performed to further characterize the immune responses
that are generated.
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Biomarkers Analyses
Planned biomarker analyses may be deferred if emerging study data show no likelihood of
providing useful scientific information. Any biomarker samples received by the contract vendor
or sponsor after the cutoff date will not be analyzed, and therefore, excluded from the biomarker
analysis.
Changes in serum protein analytes may be summarized for the induction period and summarized
by treatment group for the maintenance period. Associations between baseline levels and changes
from baseline in select markers and response to treatment may be explored. RNA analyses from
cells in blood or urine may be summarized in a separate technical report.
The biomarker analyses will characterize the effects of guselkumab to identify PD markers and
biomarkers relevant to treatment, and to determine if these markers can predict response to
guselkumab. Results of serum, whole blood analyses, and urine analyses may be reported in a
separate technical report.
Pharmacokinetic/Pharmacodynamic Analyses
The relationship between serum concentrations of guselkumab and the efficacy measures and/or
relevant PD endpoints may be explored graphically when appropriate. If any visual trend is
observed, additional analysis may be conducted if deemed necessary, and will be summarized in
a separate report if performed.
Pharmacogenomic Analyses
Genetic (DNA) analyses will be conducted only in participants who sign the consent form to
participate in the pharmacogenomic sampling. These analyses are considered exploratory and may
be summarized in a separate technical report.
DNA samples will be analyzed for identification of genetic factors that may be associated with
clinical response. This research may consist of the analysis of 1 or more candidate genes,
assessment of SNPs or genetic modifications, or analysis of the entire genome (as appropriate) in
relation to guselkumab intervention and/or LN. Whole blood samples of approximately 30 mL will
be collected for genetic analyses as specified in the SoA (Section 1.3).
9.4.8. 
Long-Term Extension
The LTE begins after the assessments have been completed at Week 52, and will continue until
end of study (see Section 4.1.3).
The objective of the LTE is to evaluate the efficacy and safety of long-term guselkumab treatment.
Assessments during the LTE described below will be summarized by treatment group as specified
in the SoA (Section 1.3)if data permits:
 
Selected efficacy assessments including proportion of participants maintaining CRR through
Week 152.
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 
Changes in PRO assessments including LupusQOL, FACIT-Fatigue, lupus symptoms, and
PGIC over time during the long-term extension.
 
Selected safety data including analyses of AEs, clinical laboratory tests, and vital signs.
 
Serum guselkumab concentrations and antibodies to study intervention.
 
Selected biomarkers.
Details of the analyses planned for the LTE will be described in the SAP.
9.5. 
Data Monitoring Committee or Other Review Board
An external, independent DMC (consisting of at least 2 physician and at least 1 statistician), will
be established to monitor safety data on an ongoing basis until all participants reach the Week 52
visit or terminate the study prior to the Week 52 visit.
The main focus of the DMC will be on reviewing interim unblinded safety data, but the DMC may
also review efficacy data needed to ensure the full benefit:risk profile for guselkumab.
The content of the safety summaries, the DMC’s role and responsibilities, the general procedures
(including communications), and their recommendations on the study conduct are defined and
documented in the DMC charter, which will be finalized prior to the first DMC review.
In addition, during the study, the sponsor's study responsible physician (or designee) will regularly
review blinded safety data from the sites and notify the DMC and appropriate sponsor personnel
of any issues.
The inclusion and exclusion criteria will be adjudicated prior to enrollment. The adjudicated
assessment by the sponsor or designee will be the final determinant for allowing enrollment.
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10. 
SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS
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10.1. Appendix 1: Abbreviations
6-MP  
6-mercaptopurine
ACTH  
adrenocorticotropic hormone
AE 
adverse event
ACE 
angiotensin-converting enzyme
ACR  
American College of Rheumatology
ALT  
alanine aminotransferase
ANA  
antinuclear antibody
APS  
antiphospholipid syndrome
ARB  
angiotensin II receptor blocker
AST  
aspartate aminotransferase
AUC  
area under the curve
AZA  
azathioprine
BCG  
Bacille-Calmette-guérin
BSA 
body surface area
C 
complement
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CLE 
cutaneous lupus erythematosus
ClinRO  
clinician-reported outcome
Cmax  
maximum observed concentration
COVID-19 
Coronavirus Disease 2019
CRR  
complete renal response
CT  
computed tomography
CTCAE 
Common Terminology Criteria for Adverse Events
CV  
cardiovascular
DBL 
database lock
DMC  
Data Monitoring Committee
DNA  
deoxyribonucleic acid
dsDNA  
double-stranded deoxyribonucleic acid
ECG  
electrocardiogram
eCRF  
electronic case report form
eDC  
electronic data capture
eGFR  
Estimated Glomerular Filtration Rate
eC-SSRS  
electronic Columbia-Suicide Severity Rating Scale
ELISA  
enzyme-linked immunosorbent assay
EU  
European Union
EULAR  
European League Against Rheumatism
FACIT  
Functional Assessment of Chronic Illness Therapy
FAS  
Full Analyses Set
FSH  
follicle stimulating hormone
GCP  
Good Clinical Practice
HBsAg 
hepatitis B surface antigen
HBV  
hepatitis B virus
HCV  
hepatitis C virus
HIV  
human immunodeficiency virus
HRQoL 
Health-Related Quality of Life
HRT  
hormonal replacement therapy
HS  
hidradenitis suppurativa
IA  
intra-articular
IAS  
Immunogenicity Analysis Set
IB  
Investigator's Brochure
ICF  
informed consent form
ICH  
International Conference on Harmonisation
IEC  
Independent Ethics Committee
IFN  
interferon
IL 
interleukin
IM  
intramuscular
IPPI 
Investigational Product Preparation and Administration Instructions
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IRB  
Institutional Review Board
ISN  
International Society of Nephrology
IV  
intravenous
IWRS  
interactive web response system
LB  
lower bound
LN  
lupus nephritis
LTE 
long-term extension
LupusQoL 
Lupus Quality of Life
mAb 
monoclonal antibody
MMF  
mycophenolate mofetil
MMRM  
mixed effect repeat measurement
MPA  
mycophenolic acid
MTX  
methotrexate
NAbs 
neutralizing antibodies
NOAEL 
no observed adverse effect level
NSAID  
nonsteroidal anti-inflammatory drug
PBMC  
peripheral blood mononuclear cell
PD 
pharmacodynamic(s)
PDAS  
PD Analysis Set
PFS  
prefilled syringe
PFS-U 
PFS in an UltraSafe Plus™ Passive Needle Guard
PFS-Y 
PFS with YpsoMate autoinjector
PGA  
Physician's Global Assessment
PGIC  
Patient Global Impression of Change
PK 
pharmacokinetic(s)
PKAS  
PK analysis set
PO 
orally
PRO  
patient-reported outcome(s) (paper or electronic as appropriate for this study)
PsA  
psoriatic arthritis
q4w  
every 4 weeks
q8w  
every 8 weeks
RA  
rheumatoid arthritis
RNA  
ribonucleic acid
RPS  
Renal Pathology Society
SAE 
serious adverse event
SAP  
statistical analysis plan
SAS  
Safety Analysis Set
SC 
subcutaneous
SD 
standard deviation
SLE 
systemic lupus erythematosus
SLEDAI-2K 
systemic lupus erythematosus disease activity index 2000
SNP  
single nucleic polymorphisms
SoA  
Schedule of Activities
SUSAR  
suspected unexpected serious adverse reaction
T1/2 
half-life
TB  
tuberculosis
TF 
Treatment Failure
TH 
T-helper
Tmax  
time to maximal concentration
TNF  
tumor necrosis factor
UC  
ulcerative colitis
ULN  
upper limit of normal
UPCR  
Urine Protein to Creatinine Ratio
US  
United States
WBC  
white blood cells
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10.2. Appendix 2: 2019 EULAR/ACR Classification Criteria
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10.3. Appendix 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. Participants should never be allowed to read their own tuberculin skin
test results. If a participant fails to show up for the scheduled reading, a positive reaction may still be measurable up
to 1 week after testing. However, if a participant 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 participants may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin skin test is considered
to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be
consulted for the interpretation of tuberculin skin test results. If no local country guidelines for immunocompromised
patients exist, US guidelines must be followed.
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous
treatment regimens for latent TB. If no local country guidelines for immunocompromised patients exist, US guidelines
must be followed.
References
Centers for Disease Control and Prevention. Core curriculum on tuberculosis: What the clinician should know
(Fourth Edition).  Atlanta, GA: Department of Health and Human Services; Centers for Disease Control and
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86.
Menzies RI. Tuberculin skin testing. In: Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive
international approach. 2nd ed. New York, NY: Marcel Dekker, Inc; 2000:279-322.
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10.5. Appendix 5: Contraceptive and Barrier Guidance and Collection of
Pregnancy Information
Participants must follow contraceptive measures as outlined in Section 5.1, Inclusion Criteria.
Pregnancy information will be collected and reported as noted in Section 8.3.5, Pregnancy and
Appendix 10 [Section 10.10] Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting.
Definitions
Woman of Childbearing Potential (WOCBP)
A woman is considered fertile following menarche and until becoming postmenopausal unless
permanently sterile (see below).
Woman Not of Childbearing Potential
 
premenarchal
A premenarchal state is one in which menarche has not yet occurred.
 
postmenopausal
A postmenopausal state is defined as no menses for 12 months without an alternative medical
cause. A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the
postmenopausal range may be used to confirm a postmenopausal state in women not using
hormonal contraception or hormonal replacement therapy (HRT), however in the absence of
12 months 
of 
amenorrhea, 
a 
single 
FSH 
measurement 
is 
insufficient.
If there is a question about menopausal status in women on HRT, the woman will be required
to use one of the non-estrogen-containing hormonal highly effective contraceptive methods if
she wishes to continue HRT during the study.
 
permanently sterile
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal
occlusion/ligation procedures, and bilateral oophorectomy.
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually
active becomes active), a woman must begin a highly effective method of contraception, as
described throughout the inclusion criteria.
If reproductive status is questionable, additional evaluation should be considered.
Contraceptive (birth control) use by men or women should be consistent with local regulations
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should
be consistent with local regulations regarding the use of contraceptive methods for participants in
clinical studies.
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Examples of Contraceptives
EXAMPLES OF CONTRACEPTIVESa ALLOWED DURING THE STUDY INCLUDE:
USER INDEPENDENT
Highly Effective Methods That Are User Independent Failure rate of <1% per year when used consistently
and correctly.
 Implantable progestogen-only hormone contraception associated with inhibition of ovulationb
 Intrauterine device (IUD)
 Intrauterine hormone-releasing system (IUS)
 Bilateral tubal occlusion
 Vasectomized partner
(Vasectomized partner is a highly effective contraceptive method provided that the partner is the sole sexual
partner of the woman of childbearing potential and the absence of sperm has been confirmed. If not,
additional highly effective method of contraception should be used. Spermatogenesis cycle is approximately
74 days.)
USER DEPENDENT
Highly Effective Methods That Are User Dependent Failure rate of <1% per year when used consistently
and correctly.
 Combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of
ovulationb
 oral
 intravaginal
 transdermal
 injectable
 Progestogen-only hormone contraception associated with inhibition of ovulationb
 oral
 injectable
 Sexual abstinence
(Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual
intercourse during the entire period of risk associated with the study intervention. The reliability of sexual
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle
of the participant.)
NOT ALLOWED AS SOLE METHOD OF CONTRACEPTION DURING THE STUDY (not considered
to be highly effective - failure rate of ≥1% per year)
 Progestogen-only oral hormonal contraception where inhibition of ovulation is not the primary mode of
action.
 Male or female condom with or without spermicidec
 Cap, diaphragm, or sponge with spermicide
 A combination of male condom with either cap, diaphragm, or sponge with spermicide (double-barrier
methods)c
 Periodic abstinence (calendar, symptothermal, post-ovulation methods)
 Withdrawal (coitus-interruptus)
 Spermicides alone
 Lactational amenorrhea method (LAM)
a) Typical use failure rates may differ from those when used consistently and correctly. Use should be
consistent with local regulations regarding the use of contraceptive methods for participants in clinical
studies.
b) Hormonal contraception may be susceptible to interaction with the study intervention or concomitant
medications (eg, mycophenolate mofetil [MMF]/mycophenolic acid [MPA] in combination with oral
hormonal contraceptives), which may reduce the efficacy of the contraceptive method. In female participants
who are of childbearing potential and are receiving MMF/MPA, a barrier contraceptive method should be
used concurrently with oral hormonal contraception methods (Section 5.1, Inclusion Criterion #17).
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c) Male condom and female condom should not be used together (due to risk of failure with friction).
Pregnancy During the Study
All initial reports of pregnancy in female participants or partners of male participants must be
reported to the sponsor or designee by the study-site personnel within 24 hours of their knowledge
of the event using the appropriate pregnancy notification form. Abnormal pregnancy outcomes
(eg, spontaneous abortion, fetal death, stillbirth, congenital anomalies, ectopic pregnancy) are
considered serious adverse events (SAEs) and must be reported using the Serious Adverse Event
Form. Any participant who becomes pregnant during the study must discontinue further study
intervention.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the
infant will be required.
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10.6. Appendix 6: CLASI
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10.7. Appendix 7: Glucocorticoid Taper
As described in Section 6.5.2, participants are to have their glucocorticoid dose tapered starting
from Week 2 down to 5 mg by Week 12. A table showing tapering by the starting prednisone dose
is shown below in Table 1.
Table 1: Glucocorticoid Taper Schedule
Week  
Taper by Starting Prednisone Equivalent Dose (mg)
2 
60 
50 
40 
30 
20 
15 
10
3 
40 
30 
30 
30 
20 
15 
10
4 
20 
20 
20 
20 
20 
15 
10
5 
20 
20 
20 
20 
20 
15 
10
6 
15 
15 
15 
15 
15 
15 
10
7 
15 
15 
15 
15 
15 
15 
10
8 
10 
10 
10 
10 
10 
10 
10
9 
10 
10 
10 
10 
10 
10 
10
10 
10 
10 
10 
10 
10 
10 
10
11 
10 
10 
10 
10 
10 
10 
10
12 
5 
5 
5 
5 
5 
5 
5
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In the microscopic examination, observations other than the presence of WBC, RBC
and casts may also be reported by the laboratory.
Specific gravity, pH, glucose, protein, blood, ketones, bilirubin, and urobilinogen will
be determined using a dipstick. Red blood cells, WBCs, epithelial cells, crystals, casts,
and bacteria will be measured using or microscopy.
Crystals, casts and bacteria will only be reported if they are present.
Other Tests 
 
Urine Pregnancy Testing for women of childbearing potential only (performed
locally)
 
Serology (HIV antibody, hepatitis B surface antigen [HBsAg], and Hepatitis B,
surface antibody [anti-HBs], Hepatitis B core antibody [anti-HBc], hepatitis C
virus antibody, and HCV RNA [if applicable], screening only)
 
PT, PTT, INR
 
Anti-dsDNA
 
Complement - C3, C4
 
Antiphospholipid antibodies (anti-cardiolipin immunoglobulin [Ig]G and IgM,
anti-β2 glycoprotein IgG and IgM, and lupus anticoagulant)
 
B-Cell flow cytometry (for those as specified in SoA), screening only
 
Anti-Smith, 
anti-Sjögren's-syndrome-related 
antigen 
A, 
anti-Sjögren’s-
syndrome-related antigen B, anti-ribonucleoprotein
 
Anti-cyclic citrullinated peptide, Rheumatoid Factor, screening only
 
Immunoglobulin isotype profile
 
Antibodies to study intervention –done by sponsor laboratory
 
24-hour urine analyses –total volume, creatinine, protein
 
Hep B DNA
 
Cystatin C
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10.9. Appendix 9: Regulatory, Ethical, and Study Oversight Considerations
10.9.1. 
Regulatory and Ethical Considerations
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 participants.
Compliance with this standard provides public assurance that the rights, safety, and well-being of
study participants are protected, consistent with the principles that originated in the Declaration of
Helsinki, and that the study data are credible.
Protocol Clarification Communications
If text within a final approved protocol requires clarification (eg, current wording is unclear or
ambiguous) that does not change any aspect of the current study conduct, a protocol clarification
communication (PCC) may be prepared. The PCC Document will be communicated to the
Investigational Site, Site Monitors, Local Trial Managers (LTMs), Clinical Trial Managers
(CTMs), and/or Contract Research Organizations (CROs) who will ensure that the PCC
explanations are followed by the investigators.
The PCC Document may be shared by the sites with Independent Ethics Committees/Institutional
Review Boards (IECs/IRBs) per local regulations.
The PCC Documents must NOT be used in place of protocol amendments, but the content of the
PCC Document must be included in any future protocol amendments.
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 participants, 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) involve only logistic or administrative aspects of the study, the IEC/IRB (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
listed in the Contact Information page(s), which will be provided as a separate document. 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
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situation and agree on an appropriate course of action. The data recorded in the eCRF and source
documents will reflect any departure from the protocol, and the source documents will describe
this departure and the circumstances requiring it.
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.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study intervention
to the study site:
 
Protocol and amendment(s), if any, signed and dated by the principal investigator
 
A copy of the dated and signed (or sealed, where appropriate per local regulations), written
IEC/IRB approval of the protocol, amendments, ICF, any recruiting materials, and if
applicable, participant 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 FDA 1572), if applicable
 
Documentation of investigator qualifications (eg, curriculum vitae)
 
Completed investigator financial disclosure form from the principal investigator, where
required
 
Signed and dated Clinical Trial Agreement, which includes the financial agreement
 
Any other documentation required by local regulations
The following documents must be provided to the sponsor before enrollment of the first
participant:
 
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
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 
Local laboratory documentation demonstrating competence and test reliability
(eg, accreditation/license), if applicable
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 participants)
 
IB (or equivalent information) and amendments/addenda
 
Sponsor-approved participant recruiting materials
 
Information on compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
 
Information regarding funding, name of the sponsor, institutional affiliations, other potential
conflicts of interest, and incentives for participants
 
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
participants, data or study conduct, unless required locally), the ICF, applicable recruiting
materials, and participant 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 samples for research and for the corresponding ICF must
be obtained from the IEC/IRB. Approval for the protocol can be obtained independent of this
optional research component.
During the study the investigator (or sponsor where required) will send the following documents
and updates to the IEC/IRB for their review and approval, where appropriate:
 
Protocol amendments (excluding the ones that are purely administrative, with no
consequences for participants, data or study conduct)
 
Revision(s) to ICF and any other written materials to be provided to participants
 
If applicable, new or revised participant recruiting materials approved by the sponsor
 
Revisions to compensation for study-related injuries or payment to participants for
participation in the study, if applicable
 
New edition(s) of the IB and amendments/addenda
 
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at
least annually)
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 
Reports of adverse events (AEs) that are serious, unlisted/unexpected, and associated with the
study intervention
 
New information that may adversely affect the safety of the participants or the conduct of the
study
 
Deviations from or changes to the protocol to eliminate immediate hazards to the participants
 
Report of deaths of participants 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 participants, data or study conduct), the amendment and applicable ICF revisions
must be submitted promptly to the IEC/IRB for review and approval before implementation of the
change(s).
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required.
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about
the study completion (if applicable, the notification will be submitted through the head of
investigational institution).
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 if the need for the product persists, unless explicitly
addressed as a specific ethical consideration in Section  4.2.3, Study-Specific Ethical Design
Considerations.
Other Ethical Considerations
For study-specific ethical design considerations, refer to Section 4.2.3.
10.9.2. 
Financial Disclosure
Investigators and subinvestigators will provide the sponsor with sufficient, accurate financial
information in accordance with local regulations to allow the sponsor to submit complete and
accurate financial certification or disclosure statements to the appropriate regulatory authorities.
Investigators are responsible for providing information on financial interests during the course of
the study and for 1 year after completion of the study.
Refer to Required Prestudy Documentation (above) for details on financial disclosure.
10.9.3. 
Informed Consent Process
Each participant 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
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IEC/IRB and be in a language that the participant 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 participants the aims, methods, reasonably anticipated benefits,
and potential hazards of the study, and any discomfort participation in the study may entail.
Participants 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 participant will receive. Finally, they will be told that the investigator will
maintain a participant 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 participant, to the extent permitted by the applicable law(s) or
regulations. By signing the ICF the participant is authorizing such access, which includes
permission to obtain information about his or her survival status. It also denotes that the participant
agrees to allow his or her study physician to recontact the participant for the purpose of obtaining
consent for additional safety evaluations, and subsequent disease-related treatments, if needed.
The physician may also recontact the participant for the purpose of obtaining consent to collect
information about his or her survival status.
The participant 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 participant's personally dated signature. After having obtained the consent, a copy of
the ICF must be given to the participant.
Participants who are rescreened are required to sign a new ICF.
Participants 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 participant
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 participant.
Where local regulations require, a separate ICF may be used for the required DNA component of
the study.
10.9.4. 
Data Protection
Privacy of Personal Data
The collection and processing of personal data from participants 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.
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Sponsor personnel whose responsibilities require access to personal data agree to keep the identity
of participants confidential.
The informed consent obtained from the participant 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 participant 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, PD, biomarker, PK, and immunogenicity research is not conducted under
standards appropriate for the return of data to participants. 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 participants 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.
10.9.5. 
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local regulations)
for additional research. Samples will only be used to understand guselkumab, to understand LN,
to understand differential intervention  responders, and to develop tests/assays related to
guselkumab and LN. 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. Participants may withdraw their consent for their samples to be
stored for research (refer to Section 7.2.1, Withdrawal From the Use of Research Samples).
10.9.6. 
Committees Structure
Data Monitoring Committee
Detail regarding the adjudication and DMC are presented in Section 9.5.
10.9.7. 
Publication Policy/Dissemination of Clinical Study Data
All information, including but not limited to information regarding guselkumab 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 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
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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 ofguselkumab, 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 data from all study sites that participated in the study as per protocol. 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 for the study. Results of 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 participant 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 (ICMJE) 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 18 months after the study end date, 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 ICMJE Recommendations
for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals, which
state that the named authors must have made a significant contribution to the conception or design
of the work; or the acquisition, analysis, or interpretation of the data for the work; and drafted the
work or revised it critically for important intellectual content; and given final approval of the
version to be published; and agreed to be accountable for all aspects of the work in ensuring that
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questions related to the accuracy or integrity of any part of the work are appropriately investigated
and resolved.
Registration of Clinical Studies and Disclosure of Results
The sponsor will register and disclose the existence of and the results of clinical studies as required
by law. The disclosure of the final study results will be performed after the end of study in order
to ensure the statistical analyses are relevant.
10.9.8. 
Data Quality Assurance
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 eCRF completion will be provided and reviewed with study-site personnel before
the start of the study. The sponsor will review eCRF 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.
10.9.9. 
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each participant in electronic
format. All data relating to the study must be recorded in eCRF. All eCRF entries, corrections, and
alterations must be made by the investigator or authorized study-site personnel. The investigator
must verify that all data entries in the eCRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an
eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any
such worksheets will become part of the participant's source documents. Data must be entered into
eCRF in English. The eCRF must be completed as soon as possible after a participant visit and the
forms should be available for review at the next scheduled monitoring visit.
All participative measurements (eg, pain scale information or other questionnaires) will be
completed by the same individual who made the initial baseline determinations whenever possible.
If necessary, queries will be generated in the electronic data capture (eDC) tool. If corrections to
a eCRF are needed after the initial entry into the eCRF, this can be done in either of the following
ways:
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 Investigator and 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).
 Sponsor or sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.
10.9.10. 
Source Documents
At a minimum, source documents consistent in the type and level of detail with that commonly
recorded at the study site as a basis for standard medical care must be available for the following:
participant identification, eligibility, and study identification; participant diary card, study
discussion and date of signed informed consent; dates of visits; results of safety and efficacy
parameters as required by the protocol; record of all AEs and follow-up of AEs; concomitant
medication; intervention receipt/dispensing/return records; study intervention  administration
information; and date of study completion and reason for early discontinuation of study
intervention or withdrawal from the study, if applicable.
The author of an entry in the source documents should be identifiable. Given that PROs are reports
of a patient's health condition that come directly from the patient, without interpretation by a
clinician or anyone else, the responses to PRO measures entered by trial participants into source
records cannot be overridden by site staff or investigators.
Specific details required as source data for the study and source data collection methods 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 eCRF and will be considered source date:
 Race
 History of all nicotine use, eg, cigarettes (including e-cigarettes or the equivalent of e-
cigarettes), cigars, chewing tobacco, patch, gum
 Blood pressure and pulse/heart rate
 Height and weight
 Details of physical examination
The following data will be added into the electronic device and will be considered source data:
 
PRO
 
Physician global assessment of disease activity
The minimum source documentation requirements for Section 5.1, Inclusion Criteria and
Section 5.1.1, 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
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 Discharge summaries
Inclusion and exclusion criteria not requiring documented medical history must be verified at a
minimum by participant interview or other protocol required assessment (eg, physical
examination, laboratory assessment) and documented in the source documents.
An eSource system may be utilized, which contains data traditionally maintained in a hospital or
clinic record to document medical care (eg, electronic source documents) as well as the clinical
study-specific data fields as determined by the protocol. This data is electronically extracted for
use by the sponsor. If eSource is utilized, references made to the eCRF in the protocol include the
eSource system but information collected through eSource may not be limited to that found in the
eCRF.
10.9.11. 
Monitoring
The sponsor will use a combination of monitoring techniques central, remote, 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, as allowed by
local regulation. 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 eCRF with the source
documents (eg, hospital/clinic/physician’s office medical records). The nature and location of all
source documents will be identified to ensure that all sources of original data required to complete
the eCRF 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 documents (medical records) must be allowed for the purpose of verifying
that the recorded data are consistent with the original source data. Findings from this review 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 documents 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.
Central monitoring will take place for data identified by the sponsor as requiring central review.
10.9.12. 
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. Participant privacy must, however, be
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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.
10.9.13. 
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each participant, as well as all study
documents as specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical
Trial, and all study documents as specified by the applicable regulatory requirement(s). The
investigator/institution will take measures to prevent accidental or premature destruction of these
documents.
Essential documents must be retained until at least 2 years after the last approval of a marketing
application in an ICH region and until there are no pending or contemplated marketing applications
in an ICH region or until at least 2 years have elapsed since the formal discontinuation of clinical
development of the investigational product. These documents will be retained for a longer period
if required by the applicable regulatory requirements or by an agreement with the sponsor. It is the
responsibility of the sponsor to inform the investigator/institution as to when these documents no
longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the
responsibility of keeping the study records, custody must be transferred to a person who will accept
the responsibility. The sponsor must be notified in writing of the name and address of the new
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents
before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any
documentation relating to this study, the investigator/institution must permit access to such reports.
10.9.14. 
Study and Site Start and Closure
First Act of Recruitment
The first site open is considered the first act of recruitment and it becomes the study start date.
Study/Site 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.
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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 participants by the investigator
 Discontinuation of further study intervention development
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10.10. Appendix 10: Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for
Recording, Evaluating, Follow-up, and Reporting
10.10.1. 
Adverse Event Definitions and Classifications
Adverse Event
An adverse event (AE) is any untoward medical occurrence in a clinical study participant
administered a pharmaceutical (investigational or non-investigational) product. An AE does not
necessarily have a causal relationship with the intervention. An AE can therefore be any
unfavorable and unintended sign (including an abnormal finding), symptom, or disease temporally
associated with the use of a medicinal (investigational or non-investigational) product, whether or
not related to that medicinal (investigational or non-investigational) product. (Definition per
International Conference on Harmonisation [ICH])
This includes any occurrence that is new in onset or aggravated in severity or frequency from the
baseline condition, or abnormal results of diagnostic procedures, including laboratory test
abnormalities.
Note: The sponsor collects adverse events (AEs) starting with the signing of the ICF (refer to All
Adverse Events under Section 8.3.1, Time Period and Frequency for Collecting Adverse Events
and Serious Adverse Events Information, for time of last adverse event recording).
For combination products with a device constituent, AEs include those resulting from insufficient
or inadequate instructions for use, deployment, implantation, installation, or operation, or any
malfunction of the device. It includes any adverse event resulting from use error or from intentional
misuse of the investigational device.
Serious Adverse Event
A serious adverse event (SAE) based on ICH and EU Guidelines on Pharmacovigilance for
Medicinal Products for Human Use is any untoward medical occurrence that at any dose:
 
Results in death
 
Is life-threatening
(The participant was at risk of death at the time of the event. It does not refer to an event that
hypothetically might have caused death if it were more severe.)
 
Requires inpatient hospitalization or prolongation of existing hospitalization
 
Results in persistent or significant disability/incapacity
 
Is a congenital anomaly/birth defect
 
Is a suspected transmission of any infectious agent via a medicinal product
 
Is Medically Important*
*Medical and scientific judgment should be exercised in deciding whether expedited reporting is
also appropriate in other situations, such as important medical events that may not be immediately
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life-threatening or result in death or hospitalization but may jeopardize the participant or may
require intervention to prevent one of the other outcomes listed in the definition above. These
should usually be considered serious.
The cause of death of a participant in a study within 12 weeks of the last dose of study intervention,
whether or not the event is expected or associated with the study intervention, is considered an
SAE.
For combination products with a device constituent, SAEs include adverse device effects that
resulted in any of the consequences characteristic of an SAE. An unanticipated serious adverse
device effect is a serious adverse device effect which by its nature, incidence, severity, or outcome
has not been identified in the current version of the risk analysis report (see Section 2.3. Benefit-
Risk Assessment).
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 guselkumab, the expectedness of an adverse event will
be determined by whether or not it is listed in the IB. For mycophenolate mofetil (MMF),
mycopehnoloic acid (MPA), glucocorticoids, ACE inhibitors or ARBs with a marketing
authorization, the expectedness of an adverse event will be determined by whether or not it is listed
in the EU SmPC.
10.10.2. 
Attribution Definitions
Assessment of Causality
The causal relationship to study intervention is determined by the investigator. The following
selection should be used to assess all AE.
Related
There is a reasonable causal relationship between study intervention administration and the AE.
Not Related
There is not a reasonable causal relationship between study intervention administration and the
AE.
The term "reasonable causal relationship" means there is evidence to support a causal relationship.
10.10.3. 
Severity Criteria
An assessment of severity grade will be made using the following general categorical descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
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Severe: Extreme distress, causing significant impairment of functioning or incapacitation.
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly
experienced by the participant (eg, laboratory abnormalities).
10.10.4. 
Special Reporting Situations
Safety events of interest on a sponsor study intervention in an interventional studythat may require
expedited reporting or safety evaluation include, but are not limited to:
 
Overdose of a sponsor study intervention
 
Suspected abuse/misuse of a sponsor study intervention
 
Accidental or occupational exposure to a sponsor study intervention
 
Medication error, intercepted medication error, or potential medication error involving a
sponsor medicinal product (with or without patient exposure to the sponsor’s medicinal
product, eg, product name confusion, product label confusion, intercepted prescribing or
dispensing errors)
 
Exposure to a sponsor study intervention from breastfeeding
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of a serious adverse event should be recorded on the serious adverse event page
of the eCRF.
10.10.5. 
Procedures
All Adverse Events
All AEs, regardless of seriousness, severity, or presumed relationship to study intervention, must
be recorded using medical terminology in the source document and the eCRF. 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 eCRF their opinion concerning the relationship of the
adverse event to study therapy. All measures required for AE management must be recorded in the
source document and reported according to sponsor instructions.
For all studies with an outpatient phase, including open-label studies, the participant 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 participant 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 personnel only)
 
Site number
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 
Participant number
 
Any other information that is required to do an emergency breaking of the blind
Serious Adverse Events
All SAEs that have not resolved by the end of the study, or that have not resolved upon the
participant's discontinuation from 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 intervention or to factors unrelated
to study conduct
 
It becomes unlikely that any additional information can be obtained (participant or health care
practitioner refusal to provide additional information, lost to follow-up after demonstration of
due diligence with follow-up efforts)
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during
participation in the study must be reported as an SAE, except hospitalizations for the following:
 
Hospitalization related to biopsy procedures
 
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 eCRF).
Note: Hospitalizations that were planned before the signing of the ICF, and where the
underlying condition for which the hospitalization was planned has not worsened, will not be
considered SAEs. Any adverse event that results in a prolongation of the originally planned
hospitalization is to be reported as a new serious adverse event
 
For convenience the investigator may choose to hospitalize the participant for the duration of
the intervention period
Disease progression should not be recorded as an AE or SAE term; instead, signs and symptoms
of clinical sequelae resulting from disease progression/lack of efficacy will be reported if they
fulfill the serious adverse event definition (refer to Adverse Event Definitions and Classifications
in Appendix 10 [Section 10.10], Adverse Events, Serious Adverse Events, Product Quality
Complaints, and Other Safety Reporting: Definitions and Procedures for Recording, Evaluating,
Follow-up, and Reporting). Flares of lupus activity, including LN (see Section 4.1.1), that meet
the definition of an SAE will be reported to the sponsor but will not be reported to the Heath
Authorities during the trial so that blinding may be retained in order to ensure study integrity.
Expected progression of disease should not be considered an adverse event (or serious adverse
event). However, if determined by the investigator to be more likely related to the study
intervention than the underlying disease, the clinical signs or symptoms of progression and the
possibility that the study intervention is enhancing disease progression, should be reported per the
usual reporting requirements.
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Information regarding SAEs will be transmitted to the sponsor using anSAE reporting form, which
must be completed and signed by a physician from the study site, and transmitted in a secure
manner to the sponsor within 24 hours. The initial and follow-up reports of an SAE should be
made by facsimile (fax). Telephone reporting should be the exception and the reporter should be
asked to complete the appropriate form(s) first.
10.10.6. 
Product Quality Complaint Handling
Definition
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, reliability, or performance of a distributed product, including its labeling, drug delivery
system, or package integrity. A PQC may have an impact on the safety and efficacy of the product.
In addition, it includes any technical complaints, defined as any complaint that indicates a potential
quality issue during manufacturing, packaging, release testing, stability monitoring, dose
preparation, storage, or distribution of the product or the drug delivery system.
This definition includes any PQC related to a device constituent in a combination product,
including those used in the administration of the study intervention or the comparator. A device
deficiency is an inadequacy of a device with respect to its identity, quality, durability, reliability,
safety, or performance. Device deficiencies include malfunctions, use errors, and inadequate
labeling.
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.
A sample of the suspected product should be maintained under the correct storage conditions until
a shipment request is received from the sponsor.
10.10.7. 
Contacting Sponsor Regarding Safety, Including Product Quality
The names (and corresponding telephone numbers) of the individuals who should be contacted
regarding safetyissues, PQC, or questions regarding the studyare listedin the Contact Information
page(s), which will be provided as a separate document.
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10.11. Appendix 11: Liver Safety: Suggested Actions and Follow-up
Assessments
10.11.1. 
Stopping Algorithm
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are
met.
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10.11.2. 
Follow-up Assessments
10.11.2.1. 
Phase 2 Liver Chemistry Stopping Criteria and Follow-up
Assessments
Phase 2 liver chemistry stopping criteria are designed to assure participant safety and to evaluate
liver event etiology.
Liver Chemistry Stopping Criteria
ALT/AST-- 
absolute
ALT or AST- 5xULN
ALT/AST- 
Increase 
If cannot monitor:
ALT or AST- 3 xULN and cannot be monitored weekly for 4 weeks
Or if able to monitor:
ALT or AST- 3xULN persists for 4 weeks
Total 
bilirubin1, 2 
ALT or AST- 3xULN and total bilirubin 2xULN (or at least a doubling
of direct bilirubin in known Gilbert’s syndrome)
INR2 
ALT or AST- 3xULN and international normalized ratio (INR) >1.5, if
INR measured
Symptomatic3 
ALT or AST- 3xULN associated with symptoms (new or worsening)
believed to be related to liver injury or hypersensitivity
Suggested Actions, Monitoring and Follow-up Assessments
Actions 
Follow-up Assessments
 Immediately stop study intervention
 Report the event to the sponsor within
24 hours
 Complete an SAE form
 Perform follow-up assessments as described in
the Follow Up Assessment column
 Monitor the participant until liver chemistry
test abnormalities resolve, stabilize, or return
to baseline (see MONITORING)
MONITORING:
If ALP <2xULN, ALT or AST- 3xULN AND
total bilirubin 2xULN (or at least a doubling
of direct bilirubin in known Gilbert’s
syndrome) or INR >1.5 (if measured):
 Repeat liver chemistry tests (include ALT,
aspartate transaminase [AST], alkaline
phosphatase, total and direct bilirubin and
INR) and perform liver event follow-up
assessments within 24 hours
 Monitor participant twice weekly until liver
chemistry test abnormalities resolve, stabilize,
or return to baseline
 Viral hepatitis serology4
 Obtain INR and recheck with each
liver chemistry assessment until the
transaminases values show downward
trend
 Obtain blood sample for
pharmacokinetic (PK) analysis after
the most recent dose5
 Obtain serum creatine phosphokinase
(CPK), lactate dehydrogenase (LDH),
gamma-glutamyltransferase [GGT],
glutamate dehydrogenase [GLDH],
and serum albumin
 Fractionate bilirubin
 Obtain complete blood count with
differential to assess eosinophilia
 Record the appearance or worsening of
clinical symptoms of liver injury, or
hypersensitivity, on the CRF as per
CRF completion guidelines
 Record use of concomitant
medications (including
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 A specialist or hepatology consultation is 
recommended 
If ALT or AST- 3xULN AND total bilirubin 
<2xULN and INR 1.5: 
 Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, total and direct 
bilirubin and INR) and perform liver chemistry 
follow-up assessments within 24 to 72 hours 
 Monitor participant weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to baseline 
RESTART/RECHALLENGE  
 If liver event causality is determined to be 
“not related”, restart may be permitted 
upon written approval of the sponsor. See 
restart guidelines 
acetaminophen, herbal remedies,
recreational drugs and other over-the-
counter medications)
 Record alcohol use on the CRF as per
CRF completion guidelines
If ALT or AST- 3xULN AND total
bilirubin 2xULN or INR >1.5 (if
measured) obtain the following in
addition to the assessments listed above:
 Anti-nuclear antibody, anti-smooth
muscle antibody, Type 1 anti-liver
kidney microsomal antibodies, and
quantitative total immunoglobulin G
(IgG) or gamma globulins
 Serum acetaminophen adduct assay,
when available, to assess potential
acetaminophen contribution to liver
injury in participants with definite or
likely acetaminophen use in the
preceding week
 Liver imaging (ultrasound, magnetic
resonance, or computerized
tomography) and/or liver biopsy to
evaluate liver disease; complete  CRF
as per CRF completion guidelines
 Liver biopsy may be considered and
discussed with local specialist if
available:
 In participants when serology raises
the possibility of autoimmune
hepatitis (AIH)
 In participants when suspected
DILI progresses or fails to resolve
on withdrawal of study intervention
 In participants with acute or chronic
atypical presentation
 If liver biopsy conducted complete
CRF as per CRF completion
guidelines
1.Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not
immediately available, discontinue study intervention if ALT or AST 3xULN and total bilirubin 2xULN.
Additionally, if serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable
urinary bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury.
2.All events of ALT or AST- 3 xULN and total bilirubin 2xULN (or at least a doubling of direct bilirubin in
known Gilbert’s syndrome), ALT or AST- 3 xULN and INR >1.5 (if measured) may indicate severe liver
injury (possible ‘Hy’s Law’) and must be reported to sponsor in an expedited manner as an SAE. The INR
stated threshold value will not apply to participants receiving anticoagulants.
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3.New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).
4.Includes: hepatitis A immunoglobulin M (IgM) antibody; HBsAg and HBcAB; hepatitis C RNA; cytomegalovirus
IgM antibody; Epstein-Barr viral capsid antigen IgM antibody (or if unavailable, heterophile antibody or
monospot testing); and hepatitis E IgM antibody.
5.PK sample may not be required for participants known to be receiving placebo or non-comparator interventions.
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior
to the blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s best
approximation. If the date/time of the last dose cannot be approximated, do not obtain a PK sample. Instructions
for sample handling and shipping are in the laboratory manual.
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10.12. Appendix 12: Guidance on Study Conduct during the COVID -19 Pandemic
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on
the conduct of this clinical study due to, for example, self-isolation/quarantine by participants and
study-site personnel; travel restrictions/limited access to public places, including hospitals; study
site personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for
study-related participant management in the event of disruption to the conduct of the study. This
guidance does not supersede any local or government requirements or the clinical judgement of
the investigator to protect the health and well-being of participants and site staff. If at any time a
participant’s safety is considered to be at unacceptable risk, study intervention will be
discontinued, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in-person at the study site will be performed to the extent
possible remotely/virtually or delayed until such time that on-site visits can be resumed. At each
contact, participants will be interviewed to collect safety data. Key efficacy endpoint assessments
should be performed if required and as feasible. Participants will also be questioned regarding
general health status to fulfill any physical examination requirement.
Every effort should be made to adhere to protocol-specified assessments for participants on study
intervention, including follow up. Modifications to protocol-required assessments may be
permitted via COVID-19 Appendix after consultation between the participant and investigator,
and with the agreement of the sponsor (see below).
The sponsor will continue to monitor the conduct and progress of the clinical study, and any
changes will be communicated to the sites and to the health authorities according to local guidance.
If a participant has tested positive for COVID-19, the investigator should contact the sponsor’s
responsible medical officer to discuss plans for study intervention and follow-up. Modifications
made to the study conduct as a result of the COVID-19 pandemic should be summarized in the
clinical study report.
ADDITIONAL ELEMENTS, WHERE APPLICABLE:
 
Certain protocol-mandated visits to the study site may not be possible during the COVID-19
outbreak. Therefore, temporary measures may be implemented if considered appropriate by
the sponsor and investigator to maintain continuity of participant care and study integrity.
Certain measures, such as those listed below, may be necessary and should be instituted in
accordance with applicable (including local) laws, regulations, guidelines, and procedures:
o remote (eg, by phone/telemedicine) or in-person, off-site (eg, in-home) interactions
between site staff (or designees) and participants for study procedures eg, those related
to safety monitoring/efficacy evaluation/study intervention storage and administration
(including training where pertinent)
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o procurement of study intervention by participants (or designee) or shipment of study
intervention from the study site directly to participants for at home administration
(including the potential for self-administration of study intervention)
o laboratory assessments using a suitably accredited local laboratory; for selected
measures (eg, urine pregnancy), home testing may be employed
o other procedures, eg, imaging, may be conducted at an appropriate facility
 
Missed assessments/visits will be captured in the clinical trial management system for
protocol deviations. Discontinuations of study interventions and withdrawal from the study
should be documented with the prefix “COVID-19-related” in the case report form (CRF).
o other relevant study data elements impacted by the pandemic should also be
documented/labeled as “COVID-19-related” in CRFs and/or other study systems, as
directed by detailed sponsor guidance. These may include missed/delayed/modified
study visits/assessments/dosing, and instances where temporary measures such as those
above are implemented.
 
The sponsor will evaluate the totality of impact of COVID-19 on collection of key study data
and additional data analyses will be outlined in study SAP(s).
 
Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those aged
over 65 years), follow guidance from local health authorities when weighing the potential
benefits and risks of enrolling in the study, and during participation in the study.
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10.13. Appendix 13: Protocol Amendment History
The Protocol Amendment Summary of Changes Table for the current amendment is located
directly before the Table of Contents (TOC).
Amendment 3 [29 March 2022]
Overall Rationale for the Amendment: To revise the inclusion and exclusion criteria on the use
of glucocorticoids and cyclophosphamide to better align with standard of care treatment for lupus
nephritis and to enhance enrollment in the study without affecting the Sponsor’s ability to fulfill
the objectives of the study. The requirement for collection of plasma biomarkers samples in the
long-term extension (LTE) was removed. In addition, Cystatin C testing is now required.
Additional changes are also listed in the amendment table below.
Section number 
and Name
Description of Change 
Brief Rationale
1.1, Synopsis; 
4.1.1, Main Study  
A sentence was added reporting that participants 
who experience an LN flare during the main study 
should discontinue study intervention.
To clarify that participants who
experience an LN flare during the
main study should discontinue
study treatment. In earlier versions
of the protocol, this was only
included in the LTE section of the
protocol.
1.1, Synopsis; 1.3,
Schedule of
activities; 4.1.1,
Main study; 5.1,
Eligibility criteria;
5.4, Screen failures;
8, Study
Assessments and
Procedures
The extension of screening for participants who
start with mycophenolate mofetil
(MMF)/mycophenolic acid (MPA) at/or within
2 weeks of screening was changed from 2 weeks to
4 weeks.
To allow time for all required
screening procedures to occur
before the screening window
expires for patients newly or
recently started on MMF/MPA.
1.1, Synopsis; 1.2,
Schema
The sentence specifying which participants may
have the option to enroll in the LTE was updated to
clarify that participants have to achieve complete
renal response (CRR) at Week 48 in addition to
Week 52 and have completed the Week 52
assessments to have the option to participate.
The sentence was updated to clarify
which participants have the option
to enter the LTE.
1.3, Schedule of
Activities
A clarification was added when the post-dose
24-hour urine for pharmacokinetic (PK) collection
should begin and end relative to the first infusion.
A more detailed instruction was
required.
1.3, Schedule of
Activities
Plasma biomarker collection was deleted in the
LTE.
Plasma biomarker collection was
deleted as it was mistakenly listed
as a procedure in the LTE in
Protocol Amendment 2.
1.3, Schedule of
activities; 8, Study
Assessments and
Procedures
The order of the clinician-reported outcome
(ClinRo) procedures was removed.
An order for completion of the
ClinRos procedures was not
needed.
1.3, Schedule of
activities; 10.8,
Appendix 8 Clinical
Laboratory Tests
Cystatin C was added to list of required laboratory
assessments.
The Cystatin C test was added
given recent evidence showing that
using Cystatin C-based equations
for estimating GFR may be more
accurate than creatinine-based
equations. Use of Cystatin-C based
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Section number
and Name
Description of Change 
Brief Rationale
equations will not be used in the
primary endpoint analysis.
2.1.1, Unmet Need
in Lupus Nephritis;
11, References
Belimumab and voclosporin are now mentioned as 
approved LN medications. The applicable 
references were added. 
To update the section on Unmet
Need in LN to reflect that
belimumab and voclosporin were
approved for the treatment of LN.
2.3.1, Risk for Study
Participation; 4.2,
Scientific Rationale
for Study Design;
5.1, Eligibility
criteria
Clarified the inclusion criterion for oral 
glucocorticoid dosing during the study.  
To clarify the required oral
glucocorticoid dosing.
2.3.1, Risk for Study
Participation;
5.2, Exclusion
criteria
The timeframe for receipt of IV cyclophosphamide 
prior to randomization that would exclude a 
participant from the study was changed from 
6 months to 3 months.  
Align with standard clinical
practice of patients with LN and
duration of biologic effect of prior
oral and IV cyclophosphamide with
respect to a participant’s study
eligibility.
3, Objectives and
Endpoints
The alternate thresholds for renal response were 
deleted. 
To clarify the definition for
complete renal response used in
this study.
4.1.1, Main Study;
6.5, Concomitant
Therapy; 8.3.6,
Disease-Related
Events and Disease-
Related Outcomes
Not Qualifying as
Adverse Events or
Serious Adverse
Events
The definition of an LN flare was added. 
To clarify that the definition of LN
flare applies to the main study and
the LTE.
5.1, Main Study
Inclusion Criteria
The definition of a positive anti-dsDNA antibody
level at screening was specified.
To clarify the eligibility criteria for
anti-dsDNA antibody level based
on central laboratory testing, which
aligns with the eligibility for a
anti-dsDNA antibody level at
screening in other clinical trials in
lupus nephritis.
5.1, Main Study
Inclusion Criteria
A clarification was added that the participant
should have active ISN/RPS proliferative nephritis
(with or without Class V membranous nephritis).
An update was needed to clarify
that active glomerulonephritis is
required for study entry, as opposed
to only sclerotic (inactive) lesions.
5.2, Main Study
Exclusion Criteria
The term “majority” was removed from the
exclusion criteria which states that isolated or
predominant Class V LN without coexisting Class
III/IV nephritis should be excluded.
It is difficult to quantify which
class of LN is dominant and
therefore the term “majority” is not
applicable.
5.2, Main Study
Exclusion Criteria;
6.5.7, Prohibited
Therapies
The use of the immunomodulatory agent
voclosporin is now specifically mentioned in the
exclusion criteria.
Voclosporin is a systemic
immunomodulatory agent that is
now an approved treatment for
lupus nephritis and is prohibited.
5.2, Main Study
Exclusion Criteria;
6.5, Concomitant
Therapy; 6.5.2,
Glucocorticoid
Therapy
Participants who have received epidural, IV, or IM
administration of glucocorticoids less than or equal
to 125 mg/day 6 weeks prior to randomization are
now eligible.
To clarify the allowed epidural, IV,
or IM glucocorticoids.
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Section number
and Name
Description of Change 
Brief Rationale
5.2, Exclusion
Criteria; 6.5,
Concomitant
Therapy; 6.5.2,
Glucocorticoid
Therapy
The exclusion criterion regarding the use of high
dose, IV corticosteroids was changed.
To allow for the previous use of
high-dose, IV corticosteroids that
are standard of care for the
treatment of lupus nephritis, while
also preserving study integrity by
excluding the use of high-dose
intravenous corticosteroids during
screening, which can affect
proteinuria levels.
5.2.1, Long-Term
Extension Exclusion
Criteria
A reference to Section 4.1.1 was added for the
definition of an LN flare.
To align the definition of an LN
flare within the protocol.
6.5, Concomitant
Therapy
The administration of COVID-19 vaccinations and
treatments must be recorded.
To align the protocol with the
sponsor-related COVID-19 text.
6.5, Concomitant
Therapy; 6.5.2,
Glucocorticoid
Therapy
An updated sentence reporting that changes in any
immunomodulatory treatment beyond those
allowed per protocol would lead to discontinuation
was moved from Section 6.5.2 to 6.5.
The previous sentence in this
section only mentioned changes in
glucocorticoids which may cause
confusion about which changes
would lead to discontinuation.
6.5, Concomitant
Therapy; 6.5.7,
Prohibited therapies
Voclosporin and everolimus were added to the list
of prohibited therapies.
Voclosporin and everolimus are
systemic immunomodulatory
agents and are therefore prohibited
per exclusion criterion 23, but were
not specifically mentioned
previously. Voclosporin was
previously an investigational agent
but was approved for the treatment
of LN during the conduct of the
study; the use of it is prohibited
during the study.
6.5, Concomitant
Therapy; 6.5.3,
Nonsteroidal Anti-
inflammatory Drugs
A clarification was added that the initiation of
NSAID treatment should be avoided.
The initiation of NSAID
medications may affect
measurement of kidney function
and proteinuria.
6.5, Concomitant
Therapy; 6.5.4,
Anti-hypertensive
Medications
A clarification was added that the initiation of
treatment with ARB or ACE inhibitors should be
avoided.
The initiation of ARB or ACE
inhibitors may affect measurement
of kidney function and proteinuria.
6.5.2,
Glucocorticoid
Therapy
“Weeks 2 to 12” was added to the section that
describes permitted deviation from the steroid
taper.
To specify during which part of the
steroid taper the investigator can
consider deviating from the taper
schedule.
6.5.2,
Glucocorticoid
Therapy
To clarify that increases above 10 mg/day
prednisone equivalent are considered a TF.
To clarify the amount of
glucocorticoid increase that would
result in a TF.
6.5.2,
Glucocorticoid
Therapy
A sentence was added that if epidural, IV or IM
glucocorticoids are planned, discussion with a
medical monitor is recommended.
To ensure that the planned use of
epidural, IV, or IM glucocorticoids
is acceptable per protocol.
6.5.2,
Glucocorticoid
Therapy; 10.7
Appendix 7:
Glucocorticoid taper
Participants are now required to follow the steroid
tapering schedule as closely as possible.
A clarification was needed as there
was a discrepancy between the
glucocorticoid therapy section, in
which it was stated that following
the steroid tapering schedule was
required, and the glucocorticoid
taper appendix in which the
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Status: Approved, Date: 24 May 2022
Section number 
and Name
Description of Change 
Brief Rationale
schedule could be interpreted as a
suggestion.
6.5.7, Prohibited 
Therapies 
Sirolimus was removed from the list of calcineurin 
inhibitors. 
Sirolimus was erroneously listed as
a calcineurin inhibitor.
6.5.8 Rescue 
Medications 
MTX and AZA/6-MP were removed from the list 
of rescue medications. 
The use of the systemic
immunomodulatory agents MTX
and AZA/6-MP are prohibited per
protocol. There was a discrepancy
regarding MTX and AZA/6-MP
between Section 6.5.7 (Prohibited
Therapies) and Section 6.5.8
(Rescue Medication). The use of
the systemic immunomodulatory
agents such as MTX and
AZA/6-MP are prohibited per
Section 6.5.7 of the protocol.
8, Study 
Assessments and 
Procedures 
Additional information regarding the kidney biopsy 
for confirming the nephritis was added. 
A more detailed instruction was
required to clarify that patients with
concomitant class V lupus nephritis
in addition to class III or IV lupus
nephritis are eligible.
8.3.6, Disease- 
Related Events and 
Disease-Related 
Outcomes Not 
Qualifying as
Adverse Events or
Serious Adverse
Events;10.10.1,
Adverse Event
Definitions and
Classifications
A sentence mentioning that the cause of death 
within 12 weeks after the last dose is considered an 
SAE was moved from Section 8.3.6 to Section 
10.10.1.
The sentence was moved to align
with the Janssen Research &
Development protocol template.
10.10.5, Procedures 
A reference to Section 4.1.1, which includes for a
definition of LN flare, was added.
A definition of LN flare was added
in Section 4.1.1 which is relevant
for this section.
10.13, Appendix 13 
Protocol 
Amendment History
The final efficacy visit during the LTE visit was
changed from Week 148 to Week 152.
The final efficacy visit was
erroneously listed as Week 148 in
the Protocol Amendment Summary
of Changes Table in Protocol
Amendment 2.
Throughout the
Protocol
Minor grammatical, formatting, or spelling changes
were made.
Minor errors were noted
Amendment 2 [20 May 2021]
Overall Rationale for the Amendment:To add a long-term extension (LTE) to the study for an additional
2 years in order to evaluate long-term efficacy and safety of guselkumab treatment in lupus nephritis.
Eligible participants must have achieved complete renal response (CRR) at Weeks 48 and 52. This
amendment also addresses the use of oral contraceptives (using oral contraceptives with a second method
of contraception) with concomitant mycophenolate mofetil (MMF)/mycophenolic acid (MPA) due to
changes in their label. Additional changes are also listed on the amendment table below.
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Section number
and Name
Description of Change 
Brief Rationale
The subsequent tables in the protocol were
renumbered accordingly.
4.4, End of Study
Definition
The definition for study completion of the main 
study was updated to include participants who 
complete assessments through Week 52 and enter
the LTE.
To update the definition of study
completion.
5.1, Main Study
Inclusion Criteria;
5.1.1, Long-Term
Extension Inclusion
Criteria; 5.2, Main
Study Exclusion
Criteria; 5.2.1,
Long-Term
Extension Exclusion
Criteria; 5.3,
Lifestyle
Considerations
The sections for the original inclusion and 
exclusion criteria for the study were renamed to 
the main study inclusion and exclusion criteria. 
Sections were added for the LTE inclusion and
exclusion criteria. For LTE inclusion criteria,
3 criteria were added. For LTE exclusion, 2 criteria
were added.
Specified the lifestyle considerations for the study
includes the LTE and added a lifestyle
consideration to be willing and able to complete a
participant diary card.
Inclusion and exclusion criteria and
lifestyle considerations were added
for the LTE.
6.1.2, Combination
Products; 6.2
Preparation,
Handling, Storage,
Accountability
The description of the combination product that
will be used in the main study was updated.
The description of the combination product that
will be used in the LTE was added.
To specify the combination product
that will be used during the main
study and LTE.
6.3, Measures to
Minimize Bias:
Randomization and
Blinding
Added the blind will be maintained in the LTE
until after the last follow-up assessment or study
discontinuation for the last participant at Week 60
in the main study.
To specify when the study will be
unblinded during the LTE.
6.5, Concomitant
Therapy; 6.5.1,
Antimalarial
Medications; 6.5.2,
Glucocorticoid
Therapy; 6.5.4,
Anti-hypertensive
Medications
Requirements for antimalarial medications,
glucocorticoid therapy, and anti-hypertensive
medications during the LTE were added.
In Section 6.5.2, revised the sentence describing
short courses of oral glucocorticoids to be 10 days
or less.
To specify requirements for
concomitant therapies during the
LTE.
Revised for clarification.
6.7, Continued
Access to Study
Intervention After
the End of the Study
“Main” was added to the following fragment: “At
the end of their participation in the main study”
Added the Week 48 timepoint to the following
fragment: “as determined by meeting CRR at
Weeks 48 and 52”
To describe/clarify the timepoint
during the study (main and LTE).
7.1.1, Long-Term
Extension
Section 7.1.1 was added to specify study
intervention will be discontinued if the participant
has an LN flare that requires a change in
medication during the LTE.
To describe discontinuation of
study intervention during the LTE.
8, Study
Assessments and
Procedures
Under Blood Sample Collection, added the
approximate blood volume to be collected from
each participant during the LTE from sites
collecting biomarkers and from sites not collecting
biomarkers.
To specify the approximate amount
of blood volume collected during
the LTE.
8, Study
Assessments and
Procedures
Added participant diary card to the list of
study-specific materials.
Participants who self-inject study
intervention at home during the
LTE will record the injection on a
diary card.
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Status: Approved, Date: 24 May 2022
Section number 
and Name
Description of Change 
Brief Rationale
7.1, Discontinuation 
of Study 
Intervention; 8.2.4, 
Clinical Safety 
Laboratory 
Assessments; 10.8, 
Appendix 8: Clinical 
Laboratory Tests; 
10.11, Appendix 11: 
Liver Safety:
Suggested Actions 
and Follow-up 
Assessments 
Removed specific language/details regarding liver 
function tests in Section 7.1 and replaced with 
template language that cross-references 
Appendix 11. 
Removed specific language/details regarding liver
function tests in Section 8.2.4 and Appendix 8, and
replaced with template language that
cross-references Appendix 11.
The title of the Appendix was updated as follows:
Liver Safety: Suggested Actions and Follow-up
Assessments.
The following new subsections were added:
10.11.1, Stopping Algorithm; 10.11.2, Follow-up
Assessments; and 10.11.2.1, Phase 2 Liver
Chemistry Stopping Criteria and Follow-up
Assessments.
The Sponsor’s template was
updated to provide guidance and
evaluations to be obtained in the
setting of specific patterns of liver
enzymes abnormalities.
8, Study 
Assessments and 
Procedures 
The following sentence under Screening Phase was 
bolded: Participants must meet criteria for UPCR, 
hematology, and chemistry after at least 8 weeks of
MMF/MPA.
To emphasize that participants
must meet these criteria.
8.1.2, Physician's 
Global Assessment 
of Disease Activity  
Verbal anchors were updated to “No disease 
activity” and “Severe disease activity”. 
Updated the verbal anchors to align
with the PGA that is in use for the
study.
8.1.6, Patient Global 
Impression of 
Change; 11, 
References. 
Revised the description of the Patient Global 
Impression of Change and updated reference.
Added the following reference: Guy W (1976), Ed.
ECDEU Assessment Manual for
Psychopharmacology. Rockville, MD: US
Department of Health, Education, and Welfare
Public Health Service Alcohol, Drug Abuse, and
Mental Health Administration, 1976:217-222. The
reference list was renumbered accordingly.
Revised for clarification.
8.3.1, Time Period 
and Frequency for 
Collecting Adverse
Event and Serious
Adverse Event
Information
A definition was provided to clarify what 
constitutes a possible Hy’s Law case.
Added for clarification.
10.4, Appendix 4: 
Hepatitis B Virus 
(HBV) Screening 
with HBV DNA
Testing
Removed the following text from the last bullet
point before Table 1: “are Not eligible for this
protocol”. Provided eligibility criteria for
participants who test positive only for core
antibody ((anti-HBc+).
In Table 1, updated language about eligibility
criteria for participants who test positive for core
antibody (anti-HBc+) and added a footnote
designated with *.
To specify eligibility criteria for
participants who test positive for
core antibody (anti-HBc+).
10.8, Appendix 8:
Clinical Laboratory
Tests
Added Hep B DNA as a laboratory parameter
under Other Test.
Clinical Chemistry footnote description about liver
abnormalities was removed and replaced with
Added Hep B DNA as a laboratory
parameter. Clinical Chemistry
footnote updated to align with the
Sponsor’s most current version.
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Section number
and Name
Description of Change 
Brief Rationale
template language that cross-references
Appendix 11. Potential Hy’s Law case description
was added (cross-reference to Section 8.3.1).
10.9.1, Appendix 10:
Regulatory, Ethical,
and Study Oversight
Considerations
Added text regarding the use of a “Protocol 
Clarification Communication”. 
The Sponsor’s template was
updated to include potential use of
a “Protocol Clarification
Communication”.
10.12, Appendix 12:
Guidance on Study
Conduct during the
COVID-19
Pandemic
Minor edits were made. 
Appendix was updated to align
with the Sponsor’s most current
version.
Throughout the
protocol
Minor grammatical, formatting, or spelling
changes were made.
Minor errors were noted.
Amendment 1 [07 May 2020]
Overall Rationale for the Amendment:  It is recognized that the Coronavirus Disease 2019 (COVID-19)
pandemic may have an impact on the conduct of this clinical study. In alignment with recent health authority
guidance, the Sponsor is providing options for study related participant management in the event of
COVID-19 related disruption to the conduct of the study. Additionally, text defining the combination
product was added, as well as updated template text, and other minor changes.
Section Number 
and Name
Description of Change 
Brief Rationale
5.2 Exclusion
Criteria;
10.12 Appendix 12:
Guidance on Study
Conduct during the
COVID-19
Pandemic
An exclusion criterion related to COVID-19 was
added (exclusion #56), and additional information
on COVID-19 was added in an appendix.
Clinical study instructions were
added to assist sites with the
COVID-19 pandemic.
6.1.1 Combination
Products
A new subsection was made describing the 
combination product. 
The Sponsor’s template was
updated to include a description of
combination products, and
therefore, the Sponsor has updated
the text accordingly.
Synopsis: 
3 Objectives and 
Endpoints 
An endpoint regarding serum anti-guselkumab 
antibodies was updated from Week 52 to Week 60 
The text was updated to reflect that
cumulative data through Week 60
will be used.
Synopsis 
Updated text summarizing PROs being assessed. 
Clarifying to address the concept
that is being assessed with each
measure.
Synopsis; 
9.4.6 Other 
Analyses 
It was clarified that urine guselkumab 
concentrations and 
pharmacokinetic(PK)/pharmacodynamic (PD) 
additional analyses would be described in separate 
technical reports.
Clarification was added that urine
PK and the PK/PD will be
summarized in separate reports and
not in the clinical study report.
4.1 Overall Design 
Text regarding a futility analysis was deleted. 
The Data Monitoring Committee
(DMC) will perform periodic safety
and efficacy assessments to ensure
safety of the subjects and viability
of continuing the study.
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Status: Approved, Date: 24 May 2022
Section Number 
and Name
Description of Change 
Brief Rationale
5.1 Inclusion 
Criteria 
A new inclusion (inclusion #23) regarding reading 
and writing was added. 
To align with feedback on patient-
reported outcome (PRO)
completion.
5.2 Exclusion 
Criteria
Hemoglobin unit was corrected (exclusion #15). 
Minor error was noted.
9.5 Interim Analysis Text regarding an interim analysis was removed. 
The text in this section was
duplicative to the text in the section
regarding DMC or Other Review
Board. The study will not include
an interim analysis, rather, a DMC
will be reviewing unblinded data
which is already described in the
section regarding DMC or Other
Review Board. This duplicative
text was removed to avoid
confusion.
10.4 Appendix 4 
Hepatitis B Virus 
(HBV) Screening
with HBV DNA
Testing
Hepatitis B core antibody testing information was 
updated. 
Updated to align with eligibility
critiera.
10.8 Appendix 8 
Clinical Laboratory
Tests
Clinical chemistry test names were updated 
Minor clarifications.
Throughout the 
protocol 
Updates were made to the safety sections based on 
template language changes. And additional 
template sentences were added regarding PROs.
The Sponsor’s protocol template
was updated.
Throughout the 
protocol 
Minor grammatical, formatting, or spelling changes 
were made.
Minor errors were noted.
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Status: Approved, Date: 24 May 2022
11. 
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CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001 Amendment 4
CONFIDENTIAL –FOIA Exemptions Apply in U.S. 
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Status: Approved, Date: 24 May 2022
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27. Petri M, Genovese M, Engle E, Hochberg M. Definition, incidence, and clinical description of flare in systemic
lupus erythematosus. A prospective cohort study. Arthritis Rheum. 1991; 34:937-944.
28. Petri M, Hellmann D, Hochberg M. Validity and reliability of lupus activity measures in the routine clinic
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30. Rodriguez F, Harrison RW, Wojdyla D, Mahaffey KW. Lost to Follow-up and Withdrawal of Consent in
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31. Rovin BH, Solomons N, Pendergraft WF, et al. A randomized, controlled double-blind study comparing the
efficacy and safety of dose-ranging voclosporin with placebo in achieving remission in patients with active
lupus nephritis. Kidney International. 2019;95,219-231.
32. Rovin BH, Teng YKO, Ginzler EM, et al. Efficacy and safety of voclosporin versus placebo for lupus nephritis
(AURORA 1): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet.
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33. Stratta P, Marengo M, Mesiano P, et al. Risk management of renal biopsy: 1387 cases over 30 years in a single
centre. European Journal of Clinical Investigation. 2007;37(12):954-963.
34. Termaat RM, Brinkman K, Nossent JC, Swaak AJ, Smeenk RJ, Berden JH. Anti-heparan sulphate reactivity in
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Immunol. 1990;82(2):268-274.
35. Touma Z, Gladman DD, Urowitz MB. SLEDAI-2K for a 30-day window. Lupus. 2010;19(1):49-51.
36. Touma Z, Urowitz M, Ibañez D, Gladman D. SLEDAI-2K 10 days versus SLEDAI-2K 30 days in a
longitudinal evaluation. Lupus. 2011b; 20(1):67-70.
37. Wallace DJ. First Edition: Lupus The Essential Clinician's Guide, Oxford, Oxford University Press 2008, page
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38. Weening JJ, D'Agati VD, Schwartz MM, et al. International Society of Nephrology Working Group on the
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Nephritis. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int.
2004;65(2):521-530.
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Status: Approved, Date: 24 May 2022
39. Winfield JB, Faiferman I, Koffler D. Avidity of anti-DNA antibodies in serum and IgG glomerular eluates
from patients with systemic lupus erythematosus.  Association of high avidity antinative DNA antibody with
glomerulonephritis. J Clin Invest. 1977;59(1):90-96.
40. Wong CK, Lit LC, Tam LS, Li EK, Wong PT, Lam CW. 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(3):385–93.
41. Xia LP, Li BF, Shen H, Lu J. Interleukin-27 and interleukin-23 in patients with systemic lupus erythematosus:
possible role in lupus nephritis. Scandinavian Journal of Rheumatology. 2015; 44(3):200-205.
42. Zickert A, Amoudruz P, Sundström Y, et al. IL-17 and IL-23 in lupus nephritis –association to histopathology
and response to treatment. BMC Immunology. 2015; 16(7):1-10.
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Clinical Protocol CNTO1959LUN2001 Amendment 4
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Status: Approved, Date: 24 May 2022
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed
regarding the study intervention, the conduct of the study, and the obligations of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature: 
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature: 
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed): 
Institution: 
Janssen Research & Development
Signature: electronic signature appended at the end of the protocol 
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the study, written notification will be
provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD
NCT04376827


Signature
User 
Date 
Reason
24-May-2022
16:27:12
(GMT)
Document Approval
PPD
NCT04376827


CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved,  Date: 24 May 2022
Janssen Research & Development *
Clinical Protocol
GUIDANCE ON STUDY CONDUCT DURING MAJOR DISRUPTION
Protocol Title
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of
Guselkumab in Subjects with Active Lupus Nephritis
ORCHID-LN
A Study of the Efficacy and Safety of Guselkumab in Participants with Active Lupus
Nephritis
Protocol CNTO1959LUN2001; Phase 2
CNTO 1959  (guselkumab)
*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 Pharmaceutica NV; Janssen Sciences Ireland
UC; Janssen Biopharma Inc.; 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.
United States (US) sites of this study will be conducted under US Food & Drug Administration
Investigational New Drug (IND) regulations (21 CFR Part 312).
EudraCT NUMBER: 2018-003155-38
Status:
Approved
Date:
24 May 2022
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-RIM-742336, Version 1.0
THIS APPENDIX APPLIES TO ALL CURRENT APPROVED VERSIONS OF PROTOCOL
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements. 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04376827


Guidance on Study Conduct During Major Disruption
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved,  Date: 24 May 2022
STUDY CONDUCT DURING A MAJOR DISRUPTION
GUIDANCE ON STUDY CONDUCT DURING MAJOR DISRUPTION
It is recognized that the major disruption involving Ukraine, Russia, and neighboring 
countries/territories may have an impact on the conduct of this clinical study due to, for example, 
isolation or quarantine of participants and study site personnel; travel restrictions/limited access to 
public places, including hospitals; study site personnel being unavailable, isolated, or reassigned 
to critical tasks. 
The sponsor is providing options for study related participant management in the event of 
disruption to the conduct of the study. This guidance does not supersede any local or government 
requirements or the clinical judgement of the investigator to protect the health and well-being of 
participants and site staff. If, at any time, a participant’s travel to the study site is considered to be 
dangerous, study participation may be interrupted, and study follow-up conducted. If it becomes 
necessary to discontinue participation in the study, the procedures outlined in the protocol for 
discontinuing study intervention will be followed.
If, as a result of the major disruption involving Ukraine, Russia, and neighboring 
countries/territories scheduled visits cannot be conducted in person at the study site, they will be 
performed to the extent possible remotely/virtually or delayed until such time that on-site visits 
can be resumed. At each contact, participants will be interviewed to collect safety data. Key 
efficacy endpoint assessments should be performed if required and as feasible. Participants will 
also be questioned regarding general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for participants on study 
intervention, including follow up. Modifications to protocol-required assessments may be 
permitted after consultation with the participant, investigator, and the sponsor.
The sponsor will continue to monitor the conduct and progress of the clinical study, and any 
changes will be communicated to the sites and to the health authorities according to local guidance. 
Modifications made to the study conduct as a result of the major disruption involving Ukraine, 
Russia, and neighboring countries/territories should be summarized in the clinical study report.

Certain protocol-mandated visits to the study site may not be possible during the major 
disruption involving Ukraine, Russia, and neighboring countries/territories. Therefore, 
temporary measures may be implemented if considered appropriate by the sponsor and 
investigator to maintain continuity of patient care and study integrity. Certain measures, such 
as those listed below, may be necessary and should be instituted in accordance with applicable 
(including local) laws, regulations, guidelines, and procedures: 

remote (eg, by phone/telemedicine) or in person, off-site (eg, in-home) interactions 
between site staff (or designees) and participants for study procedures eg, those related 
to safety monitoring/efficacy evaluation/study intervention storage and administration 
(including training where pertinent)
NCT04376827


Guidance on Study Conduct During Major Disruption
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved,  Date: 24 May 2022

study intervention administration may take place outside of the scheduled visit window, 
if the investigator determines this to be safe for the participant, due to disruption of study 
intervention shipment to the site

laboratory assessments using a suitably accredited local laboratory

Missed assessments/visits will be captured in the clinical trial management system for 
protocol deviations. Discontinuations of study interventions and withdrawal from the study 
should be documented in the electronic case report form (eCRF).

other relevant study data elements impacted by the major disruption involving Ukraine, 
Russia, and neighboring countries/territories should also be documented in eCRFs and/or 
other study systems, as directed by detailed sponsor guidance. These may include 
missed/delayed/modified study visits/assessments/dosing, and instances where 
temporary measures such as those above are implemented. 

The sponsor will evaluate the totality of impact of the major disruption involving Ukraine, 
Russia, and neighboring countries/territories on collection of key study data. 

if needed additional data analyses will be outlined in study statistical analysis plan.
NCT04376827


Guidance on Study Conduct During Major Disruption
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
4
Status: Approved,  Date: 24 May 2022
INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. 
I will conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that they 
are fully informed regarding the study intervention, the conduct of the study, and the obligations 
of confidentiality.
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Institution:
Janssen Research & Development 
Signature:
electronic signature appended at the end of the protocol
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the sponsor, and a protocol amendment will not be required.
PPD
NCT04376827

SAP_003.pdf: 
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
1
Status: Approved, Date: 16 August 2022
Janssen Research & Development
Statistical Analysis Plan
Amendment 1
A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel-group Study of 
Guselkumab in Participants with Active Lupus Nephritis
Protocol CNTO1959LUN2001; Phase 2
CNTO1959  (Guselkumab)
Status:
Approved
Date:
16 August 2022
Prepared by:
Janssen Research & Development, LLC  
Document No.: EDMS-RIM-129094, 4.0
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise.
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
2
Status: Approved, Date: 16 August 2022
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF IN-TEXT TABLES.......................................................................................................................... 5
LIST OF IN-TEXT FIGURES ........................................................................................................................ 5
VERSION HISTORY..................................................................................................................................... 6
1.
INTRODUCTION.................................................................................................................................. 7
1.1.
Objectives and Endpoints ................................................................................................................ 7
1.2.
Study Design.................................................................................................................................... 9
2.
STATISTICAL HYPOTHESES.......................................................................................................... 11
3.
SAMPLE SIZE DETERMINATION....................................................................................................11
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS.....................................................................12
5.
STATISTICAL ANALYSES............................................................................................................... 13
5.1.
General Considerations ................................................................................................................. 13
5.1.1.
Visit Windows ............................................................................................................................. 13
5.1.2.
Pooling Algorithm for Analysis Centers ...................................................................................... 13
5.1.3.
Reference Date, Study Day and Relative Day ...........................................................................13
5.2.
Participant Dispositions.................................................................................................................. 14
5.3.
Primary Endpoint Analysis ............................................................................................................. 14
5.3.1.
Definition of Endpoint(s) ............................................................................................................. 14
5.3.2.
Estimands ................................................................................................................................... 15
5.3.2.1.
Primary Estimand (Composite Estimand) ............................................................................... 15
5.3.2.2.
Supplementary Estimand 1 (Hypothetical)..............................................................................16
5.3.2.3.
Supplementary Estimand 2 (Treatment Policy (de Facto)) ..................................................... 17
5.3.2.4.
Supplementary Estimand 3 (Composite).................................................................................18
5.3.2.5.
Supplementary Estimand 4 (Composite).................................................................................19
5.3.2.6.
Supplementary Estimand 5 (Composite).................................................................................20
5.3.3.
Analysis Methods........................................................................................................................ 21
5.3.4.
Supplementary Analyses............................................................................................................ 22
5.3.4.1.
Supplementary Analysis 1 (Supplementary Estimand 1 (Hypothetical))................................. 22
5.3.4.2.
Supplementary Analysis 2 (Supplementary Estimand 1 (Hypothetical))................................. 22
5.3.4.3.
Supplementary Analysis 3 (Supplementary Estimand 2 (Treatment Policy)) ......................... 22
5.3.4.4.
Supplementary Analysis 4 (Supplementary Estimand 3 (Composite)) ................................... 22
5.3.4.5.
Supplementary Analysis 5 (Supplementary Estimand 4 (Composite)) ................................... 22
5.3.4.6.
Supplementary Analysis 6 (Supplementary Estimand 5 (Composite)) ................................... 23
5.3.5.
Sensitivity Analyses.................................................................................................................... 23
5.3.5.1.
Sensitivity Analysis 1 (Primary Composite Estimand).............................................................23
5.3.5.2.
Sensitivity Analysis 2 (Supplementary Estimand 2 (Treatment Policy)).................................. 23
5.4.
Secondary Endpoint(s) Analysis .................................................................................................... 23
5.4.1.
Multiplicity Adjustment for Testing Procedures ..........................................................................24
5.4.2.
Key Confirmatory Secondary Endpoint(s) ..................................................................................24
5.4.2.1.
Definition of Endpoint(s) .......................................................................................................... 24
5.4.2.1.1.
Complete Renal Response (CRR).......................................................................................24
5.4.2.1.2.
Complete Renal Response 50% Pred (CRR – 50% Pred).................................................. 25
5.4.2.1.3.
Glucocorticoid (Prednisone or Prednisone Equivalent) Reduction...................................... 25
5.4.2.1.4.
Time to Achievement of Complete Renal Response (CRR)................................................ 25
5.4.2.1.5.
Time to Treatment Failure (TF)............................................................................................ 25
5.4.2.2.
Estimand(s).............................................................................................................................. 26
5.4.2.2.1.
Proportion of Participants Achieving Complete Renal Response (CRR) at Week 24 ......... 26
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
3
Status: Approved, Date: 16 August 2022
5.4.2.2.2.
Proportion of Participants Achieving a Sustained Reduction in Steroid Dose ≤10 
mg/day of Prednisone or Equivalent from Week 16 to Week 24 ......................................... 27
5.4.2.2.2.1.
Main Estimand (Composite).............................................................................................. 27
5.4.2.2.2.2.
Supplementary Estimand (Treatment Policy (de Facto)).................................................. 27
5.4.2.2.3.
Proportion of Participants Achieving at Least 50% Decrease in Proteinuria from 
Baseline at Week 52 ............................................................................................................ 28
5.4.2.2.3.1.
Main Estimand .................................................................................................................. 28
5.4.2.2.3.2.
Supplementary Estimand.................................................................................................. 29
5.4.2.2.4.
Proportion of Participants Achieving CRR at Week 52........................................................ 30
5.4.2.2.4.1.
Main estimand................................................................................................................... 30
5.4.2.2.4.2.
Supplementary Estimand 1............................................................................................... 31
5.4.2.2.4.3.
Supplementary Estimand 2............................................................................................... 32
5.4.2.2.4.4.
Supplementary Estimand 3............................................................................................... 33
5.4.2.2.5.
Proportion of Participants with Urine Protein to Creatinine Ratio (UPCR) 
<0.5 mg/mg at Week 24....................................................................................................... 34
5.4.2.2.6.
Proportion of Participants with UPCR <0.75 mg/mg at Week 24 ........................................ 36
5.4.2.2.7.
Time to Achievement of CRR through Week 24 and 52......................................................37
5.4.2.2.7.1.
Main Estimand .................................................................................................................. 37
5.4.2.2.7.2.
Supplementary Estimand 1 for Time to Achievement of CRR through Week 52............. 38
5.4.2.2.7.3.
Supplementary Estimand 2 for Time to Achievement of CRR through Week 52............. 39
5.4.2.2.7.4.
Supplementary Estimand 3 for Time to Achievement of CRR through Week 52............. 40
5.4.2.2.8.
Time to treatment failure (TF) .............................................................................................. 41
5.4.2.3.
Analysis Methods .................................................................................................................... 42
5.4.2.3.1.
Binary Endpoints (Secondary Endpoints 1-6)...................................................................... 42
5.4.2.3.2.
Time to Event Endpoints (Secondary Endpoints 7-8)..........................................................42
5.4.2.3.3.
Sensitivity Analysis of the CRR endpoint using CRR-50% Pred definition.......................... 43
5.5.
Tertiary/Exploratory Endpoint(s) Analysis...................................................................................... 43
5.5.1.
Definition of Endpoint(s) ............................................................................................................. 44
5.5.1.1.
Four (4) Points Improvement from Baseline in SLE Disease Activity Index 2000 
(SLEDAI-2K) Modified to Exclude Renal Items.......................................................................44
5.5.1.2.
Active Joints, Tender Joints, Swollen Joints ...........................................................................44
5.5.1.3.
Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) score.............. 44
5.5.1.4.
Lupus Quality of Life Questionnaire ........................................................................................ 45
5.5.1.5.
FACIT-fatigue .......................................................................................................................... 45
5.5.1.6.
Lupus Symptoms..................................................................................................................... 45
5.5.1.7.
Patient Global Impression of Change...................................................................................... 45
5.5.2.
Analysis Methods........................................................................................................................ 46
5.5.2.1.
Binary Endpoints (Tertiary/Exploratory Endpoints 1-3) ........................................................... 46
5.5.2.2.
Continuous Endpoints (Tertiary/Exploratory Endpoints 4-7)................................................... 46
5.6.
Other Supportive Endpoints........................................................................................................... 46
5.6.1.
Analysis Methods........................................................................................................................ 49
5.6.1.1.
Binary Endpoints ..................................................................................................................... 49
5.6.1.2.
Continuous Endpoints ............................................................................................................. 50
5.7.
Safety Analyses ............................................................................................................................. 50
5.7.1.
Extent of Exposure ..................................................................................................................... 50
5.7.2.
Adverse Events........................................................................................................................... 51
5.7.3.
Additional Safety Assessments .................................................................................................. 51
5.7.3.1.
Clinical Laboratory Tests......................................................................................................... 51
5.7.3.2.
Electronic Columbia-Suicide Severity Rating Scale................................................................ 52
5.7.3.3.
Vital Signs and Physical Examination Findings....................................................................... 53
5.8.
Other Analyses............................................................................................................................... 53
5.8.1.
Pharmacokinetics ....................................................................................................................... 53
5.8.2.
Immunogenicity........................................................................................................................... 54
5.8.3.
Pharmacodynamics / Biomarker Analyses.................................................................................56
5.8.4.
Pharmacokinetic/Pharmacodynamic Relationships ................................................................... 56
5.8.5.
Definition of Subgroups .............................................................................................................. 56
5.9.
Interim Evaluations......................................................................................................................... 58
5.9.1.
Interim Efficacy Evaluations ....................................................................................................... 58
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
5.9.1.1.
First Interim Efficacy Evaluation .............................................................................................. 59
5.9.1.2.
Second and Third Interim Efficacy Evaluation......................................................................... 59
5.9.2.
Data Monitoring Committee........................................................................................................ 60
REFERENCES............................................................................................................................................ 61
APPENDICES............................................................................................................................................. 62
APPENDIX 1:
LIST OF ABBREVIATIONS ..........................................................................................62
APPENDIX 2:
CHANGES TO PROTOCOL-PLANNED ANALYSES .................................................. 64
APPENDIX 3:
DEMOGRAPHICS AND BASELINE CHARACTERISTICS ......................................... 65
APPENDIX 4:
PROTOCOL DEVIATIONS............................................................................................67
APPENDIX 5:
PRIOR AND CONCOMITANT MEDICATIONS ............................................................ 68
APPENDIX 6:
MEDICAL HISTORY...................................................................................................... 69
APPENDIX 7:
INTERVENTION COMPLIANCE...................................................................................70
APPENDIX 8:
ADVERSE EVENTS OF SPECIAL INTEREST.............................................................71
APPENDIX 9:
MEDICATIONS OF SPECIAL INTEREST .................................................................... 72
APPENDIX 10:
LABORATORY TOXICITY GRADING.......................................................................... 73
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
5
Status: Approved, Date: 16 August 2022
LIST OF IN-TEXT TABLES
Table 1:
Power to Detect Difference in Proportions of Participants with ≥50% Decrease in 
Proteinuria Between the Guselkumab and Placebo Intervention Groups at Week 24............. 12
Table 2:
Description of analysis sets used to analyze the data in the study. ......................................... 12
Table 3:
Endpoints, Intercurrent Events Strategy and Analysis for Other Supportive Endpoints........... 47
Table 4:
Abnormal Vital Sign Parameters............................................................................................... 53
Table 5:
Demographic Variables............................................................................................................. 65
Table 6:
Baseline Disease Characteristics Variables .............................................................................66
LIST OF IN-TEXT FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 11
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
6
Status: Approved, Date: 16 August 2022
VERSION HISTORY
SAP Version History Summary
SAP Version
Approval Date
Change
Rationale
1.0
13 August 2020
Not Applicable
Initial release, draft approved for 
dossier use
2.0
16 August 2022 
All sections: Added and/or 
modified text at the beginning of 
sections and subsections to clarify 
changes in the statistical analysis 
plan due to early study 
termination, and to clarify the 
analyses that will be included in 
the CSR.
Statistical analysis plan is 
changed due to early termination 
of the study
Section 1.2: Minor updates on 
study design per protocol; 
Section 5.1: Removed baseline 
definition for proteinuria as the 
general baseline definition will be 
used;
Section 5.2: Updated the 
timepoint for disposition 
summary;
Section 5.4.2.2.7.1: Updated 
ICEs for the main estimand for 
time to achievement of CRR;
Section 5.4.2.3: Updated analysis 
method for Secondary Endpoint 
2.
Section 5.5.1: Minor updates on 
definition of endpoints for clarity;
Section 5.6: Minor updates in 
analysis methods.
Section 5.7: Minor edits for 
clarity.
Minor updates for clarification
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
7
Status: Approved, Date: 16 August 2022
1.
INTRODUCTION
This Statistical Analysis Plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical methods for all planned analyses of efficacy, safety, tolerability, pharmacokinetics (PK), 
pharmacodynamics (PD) and immunogenicity of guselkumab.  This SAP incorporates all analyses 
through the final database lock (DBL) for the CNTO1959LUN2001 study.
Early Termination Note: The original study design included a target of approximately 60 
participants to be randomly assigned with approximately 30 participants planned per intervention 
group. Due to the Sponsor’s decision to stop screening of new participants as a result of enrollment 
challenges, fewer than 60 participants will be enrolled in the study. The end of study will occur 
after all enrolled participants have completed the Week 20 visit or discontinued study intervention 
prior to Week 24, and all participants have completed their final efficacy and safety visits per the 
Schedule of Activities (SoA). 
There will be only one database lock that will occur at the end the study. All data through the end 
of the study including the long term extension (LTE) data will be summarized together. Analyses 
that will be performed and included in the abbreviated Clinical Study Report (CSR) are noted
below at the beginning of each respective section. The analyses not performed will be retained in 
this SAP for completeness.   
1.1.
Objectives and Endpoints
Due to the Sponsor’s decision to terminate the study early, only the primary endpoint, major 
secondary endpoints, and safety endpoints will be reported in the CSR. Details will be described 
in each respective section.
For informational purposes, the below table outlines the objectives and endpoints originally 
planned for the study.
Objectives
Endpoints
Primary
!
To evaluate the efficacy of 
guselkumab in participants with 
active lupus nephritis (LN)
Primary endpoint: Proportion of participants achieving at least 
50% decrease in proteinuria from baseline at Week 24 
Secondary endpoints to include:
!
Proportion of participants achieving complete renal 
response (CRR) at Week 24
!
Proportion of participants achieving a sustained reduction 
in steroid dose ≤10 mg/day of prednisone or equivalent 
from Week 16 to Week 24
!
Proportion of participants achieving at least 50% decrease 
in proteinuria from baseline at Week 52
!
Proportion of participants achieving CRR at Week 52 
!
Proportion of participants with Urine Protein to Creatinine 
Ratio (UPCR) <0.5 mg/mg at Week 24
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
Objectives
Endpoints
!
Proportion of participants with UPCR <0.75 mg/mg at 
Week 24
!
Time to achievement of CRR
!
Time to treatment failure (TF) 
Secondary
!
To evaluate the safety and 
tolerability of guselkumab in 
participants with active LN
!
Frequency and type of adverse events (AEs), serious 
adverse events (SAEs), reasonably related AEs, AEs 
leading to discontinuation of study intervention, infections, 
serious infections, and infections requiring oral or 
parenteral 
antimicrobial 
treatment, 
AEs temporally 
associated with an infusion, and injection-site reactions
!
Laboratory parameters and change from baseline in 
laboratory parameters (hematology and chemistry)
!
Summary of maximum Common Terminology Criteria for 
Adverse Events (CTCAE) toxicity grade for postbaseline 
laboratory values (hematology and chemistry)
!
Systolic and diastolic blood pressures over time
!
To 
evaluate 
the 
PK, 
immunogenicity, in participants 
with active LN
!
Serum guselkumab levels over time
!
Serum anti-guselkumab antibodies through Week 24, 
through Week 52, and in participants discontinuing study 
intervention early
Tertiary/Exploratory
!
To evaluate the efficacy of 
guselkumab in extrarenal lupus 
manifestations
!
Proportion of participants with ≥4-point improvement at 
Week 24 in systemic lupus erythematosus disease activity 
index 2000 (SLEDAI-2K) modified to exclude renal items
!
Proportion of participants with baseline arthritis (with at 
least 4 active joints at baseline) who have ≥50% reduction 
in active joints at Week 24
!
Proportion 
of 
participants 
with 
baseline 
active 
mucocutaneous lupus manifestations (CLASI score ≥8) and 
≥50% reduction in Cutaneous Lupus Erythematosus 
Disease Area and Severity Index (CLASI) scores at 
Week 24
!
To evaluate the impact of 
guselkumab on Health-Related 
Quality of Life (HRQoL) and 
fatigue in participants with 
active LN
!
Change from baseline in Lupus Quality of Life (LupusQoL) 
individual domains at Week 24 
!
Change from baseline in Functional Assessment of Chronic 
Illness Therapy (FACIT)-fatigue score at Week 24
!
Change from baseline in lupus symptoms (joint pain, joint 
stiffness, rash, and swelling [peripheral edema]) at Week 24 
!
Patient Global Impression of Change (PGIC) - Change in 
LN (health condition) at Week 24 and Week 52 
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
Objectives
Endpoints
!
To evaluate biomarkers of LN, 
pharmacodynamic (PD) effects 
of guselkumab, and to identify 
participants 
most 
likely 
to 
benefit from treatment with 
guselkumab
!
Serum biomarkers including IL-23, IL-17A, IL-17F, IL-22, 
complement (C)3, C4, C1q, or autoantibodies, eg, 
anti-dsDNA 
!
Cellular (urine and peripheral blood mononuclear cell 
[PBMC]) and whole blood gene expression
!
Urine biomarkers (protein and /or nucleic acids)
!
Perform analyses of pre- and 
post-treatment renal biopsies 
(optional)
!
Histopathology of glomeruli and tubulointerstitial tissue, 
immunohistochemistry for resident and infiltrating cell 
types and inflammatory mediators (including IL-23, IL-17, 
IL-21, interferon-gamma, chemokines), and/or tissue gene 
expression
1.2.
Study Design
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.   
CNTO1959LUN2001 is a randomized, double-blind, placebo-controlled, parallel, multicenter, 
interventional Phase 2 study in participants aged 18 to 75 (inclusive) with active lupus nephritis 
(LN). The total duration of the study is up to 68 weeks: a ≤8-week screening period (rescreening 
is permitted once per participant), a 48-week double-blind treatment period, and a 12-week safety 
follow-up period after the last dose (8 weeks after the final efficacy visit). Participants starting 
mycophenolate mofetil (MMF) / mycophenolic acid (MPA) at/or within 2 weeks of screening may 
extend screening for up to 2 additional weeks. 
Efficacy, safety, PK, immunogenicity, and biomarkers (where local regulations permit) will be 
assessed according to the SoA in the study protocol. An optional pharmacogenomic blood sample 
will be collected from participants who consent to the collection of these samples (where local 
regulations permit). 
The primary efficacy analysis will be performed after all participants have completed Week 24 
efficacy assessments (or discontinued). Additional secondary endpoints will be completed at 
Week 24 and Week 52. 
Every reasonable effort should be made to keep concomitant medications stable as defined in the 
protocol. Beginning at the screening visit, all concomitant therapies and all changes in concomitant 
therapies should be recorded throughout the study.
Key safety assessments include AEs, clinical laboratory tests (hematology and chemistry), systolic 
and diastolic blood pressures over time, monitoring for hypersensitivity reactions, AEs temporally 
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
10
Status: Approved, Date: 16 August 2022
associated with infusion, injection-site reactions, suicidality assessment, and early detection of 
active tuberculosis.
Participants who complete the Week 52 visit and achieve a CRR, may have the option to participate 
in a LTE study. 
Due to study termination, only one DBL will occur at the end of study.
An external, independent Data Monitoring Committee (DMC) will be commissioned for this study. 
The DMC will review unblinded data on a periodic basis to ensure the safety of participants 
enrolled in the study. The main focus of the DMC will be on reviewing interim unblinded safety 
data, but the DMC may also review efficacy data needed to ensure the full benefit:risk profile for 
guselkumab. The DMC responsibilities, authorities, and procedures will be documented in a 
separate DMC charter.
NUMBER OF PARTICIPANTS
A target of approximately 60 participants will be randomly assigned in a 1:1 ratio to study 
intervention in this study, with approximately 30 participants planned per intervention group.
INTERVENTION GROUPS AND DURATION
Participants in the study will maintain their standard-of-care treatment of mycophenolate mofetil 
(MMF)/mycophenolic acid (MPA) and background glucocorticoid. Participants’ glucocorticoid 
dose will be tapered. 
Participants will be randomized to 1 of 2 intervention groups in a 1:1 ratio as described below:
!
Guselkumab: Participants will receive guselkumab 400 mg intravenously (IV) at Weeks 0, 4 
and 8 (ie, 3 IV doses) and guselkumab 200 mg subcutaneous (SC) every 4 weeks (q4w) from 
Week 12 through Week 48.
!
Placebo: Participants will receive placebo IV at Weeks 0, 4 and 8 (ie, 3 IV doses) and placebo 
SC q4w from Week 12 through Week 48.
Participants will be stratified by geographic region (North America, Latin America, Asia Pacific 
and Europe) and Urine Protein to Creatinine Ratio (UPCR) level (<3 mg/mg and ≥3 mg/mg).
Participants will remain on their assigned treatment through Week 48. All participants will receive 
an IV infusion (either active or placebo) at Weeks 0, 4, and 8 and 2 SC injections (either active or 
placebo) at Week 12 then q4w through Week 48.
Eligible participants will continue to receive the same study intervention q4w (placebo or 
guselkumab) in the LTE. The first dose in the LTE will be at Week 52. 
The study participants will remain blinded throughout the study (including the LTE). Due to study 
termination, one DBL for the study will occur at the end of study. The end of study will occur after 
all enrolled participants have completed the Week 20 visit or discontinued study intervention prior 
to Week 24, and all participants have completed their final efficacy and safety visits per the SoA. 
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
11
Status: Approved, Date: 16 August 2022
The study schema is provided in Figure 1.
Figure 1:
Schematic Overview of the Study
Abbreviations: CRR=complete renal response; DBL=database lock; F/U=follow-up; LTE=long-term extension; IV=intravenous; MSE=major 
secondary endpoint; N=number of participants; PE=primary endpoint, R=randomization; SC=subcutaneous; SOC=standard-of-care.
2.
STATISTICAL HYPOTHESES
The primary hypothesis of this study is that guselkumab plus standard-of-care is superior to 
placebo plus standard-of-care in participants with active LN as measured by the proportion of 
participants inducing at least a 50% reduction of proteinuria with protocol specified steroid 
tapering regimen at Week 24.
3.
SAMPLE SIZE DETERMINATION
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
The sample size section below is the originally planned sample size.  
Approximately 60 participants are planned to be randomized into the study.
The study will be considered a success if the 1-sided p-value for testing the difference in proportion 
of participants with ≥50% decrease in proteinuria between the guselkumab and placebo 
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
12
Status: Approved, Date: 16 August 2022
intervention groups based on a logistic mixed effect repeat measurement longitudinal model is less 
than a 1-sided alpha level of 10%.
Table 1 shows the sensitivity, with respect to various assumed between group difference, of 
estimated power to detect a difference in proportions of participants with ≥50% decrease in 
proteinuria between the guselkumab and placebo intervention groups at Week 24.
Table 1:
Power to Detect Difference in Proportions of Participants with ≥50% Decrease in Proteinuria 
Between the Guselkumab and Placebo Intervention Groups at Week 24
Difference in proportion of participants with ≥50% 
decrease in proteinuria between the intervention 
groups
Power (%)
20%
56.34
25%
79.61
30%
89.84
35%
96.08
Notes:
•
Proportion of placebo participants with ≥50% decrease in proteinuria is assumed to be 49%.
•
Power calculation is based on 1-sided α of 0.10.
•
Total sample size is 60.
If the proportion of placebo participants with ≥50% decrease in proteinuria is 49%, and the 
difference in proportion between the intervention groups is 30%, a total sample size of 60 with a 
1-sided alpha of 10% will provide approximately 90% power for success.
4.
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
To adapt this study change, one new analysis set is added for the efficacy analysis.  
The populations for analysis are defined in Table 2 below.
Table 2:
Description of analysis sets used to analyze the data in the study.
Analysis Sets
Description
Enrolled
All participants who sign the ICF
Randomized
The randomized analysis set includes all participants 
who were randomized in the study.
Full Analysis Set (FAS)
The FAS includes all randomized participants who 
received at least 1 dose of any study intervention.
Full Analyses Set for Week 52 (FASC52)
The FASC52 includes all randomized participants who 
received at least 1 dose of any study intervention and 
have the opportunity to complete the Week 52 visit prior 
to study termination
Safety
The safety analysis set includes all participants who 
received at least 1 dose of any study intervention.
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
13
Status: Approved, Date: 16 August 2022
Table 2:
Description of analysis sets used to analyze the data in the study.
Analysis Sets
Description
Pharmacokinetics Analysis Set
The PK analysis set is defined as participants who 
received at least 1 dose of any active study intervention 
and have at least 1 valid post initial dose blood sample 
drawn for PK analysis.
Immunogenicity Analysis Set
The immunogenicity analysis set is defined as all 
participants who received at least 1 dose of active study 
intervention and have at least 1 post initial dose sample 
collection.
Biomarker Analysis Set
The biomarker analysis set is defined as participants 
who received at least 1 dose of any study intervention 
and have at least one sample for biomarker analysis
5.
STATISTICAL ANALYSES
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
The statistical analyses section below is the originally planned analyses section. The analyses to 
be summarized in the study CSR will be noted at the beginning of each section below.  For efficacy 
analyses, only the primary and secondary endpoints will be included in the CSR. Selected PK and 
biomarker analyses will be included in the CSR. All safety information collected will be 
summarized in the CSR.  See below for details.   
5.1.
General Considerations
The statistical analyses will include all analyses from Week 0 through Week 60 (the final safety 
follow-up).
In general, baseline is defined as the last observation prior to or at the time of the first study agent 
administration, unless otherwise specified.  
5.1.1.
Visit Windows
Unless otherwise specified, nominal visits will be used for all by visit analyses. The study visits 
scheduled after randomization should occur at the time delineated in the SoA.
5.1.2.
Pooling Algorithm for Analysis Centers
Unless otherwise specified, data from all investigational centers/sites will be pooled for analyses.
5.1.3.
Reference Date, Study Day and Relative Day
The Reference Date is the date of the first study agent administration. If the date of the first study 
agent administration is missing or the first study agent administration is not done, then the 
Reference Date equals the corresponding visit date (eg, Week 0 visit date). If the corresponding 
visit date is also missing, then the Reference Date equals the randomization date.
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
14
Status: Approved, Date: 16 August 2022
Study Day 1 or Day 1 refers to the reference date (there is no Study Day 0). All efficacy and safety 
assessments at all visits will be assigned a day relative to this date.
5.2.
Participant Dispositions
Screened participants and reason for screen failures will be summarized overall.
The number of participants in the following disposition categories will be summarized throughout 
the study by intervention group and overall:
!
Participants randomized
!
Participants who received study intervention
!
Participants who completed the study
!
Participants who discontinued study intervention
∀
Reasons for discontinuation of study intervention (including discontinuation due to 
COVID-19 related reasons)
!
Participants who terminated study prematurely
∀
Reasons for termination of study (including termination due to COVID-19 related 
reasons)
The above categories will include summaries through the end of study.
A listing of participants will be provided for the following categories:
!
Participants who discontinued study intervention
!
Participants who terminated study participation prematurely
!
Participants who were unblinded during the study period
!
Participants who were randomized but did not receive study intervention.
5.3.
Primary Endpoint Analysis
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
For the CSR, the analysis of the primary composite estimand (Section 5.3.2.1) will be performed
using the analysis method specified in Section 5.3.3. All other analyses that are described in this 
section will not be performed for the CSR. 
5.3.1.
Definition of Endpoint(s)
The primary endpoint is the proportion of participants achieving at least 50% decrease in 
proteinuria from baseline at Week 24.  Proteinuria is based on UPCR.
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
Variable specific data handling rules:  Observed data will be used for the analysis.
5.3.2.
Estimands
Primary Trial Objective: To evaluate the efficacy of guselkumab in participants with active LN 
on standard-of-care.
Estimand Scientific Question of Interest: What is the proportion of participants considered to 
have benefited from guselkumab versus placebo for the pre-specified duration (24 weeks), 
administered together with the protocol-allowed background standard-of-care medication?
5.3.2.1.
Primary Estimand (Composite Estimand)
a.
Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
b.
Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism 
(EULAR)/ACR, having a Class III or IV predominant kidney biopsy documentation of 
ISN/RPS proliferative nephritis within the last 6 months prior to or during screening 
despite receiving one or more standard-of-care treatments.
c.
Variable: Responder binary variable, defined as a participant achieving at least 50% 
decrease in proteinuria from baseline at Week 24 who does not:

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (e) below
d.
Summary measure (Population-level summary): Difference in proportion between 
the study interventions
e.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention 
for any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have achieved 
at least 50% decrease in proteinuria after this event, 
the occurrence of this intercurrent event being 
captured in the variable definition.
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Status: Approved, Date: 16 August 2022
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone 
equivalent after Week 12, use of new or 
increased 
dose 
of 
concomitant 
medication related to LN or other 
immunosuppressive agents, within 8 
weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
5.3.2.2.
Supplementary Estimand 1 (Hypothetical)
a. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
b. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism 
(EULAR)/ACR, having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative 
nephritis within the last 6 months prior to or during screening despite receiving one or more 
standard-of-care treatments.
c.
Variable: Responder binary variable, defined as a participant achieving at least 50% decrease 
in proteinuria from baseline at Week 24 
d. Summary measure (Population-level summary): Difference in proportion between the 
study interventions
e.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Hypothetical strategy: The intercurrent event is
addressed with a hypothetical strategy, as if 
these intercurrent events would not have 
occurred.
Medication Intercurrent Event
Hypothetical Strategy: Same as above
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents, within 8 weeks prior to the 
endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Note: Data after the intercurrent event will not be 
utilized in the analysis
Difference from Primary Estimand:  The strategy to address the intercurrent events is to 
assume that participants with this intercurrent event is considered to have missing data at and 
after the event occurred instead of not having achieved at least 50% decrease in proteinuria 
after this event as in the primary estimand.
5.3.2.3.
Supplementary Estimand 2 (Treatment Policy (de Facto))
a. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
b. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism 
(EULAR)/ACR, having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative 
nephritis within the last 6 months prior to or during screening despite receiving one or more 
standard-of-care treatments.
c.
Variable: Responder binary variable, defined as a participant achieving at least 50% decrease 
in proteinuria from baseline at Week 24 
d. Summary measure (Population-level summary): Difference in proportion between the 
study interventions
e.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events 
and Its Description
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
18
Status: Approved, Date: 16 August 2022
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Treatment Policy Strategy: The intercurrent
event addressed with a treatment policy 
strategy, targeting the effect of the 
assignment to the treatment group, regardless 
of the occurrence of the intercurrent events.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents, within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Treatment Policy Strategy: Same as above
Note: Under the Treatment Policy strategy, all 
data are utilized/used, regardless of the 
occurrence of an intercurrent event.
Difference from Primary Estimand:  The strategy to address the intercurrent events is that 
the intercurrent events do not affect the outcome, and the data collected at and after the event 
will be used for analysis, instead of assuming participants have not achieved at least 50% 
decrease in proteinuria after the event as in the primary estimand.
5.3.2.4.
Supplementary Estimand 3 (Composite)
a. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
b. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism 
(EULAR)/ACR, having a Class III or IV predominant kidney biopsy documentation of 
ISN/RPS proliferative nephritis within the last 6 months prior to or during screening despite 
receiving one or more standard-of-care treatments.
c.
Variable: Responder binary variable, defined as a participant achieving at least 50% decrease 
in proteinuria from baseline at Week 24 who does not:

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (e) below
d. Summary measure (Population-level summary): Difference in proportion between the 
study interventions
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
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Status: Approved, Date: 16 August 2022
e.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
worsening of LN
Composite Strategy: A participant with this 
intercurrent event is considered to not have achieved 
at least 50% decrease in proteinuria after this event, 
the occurrence of this intercurrent event being 
captured in the variable definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone equivalent 
after Week 12, use of new or increased dose 
of concomitant medication related to LN or 
other immunosuppressive agents, within 8 
weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Difference from Primary Estimand:  The intercurrent event “discontinuation of study 
intervention for any reason” is changed to “discontinuation of study intervention for 
worsening of LN”.
5.3.2.5.
Supplementary Estimand 4 (Composite)
a. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
b. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism 
(EULAR)/ACR, having a Class III or IV predominant kidney biopsy documentation of 
ISN/RPS proliferative nephritis within the last 6 months prior to or during screening despite 
receiving one or more standard-of-care treatments.
c.
Variable: Responder binary variable, defined as a participant achieving at least 50% decrease 
in proteinuria from baseline at Week 24 who does not:

discontinue study intervention for any reason or

meet the Medication Intercurrent Event in Section (e) below
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
d. Summary measure (Population-level summary): Difference in proportion between the 
study interventions
e.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention 
for any reason excluding COVID-19 related 
discontinuations 
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved at least 50% decrease in proteinuria after 
this event, the occurrence of this intercurrent event 
being captured in the variable definition.  
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive
agents, within 8 weeks prior to the 
endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Discontinued study intervention due to 
COVID-19 related reasons
Hypothetical strategy: The intercurrent event is
addressed with a hypothetical strategy, as if 
these intercurrent events would not have 
occurred.
Note: Data after the intercurrent event will not be 
utilized in the analysis
Difference from Primary Estimand:  For discontinuations due to COVID-19 related event 
or situations, the participant’s data after the event will not be used after the intercurrent event.
5.3.2.6.
Supplementary Estimand 5 (Composite)
a. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
b. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism 
(EULAR)/ACR, having a Class III or IV predominant kidney biopsy documentation of 
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
21
Status: Approved, Date: 16 August 2022
ISN/RPS proliferative nephritis within the last 6 months prior to or during screening despite 
receiving one or more standard-of-care treatments.
c.
Variable: Responder binary variable, defined as a participant achieving at least 50% decrease 
in proteinuria from baseline at Week 24 who does not:

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (e) below
d. Summary measure (Population-level summary): Difference in proportion between the 
study interventions
e.
Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention 
for any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved at least 50% decrease in proteinuria after 
this event, the occurrence of this intercurrent event 
being captured in the variable definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone 
equivalent after Week 12, use of new or 
increased
dose 
of
concomitant 
medication related to LN or other 
immunosuppressive agents
3.
Initiation of prohibited medications at 
any time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
4. Difference from Primary Estimand:  The first Medication Intercurrent Event, “Increase 
above 10 mg/d prednisone equivalent, use of new or increased dose of concomitant medication 
related to LN or other immunosuppressive agents” can occur at any time after Week 12, not 
just within 8 weeks prior to the endpoint.
5.3.3.
Analysis Methods
Unless otherwise specified, the population for analysis will be the FAS defined in Section 4 for 
the primary and its respective sensitivity analyses.
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
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Status: Approved, Date: 16 August 2022
Simple descriptive statistics, such as n, mean, standard deviation (SD), median, interquartile (IQ)
range, minimum and maximum for continuous variables and counts and percentages for discrete 
variables will be used to summarize most data.
For the primary analysis, the primary composite estimand will be targeted.
Generalized linear model with logit link for a binary mixed effects repeated measures model 
(MMRM) will be used to analyze the data.  The model will include all available observed data 
after applying intercurrent events with treatment, visit, region, baseline UPCR level (<3 mg/mg 
and ≥3 mg/mg), and treatment and visit interaction in the model will be used to analyze the data.  
The 1-sided p-value from the difference in proportion of participants with ≥50% decrease in 
proteinuria from baseline at Week 24 between the intervention groups will be provided.  In 
addition, the estimate and its 80% confidence interval (CI) estimated from the model will also be 
provided.
5.3.4.
Supplementary Analyses
5.3.4.1.
Supplementary Analysis 1 (Supplementary Estimand 1 (Hypothetical))
The primary endpoint will be analyzed using the Supplementary Estimand 1 (Hypothetical).  A
Cochran-Mantel-Haenszel (CMH) test stratified by region, baseline UPCR level (<3 mg/mg, ≥3 
mg/mg) will be used to analyze the data.  An 80% CI for the difference in study intervention will 
be provided based on the Wald statistic.
5.3.4.2.
Supplementary Analysis 2 (Supplementary Estimand 1 (Hypothetical))
The primary endpoint will be analyzed using the Supplementary Estimand 1 (Hypothetical).  
Missing data will be imputed using multiple imputation methods. The imputation model will 
include study intervention, region, baseline UPCR level (<3 mg/mg and ≥3 mg/mg), race (African 
vs non-African) as covariates.  300 imputed datasets will be created.  A CMH test stratified by 
region, baseline UPCR level (< 3 mg/mg, ≥3 mg/mg) will be used to obtain the CMH test statistic
for each imputed dataset. A Wilson Hilferty transformation was used to aggregate estimates and 
obtain overall p-value for the CMH test.
5.3.4.3.
Supplementary Analysis 3 (Supplementary Estimand 2 (Treatment 
Policy))
The primary endpoint will be analyzed utilizing the Supplementary Estimand 2 (Treatment Policy). 
The analysis method for the primary analysis in Section 5.3.3 will be used.
5.3.4.4.
Supplementary Analysis 4 (Supplementary Estimand 3 (Composite))
The primary endpoint will be analyzed utilizing the Supplementary Estimand 3 (Composite). The 
analysis method for the primary analysis in Section 5.3.3 will be used.
5.3.4.5.
Supplementary Analysis 5 (Supplementary Estimand 4 (Composite))
The primary endpoint will be analyzed utilizing the Supplementary Estimand 4 (Composite). The 
analysis method for the Supplementary Analysis 1 (Section 5.3.4.1) will be used.
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
5.3.4.6.
Supplementary Analysis 6 (Supplementary Estimand 5 (Composite))
The primary endpoint will be analyzed utilizing the Supplementary Estimand 5 (Composite). The 
analysis method for the primary analysis in Section 5.3.3 will be used.
5.3.5.
Sensitivity Analyses
5.3.5.1.
Sensitivity Analysis 1 (Primary Composite Estimand)
“Tipping Point” via exhaustive scenarios will be used.  A two-dimensional tipping point analysis 
of exhaustive scenarios for all missing data at Week 24 will be performed on the primary endpoint 
to evaluate the missing at random assumption for the Composite Estimand.  For participants with 
missing proteinuria data at Week 24, the data will be imputed in an increasing manner by 
participant for each treatment intervention.  Specifically, imputation starts where all participants
do not achieve 50% decrease in proteinuria up to the scenario where all participants achieved 50% 
decrease in proteinuria.  This would include all possible scenarios including scenarios where 
participants on guselkumab have worse outcomes than participants on placebo.  The analysis 
method for the primary analysis in Section 5.3.3 will be used.
5.3.5.2.
Sensitivity Analysis 2 (Supplementary Estimand 2 (Treatment Policy))
“Tipping Point” via exhaustive scenarios as in Sensitivity Analysis 1 will be performed on the 
Supplementary Estimand 2 (Treatment Policy).  The analysis method for the primary analysis in 
Section 5.3.3 will be used.
5.4.
Secondary Endpoint(s) Analysis
Early Termination Note:  Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.   
For secondary endpoints in the CSR, only analysis of the main estimand for each secondary 
endpoint that is listed below will be performed using the analysis methods specified in 
Sections 5.4.2.3.1 and 5.4.2.3.2:
!
Proportion of participants achieving complete renal response (CRR) at Week 24 
(Section 5.4.2.2.1)
!
Proportion of participants achieving a sustained reduction in steroid dose ≤10 mg/day of 
prednisone or equivalent from Week 16 to Week 24 (Section 5.4.2.2.2.1)
!
Proportion of participants achieving at least 50% decrease in proteinuria from baseline at 
Week 52 (Section 5.4.2.2.3.1)
!
Proportion of participants achieving CRR at Week 52 (Section 5.4.2.2.4.1)
!
Proportion of participants with UPCR <0.5 mg/mg at Week 24 (Section 5.4.2.2.5)
!
Proportion of participants with UPCR <0.75 mg/mg at Week 24 (Section 5.4.2.2.6)
!
Time to achievement of CRR (Section 5.4.2.2.7.1)
!
Time to treatment failure (TF) (Section 5.4.2.2.8)
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
The analysis population will be the FAS except for the endpoints at Week 52, for which the 
FASC52 analysis set will be used.
All other analyses that are described in this section will not be performed for the CSR.
5.4.1.
Multiplicity Adjustment for Testing Procedures
No multiplicity adjustments will be made for any testing procedures.
5.4.2.
Key Confirmatory Secondary Endpoint(s)
Objective:  To evaluate the efficacy of guselkumab in participants with active LN  
The secondary endpoints are the following:
1. Proportion of participants achieving complete renal response (CRR) at Week 24
2. Proportion of participants achieving a sustained reduction in steroid dose ≤10 mg/day of 
prednisone or equivalent from Week 16 to Week 24
3. Proportion of participants achieving at least 50% decrease in proteinuria from baseline at Week 
52
4. Proportion of participants achieving CRR at Week 52 
5. Proportion of participants with UPCR <0.5 mg/mg at Week 24
6. Proportion of participants with UPCR <0.75 mg/mg at Week 24
7. Time to achievement of CRR
8. Time to treatment failure (TF)
5.4.2.1.
Definition of Endpoint(s)
5.4.2.1.1.
Complete Renal Response (CRR)
Complete renal response (CRR) is defined as :
-Urine Protein to Creatinine Ratio (UPCR) <0.5 mg/mg (alternative thresholds of 0.75, and 
possibly others will be examined, separately).
AND
∀
Estimated Glomerular Filtration Rate (eGFR) ≥60 mL/min/m2 or no confirmed decrease 
≥20% from baseline. 
AND
∀
Prednisone dose ≤10 mg/d. 
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
25
Status: Approved, Date: 16 August 2022
5.4.2.1.2.
Complete Renal Response 50% Pred (CRR – 50% Pred)
Complete Renal Response 50% Pred is defined as CRR above (Section 5.4.2.1.1 except for 
prednisone dose, whereby if a participant enters the study with baseline prednisone of 10 mg/d, 
then the prednisone dose must be <10 mg/d with at least a 50% reduction in dose.
5.4.2.1.3.
Glucocorticoid (Prednisone or Prednisone Equivalent) Reduction
1. Participants with a sustained reduction in steroid dose ≤10 mg/day of prednisone or 
equivalent are participants who sustained a continuous reduction in steroid to ≤10 
mg/day of prednisone or equivalent for the time duration measured.
The average daily dose for any given day is the average of the last available (non-
missing) values within 7 days, including the day of interest.
2. Reduction of glucocorticoid dose is defined as:
!
A reduction in average daily oral glucocorticoid dose down to ≤10 mg/day by 
Week 12 
and
!
at least a 50% decrease from baseline dose.
3. Other considerations to meet sustained reduction of glucocorticoid dose include
Dose adjustments after starting reduction of glucocorticoid dose are permitted and 
participants will still be considered to have sustained reduction unless they return to 
or exceed their baseline (Week 0) dose. These dose adjustments are permitted up to 
the Week 12 visit only. 
Note: 10 mg of prednisone equivalent is used here although the tapering target is 5 
mg.  Dose increases above 10 mg of prednisone equivalent or above 50% of baseline 
dose after Week 12 will not be considered as sustained reduction in glucocorticoids.
5.4.2.1.4.
Time to Achievement of Complete Renal Response (CRR)
Time to achievement of CRR is defined as the time to the first observation of CRR from baseline.
5.4.2.1.5.
Time to Treatment Failure (TF)
Time to TF is defined as time to the first occurrence of TF from baseline.  TF is defined as the 
intercurrent events for the Supplementary Composite Estimand 5 of the primary endpoint in 
Section 5.3.2.6.
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
26
Status: Approved, Date: 16 August 2022
5.4.2.2.
Estimand(s)
5.4.2.2.1.
Proportion of Participants Achieving Complete Renal Response 
(CRR) at Week 24
Composite Estimand 
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Responder binary variable, defined as a participant achieving Complete Renal 
Response (CRR) at Week 24 who does not:

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (5) below
4. Summary measure (Population-level summary): Difference in proportion between the 
study interventions
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved CRR after this event, the occurrence of 
this intercurrent event being captured in the variable 
definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents, within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
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Status: Approved, Date: 16 August 2022
5.4.2.2.2.
Proportion of Participants Achieving a Sustained Reduction in 
Steroid Dose ≤10 mg/day of Prednisone or Equivalent from Week 16 
to Week 24
5.4.2.2.2.1.
Main Estimand (Composite)
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Responder binary variable, defined as a participant achieving a sustained reduction 
in steroid dose ≤10 mg/day of prednisone or equivalent from Week 16 to Week 24
4. Summary measure (Population-level summary): Difference in proportion between the 
study interventions
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved  Sustained Reduction in Steroid Dose after 
this event, the occurrence of this intercurrent event 
being captured in the variable definition.
Medication Intercurrent Event
1.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
5.4.2.2.2.2.
Supplementary Estimand (Treatment Policy (de Facto))
All attributes (1-4) of the supplementary estimand are the same as above main estimand
(Section 5.4.2.2.2.1) except for the intercurrent events, where a treatment policy strategy is 
used instead.
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CNTO1959  (Guselkumab)
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Status: Approved, Date: 16 August 2022
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Treatment Policy Strategy: The intercurrent event 
addressed with a treatment policy strategy, 
targeting the effect of the assignment to the 
treatment group, regardless of the occurrence 
of the intercurrent events.
Medication Intercurrent Event
1.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Treatment Policy Strategy: Same as above
Note: Under the Treatment Policy strategy, all data 
are utilized/used, regardless of the occurrence of an 
intercurrent event.
Difference from Main Estimand:  The treatment policy strategy is used instead of the 
composite strategy.
5.4.2.2.3.
Proportion of Participants Achieving at Least 50% Decrease in 
Proteinuria from Baseline at Week 52
5.4.2.2.3.1.
Main Estimand 
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Responder binary variable, defined as a participant achieving at least 50% decrease 
in proteinuria from baseline at Week 52 who does not:

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (5) below
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
29
Status: Approved, Date: 16 August 2022
4. Summary measure (Population-level summary): Difference in proportion between the study 
interventions
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have achieved 
50% decrease in proteinuria after this event, the 
occurrence of this intercurrent event being captured 
in the variable definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone equivalent 
after Week 12, use of new or increased dose 
of concomitant medication related to LN or 
other immunosuppressive agents, within 8 
weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Sustained increase of prednisone equivalent 
between Week 24 and Week 44 is allowed up to 
40 mg/d for ≤10 days once for non-SLE/LN 
treatment (eg, COPD, asthma, contact dermatitis).
Treatment Policy Strategy: The intercurrent event 
addressed with a treatment policy strategy, 
targeting the effect of the assignment to the 
treatment group, regardless of the occurrence of 
the intercurrent events.
Note: Under the Treatment Policy strategy, all data 
are utilized/used, regardless of the occurrence of an 
intercurrent event.
5.4.2.2.3.2.
Supplementary Estimand
All attributes (1-4) of the supplementary estimand are the same as above main estimand 
(Section 5.4.2.2.3.1) except for the intercurrent events, where the treatment policy strategy is 
omitted.
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
30
Status: Approved, Date: 16 August 2022
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved 50% decrease in proteinuria after this 
event, the occurrence of this intercurrent event 
being captured in the variable definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Difference from Main Estimand:  Participants with sustained increase of prednisone 
equivalent between Week 24 and Week 44  will not be allowed up to 40 mg/d for ≤10 days 
once for non-SLE/LN treatment (eg, COPD, asthma, contact dermatitis), and will not achieve 
CRR after the event.
5.4.2.2.4.
Proportion of Participants Achieving CRR at Week 52 
5.4.2.2.4.1.
Main estimand
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Responder binary variable, defined as a participant achieving CRR at Week 52 who 
does not:
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
31
Status: Approved, Date: 16 August 2022

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (5) below
4.  Summary measure (Population-level summary): Difference in proportion between the study 
interventions
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved CRR after this event, the occurrence of 
this intercurrent event being captured in the variable 
definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents, within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Sustained increase of prednisone equivalent 
between Week 24 and Week 44 is allowed up to 
40 mg/d for ≤10 days once for non-SLE/LN 
treatment (eg, COPD, asthma, contact 
dermatitis).
Treatment Policy Strategy: The intercurrent event 
addressed with a treatment policy strategy, 
targeting the effect of the assignment to the 
treatment group, regardless of the occurrence 
of the intercurrent events.
Note: Under the Treatment Policy strategy, all data 
are utilized/used, regardless of the occurrence of an 
intercurrent event.
5.4.2.2.4.2.
Supplementary Estimand 1
All attributes (1-4) of the supplementary estimand are the same as above main estimand
(Section 5.4.2.2.4.1) except for the intercurrent events, where the treatment policy strategy is 
omitted.
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
32
Status: Approved, Date: 16 August 2022
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved CRR after this event, the occurrence of 
this intercurrent event being captured in the variable 
definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Difference from Main Estimand:  Participants with sustained increase of prednisone 
equivalent between Week 24 and Week 44  will not be allowed up to 40 mg/d for ≤10 days 
once for non-SLE/LN treatment (eg, COPD, asthma, contact dermatitis), and will not achieve 
CRR after the event.
5.4.2.2.4.3.
Supplementary Estimand 2
All attributes (1-4) of the supplementary estimand are the same as above main estimand 
(Section 5.4.2.2.4.1) except for the intercurrent events, where a composite strategy is added 
for participants not achieving CRR due to intercurrent events at Week 24 will also be non-
achievers through Week 52.
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Participants who do not achieve CRR due to 
intercurrent events at Week 24 will also be non-
achievers through Week 52
Composite Strategy: A participant with this 
intercurrent event is considered to not have achieved 
CRR after this event, the occurrence of this 
intercurrent event being captured in the variable 
definition.
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: Same as above
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CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
33
Status: Approved, Date: 16 August 2022
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone equivalent 
after Week 12,  use of new or increased dose 
of concomitant medication related to LN or 
other immunosuppressive agents, within 8 
weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Sustained increase of prednisone equivalent 
between Week 24 and Week 44 is allowed up to 
40 mg/d for ≤10 days once for non-SLE/LN 
treatment (eg, COPD, asthma, contact dermatitis).
Treatment Policy Strategy: The intercurrent event 
addressed with a treatment policy strategy, 
targeting the effect of the assignment to the 
treatment group, regardless of the occurrence of 
the intercurrent events.
Note: Under the Treatment Policy strategy, all data 
are utilized/used, regardless of the occurrence of an 
intercurrent event.
Difference from Main Estimand:  Participants who do not achieve CRR due to intercurrent 
events at Week 24 will also be non-achievers through Week 52.
5.4.2.2.4.4.
Supplementary Estimand 3
All attributes (1-4) of the supplementary estimand are the same as above Main Estimand 
(Section 5.4.2.2.4.1) except for the intercurrent events, where the treatment policy strategy is 
omitted, and a composite strategy is added for participants not achieving CRR due to 
intercurrent events at Week 24 will also be non-achievers through Week 52.
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
34
Status: Approved, Date: 16 August 2022
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Participants who do not achieve CRR due to 
intercurrent events at Week 24 will also be non-
achievers through Week 52
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved CRR after this event, the occurrence of 
this intercurrent event being captured in the variable 
definition.
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: Same as above
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
Difference from main estimand:  Participants who do not achieve CRR due to intercurrent 
events at Week 24 will also be non-achievers through Week 52.  In addition, participants with 
sustained increase of prednisone equivalent between Week 24 and Week 44  will not be 
allowed up to 40 mg/d for ≤10 days once for non-SLE/LN treatment (eg, COPD, asthma, 
contact dermatitis), and will not achieve CRR after the event.
5.4.2.2.5.
Proportion of Participants with Urine Protein to Creatinine Ratio 
(UPCR) <0.5 mg/mg at Week 24
Composite Estimand 
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
35
Status: Approved, Date: 16 August 2022
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Responder binary variable, defined as a participant with UPCR <0.5 mg/mg at 
Week 24 who does not:

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (5) below
4. Summary measure (Population-level summary): Difference in proportion between the study 
interventions
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved UPCR <0.5 mg/mg after this event, the 
occurrence of this intercurrent event being captured 
in the variable definition.
Medication Intercurrent Event
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents, within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Composite Strategy: Same as above
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
36
Status: Approved, Date: 16 August 2022
5.4.2.2.6.
Proportion of Participants with UPCR <0.75 mg/mg at Week 24
Composite Estimand 
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Responder binary variable, defined as a participant with UPCR <0.75 mg/mg at 
Week 24 who does not:

discontinue study intervention for any reason excluding COVID-19 related 
discontinuations or

meet the Medication Intercurrent Event in Section (5) below
4. Summary measure (Population-level summary): Difference in proportion between the study 
interventions
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this
intercurrent event is considered to not have 
achieved UPCR <0.75 mg/mg after this event, the 
occurrence of this intercurrent event being captured 
in the variable definition.
Medication Intercurrent Event
Composite Strategy: Same as above
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
37
Status: Approved, Date: 16 August 2022
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents, within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
5.4.2.2.7.
Time to Achievement of CRR through Week 24 and 52
5.4.2.2.7.1.
Main Estimand 
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Time to CRR 
4. Summary measure (Population-level summary): Hazard ratio of the guselkumab intervention 
group vs. the placebo intervention group
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved CRR after this event, the occurrence of 
this intercurrent event being captured in the variable 
definition.
Medication Intercurrent Event
Composite Strategy: Same as above
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
38
Status: Approved, Date: 16 August 2022
1.
Exceeding baseline glucocorticoid dose 
2.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents within 8 weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Sustained increase of prednisone equivalent 
between Week 24 and Week 44 is allowed up to 
40 mg/d for ≤10 days once for non-SLE/LN 
treatment (eg, COPD, asthma, contact 
dermatitis).
Treatment Policy Strategy: The intercurrent event 
addressed with a treatment policy strategy, targeting 
the effect of the assignment to the treatment group, 
regardless of the occurrence of the intercurrent 
events.
Note: Under the Treatment Policy strategy, all data 
are utilized/used, regardless of the occurrence of an 
intercurrent event.
5.4.2.2.7.2.
Supplementary Estimand 1 for Time to Achievement of CRR 
through Week 52
All attributes (1-4) of the supplementary estimand are the same as above (Section 5.4.2.2.7.1) 
except for the intercurrent events, where a composite strategy is added for participants not 
achieving CRR due to intercurrent events at Week 24 will also be non-achievers through 
Week 52.
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Participants who do not achieve CRR due to 
intercurrent events at Week 24 will also be non-
achievers through Week 52
Composite Strategy: A participant with this 
intercurrent event is considered to not have achieved 
CRR after this event, the occurrence of this 
intercurrent event being captured in the variable 
definition.
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: Same as above
Medication Intercurrent Event
Composite Strategy: Same as above
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
39
Status: Approved, Date: 16 August 2022
4.
Exceeding baseline glucocorticoid dose 
5.
Increase above 10 mg/d prednisone equivalent 
after Week 12, use of new or increased dose 
of concomitant medication related to LN or 
other immunosuppressive agents, within 8 
weeks prior to the endpoint
6.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Sustained increase of prednisone equivalent 
between Week 24 and Week 44 is allowed up to 
40 mg/d for ≤10 days once for non-SLE/LN 
treatment (eg, COPD, asthma, contact dermatitis).
Treatment Policy Strategy: The intercurrent event 
addressed with a treatment policy strategy, targeting 
the effect of the assignment to the treatment group, 
regardless of the occurrence of the intercurrent 
events.
Note: Under the Treatment Policy strategy, all data 
are utilized/used, regardless of the occurrence of an 
intercurrent event.
Difference from Main Estimand:  Participants who do not achieve CRR due to intercurrent 
events at Week 24 will also be non-achievers through Week 52.
5.4.2.2.7.3.
Supplementary Estimand 2 for Time to Achievement of CRR 
through Week 52
All attributes (1-4) of the supplementary estimand are the same as above main estimand
(Section 5.4.2.2.7.1) except for the intercurrent events, where only a composite strategy is 
used instead.
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: A participant with this 
intercurrent event is considered to not have achieved 
CRR after this event, the occurrence of this 
intercurrent event being captured in the variable 
definition.
Medication Intercurrent Event
Composite Strategy: Same as above
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
40
Status: Approved, Date: 16 August 2022
1.
Exceeding baseline glucocorticoid dose 
2.
Increase above 10 mg/d prednisone equivalent 
after Week 12, use of new or increased dose 
of concomitant medication related to LN or 
other immunosuppressive agents within 8 
weeks prior to the endpoint
3.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Difference from Main Estimand:  Participants with sustained increase of prednisone 
equivalent between Week 24 and Week 44  will not be allowed up to 40 mg/d for ≤10 days 
once for non-SLE/LN treatment (eg, COPD, asthma, contact dermatitis), and will not achieve 
CRR after the event.
5.4.2.2.7.4.
Supplementary Estimand 3 for Time to Achievement of CRR 
through Week 52
All attributes (1-4) of the supplementary estimand are the same as above Main Estimand
(Section 5.4.2.2.7.1) except for the intercurrent events, where the treatment policy strategy is 
omitted, and a composite strategy is added for participants not achieving CRR due to 
intercurrent events at Week 24 will also be non-achievers through Week 52.
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
Participants who do not achieve CRR due to 
intercurrent events at Week 24 will also be non-
achievers through Week 52
Composite Strategy: A participant with this 
intercurrent event is considered to not have 
achieved CRR after this event, the occurrence of 
this intercurrent event being captured in the variable 
definition.
Discontinuation (DC) of study intervention for 
any reason excluding COVID-19 related 
discontinuations
Composite Strategy: Same as above
Medication Intercurrent Event
Composite Strategy: Same as above
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
41
Status: Approved, Date: 16 August 2022
4.
Exceeding baseline glucocorticoid dose 
5.
Increase 
above 
10 
mg/d 
prednisone 
equivalent after Week 12, use of new or 
increased dose of concomitant medication 
related to LN or other immunosuppressive 
agents within 8 weeks prior to the endpoint
6.
Initiation of prohibited medications at any 
time prior to the endpoint
Note: adjustments in glucocorticoids are 
permitted up to and including Week 12. 
Nonsystemic glucocorticoids, NSAIDs, 
antimalarials and topical agents will not be 
considered an intercurrent event.
Difference from main estimand:  Participants who do not achieve CRR due to intercurrent 
events at Week 24 will also be non-achievers through Week 52.  In addition, participants with 
sustained increase of prednisone equivalent between Week 24 and Week 44  will not be 
allowed up to 40 mg/d for ≤10 days once for non-SLE/LN treatment (eg, COPD, asthma, 
contact dermatitis), and will not achieve CRR after the event.
5.4.2.2.8.
Time to treatment failure (TF)
Treatment Policy Estimand 
1. Study intervention:

Guselkumab (experimental treatment/intervention) in addition to standard-of-care

Placebo in addition to standard-of-care
2. Population: Participants between 18 and 75 with active LN (defined by meeting the 
classification criteria for SLE by the 2019 European League Against Rheumatism (EULAR)/ACR, 
having a Class III-IV kidney biopsy documentation of ISN/RPS proliferative nephritis within the 
last 6 months prior to or during screening despite receiving one or more standard-of-care 
treatments.
3. Variable: Time to TF 
4. Summary measure (Population-level summary): Hazard ratio of the guselkumab intervention 
group vs. the placebo intervention group
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
42
Status: Approved, Date: 16 August 2022
5. Intercurrent events and their corresponding strategies:
Intercurrent Events
Strategy for Addressing Intercurrent Events and 
Its Description
No intercurrent events for this endpoint
NA
5.4.2.3.
Analysis Methods
Unless otherwise specified, the analysis population will be the FAS defined in Section 4.  The 
endpoints will be summarized by study intervention groups.
Simple descriptive statistics, such as n, mean, SD, median, IQ range, minimum and maximum for 
continuous variables and counts and percentages for discrete variables will be used to summarize 
most data.
5.4.2.3.1.
Binary Endpoints (Secondary Endpoints 1-6)
Analyses for binary secondary endpoints (proportion of response, improvement, reduction) will 
be based upon the estimands in Section 5.4.2.2.1 through Section 5.4.2.2.6.  
Generalized linear model with logit link for a binary MMRM will be used to analyze the data for 
Secondary Endpoints 1 and 3-6 (main and supplementary).  The model will include all available 
observed data after applying intercurrent events with treatment, visit, region, baseline UPCR level 
(<3 mg/mg and ≥3 mg/mg), and treatment and visit interaction in the model will be used to analyze 
the data.  The 1-sided p-value from the difference in proportion of participants between the 
intervention groups will be provided.  In addition, the estimate and its 80% CI estimated from the 
model will also be provided.
Logistic regression model will be used to analyze Secondary Endpoint 2 (main and supplementary). The
model will include treatment, region, and baseline UPCR level (<3 mg/mg and ≥3 mg/mg). The 1-sided p-
value, the odds ratio and the corresponding 80% CI between the intervention groups from the model will 
be provided.
5.4.2.3.2.
Time to Event Endpoints (Secondary Endpoints 7-8)
Analyses for time to event endpoints will be based upon the estimands in Section 5.4.2.2.7
through Section 5.4.2.2.8.
The hazard ratio will be estimated using the Cox proportional hazards model, adjusting for region, 
baseline UPCR level (<3 mg/mg and ≥3 mg/mg), and its 80% CI will be calculated. The 
proportional hazards assumption will be verified with appropriate methods (e.g. log-minus-log 
plots) as part of the analysis.  The reported p-values for time to first flare analyses will be derived 
from a log-rank test. The survival curves will be estimated using Kaplan-Meier estimates. 
In general, point estimates and 80% CIs for comparison between treatment groups will be reported.
NCT04376827


CNTO1959  (Guselkumab)
Statistical Analysis Plan CNTO1959LUN2001
CONFIDENTIAL – FOIA Exemptions Apply in U.S.
43
Status: Approved, Date: 16 August 2022
5.4.2.3.3.
Sensitivity Analysis of the CRR endpoint using CRR-50% Pred 
definition
Secondary endpoints 1 and 4 will be analyzed using the same estimands as in Section 5.4.2.2.1
and 5.4.2.2.4.  The difference is that the definition of CRR is replaced with CRR - 50% Pred 
(Section 5.4.2.1.2).
5.5.
Tertiary/Exploratory Endpoint(s) Analysis
Early Termination Note:  Due to the Sponsor’s decision to stop screening of new participants 
as a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The 
end of study will occur after all enrolled participants have completed the Week 20 visit or 
discontinued study intervention prior to Week 24, and all participants have completed their final 
efficacy and safety visits per the SoA.
For the CSR, the analyses of tertiary/exploratory endpoints that are described in this section will 
not be performed.
Objective: To evaluate the efficacy of guselkumab in extrarenal lupus manifestations
The tertiary/exploratory endpoints to address the objective above are the following:
1.
Proportion of participants with ≥4-point improvement at Week 24 in systemic lupus 
erythematosus disease activity index 2000 (SLEDAI-2K) modified to exclude renal items
2.
Proportion of participants with baseline arthritis (with at least 4 active joints at baseline) 
who have ≥50% reduction in active joints at Week 24
3.
Proportion of participants with baseline active mucocutaneous lupus manifestations 
(CLASI score ≥8) and ≥50% reduction in Cutaneous Lupus Erythematosus Disease Area 
and Severity Index (CLASI) scores at Week 24
Objective: To evaluate the impact of guselkumab on Health-Related Quality of Life (HRQoL) 
and fatigue in participants with active LN
The tertiary/exploratory endpoints to address the objective above are the following:
4.
Change from baseline in Lupus Quality of Life (LupusQoL) individual domains at 
Week 24 
5.
Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-
fatigue score at Week 24
6.
Change from baseline in lupus symptoms (joint pain, joint stiffness, rash, and swelling 
[peripheral edema]) at Week 24 
7.
Patient Global Impression of Change (PGIC) - Change in LN (health condition) at 
Week 24 and Week 52
Note:  Other timepoints for these analyses will also be analyzed (Section 5.6).
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5.5.1.
Definition of Endpoint(s)
5.5.1.1.
Four (4) Points Improvement from Baseline in SLE Disease Activity 
Index 2000 (SLEDAI-2K) Modified to Exclude Renal Items
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; the index 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 (Touma Z, et al, 2010; Touma Z, et al 2011b)  The baseline measurement for the 
SLEDAI-2K is defined as the closest measurement taken prior to the initiation of the Week 0 study 
intervention administration.
SLEDAI improvement is defined as a reduction from baseline in total SLEDAI-2K score. No 
worsening of total SLEDAI-2K from baseline is defined as a change ≤0 in SLEDAI-2K score and 
meaningful improvement is best defined as a reduction in SLEDAI-2 K of 4 or more.
The SLEDAI-2K score will be calculated excluding the renal items (i.e., urinary casts, hematuria, 
proteinuria, pyuria).
5.5.1.2.
Active Joints, Tender Joints, Swollen Joints
Assessment of active joints (defined as joints demonstrating tenderness and signs of 
inflammation), tender joints, and swollen joints will be performed at visits indicated in the SoA of 
the protocol. To be considered an active joint, an affected joint must demonstrate tenderness and 
at least one additional sign of inflammation (eg, observed swelling such as edema or effusion) on 
physical examination as determined by the joint assessor. Each of 28 joints will be evaluated for 
tenderness and swelling.
The joint assessment should be performed by an adequately trained joint assessor. Training on how 
the joint count will be performed will be provided by the Sponsor. An independent joint assessor 
would be preferred but if not available at the site, is not mandatory. It is strongly recommended 
that the same joint assessor perform these assessments at every visit. It is recommended that the 
designated assessor identify an appropriate back-up joint assessor in case the designated joint 
assessor is unavailable. 
The arthritis score on the SLEDAI-2K should be in agreement with the active joint count 
assessment as calculated in the eCRF.
The endpoint is defined as a ≥50% reduction in active joints at Week 24 from baseline among 
participants with baseline arthritis (with at least 4 active joints at baseline).  
5.5.1.3.
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
(CLASI) score
Cutaneous lupus disease activity and severity will be measured by the CLASI. The CLASI is an 
instrument to assess the disease activity and damage caused to the skin for cutaneous lupus 
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erythematosus (CLE) patients with or without systemic involvement (Albrecht J, et al, 2005). The 
CLASI consists of 2 scores; the first summarizes the activity of the disease while the second is a 
measure of the damage caused by the disease (CLASI Activity and CLASI Damage scores). 
Activity is scored by the Investigator based on 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 (Albrecht J, et al, 2005).
!
CLASI scores range from 0-70 for activity and 0-56 for damage, with higher scores indicating 
worse disease activity.
The endpoint is defined as a ≥50% reduction in CLASI score from baseline among participants 
with baseline active mucocutaneous lupus manifestations (CLASI ≥8).  CLASI Activity and 
CLASI Damage will be analyzed independently.
5.5.1.4.
Lupus Quality of Life Questionnaire
The LupusQoL questionnaire is a valid, lupus-specific HRQoL instrument consisting of 34 items 
across 8 domains (Physical health, Emotional health, Body image, Pain, Planning, Fatigue, 
Intimate relationships, and Burden to others) for self-administration. The final LupusQoL has a 
5-point Likert response format, where 0=all the time, 1=most of the time, 2=a good bit of the time, 
3=occasionally, and 4=never, and uses a 4-week recall period. The LupusQoL is scored by domain, 
with a higher score reflecting better HRQoL (McElhone K, et al, 2007).
5.5.1.5.
FACIT-fatigue
The FACIT-fatigue version 4.0 is a 13-item questionnaire formatted for self-administration that 
assesses patient-reported fatigue and its impact upon daily activities and function over the past 7 
days. Participants will be asked to answer each question using a 5-point Likert-type scale (0=Not 
at all; 1=A little bit; 2=Somewhat; 3=Quite a bit; and 4=Very Much). The interpretation of FACIT-
fatigue scores is such that a higher score indicates less fatigue, with a range of possible scores of 
0-52, with 0 being the worst possible score and 52 the best (FACIT, Lai J, et al, 2011) 
Questions 1-6 and 9-13 are scored in reverse order. If 7 or more questions are answered, then the
score can be calculated and is adjusted by the number of available questions.
5.5.1.6.
Lupus Symptoms
Participants will be asked to report their worst severity of their joint pain, joint stiffness, skin rash, 
and swelling in legs and/or feet over the past 7 days on a 0 to 10 numeric rating scale, with the left 
anchor indicating “No [specific symptom]” and the right anchor, “Severe [specific symptom]”. 
The items are scored individually, with higher scores reflecting greater symptom severity. The 
administration frequency is described in the SoA of the protocol.
5.5.1.7.
Patient Global Impression of Change
The PGIC in LN is a 1-item questionnaire based on the clinical global impressions assessment and 
is designed to assess a patient’s impression of the change in their health condition subsequent to 
receiving study treatment (Guy W, 1976). PGIC is a 7-point scale depicting a patient's rating of 
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overall change in their health condition following treatment. Patients rate their change in their LN 
since baseline by choosing one of the following response options: “very much improved,” “much 
improved,” “minimally improved,” “no change,” “minimally worse,” “much worse,” or “very 
much worse.” The PGIC will also serve as an anchor measure to explore clinically meaningful 
change thresholds for the other patient-reported outcome measures included in the study.
5.5.2.
Analysis Methods
Unless otherwise specified, the analysis population will be the FAS defined in Section 4.  The 
endpoints will be summarized by randomized study intervention groups.
Simple descriptive statistics, such as n, mean, SD, median, IQ range, minimum and maximum for 
continuous variables and counts and percentages for discrete variables will be used to summarize 
most data.
P-values provided for exploratory analyses will be nominal.
5.5.2.1.
Binary Endpoints (Tertiary/Exploratory Endpoints 1-3)
Analyses for binary tertiary/exploratory endpoints (proportion of response, improvement, 
reduction) will be based upon the Composite Estimand (Section 5.4.2.2.3 for intercurrent events 
and strategies).  
Generalized linear model with logit link for a binary MMRM will be used to analyze the data.  The 
model will include all available observed data after applying intercurrent events with treatment, 
visit, region, baseline UPCR level (<3 mg/mg and ≥3 mg/mg), and treatment and visit interaction
in the model will be used to analyze the data.  The 1-sided p-value from the difference in proportion 
of participants between the intervention groups will be provided.  In addition, the estimate and its
80% CI estimated from the model will also be provided.
5.5.2.2.
Continuous Endpoints (Tertiary/Exploratory Endpoints 4-7)
Analyses for continuous endpoints will be based upon the Treatment Policy estimand.
The analysis will be performed using a MMRM based on observed data.  The terms for this model 
are study intervention, region, baseline UPCR level (< 3 mg/mg, ≥ 3 mg/mg), baseline score, visit, 
and an interaction of treatment and visit. An unrestricted (UN) variance-covariance matrix for 
repeated measures within a participant will be used unless there are issues related to convergence, 
wherein an autoregressive matrix structure will be used instead. The 1-sided p-value from the 
difference between the intervention groups will be provided.  In addition, the estimate and its 80% 
CI estimated from the model will also be provided.
5.6.
Other Supportive Endpoints
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
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For the CSR, the analyses of other supportive endpoints that are described in this section will not 
be performed.
In addition to the primary, secondary and tertiary/exploratory endpoints, other supportive efficacy 
analyses will be performed over time through Week 24 and 52.
Table 3 provides the list of supportive estimands and the respective analysis methods.
Table 3:
Endpoints, Intercurrent Events Strategy and Analysis for Other Supportive Endpoints
Endpoint
Intercurrent 
Event 
Strategy
Analysis 
(Section 5.6.1.1
and 5.6.1.2)
Endpoint Type
Objective: To evaluate the efficacy of guselkumab in participants with active LN
Proportion of participants 
achieving at least 50% decrease 
in proteinuria from baseline 
over time
Treatment 
Policy
Binary MMRM
Binary
Proportion of participants 
achieving complete renal 
response (CRR) over time
Treatment 
Policy
Binary MMRM
Binary
Proportion of participants with 
Urine Protein to Creatinine 
Ratio (UPCR) <0.5 mg/mg over 
time
Treatment 
Policy
Binary MMRM
Binary
Proportion of participants with 
UPCR <0.75 mg/mg over time
Treatment 
Policy
Binary MMRM
Binary
Proportion of participants who 
achieve reduction in 
glucocorticoid dose by Week 12
and sustain that reduction 
through at least Week 24 or 
through Week 52 to ≤ 10 
mg/day of prednisone or 
equivalent
Treatment 
Policy
Logistic regression
Binary
Cumulative average daily 
glucocorticoid dose over time 
through Week 12, 24, 52
Treatment 
Policy
Summaries only
Continuous
Objective: To evaluate the efficacy of guselkumab in extrarenal lupus manifestations
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Proportion of participants with 
≥4-point improvement in 
systemic lupus erythematosus 
disease activity index 2000 
(SLEDAI-2K) modified to 
exclude renal items over time
Treatment 
Policy
Binary MMRM 
Binary
Change from baseline in 
(SLEDAI-2K) modified to 
exclude renal items over time
Treatment 
Policy
MMRM
Continuous
Proportion of participants with 
baseline arthritis (with at least 4 
active joints at baseline) who 
have ≥50% reduction in active 
joints over time
Treatment 
Policy
Binary MMRM
Binary
Change from baseline in active, 
swollen and tender joints among 
participants with baseline 
arthritis (with at least 4 active 
joints at baseline) over time
Treatment 
Policy
MMRM
Continuous
Proportion of participants with 
baseline active mucocutaneous 
lupus manifestations (CLASI 
score ≥8) and ≥50% reduction 
in Cutaneous Lupus 
Erythematosus Disease Area 
and Severity Index (CLASI) 
scores over time
Treatment 
Policy
Binary MMRM
Binary
Change from baseline in CLASI 
scores for participants with 
baseline active mucocutaneous 
lupus manifestations (CLASI 
score ≥8) over time
Treatment 
Policy
MMRM
Continuous
Change from baseline in 
Physician's Global Assessment 
of Disease Activity (PGA) over 
time
Treatment 
Policy
MMRM
Continuous
Objective: To evaluate the impact of guselkumab on HRQoL and fatigue in participants with 
active LN
Change from baseline in Lupus 
Quality of Life (LupusQoL) 
individual domains over time 
Treatment 
Policy
MMRM
Continuous
Proportion of participants who 
achieve minimum clinically 
important differences (MCID) 
Treatment 
Policy
Binary MMRM
Binary
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cutoff of LupusQoL by domain 
over time
Change from baseline in 
Functional Assessment of 
Chronic Illness Therapy 
(FACIT)-fatigue score over 
time
Treatment 
Policy
MMRM
Continuous
Proportion of participants Who 
Achieved ≥4-point 
Improvement from Baseline in 
FACIT-Fatigue over time
Treatment 
Policy
Binary MMRM
Binary
Change from baseline in lupus 
symptoms (joint pain, joint 
stiffness, rash, and swelling 
[peripheral edema]) over time
Treatment 
Policy
MMRM
Continuous
Patient Global Impression of 
Change (PGIC) - Change in LN 
(health condition) over time
Treatment 
Policy
MMRM
Continuous
5.6.1.
Analysis Methods
Unless otherwise specified, the analysis population will be the FAS defined in Section 4.  The 
endpoints will be summarized by study intervention groups.
Summaries over time will be for all visits data is collected through Week 52.  Simple descriptive 
statistics, such as n, mean, SD, median, IQ range, minimum and maximum for continuous variables 
and counts and percentages for discrete variables will be used to summarize most data.
P-values provided for supportive analyses will be nominal.
5.6.1.1.
Binary Endpoints 
Analyses for binary secondary endpoints (proportion of response, improvement, reduction) will be 
based upon the Treatment Policy estimand.  
!
Binary MMRM - Generalized linear model with logit link for a binary MMRM will be used 
to analyze the data.  The model will include all available observed data after applying 
intercurrent events with treatment, visit, region, baseline UPCR level (<3 mg/mg and 
≥3 mg/mg), and treatment and visit interaction in the model will be used to analyze the data.  
The 1-sided p-value from the difference in proportion of participants between the intervention 
groups will be provided.  In addition, the estimate and its 80% CI estimated from the model 
will also be provided.
!
Logistic regression - A logistic regression model including treatment, region, and baseline 
UPCR level (<3 mg/mg and ≥3 mg/mg]) will be used to compare treatment groups. The 1-
sided p-value, the odds ratio and the corresponding 80% Wald CI between intervention 
groups from the model will be provided.
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5.6.1.2.
Continuous Endpoints 
Analyses for continuous endpoints will be based upon the Treatment Policy estimand.
MMRM - The analysis will be performed using a MMRM based on observed data.  The terms for 
this model are study intervention, region, baseline UPCR level (<3 mg/mg, ≥3 mg/mg), baseline 
score, visit, and an interaction of treatment and visit. An unrestricted (UN) variance-covariance 
matrix for repeated measures within a participant will be used unless there are issues related to 
convergence, wherein an autoregressive matrix structure will be used instead. The 1-sided p-value 
from the difference between the intervention groups will be provided.  In addition, the estimate 
and its 80% CI estimated from the model will also be provided.
5.7.
Safety Analyses
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
For the CSR, all safety analyses described below will be performed on all available data through 
the end of study.
All safety analyses will be based on the safety analysis set based on actual intervention received, 
unless otherwise specified.
For all continuous safety variables, descriptive statistics by intervention group will include the N, 
mean, SD, median, minimum, and maximum. Categorical variables will be summarized by 
intervention group using frequency counts and percentages.
5.7.1.
Extent of Exposure
The number and percentage of participants who receive IV or SC study interventions (guselkumab 
and placebo) will be summarized separately. The number and percentage of participants will also 
be summarized by visit.
Descriptive statistics for duration of study interventions (N, mean, SD, median, and range 
[minimum, maximum]) will be summarized. Participant-weeks of interventions are calculated as 
days of intervention/7. Participant-weeks will be presented by intervention group.
Study intervention duration is defined as (date of last dose of study intervention – date of first dose 
of study intervention) +1.
The number and percentage of participants with doses not administered will be summarized by 
intervention group. Reasons for doses not administered will also be summarized.
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For IV and SC study intervention:
Descriptive statistics will be presented for the following parameters:
!
Number of administrations
!
Cumulative total dose
Study intervention compliance will be summarized descriptively. See Appendix 7 for further 
details.
5.7.2.
Adverse Events
The verbatim terms used in the case report form by investigators to identify AEs will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after 
the initial administration of study intervention is considered to be treatment emergent. If the event 
occurs on the day of the initial administration of study intervention, and either event time or time 
of administration are missing, then the event will be assumed to be treatment emergent. If the event 
date is recorded as partial or completely missing, then the event will be considered to be treatment 
emergent unless it is known to be prior to the first administration of study intervention based on 
partial onset date or resolution date. All reported treatment-emergent AEs will be included in the 
analysis.  For each adverse event, the number and percentage of participants who experience at 
least 1 occurrence of the given event will be summarized by intervention group.
Summary tables and listings will be provided for treatment-emergent AEs:
!
AEs
!
Serious AEs (SAEs)
!
AEs by severity, NCI-CTCAE toxicity grade
!
AEs reasonably related to study intervention
!
Had AEs leading to discontinuation of study intervention/termination of study participation
Summaries and listings of other treatment-emergent AEs of special interest will be provided. These 
include infections, serious infections, opportunistic infections, malignancies, hypersensitivity 
reactions, tuberculosis, AEs related to COVID-19, injection-site reactions, and AEs temporally 
associated with infusions.
Deaths will be displayed by actual study intervention received. A listing of study participants who 
died will be provided.
5.7.3.
Additional Safety Assessments 
5.7.3.1.
Clinical Laboratory Tests
Clinical laboratory tests will be displayed for the participants included in the safety analysis set.
Descriptive statistics and graphical displays will be presented for selected chemistry and
hematology, laboratory tests at scheduled time points.
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Change from baseline through Week 24 and Week 52 will be summarized for chemistry and
hematology  tests and displayed by intervention group. A box plot of change from baseline through
Week 24 and Week 52 will be provided.
!
Hematology assessments will include but are not limited to the following: hemoglobin, 
hematocrit, platelet count, total and differential White Blood Cell count, B-cell analysis.
!
Blood chemistry assessments will include but are not limited to the following: chemistry 
panel (total and direct bilirubin, alanine aminotransferase, aspartate aminotransferase, alkaline 
phosphatase, albumin, total protein, calcium, phosphate, sodium, potassium, chloride, blood 
urea nitrogen/urea, and creatinine).
The National Cancer Institute’s Common Terminology Criteria for Adverse Events (NCI-CTCAE; 
version 5.0) will be used in the summary of laboratory data (Grade 0-4).  The proportion of 
participants with post-baseline values by maximum toxicity grade for clinical laboratory tests will 
be summarized by study intervention group.  Participants with toxicity grades ≥ 2 will be listed.
5.7.3.2.
Electronic Columbia-Suicide Severity Rating Scale
The Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) will be used as a screening 
tool to prospectively evaluate suicidal ideation and behavior among study participants. The 
eC-SSRS measures 5 possible levels of suicidal ideation and 4 possible suicidal behaviors, as well 
as non-suicidal self-injurious behavior. The assessment is a fully-structured, participant self-report 
eC-SSRS questionnaire, including standardized questions, follow-up prompts, error handling 
routines, and scoring conventions (Mundt JC, et al, 2013; Posner K, et al, 2011). Two versions of 
the eC-SSRS will be used in this study, the Lifetime version and the Since Last Contact version. 
The Lifetime version will be conducted during the screening visit and the Since Last Contact
version will be conducted at all other visits.
At the conclusion of each assessment, the eC-SSRS Findings Report can be viewed electronically. 
At screening (“In the last 6 months”) and Week 0, participants with an Ideation level (1-5) or any 
suicidal behaviors or with a response of “YES” for non-suicidal, self-injurious behavior must be 
determined to be not at risk by the investigator based on an evaluation by a mental health 
professional in order to be randomized. Participants with an Ideation level (1-5) on the eC-SSRS 
or any suicidal behaviors or with a response of “YES” for non-suicidal, self-injurious behavior at 
any postbaseline visit will also be referred to an appropriate mental health professional for 
evaluation. If a participant’s psychiatric disorder can be adequately treated with psychotherapy 
and/or pharmacotherapy then the participant, at the discretion of the investigator, should be 
continued with treatment. Ultimately, the determination of suicidality and risk is up to the 
investigator’s clinical judgment following evaluation by a mental health professional 
(eg, psychiatrist, psychologist, or appropriately trained social worker or nurse).
The eC-SSRS Findings Report will be summarized by intervention group for each finding:  
Ideation 1-5, and Behaviors (Actual (non-fatal and completed), Interrupted, Aborted and 
Preparatory attempts).  
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5.7.3.3.
Vital Signs and Physical Examination Findings
Continuous vital sign parameters including weight, height, pulse, and blood pressure (systolic and 
diastolic) will be summarized at each assessment time point. Change from baseline of the vital 
sign parameters will be summarized for through Week 24 and through Week 60. Descriptive 
statistics (mean, SD, median, minimum and maximum) will be presented.
Summaries of treatment-emergent abnormal vital signs during intervention, as defined in Table 4, 
will be provided for participants who had a baseline assessment and at least 1 postbaseline 
assessment for that vital sign. A listing of participants with treatment-emergent abnormal vital 
signs will be presented.
Table 4:
Abnormal Vital Sign Parameters
Vital Sign
Criteria
Pulse
>130 bpm or <50
Systolic blood pressure
>180 mm Hg or <85 mm Hg
Diastolic blood pressure
>115 mm Hg or <55 mm Hg
Weight
Increase/decrease 10 kg from baseline
5.8.
Other Analyses
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
For the CSR, PK Active Study Intervention serum concentration over time will be summarized
and displayed graphically. Antibodies to guselkumab status over time will be summarized and a 
listing of participants positive for antibodies to guselkumab may be presented when appropriate. 
All other analyses that are specified in this section will not be reported in the CSR.
5.8.1.
Pharmacokinetics
PK analyses will be performed on the PK analysis set, defined as participants who have received 
at least 1 dose of Active Study Intervention and have at least 1 post initial dose blood sample drawn 
for PK analysis.
If anti-Active Study Intervention antibodies are detected in certain participants, PK parameters 
may be summarized with and without these participants.
Descriptive statistics (N, mean, SD, median, range, and IQ range) will be used to summarize Active 
Study Intervention/Analyte serum concentrations at each sampling time point. PK data will be 
displayed graphically, such as mean +/- SD PK concentrations over time by intervention group.
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Active Study Intervention concentrations below the lower limit of quantification×minimum required 
dilution will be imputed as zero in the summary statistics.
Active Study Intervention concentrations will be presented based on baseline body weight 
quartiles at each time point.
PK data may be displayed graphically, such as mean +/- SD PK concentrations over time by weight 
group.
If sufficient data are available, then population PK analysis using serum concentration-time data 
of Active Study Intervention will be performed using nonlinear mixed-effects modeling. Details 
will be given in a population PK analysis plan and the results of the analysis will be presented in 
a separate report.
Urine/PK concentration will be summarized in a separate report.
5.8.2.
Immunogenicity
“Sample ADA status” and sample titer as well as the cumulative “participant ADA status” and 
peak titer through the visit will be coded and provided by the bioanalytical group. 
Participants evaluable for immunogenicity are defined as having at least one postdose anti-drug 
antibody (ADA) time point collected for anti-guselkumab antibody detection.
Participants with treatment-emergent anti-guselkumab antibodies include participants with 
treatment-induced anti-guselkumab antibodies and treatment-boosted anti-guselkumab antibodies.
Participants with treatment-induced anti-guselkumab antibodies have an anti-guselkumab 
antibodies negative sample prior to guselkumab administration and at least one anti-guselkumab
antibodies positive sample after guselkumab.
Participants with treatment-boosted anti-guselkumab antibodies have an anti-guselkumab
antibodies positive sample prior to guselkumab administration and at least one anti-guselkumab
antibodies positive sample after guselkumab with a [2]-fold increase in titer over baseline.
In participants who have a positive sample prior to guselkumab administration, if  titer remains the 
same after intervention or if ADA titer reduces or ADA disappears, the participant is classified as 
“treatment-emergent ADA negative”. Participants that are unavailable for treatment-emergent 
ADA following intervention will be classified as “participants with baseline samples only”, ie, no 
appropriate sample is available after intervention.
The anti-guselkumab antibodies summary and analysis will be based on the observed data; 
therefore no imputation of missing data will be performed. Note: participant status is through each 
visit, thus, participant status and peak titers may change as the study progresses over time. 
Therefore, the ‘participant ADA status’ at a visit represents the cumulative ADA status through 
that visit. For example, if a study has a lock at Week 24, datasets through Week 24 will have 
participant level status (eg, negative) but at Week 52, they may have developed ADA and the 
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participant status becomes “treatment-emergent ADA positive” from the interim to the final DBL. 
Peak titers can also change (increase) if a higher titer occurs after an initial DBL.
The summary of participants with baseline positive samples is taken from the sample status at 
baseline. There is no participant level status at baseline.
Incidence of antibody (evaluable, treatment-emergent ADA positive, treatment-emergent ADA 
negative) status and neutralizing antibodies to guselkumab will be summarized by intervention 
group.
In addition, listings of participants with baseline positive ADA samples, participants who are 
classified as positive for treatment-emergent anti-guselkumab antibodies and participants who 
discontinue the study by anti-guselkumab antibodies status as well as graphical representation of 
median serum guselkumab concentration by antibody status may be presented.
The Peak Titer for participants positive for treatment-emergent anti-guselkumab antibodies will 
be grouped by Peak Titer categories. Example: <=1:10, 10 to 100, 100 to 1000, >1000, if needed.
Incidence of treatment-emergent positive antibody across Peak Titer categories might be 
summarized.
Descriptive statistics (N, mean, SD, median, range, and IQ range) and incidence (N, %) of the 
relationship between treatment-emergent anti-guselkumab antibodies status (positive or negative) 
and PK concentration will be assessed.
Participants in response (N, %) for treatment-emergent anti-guselkumab antibodies status (positive 
or negative) and efficacy endpoints will be assessed:
!
Participants evaluable for immunogenicity
!
Efficacy endpoints repeated for different levels of response (eg, proportion of participants 
achieving at least 50% decrease in proteinuria from baseline at Week 24, proportion of 
participants achieving complete renal response (CRR) at Week 52 and change in UPCR)
∀
Number of participants (N)
o
Participants in response (N, %)
Incidence (N, %) between treatment-emergent anti-guselkumab antibodies status (positive or 
negative) and infusion-related reactions will be assessed:
!
Participants evaluable for immunogenicity
!
Participants with infusion-related reaction
!
Participants with severe infusion-related reaction
!
Participants with serious infusion-related reaction
!
Participants with infusion-related reaction leading to discontinuation
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!
Guselkumab infusions with infusion-related reactions (out of total number of guselkumab
infusions)
!
Placebo infusions with infusion-related reactions (out of total number of placebo infusions).
Incidence (N, %) between treatment-emergent anti-guselkumab antibodies status (positive or 
negative) and injection site reactions will be assessed:
!
Participants evaluable for immunogenicity
!
Participants with injection site reaction
!
Participants with severe injection site reaction
!
Participants with serious injection site reaction
!
Participants with injection site reaction leading to discontinuation
!
Guselkumab injections with injection site reactions (out of total number of guselkumab
injections)
!
Placebo injections with injection site reactions (out of total number of placebo injections).
5.8.3.
Pharmacodynamics / Biomarker Analyses
Changes in the concentration and proportion of subjects with abnormalities of individual 
pharmacodynamic biomarkers from baseline to the selected post treatment time points will be 
summarized.  These include but are not limited to antinuclear antibody, anti-phospholipid 
antibodies, anti-ds-DNA, C3 and C4 complement, Cystatin C, IgA, IgG, and IgM.
It should be noted that a separate pharmacodynamics / biomarker report will be produced and 
associated analyses of serum, cellular and whole blood gene expression will be reported in that 
document.
5.8.4.
Pharmacokinetic/Pharmacodynamic Relationships
If deemed feasible and necessary, exposure-response analyses may be performed. The analysis 
methods may be summarized in a separate analysis plan. Results of such analyses may be presented 
in a separate technical report.
5.8.5.
Definition of Subgroups
To evaluate the consistency of the primary efficacy endpoint (proportion of participants with 
achieving at least 50% decrease in proteinuria from baseline at Week 24) subgroup analyses may 
be performed when the number of participants in the subset permits (at least 5 participants for each 
treatment group within a subset).  
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The subgroups for subgroup analysis may include, but are not limited to, the following:  
1.
Demographic subgroups
Subgroup
Variant
Definition
Region
1
Define based on UN guidance as per the M49 standard
! Asia Pacific
! North America
! Latin America
! Europe
Age Group
1
! <55
! ≥55
Body Mass Index (BMI)
1
! normal <25 kg/m2
! overweight 25-<30 kg/m2
! obese >=30 kg/m2
Body Weight Group
1 (Quartiles)
!
Race
1
! White 
! Black 
! Asian
! All other categories
Ethnicity
1
! Hispanic or Latino
! Not Hispanic or Latino
Gender
1
! Male
! Female
Participants age at LN 
diagnosis
1
! < 21 years
! ≥ 21 years
2.
Disease Characteristics subgroups
Subgroup
Variant
Definition
Renal biopsy classes
! III
! III + V
! IV
! IV + V
Nephrotic proteinuria defined as urine 
P/C ratio of >=3
1
! UPCR <3
! UPCR ≥3
2
! < Median 
! ≥ Median
eGFR
! eGFR ≥ 90
! eGFR ≥ 60 and < 90
! eGFR ≥ 30 and < 60
! eGFR < 30
SLEDAI-2K Score 
! < Median 
! ≥ Median
PGA Score 
! < Median 
! ≥ Median
Serologic status individually and collectively for anti-dsDNA, C3 and C4 
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Subgroup
Variant
Definition
(i)
dsDNA (positive, negative)
! Positive
! Negative
(ii)
Complement C3, C4 
! Normal
! Abnormal
3.
Prior Medication subgroups
Subgroup
Variant
Definition
Glucocorticoids only
Yes or No
Glucocorticoids + Antimalarials
Yes or No
Glucocorticoids + Immunosuppressants
Yes or No
Glucocorticoids + Ace-inhibitors
Yes or No
Antimalarials + Immunosuppressants
Yes or No
Antimalarials + Ace-inhibitors
Yes or No
Immunosuppressants + Ace-inhibitors
Yes or No
Glucocorticoids + Antimalarials + Immunosuppressants
Yes or No
Glucocorticoids + Antimalarials + Ace-inhibitors
Yes or No
Antimalarials + Immunosuppressants + Ace-inhibitors
Yes or No
Glucocorticoids + Antimalarials + Immunosuppressants + Ace-inhibitors
Yes or No
5.9.
Interim Evaluations
Early Termination Note: Due to the Sponsor’s decision to stop screening of new participants as 
a result of enrollment challenges, fewer than 60 participants will be enrolled in the study. The end 
of study will occur after all enrolled participants have completed the Week 20 visit or discontinued 
study intervention prior to Week 24, and all participants have completed their final efficacy and 
safety visits per the SoA.
The first interim efficacy evaluation occurred on December 28, 2021. Due to early termination of 
the study, the second and third interim efficacy evaluations will not be performed.
Details of the Data Monitoring Committee (DMC) safety reviews and interim analysis assessments 
are included in a separate DMC Charter and 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 evaluation of efficacy as required 
by the DMC Charter.  Additionally, a dedicated DMC Data Presentation Specifications (DPS) 
document details output and programming specifications.
The follow offers a high-level summary of the DMC activities.
5.9.1.
Interim Efficacy Evaluations 
Three interim efficacy evaluations will be conducted, when approximately 10, 25 and 40 
participants respectively complete the Week 24 visit. The first interim efficacy evaluation is 
contingent to occur prior to the first participant entering the long-term extension, based on 
enrollment, that is when ~10 participants complete the Week 24 visit.  
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It should be noted that the first interim efficacy evaluation will occur 2 months prior to the first 
patient entering the LTE.   It is projected that at that time, ~10 participants will complete the 
Week 24 visit.  If enrollment is expedited and as many as ~25 patients reach the Week 24 visit 
instead, then the first and second interim efficacy evaluations will be combined.  Otherwise, the 
first and second interim efficacy evaluation will occur separately. This decision to combine the 
first and second interim efficacy evaluation will be made ~4 months prior to the first patient 
entering LTE.
The DMC will review the unblinded efficacy data and make observations about the next step of 
study/program conduct, based upon the results of the interim efficacy evaluations.
The primary endpoint will be used for the interim efficacy evaluations.  
A Bayesian predictive analysis based on a beta-binomial distribution on longitudinal data will be 
used for the analysis at each evaluation.  At each of the three interim efficacy evaluations, if the 
predictive probability of success at the end of the study (the 1-sided p-value from the difference in 
proportion of participants with ≥50% decrease in proteinuria between the guselkumab and placebo 
intervention groups is less than a 1-sided alpha of 10%), given the current results, is <10% then 
the futility criteria would be met.  
5.9.1.1.
First Interim Efficacy Evaluation
At the first interim efficacy evaluation meeting (prior to the first participant entering the long-term 
extension, when approximately 10 participants complete their Week 24 visit), the DMC will 
examine efficacy for futility of advancing to the long-term extension based upon the predictive 
probability of success of the study given the available data up to Week 24 at that point.  The 
possible recommendations of the DMC concerning efficacy at the first meeting include:
1. Criteria for evidence for futility was met.  If the futility criterion is met, the DMC will 
recommend not advancing to the long-term extension of the study.
2. Criteria for evidence of futility was NOT met. If the futility criterion is not met, the 
DMC will recommend the participants that qualify continue to advance to the long-term 
extension of the study.
5.9.1.2.
Second and Third Interim Efficacy Evaluation
At the second and third DMC interim efficacy evaluation (when approximately 25 and 40 
participants, respectively, complete their Week 24 visit), the DMC will examine efficacy for 
futility based on the predictive probability of success given the available data up to Week 24 at 
that point.  The possible observations of the DMC concerning efficacy at the second and third 
meeting include:
1.
Criteria for evidence of futility was met.  If the futility criterion is met, the DMC will 
recommend to stop the study.  Furthermore, the DMC will recommend to stop 
enrollment of additional participants due to futility if all planned participants have not 
been enrolled.
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2.
Criteria for evidence of futility was not met. If the futility criterion is not met, the 
DMC will recommend continuing the study.
Details are outlined in the DMC SAP.
5.9.2.
Data Monitoring Committee
The independent DMC will monitor data on an ongoing basis to ensure the continuing safety of 
the participants enrolled in the study.  The committee will meet periodically to review interim data.  
After the review, the DMC will make recommendations regarding the continuation of the study.  
Any safety concerns will be communicated to the Sponsor Committee Chairperson.
None of the DMC members will be participating in the study; they will be independent of the 
Sponsor.  The independent DMC consists of 2 medical experts in relevant therapeutic areas and 1 
statistician and are to be specified before study initiation.  The major function of the DMC is to 
monitor the safety of the study intervention, to evaluate  efficacy data and provide 
recommendations for placing the study on hold or stopping the study in the event of serious safety 
concerns or futility.
Periodic safety reviews will occur as outlined in the DMC Charter, initiating when the 5th
participant has been randomized or 3 months after the first participant is dosed, whichever comes 
first. Subsequent meetings will occur approximately every 4 months until the last meeting which 
will be within 6 months of the Week 60 DBL.  
Serious adverse events will be reported to the DMC members on an ongoing basis.  The DMC will 
have access to the unblinded data and review tabulated safety summaries (if appropriate) and any 
additional safety data that the DMC may request.
The content of the safety summaries and interim efficacy evaluations, the DMC roles and 
responsibilities and the general procedures (including communication plan) and their possible 
recommendations on study conduct will be defined and documented in the DMC Charter prior to 
the first DMC review.
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REFERENCES
Albrecht J, Taylor L, Berlin JA, et al. The CLASI (Cutaneous Lupus Erythematosus Disease Area and Severity 
Index): an outcome instrument for cutaneous lupus erythematosus. J Invest Dermatol. 2005; 125(5):889-894.
FACIT. www.facit.org. Accessed 01 Oct 2017.
Guy W (1976), Ed. ECDEU Assessment Manual for Psychopharmacology. Rockville, MD: US Department of 
Health, Education, and Welfare Public Health Service Alcohol, Drug Abuse, and Mental Health Administration, 
1976:217-222. 
Lai J, Beaumont JL, Ogale S, Brunetta P, Cella D. Validation of the functional assessment of chronic illness 
therapy-fatigue scale in patients with moderately to severely active systemic lupus erythematosus, participating in a 
clinical study. J Rheumatol. 2011; 38(4):672-679. 
McElhone K, Abbott J, Shelmerdine J, et al. Development and validation of a disease-specific health-related quality 
of life measure, the LupusQol, for adults with systemic lupus erythematosus. ArthritisRheum. 2007;57(6):372-979.
Mundt JC, Greist JH, Jefferson JW, et al. Prediction of suicidal behavior in clinical research by lifetime suicidal 
ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale. J Clin Psych. 
2013;74(9):887-893.
Posner K, Brown GK, Stanley B, et al. The Columbia-Suicide Severity Rating Scale: Initial validity and internal 
consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 2011;168(12):1266-
1277.
Touma Z, Gladman DD, Urowitz MB. SLEDAI-2K for a 30-day window. Lupus. 2010;19(1):49-51. 
Touma Z, Urowitz M, Ibañez D, Gladman D. SLEDAI-2K 10 days versus SLEDAI-2K 30 days in a longitudinal 
evaluation. Lupus. 2011b; 20(1):67-70. 
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APPENDICES
APPENDIX 1:
LIST OF ABBREVIATIONS
ACR
American College of Rheumatology
ADA
anti-drug antibody
AE
adverse event
ANCOVA
analysis of covariance
Anti-dsDNA
anti-double stranded deoxyribonucleic acid
ATC
anatomic and therapeutic class
BMI
body mass index
CI
confidence interval
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CMH
Cochran-Mantel-Haenszel
Cx
Complementx (eg, C3)
COPD
chronic obstructive pulmonary disease
COVID-19
coronavirus disease 2019
CRR
Complete Renal Response
CSR
Clinical Study Report
CTCAE
Common Terminology Criteria for Adverse Events
DBL
database lock
DC
discontinuation
DMC
Data Monitoring Committee
DPS
Data Presentation Specifications
eCRF
electronic case report form
eC-SSRS
Electronic Columbia-Suicide Severity Rating Scale
eGFR
Estimated Glomerular Filtration Rate
EULAR
European League Against Rheumatism
FACIT-F
Functional Assessment of Chronic Illness Therapy Fatigue
FAS
full analysis set
HRQoL
Health-Related Quality of Life
IL-xx
Interleukin-xx (eg. IL-23)
IQ
interquartile
ISN/RPS
International Society of Nephrology and Renal Pathology Society
IV
intravenous
Kg
kilogram
LLN
lower limit of normal
LN
lupus nephritis
LTE
long-term extension
LupusQoL
Lupus Quality of Life
m2
meter squared
MCID
minimum clinically important differences
MedDRA
Medical Dictionary for Regulatory Activities
Mg
milligram
MI
multiple imputation
MMF
mycophenolate mofetil
MMRM
mixed effects repeated measures model
MPA
mycophenolic acid
NSAIDs
nonsteroidal anti-inflammatory drug
PBMC
peripheral blood mononuclear cell
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PD
pharmacodynamic(s)
PGA
Physician's Global Assessment of Disease Activity
PGIC
Patient Global Impression of Change
PK
pharmacokinetic(s)
q4w
every 4 weeks
SAE
serious adverse event
SAP
Statistical Analysis Plan
SC
subcutaneous
SD
standard deviation
SLE
systemic lupus erythematosus
SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
SoA
Schedule of Activities
TF
treatment failure
ULN
upper limit of normal
UPCR
Urine Protein Creatinine Ratio
V
volume distribution
WBC
white blood cell
WHO-DD
World Health Organization Drug Dictionary
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APPENDIX 2:
CHANGES TO PROTOCOL-PLANNED ANALYSES
N/A
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APPENDIX 3:
DEMOGRAPHICS AND BASELINE CHARACTERISTICS
The number of participants in each analysis set will be summarized and listed by intervention 
group, and overall. In addition, the distribution of participants by region, country, and site ID will 
be presented unless otherwise noted.
Table 5 presents a list of the demographic variables that will be summarized by intervention group, 
and overall for the FAS analysis set(s).  Demographics will also be summarized by region using 
the FAS analysis set. Table 6 presents the baseline disease characteristics variables that will be 
summarized by intervention group and overall for the FAS analysis set(s).
Table 5:
Demographic Variables
Continuous Variables:
Summary Type
Age (years)
Descriptive statistics (N, mean, 
standard deviation [SD], median 
and range [minimum and 
maximum], and IQ range).
Weight (kg)
Height (cm)
Body Mass Index (BMI) (kg/m2)
Categorical Variables
Age <55 years, and >=55 years])
Frequency distribution with the 
number and percentage of 
participants in each category.
Sex (male, female)
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Multiple)
Ethnicity (Hispanic or Latino, not Hispanic or Latino)
BMI ([normal <25 kg/m2, overweight >=25 kg/m2])
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Table 6:
Baseline Disease Characteristics Variables
Continuous Variables:
Categories
Summary Type
Proteinuria (urine P/C ratio) (mg/mg)
Descriptive statistics (N, 
mean, standard deviation 
[SD], median and range 
[minimum and maximum], 
and IQ range).
eGFR (mL/min/m2)
SLEDAI-2K score (0-105)
PGA score (0-3)
Active joints with both pain and inflammation (0-
28)
Number of joints with pain (only) (0-28)
Number of joints with swelling (only) (0-28)
CLASI Damage Score (0-56)
CLASI Activity Score (0-70)
Lupus Quality of Life (LupusQOL) score and 
individual domains
FACIT-Fatigue score
Lupus Symptoms:
    Joint pain scale (0-10)
    Joint stiffness scale (0-10)
    Rash scale (0-10)
    Swelling scale (0-10)
LN duration
SLE duration
Categorical Variables
Frequency distribution with 
the number and percentage 
of participants in each 
category.
LN Flare
! Yes
! No
Renal biopsy classes
! III
! III + V
! IV
! IV + V
Nephrotic proteinuria defined as urine P/C ratio of 
>=3
! UPCR <3
! UPCR ≥3
eGFR
! eGFR ≥ 90
! eGFR ≥ 60 and < 90
! eGFR ≥ 30 and < 60
! eGFR < 30
dsDNA (positive, negative)
! Positive
! Negative
Complement 
C3, C4 
! Normal
! Abnormal
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APPENDIX 4:
PROTOCOL DEVIATIONS
In general, the following list of major protocol deviations may have the potential to impact 
participants’ rights, safety or well-being, or the integrity and/or result of the clinical study. 
Participants with major protocol deviations will be identified prior to DBL and the participants 
with major protocol deviations will be summarized by category.
!
Developed withdrawal criteria but not withdrawn
!
Entered but did not satisfy criteria
!
Received a disallowed concomitant treatment
!
Received wrong treatment or incorrect dose
!
Other
!
Missed visit/assessment due to COVID-19
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APPENDIX 5:
PRIOR AND CONCOMITANT MEDICATIONS
Prior and Concomitant medications will be coded using the World Health Organization Drug 
Dictionary (WHO-DD). Prior medications are defined as any therapy used before the day of first 
dose (partial or complete) of study intervention. Concomitant medications are defined as any 
therapy used on or after the same day as the first dose of study intervention, including those that 
started before and continue on after the first dose of study intervention.
Summaries of concomitant medications will be presented by anatomic and therapeutic class (ATC)
term, and intervention group. The proportion of participants who receive each concomitant 
medication will be summarized as well as the proportion of participants who receive at least 1 
concomitant medication. In addition, concomitant medications of special interest will be presented.  
Prior medications will be summarized by intervention group and ATC term.
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APPENDIX 6:
MEDICAL HISTORY
Medical history of lupus and body system will be listed and summarized by intervention groups.
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APPENDIX 7:
INTERVENTION COMPLIANCE
Compliance will be summarized descriptively for each study intervention. Compliance to 
randomized intervention versus actual intervention will be presented in a summary table.
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APPENDIX 8:
ADVERSE EVENTS OF SPECIAL INTEREST
N/A
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APPENDIX 9:
MEDICATIONS OF SPECIAL INTEREST
N/A
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APPENDIX 10:
LABORATORY TOXICITY GRADING
The grading scale used for lab assessments is based on ‘Common Terminology Criteria for 
Adverse Events (CTCAE) v5.0’.
If a laboratory value falls within the grading as specified below but also within the local laboratory 
normal limits, the value is considered to be normal and will be reset to grade 0.
Pre-baseline measurements will use the same grading ranges as applied to baseline measurements. 
In case a test has two sets of ranges – one for baseline normal and one for baseline abnormal, the 
one for baseline normal will be applied for all measurements taken pre-baseline and on baseline.
Text in gray italic in the table is present in the grading scale, but is not applied by Janssen when 
grading lab data.
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